Rassegna bibliografica di articoli selezionati apparsi in letteratura nel periodo 1999 – Maggio 2004 inerenti la “DISFUNZIONE RENALE” nello “scompenso cardiaco congestizio”

Note esplicative:

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interattiva :  che basterà cliccare per scaricare direttamente l’articolo. Per ulteriori informazioni sulle riviste a libero accesso (lodevole inziativa che consente la libera circolazione delle idee) rimandiamo al sito: The Free Medical Journals Site (dove tra l’altro è inserito nella lista anche il nostro giornale.)L’indirizzo e.mail (se disponibile) che appare su alcuni abs consente una migliore interazione con gli autori (cosa di solito molto gradita) per eventuali chiarimenti, richieste di reprint etc. etc.

Buona lettura

Luigi Tarantini, Giovanni Pulignano, Guido Gigli

Butler J, Forman DE, Abraham WT, Gottlieb SS, Loh E, Massie BM, O'Connor CM, Rich MW, Stevenson LW, Wang Y, Young JB, Krumholz HM.Relationship between heart failure treatment and development of worsening renal function among hospitalized patients.Am Heart J. 2004 Feb;147(2):331-8.clicca qui per andare su PUBMEDVanderbilt University, Nashville, Tenn, USA. javed.butler@vanderbilt.edu

Comment:Lapman PG, Golduber GN, Le Jemtel TH. Heart failure treatment and renal function.Am Heart J. 2004 Feb;147(2):193-4.

BACKGROUND: Among patients who are hospitalized with heart failure (HF), worsening renal function (WRF) is associated with worse outcomes. Whether

treatment for HF contributes to WRF is unknown. In this study, we sought to assess whether acute treatment for patients who were hospitalized with HF contributes to WRF. METHODS: Data were collected in a nested case-control study on 382 subjects who were hospitalized with HF (191 patients with WRF, defined as a rise in serum creatinine level >26.5 micromol/L [0.3 mg/dL], and 191 control subjects). The association of medications, fluid intake/output, and weight with WRF was assessed. RESULTS: Calcium channel blocker (CCB) use and loop diuretic doses were higher in patients on the day before WRF (25% vs 10% for CCB; 199 +/- 195 mg vs 143 +/- 119 mg for loop diuretics; both P <.05). There were no significant differences in the fluid intake/output or weight changes in the 2 groups. Angiotensin-converting enzyme (ACE) inhibitor use was not associated with WRF. Other predictors of WRF included elevated creatinine level at admission, uncontrolled hypertension, and history of HF or diabetes mellitus. Higher hematocrit levels were associated with a lower risk. Vasodilator use was higher among patients on the day before WRF (46% vs 35%, P <.05), but was not an independent predictor in the multivariable analysis. CONCLUSIONS: Several medical strategies, including the use of CCBs and a higher dose of loop diuretics, but not ACE inhibitors, were associated with a higher risk of WRF. Although assessment of inhospital diuresis was limited, WRF could not be explained by greater fluid loss in these patients. Determining whether these interventions are responsible for WRF or are markers of higher risk requires further investigation.

Walsh CR, O'Donnell CJ, Camargo CA Jr, Giugliano RP, Lloyd-Jones DM.Elevated serum creatinine is associated with 1-year mortality after acute myocardial infarction.Am Heart J. 2002 Dec;144(6):1003-11.clicca qui per andare su PUBMEDCardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, USA.

BACKGROUND: Cardiovascular mortality is high in individuals with end-stage renal disease. However, less is known about the prognostic importance of moderate renal insufficiency in patients with acute myocardial infarction. METHODS: We studied all patients with acute myocardial infarction admitted through the emergency department to an urban, academic hospital over 1 year. Patients were classified as having elevated (>133 micromol/L [1.5 mg/dL]) or normal (< or =133 micromol/L) serum creatinine at presentation. RESULTS: Of 483 patients, 22% had elevated creatinine and 78% had normal creatinine. By 1 year, 46% of patients with elevated creatinine and 15% of patients with normal creatinine had died (P <.001). The unadjusted hazard ratio for 1-year mortality was increased in patients with elevated creatinine compared with those with normal creatinine (hazard ratio 3.85, 95% CI 2.61-5.67). After adjustment for baseline characteristics and treatment, the multivariable-adjusted hazard ratio for 1-year mortality remained increased in patients with elevated creatinine compared with those with normal creatinine (hazard ratio 2.40, 95% CI 1.55-3.72). There was an important modification of the prognostic value of creatinine by the presence of congestive heart failure at presentation (P value for interaction =.04). The adjusted hazard ratio for 1-year death associated with elevated creatinine compared with normal creatinine was 3.89 (95% CI 1.87-8.07) in patients without congestive heart failure and 1.92 (95% CI 1.10-3.36) in patients with congestive heart failure. CONCLUSIONS: Elevated serum creatinine at presentation is associated with 1-year mortality after acute myocardial infarction. Further study is needed to optimize treatment after myocardial infarction in this high-risk group.

Havranek EP, Masoudi FA, Westfall KA, Wolfe P, Ordin DL, Krumholz HM.Spectrum of heart failure in older patients: results from the National HeartFailure project.Am Heart J. 2002 Mar;143(3):412-7.

clicca qui per andare su PUBMEDColorado Foundation for Medical Care, Aurora, Colo, USA. EHavrane@DHHA.org

BACKGROUND: The elderly make up the majority of patients with heart failure(HF), but information on this segment of the HF population is lacking becauseclinical trials typically enroll younger patients and population-based studieslack clinical detail. We sought to describe a contemporary national sample ofelderly patients with HF and to examine the sample for age-related trends inclinical characteristics. METHODS: We studied the charts of 800 Medicarepatients per state who were hospitalized with a principal diagnosis of HFbetween April 1998 and March 1999. There were 34,587 patients in the sampleafter exclusion of patients who were <65 years old, repeat discharges,discharges to another acute care facility or against medical advice, orreceiving long-term hemodialysis. RESULTS: Comorbidity was common. About onethird of patients had chronic obstructive pulmonary disease, about 40% haddiabetes, more than half had coronary heart disease, and more than half had ahistory of hypertension, but comorbidity rates declined with age. Leftventricular ejection fraction was <40% in only 50.4% of patients in whom it wasassessed. Associated laboratory abnormalities were relatively constant acrossthe age spectrum, but renal insufficiency was more common with advancing age.The likelihood that patients were in long-term care facilities before admissionrose quite steeply with age. CONCLUSIONS: Elderly patients with HF are aheterogeneous group and appear to differ substantially from patients enrolled inclinical trials. Evidence-based guidance for treatment in the context ofmultiple comorbid conditions, poor renal function, HF with preserved leftventricular systolic function, and residence in long-term care facilities isurgently needed.

Devereux RB, Roman MJ, Paranicas M, Lee ET, Welty TK, Fabsitz RR, Robbins D,Rhoades ER, Rodeheffer RJ, Cowan LD, Howard BV.A population-based assessment of left ventricular systolic dysfunction inmiddle-aged and older adults: the Strong Heart Study.Am Heart J. 2001 Mar;141(3):439-46. clicca qui per andare su PUBMEDDepartment of Medicine, Cornell Medical Center, New York, NY, USA.rbdevere@med.cornell.edu

BACKGROUND: Although clinical congestive heart failure (CHF) is increasinglycommon, few data document the prevalence and correlates of underlying leftventricular (LV) systolic dysfunction (D) in population-based samples. METHODS:Echocardiography was used in the second Strong Heart Study (SHS) examination toidentify mild and severe LVD (LV ejection fraction [EF] 40%-54% and <40%,respectively) in 3184 American Indians. RESULTS: Mild and severe LVD were morecommon in men than women (17.4% vs 7.2% and 4.7% vs 1.8%) and in diabetic thannondiabetic participants (12.7% vs 9.1% and 3.5% vs 1.6%). Stepwise increaseswere observed from participants with normal EF to those with mild and severe LVDin age (mean 60 vs 61 and 63 years, P <.001), prevalence of overt CHF (2% vs 6%and 28%) and definite coronary heart disease (3% vs 11% and 32%), systolicpressure (129 vs 135 and 136 mm Hg), serum creatinine level (0.98 vs 1.34 and2.16 mg/dL), and log urinary albumin/creatinine level (3.2 vs 3.7 and 4.7); anegative relation was seen with body mass index (31.1 vs 31.0 and 28.4 kg/m(2))(all P <.001). In multivariate analyses lower LVEFs were independentlyassociated with clinical CHF and coronary heart disease, lower myocardialcontractility, male sex, hypertension, overweight, arterial stiffening (higherpulse pressure/stroke volume) and renal dysfunction (higher serum creatininelevel), higher LV mass, and lower relative wall thickness. CONCLUSIONS: LVD,present in approximately 14% of middle-aged to elderly adults, is independentlyassociated with overt heart failure and coronary heart disease, male sex,hypertension, overweight, arterial stiffening, and renal target organ damageand, less consistently, with older age and diabetes.

Echemann M, Zannad F, Briancon S, Juilliere Y, Mertes PM, Virion JM, VillemotJP.Determinants of angiotensin-converting enzyme inhibitor prescription in severeheart failure with left ventricular systolic dysfunction: the EPICAL study.Am Heart J. 2000 Apr;139(4):624-31. clicca qui per andare su PUBMEDService d'Epidemiologie et d'Evaluation Cliniques, Hopital Marin, France.

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors have beendemonstrated to reduce morbidity and mortality rates in patients with heartfailure with left ventricular systolic dysfunction. Nevertheless, these drugsare underutilized in current practice and prescribed at doses below thoseusually recommended. The aim of this work was to identify the social,demographic, laboratory, clinical, and therapeutic factors associated withnonprescription of ACE inhibitors and/or their prescription at doses below thoserecommended in the treatment of severe long-term congestive heart failure (CHF).METHODS AND RESULTS: An epidemiologic observational study, EPICAL (EPidemiologiede l'Insuffisance Cardiaque Avancee en Lorraine), studied 417 patients withsevere CHF surviving after the index hospitalization. Multivariate logisticregression determined the factors associated with ACE inhibitor nonprescriptionand with their prescription at lower-than-recommended doses. ACE inhibitors weretaken by 75% of the patients but 38% took lower-than-recommended doses. Factorsshown to be associated with nonprescription included patients >65 years of agewith renal impairment (odds ratio 19.5, confidence interval [CI] 7.9-48.0),nonsinus cardiac rhythm (odds ratio 2.0, CI 1.2-3.2), and prescription ofpotassium-sparing diuretics (odds ratio 2.4, CI 1. 2-4.7). Renal impairment wasthe single most important factor associated with prescription oflower-than-recommended doses, particularly in elderly patients. CONCLUSIONS: Ourresults underline the need for optimal and better use of ACE inhibitor therapy.CHF treatment guidelines must be more uniformly applied by all physicians caringfor patients with heart failure.

Knight EL, Glynn RJ, McIntyre KM, Mogun H, Avorn J.Predictors of decreased renal function in patients with heart failure duringangiotensin-converting enzyme inhibitor therapy: results from the studies ofleft ventricular dysfunction (SOLVD)Am Heart J. 1999 Nov;138(5 Pt 1):849-55. clicca qui per andare su PUBMED

Editoriale: Bart BA. Concern for azotemia with angiotensin-converting enzyme inhibitors: public health implications and clinical relevance.Am Heart J. 1999 Nov;138(5 Pt 1):801-3.clicca qui per andare su PUBMED

Division of Pharmacoepidemiology, Department of Medicine, Brigham and Women'sHospital and Harvard Medical School, Boston, MA 02115, USA.

BACKGROUND: Although angiotensin-converting enzyme inhibitor therapy reducesmortality rates in patients with congestive heart failure (CHF), it may alsocause decreased renal function. Little information is available to predict whichpatients are at highest risk for this complication. OBJECTIVE: To quantifyspecific clinical predictors of reduction in renal function in patients with CHFwho are prescribed angiotensin-converting enzyme inhibitor therapy. METHOD: Weanalyzed data from the Studies of Left Ventricular Dysfunction (SOLVD), arandomized, double-blind, placebo-controlled trial of enalapril for thetreatment of CHF. There were 3379 patients randomly assigned to enalapril with a

median follow-up of 974 days and 3379 patients randomly assigned to placebo witha mean follow-up of 967 days. Decreased renal function was defined as a rise inserum creatinine >/=0.5 mg/dL (44 micromol/L) from baseline. We usedtime-to-event analysis to identify potential predictors of decrease in renalfunction including age, baseline ejection fraction, baseline creatinine, lowsystolic blood pressure (<100 mm Hg), history of hypertension, diabetes, and useof antiplatelet, diuretic, and beta-blocker therapy. RESULTS: Patients randomlyassigned to enalapril had a 33% greater likelihood of decreased renal functionthan controls (P =.003). By multivariate analysis, in both the placebo andenalapril groups older age, diuretic therapy, and diabetes were associated withdecreased renal function, whereas beta-blocker therapy and higher ejectionfraction were renoprotective. Older age was associated with a greater risk ofdeveloping decreased renal function in both groups, but significantly more so inthe enalapril group (enalapril: risk ratio [RR] 1.42 per 10 years, 95%confidence interval [CI] 1.32-1.52 with enalapril; placebo: RR 1.18, 95% CI1.12-1.25). Diuretic therapy was likewise associated with a greater risk ofdecreased renal function in the enalapril group (RR 1.89, 95% CI 1.70-2.08) thanin the placebo group (RR 1.35, 95% CI 1.09-1.66). Conversely, enalapril had arelative renoprotective effect (RR 1.33, 95% CI 1.13-1.53) compared with placebo(RR 1.96, 95% CI 1.57-2.44) in patients with diabetes. A lower risk of renalimpairment was seen in both groups with beta-blocker therapy (RR 0.70, 95% CI0.57-0.85) and higher baseline ejection fraction (RR 0.93 per 5% increment, 95%CI 0.91-0. 96). CONCLUSIONS: Enalapril use caused a 33% increase in the risk ofdecreased renal function in patients with CHF. Diuretic use and advanced ageincreased this risk. Diabetes was associated with an increased risk of renalimpairment in all patients with CHF, but this risk was reduced in the enalaprilgroup compared with the placebo group. beta-Blocker therapy and higher ejectionfraction were renoprotective in all patients regardless of therapy.

Weinfeld MS, Chertow GM, Stevenson LW.Aggravated renal dysfunction during intensive therapy for advanced chronic heartfailure.Am Heart J. 1999 Aug;138(2 Pt 1):285-90. clicca qui per andare su PUBMED

Comment in: Bart BA, Goldsmith SR.

Aggravated renal dysfunction and the acute management of advanced chronic heart failure.Am Heart J. 1999 Aug;138(2 Pt 1):200-2.clicca qui per andare su PUBMED

Cardiovascular Division, Department of Medicine, Brigham Women's Hospital,Boston, MA 02115, USA.

BACKGROUND: Chronic heart failure is associated with impaired renal function,which may worsen during therapy. The incidence, predictors, and consequences ofaggravated renal dysfunction (ARD) in patients undergoing intensive therapy foradvanced chronic heart failure are unknown. METHODS: We reviewed the experienceof 48 consecutive patients hospitalized for treatment of advanced chronic heartfailure who underwent intravenous diuretic therapy with a weight loss of >/=2kg. Evaluation included baseline renal function and echocardiography in allpatients and hemodynamic measurements in 38 (79%) patients. RESULTS: ARD,defined as >/=25% increase in serum creatinine concentration to >/=2 mg/dL,developed in 10 (21%) patients. Patients with ARD developing were older (aged 58+/- 16 years vs 51 +/- 13 years; P =.006) and had lower baseline creatinineclearance (49 +/- 21 mL/min vs 74 +/- 26 mL/min; P =.01) but had the same serumcreatinine at baseline. They were more likely to have atrial fibrillation (70%vs 29%, P =.02) but did not have lower filling pressures, cardiac output, orestimated renal perfusion pressure. Length of stay was longer if ARD developed(median 17 vs 9 days, P =.02). Mortality rate after discharge was increased in

the patients with ARD (relative risk 5.3, P =.002). CONCLUSIONS: In patientsundergoing intensive treatment for heart failure, ARD is common and clinicallysignificant. The relation among baseline factors, ARD, and worsened outcome mayreflect complex cardiorenal interactions. Better understanding of the causes andprevention of ARD during heart failure therapy may in the future lead to betteroutcomes.

Bello D, Shah NB, Edep ME, Tateo IM, Massie BM.Self-reported differences between cardiologists and heart failure specialists inthe management of chronic heart failure.Am Heart J. 1999 Jul;138(1 Pt 1):100-7. clicca qui per andare su PUBMED

Comment in:Smith JJ, Konstam MA.Heart failure: A case for subspecialized care management. Am Heart J. 1999 Jul;138(1 Pt 1):14-6.clicca qui per andare su PUBMED

Department of Medicine and Cardiovascular Research Institute of the Universityof California, San Francisco, USA.

BACKGROUND: Heart failure (HF) is responsible for considerable mortalitymorbidity rates and resource utilization. Recently, several studies havereported improved outcomes when patients are managed by special HF clinics, butit is uncertain whether this improvement reflects differences in physicianpractices or other aspects of the operation of these clinics. OBJECTIVES: Thisstudy was designed to identify differences in HF management practices betweengeneral cardiologists and cardiologists specializing in the treatment ofpatients with HF. METHODS: A survey examining diagnostic and treatment practicesin patients with HF was sent to a sample of cardiologists derived from theAmerican Medical Association Masterfile and to HF specialists who were membersof the Society of Transplant Cardiologists or principal investigators in HFtrials. Responses were examined in relation to guidelines issued by the Agencyfor Health care Policy and Research released 9 months previously. RESULTS: Ingeneral both groups practice in conformity with published guidelines. However,there were important differences between the practice patterns of generalcardiologists and HF specialists. For instance, in patients being evaluated forthe first time, cardiologists reported using a chest radiograph to assist in thediagnosis more than did HF specialists (47% vs 12%), whereas HF specialists weremore likely to use an echocardiogram (73% vs 48%). Both groups were likely toevaluate their patients for ischemia and possible revascularization, even inpatients not having angina. However, HF specialists tended to use coronaryangiography as the initial diagnostic test, whereas cardiologists were morelikely to use stress testing. HF specialists more often usedangiotensin-converting enzyme inhibitors as part of their initial therapy inpatients with mild to moderate HF (94% vs 86%) and during maintenance therapy(91% vs 80%). Also, HF specialists were more likely than cardiologists totitrate angiotensin-converting enzyme inhibitors to higher doses (75% vs 35%),even in the presence of renal dysfunction. CONCLUSION: Cardiologists and HFspecialists generally manage their patients in conformity with guidelines.However, in many areas, such as angiotensin-converting enzyme inhibitor use, HFspecialists do so more aggressively. These approaches may, in part, explain thesuccess of the HF clinic model and raise the possibility that some portion ofthe HF population may be more optimally managed by cardiologists with a specialinterest in and additional training or experience with this condition.

McAlister FA, Teo KK, Taher M, Montague TJ, Humen D, Cheung L, Kiaii M, Yim R,Armstrong PW.Insights into the contemporary epidemiology and outpatient management of

congestive heart failure.Am Heart J. 1999 Jul;138(1 Pt 1):87-94. clicca qui per andare su PUBMED

Comment in:Ghali JK.Contemporary issues in heart failure. Am Heart J. 1999 Jul;138(1 Pt 1):5-8.clicca qui per andare su PUBMEDDivision of General Internal Medicine, University of Alberta, Edmonton, Canada.

OBJECTIVES: To evaluate the epidemiology, prognosis, and patterns of practice inpatients with chronic congestive heart failure (CHF) treated and followed at aspecialized clinic. METHODS: Prospective cohort study of consecutive patientsreferred to and followed up in a specialized heart failure clinic betweenSeptember 1989 and March 1996. RESULTS: Of the 628 patients referred, 566 wereconfirmed to have CHF. Mean duration of follow-up was 518 +/- 490 days (range 1to 2192 days). Vital status was available for 99.3% of patients. Mean age atenrollment was 66 years, 68% were men, 67% had an ischemic cause of heartdisease, and 78% had systolic dysfunction. Patients with preserved systolicfunction were older, more often female, had higher mean systolic bloodpressures, and a lower prevalence of ischemic heart disease, ventriculararrhythmias, or impaired renal function when compared with those with systolicdysfunction (all P </=.001). Although there was a significant negative trend insurvival with decreasing ejection fraction (P =. 03), the survival experience ofthose with CHF and preserved systolic function did not significantly differ fromthose with systolic failure (P =.25). Multiple logistic regression analysisshowed increased mortality risk was associated with increasing age, New YorkHeart Association class IV, ischemic cause of disease, elevated serum creatininelevel, use of diuretics, and systolic dysfunction, whereas use of beta-blockerswas associated with reduced risk. CONCLUSIONS: Our data suggest that aspecialized outpatient clinic can improve practice patterns in patients withCHF. The high mortality risk in CHF with preserved systolic function suggeststhe need to find efficacious (and effective) therapies for this condition.

Kawai K, Hata K, Tanaka K, Kubota Y, Inoue R, Masuda E, Miyazaki T, Yokoyama M.Attenuation of biologic compensatory action of cardiac natriuretic peptidesystem with aging.Am J Cardiol. 2004 Mar 15;93(6):719-23. clicca qui per andare su PUBMED

Department of Internal Medicine, Kanzaki General Municipal Hospital, Hyogo,Japan. kkwai@river.sannet.ne.jp

Although plasma B-type natriuretic peptide (BNP) levels increase with age, themechanisms responsible for this increase are unknown. We investigated thepredictors of elevated BNP in older subjects without cardiac systolicdysfunction and overt renal dysfunction. Furthermore, we analyzed the relationsbetween BNP and its second messenger, cyclic guanosine monophosphate (cGMP), toaging. In 252 subjects (mean age 69 +/- 12 years) with left ventricular ejection

fraction >/=50% and creatinine levels <==1.5 mg/dl, plasma levels of BNP, cGMP,blood urea nitrogen, creatinine, and beta2-microglobulin (an endogenous markerof renal function), estimated glomerular filtration rate, and echocardiographicdata were prospectively evaluated. Plasma BNP levels increased with age (r =0.4, p <0.0001). With use of multivariate analysis, predictors of elevated BNPlevels were age, use of beta blockers, and serum beta2-microglobulin levels. Themolar ratio of cGMP to BNP significantly decreased with aging (r = 0.55, p<0.0001). Elevated BNP in older subjects with normal cardiac systolic functionmay be due in part to renal impairment. With aging, biologic compensation of thecardiac natriuretic peptide system may be attenuated.

Cioffi G, Stefenelli C, Tarantini L, Opasich C.Hemodynamic response to intensive unloading therapy (furosemide andnitroprusside) in patients >70 years of age with left ventricular systolicdysfunction and decompensated chronic heart failure.Am J Cardiol. 2003 Nov 1;92(9):1050-6.clicca qui per andare su PUBMED

Department of Cardiology, Villa Bianca Hospital, Trento, Italy.gcioffi@albaclick.com

In patients with decompensated chronic congestive heart failure (CHF), intensiveunloading therapy allows an acute decrease in ventricular filling pressures andimproves long-term prognosis. Because elderly patients do not routinely undergoinvasive hemodynamic evaluation, they are generally denied such a pharmacologicapproach. We prospectively characterized the acute hemodynamic response tointensive unloading and its prognostic significance in a elderly population withCHF who were hospitalized for cardiac decompensation. Fifty-nine patients aged>70 years with left ventricular systolic dysfunction underwent intensiveunloading therapy (furosemide and nitroprusside) tailored to reduce ventricularfilling pressures to near-normal levels. The hemodynamic parameters weremonitored by Doppler echocardiography. At baseline, left and right ventricularfilling pressures were 21 +/- 3 and 10 +/- 3 mm Hg, respectively. Although allpatients experienced a relevant improvement in clinical status during hospitalstay, a significant reduction of ventricular filling pressures was detected atdischarge in only 40 of them (68%) (responders), whereas 19 patients (32%) had adeficient response to therapy (nonresponders). This unfavorable behavior waspredicted by the presence of renal dysfunction at admission. During 19-monthfollow-up, death due to cardiovascular causes occurred in 8 of 40 responders(20%) and in 9 of 19 nonresponders (47%) (p <0.005). Hospitalizations forcardiovascular causes were more frequent in the nonresponders (58% vs 8%, p<0.0001). Thus, a deficient hemodynamic response to intensive unloadingtreatment is not infrequent in elderly patients with decompensated CHF. Thisbehavior is predicted by renal dysfunction at admission and is associated withpoorer outcome.

Chae CU, Albert CM, Glynn RJ, Guralnik JM, Curhan GCMild renal insufficiency and risk of congestive heart failure in men and women > or =70 years of age.Am J Cardiol. 2003 Sep 15;92(6):682-6.clicca qui per andare su PUBMED

Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, 900 Commonwealth Avenue East, Boston, MA 02215-1204, USA. cchae@partners.org

Mild renal insufficiency is increasingly recognized as an independent risk factor for cardiovascular disease. However, few data exist regarding its

relation to risk of congestive heart failure (CHF), a major public health problem in the elderly. To determine if mild renal insufficiency is associated with risk of incident CHF in the elderly, we analyzed data from 3,618 participants in the prospective, community-based Established Populations for Epidemiologic Studies of the Elderly (EPESE), who had no known CHF and had serum creatinine levels measured from 1987 to 1989. Mean age of the study population was 78.3 +/- 5.4 years; 84% had creatinine values <1.5 mg/dl and 98% had creatinine values < or =2.0 mg/dl. Creatinine clearance (CrCl) was calculated using the Cockcroft-Gault equation. During 3.9 years of follow-up, 488 subjects developed incident CHF as defined by hospital discharge and death certificate data. In a multivariate proportional hazards model, CrCl was inversely associated with CHF risk (p value for trend <0.001). Those in the lowest quartile of CrCl (< or =36.9 ml/min) had a nearly twofold (hazards ratio [HR] 1.99, 95% confidence intervals [CI] 1.43 to 2.79) greater risk of incident CHF compared with those in the highest quartile (>57.4 ml/min). Renal insufficiency, defined as creatinine > or =1.5 mg/dl in men and > or =1.3 mg/dl in women, was also associated with increased CHF risk (multivariate HR 1.43, 95% CI 1.17 to 1.74). Thus, mild renal insufficiency was a strong independent predictor of CHF in this cohort, suggesting that serum creatinine may offer a readily accessible tool to identify elderly patients at risk for CHF.

Devereux RB, Roman MJ, Liu JE, Welty TK, Lee ET, Rodeheffer R, Fabsitz RR,Howard BV.Congestive heart failure despite normal left ventricular systolic function in apopulation-based sample: the Strong Heart Study.Am J Cardiol. 2000 Nov 15;86(10):1090-6. clicca qui per andare su PUBMED

Department of Medicine, The New York Presbyterian Hospital-Weill Cornell MedicalCenter, New York 10021, USA. rbdevere@med.cornell.edu

In selected clinical series, > or = 50% of adults with congestive heart failure(CHF) do not have left ventricular (LV) systolic dysfunction. Little is known ofthe prevalence of this phenomenon in population samples. Therefore, clinicalexamination and echocardiography were used in the second examination of theStrong Heart Study (3,184 men and women, 47 to 81 years old) to identify 95participants with CHF, 50 of whom had normal LV ejection fraction (EF) (> 54%),19 of whom had mildly reduced EF (40% to 54%), and 26 of whom had EF < or = 40%.Compared with those with no CHF, participants with CHF and no, mild, or severedecrease in EF had higher creatinine levels (2.34 to 2.85 vs 1.01 mg/dl, p <0.001) and higher prevalences of diabetes (60% to 70% vs 50%) and hypertension(75% to 96% vs 46%, p < 0.05). Compared with those with no CHF, participantswith CHF and normal EF had prolonged deceleration time (233 vs 204 ms, p < 0.05)and a reduced E/A, whereas those with CHF and EF < or = 40% had shortdeceleration time (158 ms, p < 0.05) and high E/A (1.70, p < 0.001); patientswith CHF and normal EF had higher LV mass (98 vs 84 g/m2, p < 0.001) andrelative wall thickness (0.37 vs 0.35, p < 0.05) than those without CHF.Patients with CHF with normal EF were, compared with those without CHF or withCHF and EF < or = 40%, disproportionately women (mean 84% vs 63% and 42%, p <0.001), older (mean 64 vs 60 years and 63 years, respectively, p < 0.01), hadhigher body mass index (mean 33.1 vs 31.0 and 27.7 kg/m2, p < 0.05), and highersystolic blood pressure (mean 137 vs 130 and 128 mm Hg, both p < 0.05). Thus, ina population-based sample, patients with CHF and normal LV EF were older andoverweight, more often women, had renal dysfunction, impaired early diastolic LVrelaxation, and concentric LV geometry, whereas patients with CHF and severe LVdysfunction were more often men, had lower body mass index, a restrictivepattern of LV filling, and eccentric LV hypertrophy.

Krumholz HM, Chen YT, Vaccarino V, Wang Y, Radford MJ, Bradford WD, Horwitz RI.Correlates and impact on outcomes of worsening renal function in patients > or=65 years of age with heart failure.Am J Cardiol. 2000 May 1;85(9):1110-3. clicca qui per andare su PUBMED

Section of Cardiovascular Medicine, Department of Medicine, Yale UniversitySchool of Medicine, New Haven, CT 06520-8025, USA. harlan.krumholz@yale.edu

Despite the potential importance of a rising creatinine level in patients hospitalized for heart failure, there is little information about factors that may predispose patients to this condition or its association with outcomes. We sought to determine the incidence and identify factors associated with the development of worsening renal function in elderly patients admitted with heart failure, and to examine the impact of worsening renal function on clinical and

economic outcomes. The study sample included 1,681 patients aged 65 years, discharged with heart failure at 18 Connecticut hospitals, who did not have clear precipitants for renal dysfunction. Worsening renal function (defined as an increase in serum creatinine level of >0.3 mg/dl during hospitalization from admission) occurred in 28% of the cohort and was associated with male gender, hypertension, rales > basilar, pulse >100 beats/min, systolic blood pressure >200 mm Hg, and admission creatinine >1.5 mg/dl. Based on the number of these factors, a patient's risk for developing worsening renal function ranged between

16% ( 1 factor) and 53% ( 5 factors). After adjusting for confounding effects, worsening renal function was associated with a significantly longer length of stay by 2.3 days, higher in-hospital cost by $1,758, and an increased risk of in-hospital mortality (odds ratio 2.72; 95% confidence interval 1.62 to 4.58). In conclusion, worsening renal function, an event that frequently occurs in elderly patients hospitalized with heart failure, confers a substantial burden to patients and the healthcare system and can be predicted by 6 admission characteristics

McCullough PA, Duc P, Omland T, McCord J, Nowak RM, Hollander JE, Herrmann HC,Steg PG, Westheim A, Knudsen CW, Storrow AB, Abraham WT, Lamba S, Wu AH, PerezA, Clopton P, Krishnaswamy P, Kazanegra R, Maisel AS; Breathing Not ProperlyMultinational Study Investigators.B-type natriuretic peptide and renal function in the diagnosis of heart failure:an analysis from the Breathing Not Properly Multinational Study.Am J Kidney Dis. 2003 Mar;41(3):571-9.clicca qui per andare su PUBMED

University of California, San Diego Veteran's Affairs Medical Center, San Diego,CA, USA. mailto:pmc975@yahoo.com

BACKGROUND: Both B-type natriuretic peptide (BNP) and renal function areprognostic indicators of survival in patients with congestive heart failure(CHF). However, relationships between BNP, renal function, and heart failure asan emergency diagnosis are unknown. METHODS: The Breathing Not ProperlyMultinational Study was a prospectively designed diagnostic test evaluationstudy conducted in seven centers. Of 1,586 participants who presented with acutedyspnea, 1,452 patients (91.6%) had both BNP level and baseline estimated

glomerular filtration rate (eGFR) available. Patients with an eGFR less than 15mL/min/1.73 m2 and those on dialysis therapy were excluded. The final diagnosiswas adjudicated by two independent cardiologists who were blinded to BNPresults. RESULTS: The final diagnosis was CHF in 715 patients (49.2%). Raw andlog-log transformed correlations between BNP and eGFR values were r = -0.19 andr = -0.17 for those with CHF and r = -0.20 and r = -0.31 for those without CHF(both P < 0.0001 for r not equal 0). Mean BNP levels were 561.6 pg/mL (162.3fmol/mL), 647.5 pg/mL (187.1 fmol/mL), 745.6 pg/mL (215.5 fmol/mL), and 850.7pg/mL (245.8 fmol/mL) for those with CHF and 85.4 pg/mL (24.7 fmol/mL), 131.7pg/mL (38.1 fmol/mL), 297.2 pg/mL (85.9 fmol/mL), and 285.0 pg/mL (82.3 fmol/mL)for those without CHF in eGFR categories of 90 or greater, 89 to 60, 59 to 30,and less than 30 mL/min/1.73 m2, respectively. The area under the receiveroperating characteristic curve and optimum cut points for BNP were 0.91 and 70.7pg/mL (20.4 fmol/mL), 0.90 and 104.3 pg/mL (30.1 fmol/mL), 0.81 and 201.2 pg/mL(58.1 fmol/mL), and 0.86 and 225.0 pg/mL (65.0 fmol/mL) for the eGFR categoriesof 90 or greater, 89 to 60, 59 to 30, and less than 30 mL/min/1.73 m2,respectively. CONCLUSION: Renal function correlates weakly with BNP andinfluences the optimal cut point for BNP, particularly in those with an eGFRless than 60 mL/min/1.73 m2.

Krumholz HM, Chen YT, Bradford WD, Cerese J.Variations in and correlates of length of stay in academic hospitals amongpatients with heart failure resulting from systolic dysfunction.Am J Manag Care. 1999 Jun;5(6):715-23. clicca qui per andare su PUBMED

Comment in:Weintraub WS, Deaton C.Variation in length of stay in patients hospitalized with congestive heart failure.

Am J Manag Care. 1999 Jun;5(6):800-2.clicca qui per andare su PUBMED

Yale University School of Medicine, New Haven, CT, USA. harlan.krumholz@yale.edu

OBJECTIVE: Given the high cost of caring for patients with congestive heartfailure, there are strong incentives to decrease hospital costs by shorteninglength of hospital stay. We sought to identify factors associated with length ofstay among patients admitted for the treatment of heart failure resulting fromsystolic dysfunction. STUDY DESIGN: Retrospective cohort study. METHODS: Weexamined data from patients with a principal discharge diagnosis of congestiveheart failure who had been admitted to 1 of the 49 academic hospitals across theUnited States that participated in the CHF Benchmark Project, a largecollaborative quality improvement project coordinated by the UniversityHealthSystem Consortium. Patients were discharged between January 1 and June 30,1996. We obtained patient characteristics and hospitalization data byretrospectively reviewing medical records. We used linear regression models toidentify major determinants of length of stay. RESULTS: Among the 1046 patientseligible for the study, 59% were women, 55% were white, and 58% were aged 65years or older. Adjusting for patient demographic and admission clinicalcharacteristics, the mean length of stay was 4.9 +/- 0.9 days. Length of stayvaried significantly among hospitals, even after adjusting for differences inpatient characteristics. In multivariate regression models, factors that were

independently associated with a significantly longer length of stay were priorrenal failure, peripheral edema, atrial fibrillation, hyponatremia, urinarycatheter on admission, initiation of an antiarrhythmic or warfarin, and majorcomplications. Patient characteristics and hospital events combined explained16% of the variation in the length of stay. Adjusting for the individualhospitals explained an additional 10% of the variation in the length of stay.CONCLUSIONS: Although a number of patient and hospitalization factors wereassociated with length of stay in patients with congestive heart failureresulting from systolic dysfunction, much unexplained variation remained.Clinical factors alone explained about 50% more variation than did factorsspecific to the individual hospitals.

Aronson D, Mittleman MA, Burger AJ.Elevated blood urea nitrogen level as a predictor of mortality in patientsadmitted for decompensated heart failure.Am J Med. 2004 Apr 1;116(7):466-73. clicca qui per andare su PUBMED

Division of Cardiology, Rambam Medical Center, Haifa, Israel.

BACKGROUND: Hospitalization for decompensated heart failure is associated withhigh mortality after discharge. In heart failure, renal function involves bothcardiovascular and hemodynamic properties. We studied the relation between renaldysfunction and mortality in patients admitted for decompensated heart failure.METHODS: The prognostic importance of four measures of renal function-blood ureanitrogen, serum creatinine, blood urea nitrogen/creatinine ratio, and estimatedcreatinine clearance-was evaluated in 541 patients (mean [+/- SD] age, 63 +/- 14years; 377 men [70%]) with a previous diagnosis of heart failure (96% with NewYork Heart Association class III or IV symptoms) who were admitted for clinicaldecompensation. RESULTS: During a mean follow-up of 343 +/- 185 days, 177patients (33%) died. In multivariable Cox regression models, the risk ofall-cause mortality increased with each quartile of blood urea nitrogen, with anadjusted relative risk of 2.3 in patients in the upper compared with the lowerquartiles (95% confidence interval [CI]: 1.3 to 4.1; P = 0.005). Creatinine andestimated creatinine clearance were not significant predictors of mortalityafter adjustment for other covariates. Blood urea nitrogen/creatinine ratioyielded similar prognostic information as blood urea nitrogen (adjusted relativerisk = 2.3; 95% CI: 1.4 to 3.8; P = 0.0007 for patients in the upper comparedwith the lower quartiles). CONCLUSION: Blood urea nitrogen is a simple clinicalvariable that provides useful prognostic information in patients admitted fordecompensated heart failure. In this setting, elevated blood urea nitrogenlevels probably reflect the cumulative effects of hemodynamic and neurohormonalalterations that result in renal hypoperfusion.

Brophy JM, Dagenais GR, McSherry F, Williford W, Yusuf S.A multivariate model for predicting mortality in patients with heart failure andsystolic dysfunction.Am J Med. 2004 Mar 1;116(5):300-4. clicca qui per andare su PUBMED

Division of Cardiology and Clinical Epidemiology, McGill University HealthCenter, Montreal, Quebec, Canada. jbroph@po-box.mcgill.ca

BACKGROUND: Heart failure is a leading cause of morbidity and mortality, butthere are no reliable models based on readily available clinical variables topredict outcomes in patients taking angiotensin-converting enzyme (ACE)inhibitors. METHODS: A multivariate statistical model to predict mortality wasdeveloped in a random sample (n = 4277 patients [67%]) of the 6422 patientsenrolled in the Digitalis Investigation Group trial who had a depressed ejectionfraction (<or=45%), were in sinus rhythm, and were taking ACE inhibitors. Themodel was then validated in the remaining 2145 patients. RESULTS: Totalmortality in the derivation sample was 11.2% (n = 480) at 12 months and 29.9% (n= 1277) at 36 months. Lower ejection fraction, worse renal function,cardiomegaly, worse functional class, signs or symptoms of heart failure, lowerblood pressure, and lower body mass index were associated with reduced 12-monthsurvival. This model provided good predictions of mortality in the verificationsample. The same variables, along with age and the baseline use of nitrates,were also predictive of 36-month mortality. CONCLUSION: Routine clinicalvariables can be used to predict short- and long-term mortality in patients withheart failure and systolic dysfunction who are treated with ACE inhibitors.

Marenzi G, Lauri G, Guazzi M, Assanelli E, Grazi M, Famoso G, Agostoni P.Cardiac and renal dysfunction in chronic heart failure: relation to neurohumoralactivation and prognosis.Am J Med Sci. 2001 Jun;321(6):359-66. clicca qui per andare su PUBMED

IRCCS, Institute of Cardiology, University of Milan, Italy.giancarlo.marenzi@cardiologicomonzino.it

BACKGROUND: In chronic heart failure (CHF), cardiac dysfunction is consideredthe major determinant of neurohumoral activation but the role of renalimpairment has not been defined. We investigated the relationship between bothcardiac and renal dysfunction and neurohumoral activation, and their possibleinfluence on prognosis. METHODS: Hemodynamics, renal function, plasmaneurohormones, and long-term follow-up were evaluated in 148 CHF patients,grouped according to systolic volume index (SVI) and serum creatinine (CRE)values: SVI > 28 mL/m2 and CRE < 1.5 mg/dL (group I, n = 55), SVI < 28 mL/m2 andCRE < 1.5 mg/dL (group II, n = 37), SVI > 28 mL/m2 and CRE > 1.5 mg/dL (groupIII, n = 25), SVI < 28 mL/m2 and CRE > 1.5 mg/dL (group IV, n = 31). RESULTS:Neurohormones progressively increased from Group I through IV and correlatedwith both cardiac and renal function. The hemodynamic pattern was similar inpatients with normal or abnormal renal function, whereas neurohormones were onlymoderately increased in the former group and markedly increased in the lattergroup. Long-term survival progressively decreased from Group I through IV andwas significantly poorer in patients with renal dysfunction. CONCLUSIONS: Our

study confirms that, in CHF, neurohumoral activation is strictly related tolong-term survival and that many factors contribute to its development andprogression; among these, cardiac and renal dysfunction seem to play a majorrole.

Massie BM, Armstrong PW, Cleland JG, Horowitz JD, Packer M, Poole-Wilson PA,Ryden L.Toleration of high doses of angiotensin-converting enzyme inhibitors in patientswith chronic heart failure: results from the ATLAS trial. The Assessment ofTreatment with Lisinopril and Survival.Arch Intern Med. 2001 Jan 22;161(2):165-71. clicca qui per andare su PUBMED

Department of Medicine, University of California-San Francisco and theDepartment of Veterans Affairs Medical Center, USA. Barry.Massie@med.va.gov

BACKGROUND: Treatment with angiotensin-converting enzyme (ACE) inhibitorsreduces mortality and morbidity in patients with chronic heart failure (CHF),but most affected patients are not receiving these agents or are being treatedwith doses lower than those found to be efficacious in trials, primarily becauseof concerns about the safety and tolerability of these agents, especially at therecommended doses. The present study examines the safety and tolerability ofhigh- compared with low-dose lisinopril in CHF. METHODS: The Assessment ofLisinopril and Survival study was a multicenter, randomized, double-blind trialin which patients with or without previous ACE inhibitor treatment werestabilized receiving medium-dose lisinopril (12.5 or 15.0 mg once daily [OD])for 2 to 4 weeks and then randomized to high- (35.0 or 32.5 mg OD) or low-dose(5.0 or 2.5 mg OD) groups. Patients with New York Heart Association classes IIto IV CHF and left ventricular ejection fractions of no greater than 0.30 (n =3164) were randomized and followed up for a median of 46 months. We examined theoccurrence of adverse events and the need for discontinuation and dose reductionduring treatment, with a focus on hypotension and renal dysfunction. RESULTS: Of405 patients not previously receiving an ACE inhibitor, doses in only 4.2% couldnot be titrated to the medium doses required for randomization because ofsymptoms possibly related to hypotension (2.0%) or because of renal dysfunctionor hyperkalemia (2.3%). Doses in more than 90% of randomized patients in thehigh- and low-dose groups were titrated to their assigned target, and the meandoses of blinded medication in both groups remained similar throughout thestudy. Withdrawals occurred in 27.1% of the high- and 30.7% of the low-dosegroups. Subgroups presumed to be at higher risk for ACE inhibitor intolerance(blood pressure, <120 mm Hg; creatinine, > or =132.6 micromol/L [> or =1.5mg/dL]; age, > or =70 years; and patients with diabetes) generally tolerated thehigh-dose strategy. CONCLUSIONS: These findings demonstrate that ACE inhibitortherapy in most patients with CHF can be successfully titrated to and maintainedat high doses, and that more aggressive use of these agents is warranted.

McAlister FA, Ezekowitz J, Tonelli M, Armstrong PW.Renal insufficiency and heart failure: prognostic and therapeutic implications from a prospective cohort study.Circulation. 2004 Mar 2;109(8):1004-9. Epub 2004 Feb 09.clicca qui per andare su PUBMEDDivision of General Internal Medicine, University of Alberta, Edmonton, Canada. Finlay.McAlister@ualberta.ca

BACKGROUND: The prevalence, prognostic import, and impact of renal insufficiency on the benefits of ACE inhibitors and beta-blockers in community-dwelling patients with heart failure are uncertain. METHODS AND RESULTS: We analyzed data from a prospective cohort of 754 patients with heart failure who had ejection fraction, serum creatinine, and weight measured at baseline. Median age was 69 years, and 43% had an ejection fraction > or =35%. By the Cockcroft-Gault equation, 118 patients (16%) had creatinine clearances < or =30 mL/min and 301 (40%) had creatinine clearances between 30 and 59 mL/min. During follow-up (median 926 days), 385 patients (37%) died. Even after adjustment for all other prognostic factors, survival was significantly associated with renal function (P=0.002) in patients with either systolic or diastolic dysfunction; patients exhibited a 1% increase in mortality for each 1-mL/min decrease in creatinine clearance. The associations with 1-year mortality reductions were similar for ACE inhibitors (OR 0.46 [95% CI 0.26 to 0.82] versus OR 0.28 [95% CI 0.11 to 0.70]) and beta-blockers (OR 0.40 [95% CI 0.23 to 0.70] versus OR 0.41 [95% CI 0.19 to 0.85]) in patients with creatinine clearances <60 mL/min versus > or =60 mL/min, although these drugs were used less frequently in patients with renal insufficiency. CONCLUSIONS: Renal insufficiency is more prevalent in patients with heart failure than previously reported and is an independent prognostic factor in diastolic and systolic dysfunction. ACE inhibitors and beta-blockers were associated with similar reductions in mortality in patients with and without renal insufficiency.

Arnold JM, Yusuf S, Young J, Mathew J, Johnstone D, Avezum A, Lonn E, Pogue J, Bosch J; HOPE Investigators.Prevention of Heart Failure in Patients in the Heart Outcomes Prevention Evaluation (HOPE) Study.Circulation. 2003 Mar 11;107(9):1284-90

  London Health Sciences Centre, London, Canada. malcolm.arnold@lhsc.on.ca

BACKGROUND: Previous trials in the prevention of heart failure have been restricted to patients with low ejection fraction or hypertension. We assessed an angiotensin-converting enzyme (ACE) inhibitor, ramipril, to prevent the development of heart failure in high-risk patients without known low ejection fraction or heart failure. METHODS AND RESULTS: We randomly assigned 9297 patients to receive double-blind ramipril (10 mg daily) or matching placebo for 4.5 years. Death attributable to heart failure, hospitalization for heart failure, initiation of open-label ACE inhibitor for heart failure, or development of typical signs or symptoms of heart failure developed in 951 patients and was associated with a 4.01-fold increase in the risk of death (P<0.0001). The rate of developing heart failure was significantly increased

with coronary disease (risk ratio, 2.17), microalbuminuria (1.82), left ventricular hypertrophy (1.47), increasing age (by decade, 1.37), and diabetes (1.36). Ramipril reduced new-onset heart failure rate from 11.5% to 9.0% (relative risk, 0.77; 95% CI, 0.68 to 0.87; P<0.0001). Ramipril consistently reduced heart failure rate both in those with (relative risk, 0.87) and those without an interim myocardial infarction (relative risk, 0.78). Ramipril also reduced the heart failure rate more in patients with baseline systolic pressure above the median (139 mm Hg) (relative risk, 0.67) compared with those below the median (relative risk, 0.91; P=0.024 for interaction of group by treatment). CONCLUSION: Ramipril significantly reduces the rate of development of heart failure in patients at high risk of cardiovascular events.

Sarnak MJ, Levey AS, Schoolwerth AC, Coresh J, Culleton B, Hamm LL, McCullough PA, Kasiske BL, Kelepouris E, Klag MJ, Parfrey P, Pfeffer M, Raij L, Spinosa DJ, Wilson PW; American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention.Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention.Circulation. 2003 Oct 28;108(17):2154-69

 

Schoolwerth AC, Sica DA, Ballermann BJ, Wilcox CS; Council on the Kidney in Cardiovascular Disease and the Council for High Blood Pressure Research of the American Heart Association.Renal considerations in angiotensin converting enzyme inhibitor therapy: a statement for healthcare professionals from the Council on the Kidney in Cardiovascular Disease and the Council for High Blood Pressure Research of the American Heart Association.Circulation. 2001 Oct 16;104(16):1985-91

 

Hillege HL, Girbes AR, de Kam PJ, Boomsma F, de Zeeuw D, Charlesworth A, HamptonJR, van Veldhuisen DJ.Renal function, neurohormonal activation, and survival in patients with chronicheart failure.Circulation. 2000 Jul 11;102(2):203-10.

 

Department of Clinical Pharmacology, State University Groningen, TheNetherlands.

BACKGROUND: Because renal function is affected by chronic heart failure (CHF)and it relates to both cardiovascular and hemodynamic properties, it should haveadditional prognostic value. We studied whether renal function is a predictorfor mortality in advanced CHF, and we assessed its relative contributioncompared with other established risk factors. In addition, we studied the

relation between renal function and neurohormonal activation. METHODS ANDRESULTS: The study population consisted of 1906 patients with CHF who wereenrolled in a recent survival trial (Second Prospective Randomized study ofIbopamine on Mortality and Efficacy). In a subgroup of 372 patients, plasmaneurohormones were determined. The baseline glomerular filtration rate (GFR(c))was calculated using the Cockroft Gault equation. GFR(c) was the most powerfulpredictor of mortality; it was followed by New York Heart Association functionalclass and the use of angiotensin-converting enzyme inhibitors. Patients in thelowest quartile of GFR(c) values (<44 mL/min) had almost 3 times the risk ofmortality (relative risk, 2. 85; P<0.001) of patients in the highest quartile(>76 mL/min). Impaired left ventricular ejection fraction (LVEF) was onlymodestly predictive (P=0.053). GFR(c) was inversely related with N-terminalatrial natriuretic peptide (ANP; r=-0.53) and, to a lesser extent, with ANPitself (r=-0.35; both P<0.001). CONCLUSIONS: Impaired renal function (GFR(c)) isa stronger predictor of mortality than impaired cardiac function (LVEF and NewYork Heart Association class) in advanced CHF, and it is associated withincreased levels of N-terminal ANP. Moreover, impaired renal function was notrelated to LVEF, which suggests that factors other than reduced cardiac outputare causally involved.

Middlekauff HR, Nitzsche EU, Hoh CK, Hamilton MA, Fonarow GC, Hage A, MoriguchiJD.Exaggerated renal vasoconstriction during exercise in heart failure patients.Circulation. 2000 Feb 22;101(7):784-9.

 

Division of Cardiology, Department of Medicine, UCLA School of Medicine, LosAngeles, CA 90095, USA.

BACKGROUND: During static exercise in normal healthy humans, reflex renalcortical vasoconstriction occurs. Muscle metaboreceptors contribute importantlyto this reflex renal vasoconstriction. In patients with heart failure, in whomrenal vascular tone is already increased at rest, it is unknown whether there isfurther reflex renal vasoconstriction during exercise. METHODS AND RESULTS:Thirty-nine heart failure patients (NYHA functional class III and IV) and 38age-matched control subjects (controls) were studied. Renal blood flow wasmeasured by dynamic positron emission tomography. Graded handgrip exercise andpost-handgrip ischemic arrest were used to clarify the reflex mechanismsinvolved. During sustained handgrip (30% maximum voluntary contraction), peakrenal vasoconstriction was significantly increased in heart failure patientscompared with controls (70+/-13 versus 42+/-1 U, P=0.02). Renal vasoconstrictionreturned to baseline in normal humans by 2 to 5 minutes but remainedsignificantly increased in heart failure patients at 2 to 5 minutes and hadreturned to baseline at 20 minutes. In contrast, during post-handgripcirculatory arrest, which isolates muscle metaboreceptors, peak renalvasoconstriction was not greater in heart failure patients than in normalcontrols. In fact, the increase in renal vasoconstriction was blunted in heartfailure patients compared with controls (20+/-5 versus 30+/-2 U, P=0.05).CONCLUSIONS: During sustained handgrip exercise in heart failure, both themagnitude and duration of reflex renal vasoconstriction are exaggerated in heartfailure patients compared with normal healthy humans. The contribution of themuscle metaboreceptors to reflex renal vasoconstriction is blunted in heartfailure patients compared with normal controls.

Silverberg DS, Wexler D, Blum M, Tchebiner J, Sheps D, Keren G, Schwartz D,Baruch R, Yachnin T, Shaked M, Zubkov A, Steinbruch S, Iaina A.The correction of anemia in severe resistant heart failure with erythropoietinand intravenous iron prevents the progression of both the heart and the renalfailure and markedly reduces hospitalization.Clin Nephrol. 2002 Jul;58 Suppl 1:S37-45.clicca qui per andare su PUBMED

Department of Nephrology and Cardiology, Tel Aviv Medical Center, Israel.donald@netvision.net.il

Both Congestive Heart Failure (CHF) and Chronic Renal Failure (CRF) areincreasing steadily in the community. We propose that there is a vicious circleestablished whereby CHF and CRF both cause anemia and the anemia then worsensboth the CHF and CRF causing more anemia and so on. We call this the CardioRenal Anemia (CRA) syndrome. By the combination of active treatment of the CHFand control of the anemia with subcutaneous erythropoietin and intravenous iron,the progression of both the CHF and the CRF can be slowed or stopped in mostcases, the quality of life improved and the need for recurrent hospitalizationreduced. This will involve cooperation between internists, cardiologists, andnephrologists to allow early and maximal therapy of both the CHF and the anemia.

Capes SE, Gerstein HC, Negassa A, Yusuf S.Enalapril prevents clinical proteinuria in diabetic patients with low ejectionfraction.Diabetes Care. 2000 Mar;23(3):377-80.

 

Department of Medicine, McMaster University, Hamilton, Ontario, Canada.scapes@fhs.csu.mcmaster.ca

OBJECTIVE: Clinical proteinuria is a risk factor for both end-stage renaldisease and cardiovascular disease. The prevalence of clinical proteinuria, itscorrelates and predictive value, and the effect of ACE inhibitors in preventingclinical proteinuria in diabetic and nondiabetic patients with left ventricular(LV) dysfunction are unknown. RESEARCH DESIGN AND METHODS: The Studies of LeftVentricular Dysfunction (SOLVD) trials were analyzed to determine the baselinedistribution of clinical proteinuria and related cardiovascular risk factors,the effect of baseline proteinuria on the risk of hospitalization for congestive

heart failure (CHF) and mortality, and the effect of enalapril in preventing newclinical proteinuria. RESULTS: A total of 5,487 out of 6,797 SOLVD participants(81%) were assessed for proteinuria at baseline. A total of 177 patients (3.2%)had baseline proteinuria. These patients had significantly higher systolic (137vs. 125 mmHg, P < or = 0.001) and diastolic (83 vs. 77 mmHg, P < or = 0.001)blood pressure levels, a higher prevalence of diabetes (41 vs. 18%, P < or =0.001), a lower ejection fraction (26.2 vs. 27.3%, P < or = 0.05), and greaterdegree of CHF (New York Heart Association [NYHA] class III/IV in 22 vs. 10%, P <or = 0.001) than patients without baseline proteinuria. Patients with baselineproteinuria also had higher rates of hospitalization for CHF (relative risk 1.81[95% CI 1.37-2.41], P = 0.0001) and mortality (1.73 [1.34-2.24], P = 0.0001).Enalapril prevented clinical proteinuria in diabetic patients (0.38 [0.17-0.81],P = 0.0123) but not in nondiabetic patients (1.43 [0.77-2.63], P = 0.2622)without baseline proteinuria. CONCLUSIONS: Clinical proteinuria is anindependent predictor of hospitalization for CHF and mortality in diabetic andnondiabetic patients with LV dysfunction. Enalapril significantly reduces therisk of clinical proteinuria in diabetic patients with LV dysfunction.

Komajda M, Follath F, Swedberg K, Cleland J, Aguilar JC, Cohen-Solal A, Dietz R,Gavazzi A, Van Gilst WH, Hobbs R, Korewicki J, Madeira HC, Moiseyev VS, Preda I,Widimsky J, Freemantle N, Eastaugh J, Mason J; Study Group on Diagnosis of theWorking Group on Heart Failure of the European Society of Cardiology.The EuroHeart Failure Survey programme--a survey on the quality of care amongpatients with heart failure in Europe. Part 2: treatment.Eur Heart J. 2003 Mar;24(5):464-74. clicca qui per andare su PUBMED

BACKGROUND: National surveys suggest that treatment of heart failure in dailypractice differs from guidelines and is characterized by underuse of recommendedmedications. Accordingly, the Euro Heart Failure Survey was conducted toascertain how patients hospitalized for heart failure are managed in Europe andif national variations occur in the treatment of this condition. METHODS: Thesurvey screened discharge summaries of 11304 patients over a 6-week period in115 hospitals from 24 countries belonging to the ESC to study their medicaltreatment. RESULTS: Diuretics (mainly loop diuretics) were prescribed in 86.9%followed by ACE inhibitors (61.8%), beta-blockers (36.9%), cardiac glycosides(35.7%), nitrates (32.1%), calcium channel blockers (21.2%) and spironolactone(20.5%). 44.6% of the population used four or more different drugs. Only 17.2%were under the combination of diuretic, ACE inhibitors and beta-blockers.Important local variations were found in the rate of prescription of ACEinhibitors and particularly beta-blockers. Daily dosage of ACE inhibitors andparticularly of beta-blockers was on average below the recommended target dose.Modelling-analysis of the prescription of treatments indicated that theaetiology of heart failure, age, co-morbid factors and type of hospital wardinfluenced the rate of prescription. Age <70 years, male gender and ischaemicaetiology were associated with an increased odds ratio for receiving an ACE

inhibitor. Prescription of ACE inhibitors was also greater in diabetic patientsand in patients with low ejection fraction (<40%) and lower in patients withrenal dysfunction. The odds ratio for receiving a beta-blocker was reduced inpatients >70 years, in patients with respiratory disease and increased incardiology wards, in ischaemic heart failure and in male subjects. Prescriptionof cardiac glycosides was significantly increased in patients withsupraventricular tachycardia/atrial fibrillation. Finally, the rate ofprescription of antithrombotic agents was increased in the presence ofsupraventricular arrhythmia, ischaemic heart disease, male subjects but wasdecreased in patients over 70. CONCLUSION: Our results suggest that theprescription of recommended medications including ACE inhibitors andbeta-blockers remains limited and that the daily dosage remains low,particularly for beta-blockers. The survey also identifies several importantfactors including age, gender, type of hospital ward, co morbid factors whichinfluence the prescription of heart failure medication at discharge.

Hillege HL, van Gilst WH, van Veldhuisen DJ, Navis G, Grobbee DE, de Graeff PA,de Zeeuw D; CATS Randomized Trial.Accelerated decline and prognostic impact of renal function after myocardialinfarction and the benefits of ACE inhibition: the CATS randomized trial.Eur Heart J. 2003 Mar;24(5):412-20. clicca qui per andare su PUBMED

Comment in:Mann JF, Dulau-Florea I, Franke J.Looking for people at high cardiovascular risk? Look at serum-creatinineEur Heart J. 2003 Mar;24(5):381-3.clicca qui per andare su PUBMED

Department of Cardiology/Thoraxcenter, University Hospital Groningen, Hanzeplein1, 9700 Groningen, The Netherlands. h.hillege@tcc.azg.nl

AIMS: Information regarding the cardiorenal axis in patients after a myocardialinfarction (MI) is limited. We examined the change in renal function after afirst MI, the protective effect of angiotensin converting enzyme (ACE)inhibition and the prognostic value of baseline renal function. METHODS ANDRESULTS: The study population consisted of 298 patients with a first anteriorwall MI who were randomized to the ACE inhibitor captopril or placebo aftercompletion of streptokinase infusion. Renal function, by means of glomerularfiltration rate (GFR), was calculated using the Cockroft-Gault equation(GFR(c)). In the placebo group, renal function (GFR(c)) declined by 5.5min(-1)within 1 year, vs only 0.5 ml min(-1)in the ACE inhibitor group (P<0.05).This beneficial effect of captopril was most pronounced in patients with themost compromised renal function at baseline. The incidence of chronic heartfailure (CHF) within 1 year increased significantly with decreasingGFR(c)(divided into tertiles: 24.0, 28.9, and 41.2%; P<0.01). The risk-ratio forGFR(c)<81 ml min(-1)vs >103 mL min(-1)was 1.86 (95% CI 1.11-3.13; P=0.019).CONCLUSIONS: Renal function markedly deteriorates after a first MI, but issignificantly preserved by ACE inhibition. Furthermore, an impaired baselinerenal function adds to the prognostic risk of developing CHF in patients after afirst anterior MI.

Maxwell AP, Ong HY, Nicholls DP.Influence of progressive renal dysfunction in chronic heart failure.Eur J Heart Fail. 2002 Mar;4(2):125-30.clicca qui per andare su PUBMEDRegional Nephrology Unit, Belfast City Hospital, Northern Ireland, Belfast, UK.

Chronic heart failure (CHF) is often associated with impaired renal function due to hypoperfusion. Such patients are very sensitive to changes in renal perfusion pressure, and may develop acute tubular necrosis if the pressure falls too far. The situation is complicated by the use of diuretics, ACE inhibitors and spironolactone, all of which may affect renal function and potassium balance. Chronic renal failure (CRF) may also be associated with fluid overload. Anaemia and hypertension in CRF contribute to the development of left ventricular hypertrophy (LVH), which carries a poor prognosis, so correction of these factors is important.

Bouvy ML, Heerdink ER, Leufkens HG, Hoes AW.Predicting mortality in patients with heart failure: a pragmatic approach.Heart. 2003 Jun;89(6):605-9. clicca qui per andare su PUBMED

Comment in:Cowie MR.Estimating prognosis in heart failure: time for a better approach. Heart. 2003 Jun;89(6):587-8.clicca qui per andare su PUBMED

Department of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute forPharmaceutical Sciences, Utrecht, Netherlands. m.bouvy@pharm.uu.nl

OBJECTIVE: To develop a comprehensive and easily applicable prognostic modelpredicting mortality risk in patients with moderate to severe heart failure.DESIGN: Prospective follow up study. SETTING: Seven general hospitals in theNetherlands. PATIENTS: 152 outpatients with heart failure or patients admittedto hospital because of heart failure, who were included in a randomised trial toassess the impact of a pharmacist led intervention to improve drug compliance.Duration of follow up was at least 18 months. MAIN OUTCOME MEASURES:Multivariable logistic regression modelling was used to evaluate informationfrom history, physical examination (for example, blood pressure), drug use, andquality of life questionnaires that independently contributed to the predictionof death. The area under receiver operating characteristic curves (AUC) was used

to estimate the predictive ability of the prognostic models. RESULTS: During the18 months of follow up, 51 patients (34%) died. Independent predictors ofmortality were diabetes mellitus, a history of renal dysfunction (or highercreatinine), New York Heart Association (NYHA) functional class III or IV, lowerweight or body mass index, lower blood pressure, ankle oedema, and higher scoreson a disease specific quality of life questionnaire. The use of beta blockerswas predictive of a better prognosis. These factors were used to derive variousprediction formulas. A model based on medical history, weight, presence ofoedema, and lower blood pressure had an AUC of 0.77. Addition of use of betablockers to this model improved the AUC to 0.80. Addition of NYHA classincreased the AUC to 0.84. Data on quality of life did not improve the AUCfurther (AUC 0.85). CONCLUSIONS: A prognostic model produced on the basis ofeasily obtainable information from medical history and physical examination canadequately stratify heart failure patients according to their short term risk ofdeath.

Juenger J, Schellberg D, Kraemer S, Haunstetter A, Zugck C, Herzog W, Haass M.Health related quality of life in patients with congestive heart failure:comparison with other chronic diseases and relation to functional variables.Heart. 2002 Mar;87(3):235-41. clicca qui per andare su PUBMED

Departments of General Internal and Psychosomatic Medicine, University ofHeidelberg, Heidelberg, Germany. jana_juenger@med.uni-heidelberg.de

OBJECTIVE: To assess health related quality of life of patients with congestiveheart failure; to compare their quality of life with the previouslycharacterised general population and in those with other chronic diseases; andto correlate the different aspects of quality of life with relevant somaticvariables. SETTING: University hospital. PATIENTS AND DESIGN: A German versionof the generic quality of life measure (SF-36) containing eight dimensions wasadministered to 205 patients with congestive heart failure and systolicdysfunction. Cardiopulmonary evaluation included assessment of New York HeartAssociation (NYHA) functional class, left ventricular ejection fraction, peakoxygen uptake, and the distance covered during a standardised six minute walktest. RESULTS: Quality of life significantly decreased with NYHA functionalclass (linear trend: p < 0.0001). In NYHA class III, the scores of five of theeight quality of life domains were reduced to around one third of those in thegeneral population. The pattern of reduction was different in patients withchronic hepatitis C and major depression, and similar in patients on chronichaemodialysis. Multiple regression analysis showed that only the NYHA functionalclass was consistently and closely associated with all quality of life scales.The six minute walk test and peak oxygen uptake added to the explanation of thevariance in only one of the eight quality of life domains (physicalfunctioning). Left ventricular ejection fraction, duration of disease, and ageshowed no clear association with quality of life. CONCLUSIONS: In congestiveheart failure, quality of life decreases as NYHA functional class worsens.Though NYHA functional class was the most dominant predictor among the somaticvariables studied, the major determinants of reduced quality of life remainunknown.

Silverberg DS, Wexler D, Blum M, Schwartz D, Keren G, Sheps D, Iaina AEffect of correction of anemia with erythropoietin and intravenous iron inresistant heart failure in octogenarians.Isr Med Assoc J. 2003 May;5(5):337-9. clicca qui per andare su PUBMED

Department of Nephrology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.donald@netvision.net.il

BACKGROUND: Congestive heart failure is extremely common in octogenarians and isassociated with severe fatigue, shortness of breath, recurrent hospitalizations,and death. These patients, many of whom are anemic, are often resistant tostandard CHF therapy including angiotensin-converting enzyme inhibitors,beta-blockers and diuretics. OBJECTIVES: To examine whether correction of theanemia (hemoglobin < 12 g/dl) in CHF patients can improve their clinicalcondition. METHODS: Forty octogenarians with anemia and severe resistant CHFwere administered a combination of subcutaneous erythropoietin and intravenousiron sucrose. RESULTS: This combination therapy led to a marked improvement incardiac function, shortness of breath and fatigue, a marked reduction in therate of hospitalization and a stabilizing of renal function. CONCLUSION: Anemiaappears to be an important but ignored contributor to the progression of CHF,and its correction may improve cardiac and renal status as well as the qualityof life in elderly patients.

Troughton RW, Prior DL, Pereira JJ, Martin M, Fogarty A, Morehead A, Yandle TG,Richards AM, Starling RC, Young JB, Thomas JD, Klein AL.Plasma B-type natriuretic peptide levels in systolic heart failure: importanceof left ventricular diastolic function and right ventricular systolic function.J Am Coll Cardiol. 2004 Feb 4;43(3):416-22. clicca qui per andare su PUBMEDDepartment of Cardiovascular Medicine, Cleveland Clinic Foundation, 9500 EuclidAvenue, Cleveland, Ohio 44195, USA.

OBJECTIVES: This study was designed to characterize the importance ofechocardiographic indexes, including newer indexes of diastolic function, asdeterminants of plasma B-type natriuretic peptide (BNP) levels in patients withsystolic heart failure (SHF). BACKGROUND: Plasma BNP levels have utility fordiagnosing and managing heart failure. However, there is significantheterogeneity in BNP levels that is not explained by left ventricular size andfunction alone. METHODS: In 106 patients with symptomatic SHF (left ventricularejection fraction [LVEF] <0.35), we measured plasma BNP levels and performedcomprehensive echocardiography with assessment of left ventricular diastolicfunction, including color M-mode (CMM) and tissue Doppler imaging (TDI), and ofright ventricular (RV) function. RESULTS: Median plasma BNP levels were elevatedand increased with greater severity of diastolic dysfunction. We foundsignificant correlations (p < 0.001 for all) between BNP and indexes ofmyocardial relaxation (early diastolic velocity: r = -0.26), compliance(deceleration time: r = -0.55), and filling pressure (early transmitral to early

annular diastolic velocity ratio: r = 0.51; early transmitral flow to thevelocity of early left ventricular flow propagation ratio: r = 0.41). Inmultivariate analysis, overall diastolic stage, LVEF, RV systolic dysfunction,mitral regurgitation (MR) severity, age and creatinine clearance wereindependent predictors of BNP levels (model fit r = 0.8, p < 0.001).CONCLUSIONS: Plasma BNP levels are significantly related to newer diastolicindexes measured from TDI and CMM in SHF. Heterogeneity of BNP levels inpatients with SHF reflects the severity of diastolic abnormality, RVdysfunction, and MR in addition to LVEF, age, and renal function. These findingsmay explain the powerful relationship of BNP to symptoms and prognosis in SHF.

Forman DE, Butler J, Wang Y, Abraham WT, O'Connor CM, Gottlieb SS, Loh E, MassieBM, Rich MW, Stevenson LW, Young JB, Krumholz HM.Incidence, predictors at admission, and impact of worsening renal function amongpatients hospitalized with heart failure.J Am Coll Cardiol. 2004 Jan 7;43(1):61-7. clicca qui per andare su PUBMED

Section of Cardiology, Boston Medical Center, Boston, Massachusetts 02188, USA.Daniel.Forman@bmc.org

OBJECTIVES: The goal of this study was to determine the prevalence of worseningrenal function (WRF) among hospitalized heart failure (HF) patients, clinicalpredictors of WRF, and hospital outcomes associated with WRF. BACKGROUND:Impaired renal function is associated with poor outcomes among chronic HFpatients. METHODS: Chart reviews were performed on 1,004 consecutive patientsadmitted for a primary diagnosis of HF from 11 geographically diverse hospitals.Cox regression model analysis was used to identify independent predictors forWRF, defined as a rise in serum creatinine of >0.3 mg/dl (26.5 micromol/l).Bivariate analysis was used to determine associations of development of WRF withoutcomes (in-hospital death, in-hospital complications, and length of stay).RESULTS: Among 1,004 HF patients studied, WRF developed in 27%. In the majorityof cases, WRF occurred within three days of admission. History of HF or diabetesmellitus, admission creatinine > or =1.5 mg/dl (132.6 micromol/l), and systolicblood pressure >160 mm Hg were independently associated with higher risk of WRF.A point score based on these characteristics and their relative risk ratiospredicted those at risk for WRF. Hospital deaths (adjusted risk ratio [ARR] 7.5;95% confidence intervals [CI] 2.9, 19.3), complications (ARR 2.1; CI 1.5, 3.0),and length of hospitalizations >10 days (ARR 3.2, CI 2.2, 4.9) were greateramong patients with WRF. CONCLUSIONS: Worsening renal function occurs frequentlyamong hospitalized HF patients and is associated with significantly worseoutcomes. Clinical characteristics available at hospital admission can be usedto identify patients at increased risk for developing WRF.

Gibson CM, Pinto DS, Murphy SA, Morrow DA, Hobbach HP, Wiviott SD, Giugliano RP,Cannon CP, Antman EM, Braunwald E; TIMI Study Group.Association of creatinine and creatinine clearance on presentation in acutemyocardial infarction with subsequent mortality.J Am Coll Cardiol. 2003 Nov 5;42(9):1535-43. clicca qui per andare su PUBMEDTIMI Study Chairman's Office, Department of Medicine, Brigham and Women'sHospital, Boston, MA, USA. mgibson@tini.org

Comment in:French WJ, Wright RS.Renal insufficiency and worsened prognosis with STEMI: a call for action.J Am Coll Cardiol. 2003 Nov 5;42(9):1544-6.clicca qui per andare su PUBMED

OBJECTIVES: We hypothesized that impaired renal function would also beassociated with poorer clinical outcomes among patients with ST-segmentelevation myocardial infarction (STEMI) treated with fibrinolysis. BACKGROUND:Previous studies have demonstrated that impaired renal function is associatedwith poorer clinical outcomes in the setting of unstable angina and non-STEMIand after percutaneous coronary intervention. METHODS: Data were drawn from theThrombolysis In Myocardial Infarction (TIMI)-10, TIMI-14, and Intravenous nPAfor the Treatment of Infarcting Myocardium Early (InTIME-II) trials. RESULTS:Within each TIMI risk score (TRS) for STEMI category (0 to 2, 3 to 4, >/=5),30-day mortality increased stepwise among patients with normal (creatinine [Cr]</=1.2 mg/dl), mildly (Cr >1.2 to 2 mg/dl), and severely (Cr >2.0 mg/dl)impaired renal function (p < 0.001) and in patients with normal (creatinineclearance [CrCl] >/=90 ml/min), mildly (60 to <90 ml/min), moderately (30 to <60ml/min), and severely (<30 ml/min) impaired CrCl (p < 0.001). Impaired renalfunction was associated with increased mortality after adjusting for previouslyidentified correlates of mortality (using Cr: odds ratio [OR] for mildimpairment 1.52, 95% confidence interval [CI] 1.30 to 1.77, p < 0.001; OR forsevere impairment 3.73, 95% CI 2.55 to 5.45, p < 0.001; using CrCl: OR for mildimpairment 1.38, 95% CI 1.10 to 1.73, p = 0.006; OR for moderate impairment2.06, 95% CI 1.59 to 2.66, p < 0.001; OR for severe impairment 3.81, 95% CI 2.57to 5.65, p < 0.001). CONCLUSIONS: In the setting of STEMI, elevated Cr and/orimpaired CrCl on presentation is associated with increased mortality,independent of other conventional risk factors and TRS. This association doesnot appear to be mediated by reduced fibrinolytic efficacy among patients withimpaired renal function or by the presence of congestive heart failure onpresentation.

Kittleson M, Hurwitz S, Shah MR, Nohria A, Lewis E, Givertz M, Fang J, Jarcho J,Mudge G, Stevenson LW.Development of circulatory-renal limitations to angiotensin-converting enzymeinhibitors identifies patients with severe heart failure and early mortality.J Am Coll Cardiol. 2003 Jun 4;41(11):2029-35. clicca qui per andare su PUBMED

Departments of Medicine and Cardiology, Brigham and Women's Hospital, 75 FrancisStreet, Boston, MA 02115, USA.

OBJECTIVES: This study examined the hypothesis that patients who developangiotensin-converting enzyme inhibitor intolerance attributable tocirculatory-renal limitations (CRLimit) have more severe underlying disease andworse outcome. BACKGROUND: Although the renin-angiotensin system contributes tothe progression of heart failure (HF), it also supports the failing circulation.Patients with the most severe disease may not tolerate inhibition of thissystem. METHODS: Consecutive inpatient admissions to the cardiomyopathy serviceof the Brigham and Women's Hospital between 2000 and 2002 were reviewedretrospectively for initial profiles, discharge medications, and documentedreasons for discontinuation of angiotensin-converting enzyme inhibitors.Outcomes of death and transplantation were determined. RESULTS: Of the 259patients, 86 were not on an angiotensin-converting enzyme inhibitor atdischarge. Circulatory-renal limitations of symptomatic hypotension, progressiverenal dysfunction, or hyperkalemia were documented in 60 patients (23%); otheradverse effects, including cough, in 24 patients; and absent reasons in 2patients. Compared with patients on angiotensin-converting enzyme inhibitors,patients with CRLimit were older (60 vs. 55 years; p = 0.006), with longerhistory of HF (5 vs. 2 years; p = 0.009), lower systolic blood pressure (104 vs.110 mm Hg; p = 0.05), lower sodium (135 vs. 138 mEql/l; p = 0.002), and higherinitial creatinine (2.5 vs. 1.2 mg/dl; p = 0.0001). Mortality was 57% inpatients with CRLimit and 22% in the patients on angiotensin-converting enzyme

inhibitors during a median 8.5-month follow-up (p = 0.0001). CONCLUSIONS:Development of CRLimit to angiotensin-converting enzyme inhibitor intoleranceidentifies patients with severe disease who are likely to die during the nextyear. New treatment strategies should be targeted to this population.

Fried LF, Shlipak MG, Crump C, Bleyer AJ, Gottdiener JS, Kronmal RA, Kuller LH, Newman AB.Renal insufficiency as a predictor of cardiovascular outcomes and mortality in elderly individuals.J Am Coll Cardiol. 2003 Apr 16;41(8):1364-72.clicca qui per andare su PUBMEDRenal Section, VA Pittsburgh Healthcare System, Pennsylvania 15240, USA. lff9+@pitt.edu

OBJECTIVES: This study was designed to evaluate the relationship between elevated creatinine levels and cardiovascular events. BACKGROUND: End-stage renal disease is associated with high cardiovascular morbidity and mortality. The association of mild to moderate renal insufficiency with cardiovascular outcomes remains unclear. METHODS: We analyzed data from the Cardiovascular Health Study, a prospective population-based study of subjects, aged >65 years, who had a serum creatinine measured at baseline (n = 5,808) and were followed for a median of 7.3 years. Proportional hazards models were used to examine the association of creatinine to all-cause mortality and incident cardiovascular mortality and morbidity. Renal insufficiency was defined as a creatinine level > or =1.5 mg/dl in men or > or =1.3 mg/dl in women. RESULTS: An elevated creatinine level was present in 648 (11.2%) participants. Subjects with elevated creatinine had higher overall (76.7 vs. 29.5/1,000 years, p < 0.001) and cardiovascular (35.8 vs. 13.0/1,000 years, p < 0.001) mortality than those with normal creatinine levels. They were more likely to develop cardiovascular disease (54.0 vs. 31.8/1,000 years, p < 0.001), stroke (21.1 vs. 11.9/1,000 years, p < 0.001), congestive heart failure (38.7 vs. 17/1,000 years, p < 0.001), and symptomatic peripheral vascular disease (10.6 vs. 3.5/1,000 years, p < 0.001). After adjusting for cardiovascular risk factors and subclinical disease measures, elevated creatinine remained a significant predictor of all-cause and cardiovascular mortality, total cardiovascular disease (CVD), claudication, and congestive heart failure (CHF). A linear increase in risk was observed with increasing creatinine. CONCLUSIONS: Elevated creatinine levels are common in older adults and are associated with increased risk of mortality, CVD, and CHF. The increased risk is apparent early in renal disease.

Khot UN, Mishra M, Yamani MH, Smedira NG, Paganini E, Yeager M, Buda T, McCarthyPM, Young JB, Starling RC.Severe renal dysfunction complicating cardiogenic shock is not acontraindication to mechanical support as a bridge to cardiac transplantation.J Am Coll Cardiol. 2003 Feb 5;41(3):381-5. clicca qui per andare su PUBMED

Department of Cardiovascular Medicine, Kaufman Center for Heart Failure, TheCleveland Clinic Foundation, Cleveland, Ohio, USA. khot@cvresearch.net

OBJECTIVES: This study investigated outcomes in patients with cardiogenic shockand severe renal dysfunction treated with ventricular assist devices (VAD) as abridge to cardiac transplantation. BACKGROUND: Previous reports have documentedpoor survival in patients with cardiogenic shock and severe renal dysfunctiontreated with VAD. METHODS: We surveyed 215 consecutive patients who received aVAD from 1992 to 2000 and selected patients who had a serum creatinine > or =3.0mg/dl at the time of VAD placement. Demographic, laboratory, and clinicaloutcome data were collected. RESULTS: Eighteen patients met the inclusion

criteria. Mean serum creatinine at the time of VAD placement was 4.0 +/- 0.7mg/dl (range 3.0 to 5.2 mg/dl). Seven patients required temporary renal supportwith continuous venovenous hemodialysis (CVVHD). Eleven patients underwentcardiac transplantation. At six months post-transplantation, mean serumcreatinine was 2.0 +/- 0.6 mg/dl (range 1.3 to 3.5 mg/dl). None of thetransplanted patients required subsequent renal support. Seven patients diedwith a VAD before transplantation. Three died early (<1 month) after VADplacement, and all three required CVVHD until death. Four patients survived for>1 month after VAD placement; all four had resolution of renal dysfunction withmean serum creatinine of 1.9 +/- 1.2 mg/dl (range 0.8 to 3.6 mg/dl) without theneed for renal support. Overall 30-day and six-month survival after VADplacement, survival to transplantation, and survival one yearpost-transplantation were similar to patients without severe renal dysfunction.CONCLUSIONS: Contemporary use of VAD leads to resolution of severe renaldysfunction in most cardiogenic shock patients and comparable long-term outcomesto patients without renal dysfunction.

Mahon NG, Blackstone EH, Francis GS, Starling RC 3rd, Young JB, Lauer MS.The prognostic value of estimated creatinine clearance alongside functionalcapacity in ambulatory patients with chronic congestive heart failure.J Am Coll Cardiol. 2002 Sep 18;40(6):1106-13. clicca qui per andare su PUBMED

Comment in:Lepor NE.Renal insufficiency. The prognostic value of renal function in patients with congestive heart failure and acute myocardial infarction.Rev Cardiovasc Med. 2003 Summer;4(3):192-4.

 

Cardiology, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.

OBJECTIVES: The goal of this study was to determine the prognostic significanceof estimated creatinine clearance (CrCl) in relation to 6-min walk distance inambulatory patients with congestive heart failure (HF). BACKGROUND: Althoughmeasurement of renal function is integral to the management of chroniccongestive HF, its prognostic implications are not well described and have notbeen formally evaluated relative to measures of functional capacity. METHODS: Weanalyzed outcomes of the 585 participants of the 6-min walk substudy of theDigitalis Investigation Group (DIG) trial. The CrCl was estimated using theCockcroft-Gault equation. Predictors of all-cause mortality were identifiedusing semiparametric Cox proportional hazards regression and completelyparametric hazard analyses. RESULTS: Most subjects (85%) were New York HeartAssociation functional class II and III. Mean age was 65 (+/-12) years and meanejection fraction (EF) 35% (+/-13%). There were 153 (26%) deaths during a medianof 2.6 years of follow-up. Mortality by increasing quartiles of estimated CrClwas 37% (18 to 48 ml/min), 29% (47 to 64 ml/min), 18% (64 to 86 ml/min), and 21%(86 to 194 ml/min) with corresponding hazard ratios (HRs) relative to the topquartile of 2.1 (95% confidence interval [CI], 1.4 to 3.3), 1.6 (95% CI, 1.0 to2.5), and 0.9 (95% CI, 0.5 to 1.5), respectively. In Cox regression analyses,independent predictors of mortality were estimated CrCl (adjusted HR [quartile1:quartile 4] 1.5; 95% CI, 1.1 to 2.1), 6-min walk distance < or =262 m[adjusted HR, 1.63; 95% CI, 1.12 to 2.27]), EF, recent hospitalization forworsening HF, and need for diuretic treatment. Parametric (hazard) analysisconfirmed consistent effects of estimated CrCl on mortality in several subgroupsincluding that of patients with EF >45%. CONCLUSION: In ambulatory patients withcongestive HF, estimated CrCl predicts all-cause mortality independently ofestablished prognostic variables.

Kearney MT, Fox KA, Lee AJ, Prescott RJ, Shah AM, Batin PD, Baig W, Lindsay S, Callahan TS, Shell WE, Eckberg DL, Zaman AG, Williams S, Neilson JM, Nolan J.Predicting death due to progressive heart failure in patients with mild-to-moderate chronic heart failure.J Am Coll Cardiol. 2002 Nov 20;40(10):1801-8clicca qui per andare su PUBMEDDepartment of Cardiology, GKT School of Medicine, King's College London, Bessemer Road, Denmark Hill, London SE5 9PJ, United Kingdom. mark.kearney@kcl.ac.uk

OBJECTIVES: The aim of this study was to explore the value of noninvasive predictors of death/mode of death in ambulant outpatients with chronic heart failure (HF). BACKGROUND: Mortality in chronic HF remains high, with a significant number of patients dying of progressive disease. Identification of these patients is important. METHODS: We recruited 553 ambulant outpatients age 63 +/- 10 years with symptoms of chronic HF (New York Heart Association functional class, 2.3 +/- 0.5) and objective evidence of left ventricular dysfunction (ejection fraction <45%, cardiothoracic ratio >0.55, or pulmonary edema on chest radiograph). After 2,365 patient-years of follow-up, 201 patients had died, with 76 events due to progressive HF. RESULTS: Independent predictors of all-cause mortality assessed with the Cox proportional hazards model were as follows: a low standard deviation of all normal-to-normal RR intervals (SDNN); lower serum sodium and higher creatinine levels; higher cardiothoracic ratio; nonsustained ventricular tachycardia; higher left ventricular end-systolic diameter; left ventricular hypertrophy; and increasing age. Independent predictors of death specific to progressive HF were SDNN, serum sodium and creatinine levels. The hazard ratio of progressive HF death for a 10% decrease in SDNN was 1.06 (95% confidence interval [CI], 1.01 to 1.12); for a 2 mmol/l decrease in serum sodium, 1.22 (95% CI, 1.08 to 1.38); and for a 10 micromol/l increase in serum creatinine, 1.14 (95% CI, 1.09 to 1.19) (all p < 0.01). CONCLUSIONS: In ambulant outpatients with chronic HF, low serum sodium and SDNN and high serum creatinine identify patients at increased risk of death due to progressive HF.

283: Redfield MM, Rodeheffer RJ, Jacobsen SJ, Mahoney DW, Bailey KR, Burnett JC Jr.Plasma brain natriuretic peptide concentration: impact of age and gender.J Am Coll Cardiol. 2002 Sep 4;40(5):976-82.clicca qui per andare su PUBMED

Division of Cardiovascular Diseases, Mayo Clinic and Foundation, Rochester,Minnesota 55905, USA. redfield.margaret@mayo.edu

OBJECTIVES: We wished to examine the effects of age and gender on plasma brainnatriuretic peptide (BNP) concentration in a population-based study. BACKGROUND:Measurement of BNP concentration is approved for use in the diagnosis of heartfailure and may aid in the detection of left ventricular dysfunction. AlthoughBNP is approved for clinical use, there are few data regarding the range of BNPobserved in persons without cardiovascular disease or cardiac dysfunction. Thesedata are essential for the interpretation of BNP. METHODS: In 2,042 randomlyselected residents of Olmsted County, Minnesota, >44 years old, BNP (Shionogiand Biosite assays), Doppler echocardiography, and medical record review wereperformed. A normal subset of subjects (n = 767) in sinus rhythm withoutcardiovascular, renal, or pulmonary disease or diabetes; on no cardiovascularmedications; and with normal systolic, diastolic, and valvular function wasidentified. RESULTS: Within the normal subset, the distribution of BNP differedby age, gender, and assay system. With both assays, BNP increased significantlywith age and was significantly higher in women than men, leading to age-,gender-, and assay-specific reference ranges. Receiver operating characteristic

analysis for the ability of BNP to detect an ejection fraction < or = 40% wasperformed in each age/gender stratum in the entire cohort (n = 2,042) andconfirmed that discriminatory values for BNP for detection of reduced ejectionfraction were higher in women and older persons and were different between thetwo assays. CONCLUSIONS: Interpretation of BNP should include consideration ofage-, gender-, and assay-specific partition values.

Krumholz HM, Chen J, Chen YT, Wang Y, Radford MJ.Predicting one-year mortality among elderly survivors of hospitalization for anacute myocardial infarction: results from the Cooperative CardiovascularProject.J Am Coll Cardiol. 2001 Aug;38(2):453-9. clicca qui per andare su PUBMED

Comment in:Teo KK, Catellier DJ.Risk prediction after myocardial infarction in the elderly J Am Coll Cardiol. 2001 Aug;38(2):460-3.clicca qui per andare su PUBMED

Department of Medicine, Yale University School of Medicine, New Haven,Connecticut 06520-8025, USA.

OBJECTIVES: We sought to develop a model based on information available from themedical record that would accurately stratify elderly patients who survivehospitalization with an acute myocardial infarction (AMI) according to theirrisk of one-year mortality. BACKGROUND: Prediction of the risk of mortalityamong older survivors of an AMI has many uses, yet few studies have determinedthe prognostic importance of demographic, clinical and functional data that areavailable on discharge in a population-based sample. METHODS: In a cohort ofpatients aged > or = 65 years who survived hospitalization for a confirmed AMIfrom 1994 to 1995 at acute care, nongovernmental hospitals in the U.S., wedeveloped a parsimonious model to stratify patients by their risk of one-yearmortality. RESULTS: The study sample of 103,164 patients, with a mean age of76.8 years, had a one-year mortality of 22%. The factors with the strongestassociation with mortality were older age, urinary incontinence, assistedmobility, presence of heart failure or cardiomegaly any time before discharge,presence of peripheral vascular disease, body mass index <20 kg/m2, renaldysfunction (defined as creatinine >2.5 mg/dl or blood urea nitrogen >40 mg/dl)and left ventricular dysfunction (left ventricular ejection fraction <40%). Onthe basis of the coefficients in the model, patients were stratified into riskgroups ranging from 7% to 49%. CONCLUSIONS: We demonstrate that a simple riskmodel can stratify older patients well by their risk of death one year afterdischarge for AMI.

Silverberg DS, Wexler D, Blum M, Keren G, Sheps D, Leibovitch E, Brosh D,Laniado S, Schwartz D, Yachnin T, Shapira I, Gavish D, Baruch R, Koifman B,Kaplan C, Steinbruch S, Iaina A.The use of subcutaneous erythropoietin and intravenous iron for the treatment ofthe anemia of severe, resistant congestive heart failure improves cardiac andrenal function and functional cardiac class, and markedly reduces hospitalizations.J Am Coll Cardiol. 2000 Jun;35(7):1737-44. clicca qui per andare su PUBMEDDepartment of Nephrology and Cardiology, Tel Aviv Medical Center, Israel.

OBJECTIVES: This study evaluated the prevalence and severity of anemia inpatients with congestive heart failure (CHF) and the effect of its correction on

cardiac and renal function and hospitalization. BACKGROUND: The prevalence andsignificance of mild anemia in patients with CHF is uncertain, and the role oferythropoietin with intravenous iron supplementation in treating this anemia isunknown. METHODS: In a retrospective study, the records of the 142 patients inour CHF clinic were reviewed to find the prevalence and severity of anemia(hemoglobin [Hb] <12 g). In an intervention study, 26 of these patients, despitemaximally tolerated therapy of CHF for at least six months, still had had severeCHF and were also anemic. They were treated with subcutaneous erythropoietin andintravenous iron sufficient to increase the Hb to 12 g%. The doses of the CHFmedications, except for diuretics, were not changed during the interventionperiod. RESULTS: The prevalence of anemia in the 142 patients increased with theseverity of CHF, reaching 79.1% in those with New York Heart Association classIV. In the intervention study, the anemia of the 26 patients was treated for amean of 7.2 +/- 5.5 months. The mean Hb level and mean left ventricular ejectionfraction increased significantly. The mean number of hospitalizations fell by91.9% compared with a similar period before the study. The New York HeartAssociation class fell significantly, as did the doses of oral and intravenousfurosemide. The rate of fall of the glomerular filtration rate slowed with thetreatment. CONCLUSIONS: Anemia is very common in CHF and its successfultreatment is associated with a significant improvement in cardiac function,functional class, renal function and in a marked fall in the need for diureticsand hospitalization.

Dries DL, Exner DV, Domanski MJ, Greenberg B, Stevenson LW.The prognostic implications of renal insufficiency in asymptomatic andsymptomatic patients with left ventricular systolic dysfunction.J Am Coll Cardiol. 2000 Mar 1;35(3):681-9. clicca qui per andare su PUBMED

Division of Cardiology, Brigham and Women's Hospital, Boston, Massachusetts02115, USA.

OBJECTIVES: The present analysis examines the prognostic implications ofmoderate renal insufficiency in patients with asymptomatic and symptomatic leftventricular systolic dysfunction. BACKGROUND: Chronic elevations in intracardiacfilling pressures may lead to progressive ventricular dilation and heart failureprogression. The ability to maintain fluid balance and prevent increasedintracardiac filling pressures is critically dependent on the adequacy of renalfunction. METHODS: This is a retrospective analysis of the Studies of LeftVentricular Dysfunction (SOLVD) Trials, in which moderate renal insufficiency isdefined as a baseline creatinine clearance <60 ml/min, as estimated from theCockroft-Gault equation. RESULTS: In the SOLVD Prevention Trial, multivariateanalyses demonstrated moderate renal insufficiency to be associated with anincreased risk for all-cause mortality (Relative Risk [RR] 1.41; p = 0.001),

largely explained by an increased risk for pump-failure death (RR 1.68; p =0.007) and the combined end point death or hospitalization for heart failure (RR1.33; p = 0.001). Likewise, in the Treatment Trial, multivariate analysesdemonstrated moderate renal insufficiency to be associated with an increasedrisk for all-cause mortality (RR 1.41; p = 0.001), also largely explained by anincreased risk for pump-failure death (RR 1.49; p = 0.007) and the combined endpoint death or hospitalization for heart failure (RR 1.45; p = 0.001).CONCLUSIONS: Even moderate degrees of renal insufficiency are independentlyassociated with an increased risk for all-cause mortality in patients with heartfailure, largely explained by an increased risk of heart failure progression.These data suggest that, rather than simply being a marker of the severity ofunderlying disease, the adequacy of renal function may be a primary determinantof compensation in patients with heart failure, and therapy capable of improvingrenal function may delay disease progression.

Ruilope LM, van Veldhuisen DJ, Ritz E, Luscher TF.Renal function: the Cinderella of cardiovascular risk profile.J Am Coll Cardiol. 2001 Dec;38(7):1782-7.clicca qui per andare su PUBMEDUnidad de Hipertension, Hospital 12 de Octubre, Madrid, Spain. Luis_M_Ruilope@teleline.es

The presence of an altered renal function in essential hypertension, advanced heart failure (HF) and after a myocardial infarction (MI) is associated with higher cardiovascular morbidity and mortality. Indices of altered renal function (e.g., microalbuminuria, increased serum creatinine concentrations, decrease in estimated creatinine clearance or overt proteinuria) are independent predictors of cardiovascular morbidity and mortality in any of the three clinical situations. These parameters should then be routinely evaluated in clinical practice. These facts have several therapeutic implications. First, although there is no evidence-based information on the level of blood pressure that confers optimal renal protection, levels substantially lower than past recommendations are advisable. Second, hypertensive kidney damage should be prevented by early treatment of hypertensive patients, particularly those with microalbuminuria. Finally, to avoid further aggravation of high cardiovascular risk, antihypertensive agents devoid of unwanted metabolic side effects should be used for the treatment of hypertensive vascular damage. In HF, the combination of an angiotensin-converting enzyme (ACE) inhibitor and a beta-blocker seem to be the most renoprotective. Renal outcome is also improved by ACE inhibition after an MI. Finally, renal and cardiovascular outcome seem to run in parallel in all these situations.

Mills RM, LeJemtel TH, Horton DP, Liang C, Lang R, Silver MA, Lui C, ChatterjeeK.Sustained hemodynamic effects of an infusion of nesiritide (human b-typenatriuretic peptide) in heart failure: a randomized, double-blind,placebo-controlled clinical trial. Natrecor Study Group.J Am Coll Cardiol. 1999 Jul;34(1):155-62clicca qui per andare su PUBMED

Division of Cardiovascular Medicine, University of Florida, Gainesville, USA.

OBJECTIVES: The goal of this study was to further define the role of nesiritide(human b-type natriuretic peptide) in the therapy of decompensated heart failure(HF) by assessing the hemodynamic effects of three doses (0.015, 0.03 and 0.06microg/kg/min) administered by continuous intravenous (IV) infusion over 24 h ascompared with placebo. BACKGROUND: Previous studies have shown beneficialhemodynamic, neurohormonal and renal effects of bolus dose and 6-h infusionadministration of nesiritide in HF patients. Longer term safety and efficacyhave not been studied. METHODS: This randomized, double-blind,placebo-controlled multicenter trial enrolled subjects with symptomatic HF andsystolic dysfunction (left ventricular ejection fraction < or =35%). Centralhemodynamics were assessed at baseline, during a 24-h IV infusion and for 4 hpostinfusion. RESULTS: One hundred three subjects with New York HeartAssociation class II (6%), III (61%) or IV (33%) HF were enrolled. Nesiritideproduced significant reductions in pulmonary wedge pressure (27% to 39% decreaseby 6 h), mean right atrial pressure and systemic vascular resistance, along withsignificant increases in cardiac index and stroke volume index, with nosignificant effect on heart rate. Beneficial effects were evident at 1 h andwere sustained throughout the 24-h infusion. CONCLUSIONS: The rapid andsustained beneficial hemodynamic effects of nesiritide observed in this studysupport its use as a first-line IV therapy for patients with symptomaticdecompensated HF.

Ahmed A.Use of angiotensin-converting enzyme inhibitors in patients with heart failure and renal insufficiency: how concerned should we be by the rise in serum creatinine?J Am Geriatr Soc. 2002 Jul;50(7):1297-300.clicca qui per andare su PUBMEDDivision of Gerontology/Geriatric Medicine, Department of Medicine, School of Medicine, Center for Aging, University of Alabama at Birmingham, 35294, USA. aahmed@uab.edu

PURPOSE: To determine the association between the early rise in serum creatinine levels associated with the use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) and the long-term renoprotective properties of these drugs in patients with chronic renal insufficiency. BACKGROUND: Large-scale clinical trials have demonstrated survival benefits of ACE inhibitors in patients with heart failure. In patients with renal insufficiency, whether associated with diabetes mellitus or not, use of ACE inhibitors is associated with slowing in the progression of renal disease. In fact, patients who have the most advanced renal insufficiency at baseline are the ones who show the maximum slowing of the disease progression, but these patients are also more likely to show an early rise in serum creatinine levels after ACE inhibitor therapy. There is evidence that patients with renal insufficiency often do not receive ACE inhibitors. There is also evidence that patients with heart failure are not receiving this life-saving drug or are receiving it at dosages lower than that used in the clinical trials. One of the main reasons for this underutilization of ACE inhibitors in patients with heart failure is the underlying renal insufficiency or the rise in serum creatinine level after initiation of therapy with an ACE inhibitor. METHODS: The authors reviewed 12 randomized clinical trials of ACE inhibitor or ARB therapy in patients with preexisting chronic renal insufficiency, with or without diabetes mellitus or heart failure. Studies were included for review if they met the following criteria: subjects were randomized to receive ACE inhibitor; subjects were followed up for a minimum of 2 years; and most of the subjects had baseline chronic renal insufficiency (>or=25% loss of renal function), irrespective of cause. Of the 12 studies that met these criteria, six were multicenter double-blind placebo-controlled studies. The other six were smaller randomized studies. The studies had a mean +/- standard deviation follow-up of 3.2 +/- 0.3 years. One thousand one hundred two patients were randomized to receive ACE inhibitors or ARBs. Of these, 705 (64%) had data on renal function at baseline (within 6 months of the start) and at the end of the study. The authors examined the changes in serum creatinine levels or glomerular filtration rates (GFR) in patients who were randomized to receive ACE inhibitors. The authors also assessed the blood pressures achieved in the trials. RESULTS: Patients with preexisting chronic renal insufficiency who achieved their blood pressure control goals were likely to demonstrate an early rise in serum creatinine levels, approximately 25% above the baseline (approximately 1.7 mg/dL) after initiation of ACE inhibitor or ARB therapy. This rise in serum creatinine was more acute (by approximately 15% from the baseline) during the first 2 weeks of therapy and was more gradual (additional approximately 10%) during the third and fourth weeks of therapy (Figure 1). The serum creatinine level was likely to stabilize after about 4 weeks, provided patients had a normal salt and fluid

intake. In addition, patients who did not show a rise in serum creatinine level during the first 2 to 4 weeks of therapy, were less likely to experience one after that period, unless they were dehydrated from use of diuretics or gastroenteritis or had used a nonsteroidal antiinflammatory drug (NSAID). In spite of this early rise in serum creatinine in patients with chronic renal insufficiency (a serum creatinine level of >or=124 micromol/L or >or=1.4 mg/dL) who were randomized to receive an ACE inhibitor, these patients receiving the drug showed a 55% to 75% lower risk of worsening renal function than those with normal renal function receiving the drug. The rate of risk reduction was inversely related to the severity of renal impairment at baseline, but data were limited on the benefit of ACE inhibitors in patients with more advanced renal insufficiency (GFR <30 mL/min). The authors noted that those aged 65 and older were likely to have much lower GFRs for given levels of serum creatinine than younger patients and were therefore likely to have advanced renal insufficiency at serum creatinine levels as low as 2 mg/dL (vs 4 mg/dL for younger patients). Patients with normal renal function were likely to show a much smaller rise in serum creatinine level (approximately 10% above the baseline of 0.9 mg/dL), mostly occurring during the first week after initiation of therapy, with subsequent stabilization, whereas patients with normal renal function suffering from heart failure, volume depletion, or bilateral renal artery stenosis experienced a significant rise (approximately 225% above baseline) in serum creatinine level, much higher in magnitude and rate than that experienced by those with renal insufficiency (Figure 1). Serum creatinine levels in these patients sharply increased (by approximately 75% above baseline) in the 2 weeks after the initiation of therapy with an ACE inhibitor, followed by an even sharper increase (another approximately 150%) during the subsequent 2 weeks. Patients with chronic renal insufficiency (serum creatinine>1.5 mg/dL) who received therapy with ACE inhibitors had about a five times higher risk of developing hyperkalemia than those with normal renal function, whereas presence of heart failure increased the risk of hyperkalemia by about three times over those without heart failure. Concomitant use of diuretics was associated with an approximately 60% reduction in risk of hyperkalemia. CONCLUSION: The authors conclude that, in patients with renal insufficiency (serum creatinine>1.4 mg/dL) treated with ACE inhibitors, there is a strong association between early (within the first 2 months) and moderate (not exceeding 30% over baseline) rise in serum creatinine and slowing of the renal disease progression in the long run. The authors recommend that ACE inhibitor therapy should not be discontinued unless serum creatinine level rise above 30% over baseline during the first 2 months after initiation of therapy or hyperkalemia (serum potassium level >or=5.6 mmol/L) develops.

Philbin EF, Santella RN, Rocco TA Jr.Angiotensin-converting enzyme inhibitor use in older patients with heart failureand renal dysfunction.J Am Geriatr Soc. 1999 Mar;47(3):302-8. clicca qui per andare su PUBMED

Section on Cardiac Transplantation, Division of Cardiovascular Medicine, HenryFord Hospital, Detroit, Michigan 48202, USA.

OBJECTIVE: To examine the relationship between angiotensin-converting enzyme(ACE) inhibitor use and clinical outcomes among recently hospitalized patientswith congestive heart failure (CHF) and coexisting renal insufficiency. DESIGN:A prospective cohort study. SETTING: Ten community hospitals in upstate NewYork. PARTICIPANTS: A total of 1076 hospital survivors identified from aconsecutive series of CHF inpatients. MEASUREMENTS: Patients were followedprospectively for 6 months after hospital discharge to track mortality, hospitalreadmission, and quality of life. Clinical outcomes were stratified by ACEinhibitor use among those with renal dysfunction, defined as serum creatinine >or = 2.0 mg/dL, and among the remaining patients, whose serum creatinine was <

or = 1.9. RESULTS: ACE inhibitor use was lower among 187 patients with renaldysfunction than among 889 patients with preserved function (41 vs 69%, P <.001). Age and sex were among the significant determinants of drug use in bothgroups. After adjustment for covariables, ACE inhibitor use among those withabnormal renal function was not associated with a lower risk for death orreadmission, or better quality of life. By comparison, ACE inhibition conferredmeaningful clinical benefit among those whose creatinine was < or = 1.9 mg/dL.CONCLUSION: Convincing evidence of clinical benefit from ACE inhibitor use isnot readily detectable among a sample of 187 unselected older patients with CHFand moderate or severe renal insufficiency. Further studies to identify subsetsof this group who might benefit are warranted.

Mehta RL, Pascual MT, Soroko S, Chertow GM; PICARD Study Group.Diuretics, mortality, and nonrecovery of renal function in acute renal failure.JAMA. 2002 Nov 27;288(20):2547-53.clicca qui per andare su PUBMED

Comment in:Lameire N, Vanholder R, Van Biesen W.Loop diuretics for patients with acute renal failure: helpful or harmful?JAMA. 2002 Nov 27;288(20):2599-601.

JAMA. 2003 Mar 19;289(11):1379-80; author reply 1380-1. JAMA. 2003 Mar 19;289(11):1379; author reply 1380-1. JAMA. 2003 Mar 19;289(11):1379; author reply 1380-1. JAMA. 2003 Mar 19;289(11):1380; author reply 1380-1. JAMA. 2003 Mar 19;289(11):1380; author reply 1380-1.

CONTEXT: Acute renal failure is associated with high mortality and morbidity. Diuretic agents continue to be used in this setting despite a lack of evidence supporting their benefit. OBJECTIVE: To determine whether the use of diuretics is associated with adverse or favorable outcomes in critically ill patients with acute renal failure. DESIGN: Cohort study conducted from October 1989 to September 1995. PATIENTS AND SETTING: A total of 552 patients with acute renal failure in intensive care units at 4 academic medical centers affiliated with the University of California. Patients were categorized by the use of diuretics on the day of nephrology consultation and, in companion analyses, by diuretic use at any time during the first week following consultation. MAIN OUTCOME MEASURES: All-cause hospital mortality, nonrecovery of renal function, and the combined outcome of death or nonrecovery. RESULTS: Diuretics were used in 326 patients (59%) at the time of nephrology consultation. Patients treated with diuretics on or before the day of consultation were older and more likely to have a history of congestive heart failure, nephrotoxic (rather than ischemic or multifactorial) origin of acute renal failure, acute respiratory failure, and lower serum urea nitrogen concentrations. With adjustment for relevant covariates and propensity scores, diuretic use was associated with a significant increase in the risk of death or nonrecovery of renal function (odds ratio, 1.77; 95% confidence interval, 1.14-2.76). The risk was magnified (odds ratio, 3.12; 95% confidence interval, 1.73-5.62) when patients who died within the first week following consultation were excluded. The increased risk was borne largely by patients who were relatively unresponsive to diuretics. CONCLUSIONS: The use of diuretics in critically ill patients with acute renal failure was associated with an increased risk of death and nonrecovery of renal function. Although observational data prohibit causal inference, it is unlikely that diuretics afford any material benefit in this clinical setting. In the absence of compelling contradictory data from a randomized, blinded clinical trial, the

widespread use of diuretics in critically ill patients with acute renal failure should be discouraged.

Zoccali C, Mallamaci F, Benedetto FA, Tripepi G, Parlongo S, Cataliotti A, Cutrupi S, Giacone G, Bellanuova I, Cottini E, Malatino LS; Creed Investigators.Cardiac natriuretic peptides are related to left ventricular mass and function and predict mortality in dialysis patients.J Am Soc Nephrol. 2001 Jul;12(7):1508-15.

 

Centro di Fisiologia Clinica del CNR e Divisione di Nefrologia, Via Sbarre Inferiori 39, 89100, Reggio Calabria, Italy. czoccali@diel.it

This study was designed to investigate the relationship among brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) and left ventricular mass (LVM), ejection fraction, and LV geometry in a large cohort of dialysis patients without heart failure (n = 246) and to test the prediction power of these peptides for total and cardiovascular mortality. In separate multivariate models of LVM, BNP and ANP were the strongest independent correlates of the LVM index. In these models, the predictive power of BNP was slightly stronger than that of ANP. Both natriuretic peptides also were the strongest independent predictors of ejection fraction, and again BNP was a slightly better predictor of ejection fraction than ANP. In separate multivariate Cox models, the relative risk of death was significantly higher in patients of the third tertile of the distribution of BNP and ANP than in those of the first tertile (BNP, 7.14 [95% confidence interval (CI), 2.83 to 18.01, P = 0.00001]; ANP, 4.22 [95% CI, 1.79 to 9.92, P = 0.001]), and a similar difference was found for cardiovascular death (BNP, 6.72 [95% CI, 2.44 to 18.54, P = 0.0002]; ANP, 3.80 [95% CI, 1.44 to 10.03, P = 0.007]). BNP but not ANP remained as an independent predictor of death in a Cox's model including LVM and ejection fraction. Cardiac natriuretic peptides are linked independently to LVM and function in dialysis patients and predict overall and cardiovascular mortality. The measurement of the plasma concentration of BNP and ANP may be useful for risk stratification in these patients.

Foley RN, Parfrey PS, Kent GM, Harnett JD, Murray DC, Barre PE.Serial change in echocardiographic parameters and cardiac failure in end-stage renal disease.J Am Soc Nephrol. 2000 May;11(5):912-6.

  Divisions of Nephrology and Clinical Epidemiology, Memorial University, St. John's, Newfoundland, Canada. rfoley@hope.srht.nhs.uk

Echocardiographic abnormalities are the rule in patients starting dialysis therapy and are associated with the development of cardiac failure and death. It

is unknown, however, whether regression of these abnormalities is associated with an improvement in prognosis. As part of a prospective cohort study with mean follow-up of 41 mo, 227 patients had echocardiography at inception and after 1 yr of dialysis therapy. Improvements in left ventricular (LV) mass index, volume index, and fractional shortening were seen in 48, 48, and 46%, respectively. Ninety patients had developed cardiac failure by 1 yr of dialysis therapy. Twenty-six percent of the remaining 137 patients subsequently developed new-onset cardiac failure. The mean changes in LV mass index were 17 g/m(2) in those who subsequently developed cardiac failure compared with 0 g/m(2) among those who did not (P = 0.05). The corresponding values were -8 versus 0% for fractional shortening (P < 0.0001). The associations between serial change in both LV mass index and fractional shortening and subsequent cardiac failure persisted after adjusting for baseline age, diabetes, ischemic heart disease, and the corresponding baseline echocardiographic parameter. Regression of LV abnormalities is associated with an improved cardiac outcome in dialysis patients. Serial echocardiography adds prognostic information to one performed at baseline.

Lindelow B, Bergh CH, Herlitz H, Waagstein F.Predictors and evolution of renal function during 9 years following hearttransplantation.J Am Soc Nephrol. 2000 May;11(5):951-7.

 

Department of Cardiology, Sahlgrenska University Hospital, Goteborg, Sweden.

Over a 9-yr period, heart transplantation was performed in 200 patients atSahlgrenska University Hospital. Of these 200 patients, 151 were followed for 1to 9 yr with regard to renal function, hemodynamics, cyclosporin Aconcentrations, and complications. Patients with a preoperative serum creatinine>130 micromol/L received inotropic drugs to test for reversibility of renaldysfunction. The end point was graft failure. The average preoperative GFR of 66+/- 17 ml/min per 1.73 m(2) declined to 52 +/- 19, 44 +/- 16, and 37 +/- 17 at1, 5, and 9 yr after heart transplantation, respectively. Altogether, theaverage GFR declined by 44%. There was no significant correlation between thepreoperative GFR and postoperative renal function or survival. Recipient age wasa predictor of renal function during the entire follow-up. Severe renaldysfunction (GFR <20 ml/min per 1.73 m(2)) developed in 20% of the patients,which was predicted by the recipient age at transplantation together with theGFR 1 yr after transplantation. A nomogram that shows the risk of developingsevere renal dysfunction after heart transplantation is presented. Cyclosporin Aconcentrations and treatment with statins, calcium channel blockers, orangiotensin-converting enzyme inhibitors did not correlate with the evolution ofrenal function. Patients with a preoperative depressed renal function whoimproved on inotropic treatment seemed to have a poorer outcome compared withthe other study patients.

Kumagai J, Yorioka N, Kawanishi H, Moriishi M, Komiya Y, Asakimori Y, TakahashiN, Tsuchiya S.Relationship between erythropoietin and chronic heart failure in patients onchronic hemodialysis.J Am Soc Nephrol. 1999 Nov;10(11):2407-11.

 

Second Department of Internal Medicine, Hiroshima University School of Medicine,

Japan.

In the present study, the relationship between the blood erythropoietin leveland cardiac function was investigated in 15 patients on chronic hemodialysis whodeveloped chronic heart failure. Another 45 patients without cardiac dysfunctionwere selected as a control group that was matched for gender, age, and theduration of dialysis. The erythropoietin level was 256.3 +/- 481.8 mU/ml in theheart failure group, which was significantly higher than that in the controlgroup (17.0 +/- 10.0 mU/ml, P < 0.01). Eight of the 15 patients in the heartfailure group maintained a hematocrit of more than 30% without receivingrecombinant human erythropoietin therapy, whereas 29 of the 45 patients in thecontrol group required erythropoietin. In the heart failure group, theerythropoietin level was significantly correlated with the levels of atrialnatriuretic peptide and brain natriuretic peptide (P < 0.01). These resultssuggest that heart failure can increase the erythropoietin level in proportionto the severity of cardiac dysfunction, even in patients on long-term dialysis.

Smith GL, Vaccarino V, Kosiborod M, Lichtman JH, Cheng S, Watnick SG, KrumholzHM.Worsening renal function: what is a clinically meaningful change in creatinineduring hospitalization with heart failure?J Card Fail. 2003 Feb;9(1):13-25. clicca qui per andare su PUBMEDComment in:

Shlipak MG, Chertow GC, Massie BM.Beware the rising creatinine level.J Card Fail. 2003 Feb;9(1):26-8.clicca qui per andare su PUBMED

Department of Medicine, Yale University School of Medicine, New Haven,Connecticut 06520, USA.

INTRODUCTION: Worsening renal function during hospitalization for heart failure,defined as elevation in creatinine during admission, predicts adverse outcomes.Prior studies define worsening renal function using various creatinineelevations, but the relative value of definitions is unknown. METHODS ANDRESULTS: In a prospective cohort of 412 patients hospitalized for heart failure,we compared a spectrum of worsening renal function definitions (absolutecreatinine elevations >/=0.1 to >/=0.5 mg/dL and 25% relative elevation frombaseline) and associations with 6-month mortality, readmission, and functionaldecline. Creatinine elevation >/=0.1 mg/dL occurred in 75% of patients, andelevation >/=0.5 mg/dL occurred in 24% of patients. Risk of death rose withhigher creatinine elevations (adjusted hazard ratio [HR] = 0.89, 1.19, 1.67,1.91, and 2.90 for elevations >/=0.1 to >/=0.5 mg/dL). Maximum sensitivity ofany definition for predicting mortality was 75% and maximum specificity was 79%.High creatinine elevation was a more important predictor of death than was asingle measure of baseline creatinine. CONCLUSIONS: Larger creatinine elevationspredict highest risk of death, yet even minor changes in renal function areassociated with adverse outcomes. The choice of a "best definition" forworsening renal function has implications for the number of patients identified

with this risk factor and the magnitude of risk for mortality.

Gottlieb SS, Abraham W, Butler J, Forman DE, Loh E, Massie BM, O'connor CM, Rich MW, Stevenson LW, Young J, Krumholz HM.The prognostic importance of different definitions of worsening renal function in congestive heart failure.J Card Fail. 2002 Jun;8(3):136-41.clicca qui per andare su PUBMED

Division of Cardiology, University of Maryland School of Medicine and the D.V.A. Medical Center, Baltimore, Maryland 21201, USA.

BACKGROUND: Worsening renal function in patients hospitalized for heart failure portends a poor prognosis. However, criteria used to define worsening renal function are arbitrary, and the implications of different definitions remain unclear. We therefore compared the prognostic importance of various definitions of worsening renal function in 1,002 patients hospitalized for congestive heart failure (CHF). METHODS AND RESULTS: The patient population was 49% female, aged 67 +/- 15 years. Twenty-three percent had a prior history of renal failure, 73% had known depressed ejection fraction, and 63% had known CHF. On admission to the hospital, 47% were receiving ACE inhibitors, 22% beta-blockers, 70% diuretics and 6% NAID's. 72% developed increased serum creatinine during the hospitalization, with 20% developing an increase of > or = 0.5 mg/dL. Worsening renal function predicted both in-hospital mortality and length of stay > 10 days. Even an increased creatinine of 0.1 mg/dL was associated with worse outcome. Sensitivity for death decreased from 92% to 65% as the threshold for increased creatinine was raised from 0.1 to 0.5 mg/dL, with specificity increasing from 28% to 81%. At a threshold of a 0.3 mg/dL increase, sensitivity was 81% and specificity was 62% for death and 64% and 65% for length of stay >10 days. Adding a requirement of final creatinine of > or = 1.5 mg/dL improved specificity. CONCLUSIONS: This analysis demonstrates that any detectable decrease in renal function is associated with increased mortality and prolonged hospital stay. This suggests that therapeutic interventions which improve renal function might be beneficial.

Rea TD, Siscovick DS, Psaty BM, Pearce RM, Raghunathan TE, Whitsel EA, Cobb LA,Weinmann S, Anderson GD, Arbogast P, Lin D.Digoxin therapy and the risk of primary cardiac arrest in patients withcongestive heart failure: effect of mild-moderate renal impairment.J Clin Epidemiol. 2003 Jul;56(7):646-50.clicca qui per andare su PUBMED

Cardiovascular Health Research Unit, University of Washington, Department ofMedicine, Metropolitan Park, 1730 Minor Avenue, East Tower, Seattle, WA 98101,USA. rea123@u.washington.edu

BACKGROUND AND OBJECTIVE: The cardiac safety of digoxin therapy for congestiveheart failure (CHF) is a source of concern, especially among those with renal

impairment. METHODS: Using a case-control design, we examined the risk ofprimary cardiac arrest (PCA) associated with digoxin therapy within three levelsof renal function. RESULTS: After adjustment for other clinical characteristics,digoxin therapy for CHF was not associated with an increased risk of PCA [oddsratio (OR)=0.97, 95% confidence interval (CI) 0.59-1.62] among patients withnormal renal function (serum creatinine </=1.1 mg/dL). In contrast, digoxintherapy was associated with a modest increase in risk (OR=1.58, CI 0.89-2.80)among patients with mild renal impairment (serum creatinine=1.2-1.4 mg/dL); anda twofold increase in risk (OR=2.39, CI 1.37-4.18) among patients with moderaterenal impairment (serum creatinine=1.5-3.5 mg/dL). CONCLUSIONS: These findingssuggest that the risks of digoxin may offset the benefits among patients withmoderately impaired renal function, but not among patients with normal renalfunction.

Vossler MR, Ni H, Toy W, Hershberger RE.Pre-operative renal function predicts development of chronic renal insufficiencyafter orthotopic heart transplantation.J Heart Lung Transplant. 2002 Aug;21(8):874-81. clicca qui per andare su PUBMED

Oregon Cardiac Transplant Program, Division of Cardiology, Oregon HealthSciences University, Portland 97201, USA.

BACKGROUND: Risk factors for the development of chronic renal insufficiencyafter solid-organ transplantation remain unclear. METHODS: We conducted a 5-yearretrospective analysis of all adult patients (n = 160) who survived >1 yearafter orthotopic heart transplantation at our institution from 1985 through1992. Study subjects were classified into 3 groups based on peri-operative renalfunction: (1) pre-operative creatinine concentration <1.5 mg/dl and apost-operative (first 4 days) creatinine <2.0 mg/dl (n = 75); (2) pre-operativecreatinine of <1.5 mg/dl but a post-operative creatinine of >2.0 mg/dl (n = 47);(3) pre-operative creatinine of >1.5 mg/dl (n = 38). The association betweendevelopment of chronic renal insufficiency and peri-operative renal dysfunctionwas evaluated using the Cox proportional hazard model. RESULTS: A total of 47(29.4%) patients experienced chronic renal insufficiency (serial serumcreatinine >2.0 mg/dl on 2 or more monthly examinations). The mean pre-operativeserum creatinine was 1.6 mg/dl in patients who experienced chronic renalinsufficiency, whereas it was 1.3 mg/dl in patients who did not (p < 0.01). Thefraction of patients in whom chronic renal insufficiency developed was highestin Group 3 (55.3%), lower in Group 2 (25.5%), and lowest in Group 1 (18.7%) (p <0.01). After adjusting for multiple potential confounding variables, includingcyclosporine dosage, the risk of chronic renal insufficiency linearly decreasedin the 3 groups, stratified by peri-operative renal function (relative risk,1.82; 95% confidence interval, 1.23-2.7). However, the difference in relativerisk of renal insufficiency was not statistically significant between Group 2and Group 1. CONCLUSION: Pre-operative serum creatinine concentration predictsdevelopment of renal insufficiency after heart transplantation.

Snell GI, Levvey BJ, Chin W, Kotsimbos T, Whitford H, Waters KN, Richardson M,Williams TJ.

Sirolimus allows renal recovery in lung and heart transplant recipients withchronic renal impairment.J Heart Lung Transplant. 2002 May;21(5):540-6. clicca qui per andare su PUBMEDLung & Heart Transplant Services, Alfred Hospital, Prahran, Melbourne, Victoria,Australia.

BACKGROUND: Until recently, there has been no practical alternative to the useof calcineurin inhibitors (CIs) as primary immunosuppressants in lungtransplantation (LTx) and heart transplantation (HTx). Sirolimus (SRL) is anovel powerful immunosuppressant without renal toxicity, a commonpost-transplant problem associated with CI therapy. METHODS: SRL was used in 20LTx and 5 HTx recipients >90 days post-transplant, where serious renalimpairment was limiting CI dosing. Patients started on 2 to 5 mg/day orally at amedian of 1,185 days post-transplant. Dosage adjustments were made according totrough levels, toxicity and perceived efficacy. With SRL initiation, 48% ceasedCI therapy and the remainder decreased their dose substantively. RESULTS: After30 days, 4 of 5 dialyzed patients ceased dialysis and 15 of 20 patients with anelevated serum creatinine (Cr) (mean Cr 0.29 mmol/liter) improved their Cr. Thedirection of change in Cr at 30 days predicted longer term Cr. The starting Crdid not predict the 30-day or long-term value. There were two bouts of acute andone bout of chronic rejection. There were 35 infectious complications in 16patients and 24 episodes of potential SRL-related toxicity in 17 patients. Theseevents generally responded to dose reduction or temporary cessation and werelevel-related. Fifteen recipients presently remain on the drug. None of the 7deaths could be directly related to toxicity. CONCLUSION: SRL is a usefulalternative immunosuppressant, allowing significant CI withdrawal in transplantrecipients with renal impairment. Whether the resulting improvement in Cr can bemaintained in the long term probably depends on the balance between the extentof acute and chronic renal damage.

Watanabe G, Tomiyama H, Doba N.Effects of oral administration of L-arginine on renal function in patients withheart failure.J Hypertens. 2000 Feb;18(2):229-34. clicca qui per andare su PUBMED

The Third Department of Internal Medicine, Teikyo University Ichihara Hospital,Chiba, Japan.

OBJECTIVES: Although the beneficial effects of L-arginine on systemichaemodynamics have been reported in patients with heart failure, its effect onrenal function has not been examined. We evaluated the effects of oraladministration of L-arginine on renal haemodynamics, sodium and water handling,and various hormonal factors in patients with chronic heart failure. SUBJECTSAND METHODS: A double-blind crossover trial was performed in 17 patients withchronic congestive heart failure (NYHA II-III, 56 +/- 12 years of age) who wererandomly assigned to receive oral L-arginine (15 g/day) and placebo or placeboand arginine sequentially for 5 days each. Twenty-four hour creatinine clearance(Ccr), and 24-h urinary cyclic guanosine 5-monophosphate (GMP) excretion weredetermined. Saline loading was performed on day 5 of each treatment Renal bloodflow, glomerular filtration rate (GFR), and urinary sodium excretion rate (UNa)were assessed before and after saline loading. RESULTS: Twenty-four hour GMPexcretion (1.4 +/- 1.1 versus 0.8 +/- 0.5 micromol/day, P < 0.01) and Ccr (150

+/- 43 versus 125 +/- 42 ml/min, P < 0.05) were higher and plasma endothelinlevel (2.5 +/- 0.6 versus 3.1 +/- 0.8 pg/ml, P < 0.05) was lower with L-argininetreatment compared to placebo treatment In addition, the relative increase ofUNa and GFR after saline loading were significantly higher in L-argininetreatment (UNa, 47 +/- 12%; GFR, 44 +/- 31%) than in placebo treatment (UNa, 34+/- 9%; GFR, 22 +/- 29%) (P < 0.05). CONCLUSIONS: Oral administration ofL-arginine has beneficial effects on glomerular filtration rate, natriuresis,and plasma endothelin level in patients with chronic congestive heart failure.

Kyuma M, Nakata T, Hashimoto A, Nagao K, Sasao H, Takahashi T, Tsuchihashi K,Shimamoto K.Incremental prognostic implications of brain natriuretic peptide, cardiacsympathetic nerve innervation, and noncardiac disorders in patients with heartfailure.J Nucl Med. 2004 Feb;45(2):155-63clicca qui per andare su PUBMED

Second Department of Internal Medicine (Cardiology), Sapporo Medical UniversitySchool of Medicine, S-1 W-16, Chuo-ku, Sapporo 060-8543, Japan.

Plasma brain natriuretic peptide (BNP) level and cardiac autonomic function areclosely related to prognosis in patients with heart failure. However, theircorrelation and incremental prognostic values in human heart failure areunclear. We sought to evaluate the correlation between BNP level and cardiacsympathetic innervation assessed by (123)I-metaiodobenzylguanidine ((123)I-MIBG)and the prognostic value of combined assessment of risk factors for mortality inpatients with heart failure. METHODS: After conventional examinations andmeasurements of plasma BNP level and heart-to-mediastinum ratio (HMR) of cardiac(123)I-MIBG activity, 158 patients with heart failure were prospectivelyfollowed with an endpoint of cardiac death for 16 mo. RESULTS: Fifteen deathsdue to pump failure and 2 sudden cardiac deaths were documented. Plasma BNPlevel correlated with HMR significantly but not so tightly (r = 0.330, P <0.0001). Univariate analysis identified plasma BNP level, HMR, chronic renaldysfunction, diabetes mellitus, age, and use of nitrates as significantpredictors of fatal pump failure, and multivariate Cox analysis showed thatplasma BNP level was the most powerful predictor of cardiac death. Patients withboth plasma BNP level of > or = 172 pg/mL and late HMR of < or =1.74 had agreater annual rate of fatal pump failure than did those without (17.5%/y vs.0%-3.9%/y, respectively). The hazard ratio of plasma BNP level (7.2) or cardiac(123)I-MIBG activity (10.1) increased to 34.4 when both variables were used, andprevalence of fatal pump failure significantly increased from 22% to 62.5% whendiabetes mellitus and chronic renal dysfunction were present with a higherplasma BNP level and low cardiac (123)I-MIBG activity. CONCLUSION: Plasma BNPlevel is a stronger predictor than other risk factors for mortality in heartfailure patients and is statistically significantly, but roughly, related tocardiac sympathetic nerve innervation. Impaired cardiac sympathetic nerveinnervation and the presence of diabetes mellitus and chronic renal dysfunction,however, improve risk stratification of patients with heart failure andincreased plasma BNP concentration.

Mallamaci F, Zoccali C, Parlongo S, Tripepi G, Benedetto FA, Cutrupi S, BonannoG, Fatuzzo P, Rapisarda F, Seminara G, Stancanelli B, Bellanuova I, CataliottiA, Malatino LS; Cardiovascular Risk Extended Evaluation in DialysisInvestigators.Diagnostic value of troponin T for alterations in left ventricular mass andfunction in dialysis patients.Kidney Int. 2002 Nov;62(5):1884-90. clicca qui per andare su PUBMED

CNR Centre of Clinical Physiology and Division of Nephrology, Reggio Calabria,Italy.

BACKGROUND: Cardiac troponin T (cTnT) is related to left ventricular (LV) massin patients with end-stage renal disease (ESRD). Furthermore, cTnT reflects theseverity of systolic dysfunction in patients with heart diseases. We tested thediagnostic value of cTnT for left ventricular hypertrophy (LVH) and LV systolicdysfunction in a large group of clinically stable hemodialysis patients withoutheart failure. RESULTS: CTnT was significantly (P < 0.001) higher in patientswith LVH than in those with normal LV mass. In a multiple logistic regressionmodel, adjusting for potential confounders (including cardiac ischemia),systolic pressure and cTnT (both P = 0.003) were the strongest correlates ofLVH. Similarly, cTnT was significantly higher (P = 0.005) in patients withsystolic dysfunction than in those with normal LV function and in a multiplelogistic regression model cTnT ranked as the second independent correlate ofthis alteration after male sex. Serum cTnT had a high positive prediction valuefor the diagnosis of LVH (87%) but its negative prediction value was relativelylow (44%). The positive predictive value of cTnT for LV dysfunction was low(25%) while its negative predictive value was high (93%). A combined analysisincluding systolic pressure (for the diagnosis of LVH) and sex (for thediagnosis of LV systolic dysfunction) augmented the diagnostic estimates to animportant extent (95% positive prediction value for LVH and 98% negativeprediction value for LV systolic dysfunction). CONCLUSIONS: CTnT has a fairlygood diagnostic potential for the identification of LVH and for the exclusion ofLV systolic dysfunction in patients with ESRD without heart failure. This markermay be useful for the screening of alterations in LV mass and function inclinically stable hemodialysis patients.

Mallamaci F, Zoccali C, Tripepi G, Benedetto FA, Parlongo S, Cataliotti A,Cutrupi S, Giacone G, Bellanuova I, Stancanelli B, Malatino LS; CREEDInvestigstors. The Cardiovascular Risk Extended Evaluation.Diagnostic potential of cardiac natriuretic peptides in dialysis patients.Kidney Int. 2001 Apr;59(4):1559-66.clicca qui per andare su PUBMED

CNR Centro Fisiologia Clinica e Divisione di Nefrologia, Ospedali Riuniti,Reggio Calabria, Italy.

BACKGROUND: In the general population, the plasma concentrations of atrialnatriuretic peptide (ANP) and brain natriuretic peptide (BNP) are useful topredict left ventricular hypertrophy (LVH) and LV systolic dysfunction. Whetherthese cardiac hormones have a similar diagnostic potential in dialysis patients

is unknown. METHODS: We studied the diagnostic value of ANP and BNP foralterations in LV mass and function in a cohort of 246 dialysis patients withoutclinical evidence of heart failure. RESULTS: Both ANP and BNP were independentlyrelated to left ventricular mass (P < 0.0001) as well as to ejection fraction (P< 0.0001). In an analysis based on a prospectively defined threshold (95thpercentile of the normal range), BNP had a significantly higher (P < 0.01)sensitivity (88%) than ANP (51%) for the diagnosis of LVH, but the positivepredictive value of the two peptides was very similar (92 and 87%, respectively,P = NS). However, the negative predictive value of BNP for excluding LVH was 22%higher than that of ANP (53 vs. 31%, P = 0.05). Both natriuretic peptides had ahigh sensitivity for the detection of LV dysfunction (87 and 94%), but theirpositive predictive value was low (25 and 15%). Importantly, both ANP and BNPproved to be very useful for excluding this alteration (negative predictivevalue 97 and 96%, respectively). An analysis based on the "best cut-offs" ofeach peptide as identified on the basis of the ROC curves augmented the positiveand negative prediction values of BNP for the diagnosis of LVH to 95 and 61%,respectively. This approach also raised the BNP-positive prediction value forthe identification of LV dysfunction to 31% but did not modify the diagnosticpotential of ANP (either for LVH or for LV dysfunction). CONCLUSIONS: Measuringthe plasma concentration of cardiac natriuretic hormones, particularly BNP, maybe useful for the identification of dialysis patients with LVH or for excludingsystolic dysfunction.

Granger CB, McMurray JJ, Yusuf S, Held P, Michelson EL, Olofsson B, Ostergren J,Pfeffer MA, Swedberg K; CHARM Investigators and Committees.Effects of candesartan in patients with chronic heart failure and reducedleft-ventricular systolic function intolerant to angiotensin-converting-enzymeinhibitors: the CHARM-Alternative trial.Lancet. 2003 Sep 6;362(9386):772-6. clicca qui per andare su PUBMED

Comment in: ACP J Club. 2004 Mar-Apr;140(2):32-3. Lancet. 2003 Nov 15;362(9396):1675-6; author reply 1678-9. Lancet. 2003 Sep 6;362(9386):754-5.

Division of Cardiology, Duke University Medical Center, Durham, NC 27710, USA.grang001@mc.duke.edu

BACKGROUND: Angiotensin-converting-enzyme (ACE) inhibitors improve outcome ofpatients with chronic heart failure (CHF). A substantial proportion of patients,however, experience no benefit from ACE inhibitors because of previousintolerance. We aimed to find out whether candesartan, an angiotensin-receptorblocker, could improve outcome in such patients not taking an ACE inhibitor.METHODS: Between March, 1999, and March, 2001, we enrolled 2028 patients withsymptomatic heart failure and left-ventricular ejection fraction 40% or less whowere not receiving ACE inhibitors because of previous intolerance. Patients wererandomly assigned candesartan (target dose 32 mg once daily) or matchingplacebo. The primary outcome of the study was the composite of cardiovascular

death or hospital admission for CHF. Analysis was by intention to treat.FINDINGS: The most common manifestation of ACE-inhibitor intolerance was cough(72%), followed by symptomatic hypotension (13%) and renal dysfunction (12%).During a median follow-up of 33.7 months, 334 (33%) of 1013 patients in thecandesartan group and 406 (40%) of 1015 in the placebo group had cardiovasculardeath or hospital admission for CHF (unadjusted hazard ratio 0.77 [95% CI0.67-0.89], p=0.0004; covariate adjusted 0.70 [0.60-0.81], p<0.0001). Eachcomponent of the primary outcome was reduced, as was the total number ofhospital admissions for CHF. Study-drug discontinuation rates were similar inthe candesartan (30%) and placebo (29%) groups. INTERPRETATION: Candesartan wasgenerally well tolerated and reduced cardiovascular mortality and morbidity inpatients with symptomatic chronic heart failure and intolerance to ACEinhibitors.

Bellomo R, Chapman M, Finfer S, Hickling K, Myburgh J.Low-dose dopamine in patients with early renal dysfunction: a placebo-controlled randomised trial. Australian and New Zealand Intensive Care Society (ANZICS) Clinical Trials Group.Lancet. 2000 Dec 23-30;356(9248):2139-43.clicca qui per andare su PUBMED

Comment in: Galley HF.Renal-dose dopamine: will the message now get through?Lancet. 2000 Dec 23-30;356(9248):2112-3.

Lancet. 2001 Mar 24;357(9260):960. Lancet. 2001 May 26;357(9269):1707-8. Lancet. 2001 May 26;357(9269):1707-8.

Cataliotti A, Malatino LS, Jougasaki M, Zoccali C, Castellino P, Giacone G,Bellanuova I, Tripepi R, Seminara G, Parlongo S, Stancanelli B, Bonanno G,Fatuzzo P, Rapisarda F, Belluardo P, Signorelli SS, Heublein DM, Lainchbury JG,Leskinen HK, Bailey KR, Redfield MM, Burnett JC Jr.Circulating natriuretic peptide concentrations in patients with end-stage renaldisease: role of brain natriuretic peptide as a biomarker for ventricularremodeling.Mayo Clin Proc. 2001 Nov;76(11):1111-9. clicca qui per andare su PUBMED

Cardiorenal Research Laboratory, Division of Cardiovascular Diseases andInternal Medicine, Mayo Clinic, Rochester, Minn 55905, USA.cataliotti.alessandro@mayo.edu

OBJECTIVES: To determine levels of natriuretic peptides (NPs) in patients withend-stage renal disease (ESRD) and to examine the relationship of thesecardiovascular peptides to left ventricular hypertrophy (LVH) and to cardiacmortality. PATIENTS AND METHODS: One hundred twelve dialysis patients withoutclinical evidence of congestive heart failure underwent plasma measurement of NPconcentrations and echocardiographic investigation for left ventricular massindex (LVMI). RESULTS: Plasma atrial natriuretic peptide (ANP) and brainnatriuretic peptide (BNP) concentrations correlated positively with LVMI andinversely with left ventricular ejection fraction, whereas C-type NP andDendroaspis NP levels did not correlate with LVMI. In dialysis patients with LVH

(LVMI >125 g/m2), plasma ANP and BNP concentrations were increased compared withthose in dialysis patients without LVH (both P<001). In a subset of 15 dialysispatients without LVH or other concomitant diseases, plasma BNP concentrationswere not significantly increased compared with those in 35 controls (mean +/-SD, 20.1+/-13.4 vs 13.5+/-9.6 pg/mL; P=.06), demonstrating that the BNPconcentration was not increased by renal dysfunction alone. Furthermore, the BNPlevel was significantly higher in the 16 patients who died from cardiovascularcauses compared with survivors (mean +/- SD, 129+/-13 vs 57+/-7 pg/mL; P<.003)and was significantly associated with greater risk of cardiovascular death inCox regression analysis (P<.001), as was the ANP level (P=.002). CONCLUSIONS:Elevation of the plasma BNP concentration is more specifically related to LVHcompared with the other NP levels in patients with ESRD independent ofcongestive heart failure. Thus, BNP serves as an important plasma biomarker forventricular hypertrophy in dialysis patients with ESRD.

Pfeffer MA, McMurray JJ, Velazquez EJ, Rouleau JL, Kober L, Maggioni AP, SolomonSD, Swedberg K, Van de Werf F, White H, Leimberger JD, Henis M, Edwards S,Zelenkofske S, Sellers MA, Califf RM; Valsartan in Acute Myocardial InfarctionTrial Investigators.Valsartan, captopril, or both in myocardial infarction complicated by heartfailure, left ventricular dysfunction, or both.N Engl J Med. 2003 Nov 13;349(20):1893-906. Epub 2003 Nov 10clicca qui per andare su PUBMEDErratum in: N Engl J Med. 2004 Jan 8;350(2):203.

Comment in: N Engl J Med. 2003 Nov 13;349(20):1963-5. N Engl J Med. 2004 Feb 26;350(9):943-5; author reply 943-5. N Engl J Med. 2004 Feb 26;350(9):943-5; author reply 943-5. N Engl J Med. 2004 Feb 26;350(9):943-5; author reply 943-5.

Cardiovascular Division, Brigham and Women's Hospital, Boston, MA 02115, USA.mpfeffer@rics.bwh.harvard.edu

BACKGROUND: Angiotensin-converting-enzyme (ACE) inhibitors such as captoprilreduce mortality and cardiovascular morbidity among patients with myocardialinfarction complicated by left ventricular systolic dysfunction, heart failure,or both. In a double-blind trial, we compared the effect of theangiotensin-receptor blocker valsartan, the ACE inhibitor captopril, and thecombination of the two on mortality in this population of patients. METHODS:Patients receiving conventional therapy were randomly assigned, 0.5 to 10 daysafter acute myocardial infarction, to additional therapy with valsartan (4909patients), valsartan plus captopril (4885 patients), or captopril (4909patients). The primary end point was death from any cause. RESULTS: During amedian follow-up of 24.7 months, 979 patients in the valsartan group died, asdid 941 patients in the valsartan-and-captopril group and 958 patients in thecaptopril group (hazard ratio in the valsartan group as compared with thecaptopril group, 1.00; 97.5 percent confidence interval, 0.90 to 1.11; P=0.98;hazard ratio in the valsartan-and-captopril group as compared with the captoprilgroup, 0.98; 97.5 percent confidence interval, 0.89 to 1.09; P=0.73). The upperlimit of the one-sided 97.5 percent confidence interval for the comparison ofthe valsartan group with the captopril group was within the prespecified marginfor noninferiority with regard to mortality (P=0.004) and with regard to the

composite end point of fatal and nonfatal cardiovascular events (P<0.001). Thevalsartan-and-captopril group had the most drug-related adverse events. Withmonotherapy, hypotension and renal dysfunction were more common in the valsartangroup, and cough, rash, and taste disturbance were more common in the captoprilgroup. CONCLUSIONS: Valsartan is as effective as captopril in patients who areat high risk for cardiovascular events after myocardial infarction. Combiningvalsartan with captopril increased the rate of adverse events without improvingsurvival. Copyright 2003 Massachusetts Medical Society

Silverberg DS, Wexler D, Blum M, Sheps D, Schwartz D, Yachnin T, Baruch R,Tchebiner J, Zubkov A, Shaked M, Steinbruch S, Keren G, Iaina A.Aggressive therapy of congestive heart failure and associated chronic renalfailure with medications and correction of anemia stops or slows the progressionof both diseases.Perit Dial Int. 2001;21 Suppl 3:S236-40. clicca qui per andare su PUBMED

Department of Nephrology, Tel Aviv Medical Center, Israel.donald@netvision.net.il

The prevalence of congestive heart failure (CHF) is increasing rapidly in thecommunity. We and others have shown that the prevalence and severity of bothanemia and chronic renal failure (CRF) increase steadily with increasingseverity of CHF. We have also shown that CHF patients may be resistant tostandard drug therapy for CHF as long as the associated anemia is not corrected,and that correction of the anemia with subcutaneous erythropoietin andintravenous iron sucrose (Venofer: Vifor International, St. Gallen, Switzerland)may improve both the CHF and CRF and markedly reduce hospitalizations withoutcausing side effects. We report here our experience with correcting anemia inthis manner in 126 cases of anemic-resistant CHF patients. As in our previousstudies, correction of the anemia improved both CHF and CRF, and reducedhospitalizations. Our studies suggest that correction of even mild anemia in CHFmay be an important addition to the treatment of patients with the combinationof CHF and CRF.

Heitmann M, Davidsen U, Stokholm KH, Rasmussen K, Burchardt H, Petersen EB.Renal and cardiac function during alpha1-beta-blockade in congestive heartfailure.Scand J Clin Lab Invest. 2002;62(2):97-104. clicca qui per andare su PUBMED

Department of Internal Medicine, Roskilde Hospital, Denmark.m.heitmann@dadlnet.dk

The kidney and the neurohormonal systems are essential in the pathogenesis ofcongestive heart failure (CHF) and the physiologic response. Routine treatmentof moderate to severe CHF consists of diuretics, angiotensin-converting enzyme(ACE) inhibition and beta-blockade. The need for control of renal functionduring initiation of ACE-inhibition in patients with CHF is well known. The aimof this study was to investigate whether supplementation by a combinedalpha1-beta-blockade to diuretics and ACE-inhibition might improve cardiacfunction without reducing renal function. METHODS: Fourteen patients treated formoderate to severe CHF with diuretics and ACE inhibitors were investigated atbaseline, after 4 months of maximum carvedilol treatment and after withdrawal ofcarvedilol. RESULTS: Carvedilol lowered blood pressure and heart rate butincreased left and right ventricular ejection fractions without changing cardiacoutput or pulmonary blood volume. At the same time, a minor fall was seen inglomerular filtration rate (GFR). but renal blood flow was unchanged andeffective renal plasma flow slightly increased. Carvedilol also lowered theplasma levels of angiotensin II and aldosterone. All changes were reversed afterwithdrawal of carvedilol. CONCLUSIONS: Carvedilol augments ACE-inhibitor-inducedvasodilation by lowering blood pressure, and angiotensin II beside reducingheart rate. The heart adapts to the haemodynamic alterations without changes incardiac output and pulmonary blood volume. GFR is slightly lowered despite nochanges in renal blood flow and a slight increase in effective renal plasmaflow. The study emphasizes the need for control of renal function duringtreatment with carvedilol in patients with CHF.