Programma Scientifico Preliminare

LUNEDI’ 27 NOVEMBRE 2017

9.00 – 9.30 Apertura Segreteria e Registrazione dei Partecipanti

9.30 -10.00 Saluto delle Autorità e Apertura dei Lavori Giovannella Baggio (Padova) Rosario Rizzuto - Rettore, Università di Padova Mario Plebani - Presidente Scuola di Medicina (Padova) Cristina Parolin - Direttore Dipartimento di Medicina Molecolare (Padova) Paolo Simioni – Presidente Ordine dei Medici (Padova)

10.00 – 11.00 LETTURE MAGISTRALI Moderatore: Sergio Pecorelli (Brescia)

10.00 - 10.30 Ruolo della Medicina di Genere nella Economia Sanitaria

Francesco Saverio Mennini (Roma)

10.30 - 11.00 Epigenetica e Genere Giuseppe Novelli (Roma)

11.00 – 13.00 UPDATE LECTURES Cardiologia e oncologia genere-specifiche Moderatori: Cecilia Politi (Isernia) Annamaria Moretti (Bari)

11.00 - 11.30 Lo Scompenso Cardiaco

Gianfranco Sinagra (Trieste)

11.30 - 12.00 Le Aritmie Cardiache Loira Leoni (Padova)

12.00 – 12.30 Differenze di genere in oncologia toraco-polmonare Giulia Pasello (Padova)

Programma Scientifico Preliminare

LUNEDI’ 27 NOVEMBRE 2017

9.00 – 9.30 Apertura Segreteria e Registrazione dei Partecipanti

9.30 -10.00 Saluto delle Autorità e Apertura dei Lavori Giovannella Baggio (Padova) Rosario Rizzuto - Rettore, Università di Padova Mario Plebani - Presidente Scuola di Medicina (Padova) Cristina Parolin - Direttore Dipartimento di Medicina Molecolare (Padova) Paolo Simioni – Presidente Ordine dei Medici (Padova)

10.00 – 11.00 LETTURE MAGISTRALI Moderatore: Sergio Pecorelli (Brescia)

10.00 - 10.30 Ruolo della Medicina di Genere nella Economia Sanitaria

Francesco Saverio Mennini (Roma)

10.30 - 11.00 Epigenetica e Genere Giuseppe Novelli (Roma)

11.00 – 13.00 UPDATE LECTURES Cardiologia e oncologia genere-specifiche Moderatori: Cecilia Politi (Isernia) Annamaria Moretti (Bari)

11.00 - 11.30 Lo Scompenso Cardiaco

Gianfranco Sinagra (Trieste)

11.30 - 12.00 Le Aritmie Cardiache Loira Leoni (Padova)

12.00 – 12.30 Differenze di genere in oncologia toraco-polmonare Giulia Pasello (Padova)

LO SCOMPENSO CARDIACO

Dr. Marco MERLOS.C. Cardiologia, ASUITs, Trieste

DISCLOSURE: None

SCOMPENSO CARDIACO

VIA FINALE COMUNE DI MOLTELICI PATOLOGIE

Scardovi et al. G Ital Cardiol 2012

SCOMPENSO CARDIACO CRONICO –FISIOPATOLOGIA

?

ALLA RICERCA DI NUOVI TARGET

DEFINIZIONE EZIOLOGICAHFpEF - HFrEF

ESC-HF guidelines. Ponikowski P. Eur Heart J 2016

COMORBIDITA’

PROGNOSI

Chioncel O et al. EJHF 2017

DONNE E SCOMPENSO CARDIACO

Cardiovascular disease in women

• Coronary artery disease• Heart attacks, angina

• Congestive heart failure• Preserved systolic function/Hypertensive• Peri-partum cardiomyopathy• Chemotherapy induced cardiomyopathy• Autoimmune related cardiomyopathy

• Arrhythmia• Atrial fibrillation

• Valvular heart disease• Aortic stenosis• Mitral regurgitation

• Stroke

• Pericardial disease

Precision Medicine in Heart Failure

Scardovi et al. G Ital Cardiol 2012

DONNE E SCOMPENSO CARDIACO

Sex differences: Physiology

• Compared to Men, Women have:• Lower LV mass

• Greater contractility

• Preserved mass with aging

• Lower rate of apoptosis

• Small coronary vessels

• Lower blood pressure

• Faster resting HR

• Less catecholamine mediated vasoconstriction

Sex Hormones

• Estrogen• Receptors on cardiac cells

• Estrogen affects hepatic gene expression

• Improved lipids

• Vascular effects: vasodilation

• Stimluates immune system• Affects cytokine/inflammatory pathways

• Testosterone• Increases inflammation/cholesterol

CHD and menopausal status

0

0,5

1

1,5

2

2,5

3

3,5

4

40-44 45-49 50-54

Pre-menopausal

Post-menopausal

An

nu

al in

cid

ence

per

10

00

Women vs. Men

• More non-ischemic etiology of HF

• More HTN, diabetes

• Older age at presentation

• Lower QOL, more depression

• More frequent LBBB

• Similar hospitalization/readmission rates

• Lower mortality/transplant rate in DCM

• Lower representation in HF trials (17-23%)

• Less procedures, including ICDs, CRT

ESC-HF guidelines. Ponikowski P. Eur Heart J 2016

HEART FAILURE SPECTRUM

HFrEF

ACE inhibitors

Beta-blockers Spironolactone/Eplerenone

ICD/CRT

Structured Follow-up Early diagnosis

Best management in HFrEF

Ivabradine

LCZ696

Simon et al. Circulation 2001

HFrEF

Shore S et al. JACC HF, 2015

Shore S et al. JACC HF, 2015

CVD –leading cause of death in women

0

50

100

150

200

250

300

350

400

450

500

CVD Stroke Breast CA

Death/100,000

AHA 2003

Coronary Heart Disease Mortality in Younger Women Higher than in Men

Vaccarino NEJM 1999;341:217

2,9

4,1

5,7

8,2

10,7

14,4

18,4

21,8

25,3

6,1

7,4

9,5

11,1

13,4

16,6

19,1

21,5

24,2

0

5

10

15

20

25

30

< 50 50-54 55-59 60-64 65-69 70-74 75-79 80-84 85-89

Dea

th d

urin

g H

ospi

taliz

atio

n (%

)

Men Women

Figure 1. Rates of death during hospitalization for Myocardial Infarction among women and men, according to age. The interaction between sex and age was significant (P<0.001).

Cardiovascular disease (CVD) mortality trends for men and women in the United States from 1979 to 2011

Women and CAD

Compared to men…..

Less classical symptoms

More related to diabetes, inactivity, obesity, depression

2/3 women who die suddenly had no previous heart attack

2x more likely to die soon after heart attack

Worse outcome after bypass surgery

Women’s Symptoms

• Prodromal• Unusual fatigue 70%

• Sleep disturbance 48%

• Shortness of breath 42%

• Indigestion 39%

• Anxiety 35%

• Acute• Shortness of breath 58%

• Weakness 55%

• Unusual fatigue 43%

• Cold sweat 39%

• Dizziness 39%

• 43% did NOT have chest pain

Total 775 patients 593 men + 182 women182 matched men

Archives of Cardiovascular Disease (2015)

Totale (N=1289) mediana, IQR

Maschi (N=952) mediana, IQR

Femmine (N=337) mediana, IQR

p

Età 66 (57 – 75) 64 (55 – 72) 74 (65 – 81) <0.001

Glicemia ingr (mg/dl)

145 (121 – 184) 142 (119 – 176) 154 (131 – 195) 0.001

GFR ingr(ml/min)

69 (50 – 85) 72 (54 – 87) 60 (43 – 76) <0.001

Tempo ischemia (ore)

3.38 (2.35 – 5.29) 3.26 (2.30 – 5.12) 4.05 (3.00 – 5.57) <0.001

FEVS (%) 52 (43 – 57) 52 (44 – 57) 52 (42 – 57) N.S.

Troponina(mcg/ml)

57 (24 – 112) 57 (25 – 119) 58 (26 – 94) N.S.

Tabella descrittiva variabili continue

Dati registro STEMI Trieste 12.2003 – 12.2012Analisi di Genere

Totale (N=1289) Maschi (N=952) Femmine (N=337) p

Età > 75 27.3% 19.1% 49.8% <0.001

Diabete 22.6% 22.0% 24.4% N.S.

Killip 3 - 4 11.7% 10.5% 14.8% 0.035

Tempo isch > 6 h 14.6% 13.1% 18.8% 0.026

SCC 23.2% 21.3% 28.6% 0.007

FEVS < 35% 8.9% 8.4% 10.6% N.S.

ACR 6.5% 7.1% 5.0% N.S.

Tabella descrittiva variabili discrete

Dati registro STEMI Trieste Dicembre 2003 - Dicembre 2012Analisi di genere

Totale (N=1289) Maschi (N=952) Femmine (N=337) p

Mortalità intraospedaliera

6.8% 5.5% 10.4% 0.002

Mortalità a 30 giorni 7.5% 6.1% 11.6% 0.001

Mortalità totale(f-up mediano 48 mesi)

13.3% 11.6% 18.4% 0.001

Mortalità in base al sesso

Dati registro STEMI Trieste Dicembre 2003 - Dicembre 2012Analisi di genere

CONSAPEVOLEZZA DI MALATTIA

Non tutte le DCM sono geneticamente determinate

Merlo M. et al. Eur J Heart Fail. In press

Shore S et al. JACC HF 2015

ETIOLOGICAL CLASSIFICATION

Takotsubo Cardiomyopathy• Reported by Japanese in 1990

• “Broken heart”, apical ballooning, stress CM

• Octopus trap appearance

• Up to 90% women, age > 60

• 70% with Severe emotional stress

• Troponin moderately elevated

• Echo resolution within ~ 30 days

Rivera et al. Med Sci Monit, 2011;17(6):RA135-147

Post-partum Cardiomyopathy

• 1/4000 live US births

• 1 month pre or 5 months post-partum

• Increased maternal age, multiparity, multiple gestations, preeclampsia/HTN

• 2.9x more likely in AA women

• ?viral, immune, stress, prolactin, tocolysis, hereditary

• Usual HF therapy, until resolved

• 4% need transplant

• Future pregnancies NOT recommended

Heart Failure and Chemotherapy

• Breast cancer most common malignancy

• Adriamycin• Dose dependent cardiotoxicity (>450 mg/m2)

• Clinical HF in 2-7% of pts; increases over time

• Herceptin• Reduces recurrence rate up to 50%

• CHF in 2-4%; up to 3-27% after combination

• Esp in pts with elevated troponin/BNP

• Cyclophosphamide, XRT

FIGURE 3. Cardiovascular death free survival.

FIGURE 1. Longitudinal trends during follow-up. Red lines are for females and black lines are for males. NYHA: New York Heart Association class; LVEF: Left ventricular ejection fraction; LVEDD: Left ventricular end-diastolic diameter; LVEDV: left ventricular end-diastolic volume; MR: mitral regurgitation; RFP: restrictive filling pattern.

TABLE 2. Events

All( N = 803 )

Males( N= 576, 72 % )

Females( N=227, 28% )

P value(Kaplan- Meier)

Mean follow-up (months)

All cause mortality/ heart transplant n(%)

Heart transplant n (%)

Cardiovascular death n (%)

Pump failure death n (%)

Unexpected sudden death n (%)

Unknown cause death n ( % )

Appropriate intervention of ICD N=40N (% of implanted patients 132: 102 men, 30 women)

FIGURE 2. Total death/ heart transplantation free survival.

FIGURE 3. Cardiovascular death free survival.

FIGURE 1. Longitudinal trends during follow-up. Red lines are for females and black lines are for males. NYHA: New York Heart Association class; LVEF: Left ventricular ejection fraction; LVEDD: Left ventricular end-diastolic diameter; LVEDV: left ventricular end-diastolic volume; MR: mitral regurgitation; RFP: restrictive filling pattern.

TABLE 2. Events

All( N = 803 )

Males( N= 576, 72 % )

Females( N=227, 28% )

P value(Kaplan- Meier)

Mean follow-up (months)

All cause mortality/ heart transplant n(%)

Heart transplant n (%)

Cardiovascular death n (%)

Pump failure death n (%)

Unexpected sudden death n (%)

Unknown cause death n ( % )

Appropriate intervention of ICD N=40N (% of implanted patients 132: 102 men, 30 women)

FIGURE 2. Total death/ heart transplantation free survival.

LVRR after OPT

Aimo et al. JACC HF 2017

Fa-Hui Yin et al. Plos One 2017

Han et al. Plos One 2017

LVRR after CRT

32,3 ‰

8,6 ‰

102,2 ‰

38,4 ‰

In an analysis of the Medicare Claims database:women were 3 times less likely than men to receive an ICD for primary preventionand 2,5 times less likely tha men to receive an ICD for secondary prevention !!!

No longer racial disparities… sex differences persisted

Likelihood of receiving evidence-based treatment

Keller et al Can J Cardiol 2016

HFpEF: HF of ELDERLY

Gori M et al. Eur J Heart Fail 2014

HFpEF: HF of WOMEN

HFpEF

HFpEF

HFpEF

Characteristic Women (n=2491) Men (n=1637) P Value

Age, y 72±7 71±7 <0.001Obesity*, % 46 35 <0.001Heart failure cause, % ischemic 19 34 <0.001Hypertension, % 91 85 <0.001Atrial fibrillation, % 27 33 <0.001Diabetes mellitus, % 28 27 0.74

Chronic obstructive pulmonary disease, %

8 13 <0.001

Smoking, % 9 32 <0.001NYHA class II/III/IV, % 20/77/2 22/75/3 0.006

Hospitalization in the last 6 mo, % 44 45 0.49

Ejection fraction, % 61±9 58±9 <0.001Minnesota living with heart failure

score45±21 39±21 <0.001

Median (Q1–Q3) NT-pro-BNP, pg/mL 301 (126–897) 413 (155–1051) <0.001Hemoglobin, g/dL 13.5±1.8 14.5±1.9 <0.001Anemia†, % 11 16 <0.001Chronic kidney disease‡, % 34 26 <0.001

Medications

Loop diuretic, % 51 53 0.08

Thiazide diuretic, % 41 34 <0.001Spironolactone, % 15 17 0.08

Angiotensin-converting enzymeinhibitor, %

23 29 <0.001

Digoxin, % 12 16 0.006

β-Blocker, % 59 59 0.93

Antiarrythmic, % 8 11 0.003

Calcium channel blocker, % 42 37 <0.001Nitrate, % 25 30 <0.001Oral anticoagulant, % 55 64 <0.001Aspirin, % 52 59 <0.001Lipid lowering, % 28 35 <0.001

Lam C et al. Circulation Heart Fail 2012

WOMEN vs. MEN in HFpEF

Outcome

Event Rate Per 100 Patient-Years Multivariable Analysis*

Women Men HR (95% CI), Women vs Men PValue

All-cause death 4.32 6.72 0.70 (0.59–0.83) <0.001All-cause hospitalization or death 19.42 25.05 0.80 (0.72–0.89) <0.001

Cardiovascular hospitalization or death 11.76 15.97 0.81 (0.72–0.92) 0.001

Noncardiovascular hospitalization or death 9.89 12.40 0.78 (0.69–0.90) <0.001

Heart failure hospitalization or death 4.43 5.02 0.94 (0.77–1.14) 0.51

First all-cause hospitalization 18.43 23.14 0.77 (0.66–0.89) <0.001

Lam C et al. Circulation Heart Fail 2012

WOMEN vs. MEN in HFpEF

Ziaeian and Fonarow, Nat Cardiol Rev. 2016

WOMEN vs. MEN in HFpEF

Summary• Compared to men, women have several differences in HF:

• Physiology• Psychological• Social• Etiology of heart failure• Response to therapy

• HFeRF: typical of man; reduced mortality --> mostly in women (except ACS)

• HFpEF: typical of women and elderly; women have better survival than men but global survival has been unchanged (complex syndrome)

• HFpEF: increasing incidence

• Heart failure types more common in women• Diastolic HF, Takotsubo CM, pregnancy

• Women in HF: • understudied gap of knowledge• Precision medicine• Social changes

GRAZIE