Fabio M Turazza - oic.it · Titolo: Curiosare fra le raccomandazioni delle linee guida ESC 2014...

Lucca, 29 Novembre 2014

CardioLucca 2014, Heart Celebration

Fabio M TurazzaResponsabile DH e Ambulatorio Cardiomiopatie e Trapianto Cardiaco

Centro A De Gasperis - Niguarda

Data: 29 Novembre 2014 Titolo: Curiosare fra le raccomandazioni delle linee guida ESC 2014 sulle cardiomiopatie

Autore: Evento: CardioLucca 2014Autore:Autore:Autore: Fabio M Turazza

Caldana, GR



Br Heart J, 1958;20:1Br Heart J, 1958;20:1--1818



“Summary…Eight cases of asymmetrical hypertrophy

or muscolar hamartoma of the heart are

discussed. Seven of these caused sudden

death in young adults. The pathological picture is one of bizarre and disorganized

arrangement of muscle bundle……”

“Summary…Eight cases of asymmetrical hypertrophy

or muscolar hamartoma of the heart are

discussed. Seven of these caused sudden

death in young adults. The pathological picture is one of bizarre and disorganized

arrangement of muscle bundle……”

Br Heart J, 1958;20:1-18



Br Heart J, 1958;20:1-18

Beta-MHC (MYH7):

- elevata penetranza

- ipertrofia +++

- aritmogenicità +++

Beta-MHC (MYH7):

- elevata penetranza

- ipertrofia +++

- aritmogenicità +++

* Hollman A, Goodwin JF, Teare D, et al.

A family with obstructive cardiomyopathy.

Br Heart J. 1960;22:449-56.

*



Principal pathways of disease progression in HCMPrincipal pathways of disease progression in HCM

Stable and benign course> 50%

Stable and benign course> 50%

Profiles in Prognosis in HCMProfiles in Prognosis in HCM

End stage5%

End stage5%

SymptomsProgression

16%

SymptomsProgression

16%

AF24%AF24%

Sudden

Death1-6%

Sudden

Death1-6%

All but one of Teare’s cases Teare’s cases n 2, 4, 5 Teare’s cases n 2, 4,



Cardiomiopatia ipertrofica 50 anni dopoCardiomiopatia ipertrofica 50 anni dopo

– Ipertrofia VS in assenza di patologia cardiaca o sistemica

– Molti pazienti asintomatici, identificati occasionalmente

– I sintomi includono dispnea, dolore toracico, palpitazioni, sincope

– Relativamente frequente (1:500, 0.2%), geneticamente determinata (60% dei casi a carattere familiare)

• trasmissione autosomica dominante

• 13 geni che codificano proteine del sarcomero (> 450 mutazioni)

• mutazioni più frequenti nei geni per

� Beta-myosin heavy chain (MYH7)(MYH7)

� Myosin binding protein C (MYBPC3)(MYBPC3)

� Cardiac troponin T (TNNT2)(TNNT2)

~ 70%



Scope of Guidelines

Uniquely for a common CV disease, there are very few

randomized, controlled, clinical trials in patients with HCM.

For this reason, the majority of the recommendations in this document are based on

�observational cohort studies and

�expert consensus opinion.



“What we’re trying to do in these guidelines is to change a mind-set, because hypertrophic cardiomyopathy is not really a diagnosis; it actually represents a family of diseases.

Running throughout this entire document is an emphasis on individualization, from diagnosis all the way through treatment”

Perry Elliott, MD



“There’s a strong emphasis on making a specific diagnosis if you possibly can, because these subtypes of cardiomyopathy have totally different natural histories and in the future will

have very different treatments.”

Perry Elliott, MD



� Effective use of ECG, ECHO (red flags!), and CMRI

� A new SCD risk stratification tool

� Suggestions regarding simple lab tests

� Focus on heart failure

� Stepwise approach to management of LVOTO

� Genetics: were are we going from here?

� Advice on reproduction



ESC 2008 cardiomyopathies classificationElliott P et al, Eur Heart J 2008

Cardiomyopathies

HCM DCM ARVC RCM Unclassified

Familial / genetic

Unidentified gene defect Disease sub-type

Non-familial/Non-genetic

Idiopathic Disease sub-type



HCMs aetiology



General approach to the diagnosis of HCM



Symptoms suggestive of specific diagnosis: clinical red flags

Modified from Rapezzi et al, Eur Heart J 2013



ECG pattern suggestive of specific diagnosis: ECG’s red flags




Echo features suggestive of specific diagnosis: Echo’s red flags


PE

Concentric hypertrophy

Ground-glass appearance



Morte cardiaca improvvisaMorte cardiaca improvvisaMorte cardiaca improvvisa



NEW!NEW!



Major clinical features associated with an increased risk of SCD in adults

2014 ESC Guidelines on Diagnosis and Management of Hypertrophic Cardiomyopathy (Eur Heart J

2014 – doi:10.1093/eurheartj/ehu284)



Pitfalls of previous models* for estimating SCD risk

• Estimation of relative, and not absolute, risk

• They do not account for the different effect size of individual risk factors

• Some risk factors (LV wall thickness) are treated as binary variables

when they are associated with a continous increase in risk**

• Consequently current risk algorithms discriminates modestly

between high and low-risk patients

•

•Maron BJ et al, JACC 2003; Gersh BJ et al, Circulation 2011

** Elliott PM et al, Lancet 2001



HCM Risk-SCD model: predictor variables for sudden cardiac death

HCMRisk-SCD is a multicentre, retrospective, longitudinal cohort study of 3675 pts that uses predictor variables that have been associated with an increased risk of SD in at least one published multivariable analysis. This excludes abnormal BP response as a risk marker.

O’Mahony C et al, Eur Heart J 2013



The HCM Risk-SCD formula is as follows:

Probability SCD at 5 years ¼ 1 – 0.998 exp(Prognostic index)

where Prognostic index ¼ [0.15939858 x maximal wall thickness

(mm)] 2 [0.00294271 x maximal wall thickness2 (mm2)] +

[0.0259082 x left atrial diameter (mm)] + [0.00446131 x maximal

(rest/Valsalva) left ventricular outflow tract gradient (mm Hg)] +

[0.4583082 x family history SCD] + [0.82639195 x NSVT] +

[0.71650361 x unexplained syncope] 2 [0.01799934 x age at clinical

evaluation (years)].

N.B. In HCM Risk-SCD there was a non-linear relationship between the

risk of SCD and maximum left ventricular wall thickness. This is

accounted for in the risk prediction model by the inclusion of a quadratic

term for maximum left ventricular wall thickness.



2014 ESC Guidelines on Diagnosis and Management of Hypertrophic Cardiomyopathy (Eur Heart J 2014 –doi:10.1093/eurheartj/ehu284) O’Mahony C et al Eur Heart J (2014) 35 (30): 2010-2020

The models provides individualized 5-year risk estimates



SCD risk stratification: open issues

� Myocardial fibrosis (contrast enhanced CMR)

Green JJ et al, JACC Cardiovasc Imaging 2012

� LV apical aneurysm

Maron MS et al, Circulation 2008

� Inheritance of multiple sarcomere protein gene mutations

Ingles J et al, J Med Genet 2005



Algorhythm for treatment of HF in HCM



Hypertrophic or Obstructive ? The swinging pendulum(1958-2008, more than 75 different terms used but…)

– Apical asymmetric septal

hypertrophyhypertrophy

– Apical hypertrophichypertrophiccardiomyopathy

–– HypertrophicHypertrophic infundibolar subaortic stenoses

–– HypertrophicHypertrophic nonobstr. cardiomyopathy

–– HypertrophicHypertrophic subaortic stenosis

�� Obstructive Obstructive cardiomyopathy

�� ObstructiveObstructivemyocardiopathy

� Muscolar subaortic

stenosesstenoses

� Functional obstructiveobstructivecardiomyopathy

� Mid-ventricular obstructionobstruction



Pre-LVOTO therapy check list



LVOTO (> 50 mmHg): a short summary

� Several unanswered questions remain, including the prognostic importance of provocable LVOTO and the

impact of treatment (medical or invasive) on SCD.

� Surgery vs. alcohol ablation (SAA): multidisciplinary,

experienced teams should assess all patients before intervention.

� SAA may be less effective in patients with extensive septal scarring on CMR and in patients with very severe

LVH (≥30 mm)

� SAA is controversial in children, adolescents and young adults

• no long-term data on the late effects of a myocardial scar

• technical difficulties and potential hazards in smaller children and infants are greater.



Flow chart for the genetic and clinical screening of probands and relatives



Most commonly implicated sarcomere protein genes



AF and thromboembolism prophylaxis

� As left atrial size is a consistent predictor for AF and stroke in patients

with HCM, patients in sinus rhythm with LA diameter ≥45mmshould

undergo 6–12 monthly 48-hour ambulatory ECG monitoring to detect AF

� As patients withHCM tend to be younger than other high risk groups and

have not been included in clinical trials of thromboprophylaxis, use of the

CHA2DS2-VASc score to calculate stroke risk is not recommended

� Given the high incidence of stroke in patients with HCM and paroxysmal,

persistent or permanent AF, it is recommended that all patients with AF

should receive treatment with VKA. In general, lifelong therapy with oral

anticoagulants is recommended, even when sinus rhythm is restored.

2014 ESC Guidelines on Diagnosis and Management of Hypertrophic Cardiomyopathy (Eur Heart J

2014 – doi:10.1093/eurheartj/ehu284)



Problemi aperti e prospettive futureProblemi aperti e prospettive future

– La diagnosi (correlazione genotipo-fenotipo)

– La morte cardiaca improvvisa

– L’imaging di nuova generazione



“If I have seen further it is by standing

on the shoulders of giants”

Isaac Newton, 1676………

Donald Teare

Russel Brock

Michael Davies

Andrew Morrow

Eugene Braunwald

John Goodwin

Fulvio Camerini

Doug Wigle

William McKenna

Barry Maron

……….



Grazie per la vostra attenzione !

Caldana

(Grosseto))

Fabio M Turazza - oic.it · Titolo: Curiosare fra le raccomandazioni delle linee guida ESC 2014...

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