Download Clinicopathologic profiles of progressive heart failure in hypertrophic

The best of the European Heart JournalCardiomyopathies
No conflict of interest
PROFILES OF HEART FAILURE IN HCM
• Clinical presentation and natural history of
hypertrophic cardiomyopathy (HCM) is
heterogeneous, ranging from benign
asymptomatic forms to more malignant
expressions.
• Although the risk for sudden cardiac death in
young patients has been a highly visible
complication, it should be underscored that
HCM is also an important cause of heart
failure-related disability and death.
NATURAL HISTORY OF HCM
Stable and Benign Course
Profiles in Prognosis for HCM
Sudden death
AF
Symptom
End - stage
progression
Modified from Maron BJ, McKenna et al. JACC 2003; 42:1687-713
AIMS
• Profiles of severe progressive heart failure
symptoms and death, or heart transplantation
deserve more complete definition.
• We have longitudinally assessed a large
consecutive single-institution cohort of HCM
patients to derive insights into the
pathophysiology of heart failure.
What is it known about severe heart failure and systolic
dysfunction designated as the “end-stage” phase?
This evolution, with or without
LV chamber remodelling has
been reported in 3-5% of HCM
cohort by Harris K M et al. and
Biagini E et al. (JACC 2005;
46:1543-1550).
Harris K M et al. Circulation 2006;114:216-225
CLINICAL PRESENTATION AND PROGRESSION
FEMALE’S DIFFERENCES?
Relative risk (RR 1.5) of progression to NYHA classes III or HF or stroke death
Cumulative risk of progression to New York Heart Association
functional classes III and IV, or heart failure or stroke death
related to age at initial evaluation and gender.
Olivotto et al., JACC 2005; 46:480-7.
PROGNOSTIC VALUE
OF CRONIC ATRIAL FIBRILLATION
Cumulative risk for adverse outcome in HCM patients with exclusively
paroxysmal (n=45) and chronic (n=62) AF. Adverse outcome was defined as
combined end point including HCM-related death, progression to NYHA
class III or IV, or stroke.
Olivotto J, et al. Circulation 2001; 104: 2517-2524
PROGNOSTIC VALUE OF OBSTRUCTION
RESULTS
Advanced Heart Failure
10 HF deaths
50 (17%)
8 heart transplants
243 (83%)
NYHA III-IV
NYHA I-II
Incidence of advanced heart failure and death was 24/1000 HCM patient-year (95% C.I.: 18-32)
BASELINE CHARACTERISTICS IN HCM WITH OR
WITHOUT ADVANCED HEART FAILURE
FEMALE
GENDER
FEMALE
GENDER
ATRIAL FIBRILLATION at entry and/or during FU
AF at entry and/or during FU
54%
64%
80
60
50
31%
60
%
30
20
20%
40
20
10
0
0
1
p=0.008
NYHA III-IV
1
p<0.0001
NYHA III-IV
NYHA I-II
LA volum e index
LA volume index
85+/-32
ml/m2
100
mL/m2
%
40
61+/-23
ml/m2
80
60
40
20
0
1
p=0.0003
NYHA III-IV
NYHA I-II
NYHA I-II
PROFILES OF HEART FAILURE OR DEATH
1. END-STAGE SYSTOLIC DYSFUNCTION
(EF< 50%) (15; 30%)
2. LEFT VENTRICLE OUTFLOW
OBSTRUCTION (11; 22%)
3. NON-OBSTRUCTIVE WITH PRESERVED
SYSTOLIC FUNCTION (24; 48%)
TIME LINES FOR THE 3 HCM PATIENT SUBGROUPS
END-STAGE SYSTOLIC DYSFUNCTION
Male, 59 yrs (age at Tx)
LA diameter 70 mm
LVEDD 62 mm
EF 30%
MaxLVWT 13 mm
TNNT2 ex 9 Arg94Leu
OBSTRUCTIVE HCM
A 67-year-old woman died of heart failure refractory to drug therapy
NON-OBSTRUCTIVE HCM WITH PRESERVED
SYSTOLIC FUNCTION AND AF
Male, 60 yrs (age at Tx)
Permanent AF
LVEDD 55mm
EF 57%
MaxLVWT 18mm
Mitral regurgitation 2+/4
MYH7 ex 27 Ile1207Met
NON-OBSTRUCTIVE HCM WITH PRESERVED SYSTOLIC FUNCTION:
RESTRICTIVE FORM OF HF DUE TO DIASTOLIC DYSFUNCTION IN SINUS
RHYTHM
Female
28 yrs (age at Tx)
LA diameter 53 mm
Normal-sized ventricles
EF 58%
MaxLVWT 17 mm
TNNI3 ex 8 Lys207Thr
NON-OBSTRUCTIVE HCM
WITH PRESERVED SYSTOLIC FUNCTION
AND MASSIVE LV HYPERTROPHY
Female, 12 yrs (age at Tx)
Normal-sized LV cavity
EF 72%
MaxLVWT 30 mm
MYBPC3 ex 11 Ala364Thr
MYBPC3 ex 12
-CS
-CMut
CONCLUSIONS
• Profiles of advanced heart failure in HCM are due to
diverse pathophysiological mechanisms, including LV
outflow obstruction and diastolic or global systolic
ventricular dysfunction.
• Atrial fibrillation proved to be the most common disease
variable associated with progressive heart failure.
• Extensive transmural myocardial scarring influences
progression to end-stage systolic dysfunction.
• No relationship between genetic substrate and HF profile.
• Recognition of the heterogeneous pathophysiology of heart
failure in HCM is relevant, given the targeted management
strategies necessary in this disease
THANK YOU
FOR THE ATTENTION
Overall Population With Hypertrophic Cardiomyopathy (HCM)
Progressive
Heart Failure
Symptoms
Genotype-Positive
None or
Phenotype-Negative Mild Symptoms
Longitudinal
Follow-up
No treatment
Or
Drug Theraphy
Drug Theraphy
High Risk of
Sudden Death
ICD
Atrial
Fibrillation
Pharmacological
Rate Control
Cardioversion
Anticoagulation
Drug-Refractory HF Symptoms
Alternatives to Surgery
Alcohol Septal Ablation
Chronic DualChamber Pacing
Obstructive HCM
(Rest or Provocation)
Nonobstructive HCM
(Rest and Provocation)
Ventricular Septal
Myotomy-Myectomy
Heart Transplantation
Modified from Maron BJ. JAMA 2002; 287:1308-1320
PATHOPHYSIOLOGIC AND HEMODYNAMIC INTERRELATIONS BETWEEN LEFT VENTRICULAR
(LV) HYPERTROPHY, SUBAORTIC OBSTRUCTION, DIASTOLIC DYSFUNCTION, AND MYOCARDIAL
ISCHEMIA IN HYPERTROPHIC CARDIOMYOPATHY.
Left ventricular hypertrophy
LV SP
LV outflow tract
obstruction
Diastolic dysfunction
EDP
PA
Relaxation Velocity
Ischemia
Small Vessel Disease
Maron BJ.et al. N Engl J Med 316:844-852, 1987