Hypertrophic Cardiomyopathy
Stephen Heitner, MDD
A Little Backround
Some Diagnostic Testing
Clinical Considerations
Tratment Considerations
14 y/o playing at school
25 y/owalking
home from work
25 y/owalking
home from work
21 y/o Running to catch a bus
21 y/ocycling in a home in a
storm
45 y/oafter mitral
valve surgery
28 y/o collapse in the street
33 y/o walking to work
Teare D. Asymmetrical hypertrophy of the heart in young adults. British heart journal 1958;20:1-8.
Morrow AG, Braunwald E. Functional aortic stenosis; a malformation characterized by resistance to left ventricular outflow without anatomic obstruction. Circulation 1959;20:181-9.
27 y/o Murmur
20 y/oDyspnea and chest
pain
16 y/o Murmur and angina
1956
Braunw
ald
1959
Hollman
1958
Teare
1960
Morrow
Brocke
nbro
ugh
1961
1964
Harriso
nBrau
nwald
Sigwart
1995
1990
Seidm
an
1990
idman
Maron
2000
1979
Echo
2006
MRI
Courtesy of Barry Maron
Perspective
HCMPossible HCMCoronary AnomaliesMyocarditisChannelopathiesRuptured AAARVCCommotio CordisOther
Maron, B.J., Sudden death in young athletes. N Engl J Med, 2003. 349(11): p. 1064-75.
New Disease
Scary Disease
Rare Disease
Discovery Phase
Less Scary Disease
Unusual Disease
Treatment Phase
Treatable Disease
Common Disease
A rose by any other name would smell as sweet
Courtesy of Barry Maron
>15mm (adult)> 2 SD (ped)
Elevated wall stressAthletic conditioning
Thick walls Non-dilated LV
No cause for LVH
Definition
Morphologic diagnosis
Normal Architecture
Myocyte Disarray
Histopathologic diagnosis
β-myosin Heavy Chain 25-30%
Myosin-binding protein C 20-30%
Trop T - 3-5%Trop I - < 5%
Tropomysin 1αReg. myosin light chain 2 - <5%
Ess. myosin L-chain 3α-Cardiac actin 1
TitinTroponin C
α-Myosin heavy chainMuscle LIM protein
Myosin light chain kinase 2LIM binding domain 3
TelethoninVinculin/metavinculin
α-Actinin 2Phospholamban
Myozenin 2Junctophilin 2
Sigmoidal40-50%
Reverse Curve30-40%
Neutral10%
Apical10%
The Mitral Valve in HCM
• SAM
• MAC
• Elongation of leaflets
• Decreased mobility of the posterior leaflet
• Abnormal papillary muscle
LVOTO
Kwon, D. H., R. M. Setser, et al. (2008). "Abnormal papillary muscle morphology is independently associated with increased left ventricular outflow tract obstruction in hypertrophic cardiomyopathy." Heart 94(10): 1295-1301.
Fabry’s Disease
Danon’s disease - LAMP2 Deficiency
PRKAγ2 Mutation
Pompe’s diseaseFabry’s disease
Not all hypertrophy is HCM
Pompe’s Disease
Hypertrophy and WPW
SCD
•< 35 yrs•Asymptomatic
AF
•CHF•CVA
CHF
•Exertional•Progressive
Presentation Benign
Maron MS, Rowin EJ, Olivotto I, et al. Contemporary Natural History and Management of Nonobstructive Hypertrophic Cardiomyopathy. J Am Coll Cardiol. 2016;67(12):1399-1409. doi:10.1016/j.jacc.2016.01.023.
Maron MS, Rowin EJ, Olivotto I, et al. Contemporary Natural History and Management of Nonobstructive Hypertrophic Cardiomyopathy. J Am Coll Cardiol. 2016;67(12):1399-1409. doi:10.1016/j.jacc.2016.01.023.
Heterogenous
Unpredictable
Obstruction to LV outflow is dynamic, varying with loading conditions and
contractility of the ventricle
•Valsava•Inotropic agents•Dehydration•Decrease afterload
•Hand-grip•Negative inotropes•Increased afterload
LV Cavity Volume or
Contractility
Increased Murmur
LV Cavity Volume or
Contractility
Decreased Murmur
CHF LVOTO
Systolic HF
Diastolic HF
LVOTO
Kwon, D. H., R. M. Setser, et al. (2008). "Abnormal papillary muscle morphology is independently associated with increased left ventricular outflow tract obstruction in hypertrophic cardiomyopathy." Heart 94(10): 1295-1301.
Physical Findings
Valvular Aortic Stenosis IHSS
Brockenbrough’s Sign
EDWIN C. BROCKENBROUGH, EUGENE BRAUNWALD and ANDREW G.A Hemodynamic Technic for the Detection of Hypertrophic Subaortic Stenosis, Circulation. 1961;23:189-194
LVOTO
Maron, M. S., I. Olivotto, et al. (2003). "Effect of left ventricular outflow tract obstruction on clinical outcome in hypertrophic cardiomyopathy." The New England journal of medicine 348(4): 295-303.
LVOTOTreatment of LVOTO
β-blockerCa++-blockerDysopirimide
Medical Septal Reduction Pacemaker
Induction of Septal Dyssynchrony
Mitral Valve Plication
ETOH Septal Ablation
Pap Realignment
Surgical Myectomy
LVOTOMedical Therapies
β-blockers 1
Non-dihydropyridine Ca++-blockers
VerapamilDiltiazem
2
Disopyrimide3
LVOTO
Sherrid, M. V., I. Barac, et al. (2005). "Multicenter study of the efficacy and safety of disopyramide in obstructive hypertrophic cardiomyopathy." Journal of the American College of Cardiology 45(8): 1251-1258.
Morrow Procedure
Ommen, S. R., B. J. Maron, et al. (2005). "Long-term effects of surgical septal myectomy on survival in patients with obstructive hypertrophic cardiomyopathy." Journal of the American College of Cardiology 46(3): 470-476.
Ball, W., J. Ivanov, et al. (2011). "Long-term survival in patients with resting obstructive hypertrophic cardiomyopathy comparison of conservative versus invasive treatment." Journal of the American College of Cardiology 58(22): 2313-2321.
LVOTO
Alcohol Septal Ablation
Infarct
Sorajja, P., U. Valeti, et al. (2008). "Outcome of alcohol septal ablation for obstructive hypertrophic cardiomyopathy." Circulation 118(2): 131-139.
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Nagueh, S. F., B. M. Groves, et al. (2011). "Alcohol septal ablation for the treatment of hypertrophic obstructive cardiomyopathy a multicenter north american registry." Journal of the American College of Cardiology 58(22): 2322-2328.
98%
96%
83%
Ommen, S. R., B. J. Maron, et al. (2005). "Long-term effects of surgical septal myectomy on survival in patients with obstructive hypertrophic cardiomyopathy." Journal of the American College of Cardiology 46(3): 470-476.
LVOTO
98%
95%
88%
LVOTO
Fananapazir, L., et al., Impact of dual-chamber permanent pacing in patients with obstructive hypertrophic cardiomyopathy with symptoms refractory to verapamil and beta-adrenergic blocker therapy. Circulation, 1992. 85(6): p. 2149-61.
Maron, B.J., et al., Assessment of permanent dual-chamber pacing as a treatment for drug-refractory symptomatic patients with obstructive hypertrophic cardiomyopathy. A randomized, double-blind, crossover study (M-PATHY). Circulation, 1999. 99(22): p. 2927-33.
LVOTO
Systolic HF β-blockerACE-I or ARBAldosterone
BlockerDiuretic
ICD +\- CRT
Transplantation
Diastolic HF
Careful Diuresis
Transplantation
SCD
•Paucity of data•Relative infrequency of HCM and SCD•Cumulative Morbidity of living with an ICD
ICD
ICD for 1o Prevention
•Personal Hx of SCD/VT/VF•Documented NSVT•Family Hx of SCD•Unexplained Syncope•Wall thickness >30mm•Abnormal exercise BP response
Established Risk Markers
O'Mahony, C., et al., A novel clinical risk prediction model for sudden cardiac death in hypertrophic cardiomyopathy (HCM risk-SCD). Eur Heart J, 2014. 35(30): p. 2010-20.
http://www.doc2do.com/hcm/webHCM.html
AF
2/3 patients are symptomatic
All patients should be anti-coagulated unless contraindicated
Common - about 1/4 patients will develop AF
Associated with a worse survival
AF
Olivotto, I., F. Cecchi, et al. (2001). "Impact of atrial fibrillation on the clinical course of hypertrophic cardiomyopathy." Circulation 104(21): 2517-2524.
Clinical Trials at OHSUEleclazine
PerherhexilineexilineB-myosin HC inhibitor
Exercise in HCMNovel predictors HCM
Thank You
40 mmHg
Effect of Isoproterenol Effect of Propranolol
Harrison DC, Braunwald E, Glick G, Mason DT, Chidsey CA, Ross J, Jr. Effects of Beta Adrenergic Blockade on the Circulation with Particular Reference to Observations in Patients with Hypertrophic Subaortic Stenosis. Circulation 1964;29:84-98.
Mitten, M. J., B. J. Maron, et al. (2005). "Task Force 12: legal aspects of the 36th Bethesda Conference recommendations." Journal of the American College of Cardiology 45(8): 1373-1375.
Phenotypic Heterogeneity
Lack of Consistent Biological Effect of Current Therapies
Need for Individualized/Targeted Therapies
Biomechanical Stress Sensing Altered Calcium Trafficking
Energy Homeostasis Fibrosis
Structural MechanicalBiochemicalMetabolic
Sarcomeric Mutation +
Stress