Hypertrophic cardiomyopathy

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  • Increased voltages c/w left ventricular hypertrophy Repolarization changes Q waves = not ischemia – reflect anterior septal thickness
  • Decreased projection of basal septum into the LVOT
  • Gold standard for pts w/ drug-refractory HCM Resect a small portion of myocardium from septum – enlarges LVOT and relieves obstruction; also causes concomitant mitral regurg to disappear Operative mortality: <1% Complications rare (heart block, VSD, aortic regurg)
  • Retrospective trial by a group at the Mayo Clinic Aim: Long-term effects of myectomy on survival Looked at mortality retrospectively among 3 groups from 1983-2001: 1) myectomy 2) LVOT obstruction w/o surgery 3) Non-obstructive HCM Mean follow-up: 6 yrs Compared to non-operative obstructive, myectomy patients had superior survival free from all-cause mortality / HCM-related mortality / sudden cardiac death.
  • Same group from Mayo Clinic Compared treatment effects of dual-chamber pacing versus septal myectomy Non-randomized prospective trial of 39 patients: 20  myectomy / 19  pacing Myectomy: greater reduction in LVOT gradients, larger improvements in NYHA class, exercise time, oxygen consumption
  • Alcohol septal ablation. A catheter is inserted into the LAD and directed into the septal branch that supplies blood to the hypertrophied portion of the septum. The septal artery catheter balloon is inflated preventing backwash of alcohol into the remainder of the coronary tree. Through a distal port on the balloon-tipped catheter,1-3 mL of ethanol is injected into the septal artery resulting in a controlled myocardial infarction. This scarring leads to progressive thinning of the septum  outflow tract enlargement (mimicking LV remodeling that occurs after myectomy).
  • Complete heart block: 30-40% in early studies, now <10% using smaller doses of alcohol more selectively Large MIs: from alcohol leakage into other coronary arteries
  • Non-randomized study – aim to determine outcomes in a tertiary referral center Of 601 patients referred between 1998-2006, 138 chose alcohol septal ablation Median age 64 yo Fewer procedural complications in patients w/ myectomy: combined post-procedural complication rate 26% in ablation vs. 5% in myectomy 2 deaths – 1 patient transferred from OSH w/ cardiogenic shock, 1 patient w/ pulmonary HTN Overall survival: 93.5% at 2 yrs, 88% at 4 yrs
  • Initial registry study in 2000 looking at the efficacy of ICDs for the prevention of SCD in HCM patients Retrospective multicenter study of 19 centers in US and Italy 128 consecutive patients enrolled; ICDs placed between 1984-1998 85 pts = primary prevention 43 pts = secondary prevention
  • Long-term athletic training can produce “athlete’s heart” = increased LV diastolic cavity dimensions/wall thickness/mass.
  • Hypertrophic cardiomyopathy

    1. 1. Hypertrophic Cardiomyopathy Dr. Fuad Farooq Resident CardiologyAga Khan University Hospital
    2. 2. Case17 years old male professional basketball player with noknown past medical history collapses on the playing floorduring practice and subsequently arrests. He had beenhaving some exertional dyspnea for a few months prior tothis incident but it did not affect his activity level. He wastold growing up that he had a “heart murmur” that wasnever formally investigated. He was taking nomedications, and there was no family history of cardiacdisease in his family. An autopsy later revealed that thepatient had hypertrophic cardiomyopathy.
    3. 3. Background Hypertrophic cardiomyopathy is a genetic disorder that is typically inherited in an autosomal dominant fashion with variable penetrance and variable expressivity The disease has complex symptomatology and potentially devastating consequences for patients and their families HCM is the leading cause of sudden cardiac death in preadolescent and adolescent children
    4. 4. Background The hallmark of the disorder is myocardial hypertrophy that is inappropriate, often asymmetrical and occurs in the absence of an obvious inciting hypertrophy stimulus This hypertrophy can occur in any region of the left ventricle but frequently involves the IVS, which results in an obstruction of flow through the LVOT
    5. 5. Background Prevalence of HCM: 0.05-0.2% of the population  This occurrence is higher than previously thought, suggesting a large number of affected but undiagnosed people Morphologic evidence of disease is found by echocardiography in approximately 25% of first-degree relatives of patients with HCM Men and African-Americans affected by almost 2:1 ratio over women and Caucasians Global disease with most cases reported from USA, Canada, Western Europe, Israel, & Asia Maron BJ et al. Circulation. Aug 15 1995;92(4):785-9
    6. 6. Historical Perspective HCM was initially described by Teare in 1958  Found massive hypertrophy of ventricular septum in small cohort of young patients who died suddenly Braunwald was the first to diagnose HCM clinically in the 1960s Many names for the disease  Idiopathic hypertrophic subaortic stenosis (IHSS)  Muscle subaortic stenosis  Hypertrophic obstructive cardiomyopathy (HOCM)
    7. 7. Genetic Basis of HCM  Autosomal dominant inheritance pattern  >450 mutations in 13 cardiac sarcomere & myofilament (myosin heavy chain, actin, tropomyosin, and titin) related genes identified  Genotype specific risks for mortality and degree of hypertrophy  Genetic basis of ventricular hypertrophy does not directly correlate with prognostic risk stratificationAlcalai et al. J Cardiovasc Electrophysiol 2008;19:104-110.
    8. 8. Genetics of HCMAlcalai et al. J Cardiovasc Electrophysiol 2008;19:105.
    9. 9. Patterns
    10. 10. Pathophysiology of HCMThe pathophysiology of HCM involves 4 interrelated processes:  Left ventricular outflow obstruction  Diastolic dysfunction  Myocardial ischemia  Mitral regurgitation
    11. 11. LV Outflow Obstruction in HCM Long-standing LV outflow obstruction is a major determinant for heart failure symptoms and death in HCM patients Subaortic outflow obstruction is caused by systolic anterior motion (SAM) of the mitral valve – leaflets move toward the septum
    12. 12. LV Outflow Obstruction in HCM Explanations for the SAM of the mitral valve1. Mitral valve is pulled against the septum by contraction of the papillary muscles, which occurs because of the valves abnormal location and septal hypertrophy altering the orientation of the papillary muscles2. Mitral valve is pushed against the septum because of its abnormal position in the outflow tract3. Mitral valve is drawn toward the septum because of the lower pressure that occurs as blood is ejected at high velocity through a narrowed outflow tract (Venturi effect)
    13. 13. LV Outflow Obstruction in HCM Physiological Consequences of Obstruction  Elevated intraventricular pressures  Prolongation of ventricular relaxation  Increased myocardial wall stress  Increased oxygen demand  Decrease in forward cardiac output
    14. 14. Freedom from HCM related deaths Maron MS et al. NEJM. 2003;348:295.
    15. 15. Pathophysiology of HCMThe pathophysiology of HCM involves 4 interrelated processes:  Left ventricular outflow obstruction  Diastolic dysfunction  Myocardial ischemia  Mitral regurgitation
    16. 16. Pathophysiology of HCM Diastolic Dysfunction  Contributing factor in 80% of patients  Impaired relaxation  High systolic contraction load  Ventricular contraction/relaxation not uniform  Accounts for symptoms of exertional dyspnea  Increased filling pressures  increased pulmonary venous pressure
    17. 17. Pathophysiology of HCMThe pathophysiology of HCM involves 4 interrelated processes:  Left ventricular outflow obstruction  Diastolic dysfunction  Myocardial ischemia  Mitral regurgitation
    18. 18. Pathophysiology of HCM Myocardial Ischemia  Often occurs without atherosclerotic coronary artery disease  Postulated mechanisms  Abnormally small and partially obliterated intramural coronary arteries as a result of hypertrophy  Inadequate number of capillaries for the degree of LV mass and increased myocardial oxygen consumption  Increased filling pressures  Resulting in subendocardial ischemia
    19. 19. Pathophysiology of HCMThe pathophysiology of HCM involves 4 interrelated processes:  Left ventricular outflow obstruction  Diastolic dysfunction  Myocardial ischemia  Mitral regurgitation
    20. 20. Pathophysiology of HCM Mitral Regurgitation  Results from the systolic anterior motion of the mitral valve  Variations in leaflet length (posterior/anterior leaflet length mismatch) – restrict the ability of the posterior leaflet to follow the anterior leaflet and to coapt effectively resulting in MR  Severity of MR directly proportional to LV outflow obstruction  Results in symptoms of dyspnea, orthopnea in HCM patients
    21. 21. Clinical Presentation Dyspnea on exertion (90%), orthopnea, PND Palpitations (PAC, PVC, sinus pauses, AF, A flutter, SVT and VT) Congestive heart failure (2o to increased filling pressures and myocardial ischemia) Angina (70-80%) Syncope (20%), Presyncope (50%)  Outflow obstruction worsens with increased contractility during exertional activities resulting in decrease in cardiac output  Secondary to arrhythmias
    22. 22. Clinical Presentation Sudden cardiac death  HCM is most common cause of SCD in young people, including athletes  Can be the first manifestation  Most common cause is arrhythmias esp. VF either denovo or AF degenerated into VF 2o accessory pathway
    23. 23. Physical Examination Carotid Pulse  Bifid – rises quickly, then declines in midsystole followed by a secondary rise in carotid pulsation during late systole short upstroke & prolonged systolic ejection Jugular Venous Pulse  Prominent a wave – decreased RV compliance Apical Impulse  Double apical impulse - forceful left atrial contraction against a highly noncompliant left ventricle  Triple apical impulse results from a late systolic bulge that occurs when the heart is almost empty and is performing near-isometric contraction
    24. 24. Physical Examination Heart Sounds  S1 usually normal  S2 usually split but in severe stenosis – paradoxically split  S3 indicate heart failure  S4 usually present due to hypertrophy  Murmur  Medium-pitch crescendo-decrescendo systolic murmur along LLSB and apex and radiates to suprasternal notch  Dynamic maneuvers  Murmur intensity increases with decreased preload (i.e. Valsalva, standing, nitrates, diuretics)  Murmur intensity decreases with increased preload (i.e. squatting, hand grip)
    25. 25. Physical Examination Holosystolic murmur at the apex and axilla of mitral regurgitation is heard in patients with systolic anterior motion of the mitral valve and significant LV outflow gradients Diastolic decrescendo murmur of aortic regurgitation is heard in 10% of patients, although mild aortic regurgitation can be detected by Doppler echocardiography in 33% of patients
    26. 26. Diagnostic Evaluation Electrocardiogram Echocardiogram Catheterization Cardiac MR
    27. 27. Electrocardiogram in HCMLVH with nonspecific ST/T wave abnormalitiesLeft or right axis deviation, LAE, Conduction abnormalitiesAbnormal and prominent Q wave in the anterior precordial and lateral limb leadsA fib with preexitation implies poor prognosisFindings on Holter monitoring include APC’s VPC’s, sinus pauses, wandering atrial pacemaker,atrial tachycardia, AF/flutter and nonsustained ventricular tachycardia.
    28. 28. Echocardiography in HCM 2-D echocardiography is diagnostic for HCM  Abnormal systolic anterior leaflet motion of the mitral valve  LV hypertrophy  Left atrial enlargement  Diastolic dysfunction  Small ventricular chamber size  Septal hypertrophy with septal to free wall ratio greater than 1.4:1 (absolute septal wall thickness >15mm)  SAM of anterior and rarely posterior mitral valve leaflet and mitral regurgitation  Decreased mid aortic flow  Partial systolic closure of the aortic valve in mid systole
    29. 29. Cardiac MRI in HCM Useful when echocardiography is questionable, particularly with apical hypertrophy Cines loops typically show obstruction and velocity mapping is useful in the assessment of peak velocities SAM of the mitral valve is clearly seen on cardiac MRI Improvement in obstruction after septal ablation or myomectomy can be demonstrated, as can the location and size of the associated infarction, which are useful for planning repeat procedures Cardiac MRI tagging identifies abnormal patterns of strain, shear, and torsion in cases of HCM, demonstrating significant dysfunction in hypertrophic areas of the ventricle
    30. 30. Cardiac MRI in HCM Gadolinium contrast cardiac MRI - differentiating HCM from other causes of cardiac hypertrophy and other types of cardiomyopathy such as, amyloidosis, athletic heart, and Fabry’s disease Late gadolinium enhancement occurring in HCM represents myocardial fibrosis  The greater the degree of late gadolinium enhancement, the more likely that the particular HCM patient has 2 or more risk factors for sudden death  More likely the patient has or will develop progression of ventricular dilation toward heart failure, thereby indicating a poorer prognosis Most patients with HCM have no gadolinium enhancement  Common benign pattern is 2 stripes running along the junction of the right ventricle insertion into the left ventricle
    31. 31. Apical HCM by Echo & CMR •64 female with CP & palpitation •ECG – extensive T wave inversion •Echo – akinetic apex & diastolic dysfunction •Cine CMR – confirmed clinical suspicion of apical HCM
    32. 32. High risk HCM•33 male with HCM and family history ofsudden death•Cine CMR showsHCM with ASH•After gadoliniumextensive lateenhancement•Patient was offered anICD
    33. 33. Cardiac Catheterization Diagnostic cardiac catheterization is useful to determine the degree of LVOT obstruction, cardiac hemodynamics, the diastolic characteristics of the left ventricle, LV anatomy and coronary anatomy Reserved for situations when invasive modalities of therapy, such as a pacemaker or surgery, are being considered Therapeutic cardiac catheterization interventions, include transcatheter septal alcohol ablation The arterial pressure tracing found on cardiac catheterization may demonstrate a "spike and dome" configuration
    34. 34. Cardiac Catheterization Approximately one fourth of patients demonstrate pulmonary hypertension - usually mild Enhancing of LVOT gradient in post PVC  Results in characteristic change recorded on arterial pressure tracing - exhibits a pulse pressure that fails to increase as expected or actually decreases (the so-called Brockenbrough- Braunwald phenomenon)  One of the more reliable signs of dynamic obstruction of the LVOT, intensity of murmur also increased
    35. 35. Cardiac Catheterization • LV gram shows hypertrophied LV • MR secondary to SAM of mitral valve • The LV cavity is often small and systolic ejection is typically vigorous, resulting in virtual obliteration of the ventricular cavity at end systole • In patients with apical involvement, the extensive hypertrophy may convey a spade-like configuration to the left ventricular angiogram
    36. 36. Disease Progression in HCM ACC Consensus Document. J Am Coll Cardiol. 2003;42(9):1693.
    37. 37. Sudden Cardiac Death in HCM Most frequent in young adults <30-35 years old Primary VF/VT Tend to die during or just following vigorous physical activity Often is 1st clinical manifestation of disease HCM is most common cause of SCD among J Am Coll Cardiol. 2003;42(9):1693. young competitive athletes
    38. 38. SCD in Competitive Athletes Maron B. Atlas of Heart Diseases. 1996
    39. 39. Natural History of HCM Heart Failure  Atrial Fibrillation  Only 10-15% progress to  Prevalent in up to 30% of NYHA III-IV older patients  Only 3% will become  Dependent on atrial kick – truly end-stage with CO decreases by 40% if AF systolic dysfunction present Endocarditis  Autonomic Dysfunction  4-5% of HCM patients  25% of HCM patients  Usually mitral valve  Associated with poor affected prognosis
    40. 40. Influence of Gender & Race Women often remain under diagnosed and are clinical recognized after they develop more pronounced symptoms1 HCM clinically under recognized in African- Americans  Most athletes with SCD due to HCM are undiagnosed African-Americans2 1 Olivotto I et al. J Am Coll Cardiol 2005;46:480. 2 Maron BJ et al. J Am Coll Cardiol 2003;41:974.
    41. 41. Treatment of HCM Medical therapy Device therapy Surgical septal myomectomy Alcohol septal ablation
    42. 42. ACC Consensus Document. J Am Coll Cardiol. 2003;42(9):1693.
    43. 43. Medical Therapy Beta-blockers  Increase ventricular diastolic filling/relaxation  Decrease myocardial oxygen consumption  Have not been shown to reduce the incidence of SCD Verapamil  Augments ventricular diastolic filling/relaxation Disopyramide  Used in combination with beta-blocker  Negative inotrope Diuretics
    44. 44. Dual-Chamber Pacing Proposed benefit:  Pacing the RV apex will decrease the outflow tract gradient by decreasing projection of basal septum into LVOT Several RCTs have found that the improvement in subjective measures provided by dual-chamber pacing is likely a placebo effect Objective measures such as exercise capacity and oxygen consumption are not improved No correlation has been found between pacing and reduction of LVOT gradient
    45. 45. Surgical Septal Myectomy Nishimura RA et al. NEJM. 2004. 350(13):1320.
    46. 46. J Am Coll Cardiol 1999;34(1):191-6.
    47. 47. Alcohol Septal Ablation
    48. 48. Alcohol Septal AblationBefore After
    49. 49. Pre Alcohol Septal Ablation
    50. 50. Post Alcohol Septal Ablation
    51. 51. Alcohol Septal Ablation Successful short-term outcomes  LVOT gradient reduced from a mean of 60-70 mmHg to <20 mmHg  Symptomatic improvements, increased exercise tolerance Long-term data not available yet Complications  Complete heart block  Large myocardial infarction No randomized efficacy trials yet for alcohol septal ablation vs. surgical myectomy
    52. 52. Overall survival: 93.5% at 2 yrs, 88% at 4 yrsCirculation. 2008; 18(2): 131-9.
    53. 53. Efficacy of Therapeutic Strategies Nishimura et al. NEJM. 2004. 350(13):1323.
    54. 54. Coil Embolization Case report of 20 patients with drug-refractory HCM Occlude septal perforator branches NYHA functional class and peak oxygen consumption improved at 6 months Significant reduction in septum thickness by echo European Heart Journal 2008;29:350.
    55. 55. Implantable CardioverterDefibrillators in HCMPrimary & Secondary Prevention
    56. 56.  Appropriate discharges in 23% of patients Rate of appropriate discharges of 7% per year Of 21 patients for which intracardiac electrograms were available, 10 shocks for VT, 9 shocks for VF Suggested role for ICDs in primary & secondary prevention of SCDMaron BJ et al. NEJM 2000;342:365-73.
    57. 57. Risk Stratification – ICDs Primary Prevention Risk Factors for SCD  Premature HCM-related sudden death in more than 1 relative  History of unexplained syncope  Multiple or prolonged NSVT on Holter  Hypotensive blood pressure response to exercise  Massive LVH How many risk factors warrant ICD placement?
    58. 58.  Multicenter registry study with 506 pts from 1986-2003 Average age 41 years old 35% pts - primary prevention received ICDs had 1 risk factor Primary Outcome: appropriate ICD interventions terminating VF/VT J Cardiovasc Electrophysiol 2008;19(10).
    59. 59.  3500 asymptomatic elite athletes (75% male), mean age 20.5 +/- 5.8 years, no family hx of HCM 12-lead ECG, 2D-Echo 53 athletes (1.5%) had LVH 3 athletes (0.08%) had ECG and echo features of HCMJ Am Coll Cardiol. 2008;51(10):1033-9.
    60. 60. HCM vs. Athlete’s Heart Circulation 1995;91.
    61. 61. Future Directions Identification of additional causative mutations Risk stratification tools Determining more precise indications for ICDs Defining most appropriate role for alcohol septal ablation ?Gene therapy
    62. 62. Thank You!

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