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Hypertrophic cardiomyopathy
- 3. • The most common of the genetic cardiovascular disease. • As an autosomal dominant disease • The most common cause of SCD in the young
- 4. HCM: Definitions • Increased left ventricular wall thickness not solely explained by abnormal loading conditions • ADULTS: LV wall thickness ≥15 mm in one or more LV myocardial segments measured by any imaging technique • CHILDREN: LV wall thickness more than two standard deviations above the predicted mean (z-score >2)
- 5. Epidemiology • Prevalence approximately 0.2% • frequency of 1 in 500 people. • presentation during all phases of life, from infancy to old age
- 6. Aetiology
- 7. • Obstruction is not an invariable feature, • 1/3 of patients have the nonobstructive form of HCM. Idiopathic hypertrophic subaortic stenosis Hypertrophic obstructive cardiomyopathy muscular subaortic stenosis • Hypertrophic cardiomyopathy (HCM) with or without outflow obstruction.
- 8. GENETICS • Mendelian trait with an autosomal dominant • mutations in 11 or more genes of cardiac sarcomere • MYH7 • MYBPC3 • Equal frequency in men and women
- 10. Indications for genetic testing in probands
- 12. FAMILY SCREENING STRATEGIES 12yrs • Begin at age of 12 yrs • (two-dimensionalechocardiography or CMR ) 12-18 months • If these studies do not show LV hypertrophy by the time full growth is achieved (at 18 to 21 years of age), it is likely that an HCM-causing mutation is absent Repeat every 5 yrs Definitive Genetic Screening
- 13. Resting and ambulatory electrocardiography • Generally shows a variable combination of LVH, ST- and T-wave abnormalities, and pathological Q-waves. • NSVT – 25% • PSVT – 38% • Ambulatory ECG monitoring is recommended at the initial clinical assessment to assess the risk of sudden cardiac death and stroke
- 15. Echocardiography • Assessment of left ventricular wall thickness it is essential that all LV segments from base to apex be examined, ensuring that the wall thickness is recorded at mitral, mid-LV and apical levels
- 16. • Associated abnormalities of the mitral valve and left ventricular outflow tract
- 18. Elongated Anterior and Posterior Mitral Leaflets
- 21. • Anterior and Basilar Displacement of the Anterolateral Papillary Muscle • Insertion of Anterolateral Papillary Muscle Directly Into the Midanterior Mitral Valve Leaflet • Anterior Mitral Tenting By Papillary Muscles and Fibrotic, Retracted Secondary Chordae • Elongated Posterior Leaflet with SAM
- 22. Should Mitral Surgery Accompany Myectomy? • No Clinical Trials. • Take clinical decision.
- 24. Left Ventricular Outflow Tract Obstruction • LVOTO – Instantaneous peak Doppler LV outflow tract pressure gradient ≥30 mm Hg at rest or during physiological provocation such as Valsalva manoeuvre, standing and exercise. • ≥50 mm Hg haemodynamically important.
- 26. Subaortic obstruction in HCM represents true mechanical impedance to LV outflow increased intraventricular pressures increasing myocardial wall stress and oxygen Demand
- 27. Recommendations for TTE evaluation in HCM
- 30. Recommendations for CMR evaluation in hypertrophic cardiomyopathy
- 32. Reverse curvature septum HCM
- 35. Apical HCM
- 37. Symptoms • Chest pain Myocardial ischaemia due to microvascular dysfunction,increased LV wall stress and LVOTO Patients with typical angina on exertion should be considered for invasive or CT coronary angiography
- 39. Heart Failure • [NYHA] class III or IV) is relatively infrequent • Principal determinants LV outflow obstruction Atrial fibrillation Diastolic dysfunction • 3% advanced (endstage) heart failure associated with systolic dysfunction • The end stage, with unrelenting heart failure symptoms, is virtually the sole indication for heart transplantation in HCM, performed in 1% of patients
- 43. Palpitations • often caused by supraventricular arrhythmia
- 44. Role of electrophysiological testing
- 45. Treatment of LV Outflow Tract Obstruction General Measures
- 46. Beta Blocker • Non-vasodilating ß-blockers titrated to maximum tolerated dose • Propranalol • Sotalol Disopyramide • Maximum tolerated dose (usually 400–600 mg/day) • QTc interval CCB • Verapamil- starting dose 40 mg three times daily to maximum 480 mg daily • diltiazem (starting dose 60 mg three times daily to maximum 360 mg daily)
- 48. Rarely, patients with severe provocable LVOTO can present with hypotension and pulmonary oedema that mimics acute myocardial ischaemia. Recognition of this scenario is important, as the use of vasodilators and positive inotropes in this setting can be life-threatening. Treatment should instead consist of oral or i.v. ß-blockers and vasoconstrictors (e.g.phenylephrine,metaraminol and norepinephrine).
- 49. Invasive treatment of LVOTO • Patients with an LVOTO gradient ≥50 mm Hg, moderateto-severe symptoms ( (NYHA) Class III–IV) and/or recurrent exertional syncope in spite of maximally tolerated drug therapy • Not in asymptomatic patient.
- 50. Ventricular septal myectomy (Morrow procedure)
- 52. Surgery vs. alcohol ablation • exclude other LV outflow tract and mitral valve abnormalities requiring surgical treatment • SAA less effective in very severe hypertrophy (≥30mm)
- 53. Left ventricular mid-cavity obstruction and apical aneurysms • 10% of patients • very symptomatic • 25% have LV apical aneurysm • high dose ß-blockers, verapamil or diltiazem
- 54. Management of symptoms in patients without left ventricular outlow tract obstruction
- 55. HEART FAILURE
- 56. Recommendations for patients with heart failure and preserved LV EF (≥50%)
- 57. Recommendations for patients with heart failure and reduced LV EF(<50%)
- 60. Left ventricular assist devices
- 61. Angina
- 62. Sudden cardiac death • annual incidence for cardiovascular death of 1–2% • SCD, • heart failure • Thromboembolism • spontaneous ventricular fibrillation (VF) • Asystole • AV block and • pulseless electrical activity
- 63. Clinical risk assessmentYOUNGER AGE ≥3 consecutive ventricular beats at ≥120 BPM lasting <30 sec. First degree relative LA size failure to increase systolic pressure by at least 20 mm Hg from rest to peak exercise or a fall of >20 mm Hg from peak pressure. severity and extent of LVH maximum wall thickness of ≥30 mm
- 64. HCMRisk-SCD
- 65. Prevention of sudden cardiac death >6% 4 – 6 % < 4%
- 66. Prevention of sudden cardiac death
- 68. Ventricular tachycardia • NSVT - three or more ventricular extrasystoles at a rate of ≥120 BPM, lasting less than 30secs • common finding on ambulatory ECG monitoring
Editor's Notes
- HCM is in news recently because last month Journal Nature published a study. This study was the first in humans to use CRISPR-Cas9 to correct a harmful mutation of HCM without causing significant off-target effects in this study The gene editing tool CRISPR-Cas9 was used to correct a mutant paternal MYBPC3 gene in human preimplantation embryos. Healthy donor eggs were injected with sperm that were heterozygous for the MYBPC3 mutation. After fertilization, recombinant Cas9 protein and single guide RNA that targeted MYBPC3 were microinjected into the zygotes. A majority of treated embryos survived and lost the mutation in this gene, without other genes being impaired. CRISPR-Cas9 targeting of MYBPC3 was found to be highly specific in the treated embryos.
- HCM is the most common of the genetic cardiovascular diseases. It is caused by a multiple mutations in genes encoding proteins of the cardiac sarcomere. It is autosomal dominant in heritance. HCM represents the most common cause of sudden death in the young, including competitive athelets
- Prevalence of the HCM phenotype in the general population is approximately 0.2%, i.e. frequency of 1 in 500 people. HCM can present during all phases of life, from infancy to old age SCD occurs in most commonly before the age of 30 to 35 years most scd occur while the victim is sedentary or engaged in only modest physical activity
- Obstruction is not an invariable feature, approximately one third of patients have the nonobstructive form of HCM; accordingly, names once in common use, such as idiopathic hypertrophic subaortic stenosis, hypertrophic obstructive cardiomyopathy, and muscular subaortic Stenosis have been largely abandoned. The preferred name for this condition is now hypertrophic cardiomyopathy with or without outflow obstruction.
- HCM is now known to be caused by mutations more than 11 genes encoding proteins of the thick and thin contractile myofilament components of the cardiac sarcomere or the adjacent Z-disc Two sarcomere genes, encoding β-myosin heavy chain (MYH7) and myosin-binding protein C (MYBPC3), are most common, accounting for 30% patients with HCM
- **Genetic counselling is recommended in all patients when HCM cannot be explained solely by a non-genetic cause. **Counselling should be performed by trained healthcare professionals, to help patients understand and manage the psychological, social, professional and ethical implications of a genetic disease The consequences of a positive test for the patient and their relatives should be explained
- *genetic testing is recommended in patients fulfilling diagnostic criteria for HCM to enable cascade genetic screening of their relatives. *It should be done from certified labs *Genetic testing in individuals with an equivocal clinical diagnosis (e.g. athletes and hypertensives), should only be performed after detailed clinical and family assessment *Genetic analysis of post-mortem tissue or DNA samples can be valuable in the assessment of surviving relatives
- When a definite causative genetic mutation is identified in a patient, his or her relatives should first be genetically tested, and then clinically evaluated if they are found to carry the same mutation When the mutation is absent, relatives should be discharged from clinic but advised to seek re-assessment if they develop symptoms or if new clinically relevant data emerge in the family. when genetic testing is not performed in the proband, or when genetic analysis fails to identify a definite mutation or reveals one or more genetic variants of unknown significance then First-degree adult relatives should be offered clinical screening with an ECG and echocardiogram. Importantly, normal clinical evaluation does not exclude the possibility of disease development in the future; first-degree relatives should therefore be offered repeat assessment
- Screening evaluations usually are performed on a 12- to 18-month basis, beginning at the age of 12 years. If these studies do not show LV hypertrophy by the time full growth is achieved i.e. 18 to 21 years of age, it is likely that an HCM-causing mutation is absent However, morphologic conversion to the HCM phenotype (i.e., with LV hypertrophy) can be delayed well into adulthood, hence it is advisable to repeat Screening evaluations every 5 yrs or do the definitive genetic testing. .
- The standard 12-lead ECG can be normal at presentation but Generally shows a variable combination of LVH, ST- and T-wave abnormalities, and pathological Q-waves Asymptomatic nonsustained ventricular tachycardia, at a rate between 120 and 200 beats per minute, occurs in 25% of adults with HCM. PSVT occur during ambulatory electrocardiographic monitoring in up to 38% of patients.
- Standard 12-lead ECG and Ambulatory ECG monitoring is recommended at the initial clinical assessment to assess the risk of sudden cardiac death and stroke
- Echocardiography is central to the diagnosis and monitoring of HCM. Measurements of LV wall thickness should be performed at end-diastole,preferably in short-axis views. M-mode measurements in the parasternal long axis should be avoided, to prevent over-estimation of septal thickness by oblique cuts. for diagnostic purposes the single most relevant parameter is the maximum LV wall thickness at any level. it is essential that all LV segments from base to apex be examined, ensuring that the wall thickness is recorded at mitral, mid-LV and apical levels
- Primary structural abnormalities of the mitral apparatus responsible for LVOTO are part of HCM phenotypic expression The mitral valve may be more than twice normal size as a consequence of elongation of both leaflets, or segmental enlargement of only the anterior leaflet or mid-scallop of the posterior leaflet.
- *Elongated leaflets protrude into the LV cavity well above the plane of the mitral annulus, a mean of 26 mm above the annulus compared with 13 mm in normal hearts. *Often, a residual portion of the anterior mitral leaflet extends past the point of coaptation, which is important in SAM pathophysiology because it is not constrained by the LV–LA pressure difference. Rather, it is only bounded by the LV and thus freely moves with LV flow, even at low velocity . *residual leaflet usually contacts the septum first . *After mitral-septal contact, the pressure difference itself pushes the obstructing mitral leaflet further into the septum The protruding mitral leaflet plays an important role in the pathophysiology of SAM. Late diastolic and early systolic flow strike the posterior surfaces of the protruding leaflets with a high angle of attack and push them into apposition with the septum
- The large majority of patients with obstructive HCM have elongated anterior and posterior mitral leaflets. In obstructive HCM, the anterior leaflet averages 34 mm versus 24 mm in normal hearts this abnormality is called the “nightcap” mitral valve because of its typical appearance on apical views at the moment of systolic coaptation
- These are the other mitral valve apparatus abnormalities seen.
- There is controversy about whether mitral valve abnormalities should be surgically repaired at the time of myectomy. Some centers generally perform mitral repair in addition to extended myectomy However, because a clinical trial has not been performed, these decisions currently rest in the realm of clinical judgments.
- 70% of patients show the propensity to develop dynamic LVOT gradients of 30 mm Hg or greater, either at rest or during exercise the true nonobstructive form accounts for approximately one third of cases. A gradient of ≥50 mm Hg is usually considered haemodynamically important One should systematically exclude obstruction that is unrelated to SAM, including sub-aortic membranes, mitral valve leaflet abnormalities and mid-cavity obstruction,
- The presence of a central- or anteriorly directed jet of mitral regurgitation should raise suspicion of an intrinsic mitral valve abnormality and prompt further assessment with TOE if necessary
- Subaortic obstruction in HCM represents true mechanical impedance to LV outflow, producing markedly increased intraventricular pressures that over time may be detrimental to LV function, probably by increasing myocardial wall stress and oxygen Demand
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- shows a predominant mid-septal convexity toward the left ventricular cavity with the cavity itself having an crescent shape. Dynamic subaortic obstruction is present in this example with systolic anterior motion (SAM) and turbulent flow in the outflow tract.
- shows a generally ovoid LV cavity with the septum being concave to the LV cavity and a prominent basal septal bulge. Subaortic obstruction is present in this example with SAM and a posteriorly directed jet of mitral regurgitation.
- shows an overall straight septum that is neither predominantly convex nor concave toward the LV cavity. Subaortic obstruction is present in this example.
- shows a predominant apical distribution of hypertrophy. Myocardial delayed enhancement is seen in the LV apex at the site of maximal hypertrophy in this example.
- shows predominant hypertrophy at the mid-ventricular level. In this example, a thinned and dyskinetic apical pouch is also present. Obstruction is at the level of the papillary muscles, where turbulence was identified. No mitral SAM. Myocardial delayed enhancement is seen in the dyskinetic apical pouch.
- Symptoms of heart failure such as exertional dyspnea or fatigue, orthopnea , PND. chest pain either typical or atypical angina pectoris, possibly resulting from structural microvasculature abnormalities. Syncope or near-syncope and lightheadedness due to arrhythmias or outflow obstruction. Palpitations are common and may be related to VT or SVT Patients with typical angina on exertion should be considered for invasive or CT coronary angiography
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- Although some degree of heart failure with exertional dyspnea is common in HCM, progression to [NYHA] class III or IV) is relatively infrequent, it occurrs in 10% to 15% of the overall patient population. The principal determinants of progressive heart failure in HCM are LV outflow obstruction, atrial fibrillation, and diastolic dysfunction. Approximately 3% of patients with HCM develop advanced heart failure associated with systolic dysfunction (ejection fraction <50%), a consequence of small vessel–mediated myocardial ischemia and diffuse transmural scarring. The end stage heart failure is virtually the sole indication for heart transplantation in HCM.
- Non-invasive cardiac imaging has largely replaced cardiac catheterization in the routine assessment of cardiac function. Invasive measurement of intra-cardiac pressures may be appropriate when non-invasive cardiac imaging is insufficient to assess the severity of LVOTO and before heart transplant procedure.
- Causes of syncope include hypovolaemia, chb, sinus node dysfunction, sustained vt, LVOTO, and abnormal vascular reflexes unexplained non-vasovagal syncope is a risk factor for sudden cardiac death,
- The routine use of electrophysiological studies (EPS) in patients with syncope or symptoms suggestive of arrhythmia is not recommended.
- Avoid dehydration Excess alcohol consumption Weight Loss Arterial and venous dilators, including nitrates and phosphodiesterase type 5 inhibitors Avoid digoxin Prompt treatment of AF By convention, LVOTO is defined as a peak instantaneous Doppler LV outflow tract gradient of ≥30 mm Hg, but the threshold for invasive treatment is usually considered to be ≥50 mm Hg.
- symptomatic LVOTO are treated initially with non-vasodilating ß-blockers titrated to maximum tolerated dose, but there are very few studies comparing individual ß-blockers. If ß-blockers alone are ineffective, disopyramide (when available), titrated up to a maximum tolerated dose (usually 400–600 mg/day),may be added. Verapamil (starting dose 40 mg TDS to maximum 480 mg daily) can be used when ß-blockers are contraindicated or ineffective but close monitoring is required in patients with severe obstruction (≥100 mm Hg) or elevated pulmonary artery systolic pressures, as it can provoke pulmonary oedema. diltiazem (starting dose 60 mg TDS to maximum 360 mg daily) should be considered in patients who are intolerant- or have contraindications to ß-blockers and verapamil. Low-dose loop or thiazide diuretics may be used cautiously to improve dyspnoea associated with LVOTO, but it is important to avoid hypovolaemia.
- The most commonly performed surgical procedure used to treat LVOTO is ventricular septal myectomy (Morrow procedure), in which a rectangular trough that extends distally to beyond the point of the mitral leaflet–septal contact is created in the basal septum below the aortic valve This substantially reduces LV outflow tract gradients in over 90% of cases, reduces SAM-related mitral regurgitation, and improves exercise capacity and symptoms.
- selective injection of alcohol into a septal perforator artery to create a localized septal scar has outcomes similar to surgery in terms of gradient reduction, symptom improvement and exercise capacity The main non-fatal complication is AV block in 7–20% of patients and the procedural mortality is similar to isolated myectomy Due to the variability of the septal blood supply, myocardial contrast echocardiography is essential prior to alcohol injection.
- The choice of therapy should be based on a systematic assessment of the mitral valve and septal anatomy that includes deliberate exclusion of other LV outflow tract and mitral valve abnormalities requiring surgical treatment. Septal ablation may be less effective in patients with extensive septal scarring on CMR and in patients with very severe hypertrophy (≥30mm) Septal alcohol ablation is associated with a higher risk of AV block, requiring permanent pacemaker implantation and larger residual LVOT gradients There are no randomized trials comparing surgery and septal alcohol ablation (SAA)
- LV mid-cavity obstruction occurs in approximately 10% of patients with HCM Patients with mid-cavity obstruction tend to be very symptomatic and have increased risk of progressive heart failure and SCD Approximately 25% of patients also have an LV apical aneurysm Patients with LV mid-cavity obstruction should be treated with high dose ß-blockers, verapamil or diltiazem, but the response is often suboptimal.
- the aim of drug therapy is to reduce LV diastolic pressures and improve LV filling by slowing the heart rate with b-blockers, verapamil or diltiazem and cautious use of loop diuretics. Restoration of sinus rhythm or ventricular rate control is essential in patients who have permanent or frequent paroxysms of AF An EF of less than 50% is recommended as the threshold for considering therapy with RAAS inhibitors because of the preservation of cavity size in patients with HCM and advanced systolic failure
- Click digoxin is not recommended in patients with preserved EF because of the potentially adverse effects of positive inotropic stimulation
- Regional heterogeneity of LV contraction and relaxation is common in patients with HCM and LV dyssynchrony may be a marker of poor prognosis.
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- increasingly used as a short-term bridge to transplant,
- Beta blocker and CCB improve diastolic function and reduce myocardial oxygen demand and, In the case of verapamil,it may improve stress-induced sub-endocardial perfusion defects. In the absence of LVOTO, cautious use of oral nitrates may be considered.
- annual incidence for cardiovascular death of 1–2%, with SCD, heart failure and thromboembolism being the main causes of death. The most commonly recorded fatal arrhythmic event is VF, but asystole, AV block and pulseless electrical activity are also described
- This is HCM risk SCD calculator given by ESC. It calculates 5years risk of SCD.
- Non-sustained ventricular tachycardia (defined as three or more ventricular extrasystoles at a rate of ≥120 BPM, lasting less than 30 seconds) is a common finding on ambulatory ECG monitoring. Its prevalence increases with age and correlates with LV wall thickness NSVT is a risk factor for SCD, but does not usually require anti-arrhythmic therapy Documented sustained monomorphic VT (≥30 seconds) is uncommon but may be more frequent in patients with apical LV aneurysms.