It is a genetic disorder due to mutations in the gene that encodes for β-Cardiac myosin heavy chain (Localised to chromosome 14). It is characterized by inappropriate myocardial hypertrophy in absence of hypertension or aortic stenosis. There is myocardial disarray and interstitial fibrosis. It has asymmetric septal hypertrophy, left ventricular outflow obstruction due to systolic anterior motion of mitral valve, LV diastolic dysfunction, myocardial ischaemia and arrhythmias. LV outflow obstruction occurs only in about 1⁄4th. The prevalence of HCM is about 0.2 per cent.
Clinical Menifestation
Patient may be asymptomatic. Chest pain, atypical or typical angina and dyspnoea are usually presenting symptoms in 30-60 per cent in 90 per cent of symptomatic patients. Unexplained syncope (15-25 per cent) and sudden death are known. It presents as cardiac failure in end stage disease.
The clinical types are (a) either symptomatic or asymptomatic. (b) non-obstructive or obstructive(at LV outflow tract or midventricular level (c) type of hypertrophy viz asymmetric septal hypertrophy (in two third), symmetric LV hypertrophy (5 per cent) and apical as in apical cardiomyopathy in Japanese population. (d) Endstage disease. This presents as cardiac failure.
It may rarely be unremarkable.Usually the apex is palpable and will be LV type and may have double apical impulse due to powerful LA contraction.Prominent S4 and systolic murmur at lower sternal border are heard. The murmur is due to labile LV outflow obstruction and
it increases with Valsalva manoeuvere, standing up from squatting position, exercise and in postextrasystolic contraction. The SM is harsh and crescendo- decrescendo in configuration. It commences sometime after S1 and is best heard between apex and left sternal border. It radiates to lower sternal border, axilla and base of the heart, but never to carotids. MR murmur may also be present. Brisk carotid pulse and sometimes prominent ‘a’ in JVP are seen.Fig. 5.5: Payhophysiology of subaortic anterior motion (SAM) of mitral valve in HOCM
Electrocardiography
The ECG changes usually precede the onset of echocardiographic changes. The abnormalities are seen in QRS, ST Changes and T-Waves. LV voltage is increased. Abnormal Q are seen in 25-50 per cent of patients, usually in inferolateral leads and may mimic myocardial infarction. Early repolarisation and other ST Changes may be seen. Giant negative T-Waves are seen in apical cardiomyopathy. LA is enlarged, Arrhythmias (NSVT 25 per cent, PSVT 35-50 per cent, AF 5 per cent) are seen. In 5 per cent WPW may be seen.
Echocardiography
It is the most important diagnostic tool. There is asymmetric septal hypertrophy as seen by septal to posterior wall thickness ratio of 1.5 or more. Maximal septal hypertrophy occurs midway between apex and base. Apical hypertrophy, midventricular hypertrophy or RV hypertrophy may be seen. LV thickness can vary from 15 mm to 60 mm. Systolic anterior motion of the mitral valve identifies LV outflow tract obstruction. There is also elongation and enlargement of mitral valve leaflets, leading to abnormal aortic outflow geometry. It contributes to pressure gradient across LV outflow and is also responsible for mitral regurgitation.
There are other echocardiographic findings viz. small LV cavity, partial systolic closure and coarse fluttering of aortic valve , reduced septal and exaggerated posterior wall motion.Fig. 5.7: M-mode echo shows premature cosure of aortic valve (due to abrupt decline in midsystole) and also prominent S 4
Diagnosis
Nonobstructive hypertrophic cardiomyopathy needs to be differentiated from silent aortic stenosis, hypertension and physiologic hypertrophy seen in athletes. Elite athletes may demonstrate LV thickness upto 16mm. (normal 12) with ECG abnormalities. However they will not show myocardial disarray or diastolic dysfunction. They will also have an excellent exercise capacity.The differential diagnosis of SM is shown in Table . The interventions that increase/decrease outflow gradient and hence SM are shown in Table 5.8. The effects of these interventions on other systolic murmurs are depicted in Table
Patient may be asymptomatic. Chest pain, atypical or typical angina and dyspnoea are usually presenting symptoms in 30-60 per cent in 90 per cent of symptomatic patients. Unexplained syncope (15-25 per cent) and sudden death are known. It presents as cardiac failure in end stage disease.
The clinical types are (a) either symptomatic or asymptomatic. (b) non-obstructive or obstructive(at LV outflow tract or midventricular level (c) type of hypertrophy viz asymmetric septal hypertrophy (in two third), symmetric LV hypertrophy (5 per cent) and apical as in apical cardiomyopathy in Japanese population. (d) Endstage disease. This presents as cardiac failure.
It may rarely be unremarkable.Usually the apex is palpable and will be LV type and may have double apical impulse due to powerful LA contraction.Prominent S4 and systolic murmur at lower sternal border are heard. The murmur is due to labile LV outflow obstruction and
it increases with Valsalva manoeuvere, standing up from squatting position, exercise and in postextrasystolic contraction. The SM is harsh and crescendo- decrescendo in configuration. It commences sometime after S1 and is best heard between apex and left sternal border. It radiates to lower sternal border, axilla and base of the heart, but never to carotids. MR murmur may also be present. Brisk carotid pulse and sometimes prominent ‘a’ in JVP are seen.Fig. 5.5: Payhophysiology of subaortic anterior motion (SAM) of mitral valve in HOCM
Electrocardiography
The ECG changes usually precede the onset of echocardiographic changes. The abnormalities are seen in QRS, ST Changes and T-Waves. LV voltage is increased. Abnormal Q are seen in 25-50 per cent of patients, usually in inferolateral leads and may mimic myocardial infarction. Early repolarisation and other ST Changes may be seen. Giant negative T-Waves are seen in apical cardiomyopathy. LA is enlarged, Arrhythmias (NSVT 25 per cent, PSVT 35-50 per cent, AF 5 per cent) are seen. In 5 per cent WPW may be seen.
Echocardiography
It is the most important diagnostic tool. There is asymmetric septal hypertrophy as seen by septal to posterior wall thickness ratio of 1.5 or more. Maximal septal hypertrophy occurs midway between apex and base. Apical hypertrophy, midventricular hypertrophy or RV hypertrophy may be seen. LV thickness can vary from 15 mm to 60 mm. Systolic anterior motion of the mitral valve identifies LV outflow tract obstruction. There is also elongation and enlargement of mitral valve leaflets, leading to abnormal aortic outflow geometry. It contributes to pressure gradient across LV outflow and is also responsible for mitral regurgitation.
There are other echocardiographic findings viz. small LV cavity, partial systolic closure and coarse fluttering of aortic valve , reduced septal and exaggerated posterior wall motion.Fig. 5.7: M-mode echo shows premature cosure of aortic valve (due to abrupt decline in midsystole) and also prominent S 4
Diagnosis
Nonobstructive hypertrophic cardiomyopathy needs to be differentiated from silent aortic stenosis, hypertension and physiologic hypertrophy seen in athletes. Elite athletes may demonstrate LV thickness upto 16mm. (normal 12) with ECG abnormalities. However they will not show myocardial disarray or diastolic dysfunction. They will also have an excellent exercise capacity.The differential diagnosis of SM is shown in Table . The interventions that increase/decrease outflow gradient and hence SM are shown in Table 5.8. The effects of these interventions on other systolic murmurs are depicted in Table
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| Differential Diagnosiso of Left Nautricular Outflow Obstruction Murmurs |
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| Mechanisms of Ischaemia in HOCM |
Complication
The clinical course is variable. The annual mortality is closer to 1 per cent. The risk of sudden death is higher in children and young adults and is close to 6 per cent. Development of atrial fibrillation will increase symptoms suddenly. The complications thus are: Progressive increase in hypertrophy, development of outflow obstruction, ischaemia arrhythmias and sudden death (Tables) and endstage disease with progressive dilation and CCF (5-10 per cent)
Table : Adverse outcome in HOCM
1 H/O sudden death/syncope
2 H/O sudden death in family members
3 Severe LVH > 33 mm
4 Extent of Myocardial disarray
5 Extent of Interstitial Fibrosis
6 Early onset of disease
7 Myocardial Ischaemia on perfusion tomography
8 Abnormal B.P. response to exercise (Failure to rise or fall of B.P.)
9 LV outflow obstruction more than 30 mmHg at rest.
10 VT/NSVT on Holter
11 “Malignant” causal mutations
12 “Malignant” modifier genes
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| Development of myocardial dysfunction in viral infection |
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| Integrated pathophysiology of HOCM |
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| Progression to endstage phase in HOCM |
Management
It is directed towards amelioration of symptoms, prevention of complications including sudden death. Risk assessment stratification should be done in all and at various stages. .
a) Asymptomatic/Mildly Symptomatic Patients
It is directed towards amelioration of symptoms, prevention of complications including sudden death. Risk assessment stratification should be done in all and at various stages. .
a) Asymptomatic/Mildly Symptomatic Patients
The treatment is controversial. Some give them betablockers/or calcium channel blockers like verapamil, in the hope of preventing progression of the disease. However there is no evidence for the same. Amiodarone is given, if Holter shows episodes of nonsustained ventricular tachycardia.
b) Moderate/Severe Symptoms
i) Medical Managementβ-blocking drugs or verapamil are useful. Beta-blocker blunt heart’s chronotropic response, thus limiting oxygen demand and improving diastolic dysfunction. 1/3 - 2/3 rd of patients have symptomatic improvement. Ca channel blockers are useful because both the hyper contractile systolic function and abnormalities of diastolic filling may be related to abnormal Ca kinetics.They block inward transport of Ca across myocardial cell. Verapamil improves exercise performance better than β-blockers. In non-obstructive patients,usually verapamil is preferred because of its greater effect on diastolic dysfunction. When either of them is not effective, a tria of disopyramide may be useful. Disopyramide is useful as it alters Ca kinetics. It is particularly useful with beta-blocker in reducing outflow gradient.
ii) Interventional Treatment
This is usually reserved for severely symptomatic patients with obstruction who do not respond to medical treatment. It is performed to relieve the sub aortic obstruction and normalize markedly increased LV systolic pressure. The indications are:
— refractory to standard medical treatment and
— gradient of at least 50mmHg across LV outflow tract, at rest or on provocation.
DDD Pacing
Although true benefit is uncertain, it is used as an appropriate medical therapy in persistently symptomatic patients, viz.
i) in whom there is an independent need for permanent pacing
ii) Severe bradycardia due to b-Blockers
iii) contraindications to surgery/septal ablation.
Septal Ablation (TASH/PTSMA)
This is a nonsurgical interventional treatment. The septal myocardium supplied by 1 st septal branch of left anterior descending artery is destroyed by alcohol, by percutaneous technique.It creates limited myocardial infarction and reduces LV outflow obstruction. It reduces mitral incompetence and improves relaxation. Improvement occurs in almost 90 per cent.However there is some concern about 2 complications viz. Heart block which needs pacing in a few patients. There is a theoretical concern that myocardial scar that follows infarction might lead to ventricular arrhythmias. It is therefore a preferred option in patients who already have a pacemaker.ICD in place or where surgery is contraindicated because of other medical conditions. It is however being widely used in select centres.
ICD Implantation
It is used as a method of secondary prevention for cardiac arrest or history of sustained hemodynamically unstable ventricular tachycardia. For primary prevention, it is used with history of sudden death in family with history of sustained ventricular tachycardia.
Surgical
Septal Myotomy/Myectomy it is widely used. About 5 gms. of hypertrophied septum are removed using a tranaortic approach (Morrow procedure). It gives sysmptomatic relief in almost 70-90 per cent of patients. It should be preferred in younger patients and in whom septal ablation has failed. Occasionally mitral valve replacement or suture plication of anterior mitral leaflet are also employed.
iii) Endstage Disease
The treatment is of cardiac failure, including cardiac transplant.
b) Moderate/Severe Symptoms
i) Medical Managementβ-blocking drugs or verapamil are useful. Beta-blocker blunt heart’s chronotropic response, thus limiting oxygen demand and improving diastolic dysfunction. 1/3 - 2/3 rd of patients have symptomatic improvement. Ca channel blockers are useful because both the hyper contractile systolic function and abnormalities of diastolic filling may be related to abnormal Ca kinetics.They block inward transport of Ca across myocardial cell. Verapamil improves exercise performance better than β-blockers. In non-obstructive patients,usually verapamil is preferred because of its greater effect on diastolic dysfunction. When either of them is not effective, a tria of disopyramide may be useful. Disopyramide is useful as it alters Ca kinetics. It is particularly useful with beta-blocker in reducing outflow gradient.
ii) Interventional Treatment
This is usually reserved for severely symptomatic patients with obstruction who do not respond to medical treatment. It is performed to relieve the sub aortic obstruction and normalize markedly increased LV systolic pressure. The indications are:
— refractory to standard medical treatment and
— gradient of at least 50mmHg across LV outflow tract, at rest or on provocation.
DDD Pacing
Although true benefit is uncertain, it is used as an appropriate medical therapy in persistently symptomatic patients, viz.
i) in whom there is an independent need for permanent pacing
ii) Severe bradycardia due to b-Blockers
iii) contraindications to surgery/septal ablation.
Septal Ablation (TASH/PTSMA)
This is a nonsurgical interventional treatment. The septal myocardium supplied by 1 st septal branch of left anterior descending artery is destroyed by alcohol, by percutaneous technique.It creates limited myocardial infarction and reduces LV outflow obstruction. It reduces mitral incompetence and improves relaxation. Improvement occurs in almost 90 per cent.However there is some concern about 2 complications viz. Heart block which needs pacing in a few patients. There is a theoretical concern that myocardial scar that follows infarction might lead to ventricular arrhythmias. It is therefore a preferred option in patients who already have a pacemaker.ICD in place or where surgery is contraindicated because of other medical conditions. It is however being widely used in select centres.
ICD Implantation
It is used as a method of secondary prevention for cardiac arrest or history of sustained hemodynamically unstable ventricular tachycardia. For primary prevention, it is used with history of sudden death in family with history of sustained ventricular tachycardia.
Surgical
Septal Myotomy/Myectomy it is widely used. About 5 gms. of hypertrophied septum are removed using a tranaortic approach (Morrow procedure). It gives sysmptomatic relief in almost 70-90 per cent of patients. It should be preferred in younger patients and in whom septal ablation has failed. Occasionally mitral valve replacement or suture plication of anterior mitral leaflet are also employed.
iii) Endstage Disease
The treatment is of cardiac failure, including cardiac transplant.
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