Hypertrophic cardiomyopathy (HCM) is a primary myocardial disease characterised by hyper contracting, hypertrophic, non-dilated ventricle and this inappropriate myocardial hypertrophy is without any obvious cause such as hypertension or aortic stenosis. It was studied systematically in late 1950s, though first time described nearly a century ago.¹

Hypertrophic cardiomyopathy (HCM) is a common disorder of cardiac muscle associated with sudden cardiac death (SCD). HCM is defined by increased left ventricular wall thickness or mass, in the absence of abnormal loading conditions to account for the observed abnormality.² In most adults, the disease is inherited as an autosomal dominant trait and is caused by mutations in cardiac sarcomere protein genes.²

Hypertrophic cardiomyopathy (HCM) is one of the most common heritable cardiac conditions with an estimated prevalence in the general population of >1:500.^3-7

Most distinctive morphologic features are disproportionate hypertrophy of ventricular septum, disarray of myofiber in ventricular septum and left ventricular free wall, reduced volume of left ventricular cavity and dilated atria, mitral valve thickening and abnormal intramural coronary arteries.⁸

The purpose of this case series was to document the autopsy findings, histopathology and relevant familial predisposition of all three cases of hypertrophic cardiomyopathy

A retrospective study of 03 autopsies of sudden deaths of young adults was carried out at a tertiary care centre at Western Maharashtra. These cases were diagnosed on postmortem examination during the period of 2021-2022.

Careful gross examination of all the hearts were done during the medicolegal autopsies of these young adults. Serial cross sectioning of the coronary vessels were done to find the percentage occlusion of these vessels if present. Heart were dissected according to inflow outflow method to notice the thickness of atrial and ventricular walls along with interventricular septum. Cardiac chambers and valves were examined. Heart were weighed in electrical weighing machine.

Histopathological examination of all the hearts were done.

Apart from above methods, careful and detailed family history were taken from the deceased nearest relatives, about any such incident of sudden death to any other family members. Also detailed study of police records and inquest papers were studied to rule out any suspicious or foul play. All turned out to be sudden natural deaths

An autopsy of all three cases of sudden death, was carried out from 2001 to 2022, which reveals HCM (Hypertrophic Cardiomyopathy). All these cases were males and the age range was from 18 to 34 years (1^st male- 18 years, 2^nd male- 27 years, 3^rd male- 35 years). There was no previous history of cardiac or any other related ailment. 18-year-old male (male – A) had sudden onset of shortness of breath prior to death, 27-year-old male (male – B) had one episode of vomiting prior to death and 35-year-old male (male – C) had sudden onset of mild chest pain prior to death. In all cases ischaemic heart disease, hypertension, valvular and congenital heart disease were ruled out by taking detailed history from the relatives, checking any previous hospital and medical reports and police records.

All the three cases died while doing moderate to severe exertion. Male A was doing morning exercises and jogging before reporting shortness of breath prior to death. Male B had completed his morning gym training, after that he experienced shortness of breath and vomited at breakfast table before becoming unresponsive. Male C was doing morning yoga and exercises prior to death.

Male A had significant familial history in addition to the above history. He lost his father, aged 35 years of age, due to sudden natural death. Also his elder brother, aged 24 yrs of age, died due to sudden natural death.

Gross features:

The weight of the heart ranged from 413 to 498 grams (Male A- 498 gm, Male B- 413 gm, Male C- 493 gm.). Asymmetric hypertrophy was noted in all the three cases. The interventricular septum and the left ventricular walls were hypertrophic in all and the range of thickness of left ventricular wall was 18 millimeters to 28 millimeters (mean- 22.33 millimeters). The interventricular septal thickness varied from 19 millimeter to 31 millimeters with an average of 25.66 millimeters. (Fig: 1, 2, 3, 4, 5, 6) The coronary arteries of all three cases were patent and without evidence of atherosclerosis. Not a single case showed gross and microscopic evidence of myocardial infarction.

Figure 1: Ventricular hypertrophy (Male-A

Figure 2: Increased weight of enlarged heart (Male-A)

Figure 3: Increased left-ventricular thickness (Male-B)

Figure 4: Enlarged Heart (Male-C)

Figure 5: Myocyte disarray in HCM characterized by Hypertrophy and distinct nuclear changes as per histopathology report (Male-A)

Histopathological features:

All the three cases under study (Male A, B, C) showed myocyte hypertrophy, muscle fibre disarray, interstitial fibrosis and mild to moderate inflammatory infiltrate comprising of lymphocytes in the interstitium. The myocytes are increased in size and show nucleomegaly. Few of the myocytes showed cytoplasmic vacuoles.

The gross and histomorphological features are consistent with HCM (Hypertrophic Cardiomyopathy).

HCM is uncommon in the USA, where it affects 0.02 to 0.2% of the population and is discovered in 0.5% of all unselected patients who are referred for an echocardiogram. ⁹ The prevalence rate in Japan is 17.3 per 100,000 people, the same as in the population of the West. ¹⁰

Although the specific cause is unknown, it has been observed to occur in some families as an autosomal dominant, Mandelian-inherited illness of contractile sarcomeric proteins. ¹¹ Children and elderly people in their seventh to eighth decades of life may both exhibit symptoms of the condition. The clinical course varies greatly. The patient may experience attacks of syncope, angina, or moderate dyspnea, or they may remain asymptomatic their entire lives. The most tragic aspect of the disease's natural course is sudden death, which may be the first clinical symptom of hypertrophic cardiomyopathy, particularly in young adults. ¹²

Young age upon diagnosis, a family history of HCM with sudden fatalities, and genetic anomalies linked to a higher prevalence of sudden death are risk factors for sudden death in patients. ¹³ In our study, we had significant familial history in case of Male A.

 It is hypothesised that arrhythmias, particularly in young people, are related to activity. The mechanism of sudden death in this disease is not completely understood and likely complex, and/or ischemia may have a significant impact. ^14,15

When a young, seemingly healthy young adult passes away unexpectedly, there is worry and various assumptions are made about what happened. Everyone is curious in the precise reason of death. We were able to determine the final cause of death in these cases of unexpected fatalities by a thorough postmortem assessment that included histological and gross inspection. Therefore, the postmortem study of both natural and accidental deaths is essential for making a final diagnosis. ^16,17

Histological analysis of the conducting system may be useful when the heart is healthy and the coronary arteries are unremarkable. Most of the time, it is normal.^17,18

Our all three cases in the age range of 18 to 35 years died abruptly, which is consistent with other series' documentation, that sudden death related to HCM occurs in young people. ^19,20 Hypertrophic cardiomyopathy, however, affects people of all ages, and both young and old individuals exhibit most of the same clinical, electrocardiographic, and hemodynamic characteristics. ²¹ A Japanese study ¹⁴ found that the male to female ratio was 2.3:1, however in our investigation and case study, all the patients were male.

Exertional chest discomfort, syncopal episodes, and sudden death are just a few of the many clinical symptoms that patients with hypertrophic obstructive cardiomyopathy may experience. Angina, syncope, dyspnea, and palpitation were the main signs and symptoms in earlier studies. ^21-23  These clinical characteristics are consistent with our observations as well. In this illness, syncopal attacks may be brought on by vascular instability, which can also cause hypotension during routine everyday activity or even when at rest. ²⁴

Some individuals may present with sudden death, one of the devastating complications of this disease. In our study all 3 cases died suddenly, whereas in another Indian study ²⁵, 6 of 14 persons developed sudden death.

Angina, syncope, or sudden cardiac death may be caused by cardiac arrhythmia, haemodynamic problems, or both. Large intraventricular gradients, which can be triggered by exercise, are one type of hemodynamic cause. In our setup, this connection to activity or exertion was identified in 100% of instances, whereas in a prior study, ²⁶ sudden death from hypertrophic cardiomyopathy occurred in 79.2% of cases. They could also be brought on by a reduction in cardiac output brought on by a change in diastolic compliance caused by the thick noncompliant ventricle. ²³

The mechanisms causing sudden death are intricate and unclear. The evidence that is now available^14,33–35 indicates that the arrhythmia is what causes sudden death. In patients with hypertrophic cardiomyopathy, the degree of hypertrophy is related to the occurrence of nonsustained ventricular tachycardia. ²²

When Teare ²⁷ characterised the disease with asymmetric septal hypertrophy resulting in obstruction of the left ventricular outflow in 1958, the disorder was classified as hypertrophic obstructive cardiomyopathy or asymmetric septal hypertrophy. Numerous varieties of obstructive and nonobstructive, septal and ventricular free wall involvement, as well as asymmetrical and symmetrical types of hypertrophies, have been discovered with the development of M-mode echocardiography and subsequent postmortem studies. ²⁸ Symmetric hypertrophy has been observed in 34% of patients in a prior study. ²⁹

There is no one histological characteristic that may be used to diagnose the illness. In his investigation, Teare ²⁷ found a correlation between asymmetric septal hypertrophy, myofiber disarray, and interstitial fibrosis and rapid death. Later, it was decided that myofiber disarray alone is a nonspecific trait because it has been observed in people with congenital heart disease, normal hearts, and foetal hearts. ^30,31 Interstitial fibrosis and myofiber disorder are patchy. When quantitatively evaluated alongside other histologic findings such interstitial fibrosis and larger, hyperchromatic nuclei, it is a highly sensitive and specific marker. ³²

If the hearts are not opened correctly during necropsy, especially the heart with a tiny left ventricular cavity and no evident explanation, hypertrophic cardiomyopathy is likely to be missed by pathologists. The left ventricle and septum of these hearts exhibit asymmetrical or concentric enlargement, along with histologically obvious cellular disarray, patchy fibrosis, and larger nuclei. In this investigation, similar findings were also made.

A rare condition, hypertrophic cardiomyopathy primarily affects young people. Usually, the first sign of an illness is sudden death. Asymmetrical hypertrophy are visible in the hearts. In our instances, an important pathological finding was myocyte hypertrophy and disorder. One should consider the potential of this condition when performing the post-mortem investigation in a case of sudden cardiac death. HCM must be diagnosed with precision and should not be confounded with other syndromes that also have LVH. People with a family history of sudden death shouldn't engage in strenuous activity. Genetic testing in this situation is likely to become more important in the future. Since HCM has treatable symptoms, modern diagnostic techniques and therapy should be able to help reduce the number of unexpected deaths. Preparticipation screening measures must be implemented in order to prevent sports-related fatalities.

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