European Journal of Cardiovascular Medicine

Sudden death, as defined by the World Health Organization, occurs within 24 hours of symptom onset but has been defined variously and arbitrarily as death occurring instantaneously or within 1, 2, 6, 12 or 24 hours after onset of symptoms.^1,2 Cardiovascular diseases are responsible for 56% of natural sudden deaths, with coronary (ischemic) heart disease contributing to over 75% of sudden cardiac deaths. The World Health Organization recognizes ischemic heart disease (IHD) as a modern epidemic, noting that its onset in developing countries occurs about a decade earlier than in developed countries.³

Sudden Cardiac Death (SCD) is typically described as a near-instantaneous, electrically triggered cessation of cardiac output in individuals with otherwise functional circulatory systems.⁴ SCD as a consequence of cardiovascular event with or without an existence of cardiovascular pathology accounts for about 45 to 50% of total incidence of sudden deaths. Sudden death of young and healthy adult has a profound impact on the psyche of the society. It is estimated that 60% of coronary artery disease patients are South Asians.⁵

Over the past five decades, the incidence of SCD has risen globally, particularly in urban populations.⁶ In India, there has been a significant increase in the prevalence of Coronary Heart Disease (CHD) over the last 60 years, with rates climbing from 1% to 9-10% in urban areas and from less than 1% to 4%-6% in rural regions.⁷ The underlying cardiovascular pathology in sudden deaths in most patients in the Indian subcontinent is atherosclerosis, whose progression and acceleration is proportional to the traditional risk factors, altered lifestyles and inherent risk factors. The atherosclerotic process culminates in ischemic heart disease and current trends point to increasing incidence of ischemic heart disease in young population.⁵ To assess the prevalence of different heart diseases and their role in sudden deaths, this study was conducted, to study morphological and histopathological lesions in heart and coronary vessels in cases with history of sudden death

Present study was prospective, observational study, conducted in department of Pathology, at Lokmanya Tilak Municipal Medical College, Sion, Mumbai, India. Study duration was of 3 years, from July 2021 to June 2024. Study was approved by institutional ethical committee.

Inclusion criteria

• Deaths occurring within 24 hours of onset of symptoms with or without pre- existing comorbidities.

Exclusion criteria

• Sudden deaths due to unnatural causes such as homicide, accidents, poisoning or suicide.
• Paediatric (below 18 years of age) and perinatal
• Autolysed heart

Cases were retrieved from the Histopathological records in post- mortem histopathology section in the Department of Pathology in a tertiary care public hospital during the specified period. A detailed proforma was used to record case information. All the organs including whole heart with attached aorta, received for Histopathological study from autopsied cases of sudden deaths, were properly fixed in 10% formalin. Observations included the relationship of the great vessels and any variations. External examination of the heart included size, weight, fat deposition, coronary artery course, and any scars. All the coronaries were inspected for thickening or hardening, with 4-5 mm transverse cuts made to evaluate atherosclerotic changes.

Gross photographs documented the observed pathology. The heart was then opened along the blood flow path as per Virchow's method. For detailed examination of infarctions or concentric ventricular hypertrophy, the "Bread loaf technique" was used, involving transverse slices from the apex to the mid-septum at 1 to 1.5 cm intervals. Additional photographs were taken if lesions were detected. Following the dissection, measurements of valve circumferences and ventricular wall thickness were recorded, and the aorta along with the right and left coronary arteries were inspected for atherosclerosis, aneurysmal dilatation, and congenital anomalies.

Representative sections were taken for microscopic study based on standard protocols. This included Right and left ventricular walls, Aorta & Coronaries (LAD, LCx, RCA). Additional samples were taken from any gross pathological lesions observed. The tissue was processed routinely, paraffin blocks prepared, and 3 to 6 micron thick sections cut and stained with hematoxylin and eosin (H&E), and with special stains wherever needed. The sections were analysed, and a correlation was made between gross and microscopic findings.

Findings were categorized into: Atherosclerosis, Myocardial hypertrophy, Myocardial infarction, Myocarditis, Cardiomyopathy & No significant finding.

Data was collected and compiled using Microsoft Excel, analysed using SPSS 23.0 version. Frequency, percentage, means and standard deviations (SD) was calculated for the continuous variables, while ratios and proportions were calculated for the categorical variables. Statistical analysis was done using descriptive statistics.

Total 100 specimens of hearts with aorta were studied during this period. In our study, out of 100 autopsy cases with history of sudden death 74 (74%) showed cardiac lesions. The ages ranged from 21 years to 70 years. Majority of cases of sudden deaths were seen in the age group 41-50 years (29%) followed by 31- 40 years (25%). Males were affected more frequently (83 cases i.e. 83%) than females (17 cases i.e. 17%). The M/F ratio was 4.88:1.

Table 1: Distribution of cases of sudden deaths according to Age and Sex (N=100)

The most prevalent pathology was atherosclerosis, found in 39 cases (39%), followed by myocardial hypertrophy (18%), myocardial infarction (12%), myocarditis (4%) and cardiomyopathy (1 case). Notably, 26 cases showed no significant pathological findings.

Table 2: Various pathological lesions found in heart with their incidence (N=100)

Out of 100 cases 39 cases of atherosclerotic coronary artery disease and aortic atherosclerosis were encountered. Out of 39 cases, 33 were coronary atherosclerosis with or without aortic atherosclerosis, while 6 cases showed only aortic atherosclerosis. The lesions found were fixed coronary obstruction, complicated atherosclerotic plaque and thrombus. The age group ranged from 26 to 65 years. Majority of the cases were seen in the age group 51-60 years (25.64%) followed by 31-40 years and 41- 50 years (23.07% each). Males were affected more frequently (84.61%) than females (15.38%). The M/F ratio was 5.5:1.

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Table 3: Age and Sex wise distribution of Atherosclerosis (N=39)

The combined involvement of Right coronary (RCA), Left circumflex (LCx) and Left anterior descending (LAD) arteries was seen in 15 cases (45.45%) followed by left circumflex and left anterior descending arteries in 5 cases (15.15%).

Table 4: Incidence of atherosclerotic changes in the coronary arteries (N=33)

Double Vessel Disease was seen predominantly in 15 cases (45.45%) followed by triple vessel disease in 13 cases (39.39%).

Table 5: Incidence of number of coronary vessels involved by atherosclerosis (N=33)

Grade-2 occlusion was seen predominantly in 10 cases (30.30%) followed by grade-1 and grade-3 occlusion seen in 9 cases each (27.27%).

Table 6: Showing grades of coronary occlusion (N=33)

Myocardial hypertrophy accounted for 18% of sudden deaths in this study. Age groups ranged from 31 to 70 years. The most common age group involved by myocardial hypertrophy was 41-50 years accounting 10 cases (55.55%) of which 9 were males and one was female.

Table 7: Showing the age and sex wise incidence of Myocardial hypertrophy (N=18)

Grossly, all the hearts weighed more than 350 gm and left ventricular wall thickness varied from 1.7 cm to 2.5 cm. Out of 18 cases of Myocardial hypertrophy, left ventricular hypertrophy (LVH) was seen in highest i.e. 13 cases (72.22%), followed by 4 cases (22.22%) of combined left ventricular and right ventricular hypertrophy. One case showing right ventricular hypertrophy was seen.

Table 8: Types of myocardial hypertrophy (N=18)

Out of 100 cases, myocardial infarction was encountered in 12 cases (12%). The age groups ranged from 31 to 70 years. Majority of the cases were seen in age group of 51 to 60 years i.e. 5 cases (41.66%). Males were affected predominantly in 08 cases (66.66%) and females in 4 cases (33.33%).

Table 9: Showing the age and sex incidence of myocardial infarction (N=12)

Infarction is classified into recent up to the stage of granulation tissue formation and healed when the stage of fibrosis is seen. Healed infarction was seen in majority of cases i.e. 7 cases (58.33%) while recent infarct was seen in 5 cases (41.66%). Associated atherosclerotic lesions in aorta were seen in 04 (33.33%) cases out of 12.

Table 10: Types of myocardial infarction (N=12).

Out of 100 cases, 4 cases of myocarditis were found. Myocarditis accounted for 4% of sudden deaths in this study. Age groups ranged from 41 to 70 years. No specific age predilection was seen. 3 (75%) out of the 4 cases were males. Microscopically, there were more than two foci of inflammation, containing more than 5 inflammatory cells in each focus and associated myocyte necrosis in each histologic section.

Table 11: Showing the age and sex incidence of myocarditis. (N=4)

In 26 cases out of 100, no significant heart pathology was noted. No case of ruptured aortic aneurysm, valvular heart disease or rheumatic heart disease was found in this study.

Cardiovascular diseases significantly impact on health and longevity of an individual across both developed and developing countries. Their prevalence is notably higher in urban areas compared to rural ones, primarily due to risk factors like tobacco use, insufficient physical activity, poor dietary choices and obesity. Of particular concern is the younger age at which cardiovascular deaths occur in developing countries.

Globally, cardiac pathology is predominantly determined through autopsy. Comprehensive examination of the heart, including photographic documentation and histological analysis, remains the gold standard for assessing pre-mortem cardiological findings. The primary goal of a medicolegal autopsy is to establish the cause and manner of death, providing crucial information for public prosecutors. Ischemic heart disease remains the leading cause of death globally for both men and women. In cases where gross pathology fails to clarify the cause of death, histological examination often provides critical insights, allowing for a conclusive determination of the underlying cardiac pathology.^8,9

In the present study, cases were distributed across various age groups with ages ranging from 21 to 70 years. Majority of cases were seen in the age group of 41 to 50 years (29%) followed by 31 to 40 years (25%) with a marked male predominance (83%). The male to female ratio was 4.9:1. Similarly, in the studies by Marwah et al.,¹⁰ and Singal et al.,¹ majority of cases were seen in the age group of 41 to 50 years with a male preponderance, while in study by Mathipa S. et al.,¹¹ most cases were seen in age group 41-60 years. sThis shows predominance of sudden deaths in middle aged individual with a marked male predominance, reflecting a common trend where middle-aged males are more frequently affected by cardiac conditions leading to sudden death.

In the present study, atherosclerosis (39%) was the most commonly encountered lesion contributing to sudden death, followed by myocardial hypertrophy (18%). Similar findings were seen in the study by Singal et al.,¹ where highest i.e. 49% cases of atherosclerosis were seen followed by Myocardial hypertrophy (36%). While in the study by Mathipa S. et al.,¹¹ highest cases of atherosclerosis (46%) were seen followed by myocardial infarction (20%).

This variation could reflect differences in study populations. Atherosclerosis remains a prevalent condition in cardiac pathology, and the consistency across studies underscores its significance in cardiovascular disease. The slight decrease in our study compared to Singal et al.,¹ & Mathipa S. et al.,¹¹ might be due to variations in lifestyle and risk factors over time.

Myocardial hypertrophy was noted in 18% of cases in the present study, which is significantly lower than the 36% reported by Singal et al.,¹ and closer to the 15% found by Mathipa S. et al.,¹¹ This lower prevalence could suggest variations in demographic differences among the study populations. It might also indicate shifts in the prevalence of conditions leading to myocardial hypertrophy or changes in diagnostic practices.

The present study reported myocardial infarction in 12% of cases, which is lower than the 18% observed by Singal et al.,¹ and 20% noted by Mathipa S et al.,¹¹ This finding suggests a trend towards a lower incidence of myocardial infarction in the study population compared to previous studies. Factors such as improved preventive measures or changes in population health could contribute to this decrease.

There were 4 cases of Myocarditis and one case of hypertrophic cardiomyopathy in the present study. The lower incidence of these lesions, similarly seen in study by Singal et al.,¹ suggests that these remain a less common but significant conditions in the context of cardiac pathology leading to sudden death.

In the present study, most common coronary vessel involved by atherosclerosis was Left anterior descending artery (82%) followed by left circumflex artery in 73% cases and right coronary artery in 67% cases. Similar findings were seen in study by Mathipa S. et al.,¹¹ which showed highest involvement by left anterior descending artery (67%). The high prevalence of LADA involvement in the present study underscores its significance in coronary artery disease and could reflect a trend towards more severe or advanced cases in the current study population.

In the present study, the double vessel disease (46%) was encountered more frequently than the study by Singh et al.,¹² where Triple vessel disease (45%) was encountered more frequently. Whereas studies by Singal et al.,¹ and Mathipa S. et al.,¹¹ showed Single vessel disease to be most frequently encountered among coronary atherosclerosis cases.

In the present study, Grade 2 occlusion (25-50% occlusion) was identified as the most common, occurring with the highest frequency. This finding suggests that, a significant proportion of coronary occlusions were relatively moderate in severity. Conversely, Rao D. et al.,¹³ reported Grade 4 occlusion (75-100% occlusion) as the most common grade in their study. Grade 4 occlusions are characterized by severe blockage, which can lead to more critical clinical outcomes and typically requires more aggressive intervention.

In the present study, LVH was the most common type of myocardial hypertrophy, observed in 72% of cases. This predominance of LVH aligns with the general understanding that left ventricular hypertrophy is frequently associated with conditions such as hypertension and aortic stenosis. Similarly, Singal et al.,¹ also reported a high prevalence of LVH (86%), which further supports the view that LVH is a common form of myocardial hypertrophy. In contrast, Joshi C. et al.,¹⁴ found a different distribution, with a considerably lower prevalence of LVH (37%) and a very low occurrence of RVH (1%). Interestingly, their study revealed a high incidence of combined LVH+RVH (62%), suggesting a distinct patient population. The high rate of combined LVH+RVH could be indicative of conditions that affect both ventricles simultaneously, such as certain congenital heart diseases or specific types of cardiomyopathy.

Overall, the present study’s findings highlight the predominance of LVH with a notable proportion of combined (LVH+RVH) hypertrophy cases. This contrasts with the higher prevalence of LVH reported by Singal et al.,¹ and the substantial proportion of combined LVH+RVH observed by Joshi C. et al.,¹⁴

In the present study, the distribution shows that 58% of the cases were classified as old/healed MI, while 42% were recent/acute MI. This distribution suggests a relatively balanced occurrence of both types of MI in the study population. The higher proportion of old/healed MI indicates a significant number of patients with a history of myocardial infarction who may have undergone prior treatment or monitoring for chronic conditions.

Singal et al.,¹ reported a strikingly different distribution, with 93% of their cases categorized as old/healed MI and only 7% as recent/acute MI. This overwhelming predominance of old/healed MIs suggests that their study population predominantly consisted of individuals with chronic myocardial infarction history.

In contrast, Mathipa S. et al.,¹¹ observed a markedly higher prevalence of recent/acute MI, accounting for 80% of cases, with only 20% classified as old/healed MI. Joshi C. et al.,¹⁴ reported a distribution closer to the present study, with 47% of cases being old/healed and 53% recent/acute. This balanced distribution aligns more closely with the present study’s findings. The disparities in MI type distribution among the studies can be attributed to several factors, including differences in study design, patient selection criteria, and the clinical setting.

The study underscores the importance of early detection and management of atherosclerosis and myocardial hypertrophy. For clinicians, this means implementing regular cardiovascular evaluations for at-risk populations and focusing on preventive measures such as lifestyle modifications and pharmacotherapy to manage risk factors. Public health strategies should include increasing awareness about the risk factors associated with sudden cardiac death and promoting regular health check-ups, particularly in high-risk age groups.

Limitations of present study were, study's retrospective design limits causal inference and could introduce selection bias. The relatively small sample size and lack of diversity in the study population may limit the generalizability of the findings. Larger, multi-centre studies could enhance the robustness of the results.

Present study provides significant insights into the pathological changes in the hearts of individuals with a history of sudden death. The high prevalence of atherosclerosis and myocardial hypertrophy highlights the critical role of these conditions in sudden cardiac events. In sudden deaths, cause of death can be determined by autopsy but routine autopsy procedure is not sufficient and underscores the need for enhanced screening and preventive strategies to address cardiac pathologies and reduce the incidence of sudden death.

Conflict of Interest: None to declare

Source of funding: Nil

1. Sonawane SY, Matkari PP, Pandit GA. Pathology of heart, coronaries and aorta in autopsy cases with history of sudden death: an original article. Int J Res Med Sci. 2017;5:3287-3291.
2. Mukhopadhyay S, Dutta SS, Ghosh K, Goswami AK, Sardar T, Kundu SD. A Retrospective study of Sudden Death cases in Medical College and Hospital, Kolkata. IOSR J Dental Med Sci. 2015;14(1):9-18.33.
3. A S Kasthuri, A Handa, M Niyogi, J C Choudhury, Sudden death: A Clinicopathological Study. J Assoc Physicians India 2002; 50:551-553
4. Spooner PM, Priori SG, Myerburg RJ. Spotlight on sudden cardiac death. Cardiovascular Research 50 2001;173- 6.
5. Gaziano TA. Cardiovascular Disease in the Developing World and Its Cost-Effective Management. Circulation. 2005 Dec 6;112(23):3547–53.
6. Singal P, Kaur M, Garg V. Post mortem Study of Histopathological Lesions of Heart in Cases of Sudden Death - Incidental Findings. Ann. Int. Med. Den. Res. 2018; 4(6):PT01-PT04.
7. Gupta R, Mohan I, Narula J. Trends in Coronary heart disease Epidemiology in India. Annals of Global health .2016 ;82 (2): 307-315.
8. Tabib A, Loire R, Chalabreysse L, et al. Circumstances of death and gross and microscopic observations in a series of 200 cases of sudden death associated with arrhythmogenic right ventricular cardiomyopathy and/or dysplasia. Circula-tion. 2003;108(24):3000–5.
9. Fontaine G, Fornes P. Histology of sudden death in arrhythmogenic right ventricular cardiomyopathy/dysplasia. Circulation. 2004;110(3):e20–e5.
10. Marwah N, Sethi B, Gupta S, Duhan A, Singh S, Sen R: Histomorphological spectrum of various cardiac changes in sudden death: An autopsy study. Iranian Journal of Pathology. 6. 2011;179-186.
11. Mathipa S, T Selvaraj, Balaji VR. Autopsy Study of Sudden Death Cases With Special Reference to Histopathological Changes in Heart 2023;17(2): 90-94.
12. Singh A, Mishra R, Billey A. Cardiac lesions in sudden death: Insights from Autopsy and histopathological analysis. Int J Acad Med Pharm. 2023;
13. Rao M, Xavier D, Devi P, Sigamani A, Faruqui A, Gupta R, Kerkar P, Jain RK, Joshi R, Chidambaram N, Rao DS, Thanikachalam S, Iyengar SS, Verghese K, Mohan V, Pais P. Prevalence, treatments and outcomes of coronary artery disease in Indians: A systematic review. Indian Heart J. 2015 Jul-Aug;67(4):302-10.
14. Joshi C. Postmortem study of histopathological lesions of heart in cases of sudden death - An incidental findings. J Evid Based Med Healthc 2016; 3(6), 184-188.