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ORIGINAL ARTICLE  
Year : 2022  |  Volume : 65  |  Issue : 4  |  Page : 766-771
The occult rheumatic scourge: A clinicopathological analysis of missed rheumatic heart disease


1 Intern, Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra, India
2 Department of Pathology (Cardiovascular and Thoracic Division), Seth GS Medical College, Mumbai, Maharashtra, India
3 Queensland Children's Hospital and Faculty of Medicine, University of Queensland, Brisbane, Australia
4 Consultant Cardiologist, Mahatma Gandhi Mission Hospitals, Mumbai, Maharashtra, India

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Date of Submission28-Dec-2020
Date of Decision03-Jul-2021
Date of Acceptance08-Jul-2021
Date of Web Publication27-Apr-2022
 

   Abstract 


Aims: To study the clinical and pathological manifestations of missed cases of rheumatic heart disease (RHD) and postulate possible reasons behind a missed diagnosis. Materials and Methods: Retrospective 20-year (2000–2019) autopsy data of chronic RHD were reviewed and patients, in whom the valvular deformities had been incidental autopsy findings, were selected. The clinical details of these patients were correlated with the morphology of the affected valves. On this pathological analysis, the patients were assigned to a category of subtle or significant valvular deformity. By clinically correlating, the latter group was subdivided into clinically misdiagnosed, clinically undiagnosed, and sudden cardiac death. Statistical Analysis: Nil. Results: Among the 475 cases of chronic RHD identified at autopsy in the study period, the disease was diagnosed incidentally in 69 patients (14.5%). Significant valvular deformity was noted in 61 cases while the other 8 cases had subtle valvular deformity. The most common cause of death was cardiac failure in 39 out of 69 patients (56%). Eleven (16%) patients had experienced sudden cardiac death. Among the undiagnosed cases, 5 (7%) of them had a diagnosis of non-rheumatic cardiac disease, while the other 14 (20.5%) patients had overwhelming non-cardiac diseases. Conclusions: Our study indicates that mortality and morbidity due to RHD are underdetermined. The patients remain undiagnosed due to either insignificant valvular involvement, clinically silent in the presence of significant valvular deformity, presence of other overwhelming diseases or misdiagnosis partly due to the resemblance with the other pathologies.

Keywords: Missed disease, rheumatic heart disease, silent disease, valvular heart disease

How to cite this article:
Daga P, Vaideeswar P, Goyal A, Marathe SP, Bhargav R. The occult rheumatic scourge: A clinicopathological analysis of missed rheumatic heart disease. Indian J Pathol Microbiol 2022;65:766-71

How to cite this URL:
Daga P, Vaideeswar P, Goyal A, Marathe SP, Bhargav R. The occult rheumatic scourge: A clinicopathological analysis of missed rheumatic heart disease. Indian J Pathol Microbiol [serial online] 2022 [cited 2022 Nov 27];65:766-71. Available from: https://www.ijpmonline.org/text.asp?2022/65/4/766/344184





   Introduction Top


Chronic rheumatic heart disease (RHD) is a major sequel of the healing of acute rheumatic fever, which is a multisystem post-streptococcal autoimmune disease developing in individuals with a genetic predisposition.[1] The structures most commonly affected by this healing process are the heart valves, which culminate in an extraordinary degree of fibro-calcific distortion of the valvular apparatus. This most often results in mitral stenosis (MS) and/or regurgitation (MR), though other valves, particularly the aortic valve, may be similarly affected. Many of these afflicted individuals become symptomatic due to valvular deformities, and hence, chronic RHD remains the most common acquired heart disease in India, which is considered the RHD capital of the world.[2] In a proportion of patients, who may be asymptomatic, the disease is diagnosed on clinical assessment. However, the valvular deformities in a subset of patients may entirely escape detection and may be identified as a surprise finding at autopsy. The aim of our study was to study the pathological features of RHD, which were identified for the first time at autopsy, and understand the possible reasons for a missed diagnosis.


   Materials and Methods Top


It is a retrospective observational study conducted in the cardiovascular pathology division of a large tertiary-care center. Autopsy data over 20 years (2000–2019) of chronic RHD were reviewed. Those cases where RHD was identified for the first time at autopsy were included in the study for analysis. The demographic, clinical details, and autopsy findings of these patients were obtained from the departmental records. All hearts were dissected using the inflow-outflow technique. Particular attention was paid to the morphology of the affected valves. The abnormalities noted for the atrioventricular/arterial valves were—presence or absence of annular dilatation, fusion of the commissures, leaflet/cuspal thickening, fibrosis, and calcification, and for the atrioventricular valves, it also included chordal thickening, shortening, and fusion. All these features, if present, were subjectively graded as mild, moderate, or severe by one of the authors with extensive experience in cardiac pathology. Based on the pathological analysis (heart weight, degree of cardiomegaly, dilatation/hypertrophy of the chamber/s, and morphology of the affected valves), the functional status was categorized as valvular stenosis ± regurgitation [Figure 1]a, [Figure 1]b, [Figure 1]c, [Figure 1]d or pure regurgitation [Figure 2]a and [Figure 2]b. Using the clinicopathological features, we have categorized the missed cases into two groups: (1) Patients with subtle valvular deformities, which would have been clinically insignificant and (2) Patients with significant valvular deformities, which included those (a) whose complaints were wrongly attributed to other cardiac diseases (clinically misdiagnosed) or (b) who presented with non-cardiac diseases (clinically undiagnosed) or (c) who had sudden cardiac deaths.
Figure 1: Case of pure mitral stenosis. (a) The external aspect showing marked enlargement of the right ventricle (RV), enlarged left atrial appendage (LAA), and dilated pulmonary trunk (PT). The left ventricle (LV) appears small in size. (b) LV inflow tract showing markedly dilated and hypertrophied left atrium LA and severe mitral valvular MV/sub-valvular pathology. The case of mitral stenosis with regurgitation. (c) Anterior aspect showing moderate right ventricular RV and mild biatrial/left ventricular LV enlargement. (d) Both commissures (arrows) of mitral valve are moderately fused and calcified leading to concomitant regurgitation. Ascending aorta (AA), anterior mitral leaflet (AML), left atrial appendage (LAA), left atrial cavity (LAC), posterior mitral leaflet (PML), pulmonary trunk (PT), right atrial appendage (RAA)

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Figure 2: Case of pure mitral regurgitation. (a) On external examination, there is moderate biventricular enlargement, apex formed by both ventricles and prominent left atrial appendage (LAA). (b) The inflow tract shows jet lesion of regurgitation (white arrows) on the posterior wall of the left atrium (LA), thickening of the valvular leaflets with a ridge (black arrow) on the posterior mitral leaflet (PML) and mild fusion of the posteromedial commissure (PMC). The tendinous chords are thickened and of almost normal lengths. (c) Rheumatic mitral valvular pathology as an incidental finding at autopsy. The PMC is markedly fused with associated thickening of the adjoining anterior AML and posterior PML leaflets and chordal thickening. The anterolateral commissure (ALC) is not fused (AA: ascending aorta, LAA: left atrial appendage, LAC: left atrial cavity, LV/C: left ventricle/cavity, PT: pulmonary trunk, RAA: right atrial appendage, RV: right ventricle)

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   Results Top


A total of 475 cases were found to have pathological features of RHD during the study period of 20 years. Of these, 69 patients (14.5%) were diagnosed as RHD during the autopsy only for the first time. There were 37 males (53.6%) and 32 females (46.4%) with ages ranging from 10 to 85 years. Nine patients had hypertension, diabetes mellitus, or both, with a history of myocardial infarction in two of them. Among the 32 women, 13 had been pregnant.

Subtle valvular involvement (N = 8)

Out of the 69 cases, 8 patients (11.6%) had subtle rheumatic valvular involvement, which could not be functionally categorized. There were five males and three female patients with a mean age of 46.4 years. They had been admitted (mean duration of admission 12.5 days) for tuberculous meningitis, intracranial schwannoma, acute pyelonephritis, end-stage kidney disease, eclampsia, ischemic heart disease (IHD) with disseminated prostatic adenocarcinoma, and lower limb cellulitis (two patients). The mitral valve (MV) alone was affected in six cases [Figure 2]c, while concomitant aortic valvular involvement was seen in the remaining two cases. All the affected valves had shown the features of healed valvulitis on histology; the myocardium did not show any feature that could be attributed to the healing of acute rheumatic fever. The average heart weight was 268.8 g; the other valves were normal.

Significant valvular deformity (N = 61)

Clinically misdiagnosed

In 10 patients (16.4%), the clinical presentation was ascribed to other cardiovascular conditions. The patients (three men and seven women) had been admitted for a mean duration of 41.2 h and had been symptomatic for a period of 253.5 days (range of 4 days to 5 years). Dyspnea was the major mode of presentation, which was associated with constitutional and other non-thoracic symptoms in six of them; non-thoracic symptoms alone were present in only one patient. The heart weights ranged from 200 to 780 g (mean 381.1 g). A majority of these patients (8, 80%, mean age 37 years) had variable degrees of MS, with or without combined regurgitation (one patient) and aortic valvular deformity (four patients). Superadded infective endocarditis with its complications was also seen in two of them. The remaining two patients (20%) were children with features of rheumatic pancarditis and valvular regurgitation [Table 1].
Table 1: RHD-clinically misdiagnosed (N=10)

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Clinically undiagnosed

This was the largest group with 40 patients (65.6%) with undiagnosed significant rheumatic valvular deformities. There were 21 males and 19 females and their ages ranged from 10 to 70 years with a mean age of 42.2 years. The mean duration of admission had been 46.5 h. The patients had been symptomatic for varying durations of time from 10 h to 6 years, and not surprisingly, a good number of patients (11 cases, 27.5%) had sole non-thoracic symptoms. At autopsy, the patients were found to have mild to marked cardiomegaly with heart weights ranging from 210 to 720 g (mean 354.5 g). Moderate to severe MS was observed in 24 hearts (60%) accompanied by varying proportions of regurgitation and aortic valvular pathology. Mild MS was seen in eight other patients. Infective endocarditis, bicuspid aortic valve, and aortic regurgitation due to syphilitic aortitis were the other valvular changes seen in the stenotic group. On the other hand, mitral regurgitation was seen in only eight additional patients and was associated with aortic stenosis and/or regurgitation [Table 2].
Table 2: RHD-Clinically Undiagnosed (n=40)

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Sudden cardiac deaths

Eleven (eight males and three females, 18%) among the 61 cases had sudden cardiac deaths, two of whom were brought dead to the hospital. The remaining eight patients had hospital admissions for about 3 h. A majority (eight cases) had rapidly progressive dyspnea, which developed after cataract surgery and delivery in one patient each. The mean heart weight was 395.5 g. Moderate to severe MS was observed in six of these patients. Severe aortic stenosis was present in two patients, one of which was due to a unicommissural unicuspid aortic valve; both also had mild rheumatic MS. The remaining three hearts revealed mild to moderate valvular afflictions, with rheumatic myocarditis in one of them. The RHD coexisted with IHD in three patients [Table 3].
Table 3: RHD-Sudden Death (n=11)

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   Discussion Top


It was earlier presumed that RHD had a greater prevalence in temperate climates—a myth that was shattered by a seminal publication in 1962 by Dr. Padmavati S (the first woman cardiologist of India).[3] She stated that it is a “major public health problem” in India. Though the prevalence is said to be declining from the year 2000,[4] the disease continues to be the most 'visible' deformity (alongside IHD) in the medical and surgical practice, and this is reflected even in the cardiovascular autopsy data.[5] This is not altogether surprising since RHD still remains a disease of poverty, coupled with poor public health infrastructure. The current study focused on another aspect of RHD in the form of the missed disease. It is a well-known fact that RHD affects the left-sided heart valves and the MV in particular. All the eight patients within the category of subtle valvular involvement had a dominant mitral valvular disease, though the degree of deformity would have hardly produced any symptoms in these patients, and some may not have been noted even at autopsy.

A very common manifestation of RHD in patients (usually beyond adolescence) is MS, which occurs when the valve orifice area falls below 2.5 cm2 and can be graded as mild (≥2–2.5 cm2), moderate (1.0–1.5 cm2), or severe (<1.5 cm2). The stenosis of the MV (well outlined by Manjunath et al.[6]) in RHD is mostly associated with other valvular involvement (especially aortic) as well as concomitant regurgitation; pure MR/MS is uncommon. Individuals with severe stenosis are usually symptomatic. Despite the clinical presentation and characteristic echocardiographic findings, a group of patients surprisingly do not have auscultatory findings or have very subtle findings, which are easily missed by a less experienced clinician. This subset is referred to as silent RHD.[7] The prevalence of such silent cases is much more than the clinically diagnosed patients (21.1 per 1,000 people vs. 2.7 per 1,000 people), a noteworthy fact.[7] This paradox is explained on the basis of severe stenosis with calcification (causing attenuation of opening snap and muffling of first heart sound) and/or enlarged right ventricle with clockwise rotation of the heart (shifting the stenotic murmur from its usual mitral area toward posterior axillary line). Similarly, there is also shifting of the aorta toward the left sternal border with consequently decreased amplitude of the aortic murmur. These aspects were emphasized by a study by Carapetis et al.[8] where it was shown that auscultatory screening alone missed more than half of the pathological valvular lesions compared to echocardiographic screening. Apart from that, those patients with mild to moderate narrowing can remain without symptoms, unless there are circumstances that would tilt the delicate hemodynamic balance,[9] as seen in 13 women with pregnancy. It is also possible that the symptoms can develop due to cardiac or non-cardiac complications of RHD and also due to non-rheumatic cardiac and non-cardiac diseases, which can camouflage the underlying valvular deformity. It is well understood that the clinical diagnosis of valvular heart diseases is highly specific but insensitive for the cause of death established at autopsy.[10] A majority of the patients in the clinically misdiagnosed or undiagnosed group (44 of 50 patients, 88%) had moderate to severe valvular stenosis and/or regurgitation, most commonly involving the MV (40 of 44 patients with moderate to severe disease, 90.9%). The most common misdiagnosis made in our cases was pulmonary thromboembolism and cardiomyopathy (6 of 10 patients). These diagnoses were not confirmed on autopsy, and hence, these mimicked RHD clinically with the presence of dyspnea and chest pain. Among the 40 undiagnosed cases, only five were clinically diagnosed with cardiovascular disease, while others had non-cardiac diseases that may have necessitated more urgent evaluation, the most common being acute febrile illnesses due to various causes. But even in them, other associated cardiac diseases may also have played a role in leading to terminal cardiac failure. These associations along with pulmonary hypertension could have also contributed to the sudden deaths, though RHD by itself has also been previously reported as a cause of sudden death.[11]

As this study was conducted in a large tertiary-care hospital of a metropolitan city, a large sample of autopsied RHD cases could be studied. Furthermore, the recording of autopsy data over the years had been fairly uniform and extensive, forming a reliable source of information to conduct a retrospective study. But there have been certain limitations. As our analysis is autopsy-based, it does not indicate the true incidence of undiagnosed RHD cases in the community. There are other important factors that could not be evaluated. Ignorance for symptoms of RHD, illiteracy, poverty, and inequitable distribution of healthcare facilities are among the many social factors that contribute to the high burden and delayed diagnosis of several diseases including RHD.[12] This study has compared RHD cases from the last 20 years. During this period, multiple changes in the guidelines of RHD diagnosis and screening have taken place.[13],[14] the effectiveness of these changes on the proportion of cases missed could not be studied. Interestingly, our study indicates that most of the incidental RHD cases found on autopsy have significant valvular involvement. Hence, clinical studies aimed at studying the reasons for the severe cases to remain asymptomatic or presenting without murmur on auscultation need to be conducted. There is a need to do a large-scale screening in the endemic areas to estimate the true burden of the disease. Further, long-term follow-up of the cases identified during the echocardiographic screening needs to be conducted to study the impact of early identification on morbidity and mortality.

In conclusion, our study indicates that mortality and morbidity due to RHD are under-determined. Patients remain undiagnosed due to either insignificant valvular involvement or clinically silent in the presence of significant valvular deformity or presence of other overwhelming diseases or misdiagnosis partly due to resemblance with other pathologies.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

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Manjunath CN, Srinivas P, Ravindranath KS, Dhanalakshmi C. Incidence and patterns of valvular heart disease in a tertiary care high-volume cardiac center: A single center experience. Indian Heart J 2014;66:320-6.  Back to cited text no. 6
    
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Carapetis JR, Hardy M, Fakakovikaetau T, Taib R, Wilkinson L, Penny DJ, et al. Evaluation of a screening protocol using auscultation and portable echocardiography to detect asymptomatic rheumatic heart disease in Tongan schoolchildren. Nat Clin Pract Cardiovasc Med 2008;5:411-7.  Back to cited text no. 8
    
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Maganti K, Rigolin VH, Sarano ME, Bonow RO. Valvular heart disease: Diagnosis and management. Mayo Clin Proc 2010;85:483-500.  Back to cited text no. 9
    
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Coffey S, Harper AR, Cairns BJ, Roberts IS, Prendergast BD. Clinical information has low sensitivity for postmortem diagnosis of heart valve disease. Heart 2017;103:1031-5.  Back to cited text no. 10
    
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Henriques de Gouveia RHAM, Corte Real Goncalves FMA. Sudden cardiac death and valvular pathology. Forensic Sci Res 2019;19:280-6.  Back to cited text no. 11
    
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Coffey PM, Ralph AP, Krause VL. The role of social determinants of health in the risk and prevention of group A streptococcal infection, acute rheumatic fever and rheumatic heart disease: A systematic review. PLoS Negl Trop Dis 2018;12:e0006577.  Back to cited text no. 12
    
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Reményi B, Wilson N, Steer A, Ferreira B, Kado J, Kumar K, et al. World Heart Federation criteria for echocardiographic diagnosis of rheumatic heart disease -- An evidence-based guideline. Nat Rev Cardiol 2012;9:297-309.  Back to cited text no. 13
    
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Dougherty S, Khorsandi M, Herbst P. Rheumatic heart disease screening: Current concepts and challenges. Ann Ped Cardiol 2017;10;39-49.  Back to cited text no. 14
    

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Correspondence Address:
Pradeep Vaideeswar
Department of Pathology (Cardiovascular and Thoracic Division), Seth GS Medical College, Mumbai, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijpm.ijpm_1473_20

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