European Journal of Cardiovascular Medicine

Dilated cardiomyopathy (DCM) is a primary myocardial disorder characterised by dilatation of the left ventricle, or of both ventricles, together with impaired systolic function that cannot be explained solely by abnormal loading conditions such as hypertension or valvular disease, or by coronary artery disease sufficient to cause global systolic impairment.[1–3] The 2016 position statement of the European Society of Cardiology (ESC) proposed that DCM be regarded as a phenotype shared by diverse genetic and acquired causes, and introduced the category of hypokinetic non-dilated cardiomyopathy for patients with global systolic impairment but without ventricular dilatation.[4] DCM is the commonest cardiomyopathy phenotype and one of the leading causes of heart failure with reduced ejection fraction (HFrEF) and of cardiac transplantation in young and middle-aged adults worldwide.[5–7]

The population-based Olmsted County study estimated the incidence of idiopathic DCM at about 6 per 100,000 per year and its prevalence at about 36 per 100,000 (roughly 1 in 2,500).[8] These figures are now believed to be underestimates, because mild, subclinical and familial forms often go unrecognised.[9,10] When first-degree relatives are systematically screened, 20–35% of probands are found to have familial disease.[11,12] Clinicopathological series show that, after coronary disease is excluded, roughly half of the cases remain idiopathic, while myocarditis, peripartum cardiomyopathy, toxins (alcohol, anthracyclines), infections (including HIV), endocrine and nutritional disorders and tachycardia-mediated myocardial dysfunction account for most of the remainder.[13–16]

India is passing through a rapid epidemiological transition. Cardiovascular disease accounted for 28.1% of all deaths in India in 2016, compared with 15.2% in 1990, and it is now the leading cause of mortality in nearly every state.[17,18] The “emerging epidemic” of cardiovascular disease in developing countries[19] has been accompanied by a large and growing burden of heart failure, estimated at 1.3 to 4.6 million prevalent cases in India.[20] Registry data from Kerala show that Indian patients with heart failure are almost a decade younger than those in Western registries and have substantial in-hospital and short-term mortality.[21,22] However, these registries are dominated by ischaemic heart disease, and prospectively collected, DCM-specific clinical and echocardiographic data from Indian teaching hospitals remain sparse. The Indian aetiological mix is also distinctive: high rates of tobacco and alcohol use, anaemia and undernutrition, infectious and post-partum myocardial disease, and delayed presentation to tertiary centres may all modify the phenotype and outcome of DCM.[23,24]

Transthoracic echocardiography is the first-line imaging modality for DCM. It quantifies ventricular size, wall thickness and ejection fraction, grades functional mitral and tricuspid regurgitation, assesses diastolic function, right ventricular performance and pulmonary pressures, and detects intracardiac thrombus.[25–27] Several of these parameters carry important prognostic information.[28] A locally derived clinical and echocardiographic profile helps clinicians recognise the disease earlier, plan investigations and treatment, and counsel patients about prognosis. The present study was therefore undertaken to describe the clinical and echocardiographic profile of DCM in a tertiary care teaching hospital.

Aim and objectives

• To study the clinical profile (symptoms, signs, risk factors, electrocardiographic and laboratory findings) of patients with DCM.
• To study the echocardiographic profile of these patients and its relationship with functional (NYHA) class.
• To determine the aetiological distribution of DCM in the study population.
• To assess the short-term (three-month) outcome and the factors associated with mortality.

Study design, setting and duration

This was a hospital-based, prospective, observational study conducted in the Departments of Cardiology of Muzaffarnagar Medical College, a tertiary care teaching hospital in Muzaffarnagar. The study was carried out over 18 months (January 2022 to June 2023), and each participant was followed for three months after discharge. The study was approved by the Institutional Ethics Committee and written informed consent was obtained from every participant.

Sample size

The minimum sample size was calculated with the formula n = Z²pq/d², taking a 95% confidence level (Z = 1.96), an assumed proportion (p) of 50% for the characteristic of interest because no local estimate was available, and an absolute precision (d) of 10%. This gave n = 96, which was rounded up to 100 consecutive eligible patients.

Inclusion criteria

•          Age 18 years or older, of either sex.

•          Echocardiographic LVEF <45% with left ventricular dilatation, defined as an end-diastolic dimension more than two standard deviations above the sex- and body-surface-area-specific normal value, consistent with the ESC definition. [3,4,25]

Exclusion criteria

•          Significant coronary artery disease (≥50% luminal stenosis on coronary angiography or CT angiography, performed in all patients older than 40 years and in younger patients with risk factors, ischaemic ECG changes or regional wall-motion abnormalities).

•          Moderate-to-severe primary valvular heart disease (rheumatic or degenerative), congenital heart disease, pericardial disease, cor pulmonale, and hypertrophic or restrictive cardiomyopathy.

•          Hypertensive heart disease (long-standing uncontrolled hypertension with concentric hypertrophy) and patients who refused consent.

Data collection and aetiological classification

A pre-tested structured proforma was used to record demographic details, presenting symptoms and their duration, functional class (New York Heart Association, NYHA), personal habits, comorbidities, family history, and drug and obstetric history. Examination included vital signs, body mass index, jugular venous pressure, oedema, cardiac and respiratory examination, and hepatomegaly or ascites. Aetiology was assigned using the following operational criteria: (a) alcoholic cardiomyopathy, chronic intake of more than 80 g of alcohol per day for at least five years with no other identifiable cause;[29] (b) peripartum cardiomyopathy, heart failure developing in the last month of pregnancy or within five months of delivery;[30] (c) familial DCM, two or more affected relatives, based on history and available records;[11] (d) post-myocarditis DCM, an acute febrile or viral illness within three months before symptom onset, with raised troponin or compatible echocardiographic evolution; (e) tachycardia-induced cardiomyopathy, sustained tachyarrhythmia with ventricular function recovering after rate or rhythm control; (f) other identifiable causes (thyroid dysfunction, nutritional deficiency, anthracycline exposure, HIV infection); and (g) idiopathic DCM, when none of the above was present.

Investigations

All patients underwent a 12-lead electrocardiogram (ECG) and a postero-anterior chest radiograph. Blood tests included a complete blood count, renal function, serum electrolytes, liver function tests, thyroid function tests, HIV serology and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Transthoracic echocardiography was performed within 48 hours of admission by a single trained operator using a phased-array 2.5–3.5 MHz probe, in accordance with the American Society of Echocardiography (ASE) recommendations.[25] Measurements included left ventricular end-diastolic and end-systolic dimensions (LVEDD, LVESD), fractional shortening, interventricular septal and posterior wall thickness, relative wall thickness, left atrial diameter, and LV volumes and LVEF by the modified biplane Simpson method. Left ventricular mass was estimated by the linear method. Mitral and tricuspid regurgitation were graded by an integrated semi-quantitative approach. Diastolic function was graded as recommended,[26] and right ventricular systolic function was assessed by tricuspid annular plane systolic excursion (TAPSE), with a value <17 mm considered abnormal.[27] Pulmonary artery systolic pressure (PASP) was estimated from the tricuspid regurgitant jet and right atrial pressure, and pulmonary hypertension was defined as PASP >35 mmHg. The left ventricle was examined for thrombus and the pericardium for effusion.

Treatment and follow-up

Patients were treated according to contemporary heart failure guidelines.[31] Follow-up was done at one and three months by outpatient visit or telephone, and a repeat echocardiogram was performed at three months in those who attended. Outcome measures were in-hospital death, readmission and death within three months, change in NYHA class, and change in LVEF.

Statistical analysis

Data were entered in Microsoft Excel and analysed using SPSS version 26.0 (IBM Corp., Armonk, NY, USA). Continuous variables are expressed as mean ± standard deviation (or median with interquartile range when not normally distributed) and categorical variables as numbers and percentages. Groups were compared with the independent-samples t-test or one-way ANOVA for continuous variables and the chi-square or Fisher’s exact test for categorical variables. The paired t-test was used for before-and-after comparisons, and Pearson’s correlation coefficient (r) for association between continuous variables. A two-tailed p value <0.05 was considered statistically significant.

During the study period, 168 patients with echocardiographically detected left ventricular systolic dysfunction were screened. Sixty-eight were excluded (significant coronary artery disease 38, primary valvular heart disease 14, hypertensive heart disease 8, congenital heart disease 3, refusal of consent 5), leaving 100 patients with DCM for final analysis.

Demographic profile

The mean age of the patients was 46.8 ± 13.2 years (range 18–78 years). Most patients were in the fifth and sixth decades of life: 26% were aged 41–50 years and 25% were aged 51–60 years, so that 51% were between 41 and 60 years of age, while 33% were younger than 40 years. There were 68 men and 32 women (male-to-female ratio 2.1:1) (Table 1, Figure 1). Fifty-eight patients (58%) lived in rural areas and 42 (42%) in urban areas. The mean body mass index was 22.4 ± 3.6 kg/m².

Table 1: Age and sex distribution of the study population (N = 100)

Mean age 46.8 ± 13.2 years; male-to-female ratio 2.1:1.

Clinical presentation

Exertional dyspnoea was the commonest presenting symptom (94%), followed by fatigue (78%), pedal oedema (62%), orthopnoea (56%) and paroxysmal nocturnal dyspnoea (48%). Palpitations (34%) and abdominal distension (31%) were reported by about one-third of patients, while atypical chest pain (22%) and syncope or pre-syncope (9%) were less frequent (Table 2). Symptoms had been present for one to six months in 49% and for more than six months in 37% of patients. Most patients presented late: 46% were in NYHA class III and 37% in class IV, whereas only 17% were in class II and none in class I.

Table 2: Presenting symptoms, duration of symptoms and NYHA functional class (N = 100)

Patients could have more than one symptom; percentages therefore exceed 100.

Risk factors and aetiology

Among the 68 men, 41 (60.3%) were current or former smokers and 37 (54.4%) were chronic alcohol users; all smokers and alcohol users were male. Tobacco chewing was reported by 18 patients (14 men and 4 women). Hypertension (generally mild and controlled), diabetes mellitus and anaemia were present in 29%, 24% and 31% of patients respectively. A preceding febrile or viral illness within three months of symptom onset was noted in 17%, and a family history of cardiomyopathy, heart failure or sudden cardiac death in 8% (Table 3).

Table 3: Risk factors and associated conditions (N = 100)

Idiopathic DCM was the commonest category (46%), followed by alcohol-related DCM (21%) and post-myocarditis DCM (9%). Peripartum cardiomyopathy was diagnosed in 4 of the 32 women (12.5% of women), tachycardia-induced cardiomyopathy in 5 patients and familial DCM in 5 patients. Ten patients had other identifiable causes: thyroid dysfunction (3), nutritional deficiency (3), anthracycline exposure (2) and HIV infection (2) (Table 4). Alcohol-related DCM occurred exclusively in men.

Table 4: Aetiological distribution and left ventricular size and function by aetiology

*Thyroid dysfunction 3, nutritional deficiency 3, anthracycline exposure 2, HIV infection 2. Values are mean ± SD. Difference in LVEF across groups p = 0.31 (NS); LVEDD p = 0.04 (ANOVA).

Examination findings

The mean heart rate was 94.6 ± 14.8 beats per minute and the mean systolic blood pressure was 106.4 ± 18.2 mmHg; 14 patients (14%) had a systolic pressure below 90 mmHg. A displaced apex beat was found in 81%, a third heart sound in 63%, bilateral basal crepitations in 67% and a raised jugular venous pressure in 58%. An apical pansystolic murmur of functional mitral regurgitation was heard in 52% of patients (Table 5).

Table 5: Vital parameters and physical findings at presentation (N = 100)

ECG, chest radiograph and laboratory findings

The commonest ECG abnormalities were non-specific ST–T changes (44%), sinus tachycardia (38%), poor R-wave progression (31%) and left bundle branch block (24%). Atrial fibrillation was present in 14% and ventricular ectopics in 19%. Cardiomegaly (cardiothoracic ratio >0.5) was seen in 88% of chest radiographs and pulmonary venous congestion in 63%. The mean haemoglobin was 11.6 ± 1.9 g/dL, and 31% were anaemic. Hyponatraemia (serum sodium <135 mmol/L) was found in 46% and serum creatinine above 1.5 mg/dL in 13%. The median NT-proBNP was 3,420 pg/mL (interquartile range 1,860–6,240) (Table 6).

Table 6: Electrocardiographic, radiographic and laboratory findings (N = 100)

Echocardiographic profile

All patients had global left ventricular hypokinesia. The mean LVEF was 29.9 ± 7.5% (range 12–44%), LVEDD 62.9 ± 7.1 mm, LVESD 53.0 ± 8.0 mm and fractional shortening 15.7 ± 4.3%. The mean LV end-diastolic and end-systolic volumes were 188 ± 49 mL and 132 ± 44 mL. Wall thickness was normal or reduced (septum 8.4 ± 1.3 mm, posterior wall 8.2 ± 1.2 mm), giving a mean relative wall thickness of 0.26 and an LV mass index of about 132 g/m², in keeping with eccentric remodelling. The left atrium was enlarged (mean 42.6 ± 6.1 mm) (Table 7).

Table 7: Echocardiographic measurements (N = 100)

Seventy-nine per cent of patients had an LVEF below 40%, and 8% had a severely depressed LVEF below 20%. Functional mitral regurgitation was moderate in 32% and severe in 18%, and moderate or severe tricuspid regurgitation was present in 33%. A restrictive filling pattern (grade III diastolic dysfunction) was the commonest diastolic abnormality (41%). Right ventricular systolic dysfunction (TAPSE <17 mm) was seen in 64% and pulmonary hypertension in 63%. Left ventricular thrombus was detected in 7 patients (7%) and a small pericardial effusion in 11 (Table 8).

Table 8: Categorical echocardiographic findings (N = 100)

Echocardiographic parameters and functional class

Worsening NYHA class was accompanied by a progressive fall in LVEF and a rise in LV dimensions, left atrial size, filling pressures and pulmonary pressures, with a progressive decline in right ventricular function (Table 9, Figure 2). The mean LVEF was 35.1 ± 5.4% in class II, 31.0 ± 6.8% in class III and 26.0 ± 6.5% in class IV (p < 0.001). Across the whole cohort, NYHA class showed a moderate negative correlation with LVEF (r = −0.58, p < 0.001) and positive correlations with LVEDD (r = 0.49), PASP (r = 0.52) and left atrial diameter (r = 0.47) (all p < 0.001). LVEF was inversely related to LVEDD (r = −0.62, p < 0.001) and positively related to TAPSE (r = 0.44, p < 0.001), and the E/e′ ratio correlated with PASP (r = 0.55, p < 0.001). Duration of symptoms showed only a weak inverse correlation with LVEF (r = −0.28, p = 0.005).

Table 9: Echocardiographic parameters according to NYHA functional class (mean ± SD)

One-way ANOVA.

Treatment, outcome and predictors of mortality

Loop diuretics were used in 97% of patients. Renin–angiotensin system inhibition was possible in 92% (ACE inhibitor 52%, angiotensin receptor blocker 19%, sacubitril–valsartan 21%); the remaining 8 patients with hypotension or renal impairment received hydralazine and nitrates. Beta-blockers were given to 83% and mineralocorticoid receptor antagonists to 78%. Dapagliflozin or empagliflozin was prescribed in 34%, ivabradine in 17% and digoxin in 29%. Oral anticoagulation was started in 24 patients (atrial fibrillation 14, LV thrombus 7, other indications 3). Intravenous inotropes were needed in 22%. Device therapy was limited by cost: an implantable cardioverter-defibrillator was implanted in 3 patients and cardiac resynchronisation therapy in 2 (Table 10).

Table 10: Treatment given during hospital stay and at discharge (N = 100)

The mean hospital stay was 8.4 ± 3.7 days. Non-invasive ventilation was required in 14 patients and invasive ventilation in 9. Six patients (6%) died in hospital and three (3%) left against medical advice; 91 were discharged, of whom 85 (93.4%) completed three-month follow-up. Twenty-four of these 85 (28.2%) were readmitted with decompensated heart failure and 7 (8.2%) died after discharge, giving an overall three-month mortality of 13% (13/100). In the 78 survivors who were followed up, LVEF improved from 30.5 ± 7.2% to 35.2 ± 8.4% (p < 0.001), and 53 (68.0%) were in NYHA class I–II at three months (Table 11).

Table 11: Hospital course and three-month outcome

Patients who died within three months had a significantly lower LVEF (24.8 ± 5.4% versus 30.7 ± 7.4%), larger LVEDD and higher PASP than those who survived. Presentation in NYHA class IV, systolic blood pressure below 90 mmHg, hyponatraemia, serum creatinine above 1.5 mg/dL, right ventricular dysfunction, severe mitral regurgitation and a restrictive filling pattern were all more frequent among non-survivors. Age and sex were not significantly different between the two groups (Table 12).

Table 12: Comparison of patients who died within three months and those who survived

t-test for continuous and chi-square / Fisher’s exact test for categorical variables.

This prospective study describes the clinical and echocardiographic profile of 100 consecutive patients with DCM at a tertiary care teaching hospital. The principal findings are that the disease affected relatively young, predominantly male patients who presented late with advanced symptoms; that idiopathic and alcohol-related causes accounted for two-thirds of cases; that echocardiography showed severe biventricular dysfunction with frequent functional mitral regurgitation, restrictive filling and pulmonary hypertension; and that echocardiographic severity tracked both functional class and short-term mortality.

The mean age of 46.8 years, with 51% of patients aged 41–60 years, is consistent with the established pattern of DCM presenting in the third to sixth decades of life.[5,14] The male preponderance (68%) is similar to the roughly threefold higher incidence in men in the Olmsted County study,[8] although our male-to-female ratio of 2.1:1 is somewhat lower, possibly because peripartum and nutritional causes add women to Indian series. The age profile also matches Indian heart failure registries, in which patients are nearly a decade younger than in Western cohorts,[21,22] and it underlines the economic and social cost of the disease, as affected individuals are often the principal earners of their households.[20] More than half of our patients (58%) came from rural areas, which probably reflects the referral pattern of a tertiary teaching hospital and may contribute to delayed presentation.

Dyspnoea, fatigue, oedema and orthopnoea dominated the presentation, in agreement with the typical symptoms of left- and right-sided congestion described in heart failure guidelines and in the classic description of DCM.[5,31] Importantly, 83% of our patients were in NYHA class III or IV and 37% had symptoms for more than six months before reaching us. Late presentation is a recurring theme in the Indian studies, where limited awareness, financial constraints and fragmented primary care delay diagnosis,[20,21] and it probably explains the very high NT-proBNP values, the frequency of hypotension (14%) and hyponatraemia (46%), and the need for inotropic support in 22%. The finding of a third heart sound in 63% and functional mitral regurgitation murmur in 52% of patients emphasises that careful bedside examination remains valuable for identifying advanced disease.

Idiopathic DCM accounted for 46% of cases in our series, nearly identical to the 47–51% reported in the large clinicopathological series of Kasper et al. and Felker et al.[13,14] Alcohol-related disease was the second most common cause (21%) and, along with smoking, was confined to men. Chronic heavy alcohol consumption is a well-recognised, potentially reversible cause of DCM,[29] and the rising per-capita consumption of alcohol in India[24] together with high rates of tobacco use and regional variation in cardiovascular risk factors[23] suggest that alcohol-related cardiomyopathy may become more important in the future. Abstinence can improve ventricular function substantially, so prompt identification of this subgroup has real therapeutic value.

Post-myocarditis DCM (9%) matched the 9% of unexplained cardiomyopathies attributed to myocarditis by Felker et al.,[14] though its true frequency is likely higher because we did not perform cardiac magnetic resonance imaging or endomyocardial biopsy, and the diagnosis of myocarditis remains difficult in routine practice.[32] Peripartum cardiomyopathy affected 12.5% of the women in our series, a notable proportion that reinforces the contribution of pregnancy-related myocardial disease in India;[30,33] similar importance has been documented in African urban populations.[34] Tachycardia-induced cardiomyopathy (5%) is an important diagnosis not to miss, as ventricular function may recover with rhythm or rate control.[16] Familial DCM was identified in only 5% of our patients, far lower than the 20–35% in studies with systematic family screening;[11,12] because we relied on history rather than echocardiographic screening of first-degree relatives, familial disease is almost certainly under-diagnosed, and some patients labelled idiopathic probably have a genetic aetiology.[9] The remaining specific causes (thyroid disease, nutritional deficiency, anthracyclines and HIV) are consistent with the aetiological spectrum summarised in the American Heart Association statement on specific dilated cardiomyopathies.[15]

No ECG pattern is specific for DCM, but non-specific ST–T changes, sinus tachycardia, poor R-wave progression, left bundle branch block and atrial or ventricular arrhythmias are common, as observed here.[5,6] The 24% prevalence of left bundle branch block is clinically relevant because of its implications for cardiac resynchronisation therapy,[35] and the 14% prevalence of atrial fibrillation influences anticoagulation decisions. Cardiomegaly on chest radiography (88%) was nearly universal and supports its continued use as a simple screening test where echocardiography is not immediately available.

The mean LVEDD of 62.9 mm and LVEF of 29.9% depict a markedly dilated, globally hypokinetic ventricle. Normal reference values in the ASE/EACVI recommendations indicate that the observed dimensions lie well above the upper limits of normal for both sexes.[25] Wall thickness was normal or reduced, giving a low relative wall thickness (0.26), the classic eccentric remodelling pattern of DCM.[25,28] Left atrial enlargement (71%) reflects chronically raised filling pressures and functional mitral regurgitation, which has been associated with adverse outcomes in patients with heart failure.[36] In our series 50% had moderate or severe functional mitral regurgitation, resulting from annular dilatation and papillary muscle displacement, and the proportion with severe regurgitation was significantly higher among non-survivors.

A restrictive filling pattern, found in 41% of patients, together with a mean E/e′ of 17.2, indicates elevated left atrial pressure in a large proportion of patients.[26] Right ventricular dysfunction (TAPSE <17 mm) was present in 64% and pulmonary hypertension in 63%. Right ventricular systolic function and pulmonary artery pressure have independent and additive prognostic value in chronic heart failure,[37] which is concordant with the higher frequency of RV dysfunction (92%) and the higher PASP in our non-survivors. The 7% prevalence of left ventricular thrombus underlines the thrombo-embolic risk in patients with markedly depressed LVEF, and routine search for thrombus on echocardiography is recommended.[28]

Functional class was strongly related to echocardiographic severity: patients in higher NYHA classes had lower LVEF, larger LV and left atrial dimensions, higher E/e′ and PASP, and poorer TAPSE. The negative correlation between NYHA class and LVEF (r = −0.58) and the positive correlation with PASP (r = 0.52) show that, although symptoms in heart failure do not map perfectly on to ejection fraction, a clear gradient of echocardiographic abnormality exists with clinical severity. Echocardiography at first contact therefore adds objective information beyond symptom grading and can help to prioritise patients for early optimisation of therapy.[28,31]

Most patients received guideline-directed medical therapy comprising a renin–angiotensin system inhibitor, a beta-blocker and a mineralocorticoid receptor antagonist, agents with proven survival benefit in HFrEF.[31,38–40] Sacubitril–valsartan (21%) and SGLT2 inhibitors (34%) were used in a considerable minority of patients, reflecting recent evidence from large randomised trials,[41,42] although cost remains a barrier in the Indian setting. Device therapy was infrequent (5%) because of expense. The Danish trial found that prophylactic defibrillator implantation in non-ischaemic systolic heart failure did not reduce all-cause mortality overall,[43] and guidelines recommend individualised decisions,[31,44] but resource limitations in India mean that even patients who would qualify often cannot receive devices.

The in-hospital mortality of 6% and three-month mortality of 13% in our cohort are comparable with, or slightly better than, the short-term outcomes reported in Indian heart failure registries,[21] and the INTER-CHF study documented substantial one-year mortality in the Indian cohort, higher than in China or South America.[45] The prognosis of idiopathic DCM is generally better than that of ischaemic cardiomyopathy,[46] which may partly explain the lower mortality in our series, as patients with coronary disease were excluded. The cause also influences outcome, with infiltrative, HIV-related and anthracycline cardiomyopathies faring worst.[14] The improvement in LVEF from 30.5% to 35.2% in survivors at three months, together with improved NYHA class in two-thirds, shows that a considerable proportion of patients show early reverse remodelling when treated optimally.[10]

Univariate predictors of death in our study were NYHA class IV, hypotension, hyponatraemia, renal dysfunction, low LVEF, larger LVEDD, severe mitral regurgitation, restrictive filling, RV dysfunction and high PASP. Hyponatraemia has been recognised since the 1980s as an independent marker of poor prognosis in heart failure, reflecting neurohormonal activation,[47] and the prognostic role of right ventricular dysfunction and pulmonary hypertension has been confirmed in several cohorts.[37] These simple, inexpensive bedside and echocardiographic markers can be used to identify high-risk patients who need intensive monitoring, early specialist referral and close follow-up.

Strengths and limitations

The strengths of this study include its prospective design, consecutive recruitment, standardised echocardiography by a single operator following current recommendations, and structured follow-up with repeat imaging. Its limitations include the single-centre setting and modest sample size, which restrict generalisability and the power of subgroup analyses, particularly for rare aetiologies; the short follow-up of three months; the absence of cardiac magnetic resonance imaging, endomyocardial biopsy and genetic testing; the reliance on history for the diagnosis of familial disease; the use of univariate rather than multivariable analysis for predictors of mortality because of the small number of events; and the loss to follow-up of nine patients after discharge. Multi-centre studies with longer follow-up and genetic evaluation are needed to define the natural history of DCM in India.

DCM in this tertiary care cohort affected relatively young, predominantly male patients, most of whom presented late in NYHA class III–IV. Idiopathic and alcohol-related disease were the commonest causes, and a substantial minority had potentially reversible or preventable aetiologies such as alcohol, peripartum cardiomyopathy, tachycardia-induced cardiomyopathy and thyroid or nutritional disorders. Echocardiography revealed marked left ventricular dilatation and systolic dysfunction, frequent functional mitral regurgitation, restrictive filling, right ventricular dysfunction and pulmonary hypertension; these parameters correlated with functional class, and several were associated with short-term mortality. Early echocardiographic evaluation of patients with unexplained breathlessness, enquiry for alcohol and other reversible causes, family screening, and prompt initiation of guideline-directed therapy should improve outcomes. Larger multi-centre studies with longer follow-up are needed to confirm these findings.

1.       Richardson P, McKenna W, Bristow M, Maisch B, Mautner B, O'Connell J, et al. Report of the 1995 World Health Organization/International Society and Federation of Cardiology Task Force on the definition and classification of cardiomyopathies. Circulation. 1996;93(5):841-2.

2.       Maron BJ, Towbin JA, Thiene G, Antzelevitch C, Corrado D, Arnett D, et al. Contemporary definitions and classification of the cardiomyopathies: an American Heart Association Scientific Statement. Circulation. 2006;113(14):1807-16.

3.       Elliott P, Andersson B, Arbustini E, Bilinska Z, Cecchi F, Charron P, et al. Classification of the cardiomyopathies: a position statement from the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J. 2008;29(2):270-6.

4.       Pinto YM, Elliott PM, Arbustini E, Adler Y, Anastasakis A, Böhm M, et al. Proposal for a revised definition of dilated cardiomyopathy, hypokinetic non-dilated cardiomyopathy, and its implications for clinical practice: a position statement of the ESC Working Group on Myocardial and Pericardial Diseases. Eur Heart J. 2016;37(23):1850-8.

5.       Dec GW, Fuster V. Idiopathic dilated cardiomyopathy. N Engl J Med. 1994;331(23):1564-75.

6.       Weintraub RG, Semsarian C, Macdonald P. Dilated cardiomyopathy. Lancet. 2017;390(10092):400-14.

7.       Schultheiss HP, Fairweather D, Caforio ALP, Escher F, Hershberger RE, Lipshultz SE, et al. Dilated cardiomyopathy. Nat Rev Dis Primers. 2019;5(1):32.

8.       Codd MB, Sugrue DD, Gersh BJ, Melton LJ 3rd. Epidemiology of idiopathic dilated and hypertrophic cardiomyopathy: a population-based study in Olmsted County, Minnesota, 1975-1984. Circulation. 1989;80(3):564-72.

9.       Hershberger RE, Hedges DJ, Morales A. Dilated cardiomyopathy: the complexity of a diverse genetic architecture. Nat Rev Cardiol. 2013;10(9):531-47.

10.    Merlo M, Cannatà A, Gobbo M, Stolfo D, Elliott PM, Sinagra G. Evolving concepts in dilated cardiomyopathy. Eur J Heart Fail. 2018;20(2):228-39.

11.    Mestroni L, Maisch B, McKenna WJ, Schwartz K, Charron P, Rocco C, et al. Guidelines for the study of familial dilated cardiomyopathies. Eur Heart J. 1999;20(2):93-102.

12.    Grünig E, Tasman JA, Kücherer H, Franz W, Kübler W, Katus HA. Frequency and phenotypes of familial dilated cardiomyopathy. J Am Coll Cardiol. 1998;31(1):186-94.

13.    Kasper EK, Agema WR, Hutchins GM, Deckers JW, Hare JM, Baughman KL. The causes of dilated cardiomyopathy: a clinicopathologic review of 673 consecutive patients. J Am Coll Cardiol. 1994;23(3):586-90.

14.    Felker GM, Thompson RE, Hare JM, Hruban RH, Clemetson DE, Howard DL, et al. Underlying causes and long-term survival in patients with initially unexplained cardiomyopathy. N Engl J Med. 2000;342(15):1077-84.

15.    Bozkurt B, Colvin M, Cook J, Cooper LT, Deswal A, Fonarow GC, et al. Current diagnostic and treatment strategies for specific dilated cardiomyopathies: a scientific statement from the American Heart Association. Circulation. 2016;134(23):e579-646.

16.    Gupta S, Figueredo VM. Tachycardia mediated cardiomyopathy: pathophysiology, mechanisms, clinical features and management. Int J Cardiol. 2014;172(1):40-6.

17.    India State-Level Disease Burden Initiative CVD Collaborators. The changing patterns of cardiovascular diseases and their risk factors in the states of India: the Global Burden of Disease Study 1990-2016. Lancet Glob Health. 2018;6(12):e1339-51.

18.    Prabhakaran D, Jeemon P, Roy A. Cardiovascular diseases in India: current epidemiology and future directions. Circulation. 2016;133(16):1605-20.

19.    Reddy KS, Yusuf S. Emerging epidemic of cardiovascular disease in developing countries. Circulation. 1998;97(6):596-601.

20.    Huffman MD, Prabhakaran D. Heart failure: epidemiology and prevention in India. Natl Med J India. 2010;23(5):283-8.

21.    Harikrishnan S, Sanjay G, Anees T, Viswanathan S, Vijayaraghavan G, Bahuleyan CG, et al. Clinical presentation, management, in-hospital and 90-day outcomes of heart failure patients in Trivandrum, Kerala, India: the Trivandrum Heart Failure Registry. Eur J Heart Fail. 2015;17(8):794-800.

22.    Pillai HS, Ganapathi S. Heart failure in South Asia. Curr Cardiol Rev. 2013;9(2):102-11.

23.    Gupta R, Guptha S, Sharma KK, Gupta A, Deedwania P. Regional variations in cardiovascular risk factors in India: India Heart Watch. World J Cardiol. 2012;4(4):112-20.

24.    Prasad R. Alcohol use on the rise in India. Lancet. 2009;373(9657):17-8.

25.    Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2015;28(1):1-39.e14.

26.    Nagueh SF, Smiseth OA, Appleton CP, Byrd BF 3rd, Dokainish H, Edvardsen T, et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiography: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2016;29(4):277-314.

27.    Rudski LG, Lai WW, Afilalo J, Hua L, Handschumacher MD, Chandrasekaran K, et al. Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American Society of Echocardiography. J Am Soc Echocardiogr. 2010;23(7):685-713.

28.    Japp AG, Gulati A, Cook SA, Cowie MR, Prasad SK. The diagnosis and evaluation of dilated cardiomyopathy. J Am Coll Cardiol. 2016;67(25):2996-3010.

29.    Guzzo-Merello G, Cobo-Marcos M, Gallego-Delgado M, Garcia-Pavia P. Alcoholic cardiomyopathy. World J Cardiol. 2014;6(8):771-81.

30.    Sliwa K, Hilfiker-Kleiner D, Petrie MC, Mebazaa A, Pieske B, Buchmann E, et al. Current state of knowledge on aetiology, diagnosis, management, and therapy of peripartum cardiomyopathy: a position statement from the Heart Failure Association of the European Society of Cardiology Working Group on peripartum cardiomyopathy. Eur J Heart Fail. 2010;12(8):767-78.

31.    Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2016;37(27):2129-200.

32.    Cooper LT Jr. Myocarditis. N Engl J Med. 2009;360(15):1526-38.

33.    Bhakta P, Biswas BK, Banerjee B. Peripartum cardiomyopathy: review of the literature. Yonsei Med J. 2007;48(5):731-47.

34.    Sliwa K, Wilkinson D, Hansen C, Ntyintyane L, Tibazarwa K, Becker A, et al. Spectrum of heart disease and risk factors in a black urban population in South Africa (the Heart of Soweto Study): a cohort study. Lancet. 2008;371(9616):915-22.

35.    Cleland JGF, Daubert JC, Erdmann E, Freemantle N, Gras D, Kappenberger L, et al. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med. 2005;352(15):1539-49.

36.    Asgar AW, Mack MJ, Stone GW. Secondary mitral regurgitation in heart failure: pathophysiology, prognosis, and therapeutic considerations. J Am Coll Cardiol. 2015;65(12):1231-48.

37.    Ghio S, Gavazzi A, Campana C, Inserra C, Klersy C, Sebastiani R, et al. Independent and additive prognostic value of right ventricular systolic function and pulmonary artery pressure in patients with chronic heart failure. J Am Coll Cardiol. 2001;37(1):183-8.

38.    SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med. 1991;325(5):293-302.

39.    CIBIS-II Investigators and Committees. The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial. Lancet. 1999;353(9146):9-13.

40.    Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med. 1999;341(10):709-17.

41.    McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371(11):993-1004.

42.    McMurray JJV, Solomon SD, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA, et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med. 2019;381(21):1995-2008.

43.    Køber L, Thune JJ, Nielsen JC, Haarbo J, Videbæk L, Korup E, et al. Defibrillator implantation in patients with nonischemic systolic heart failure. N Engl J Med. 2016;375(13):1221-30.

44.    Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Drazner MH, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013;62(16):e147-239.

45.    Dokainish H, Teo K, Zhu J, Roy A, AlHabib KF, ElSayed A, et al. Global mortality variations in patients with heart failure: results from the International Congestive Heart Failure (INTER-CHF) prospective cohort study. Lancet Glob Health. 2017;5(7):e665-72.

46.    Franciosa JA, Wilen M, Ziesche S, Cohn JN. Survival in men with severe chronic left ventricular failure due to either coronary heart disease or idiopathic dilated cardiomyopathy. Am J Cardiol. 1983;51(5):831-6.

47.    Lee WH, Packer M. Prognostic importance of serum sodium concentration and its modification by converting-enzyme inhibition in patients with severe chronic heart failure. Circulation. 1986;73(2):257-67.