European Journal of Cardiovascular Medicine

Tuberculosis (TB) remains a major global health problem, ranking among the top thirteen causes of death worldwide and standing as the second leading infectious killer.¹ While pulmonary manifestations predominate, cardiovascular involvement occurs in approximately 2% of TB cases² and can significantly increase mortality and morbidity.

Cardiac TB primarily affects the pericardium, with less frequent involvement of the myocardium and valves.³ Electrocardiography and echocardiography serve as primary diagnostic modalities, supplemented by newer tests including adenosine deaminase, polymerase chain reaction, and interferon-gamma assays. Early detection and appropriate treatment with anti-tubercular therapy and corticosteroids are crucial to prevent complications such as constrictive pericarditis, pericardial effusion, and cardiac failure.

The American Society of Cardiology's NET heart project has expanded our understanding of cardiovascular complications in TB, potentially improving detection and management strategies to reduce mortality.⁴ Recent research has highlighted how even latent TB may affect the cardiovascular system through pro-inflammatory cytokines and autoimmunity mediated by Heat shock protein.⁵

Diagnosis remains challenging, particularly in resource-limited settings, and requires high clinical suspicion, especially in patients with heart failure or arrhythmias who have structurally normal hearts, or in cases of disseminated TB with underlying immunodeficiency.

The considerable symptom overlap between pulmonary TB and cardiac dysfunction complicates identification. This research prospectively examines patients with pulmonary TB without pre-existing cardiovascular disease to determine the extent of cardiovascular involvement and, critically, to assess how anti-tubercular treatment impacts the cardiovascular profile of these patients

This prospective descriptive study was conducted in the Department of Respiratory Medicine at J.J.M.M.C. and Chigateri General Hospital in Davangere over a period of 1.5 years from March 2021 to August 2022. The study population comprised new sputum-positive pulmonary tuberculosis patients aged 18 years or older of both sexes who were either newly diagnosed or had received treatment for less than two weeks.

Patients with sputum-negative pulmonary tuberculosis, pre-existing conditions (heart disease, hypertension, COPD, diabetes mellitus, bronchiectasis, other pulmonary diseases), extra-pulmonary tuberculosis, and pregnant patients were excluded. Additionally, patients under 18 years, those unwilling to participate, and patients lost to follow-up due to death or other causes were also excluded.

Based on a previous study by Mashooq Ali D et al.,6 the sample size was calculated at 72 participants using the formula N = (Zα/2)² × p × (1-p)/d², considering a prevalence of cardiac manifestation of pulmonary TB at 0.69 and a relative precision of 9%.

After obtaining approval from the institutional ethics committee and informed consent from participants, data collection began using a pre-designed performa. Demographic details and a comprehensive history of symptoms were recorded, followed by a thorough clinical examination including vital signs measurement. Diagnostic tests including chest radiograph, complete hemogram, random blood sugar, total protein and albumin levels, and HIV testing were performed.

Electrocardiographic assessment documented P wave characteristics (axis and amplitude), PR interval, QRS parameters (duration, axis, amplitude), QT interval, ST segment, T wave morphology, heart rate, and rhythm abnormalities. Echocardiography evaluated left ventricular systolic dysfunction (mild, moderate, severe), diastolic dysfunction (Grades I, II, III), cardiac tamponade, pericardial effusion, right ventricular hypertrophy or dilatation, and pulmonary artery hypertension.

Patients were followed for six months with ECG performed during the post-intensive phase of anti-tubercular treatment and again after completion of therapy to assess normalization of electrocardiographic changes. A final echocardiographic evaluation was conducted at the conclusion of antitubercular therapy.

Data was tabulated in excel sheets and analyzed using SPSS v.23 for Windows. Descriptive statistics included mean, standard deviation, median, and interquartile range for quantitative variables, while frequency and proportions were calculated for qualitative variables. The Chi-square test was applied for qualitative variable analysis, and paired t-tests were used to evaluate treatment efficacy before and after intervention when data followed normal distribution. Statistical significance was set at 5%.

The patients had a mean age of 43.64 years, with ages ranging from 20 to 75 years. There was a notable gender disparity, with males comprising 61.1% of the study population compared to 38.9% females. The symptom profile reveals that cough was nearly universal (91.7%), followed by fever (73.6%) and generalized tiredness (63.9%). Other significant symptoms included anorexia (51.4%) and breathlessness (40.3%), while hemoptysis was relatively uncommon (11.1%). These symptoms align with the classic presentation of pulmonary tuberculosis. Most patients (93.1%) were HIV non-reactive, with only 5 patients (6.9%) being HIV-positive. The clinical parameters showed that patients generally had slightly reduced oxygen saturation (SpO₂) at 91.9%, which is below the normal range of 95-100%, indicating some degree of respiratory compromise. Blood pressure readings (116.81/72.53 mmHg) were within normal limits, as was the mean body temperature (98.47°F).

Table 1: Demographic and Clinical Characteristics of Study Population (n=72)

The laboratory findings indicate several abnormalities typical in tuberculosis patients. The mean hemoglobin level was 10.44 mg/dl, suggesting mild to moderate anemia, which is a common finding in chronic infections like TB. The elevated white blood cell count (mean of 10,970.67 cells/cu mm) indicates an active inflammatory response to infection. Total protein levels (6.26 mg/dl) were within normal range, but albumin levels were slightly low at 3.03 mg/dl, suggesting possible nutritional deficiency or chronic inflammation. The erythrocyte sedimentation rate (ESR) was markedly elevated at 45.53 mm/hr, which is consistent with the chronic inflammatory state seen in tuberculosis. [Table 2]

Table 2: Laboratory Parameters (n=72)

Before treatment, 50% of patients exhibited tachycardia, which significantly improved to only 13.9% by the end of treatment (p=0.000), showing the effectiveness of therapy in reducing cardiac stress. ST segment elevations, present in 5.6% of patients initially, completely resolved by the end of treatment (p=0.045). T wave inversions also showed improvement, decreasing from 9.7% to 2.8% of patients, though this change did not reach statistical significance (p=0.058). Axis deviations (both left and right) showed modest improvement over the course of treatment. Similarly, P pulmonale, an indicator of right atrial enlargement often associated with pulmonary disease, decreased from 9.7% to 6.9% of patients. These ECG improvements demonstrate that tubercular infection can have cardiac manifestations that are largely reversible with appropriate treatment. [Table 3]

Table 3: Major ECG Findings Before and After Anti-Tubercular Therapy (n=72)

*p-value compares Before ATT vs End of ATT; **Statistically significant

Echocardiography revealed several cardiac abnormalities that improved with anti-tubercular therapy. Left ventricular systolic dysfunction was present in 9.8% of patients before treatment (5.6% moderate, 4.2% mild), but improved to 5.6% by the end of treatment, with a significant reduction in moderate dysfunction cases (from 5.6% to 1.4%, p=0.028). Pericardial effusion, present in 5.6% of patients initially, resolved completely after treatment, though this improvement narrowly missed statistical significance (p=0.057). Pulmonary artery hypertension (PHTN) decreased from 13.9% to 9.7% of patients, and right ventricular hypertrophy/dilation showed modest improvement (11.1% to 9.7%). Diastolic dysfunction was relatively uncommon and showed minimal change (5.6% to 4.2%). [Table 4]

These findings suggest that tuberculosis can lead to various cardiac abnormalities, including ventricular dysfunction, pericardial effusion, and pulmonary hypertension, most of which improve with anti-tubercular therapy. The most significant improvement was observed in left ventricular systolic function, highlighting the importance of treating the underlying infection to reverse cardiac complications.

Table 4: Echocardiographic Findings Before and After Anti-Tubercular Therapy (n=72)

*Statistically significant

The study involved 72 sputum-positive tuberculosis patients who underwent detailed electrocardiographic and echocardiographic evaluations. The mean age was 43.64 ± 15 years, with most patients in the 20-30 and 41-50 age groups. Males predominated (61.1%), similar to findings by Chandulal et al.7 and Fatehpuria et al.8 The primary symptoms were cough (91.7%), fever (73.6%), and generalized tiredness (63.9%), which aligns with findings from Ghouri et al9 and Vijayageetha et al.10

Laboratory findings showed mild anemia (mean Hb 10.44 mg/dl), hypoalbuminemia (mean 3.03 mg/dl) comparable to Maranatha et al.'s findings,11 and elevated ESR (mean 45.53 mm/hr). Unlike Patil et al.'s study,12 no significant association was found between hypoalbuminemia and cardiac dysfunction, nor between hypoxemia and heart dysfunction, despite the mean SpO₂ being 91.9%.

ECG abnormalities were observed in 59% of patients, comparable to findings by Dasti et al. (72%)6 and Gaur et al. (46.4%).13 Sinus tachycardia was the most common abnormality (50% pre-treatment, 15.3% post-treatment), followed by P pulmonale (9.7% to 6.9%) and axis deviations. These changes may result from fever, anemia, toxemia, direct cardiac involvement, or autonomic nerve irritation from enlarged lymph nodes.

Echocardiographic abnormalities were present in 23.6% of patients, similar to Rajesh et al.'s finding of 24%.3 Pre-treatment abnormalities included pulmonary hypertension (13.9%), RV hypertrophy/dilation (11.1%), LV systolic dysfunction (9.3%), and pericardial effusion (5.6%). Post-treatment evaluations showed significant reduction in LV systolic dysfunction, with complete resolution of pericardial effusion and improvement in other parameters.14

The study demonstrated that tuberculosis can cause various cardiac manifestations detectable through ECG and echocardiography, most of which improve significantly

with anti-tubercular therapy. The findings align with Patil et al.'s study12 showing cardiac dysfunction in 26% of TB patients, though with different distributions of abnormalities. LV systolic dysfunction showed the most significant improvement following treatment, highlighting the importance of anti-tubercular therapy in reversing cardiac complications.

This prospective study of 72 sputum-positive pulmonary tuberculosis patients revealed significant cardiovascular involvement, with 59% showing electrocardiographic abnormalities and 23.6% demonstrating echocardiographic abnormalities at diagnosis. Sinus tachycardia (50%), pulmonary hypertension (13.9%), right ventricular hypertrophy/dilation (11.1%), left ventricular systolic dysfunction (9.3%), and pericardial effusion (5.6%) were the most prevalent cardiac manifestations. Importantly, these abnormalities showed substantial improvement following anti-tubercular therapy, with statistically significant resolution of tachycardia, ST segment elevations, and moderate left ventricular systolic dysfunction, while pericardial effusion resolved completely. These findings emphasize the importance of cardiac evaluation in pulmonary tuberculosis patients, even without pre-existing cardiovascular disease, and highlight the role of effective anti-tubercular therapy in reversing tuberculosis-associated cardiac abnormalities, potentially reducing morbidity and improving overall outcomes.

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