Tuberculosis (TB) is a major cause of ill health, ranking among the top thirteen causes of death worldwide and standing as the second leading infectious cause of death. Especially prevalent in developing countries, TB is a chronic granulomatous infection characterized by caseation granuloma formation.1

Cardiovascular involvement occurs in 2% of TB cases,2 primarily affecting the pericardium, with rare myocardial and valvular involvement.3 Electrocardiography serves as the initial diagnostic tool, followed by echocardiography, which provides structural and functional information. Additional promising tests include adenosine deaminase, polymerase chain reaction, and interferon-gamma. Timely detection and treatment with anti-tubercular therapy and corticosteroids can prevent complications such as constrictive pericarditis, pericardial effusion, cardiac failure, and death.

The American Society of Cardiology's NET heart project has expanded knowledge about cardiovascular complications in diseases like TB, aiming to improve

detection and management while reducing mortality and morbidity.4 Recent studies suggest latent TB's involvement in the cardiovascular system through pro-inflammatory cytokines and Heat shock protein-mediated autoimmunity.5

There remains a scarcity of published data on diagnosis and management of cardiovascular involvement, with particular diagnostic challenges in resource-poor settings. Diagnosis requires high clinical suspicion, especially in patients with heart failure and arrhythmias despite structurally normal hearts, in disseminated TB cases, and in immunocompromised patients.

Despite advancements in control methods, TB remains one of the most common infectious diseases, affecting multiple organs with lungs accounting for over 80% of cases. Cardiac involvement is understudied, and there is significant symptom overlap between pulmonary TB and cardiac dysfunction. Screening and identification of cardiovascular manifestations in pulmonary TB patients will help reduce associated morbidity and mortality, which is the focus of this prospective study. This study was done to analyze electrocardiographic and echocardiographic changes in untreated cases of sputum positive pulmonary tuberculosis patients.

Methodology

This was a prospective descriptive study conducted in the Department of Respiratory Medicine at J.J.M.M.C., Davangere and Chigateri General Hospital, Davangere attached to J.J.M.M.C. The study population consisted of new sputum positive pulmonary tuberculosis patients and was carried out over a period of 1.5 years from March 2021 to August 2022.

The sample size was calculated based on a previous study by Mashooq Ali D et al., considering the prevalence of cardiac manifestation of pulmonary TB (69%) and a relative precision of 9%. Using the formula N= (Zα/2)² × p × (1-p)/d², with a confidence level of 90%, the minimum sample size was determined to be 72.

After obtaining approval and clearance from the institutional ethics committee, new sputum positive pulmonary tuberculosis cases fulfilling inclusion and exclusion criteria were enrolled in the study. The study included patients aged 18 years or older of both sexes who were newly microbiologically confirmed pulmonary tuberculosis cases or had taken treatment for less than 2 weeks without any primary lung or cardiovascular disease. Only patients who were willing to participate were included in the study.

Patients with sputum-negative pulmonary tuberculosis, pre-existing heart disease, hypertension, COPD, diabetes mellitus, bronchiectasis, other pulmonary diseases, and corpulmonale due to other causes were excluded. Cases of extra-pulmonary tuberculosis including pleural effusion, lymph node tuberculosis, abdominal tuberculosis, and genitourinary tuberculosis were also excluded. Pregnant patients, those unwilling to participate, patients younger than 18 years, and those lost to follow-up due to death or other causes were not included in the study.

The purpose of the study was explained to each participant, and data was collected with a pre-designed performa after obtaining informed consent. Demographic details and a detailed history of symptoms were recorded, followed by a thorough clinical examination. Vitals including SpO2, blood pressure, and temperature were documented. Chest radiographs, complete hemogram, random blood sugar, total protein, albumin levels, and HIV tests were performed for all participants.

Electrocardiography was conducted to assess P wave axis and amplitude, PR interval, QRS duration, axis and amplitude, QT interval, ST segment, T wave, heart rate, and rhythm abnormalities. Echocardiography was performed to evaluate left ventricular systolic dysfunction (mild, moderate, severe), diastolic dysfunction (Grade I, II, III), cardiac tamponade, pericardial effusion, right ventricular hypertrophy or dilatation, and pulmonary artery hypertension.

The data was tabulated in excel sheets and statistical analysis was conducted using SPSS v.23 for Windows. Descriptive statistics of the explanatory and outcome variables were calculated by mean, standard deviation, median, and IQR for quantitative variables, and frequency and proportions for qualitative variables. Inferential statistics, including the Chi-square test, were applied for qualitative variables. The level of statistical significance was set at 5%.

In our study of the 72 study participants, the average age of participants was 43.64 years, with a wide range from 20 to 75 years. The gender distribution shows a male predominance (61.1% males versus 38.9% females). Regarding HIV status, the majority (93.1%) were non-reactive, while a small proportion (6.9%) were HIV positive.

The clinical symptoms section indicates that cough was the most prevalent symptom, affecting 91.7% of participants, followed by fever (73.6%), generalized tiredness (63.9%), and anorexia (51.4%). Less common symptoms included breathlessness (40.3%) and hemoptysis (11.1%). This symptom profile suggests a respiratory condition with systemic manifestations. Vital parameters showed a slightly reduced mean oxygen saturation of 91.9%, while blood pressure and temperature measurements were generally within normal ranges.

The mean hemoglobin level was 10.44 mg/dl, suggesting mild anemia across the cohort, with individual values ranging from 7 to 15 mg/dl. The elevated mean white blood cell count (10,970.67 cells/cu mm) indicates an ongoing inflammatory or infectious process.

The total protein level (mean 6.26 mg/dl) was within normal range, though the lower end of the range (4.9 mg/dl) suggests some participants had hypoproteinemia. More notably, the mean albumin level of 3.03 mg/dl indicates hypoalbuminemia, a common finding in chronic disease states. The erythrocyte sedimentation rate (ESR) was markedly elevated at a mean of 45.53 mm/hr, with values reaching as high as 130 mm/hr, further confirming significant inflammation in many participants.

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

Table 2: Laboratory Investigations in Study Participants (n=72)

The majority of participants had normal ECG parameters across most metrics. Notable abnormalities included QRS axis deviations (16.6% combined), with 6.9% showing left axis deviation and 9.7% showing right axis deviation. P pulmonale, suggesting right atrial enlargement, was observed in 9.7% of participants. T wave inversions were found in 9.7% of cases, and ST segment elevations in 5.6%, both potentially indicating myocardial stress or injury.

The most striking ECG finding was abnormal heart rate, with 50% of participants exhibiting tachycardia and 4.2% showing bradycardia, leaving only 45.8% with normal heart rates. This high prevalence of tachycardia likely reflects the systemic inflammatory response and possibly respiratory compromise in these patients.

Table 3: Electrocardiographic Findings in Study Participants (n=72)

Most participants maintained normal cardiac function, though 9.8% showed left ventricular systolic dysfunction (4.2% mild, 5.6% moderate) and 5.6% had grade 1 diastolic dysfunction. Pericardial effusion, though mild, was present in 5.6% of participants.

More concerning were the findings of right ventricular hypertrophy or dilation in 11.1% of participants and pulmonary hypertension in 13.9%. These right-sided cardiac abnormalities, combined with the respiratory symptoms noted in Table 1, suggest possible chronic pulmonary disease or cor pulmonale in a subset of patients. Notably, no cases of cardiac tamponade were observed.

Table 4: Echocardiographic Findings in Study Participants (n=72)

During the study period, 72 new sputum-positive tuberculosis patients underwent detailed electrocardiographic and echocardiographic evaluations before anti-tubercular therapy.

The study involved patients across various age groups, with the majority belonging to the 20-30 years (26.4%) and 41-50 years (25%) age ranges. This distribution is similar to Chandulal et al.'s 2021 study in Northern India.6 The mean age was 43.64 ± 15 years, comparable to Dasti et al.'s findings (mean age 45.21 years).7 Notably, many patients were in their most productive years. Gender distribution showed male predominance (61.1% vs. 38.9% females), consistent with other studies including Chandulal et al.,6 Aslam Ghouri et al. (84% male),8 and Chandan M. Fatehpuria et al. (59.51% male).9

The primary symptoms were cough (66%), fever (53%), generalized tiredness (46%), anorexia (37%), breathlessness (29%), and hemoptysis (8%). These findings align with Aslam Ghouri et al.'s study, which reported fever (86%), malaise (62%), productive cough (90%), and hemoptysis (68%).8 Vijayageetha M et al.'s cross-sectional study similarly found cough to be the most common symptom.10 The mean SpO2 was 91.9 ± 8.13 at room air, though unlike SV Patil et al.'s study, no significant association between hypoxemia and heart dysfunction was observed.11

The mean hemoglobin was 10.44 mg/dl ± 1.91 mg/dl, indicating mild anemia, which Mukherjee et al. found in 60% of new pulmonary tuberculosis cases.12 This anemia likely results from suppressed erythropoiesis due to inflammatory markers, nutritional deficiency, and malabsorption.46,47 Mean albumin levels were 3.03 mg/dl ± 0.57 mg/dl, similar to Daniel Maranatha et al.'s findings (3.07 ± 0.56 mg/dl).13 Unlike S.V. Patil's study, no significant association between hypoalbuminemia and cardiac dysfunction was observed. The mean ESR was elevated at 45.53 mm/hr, reflecting the inflammatory nature of tuberculosis.11

ECG abnormalities were observed in 59% of cases, comparable to Dasti MA et al.'s findings (72%)7 and higher than SN. Gaur et al.'s study (46.4%).14 The most common abnormality was sinus tachycardia (50%), higher than rates reported by Chandulal et al. and Dasti MA et al.6,7 Other findings included P pulmonale (9.7%), right axis deviation (9.7%), left axis deviation (6.9%), T wave inversion (9.7%), and ST segment elevation (5.6%). The exact mechanism of ECG changes in pulmonary tuberculosis remains uncertain but may involve fever, anemia, toxemia, direct cardiac involvement, autonomic nerve irritation by enlarged lymph nodes, mediastinal displacement, and extensive lung destruction.15

Echocardiographic abnormalities were found in 23.6% of patients, comparable to Rajesh et al.'s finding of 24%.3 Specific abnormalities included LV systolic dysfunction (9.3%), diastolic dysfunction (5.6%), pericardial effusion (5.6%), RV hypertrophy or dilatation (11.1%), and pulmonary hypertension (13.9%). These findings are consistent with S.V. Patil et al.'s 2018 study, which documented cardiac dysfunction in 26% of tuberculosis patients.11 Rajesh S. et al.'s study identified pericardial effusion and diastolic dysfunction as the most common abnormalities.3

The present study of 72 pulmonary tuberculosis patients demonstrated significant cardiovascular involvement, with electrocardiographic abnormalities present in 59% of cases and echocardiographic abnormalities in nearly a quarter of patients. The study population consisted predominantly of young adult males presenting with classic tuberculosis symptoms including cough (91.7%), fever (73%), and fatigue (63.9%). The most common ECG findings were sinus tachycardia (50%), P pulmonale (9.7%), right axis deviation (9.7%), and T wave inversions (9.7%), while echocardiography revealed pulmonary hypertension (13.9%), right ventricular abnormalities (11.1%), and left ventricular systolic dysfunction (9.3%). Laboratory findings indicated moderate anemia, leukocytosis, and elevated inflammatory markers, though no significant associations were found between demographic factors, clinical parameters, or laboratory values and cardiac dysfunction. These findings highlight the importance of cardiac evaluation in tuberculosis patients, though the study was limited by small sample size and reliance on non-invasive assessment methods.

1. World Health Organization. Global tuberculosis report. Geneva: World Health Organization; 2021.
2. Leoni D, Rello J. Cardiac arrest among patients with infections: causes, clinical practice and research implications. Clin Microbiol Infect Dis. 2017;23(10):730–5.
3. Rajesh S, Sricharan KN, Jayaprakash K, Francis N, Monteiro P. Cardiac involvement in patients with pulmonary tuberculosis. J Clin Diagn Res. 2011;5(3):440–2.
4. Burgos LM, Farina J, Liendro MC, Saldarriaga C, Liprandi AS, Wyss F, Mendoza I, Baranchuk A. Neglected tropical diseases and other infectious diseases affecting the heart (NET-heart project). The NET-heart project: rationale and design. Glob Heart. 2020;15(1):60.
5. Shekhawat SD, Purohit HJ, Taori GM, Daginawala HF, Kashyap RS. Evaluation of heat shock proteins for discriminating between latent tuberculosis infection and active tuberculosis: a preliminary report. J Infect Public Health. 2016;9(2):143–52.
6. Chandulal, Naik RV. Electrocardiographic variations in cases with pulmonary tuberculosis related to anti-tuberculosis therapy. Int J Adv Res Med. 2021;3(1):68–71.
7. Dasti MA, Hashmi SFA, Jaffri MSA, Raza SA, Junejo SZ, Akhtar S, et al. Cardiac manifestations of pulmonary tuberculosis. Professional Med J 2015;22(6):733-737.
8. Ghouri A, Ahmed A, Bhatti KA. Frequency and variation of electrocardiographic changes in patients of pulmonary tuberculosis. Med Forum Mon. 2017;28(1):27–30.
9. Fatehpuria CM, Bhagora A, Bairwa Y, Bairwa MC. Socio-demographic characteristics of tuberculosis patients registered under RNTCP in an urban area of Jodhpur, Rajasthan. Int J Community Med Public Health. 2019;6(12):5197–200.
10. Vijayageetha M, Sen A, Subramanian S, Anuja M, Jha A, Arya AB, et al. Presumptive pulmonary tuberculosis and its associated factors among adult patients availing out-patient services in a tertiary care center, Puducherry, South India. Int J Community Med Public Health. 2020 Jul;7(7):2703-2707.
11. Patil SV, Narwade G, Gondhali G. Cardiac dysfunction in active pulmonary tuberculosis: double trouble!! Eur Respir J. 2020;56(1):1604.
12. Mukherjee A, Kaeley N, Dhar M, Kumar S, Bhushan B. Prevalence, characteristics, and predictors of tuberculosis-associated anemia. J Family Med Prim Care. 2019;8(7):2445–9.
13. Maranatha D, Krisdanti DP. The factors predicting mortality in pulmonary tuberculosis with acute respiratory failure. Clin Epidemiol Glob Health. 2021;12:100843.
14. Gaur S, Singh K, Banavaliker JN, Arshad N. Influence of anti-tuberculosis chemotherapy on electrocardiographic changes in pulmonary tuberculosis. Indian J Tuberc. 1994;41(3):135–8.
15. Dash M, Dutta P, Mishra N. Electrocardiographic changes in new and treated cases of pulmonary tuberculosis. Int J Med Res Prof.2016; 2(4); 88-90.