Tuberculosis electrocardiogram
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mashal Awais, M.D.[2]; Sophia Saad, Associate Editor - WikiDoc [3]Alejandro Lemor, M.D. [4]
Tuberculosis Electrocardiogram
Clinical role
The electrocardiogram (ECG) does not diagnose tuberculosis and is usually normal or nonspecifically abnormal in uncomplicated pulmonary disease. Its relevant roles are assessment of suspected cardiac involvement—including pericarditis, pericardial effusion, cardiac tamponade, myopericarditis, and constrictive pericarditis—and QT-interval surveillance during treatment with QT-prolonging antituberculosis drugs.[1]
Pericardial involvement occurs in approximately 2%–5% of patients with TB and is more frequent and severe with HIV coinfection. Its usually insidious, effusion-predominant presentation helps explain why the ECG may remain unremarkable.[2]
- Routine ECG is not indicated solely to establish or exclude TB.
- Obtain an ECG when cardiac involvement is suspected or a QT-prolonging regimen is planned.
- A normal ECG does not exclude clinically important effusion or tamponade; suspected cardiac involvement requires prompt echocardiography.[3][4]
Tuberculous pericarditis and myopericarditis
The parietal pericardium is electrically silent; ECG abnormalities in pericarditis principally reflect inflammation of the epicardium or adjacent myocardium. The classic sequential ECG evolution occurs in only approximately 60% of acute pericarditis, while up to 40% of tracings are atypical or nondiagnostic.[5] Widespread ST-segment elevation with PR-segment depression is reported in approximately 25%–50% of acute pericarditis in the JAMA review and in up to 60% in the 2025 ACC consensus guidance.[6][3] Changes are dynamic and may be absent initially; serial ECGs may be more informative than a single tracing.[7]
When present, the conventional evolution comprises:
- Diffuse ST-segment elevation with PR-segment depression.
- Normalization of the ST and PR segments.
- Diffuse T-wave inversion after ST-segment normalization.
- Resolution of the T-wave abnormalities.
Not every patient develops every stage.[5][8]
| Clinical setting | Possible ECG findings | Interpretation |
|---|---|---|
| Tuberculous pericarditis | Normal tracing, nonspecific ST–T changes, diffuse concave ST-segment elevation with PR-segment depression, or atrial fibrillation/flutter; atrial fibrillation or flutter is the presenting rhythm in approximately 4% of acute pericarditis cases.[6] | Findings support pericardial or adjacent myocardial inflammation but do not establish a tuberculous etiology. |
| Tuberculous myopericarditis | ST-segment elevation | In 81 patients with tuberculous pericardial effusion, ST elevation was more frequent with myopericarditis than without it (36.6% versus 10.8%) and independently predicted myopericarditis (OR 4.36; 95% CI 1.34–17.34). Measure troponin and assess ventricular function.[9] |
| Pericardial effusion or tamponade | Sinus tachycardia, low QRS voltage, PR-segment depression, or electrical alternans | Specific but insensitive findings; echocardiography determines hemodynamic significance. |
| Constrictive pericarditis | Normal or nonspecific tracing, low voltage, ST–T changes, biatrial abnormality, or atrial fibrillation | ECG is supportive only. A wide, notched, low-amplitude P wave may favor constriction over restrictive cardiomyopathy.[10] |
In the tuberculous-effusion cohort, ST-segment elevation predicted myopericarditis independently of CD4 count. Myopericarditis occurred in 53.1% and was associated with HIV seropositivity (81.4% versus 60.5%) and lower CD4 counts; 6-month case fatality did not differ significantly between patients with and without myopericarditis (14% versus 22%).[9]
Pericardial effusion and cardiac tamponade
In a diagnostic-accuracy study of 136 patients with echocardiographically confirmed effusion, including 12 with tamponade, low QRS voltage, PR-segment depression, and electrical alternans were specific but markedly insensitive.[4]
| ECG finding | Association with moderate-to-large effusion | Association with tamponade | Clinical interpretation |
|---|---|---|---|
| Low QRS voltage | OR 2.5 (95% CI 0.9–6.5) | OR 4.7 (95% CI 1.1–21.0) | Suggestive, but not diagnostic |
| PR-segment depression | Not associated | OR 2.0 (95% CI 1.0–4.0) | Insufficient as an isolated diagnostic sign |
| Electrical alternans | Not associated | Not associated | Too infrequent and insensitive for screening |
Overall specificity was high for effusion (89%–100%) and tamponade (86%–99%), but sensitivity was poor—1%–17% for effusion and 0%–42% for tamponade. Pooled sensitivity for tamponade is approximately 42% for low QRS voltage and 16%–21% for electrical alternans.[4][11]
The hemodynamic effect of an effusion depends more on the rate of accumulation than its absolute volume. Slowly accumulating tuberculous effusions may therefore become large while producing minimal or nonspecific ECG abnormalities.[3]
Cardiac output may initially be maintained by compensatory sinus tachycardia before hemodynamic deterioration. On echocardiography, a dilated inferior vena cava greater than 2.1 cm with minimal respiratory variation is a sensitive screening finding, whereas diastolic right ventricular collapse is the most specific finding. Right atrial inversion lasting more than one-third of the cardiac cycle and marked respiratory variation in ventricular inflow—transmitral greater than 30% or transtricuspid greater than 60%—are supportive.[3] Pericardiocentesis is indicated therapeutically for impending or established tamponade and diagnostically when tuberculous, bacterial, or malignant pericardial disease is suspected.[3][6]
QT-interval safety monitoring
Bedaquiline is approved, as part of combination therapy, for pulmonary TB resistant to at least rifampin and isoniazid in adults and children aged 2 years or older who weigh at least 8 kg.[12] QT surveillance is not routinely required for latent, extrapulmonary, or drug-susceptible TB treated without a QT-prolonging agent.
Use the Fridericia-corrected QT interval (QTcF); Bazett correction may overestimate QT prolongation in patients with tachycardia. Monitoring should be intensified when bedaquiline is combined with additional QT-prolonging agents such as clofazimine or moxifloxacin.[13][14] Combined bedaquiline and delamanid produces an approximately additive QT effect.[15]
The bedaquiline QT effect is mediated largely by its M2 metabolite, which accumulates slowly and may persist for weeks to months after discontinuation. By comparison, the QT effect of moxifloxacin resolves substantially more rapidly.[15][16]
Monitoring schedules
Published monitoring schedules are not harmonized and should not be treated as interchangeable.
| Source | Proposed ECG schedule | Interpretation |
|---|---|---|
| ATS/CDC/ERS/IDSA 2025 guideline | Baseline and weeks 2, 12, and 24 | Current guideline schedule; consider monthly ECGs when moxifloxacin or clofazimine is coadministered.[1] |
| ATS/CDC/ERS/IDSA 2019 guideline | Baseline, after the initial 2 weeks, and then monthly | Described as the practice of most experts; calcium, magnesium, and potassium are monitored in parallel.[17] |
| DELIBERATE investigators | Weeks 2, 8, and 16, with a later ECG if QTc is rising at week 16 | Trial-derived proposal; participants had normal baseline QTc and did not receive concomitant clofazimine.[15] |
| Pharmacokinetic–pharmacodynamic simulation | Before treatment and at weeks 2, 4, 8, and 12 | Identified 93.8% of simulated patients requiring interruption but generated 26.4% unnecessary interruptions; results beyond week 12 were often influenced by stochastic measurement error.[16] |
| FDA bedaquiline label | Before initiation, 2 weeks after initiation, during treatment as clinically indicated, and at the expected time of maximum QTc increase of any concomitantly administered QT-prolonging drug | Obtain electrolytes at baseline and during treatment and correct abnormalities as clinically indicated.[12] |
Assessment and action
| Time or circumstance | Assessment | Action |
|---|---|---|
| Before bedaquiline | Twelve-lead ECG with QTcF; serum potassium, calcium, and magnesium; review concomitant QT-prolonging drugs; screen for prior torsade de pointes, congenital long QT syndrome, current or prior hypothyroidism, current or prior bradyarrhythmia, and a history of uncompensated heart failure | Correct electrolyte abnormalities. Consider thyroid-stimulating hormone testing if baseline QTcF is prolonged. The labeled risk of QTc prolongation is increased by concomitant QT-prolonging drugs, a history of torsade de pointes, congenital long QT syndrome, current or prior hypothyroidism, current or prior bradyarrhythmias, a history of uncompensated heart failure, and serum calcium, magnesium, or potassium below the lower limit of normal.[12][1] |
| Concomitant moxifloxacin or clofazimine | Consider monthly ECG monitoring | Increase surveillance according to baseline risk and evolving QTcF.[1] |
| Syncope or suspected ventricular arrhythmia | Immediate ECG, electrolyte assessment, and medication review | Evaluate urgently for drug-associated arrhythmia. |
| QTcF greater than 500 ms on a single tracing | Repeat the ECG to confirm; simultaneously measure potassium, calcium, and magnesium and review all concomitant QT-prolonging medications | Discontinue bedaquiline if QTcF greater than 500 ms is confirmed by repeat ECG. Correct reversible electrolyte and medication-related contributors.[12] |
| Clinically significant ventricular arrhythmia | Immediate ECG and assessment for reversible contributors | Discontinue bedaquiline and manage the arrhythmia urgently.[12] |
Magnitude and timing of QTcF change
Mean QTcF may continue to increase and peak late in therapy. In a prospective South African cohort of 195 patients with rifampin-resistant TB—40% with extensively drug-resistant disease and 97% receiving clofazimine—QTcF increased continuously, with a mean rise of 23.7 ms (SD 22.7) from baseline to month 6. Only 4 patients exceeded 500 ms and 19 had an increase greater than 60 ms; no patient required permanent discontinuation of bedaquiline or clofazimine.[18]
In DELIBERATE, QTc increased by week 2 and peaked between weeks 18 and 22.[15] In a separate cohort of 94 patients receiving bedaquiline- or delamanid-based regimens, the mean maximum QTc increase over 6 months was 37.5 ms, with minimal clinical effect and movement toward baseline after discontinuation.[19]
Permanent discontinuation for QT prolongation is rare. In a pooled review, 8 of 875 bedaquiline-treated patients (0.9%) discontinued treatment for QT prolongation; two subsequently restarted bedaquiline without recurrence.[17] In a prospective 16-country cohort of 2,553 patients treated with bedaquiline and/or delamanid, 20.9% experienced a prolonged-QT event, but 95.5% of events were grade 1 or 2. Sixty-four patients (2.5%) experienced a grade 3 or higher event or serious adverse event involving QT prolongation, and only 12 (0.5%) permanently discontinued a QT-prolonging drug.[20]
The incidence rate of a first prolonged-QT event was highest during the first 6 months and lower during subsequent 6-month periods, supporting continued bedaquiline or delamanid use beyond 6 months when clinically indicated and accompanied by programmatic ECG monitoring.[20] Thus, mean QTcF magnitude may rise and peak late, while incident clinically relevant events cluster earlier; these observations are complementary rather than contradictory.
Closer surveillance is reasonable in older patients, in whom age was independently associated with QT prolongation.[18] In the Liu model, QTc prolongation occurred in 22.5% of 1,215 patients and exceeded 500 ms in 31.5% of affected patients; predictors included clofazimine, abnormal baseline QTc, creatinine, extensively drug-resistant disease, moxifloxacin, levofloxacin, and sex (C-index 0.723).[13] Adding a fluoroquinolone and/or clofazimine to bedaquiline increased the adjusted risk of QT prolongation 4.82-fold (95% CI 1.406–16.488).[14]
Limitations and common pitfalls
- No validated ECG feature distinguishes tuberculous pericarditis from other etiologies.
- Do not wait for electrical alternans before suspecting a large effusion or tamponade.
- Differentiate pericarditis from acute coronary occlusion: ischemic ST changes are characteristically regional, whereas pericarditis generally produces widespread concave ST elevation without reciprocal ST depression outside aVR and V1 and without Q-wave formation or loss of R-wave progression.[8][6]
- When differentiating pericarditis from early repolarization, an ST/T-wave amplitude ratio greater than 0.25 in V6 and PR elevation in aVR support pericarditis.[21]
- Do not discontinue bedaquiline solely because of one unconfirmed prolonged QTcF; repeat the ECG, assess electrolytes, and review concomitant QT-prolonging drugs.
- Do not substitute QTcB for QTcF during serial monitoring.
- Do not stop surveillance after the early treatment period; mean QTcF may peak late even though first clinically relevant events occur most frequently during the first 6 months.
References
- ↑ 1.0 1.1 1.2 1.3 Saukkonen JJ, Duarte R, Munsiff SS; et al. (2025). "Updates on the Treatment of Drug-Susceptible and Drug-Resistant Tuberculosis: An Official ATS/CDC/ERS/IDSA Clinical Practice Guideline". American Journal of Respiratory and Critical Care Medicine. 211 (1): 15–33. doi:10.1164/rccm.202410-2096ST.
- ↑ Farina JM, Liblik K, Iomini P; et al. (2023). "Infections and Cardiovascular Disease: JACC Focus Seminar 1/4". Journal of the American College of Cardiology. 81 (1): 71–80. doi:10.1016/j.jacc.2022.08.813.
- ↑ 3.0 3.1 3.2 3.3 3.4 Wang TKM, Klein AL, Cremer PC; et al. (2025). "2025 Concise Clinical Guidance: An ACC Expert Consensus Statement on the Diagnosis and Management of Pericarditis". Journal of the American College of Cardiology. doi:10.1016/j.jacc.2025.05.023.
- ↑ 4.0 4.1 4.2 Eisenberg MJ, de Romeral LM, Heidenreich PA, Schiller NB, Evans GT (1996). "The Diagnosis of Pericardial Effusion and Cardiac Tamponade by 12-Lead ECG: A Technology Assessment". Chest. 110 (2): 318–324. doi:10.1378/chest.110.2.318.
- ↑ 5.0 5.1 Chiabrando JG, Bonaventura A, Vecchié A; et al. (2020). "Management of Acute and Recurrent Pericarditis: JACC State-of-the-Art Review". Journal of the American College of Cardiology. 75 (1): 76–92. doi:10.1016/j.jacc.2019.11.021.
- ↑ 6.0 6.1 6.2 6.3 Cremer PC, Klein AL, Imazio M (2024). "Diagnosis, Risk Stratification, and Treatment of Pericarditis". JAMA. 332 (13): 1090–1100. doi:10.1001/jama.2024.12935.
- ↑ Saeed S, Mohamed Ali A, Wasim D; et al. (2023). "Natural Course of Electrocardiogram Changes and the Value of Multimodality Imaging in Acute Pericarditis". Cardiology. 148 (3): 219–227. doi:10.1159/000530207.
- ↑ 8.0 8.1 Troughton RW, Asher CR, Klein AL (2004). "Pericarditis". Lancet. 363 (9410): 717–727. doi:10.1016/S0140-6736(04)15648-1.
- ↑ 9.0 9.1 Syed FF, Ntsekhe M, Gumedze F, Badri M, Mayosi BM (2014). "Myopericarditis in Tuberculous Pericardial Effusion: Prevalence, Predictors and Outcome". Heart. 100 (2): 135–139. doi:10.1136/heartjnl-2013-304786.
- ↑ Geske JB, Anavekar NS, Nishimura RA, Oh JK, Gersh BJ (2016). "Differentiation of Constriction and Restriction: Complex Cardiovascular Hemodynamics". Journal of the American College of Cardiology. 68 (21): 2329–2347. doi:10.1016/j.jacc.2016.08.050.
- ↑ Roy CL, Minor MA, Brookhart MA, Choudhry NK (2007). "Does This Patient With a Pericardial Effusion Have Cardiac Tamponade?". JAMA. 297 (16): 1810–1818. doi:10.1001/jama.297.16.1810.
- ↑ 12.0 12.1 12.2 12.3 12.4 US Food and Drug Administration. SIRTURO (bedaquiline) prescribing information. Updated October 17, 2025.
- ↑ 13.0 13.1 Liu F, Gao J, Gao M; et al. (2022). "Development and Validation of a Nomogram for Prediction of QT Interval Prolongation in Patients Administered Bedaquiline-Containing Regimens in China: A Modeling Study". Antimicrobial Agents and Chemotherapy. 66 (9): e0067122. doi:10.1128/aac.00671-22.
- ↑ 14.0 14.1 Li R, Ma JB, Yang H; et al. (2023). "Effects of Bedaquiline Combined With Fluoroquinolone and/or Clofazimine on QT Interval in Patients With Multidrug-Resistant Tuberculosis: A Retrospective Study". Microbiology Spectrum. 11 (4): e0104823. doi:10.1128/spectrum.01048-23.
- ↑ 15.0 15.1 15.2 15.3 Dooley KE, Rosenkranz SL, Conradie F; et al. (2021). "QT Effects of Bedaquiline, Delamanid, or Both in Patients With Rifampicin-Resistant Tuberculosis: A Phase 2, Open-Label, Randomised, Controlled Trial". Lancet Infectious Diseases. 21 (7): 975–983. doi:10.1016/S1473-3099(20)30770-2.
- ↑ 16.0 16.1 van Beek SW, Tanneau L, Meintjes G; et al. (2022). "Model-Predicted Impact of ECG Monitoring Strategies During Bedaquiline Treatment". Open Forum Infectious Diseases. 9 (8): ofac372. doi:10.1093/ofid/ofac372.
- ↑ 17.0 17.1 Nahid P, Mase SR, Migliori GB; et al. (2019). "Treatment of Drug-Resistant Tuberculosis: An Official ATS/CDC/ERS/IDSA Clinical Practice Guideline". American Journal of Respiratory and Critical Care Medicine. 200 (10): e93–e142. doi:10.1164/rccm.201909-1874ST.
- ↑ 18.0 18.1 Brust JCM, Gandhi NR, Wasserman S; et al. (2021). "Effectiveness and Cardiac Safety of Bedaquiline-Based Therapy for Drug-Resistant Tuberculosis: A Prospective Cohort Study". Clinical Infectious Diseases. 73 (11): 2083–2092. doi:10.1093/cid/ciab335.
- ↑ Jin Y, Benkeser D, Kipiani M; et al. (2023). "The Effect of Anti-Tuberculosis Drug Pharmacokinetics on QTc Prolongation". International Journal of Antimicrobial Agents. 62 (4): 106939. doi:10.1016/j.ijantimicag.2023.106939.
- ↑ 20.0 20.1 Khan U, Rich M, Franke M; et al. (2024). "The Frequency and Incidence of QT Prolongation With Extended Use of Bedaquiline or Delamanid in a Large, Multi-Country MDR/RR-TB Cohort". Clinical Infectious Diseases: ciae601. doi:10.1093/cid/ciae601.
- ↑ Peterson TA, Turner SP, Dolezal KA (2024). "Acute Pericarditis: Rapid Evidence Review". American Family Physician. 109 (5): 441–446.