Use of torsades de pointes risk drugs among patients with out-of-hospital cardiac arrest and likelihood of shockable rhythm and return of spontaneous circulation: A nationwide study.

AIM: Treatment with certain drugs can augment the risk of developing malignant arrhythmias (e.g. torsades de pointes [TdP]). Hence, we examined the overall TdP risk drug use before out-of-hospital cardiac arrest (OHCA) and possible association with shockable rhythm and return of spontaneous circulation (ROSC). METHODS: Patients ≥18 years with an OHCA of cardiac origin from the Danish Cardiac Arrest Registry (2001-2014) and TdP risk drug use according to www.CredibleMeds.org were identified. Factors associated with TdP risk drug use and secondly how use may affect shockable rhythm and ROSC were determined by multivariable logistic regression. RESULTS: We identified 27,481 patients with an OHCA of cardiac origin (median age: 72 years [interquartile range 62.0, 80.0 years]). A total of 37% were in treatment with TdP risk drugs 0-30 days before OHCA compared with 33% 61-90 days before OHCA (p < 0.001). Most commonly used TdP risk drugs were citalopram (36.1%) and roxithromycin (10.7%). Patients in TdP risk drug treatment were older (75 vs 70 years) and more comorbid compared with those not in treatment. Subsequently, TdP risk drug use was associated with less likelihood of the presenting rhythm being shockable (odds ratio [OR] = 0.63, 95% confidence interval [CI]:0.58-0.69) and ROSC (OR = 0.73, 95% CI:0.66-0.80). CONCLUSION: TdP risk drug use increased in the time leading up to OHCA and was associated with reduced likelihood of presenting with a shockable rhythm and ROSC in an all-comer OHCA setting. However, patients in TdP risk drug treatment were older and more comorbid than patients not in treatment.

Electrocardiogram Characteristics and Their Association With Psychotropic Drugs Among Patients With Schizophrenia.

BACKGROUND: There are limited data on electrocardiogram (ECG) characteristics and their association with psychotropic drugs in schizophrenia. METHODS: Using a cross-sectional design, we included Danish primary care patients with first-time digital ECGs from 2001 to 2015. Patients diagnosed with schizophrenia before ECG recording were matched 1:5 on age, sex, and ECG recording year to controls without psychiatric disease. Multivariable logistic regression was used to compute odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: We included 4486 patients with schizophrenia matched with 22 430 controls (median age, 47 years; male, 55%). Between groups, the prevalence of abnormal ECGs was similar (54%, P = .536), but patients with schizophrenia demonstrated higher median heart rate (79 vs 69 beats per minute, P < .001) and Fridericia-corrected QT (QTc) interval (416 vs 412 ms, P < .001) than controls. QTc prolongation was also more prevalent among patients with schizophrenia (3.4% vs 1.1%, P < .001), and so were pathological Q waves (5.3% vs 3.9%, P < .001). Patients with schizophrenia less frequently demonstrated left ventricular hypertrophy (6.1% vs 9.6%, P < .001) and atrial fibrillation or flutter (0.7% vs 1.4%, P < .001). Among patients with schizophrenia only, particularly antipsychotics were associated with abnormal ECGs (OR, 1.20; 95% CI, 1.04-1.39). CONCLUSIONS: Patients with schizophrenia demonstrate a different cardiovascular risk profile than matched controls without psychiatric disease, with higher prevalence of elevated heart rate, QTc prolongation, and pathological Q waves, and lower prevalence of left ventricular hypertrophy and atrial fibrillation or flutter. Particularly antipsychotics were associated with abnormal ECGs. This underscores an integrated care approach when ECG abnormalities are detected in this group.

PR Prolongation predicts inadequate resynchronization with biventricular pacing in left bundle branch block.

BACKGROUND: PR interval prolongation is associated with poor outcome after cardiac resynchronization therapy (CRT) among patients with left bundle branch block (LBBB) but the mechanisms are unknown. We investigated clinical outcomes, electrocardiogram (ECG), and echocardiogram changes after CRT by PR interval. METHODS: This is a retrospective study of CRT recipients with a baseline ejection fraction ≤35% and ECG showing sinus rhythm and LBBB. Patients were stratified by baseline PR interval quartile and the primary combined endpoint was time to heart transplantation, left ventricular assist device (LVAD) implantation, or death. ECG, echocardiogram, and clinical variables were compared to identify mechanisms for observed differences in outcomes. RESULTS: Of 291 eligible patients, the mean age was 65 years, 60% were male, and 19% had prior atrial fibrillation. Patients with PR prolongation (quartile 4, PR > 200 ms) more frequently had a history of atrial fibrillation, coronary artery bypass graft surgery, prior implantable cardioverter defibrillator implantation, and use of amiodarone than patients in PR quartiles 1-3. A PR > 200ms was associated with an adjusted hazard ratio of 1.7 (95% CI: 1.1-2.5) for the primary endpoint. Patients with PR > 200 ms had less reduction in QRS duration and QRS area after CRT while having more increase in QT and QTc intervals than patients with PR ≤ 200 ms. No major differences were observed in echocardiography by baseline PR interval quartiles. CONCLUSIONS: PR prolongation predicts shorter survival free of heart transplantation or LVAD implantation in patients with LBBB. This may be due to inadequate ventricular resynchronization.

Cumulative anthracycline exposure and risk of cardiotoxicity; a Danish nationwide cohort study of 2440 lymphoma patients treated with or without anthracyclines.

Cardiotoxicity is a known risk of anthracycline treatment. However, the relative contribution of anthracyclines to the development of congestive heart failure (CHF), when included in a poly-chemotherapy regimen, is unclear. We examined cardiotoxicity in adult patients with diffuse large B-cell lymphoma and follicular lymphoma undergoing first-line immunochemotherapy from 2000-2012. In total, 2440 patients without previous heart disease were identified from the Danish Lymphoma Registry, of which 1994 (81·7%) were treated with anthracycline-containing chemotherapy [R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) or R-CHOEP (R-CHOP + etoposide)] and 446 (18·3%) were treated without anthracyclines (reference group). Compared to the reference group, the adjusted hazard ratio of CHF after 3-5 cycles of R-CHOP/CHOEP was 5·0 [95% confidence interval (CI) 1·4; 18·5], 6 cycles 6·8 (95% CI 2·0; 23·3) and >6 cycles 13·4 (95% CI 4·0; 45·0). The cumulative 5-year risk of CHF with all-cause mortality as competing risk was 4·6% after 3-5 cycles of R-CHOP/CHOEP, 4·5% after 6 and 7·9% after more than 6 cycles. Cumulative 5-year risk for patients treated without anthracyclines was 0·8%. Using anthracyclines in first-line lymphoma treatment increases risk of CHF in patients without previous history of heart disease. In particular, treatment with >6 cycles of R-CHOP/CHOEP is associated with a significant increase in CHF rate.