Adherence to heart failure treatment in patients with peripartum cardiomyopathy.

AIMS: Peripartum cardiomyopathy (PPCM) is characterized by left ventricular (LV) dysfunction developing towards the end of pregnancy or in the first months postpartum. Although about 60% of women with PPCM (the majority of which are prescribed evidence based heart failure [HF] medications) show LV recovery within 6 to 12 months, others remain with persistently impaired LV function. Poor adherence to medical therapy represents a major cause of avoidable hospitalizations, disability, and death in other cardiovascular conditions. In this study, we aimed to determine drug adherence to HF therapy among women with PPCM and to identify possible associations between drug adherence and LV recovery, functional status and psychological well-being. METHODS AND RESULTS: In this single-centre, prospective, observational study, we included 36 consecutive women with PPCM. Adherence to HF treatment was assessed by (i) verifying the collection of pharmacy refills and (ii) using liquid chromatography high-resolution mass spectrometry (LC-HRMS). Participants were thereby classified as 'adherent' (i.e. all prescribed HF drugs were detectable by LC-HRMS), 'partially adherent' (i.e. at least one prescribed drug detectable) or 'non-adherent' (i.e. none of the prescribed drugs detectable). Health state index scores were assessed by EQ-5D-5L and HADS-A/D (for anxiety/depression). Patients' median age was 32.4 years (IQR 27.6-36.1). At the adherence visit (which occurred at a median of 16 months [IQR 5-45] after PPCM diagnosis), prescription included beta-blockers (77.8%), angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (75%), mineralocorticoid receptor antagonists (47.2%) and loop diuretics (95.2%). Less than two thirds of patients (63.9%) collected all their pharmacy refills in the 6 months prior to adherence visit. According to LC-HRMS, 23.5% participants were classified as adherent, 53.0% as partially adherent, and 23.5% as non-adherent. Adherence was associated with significantly lower LVEDD at follow-up (47 mm [IQR 46-52), vs. 56 mm [IQR 49-64] with partial adherence, and 62 mm [IQR 55-64] with non-adherence, P = 0.022), and higher LVEF at follow-up (60% [IQR 41-65]), vs. partially adherence (46% [IQR 34-50]) and non-adherence (41.0% [IQR 29-47], P = 014). Adherent patients had a lower overall EQ- 5D score (5.5 [IQR 5-7.5], vs. 6 [IQR 5-7] in partially adherent, and 10 [IQR 8-15] in non-adherent patients, P = 0.032) suggestive of a better self-rated health status. CONCLUSIONS: Adherence to HF therapy was associated with favourable LV reverse remodelling in PPCM and better self-rated health status. Our study highlights the importance of drug adherence for functional recovery. Drug adherence should be an important component of patient communication and specific interventions in PPCM.

Cardiovascular disease in low- and middle-income countries associated with environmental factors.

There is a growing recognition that the profound environmental changes that have occurred over the past century pose threats to human health. Many of these environmental factors, including air pollution, noise pollution, as well as exposure to metals such as arsenic, cadmium, lead, and other metals, are particularly detrimental to the cardiovascular health of people living in low-to-middle income countries (LMICs). Low-to-middle income countries are likely to be disproportionally burdened by cardiovascular diseases provoked by environmental factors. Moreover, they have the least capacity to address the core drivers and consequences of this phenomenon. This review summarizes the impact of environmental factors such as climate change, air pollution, and metal exposure on the cardiovascular system, and how these specifically affect people living in LMICs. It also outlines how behaviour changes and interventions that reduce environmental pollution would have significant effects on the cardiovascular health of those from LMICs, and globally.

Socio-economic factors determine maternal and neonatal outcomes in women with peripartum cardiomyopathy: A study of the ESC EORP PPCM registry.

BACKGROUND: Peripartum cardiomyopathy (PPCM) is a global disease with substantial morbidity and mortality. The aim of this study was to analyze to what extent socioeconomic factors were associated with maternal and neonatal outcomes. METHODS: In 2011, >100 national and affiliated member cardiac societies of the European Society of Cardiology (ESC) were contacted to contribute to a global PPCM registry, under the auspices of the ESC EORP Programme. We investigated the characteristics and outcomes of women with PPCM and their babies according to individual and country-level sociodemographic factors (Gini index coefficient [GINI index], health expenditure [HE] and human developmental index [HDI]). RESULTS: 739 women from 49 countries (Europe [33%], Africa [29%], Asia-Pacific [15%], Middle East [22%]) were enrolled. Low HDI was associated with greater left ventricular (LV) dilatation at time of diagnosis. However, baseline LV ejection fraction did not differ according to sociodemographic factors. Countries with low HE prescribed guideline-directed heart failure therapy less frequently. Six-month mortality was higher in countries with low HE; and LV non-recovery in those with low HDI, low HE and lower levels of education. Maternal outcome (death, re-hospitalization, or persistent LV dysfunction) was independently associated with income. Neonatal death was significantly more common in countries with low HE and low HDI, but was not influenced by maternal income or education attainment. CONCLUSIONS: Maternal and neonatal outcomes depend on country-specific socioeconomic characteristics. Attempts should therefore be made to allocate adequate resources to health and education, to improve maternal and fetal outcomes in PPCM.

Proteomic Profiling in Patients With Peripartum Cardiomyopathy: A Biomarker Study of the ESC EORP PPCM Registry.

BACKGROUND: Peripartum cardiomyopathy (PPCM) remains an important cause of maternal morbidity and mortality globally. The pathophysiology remains incompletely understood, and the diagnosis is often missed or delayed. OBJECTIVES: This study explored the serum proteome profile of patients with newly diagnosed PPCM, as compared with matched healthy postpartum mothers, to unravel novel protein biomarkers that would further an understanding of the pathogenesis of PPCM and improve diagnostic precision. METHODS: Study investigators performed untargeted serum proteome profiling using data-independent acquisition-based label-free quantitative liquid chromatography-tandem mass spectrometry on 84 patients with PPCM, as compared with 29 postpartum healthy controls (HCs). Significant changes in protein intensities were determined with nonpaired Student's t-tests and were further classified by using the Boruta algorithm. The proteins' diagnostic performance was evaluated by area under the curve (AUC) and validated using the 10-fold cross-validation. RESULTS: Patients with PPCM presented with a mean left ventricular ejection fraction of 33.5% ± 9.3% vs 57.0% ± 8.8% in HCs (P < 0.001). Study investigators identified 15 differentially up-regulated and 14 down-regulated proteins in patients with PPCM compared with HCs. Seven of these proteins were recognized as significant by the Boruta algorithm. The combination of adiponectin, quiescin sulfhydryl oxidase 1, inter-α-trypsin inhibitor heavy chain, and N-terminal pro-B-type natriuretic peptide had the best diagnostic precision (AUC: 0.90; 95% CI: 0.84-0.96) to distinguish patients with PPCM from HCs. CONCLUSIONS: Salient biologic themes related to immune response proteins, inflammation, fibrosis, angiogenesis, apoptosis, and coagulation were predominant in patients with PPCM compared with HCs. These newly identified proteins warrant further evaluation to establish their role in the pathogenesis of PPCM and potential use as diagnostic markers.

Objectively measured medication adherence using assays for carvedilol and enalaprilat in patients with heart failure in Mozambique and Nigeria.

Background: Poor medication adherence leads to poor health outcomes and increased healthcare costs among patients with heart failure (HF). This study aimed to objectively assess medication adherence by measuring carvedilol and enalaprilat plasma concentrations among patients with HF. Methods: The present sub-study of the Safety, Tolerability, and Efficacy of Rapid Optimization, helped by NT-proBNP testing, of Heart Failure therapies (STRONG-HF) study involved adult patients with acute HF admitted in two Mozambican and two Nigerian hospitals who were not optimally treated with oral enalapril and carvedilol. Patients in the high-intensity arm of the STRONG-HF study, and those not meeting the biomarker criteria for persistent congestion, were included in the "frequent visit" (FV) arm. In the FV arm, blood for bioanalysis of plasma enalaprilat or/and carvedilol was drawn at the 2,6,12th week post-discharge. Patients in the usual care arm of STRONG-HF were included in the "standard visit" (SV) arm, which followed the usual local practice with blood sampling in week 12. Results: The study involved 113 (79 FV and 34 SV) participants with a mean age of 48.6 years and a mean left ventricular (LV) ejection fraction of 33.1%. Theenalaprilat below the lower level of quantification (LLOQ) was documented in 7.7%, 11.9%, and 15.6% of participants in FV during the 2,6 and 12th weeks. Carvedilol concentration below LLOQ was documented in 37%, 30%, and 44.4% of participants in the FV arm during the 2,6 and 12th weeks, respectively. For the SV arm, enalaprilat and carvedilol concentrations below LLOQ in the twelfth week were documented in 37.3% and 42.9% of patients, respectively. Conclusion: Up to a third of patients using enalapril and carvedilol did not take any medication during the 12 weeks of follow-up. Non adherence was more common in patients who had less follow up, emphasizing the importance of close follow up to adherence. No adherence was also more common in medications know to have more side effects such as carvedilol.

Peripartum cardiomyopathy: risk factors and predictors of outcome.

PURPOSE OF REVIEW: Peripartum cardiomyopathy (PPCM) contributes significantly to maternal morbidity and mortality worldwide. In this review, we describe the present-day epidemiology and current understanding of the pathogenesis of PPCM. We provide an updated approach to diagnosis and management of PPCM, and discuss risk factors and predictors of outcome. RECENT FINDINGS: The highest incidences of PPCM have been reported in African, Asian, and Caribbean populations. Contemporary literature supports a 'two-hit' hypothesis, whereby the 'first hit' implies a predisposition, and the 'second hit' refers to an imbalanced peripartal hormonal milieu that results in cardiomyopathy. Whereas a half of patients will have left ventricular (LV) recovery, a tenth do not survive. Clinical findings and special investigations (ECG, echocardiography, cardiac MRI, biomarkers) can be used for risk stratification. Frequent prescription of guideline-directed medical therapy is associated with improved outcomes. SUMMARY: Despite advances in elucidating the pathogenesis of PPCM, it remains unclear why only certain women develop the disease. Moreover, even with better diagnostic work-up and management, it remains unknown why some patients with PPCM have persistent LV dysfunction or die. Future research should be aimed at better understanding of the mechanisms of disease and finding new therapies that could improve survival and LV recovery.

Electrocardiographic findings and prognostic values in patients hospitalised with COVID-19 in the World Heart Federation Global Study.

BACKGROUND: COVID-19 affects the cardiovascular system and ECG abnormalities may be associated with worse prognosis. We evaluated the prognostic value of ECG abnormalities in individuals with COVID-19. METHODS: Multicentre cohort study with adults hospitalised with COVID-19 from 40 hospitals across 23 countries. Patients were followed-up from admission until 30 days. ECG were obtained at each participating site and coded according to the Minnesota coding criteria. The primary outcome was defined as death from any cause. Secondary outcomes were admission to the intensive care unit (ICU) and major adverse cardiovascular events (MACE). Multiple logistic regression was used to evaluate the association of ECG abnormalities with the outcomes. RESULTS: Among 5313 participants, 2451 had at least one ECG and were included in this analysis. The mean age (SD) was 58.0 (16.1) years, 60.7% were male and 61.1% from lower-income to middle-income countries. The prevalence of major ECG abnormalities was 21.3% (n=521), 447 (18.2%) patients died, 196 (8.0%) had MACE and 1115 (45.5%) were admitted to an ICU. After adjustment, the presence of any major ECG abnormality was associated with a higher risk of death (OR 1.39; 95% CI 1.09 to 1.78) and cardiovascular events (OR 1.81; 95% CI 1.30 to 2.51). Sinus tachycardia (>120 bpm) with an increased risk of death (OR 3.86; 95% CI 1.97 to 7.48), MACE (OR 2.68; 95% CI 1.10 to 5.85) and ICU admission OR 1.99; 95% CI 1.03 to 4.00). Atrial fibrillation, bundle branch block, ischaemic abnormalities and prolonged QT interval did not relate to the outcomes. CONCLUSION: Major ECG abnormalities and a heart rate >120 bpm were prognostic markers in adults hospitalised with COVID-19.

Effectiveness of implantable loop recorder and Holter electrocardiographic monitoring for the detection of arrhythmias in patients with peripartum cardiomyopathy.

BACKGROUND: Patients with peripartum cardiomyopathy (PPCM) are at increased risk of sudden cardiac death (SCD). However, the exact underlying mechanisms of SCD in PPCM remain unknown. By means of extended electrocardiographic monitoring, we aimed to systematically characterize the burden of arrhythmias occurring in patients with newly diagnosed PPCM. METHODS AND RESULTS: Twenty-five consecutive women with PPCM were included in this single-centre, prospective clinical trial and randomised to receiving either 24 h-Holter ECG monitoring followed by implantable loop recorder implantation (ILR; REVEAL XT, Medtronic®) or 24 h-Holter ECG monitoring alone. ILR + 24 h-Holter monitoring had a higher yield of arrhythmic events compared to 24 h-Holter monitoring alone (40% vs 6.7%, p = 0.041). Non-sustained ventricular tachycardia (NSVT) occurred in four patients (16%, in three patients detected by 24 h-Holter, and multiple episodes detected by ILR in one patient). One patient deceased from third-degree AV block with an escape rhythm that failed. All arrhythmic events occurred in patients with a severely impaired LV systolic function. CONCLUSIONS: We found a high prevalence of potentially life-threatening arrhythmic events in patients with newly diagnosed PPCM. These included both brady- and tachyarrhythmias. Our results highlight the importance of extended electrocardiographic monitoring, especially in those with severely impaired LV systolic function. In this regard, ILR in addition to 24 h-Holter monitoring had a higher yield of VAs as compared to 24 h-Holter monitoring alone. In settings where WCDs are not readily available, ILR monitoring should be considered in patients with severely impaired LV systolic dysfunction, especially after uneventful 24 h-Holter monitoring. TRIAL REGISTRATION: Pan African Clinical Trials Registry: PACTR202104866174807. Extended electrocardiographic monitoring for the detection of arrhythmias in PPCM. (CHB, complete heart block/third degree AV block; ECG, electrocardiogram; ILR, implantable loop recorder; NSVT, non-sustained ventricular tachycardia; PPCM, peripartum cardiomyopathy).

Model-Predicted Impact of ECG Monitoring Strategies During Bedaquiline Treatment.

Background: The M2 metabolite of bedaquiline causes QT-interval prolongation, making electrocardiogram (ECG) monitoring of patients receiving bedaquiline for drug-resistant tuberculosis necessary. The objective of this study was to determine the relationship between M2 exposure and Fridericia-corrected QT (QTcF)-interval prolongation and to explore suitable ECG monitoring strategies for 6-month bedaquiline treatment. Methods: Data from the PROBeX study, a prospective observational cohort study, were used to characterize the relationship between M2 exposure and QTcF. Established nonlinear mixed-effects models were fitted to pharmacokinetic and ECG data. In a virtual patient population, QTcF values were simulated for scenarios with and without concomitant clofazimine. ECG monitoring strategies to identify patients who need to interrupt treatment (QTcF > 500 ms) were explored. Results: One hundred seventy patients were included, providing 1131 bedaquiline/M2 plasma concentrations and 1702 QTcF measurements; 2.1% of virtual patients receiving concomitant clofazimine had QTcF > 500 ms at any point during treatment (0.7% without concomitant clofazimine). With monthly monitoring, almost all patients with QTcF > 500 ms were identified by week 12; after week 12, patients were predominantly falsely identified as QTcF > 500 ms due to stochastic measurement error. Following a strategy with monitoring before treatment and at weeks 2, 4, 8, and 12 in simulations with concomitant clofazimine, 93.8% of all patients who should interrupt treatment were identified, and 26.4% of all interruptions were unnecessary (92.1% and 32.2%, respectively, without concomitant clofazimine). Conclusions: Our simulations enable an informed decision for a suitable ECG monitoring strategy by weighing the risk of missing patients with QTcF > 500 ms and that of interrupting bedaquiline treatment unnecessarily. We propose ECG monitoring before treatment and at weeks 2, 4, 8, and 12 after starting bedaquiline treatment.

A global perspective on the management and outcomes of peripartum cardiomyopathy: a systematic review and meta-analysis.

AIMS: Peripartum cardiomyopathy (PPCM) remains a major contributor to maternal morbidity and mortality worldwide. The disease is associated with various complications occurring mainly early during its course. Reported adverse outcomes include decompensated heart failure, thromboembolic complications, arrhythmias and death. We sought to systematically and comprehensively review published literature on the management and outcome of women with PPCM across different geographical regions and to identify possible predictors of adverse outcomes. METHODS AND RESULTS: We performed a comprehensive search of relevant literature (2000 to June 2021) across a number of electronic databases. Cohort, case-control and cross-sectional studies, as well as control arms of randomized controlled trials reporting on 6- and/or 12-month outcomes of PPCM were considered eligible (PROSPERO registration: CRD42021255654). Forty-seven studies (4875 patients across 60 countries) met the inclusion criteria. Haemodynamic and echocardiographic parameters were similar across all continents. All-cause mortality was 8.0% (95% confidence interval [CI] 5.5-10.8, I2  = 79.1%) at 6 months and 9.8% (95% CI 6.2-14.0, I2  = 80.5%) at 12 months. All-cause mortality was highest in Africa and Asia/Pacific. Overall, 44.1% (95% CI 36.1-52.2, I2  = 91.7%) of patients recovered their left ventricular (LV) function within 6 months and 58.7% (95% CI 48.1-68.9, I2  = 75.8%) within 12 months. Europe and North America reported the highest prevalence of LV recovery. Frequent prescription of beta-blocker, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker and bromocriptine/cabergoline were associated with significantly lower all-cause mortality and better LV recovery. CONCLUSION: We identified significant global differences in 6- and 12-month outcomes in women with PPCM. Frequent prescription of guideline-directed heart failure therapy was associated with better LV recovery and lower all-cause mortality. Timely initiation and up-titration of heart failure therapy should therefore be strongly encouraged to improve outcome in PPCM.

Nutritional Heart Disease and Cardiomyopathies: JACC Focus Seminar 4/4.

This JACC Focus Seminar provides an overview of and highlights recently published research on cardiomyopathies and nutritional heart disease that have a higher prevalence in tropical regions. The development of tropical cardiomyopathies and nutritional cardiovascular disease (CVD) is complicated by high rates of poverty, fragmented health care systems, and suboptimal access to health care because of socioeconomic inequalities, leading to the fact that children, adolescents, and young adults are disproportionally affected. Such tropical cardiomyopathies and nutritional CVD that have not been prevalent in high-income countries in the past decades are now reemerging. When treating migrants or refugees, it is important for attending physicians to consider the burden of endemic diseases in the countries of origin and the likelihood that such patients might be affected. In this review, the authors propose an approach for adequate diagnostic work-up leading to appropriate care for those with suspected or confirmed tropical cardiomyopathies and nutritional CVD.

Evaluating the Efficacy of an Online Learning Tool for EEG Teaching: A Prospective Cohort Study.

OBJECTIVE: To determine the effectiveness of a 6-month, interactive, multimodal, Web-based EEG teaching program (EEGonline) in improving EEG analysis and interpretation skills for neurologists, neurology residents, and technologists, particularly in resource-limited settings. METHODS: Between June 2017 and November 2018, 179 learners originating from 20 African countries, Europe, and the United States were registered on the EEGonline course. Of these, 128 learners (91% African) participated in the study. Pre- and postcourse multiple choice question (MCQ) test results and EEGonline user logs were analyzed. Differences in pre- and posttest performance were correlated with quantified exposure to various EEGonline learning modalities. Participants' impressions of EEGonline efficacy and usefulness were assessed through pre- and postcourse satisfaction surveys. RESULTS: Ninety-one participants attempted both pre- and postcourse tests (71% response rate). Mean scores improved from 46.7% ± 17.6% to 64.1% ± 18%, respectively (p < 0.001, Cohen d 0.974). The largest improvement was in correct identification of normal features (43.2%-59.1%; p < 0.001, Cohen d 0.664) and artifacts (43.3%-61.6%; p < 0.001, Cohen d 0.836). Improvement in knowledge was associated with improved subjective confidence in EEG analysis. Overall confidence among postcourse survey respondents improved significantly from 35.9% to 81.9% (p < 0.001). Lecture notes, self-assessment quizzes, and discussion forums were the most utilized learning modalities. The majority of survey respondents (97.2%) concluded that EEGonline was a useful learning tool and 93% recommended that similar courses should be included in EEG training curricula. CONCLUSIONS: This study demonstrated that a multimodal, online EEG teaching tool was effective in improving EEG analysis and interpretation skills and may be useful in resource-poor settings.

Outcomes and complications of peripartum cardiomyopathy: protocol for a systematic review and meta-analysis.

INTRODUCTION: Peripartum cardiomyopathy (PPCM) remains a major contributor to maternal morbidity and mortality worldwide. The disease is associated with various complications, which occur predominantly during the early stages of the disease. Adverse outcomes include decompensated heart failure, thromboembolic complications, arrhythmias and death. We present a protocol for a systematic review and meta-analysis to summarise the available data on the complications and outcomes of women with PPCM. METHODS AND ANALYSIS: A comprehensive search of all articles published between 2000 (the year in which the first universal definition of PPCM was used) and 1 June 2021 will be performed on PubMed/MEDLINE, Web of Science, Scopus and EBSCO Host, including Academic Search Premier, Africa-Wide Information, Cumulative Index to Nursing and Allied Health Literature. All cohort and cross-sectional studies, as well as control arms of randomised control trials (RCTs) reporting on the complications and outcomes of PPCM will be included in the review. Methodological quality assessment of included studies will be done by assessing the risk of bias. Heterogeneity of the data will be tested by visual inspection of the forest plot and I2 and χ2 tests. This study will report the burden of complications occurring around the time of diagnosis as well as the 6-month or 12-month outcomes of women with PPCM. A summarised description in form of a pooled analysis of across multiple centres, regions and continents would help us to better understand the estimates of complications and outcomes of women with PPCM. ETHICS AND DISSEMINATION: As this research is a systematic review of published literature, ethical approval is not required. The results will be reported according to the latest guidelines for Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 statement, and will be submitted to a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42021255654.

Clinically contextualised ECG interpretation: the impact of prior clinical exposure and case vignettes on ECG diagnostic accuracy.

BACKGROUND: ECGs are often taught without clinical context. However, in the clinical setting, ECGs are rarely interpreted without knowing the clinical presentation. We aimed to determine whether ECG diagnostic accuracy was influenced by knowledge of the clinical context and/or prior clinical exposure to the ECG diagnosis. METHODS: Fourth- (junior) and sixth-year (senior) medical students, as well as medical residents were invited to complete two multiple-choice question (MCQ) tests and a survey. Test 1 comprised 25 ECGs without case vignettes. Test 2, completed immediately thereafter, comprised the same 25 ECGs and MCQs, but with case vignettes for each ECG. Subsequently, participants indicated in the survey when last, during prior clinical clerkships, they have seen each of the 25 conditions tested. Eligible participants completed both tests and survey. We estimated that a minimum sample size of 165 participants would provide 80% power to detect a mean difference of 7% in test scores, considering a type 1 error of 5%. RESULTS: This study comprised 176 participants (67 [38.1%] junior students, 55 [31.3%] senior students, 54 [30.7%] residents). Prior ECG exposure depended on their level of training, i.e., junior students were exposed to 52% of the conditions tested, senior students 63.4% and residents 96.9%. Overall, there was a marginal improvement in ECG diagnostic accuracy when the clinical context was known (Cohen's d = 0.35, p < 0.001). Gains in diagnostic accuracy were more pronounced amongst residents (Cohen's d = 0.59, p < 0.001), than senior (Cohen's d = 0.38, p < 0.001) or junior students (Cohen's d = 0.29, p < 0.001). All participants were more likely to make a correct ECG diagnosis if they reported having seen the condition during prior clinical training, whether they were provided with a case vignette (odds ratio [OR] 1.46, 95% confidence interval [CI] 1.24-1.71) or not (OR 1.58, 95% CI 1.35-1.84). CONCLUSION: ECG interpretation using clinical vignettes devoid of real patient experiences does not appear to have as great an impact on ECG diagnostic accuracy as prior clinical exposure. However, exposure to ECGs during clinical training is largely opportunistic and haphazard. ECG training should therefore not rely on experiential learning alone, but instead be supplemented by other formal methods of instruction.

Effectiveness and Cardiac Safety of Bedaquiline-Based Therapy for Drug-Resistant Tuberculosis: A Prospective Cohort Study.

BACKGROUND: Bedaquiline improves treatment outcomes in patients with rifampin-resistant (RR) tuberculosis but prolongs the QT interval and carries a black-box warning from the US Food and Drug Administration. The World Health Organization recommends that all patients with RR tuberculosis receive a regimen containing bedaquiline, yet a phase 3 clinical trial demonstrating its cardiac safety has not been published. METHODS: We conducted an observational cohort study of patients with RR tuberculosis from 3 provinces in South Africa who received regimens containing bedaquiline. We performed rigorous cardiac monitoring, which included obtaining electrocardiograms in triplicate at 4 time points during bedaquiline therapy. Participants were followed up until the end of therapy or 24 months. Outcomes included final tuberculosis treatment outcome and QT interval prolongation (QT prolongation), defined as any QT interval corrected by the Fridericia method (QTcF) >500 ms or an absolute change from baseline (ΔQTcF) >60 ms. RESULTS: We enrolled 195 eligible participants, of whom 40% had extensively drug-resistant tuberculosis. Most participants (97%) received concurrent clofazimine. Of the participants, 74% were cured or successfully completed treatment, and outcomes did not differ by human immunodeficiency virus status. QTcF continued to increase throughout bedaquiline therapy, with a mean increase (standard deviation) of 23.7 (22.7) ms from baseline to month 6. Four participants experienced a QTcF >500 ms and 19 experienced a ΔQTcF >60 ms. Older age was independently associated with QT prolongation. QT prolongation was neither more common nor more severe in participants receiving concurrent lopinavir-ritonavir. CONCLUSIONS: Severe QT prolongation was uncommon and did not require permanent discontinuation of either bedaquiline or clofazimine. Close monitoring of the QT interval may be advisable in older patients.

Neglected cardiovascular diseases and their significance in the Global North.

Due to increasing global migration, the spectrum of cardiovascular disease (CVD) is changing in developed countries. Up to 3% of migrants arriving in Europe have underlying CVD. Despite their high global prevalence, conditions such as rheumatic heart disease, Chagas disease, endomyocardial fibrosis, tuberculous pericarditis, peripartum cardiomyopathy, and pulmonary hypertension are often under-recognized, and, as a result, neglected in industrialized countries. Many of these conditions, and their causes, are often unfamiliar to the health-care providers in host countries. In this review, we summarize the epidemiology, etiology, clinical presentation, diagnostic work-up, and management of neglected CVDs that have an increasing prevalence in the Global North.

Electrocardiographic features and their echocardiographic correlates in peripartum cardiomyopathy: results from the ESC EORP PPCM registry.

AIMS: In peripartum cardiomyopathy (PPCM), electrocardiography (ECG) and its relationship to echocardiography have not yet been investigated in large multi-centre and multi-ethnic studies. We aimed to identify ECG abnormalities associated with PPCM, including regional and ethnic differences, and their correlation with echocardiographic features. METHODS AND RESULTS: We studied 411 patients from the EURObservational PPCM registry. Baseline demographic, clinical, and echocardiographic data were collected. ECGs were analysed for rate, rhythm, QRS width and morphology, and QTc interval. The median age was 31 [interquartile range (IQR) 26-35] years. The ECG was abnormal in > 95% of PPCM patients. Sinus tachycardia (heart rate > 100 b.p.m.) was common (51%), but atrial fibrillation was rare (2.27%). Median QRS width was 82 ms [IQR 80-97]. Left bundle branch block (LBBB) was reported in 9.30%. Left ventricular (LV) hypertrophy (LVH), as per ECG criteria, was more prevalent amongst Africans (59.62%) and Asians (23.17%) than Caucasians (7.63%, P < 0.001) but did not correlate with LVH on echocardiography. Median LV end-diastolic diameter (LVEDD) was 60 mm [IQR 55-65] and LV ejection fraction (LVEF) 32.5% [IQR 25-39], with no significant regional or ethnic differences. Sinus tachycardia was associated with an LVEF < 35% (OR 1.85 [95% CI 1.20-2.85], P = 0.006). ECG features that predicted an LVEDD > 55 mm included a QRS complex > 120 ms (OR 11.32 [95% CI 1.52-84.84], P = 0.018), LBBB (OR 4.35 [95% CI 1.30-14.53], P = 0.017), and LVH (OR 2.03 [95% CI 1.13-3.64], P = 0.017). CONCLUSIONS: PPCM patients often have ECG abnormalities. Sinus tachycardia predicted poor systolic function, whereas wide QRS, LBBB, and LVH were associated with LV dilatation.

Utility of mobile learning in Electrocardiography.

Aims: Mobile learning is attributed to the acquisition of knowledge derived from accessing information on a mobile device. Although increasingly implemented in medical education, research on its utility in Electrocardiography remains sparse. In this study, we explored the effect of mobile learning on the accuracy of electrocardiogram (ECG) analysis and interpretation. Methods and results: The study comprised 181 participants (77 fourth- and 69 sixth-year medical students, and 35 residents). Participants were randomized to analyse ECGs with a mobile learning strategy [either searching the Internet or using an ECG reference application (app)] or not. For each ECG, they provided their initial diagnosis, key supporting features, and final diagnosis consecutively. Two weeks later, they analysed the same ECGs, without access to any mobile device. ECG interpretation was more accurate when participants used the ECG app (56%), as compared to searching the Internet (50.3%) or neither (43.5%, P = 0.001). Importantly, mobile learning supported participants in revising their initial incorrect ECG diagnosis (ECG app 18.7%, Internet search 13.6%, no mobile device 8.4%, P < 0.001). However, whilst this was true for students, there was no significant difference amongst residents. Internet searches were only useful if participants identified the correct ECG features. The app was beneficial when participants searched by ECG features, but not by diagnosis. Using the ECG reference app required less time than searching the Internet (7:44 ± 4:13 vs. 9:14 ± 4:34, P < 0.001). Mobile learning gains were not sustained after 2 weeks. Conclusion: Whilst mobile learning contributes to increased ECG diagnostic accuracy, the benefits were not sustained over time.

Effectiveness of blended learning versus lectures alone on ECG analysis and interpretation by medical students.

BACKGROUND: Most medical students lack confidence and are unable to accurately interpret ECGs. Thus, better methods of ECG instruction are being sought. Current literature indicates that the use of e-learning for ECG analysis and interpretation skills (ECG competence) is not superior to lecture-based teaching. We aimed to assess whether blended learning (lectures supplemented with the use of a web application) resulted in better acquisition and retention of ECG competence in medical students, compared to conventional teaching (lectures alone). METHODS: Two cohorts of fourth-year medical students were studied prospectively. The conventional teaching cohort (n = 67) attended 4 hours of interactive lectures, covering the basic principles of Electrocardiography, waveform abnormalities and arrhythmias. In addition to attending the same lectures, the blended learning cohort (n = 64) used a web application that facilitated deliberate practice of systematic ECG analysis and interpretation, with immediate feedback. All participants completed three tests: pre-intervention (assessing baseline ECG competence at start of clinical clerkship), immediate post-intervention (assessing acquisition of ECG competence at end of six-week clinical clerkship) and delayed post-intervention (assessing retention of ECG competence 6 months after clinical clerkship, without any further ECG training). Diagnostic accuracy and uncertainty were assessed in each test. RESULTS: The pre-intervention test scores were similar for blended learning and conventional teaching cohorts (mean 31.02 ± 13.19% versus 31.23 ± 11.52% respectively, p = 0.917). While all students demonstrated meaningful improvement in ECG competence after teaching, blended learning was associated with significantly better scores, compared to conventional teaching, in immediate (75.27 ± 16.22% vs 50.27 ± 17.10%, p <  0.001; Cohen's d = 1.58), and delayed post-intervention tests (57.70 ± 18.54% vs 37.63 ± 16.35%, p <  0.001; Cohen's d = 1.25). Although diagnostic uncertainty decreased after ECG training in both cohorts, blended learning was associated with better confidence in ECG analysis and interpretation. CONCLUSION: Blended learning achieved significantly better levels of ECG competence and confidence amongst medical students than conventional ECG teaching did. Although medical students underwent significant attrition of ECG competence without ongoing training, blended learning also resulted in better retention of ECG competence than conventional teaching. Web applications encouraging a stepwise approach to ECG analysis and enabling deliberate practice with feedback may, therefore, be a useful adjunct to lectures for teaching Electrocardiography.