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.

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.

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).

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.

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.

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.

Valvular heart disease in patients with chronic kidney disease.

Valvular heart disease (VHD) is common in patients with impaired renal function, especially in those with end-stage renal disease (ESRD) undergoing dialysis. Progressive sclerosis and calcification of the valves and valvular annuli are major components of the etiology. These processes typically affect the aortic and mitral valve and can lead to both valvular insufficiency and stenosis. As recommended by the 2017 ESC/EACTS Guidelines for the management of VHD, surgical treatment remains the standard care for most cases of severe VHD. However, chronic kidney disease (CKD) is associated with increased mortality when compared with patients with preserved renal function. Interventional treatment options have emerged as an effective and safe alternative for patients older than 75 years and/or with increased surgical risk. Consequently, in patients with CKD at increased surgical risk who have suitable anatomical morphology, transcatheter replacement and/or repair should be discussed in the interdisciplinary "heart team."

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.

Interplay of COVID-19 and cardiovascular diseases in Africa: an observational snapshot.

The COVID-19 pandemic, which started around December 2019 has, at present, resulted in over 450,000 deaths globally, and approximately 1% of these deaths have been reported in Africa. Despite the high prevalence of COVID-19 risk factors, namely: hypertension, diabetes, chronic pulmonary disease, cardiovascular diseases (CVDs) such as rheumatic heart disease, compromised immunity and obesity, low case fatality rates have been recorded in many parts of Africa so far. COVID-19 severity has previously been shown to be worse in patients with CVD and hypertension. We observed the severity of COVID-19 and mortality rates in Africa, and compared outcomes with prevalence of established risk factors (hypertension and CVD). We stratified data as per the United Nations' 5 African subregions. North African countries show a positive association between the risk factors and the mortality rates from COVID-19. However, we observed discordant patterns in the relationship between COVID-19, and either CVD or hypertension, in sub-Saharan African countries. In this paper, we also review the pathogenesis of SARS-CoV-2 infection and how it worsens CVD and postulate that the differences in modulation of the renin-angiotensin-aldosterone system (RAAS) axis which controls angiotensin-converting enzyme (ACE)/ACE2 balance may be an important determinant of COVID-19 outcomes in Africa.

Detection and management of arrhythmias in peripartum cardiomyopathy.

Peripartum cardiomyopathy (PPCM) is an idiopathic dilated cardiomyopathy, in which previously healthy women present with heart failure secondary to left ventricular (LV) systolic dysfunction during the last months of pregnancy or up to 5 months postpartum. PPCM occurs worldwide. The incidence seems to be increasing, possibly due to increasing awareness of the condition and diagnosis thereof. Women diagnosed with PPCM present with symptoms and signs of heart failure, thromboembolism or arrhythmia. Although the incidence of arrhythmias in this condition is not well documented, patients with PPCM often have rhythm disturbances. Indeed, life-threating arrhythmias contribute significantly to sudden cardiac death (SCD) in this population, especially when patients have poor systolic function. In this review, we summarize the evidence on atrial and ventricular arrhythmias in PPCM, as detected by various diagnostic modalities. Furthermore, we summarize the management of arrhythmias in PPCM, as recommended by contemporary guidelines.

Posterior infarction: a STEMI easily missed.

Anterior ST-segment depression encompasses important differential diagnoses, including ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction and pulmonary embolism. Diagnostic accuracy is crucial, as this has important therapeutic implications. This ECG case report reviews the electrocardiographic changes seen in patients with chest pain and anterior ST-segment depression.

Irregular, narrow-complex tachycardia.

The correct differentiation of an irregular, narrow-complex tachycardia has crucial implications for the therapeutic management of these conditions. In this article we present a differential diagnostic and treatment approach to irregular, narrow-complex tachycardias.