Investigation of Copy Number Variation in South African Patients With Congenital Heart Defects.

BACKGROUND: Congenital heart disease (CHD) is a leading non-infectious cause of pediatric morbidity and mortality worldwide. Although the etiology of CHD is poorly understood, genetic factors including copy number variants (CNVs) contribute to the risk of CHD in individuals of European ancestry. The presence of rare CNVs in African CHD populations is unknown. This study aimed to identify pathogenic and likely pathogenic CNVs in South African patients with CHD. METHODS: Genotyping was performed on 90 patients with nonsyndromic CHD using the Affymetrix CytoScan HD platform. These data were used to identify large, rare CNVs in known CHD-associated genes and candidate genes. RESULTS: We identified eight CNVs overlapping known CHD-associated genes (GATA4, CRKL, TBX1, FLT4, B3GAT3, NSD1) in six patients. The analysis also revealed CNVs encompassing five candidate genes likely to play a role in the development of CHD (DGCR8, KDM2A, JARID2, FSTL1, CYFIP1) in five patients. One patient was found to have 47, XXY karyotype. We report a total discovery yield of 6.7%, with 5.6% of the cohort carrying pathogenic or likely pathogenic CNVs expected to cause the observed phenotypes. CONCLUSIONS: In this study, we show that chromosomal microarray is an effective technique for identifying CNVs in African patients diagnosed with CHD and have demonstrated results similar to previous CHD genetic studies in Europeans. Novel potential CHD genes were also identified, indicating the value of genetic studies of CHD in ancestrally diverse populations.

PROTEA, A Southern African Multicenter Congenital Heart Disease Registry and Biorepository: Rationale, Design, and Initial Results.

Objectives: The PartneRships in cOngeniTal hEart disease (PROTEA) project aims to establish a densely phenotyped and genotyped Congenital Heart Disease (CHD) cohort for southern Africa. This will facilitate research into the epidemiology and genetic determinants of CHD in the region. This paper introduces the PROTEA project, characterizes its initial cohort, from the Western Cape Province of South Africa, and compares the proportion or "cohort-prevalences" of CHD-subtypes with international findings. Methods: PROTEA is a prospective multicenter CHD registry and biorepository. The initial cohort was recruited from seven hospitals in the Western Cape Province of South Africa from 1 April 2017 to 31 March 2019. All patients with structural CHD were eligible for inclusion. Descriptive data for the preliminary cohort are presented. In addition, cohort-prevalences (i.e., the proportion of patients within the cohort with a specific CHD-subtype) of 26 CHD-subtypes in PROTEA's pediatric cohort were compared with the cohort-prevalences of CHD-subtypes in two global birth-prevalence studies. Results: The study enrolled 1,473 participants over 2 years, median age was 1.9 (IQR 0.4-7.1) years. Predominant subtypes included ventricular septal defect (VSD) (339, 20%), atrial septal defect (ASD) (174, 11%), patent ductus arteriosus (185, 11%), atrioventricular septal defect (AVSD) (124, 7%), and tetralogy of Fallot (121, 7%). VSDs were 1.8 (95% CI, 1.6-2.0) times and ASDs 1.4 (95% CI, 1.2-1.6) times more common in global prevalence estimates than in PROTEA's pediatric cohort. AVSDs were 2.1 (95% CI, 1.7-2.5) times more common in PROTEA and pulmonary stenosis and double outlet right ventricle were also significantly more common compared to global estimates. Median maternal age at delivery was 28 (IQR 23-34) years. Eighty-two percent (347/425) of mothers used no pre-conception supplementation and 42% (105/250) used no first trimester supplements. Conclusions: The cohort-prevalence of certain mild CHD subtypes is lower than for international estimates and the cohort-prevalence of certain severe subtypes is higher. PROTEA is not a prevalence study, and these inconsistencies are unlikely the result of true differences in prevalence. However, these findings may indicate under-diagnosis of mild to moderate CHD and differences in CHD management and outcomes. This reemphasizes the need for robust CHD epidemiological research in the region.

AHA/ACC vs ESC Guidelines for Management of Adults With Congenital Heart Disease: JACC Guideline Comparison.

The American Heart Association and American College of Cardiology published practice guidelines for the management of adult congenital heart disease in 2018 and the European Society of Cardiology published analogous guidelines in 2020. Although there are broad areas of consensus between the 2 documents, there are important differences that impact patient management. This review discusses key areas of agreement and disagreement between the 2 guidelines, with discussion of possible reasons for disagreement and potential implications.

Managing Rheumatic Heart Disease in Pregnancy: A Practical Evidence-Based Multidisciplinary Approach.

Rheumatic heart disease (RHD) remains a leading cause of mortality and morbidity in pregnant patients in low- to middle-income countries. Apart from the clinical challenges, these areas face poor infrastructure and resources to allow for early detection, with many women presenting to medical services for the first time when they deteriorate clinically during the pregnancy. The opportunity for preconception counselling and planning may thus be lost. It is ideal for all women to be seen before conception and risk-stratified according to their clinical state and pathology. The role of the cardio-obstetrics team has emerged over the past decade with the aim of a seamless transition to and from the appropriate levels of care during pregnancy. Severe symptomatic mitral and aortic valve stenoses portend the greatest risk to both mother and fetus. In mitral stenosis, beta-blockers are the cornerstone of therapy and only a small number of patients require balloon valvuloplasty. Regurgitant lesions mostly require diuretics alone for the treatment of heart failure. The mode of delivery is usually vaginal; caesarean section is performed in those with obstetrical indications or in cases with severe stenosis and a poor clinical state. The postpartum period presents a second high-risk period for maternal adverse events, with heart failure and arrhythmias being the most frequent. This review aims to provide a practical evidence-based multi-disciplinary approach to the management of women with RHD in pregnancy.

The Role of Multimodality Imaging in HIV-Associated Cardiomyopathy.

Despite marked advances in therapeutics, HIV infection remains a leading cause of morbidity and mortality worldwide. HIV infection is associated with cardiovascular complications including myocardial dysfunction. The description of HIV-associated cardiomyopathy (HIVAC) has evolved over time from a predominantly dilated cardiomyopathy with systolic dysfunction to one of subclinical diastolic dysfunction. Multimodality cardiovascular imaging plays an integral role in our understanding of the etiology and pathogenesis of HIVAC. Such imaging is also essential in the evaluation of individuals with chronic HIV disease who present with cardiac symptoms, especially of heart failure. In the present review, we will highlight current evidence for the role of multimodality imaging in establishing the diagnosis, etiology and pathophysiology of HIVAC as well as guiding treatment and assessing prognosis.

Cardiovascular imaging modalities in the diagnosis and management of rheumatic heart disease.

Rheumatic heart disease (RHD) is prevalent in sub-Saharan Africa, where the capacity for diagnosis and evaluation of disease severity and complications is not always optimal. While the medical history and physical examination are important in the assessment of patients suspected to have RHD, cardiovascular imaging techniques are useful for confirmation of the diagnosis. Echocardiography is the workhorse modality for initial evaluation and diagnosis of RHD. Cardiovascular magnetic resonance is complementary and may provide additive information, including tissue characteristics, where echocardiography is inadequate or non-diagnostic. There is emerging evidence on the role of computed tomography, particularly following valve replacement surgery, in the monitoring and management of RHD. This article summarises the techniques used in imaging RHD patients, considers the evidence base for their utility, discusses their limitations and recognises the clinical contexts in which indications and imaging with various modalities are expanding.

A case report: delayed right ventricular pericardial fistula and aneurysm following penetrating traumatic injury-a controversial aetiology.

BACKGROUND: Right ventricular aneurysms (RVAs) are rare. We present a case with a combined RVA and right ventricular pericardial fistula resulting in a pericardial effusion and cardiac tamponade. The RVA was detected 47 days after the patient suffered a gunshot wound. This report adds to the body of scarce literature on RVA aetiology, diagnoses, and treatment. CASE SUMMARY: A 30-year-old male patient presented with worsening respiratory distress over a 7-day period with clinical signs of cardiac tamponade following a history of a gunshot (with associated liver laceration, pulmonary embolism, right nephrectomy, and sepsis) 47 days prior. Transthoracic echocardiography showed a large circumferential pericardial effusion and an RVA. The patient was emergently taken for surgical repair of the RVA. DISCUSSION: Our case presents a delayed presentation of a gunshot heart and an aetiology with indications of and against a true aneurysm. It brings attention to possible complications of penetrating precordial injuries, with the need for consideration and possible evaluation at follow-up. The literature on the operative excision of RVA is reviewed and various aetiological factors and consequences are discussed.

Implantable cardioverter-defibrillator therapy to reduce sudden cardiac death in adults with congenital heart disease: A registry study.

INTRODUCTION: The adult congenital heart disease (ACHD) population is rapidly expanding. However, a significant proportion of these patients suffer sudden cardiac death. Recommending implantable cardioverter-defibrillator (ICD) insertion requires balancing the need for appropriate therapy in malignant arrhythmia against the consequences of inappropriate therapy and procedural complications. Here we present long-term follow-up data for ICD insertion in patients with ACHD from a large Level 1 congenital cardiac center. METHODS AND RESULTS: All patients with ACHD undergoing ICD insertion over an 18-year period were identified. Data were extracted for baseline characteristics including demographics, initial diagnosis, ventricular function, relevant medication, and indication for ICD insertion. Details regarding device insertion were gathered along with follow-up data including appropriate and inappropriate therapy and complications. A total of 136 ICDs were implanted during this period: 79 for primary and 57 for secondary prevention. The most common congenital cardiac conditions in both groups were tetralogy of Fallot and transposition of the great arteries. Twenty-two individuals in the primary prevention group received appropriate antitachycardia pacing (ATP), 14 underwent appropriate cardioversion, 17 received inappropriate ATP, and 15 received inappropriate cardioversion. In the secondary prevention group, 18 individuals received appropriate ATP, 8 underwent appropriate cardioversion, 8 received inappropriate ATP, and 7 were inappropriately cardioverted. Our data demonstrate low complication rates, particularly with leads without advisories. CONCLUSION: ICD insertion in the ACHD population involves a careful balance of the risks and benefits. Our data show a significant proportion of patients receiving appropriate therapy indicating that ICDs were inserted appropriately.

Cardiac Structure and Function in Morbidly Obese Parturients: An Echocardiographic Study.

BACKGROUND: The increasing prevalence of obesity worldwide is a major threat to global health. Cardiac structural and functional changes are well documented for obesity as well as for pregnancy, but there is limited literature on morbidly obese parturients. We hypothesized that there are both cardiac structural and functional differences between morbidly obese pregnant women and pregnant women of normal body mass index (BMI). METHODS: This prospective cross-sectional study was performed in 2 referral maternity units in Cape Town, South Africa, over a 3-month period. Forty morbidly obese pregnant women of BMI ≥40 kg·m (group O) were compared to 45 pregnant women of BMI ≤30 kg·m (group N). Cardiac structure and function were assessed by transthoracic echocardiography, according to the recommendations of the British Society of Echocardiography. The 2-sample t-test with unequal variances was used for the comparison of the mean values between the groups. RESULTS: Acceptable echocardiographic images were obtained in all obese women. Statistical significance was defined as P < .0225 after applying the Benjamini-Hochberg correction for multiple testing. Mean (standard deviation) mean arterial pressure was higher in group O (91 [8.42] vs 84 [9.49] mm Hg, P < .001). There were no between-group differences in heart rate, stroke volume, or cardiac index (84 [12] vs 79 [13] beats·minute, P = .103; 64.4 [9.7] vs 59.5 [13.5] mL, P = .069; 2551 [474] vs 2729 [623] mL·minute·m, P = .156, for groups O and N, respectively). Stroke volume index was lower, and left ventricular mass was higher in group O (30.14 [4.51] vs 34.25 [7.00] mL·m, P = .003; 152 [24] vs 115 [29] g, P < .001). S' septal was lower in group O (8.43 [1.20] vs 9.25 [1.64] cm·second, P = .012). Considering diastolic function, isovolumetric relaxation time was significantly prolonged in group O (73 [15] vs 61 [15] milliseconds, P < .001). The septal tissue Doppler index E' septal was lower in group O (9.08 [1.69] vs 11.28 [3.18], P < .001). There were no between-group differences in E' average (10.7 [2.3] vs 12.0 [2.7], P = .018, O versus N) or E/E' average (7.85 [1.77] vs 7.27 [1.68], P = .137, O versus N). Right ventricular E'/A' was lower in group O (1.07 [0.47] vs 1.29 [0.32], P = .016). CONCLUSIONS: Cardiac index did not differ between obese pregnant women and those with normal BMI. Their increased left ventricular mass and lower stroke volume index could indicate a limited adaptive reserve. Obese women had minor decreases in septal left ventricular tissue Doppler velocity, but the E/E' average values did not suggest clinically significant diastolic dysfunction.

Status and Challenges of Care in Africa for Adults With Congenital Heart Defects.

The 54 countries in Africa have an estimated total annual congenital heart defect (CHD) birth prevalence of 300,486 cases. More than half (51.4%) of the continental birth prevalence occurs in only seven countries. Congenital heart disease remains primarily a pediatric health issue in Africa because of the deficient health-care systems: the adults with CHD made up just 10% of patients with CHD in Ghana, and 13.7% of patients with CHD presenting for surgery in Mozambique. With Africa's population projected to double in the next 35 years, the already deficient health systems for CHD care will suffer unbearable strain unless determined and courageous action is undertaken by the African leaders.

Characteristics, complications, and gaps in evidence-based interventions in rheumatic heart disease: the Global Rheumatic Heart Disease Registry (the REMEDY study).

AIMS: Rheumatic heart disease (RHD) accounts for over a million premature deaths annually; however, there is little contemporary information on presentation, complications, and treatment. METHODS AND RESULTS: This prospective registry enrolled 3343 patients (median age 28 years, 66.2% female) presenting with RHD at 25 hospitals in 12 African countries, India, and Yemen between January 2010 and November 2012. The majority (63.9%) had moderate-to-severe multivalvular disease complicated by congestive heart failure (33.4%), pulmonary hypertension (28.8%), atrial fibrillation (AF) (21.8%), stroke (7.1%), infective endocarditis (4%), and major bleeding (2.7%). One-quarter of adults and 5.3% of children had decreased left ventricular (LV) systolic function; 23% of adults and 14.1% of children had dilated LVs. Fifty-five percent (n = 1761) of patients were on secondary antibiotic prophylaxis. Oral anti-coagulants were prescribed in 69.5% (n = 946) of patients with mechanical valves (n = 501), AF (n = 397), and high-risk mitral stenosis in sinus rhythm (n = 48). However, only 28.3% (n = 269) had a therapeutic international normalized ratio. Among 1825 women of childbearing age (12-51 years), only 3.6% (n = 65) were on contraception. The utilization of valvuloplasty and valve surgery was higher in upper-middle compared with lower-income countries. CONCLUSION: Rheumatic heart disease patients were young, predominantly female, and had high prevalence of major cardiovascular complications. There is suboptimal utilization of secondary antibiotic prophylaxis, oral anti-coagulation, and contraception, and variations in the use of percutaneous and surgical interventions by country income level.