Prevalence and significance of isolated left ventricular non-compaction phenotype in normal black Africans using echocardiography.

BACKGROUND: Several large, prospective screening studies of predominantly Caucasian patients have suggested that hypertrabeculation may not necessarily be pathologic unless there is concomitant left ventricular (LV) dysfunction, LV dilatation, history of arrhythmia, family history, or characteristic gene mutations. This conundrum may be magnified in blacks, in whom hypertrabeculation and LV hypertrophy is more common. We therefore investigated the frequency of hypertrabeculation/isolated LV noncompaction (ILVNC) phenotype in normal black Africans and evaluated LV function using sensitive measures of deformation and twist. METHODS: Two hundred and fifty-three volunteers were recruited and evaluated according to strict inclusion and exclusion criteria. Their mean age was 36.3 ± 12.2 years. RESULTS: Trabeculations were found in 12 (4.74%) participants. Three (1.2%) subjects had ≥ 4 LV trabeculations. The LV apex was the most common anatomical site for the location of trabeculations. Subjects with trabeculations were more likely to be males of a younger age, and had greater LV end-diastolic and end-systolic parameters and lateral e'. However, 0.8% of the population fulfilled the Stollberger criteria, and none fulfilled the Jenni, Milwaukee, or Baragwanath criteria. All subjects in this study had normal rotation patterns with no differences in rotational parameters or net twist. CONCLUSIONS: Trabeculations may be found as a normal variant in black Africans. Assessing trabeculations alone may infer ILVNC; however, utilizing the more comprehensive ILVNC criteria enables differentiation of a possible LVNC phenotype. Normal individuals with hypertrabeculation have normal LV function and normal rotation patterns, with no differences in rotational parameters or net twist.

Family screening in black patients with isolated left ventricular non-compaction: the Chris Hani Baragwanath experience.

BACKGROUND: Isolated left ventricular non-compaction (ILVNC), dilated cardiomyopathy (DCMO) and hypertrophic cardiomyopathy (HCM) are diseases that may be present in family members of patients with ILVNC. The primary aim of this study was to identify the prevalence and spectrum of cardiomyopathy in first-degree relatives of patients with ILVNC. A secondary aim was to compare a strategy of clinical screening, utilising only a clinical assessment and electrocardiogram (ECG), compared to one that included echocardiography for screening of family members of patients with ILVNC. METHODS: Eighty-three close relatives of 38 unrelated patients from the ILVNC clinic at the Chris Hani Baragwanath Hospital underwent a detailed clinical history, physical examination, ECG and echocardiogram. RESULTS: Echocardiographic screening revealed unexplained left ventricular (LV) dysfunction in 10 (12.05%) relatives. Nine out of the 10 individuals satisfied the criteria for diagnosis of DCMO. No cases of HCM or LVNC were identified. A strategy of clinical assessment and ECG had a sensitivity of 76% and a specificity of 42% versus the gold standard of echocardiographic screening. CONCLUSIONS: Echocardiographic screening detected DCMO in 10.8% of subjects. A strategy of clinical screening that included electrocardiography was sub-optimal as a screening strategy compared to echocardiographic screening.

Echocardiographic Indices of the Left and Right Heart in a Normal Black African Population.

BACKGROUND: It is unknown whether ethnic differences occur with regard to right heart echocardiographic parameters. The aim of this study therefore was to establish normative values of left and right heart parameters in a black African population and to evaluate the effect of age and body mass index (BMI) on specific right ventricle (RV) parameters. METHODS: Two hundred fifty-three normal subjects were prospectively studied. A standardized echocardiographic examination was conducted with the RV focused view used to derive RV measurements. All left and right heart measurements were made in accordance with the American Society of Echocardiography 2015 chamber guideline recommendations. Right ventricle free wall strain was assessed using an RV focused apical four-chamber view. RESULTS: The average age was 36.3 ± 12.2 years, and 59% of patients were female. The mean left ventricular ejection fraction was 62.3% ± 5.7%. The RV linear measurements (RV base, 31.0 ± 4.5 mm; midcavity, 26.3 ± 5.8 mm) were not associated with sex, age, or BMI except for the RV length (64.6 ± 8.9 mm), which was greater in male patients. Tricuspid annular plane systolic excursion (TAPSE) was 21.7 ± 2.8 mm, fractional area change was 42.1% ± 5.5%, tricuspid annular peak systolic velocity RV S' was 12.1 ± 1.9 m/sec, and RV free wall strain was -31.5% ± 8.6%. Age and BMI were not associated with right atrial (RA) volumetric measurements, RV linear measurements, or any RV functional parameters except TAPSE and RV A', which increased with BMI. CONCLUSIONS: This study establishes normal left and right heart parameters in a black African population. Aging was not associated with RA or RV parameters except for RV E' and A'. BMI does not affect RA/RV measurements but may cause variability in TAPSE and RV A'.

Is there a role for combination anti-remodelling therapy for heart failure secondary to chronic rheumatic mitral regurgitation?

INTRODUCTION: The value of combination anti-remodelling therapy for heart failure (HF) secondary to mitral regurgitation (MR) is unknown. We studied the effect of anti-remodelling therapy on clinical and echocardiographic parameters in patients with severe chronic rheumatic mitral regurgitation (CRMR) presenting in HF. METHODS: Thirty-one patients (29 females) at Chris Hani Baragwanath Academic Hospital, treated with combination therapy for HF due to CRMR and New York Heart Association functional class II-III symptoms, underwent prospective six-month follow up. RESULTS: Mean age was 50.7 ± 8.5 years. No patients died or were hospitalised for HF during the study period. No worsening of clinical symptoms or functional status, or left and right ventricular echocardiographic parameters (p > 0.05) was noted. Peak left atrial systolic strain improved at six months (18.7 ± 7.7 vs 23.6 ± 8.5%, p = 0.02). CONCLUSION: This preliminary analysis suggests that combination anti-remodelling therapy may be beneficial for HF secondary to CRMR. We had no HF-related admissions or deaths, and no deterioration in echocardiographic parameters of ventricular size and function.

Left atrial volume and strain parameters using echocardiography in a black population.

AIMS: Left atrial (LA) volume is an important predictor of morbidity and mortality in cardiovascular disease. Left atrial strain is a feasible technique for assessing LA function. The EchoNoRMAL study recently highlighted the possibility that ethnic-based differences may exist in LA size. There is a paucity of data regarding LA parameters in an African population. We sought to establish normative values for LA volumetric and strain parameters in a black population. METHODS AND RESULTS: This cross-sectional study comprised 120 individuals between 18 and 70 years of age. Left atrial volumes were measured by biplane Simpson's method, and strain parameters were measured using Philips QLAB 9 (Amsterdam, The Netherlands) speckle-tracking software. The mean age was 38.7 ± 12.8 years (50% male). Maximum LA volume indexed (LAVi), pre-atrial LAVi, and minimum LAVi were 19.7 ± 5.9, 12.2 ± 4.4, and 7.7 ± 3.2 mL/m2, respectively. Females had a higher LAVi compared with males (20.9 ± 6.3 vs. 18.6 ± 5.3 mL/m2, P = 0.04). Peak global longitudinal strain in the reservoir phase (ɛR) was 39.0 ± 8.3%, and the peak LA strain in the contractile phase (ɛCT) was -2.7 ± 2.5%. No gender differences were noted in ɛR. Body surface area, age, and weight were the main determinants of ɛR on multivariate linear regression analysis. CONCLUSION: The data reported in this study establish the normal reference values for phasic LA volumes and strain in a normal black population and serve as a platform for future studies.

Effects of age on left atrial volume and strain parameters using echocardiography in a normal black population.

OBJECTIVE: Normal cut-off values for left atrial (LA) size and function may be altered by aging and ethnic differences. No age-related reference values for LA volumetric measurements or LA strain exist in Africans. We aimed to establish normal age-appropriate values of LA size and function in black Africans. Additionally, we studied the correlation between age, LA strain and volumetric parameters. METHODS: In this prospective, cross-sectional study of 120 individuals (mean age 38.7 ± 12.8 years, 50% men), subjects were classified into four age groups: 18-29, 30-39, 40-49 and 50-70 years. LA volumes were measured by biplane Simpson's method, and Philips QLAB 9 (Amsterdam, The Netherlands) speckle-tracking software was used to measure LA peak strain in the reservoir (ƐR) and contractile phase (ƐCT). RESULTS: No significant differences in the maximum and minimum LAVi were noted among the four age categories (P = 0.1, P = 0.2). LA volumetric function assessment showed no difference in reservoir function between age groups (P > 0.05), conduit function decreased with advancing age (r = -0.3, P < 0.001) and booster function displayed a significant increase with age (LA active emptying volume index, P = 0.001). There was a significant decrease in LA ƐR (P < 0.0001) in the older age groups, whereas ƐCT remained unchanged (P = 0.27). CONCLUSION: Age-related changes in LA reservoir, conduit and contractile function in black Africans are similar to those observed in other populations, as was the trend of declining ƐR with advancing age. The preservation of ƐCT with increasing age requires further analysis.

Electrocardiographic Abnormalities in Disease-Free Black South Africans and Correlations With Echocardiographic Indexes and Early Repolarization.

Electrocardiographic abnormalities, and specifically early repolarization (ER) patterns, are increasingly found to be common variants in healthy populations free of heart disease or risk factors. Data are sparse in subjects of African descent, for which no increase in adverse cardiovascular outcomes have been demonstrated. A database of healthy disease-free adult volunteers of sub-Saharan African descent had 12 lead electrocardiograms (ECGs) and transthoracic echocardiograms performed. Statistical tests were then performed on the data to elicit associations; 396 volunteers (63.1% women) with a mean age of 37.4 years met the inclusion and exclusion criteria. An abnormal ECG was identified in 50.5% of volunteers, largely because of underlying ST elevation at the J point (ER), left ventricular hypertrophy (LVH) by voltage criteria, and T-wave inversion. Men were more likely to have abnormal ECGs (odds ratio [OR] 1.75; p <0.001), axes (OR 2.05; p = 0.023), display LVH by Sokolow-Lyon voltage criteria (OR 5.45; p <0.001), and have ER patterns (OR 11.61; p <0.001). Additionally, younger adults were also more likely to display LVH by voltage criteria and ER patterns. Volunteers with LVH by ECG had 5.7% higher LV mass indexes (p = 0.047). An abnormal ECG was not associated with a reduced left ventricular ejection fraction or diastolic dysfunction. ECG abnormalities, especially ER patterns, in black adults of Sub-Saharan descent are common, occurring in half of the normal adults.

Prednisolone and Mycobacterium indicus pranii in tuberculous pericarditis.

BACKGROUND: Tuberculous pericarditis is associated with high morbidity and mortality even if antituberculosis therapy is administered. We evaluated the effects of adjunctive glucocorticoid therapy and Mycobacterium indicus pranii immunotherapy in patients with tuberculous pericarditis. METHODS: Using a 2-by-2 factorial design, we randomly assigned 1400 adults with definite or probable tuberculous pericarditis to either prednisolone or placebo for 6 weeks and to either M. indicus pranii or placebo, administered in five injections over the course of 3 months. Two thirds of the participants had concomitant human immunodeficiency virus (HIV) infection. The primary efficacy outcome was a composite of death, cardiac tamponade requiring pericardiocentesis, or constrictive pericarditis. RESULTS: There was no significant difference in the primary outcome between patients who received prednisolone and those who received placebo (23.8% and 24.5%, respectively; hazard ratio, 0.95; 95% confidence interval [CI], 0.77 to 1.18; P=0.66) or between those who received M. indicus pranii immunotherapy and those who received placebo (25.0% and 24.3%, respectively; hazard ratio, 1.03; 95% CI, 0.82 to 1.29; P=0.81). Prednisolone therapy, as compared with placebo, was associated with significant reductions in the incidence of constrictive pericarditis (4.4% vs. 7.8%; hazard ratio, 0.56; 95% CI, 0.36 to 0.87; P=0.009) and hospitalization (20.7% vs. 25.2%; hazard ratio, 0.79; 95% CI, 0.63 to 0.99; P=0.04). Both prednisolone and M. indicus pranii, each as compared with placebo, were associated with a significant increase in the incidence of cancer (1.8% vs. 0.6%; hazard ratio, 3.27; 95% CI, 1.07 to 10.03; P=0.03, and 1.8% vs. 0.5%; hazard ratio, 3.69; 95% CI, 1.03 to 13.24; P=0.03, respectively), owing mainly to an increase in HIV-associated cancer. CONCLUSIONS: In patients with tuberculous pericarditis, neither prednisolone nor M. indicus pranii had a significant effect on the composite of death, cardiac tamponade requiring pericardiocentesis, or constrictive pericarditis. (Funded by the Canadian Institutes of Health Research and others; IMPI ClinicalTrials.gov number, NCT00810849.).

Clinical outcomes in patients with isolated left ventricular noncompaction and heart failure.

BACKGROUND: We prospectively evaluated long-term clinical outcomes of patients diagnosed with isolated left ventricular noncompaction (ILVNC) and heart failure from a sub-Saharan African population. METHODS AND RESULTS: Patients in this single-center study were followed at a tertiary care institution. Clinical follow-up was performed with the use of protocol-driven echocardiographic screening for ventricular thrombus every 4 months. Warfarin was maintained or initiated only if thrombus was detected with the use of echocardiography. Fifty-five patients were followed for 16.7 ± 5.9 (range 12-33) months. All individuals had left ventricular (LV) ejection fraction <50% (mean 29.6 ± 11.8%). Of the 55 patients, 7 (12.7%) died, and sudden cardiac death was the cause in 5 (71.4%). There were no differences in baseline clinical, echocardiographic, or electrocardiographic characteristics between survivors and nonsurvivors. Recurrent heart failure developed in 12 patients (21.8%); 1 patient developed a ventricular arrhythmia. No thromboembolic or major bleeding complications occurred in the 16 patients on warfarin; 1 episode of thromboembolism occurred in the 39 patients not on warfarin. Mean survival probability at 33 months was 0.64. CONCLUSIONS: Sudden cardiac death was the most common cause of death in patients with ILVNC and heart failure. Recurrent heart failure occurred in 21.8% of patients. Development of LV thrombus and cardioembolism is uncommon in this population.

Double trouble--a case report of mobile right atrial thrombus in the setting of acute pulmonary thromboembolism.

We report the case of a 51 year-old woman who, six weeks post hysterectomy, developed an acute on chronic pulmonary thromboembolism. On transthoracic echocardiography a mobile right atrial thrombus was detected at the entry of the coronary sinus into the right atrium. A 64 slice spiral CT angiogram confirmed the left sided superior vena cava and bilateral extensive thrombus in the proximal pulmonary arteries. Bilateral pulmonary endarterectomy, removal of atrial thrombus and ligation of the persistent left superior vena cava was performed which markedly improved the haemodynamic and functional status of the patient. The presence of right atrial thrombus in the setting of acute pulmonary embolism presents a unique therapeutic challenge which needs to be individualised based on a number of concomitant clinical factors.

Relationship between left ventricular twist and circulating biomarkers of collagen turnover in hypertensive patients with heart failure.

BACKGROUND: Left ventricular (LV) twist may be a compensatory mechanism to preserve ejection fraction (EF). In patients with hypertension, twist varies depending on the left ventricle's degree of remodeling and systolic function; it is increased in those with hypertension with normal EF (HTNEF) and diminished in those with hypertension with low EF (HTLEF). The ratio of collagen-degradation biomarkers in patients with hypertension is higher in those with low EFs than those with preserved EFs and may contribute to remodeling and systolic dysfunction. METHODS: The aim of this study was to evaluate the relationship between these biomarkers and LV twist in 82 patients with hypertension, 41 with EFs < 50% (HTLEF group) and 41 with EFs ≥ 50% (HTNEF group). Net LV twist was measured using speckle-tracking echocardiography. Markers of collagen turnover, including serum concentrations of matrix metalloproteinase-1 (MMP1), tissue inhibitor of MMP1 (TIMP1), and the ratio of MMP1 to TIMP1, were measured. RESULTS: Log TIMP1, log MMP1, and log MMP1/TIMP1 ratio levels were higher in the HTLEF group than the HTNEF group (12.3 ± 0.3 vs 11.8 ± 0.1 [P < .0001], 9.1 ± 0.3 vs 8.0 ± 0.2 [P < .0001], and -3.3 ± 0.3 vs -3.8 ± 0.2 [P < .0001], respectively). Net LV twist was lower in the HTLEF group than the HTNEF group (3.3 ± 1.1 vs 11.7 ± 0.7, P < .0001). An inverse correlation existed between log MMP1/TIMP1 and net LV twist after adjusting for age, EF, duration of heart failure, systolic blood pressure, LV mass index, and LV sphericity index at end-diastole (r = -0.43, P < .0001). CONCLUSIONS: This inverse correlation between twist and loss of myocardial collagen scaffolding in patients with hypertension with heart failure suggests that the integrity of the extracellular matrix may play an important role in preserving myocardial deformation.

Left ventricular twist in left ventricular noncompaction.

AIMS: Left ventricular (LV) twist is an important component of systolic function. The effect of abnormal LV twist on adverse remodelling of the heart in left ventricular noncompaction (LVNC) is unknown. This study used speckle-tracking echocardiography to evaluate LV twist in patients with LVNC and determine whether abnormal LV twist is associated with more adverse LV remodelling. METHODS AND RESULTS: Clinical, echocardiographic, and myocardial deformation characteristics were prospectively compared between 60 subjects diagnosed with LVNC and 59 age-matched healthy controls. Net instantaneous twist was defined as: peak apical rotation minus isochronous basal rotation. Normal rotation during systole was defined based on the 2010 ASE/EAE consensus document. Rigid body rotation (RBR) was determined present if the apex and base moved in the same direction during ejection. Rigid body rotation was found in 32 (53.3%) subjects with LVNC. The 28 subjects with LVNC and normal LV rotation had diminished apical rotation, basal rotation, and net twist compared with normal controls (P < 0.0001). Patients with LVNC and RBR had worse NYHA functional status (P < 0.0001), but similar echocardiographic indices of remodelling, ejection fraction, and strain parameters as those with LVNC and normal LV rotation. CONCLUSION: Left ventricular twist is diminished in subjects with LVNC and normal LV rotation. Rigid body rotation occurs in 53.3% of subjects with LVNC and is not associated with more adverse remodelling than subjects with LVNC and normal LV rotation.

Rationale and design of the Investigation of the Management of Pericarditis (IMPI) trial: a 2 × 2 factorial randomized double-blind multicenter trial of adjunctive prednisolone and Mycobacterium w immunotherapy in tuberculous pericarditis.

BACKGROUND: In spite of antituberculosis chemotherapy, tuberculous (TB) pericarditis causes death or disability in nearly half of those affected. Attenuation of the inflammatory response in TB pericarditis may improve outcome by reducing cardiac tamponade and pericardial constriction, but there is uncertainty as to whether adjunctive immunomodulation with corticosteroids and Mycobacterium w (M. w) can safely reduce mortality and morbidity. OBJECTIVES: The primary objective of the IMPI Trial is to assess the effectiveness and safety of prednisolone and M. w immunotherapy in reducing the composite outcome of death, constriction, or cardiac tamponade requiring pericardial drainage in 1,400 patients with TB pericardial effusion. DESIGN: The IMPI trial is a multicenter international randomized double-blind placebo-controlled 2 × 2 factorial study. Eligible patients are randomly assigned to receive oral prednisolone or placebo for 6 weeks and M. w injection or placebo for 3 months. Patients are followed up at weeks 2, 4, and 6 and months 3 and 6 during the intervention period and 6-monthly thereafter for up to 4 years. The primary outcome is the first occurrence of death, pericardial constriction, or cardiac tamponade requiring pericardiocentesis. The secondary outcome is safety of immunomodulatory treatment measured by effect on opportunistic infections (eg, herpes zoster) and malignancy (eg, Kaposi sarcoma) and impact on measures of immunosuppression and the incidence of immune reconstitution disease. CONCLUSIONS: IMPI is the largest trial yet conducted comparing adjunctive immunotherapy in pericarditis. Its results will define the role of adjunctive corticosteroids and M. w immunotherapy in patients with TB pericardial effusion.