Ntobeko Ntusi

Aetiology and risk factors of peripartum cardiomyopathy: A systematic review

BACKGROUND Peripartum cardiomyopathy (PPCM) is a disorder of unknown aetiology in which heart failure due to left ventricular dysfunction occurs between the last month of pregnancy and first five months post-partum. Theories abound concerning the specific cause and risk factors for PPCM, but none have been accepted universally. The primary objective of this review was to summarize the state of knowledge on the pathogenesis of PPCM, especially in light of recent studies. METHODS We searched MEDLINE (January 1966-September 2007), OVID, and reference lists of articles for studies containing information on the aetiology and risk factors for PPCM, and published in English. RESULTS The literature reveals a wealth of articles proposing various mechanisms for aetiology and risk factors of PPCM. There is conflicting evidence on the pathogenetic role of viral myocarditis, abnormal immune response to pregnancy, abnormal response to the haemodynamic stress of pregnancy, accelerated myocyte apoptosis, cytokine-induced inflammation, malnutrition, genetic factors, excessive prolactin production, abnormal hormonal function, increased adrenergic tone, and myocardial ischaemia. A number of factors are postulated to increase the risk of the development of PPCM. These include non-Caucasian ethnicity, advanced maternal age, multiparity, poor socioeconomic status, multiple pregnancy and prolonged tocolytic use. The authors call for a strict definition of PPCM that excludes known causes of heart failure, such as the pregnancy-induced hypertensive spectrum of disorders. CONCLUSION The aetiology and risk factors for PPCM are poorly defined. There is a need for large-scale multi-centre epidemiological studies and registries to delineate the aetiology and pathogenesis of PPCM.

Epidemiology of heart failure in sub-Saharan Africa

Heart failure has emerged as a dominant form of cardiovascular disease in Africa, and has great social and economic relevance owing to its high prevalence, mortality and impact on young, economically active individuals. The causes of heart failure in Africans remain largely nonischemic. Hypertension, cardiomyopathy, rheumatic heart disease, chronic lung disease and pericardial disease are the main contributors to the etiology of cardiac failure in sub-Saharan Africa, accounting for over 90% of cases. Hypertensive heart disease complications occur more frequently in Africans and the majority of affected patients are younger. Endemic cardiomyopathies include dilated cardiomyopathy, peripartum cardiomyopathy and endomyocardial fibrosis. Nonendemic cardiomyopathies apparently occur with the same frequency as in other parts of the world, and include hypertrophic cardiomyopathy and arrhythmogenic right ventricular dysplasia/cardiomyopathy. Coronary artery disease and its complications remain uncommon in Africa, but the situation is changing due to modifications in lifestyle, risk-prone behavior, diet, cultural attitudes and other consequences of rapid urbanization. As the prevalence of heart failure is expected to rise substantially in sub-Saharan Africa, the authors call for population-based studies and registries of the epidemiology of heart failure in Africans and the urgent study of interventions that will decrease morbidity and mortality from the causes of heart failure, with a focus both on nonischemic and ischemic risk factors.

Guideline for the optimal use of blood cultures

The incidence of sepsis is increasing globally, with high morbidity and mortality. Prompt, accurate detection of bacteraemia and fungaemia is imperative for improving patient care, yet health care professionals lack training in correct blood culture techniques. These guidelines discuss the clinical importance of blood cultures, the indications for their use and the correct technique for optimal yield of pathogenic micro-organisms that cause sepsis.

Pregnancy-Associated Heart Failure: A Comparison of Clinical Presentation and Outcome between Hypertensive Heart Failure of Pregnancy and Idiopathic Peripartum Cardiomyopathy.

Aims There is controversy regarding the inclusion of patients with hypertension among cases of peripartum cardiomyopathy (PPCM), as the practice has contributed significantly to the discrepancy in reported characteristics of PPCM. We sought to determine whether hypertensive heart failure of pregnancy (HHFP) (i.e., peripartum cardiac failure associated with any form of hypertension) and PPCM have similar or different clinical features and outcome. Methods and Results We compared the time of onset of symptoms, clinical profile (including electrocardiographic [ECG] and echocardiographic features) and outcome of patients with HHFP (n = 53; age 29.6 ± 6.6 years) and PPCM (n = 30; age 31.5 ± 7.5 years). The onset of symptoms was postpartum in all PPCM patients, whereas it was antepartum in 85% of HHFP cases (p<0.001). PPCM was more significantly associated with the following features than HHFP (p<0.05): twin pregnancy, smoking, cardiomegaly with lower left ventricular ejection fraction on echocardiography, and longer QRS duration, QRS abnormalities, left atrial hypertrophy, left bundle branch block, T wave inversion and atrial fibrillation on ECG. By contrast, HHFP patients were significantly more likely (p<0.05) to have a family history of hypertension, hypertension and pre-eclampsia in a previous pregnancy, tachycardia at presentation on ECG, and left ventricular hypertrophy on echocardiography. Chronic heart failure, intra-cardiac thrombus and pulmonary hypertension were found significantly more commonly in PPCM than in HHFP (p<0.05). There were 5 deaths in the PPCM group compared to none among HHFP cases (p = 0.005) during follow-up. Conclusion There are significant differences in the time of onset of heart failure, clinical, ECG and echocardiographic features, and outcome of HHFP compared to PPCM, indicating that the presence of hypertension in pregnancy-associated heart failure may not fit the case definition of idiopathic PPCM.

Identification of Cadherin 2 ( cdh2 ) Mutations in Arrhythmogenic Right Ventricular Cardiomyopathy

Background— Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetically heterogeneous condition caused by mutations in genes encoding desmosomal proteins in up to 60% of cases. The 40% of genotype-negative cases point to the need of identifying novel genetic substrates by studying genotype-negative ARVC families. Methods and Results— Whole exome sequencing was performed on 2 cousins with ARVC. Validation of 13 heterozygous variants that survived internal quality and frequency filters was performed by Sanger sequencing. These variants were also genotyped in all family members to establish genotype–phenotype cosegregation. High-resolution melting analysis followed by Sanger sequencing was used to screen for mutations in cadherin 2 (CDH2) gene in unrelated genotype-negative patients with ARVC. In a 3-generation family, we identified by whole exome sequencing a novel mutation in CDH2 (c.686A>C, p.Gln229Pro) that cosegregated with ARVC in affected family members. The CDH2 c.686A>C variant was not present in >200 000 chromosomes available through public databases, which changes a conserved amino acid of cadherin 2 protein and is supported as the causal mutation by parametric linkage analysis. We subsequently screened 73 genotype-negative ARVC probands tested previously for mutations in known ARVC genes and found an additional likely pathogenic variant in CDH2 (c.1219G>A, p.Asp407Asn). CDH2 encodes cadherin 2 (also known as N-cadherin), a protein that plays a vital role in cell adhesion, making it a biologically plausible candidate gene in ARVC pathogenesis. Conclusions— These data implicate CDH2 mutations as novel genetic causes of ARVC and contribute to a more complete identification of disease genes involved in cardiomyopathy.

ICU-Associated Acinetobacter baumannii Colonisation/Infection in a High HIV-Prevalence Resource-Poor Setting

Background There are hardly any data about the incidence, risk factors and outcomes of ICU-associated A.baumannii colonisation/infection in HIV-infected and uninfected persons from resource-poor settings like Africa. Methods We reviewed the case records of patients with A.baumannii colonisation/infection admitted into the adult respiratory and surgical ICUs in Cape Town, South Africa, from January 1 to December 31 2008. In contrast to colonisation, infection was defined as isolation of A.baumannii from any biological site in conjunction with a compatible clinical picture warranting treatment with antibiotics effective against A.baumannii. Results The incidence of A.baumannii colonisation/infection in 268 patients was 15 per 100 person-years, with an in-ICU mortality of 26.5 per 100 person-years. The average length of stay in ICU was 15 days (range 1–150). A.baumannii was most commonly isolated from the respiratory tract followed by the bloodstream. Independent predictors of mortality included older age (p = 0.02), low CD4 count if HIV-infected (p = 0.038), surgical intervention (p = 0.047), co-morbid Gram-negative sepsis (p = 0.01), high APACHE-II score (p = 0.001), multi-organ dysfunction syndrome (p = 0.012), and a positive blood culture for A.baumannii (p = 0.017). Of 21 A.baumannii colonised/infected HIV-positive persons those with clinical AIDS (CD4<200 cells/mm3) had significantly higher in-ICU mortality and were more likely to have a positive blood culture. Conclusion In this resource-poor setting A.baumannii infection in critically ill patients is common and associated with high mortality. HIV co-infected patients with advanced immunosuppression are at higher risk of death.

Clinical characteristics and outcomes of familial and idiopathic dilated cardiomyopathy in Cape Town: A comparative study of 120 cases followed up over 14 years

BACKGROUND It is not known whether there are differences in clinical characteristics and outcomes of patients with familial and idiopathic dilated cardiomyopathy (DCM) in an African setting. PURPOSE To compare the clinical characteristics and outcomes of familial and idiopathic DCM. METHODS We performed a retrospective study of familial and idiopathic DCM at Groote Schuur Hospital, Cape Town, between 1 February 1996 and 31 December 2009. Clinical, electrocardiographic (ECG) and imaging characteristics were compared, in addition to treatment and survival. RESULTS Eighty patients with idiopathic DCM and 40 familial cases were studied. ECG T-wave inversion was significantly more frequent in familial DCM (87.5%) than in idiopathic cases (68.8%) (p=0.014), whereas idiopathic patients had a higher prevalence of pathological Q waves (32.5%) than familial cases (12.5%) (p=0.028). Cardiac chambers were significantly more dilated with poorer systolic function in idiopathic than familial cases. A mortality rate of 40% after a median follow-up of 5 years was, however, similar in both groups. The presence of New York Heart Association functional class III and IV symptoms was an independent predictor of mortality (odds ratio (OR) 3.85, 95% confidence interval (CI) 1.30 - 48.47, p<0.001), while heart transplantation was an independent predictor of survival (OR 4.72, 95% CI 1.31 - 72.60, p=0.026) in both groups. Digoxin use without serum monitoring was a significant predictor of mortality in idiopathic DCM (OR 1.62, 95% CI 1.04 - 3.98, p=0.037). CONCLUSION Patients with idiopathic DCM have greater cardiac dysfunction than those with familiar disease, but mortality is similarly high in both groups. Digoxin use without drug level monitoring may be associated with increased mortality in idiopathic DCM.

Frequency and clinical genetics of familial dilated cardiomyopathy in Cape Town: Implications for the evaluation of patients with unexplained cardiomyopathy

BACKGROUND Studies from Europe and North America suggest that 20 - 50% of patients with dilated cardiomyopathy (DCM) may have familial disease. There is little information on the frequency and clinical genetics of familial DCM in Africa. PURPOSE To determine the frequency and probable mode of inheritance of familial DCM in patients referred for investigation of the cause of DCM at a tertiary centre in Cape Town. METHODS We conducted a retrospective analysis of consecutive patients diagnosed with DCM between 1 February 1996 and 31 December 2009 to determine the frequency of familial disease. RESULTS Of 109 unrelated patients with DCM, 29 (26.6%) had familial disease. Their mean age of onset of cardiomyopathy (28.01 (standard deviation (SD) 15.33) years) was significantly younger than that for non-familial cases (39.1 (SD 12.6) years) (p=0.001). Male predominance (N=21, 72.4%) and racial distribution (15 (48.3%) coloured patients, 10 (34.5%) black Africans, 4 (13.8%) white individuals, and 1 (3.4%) of Indian descent) of familial DCM probands were similar to the non-familial cases. Of the 29 patients with familial DCM, 2 (7%) had at least one relative diagnosed with peripartum cardiomyopathy. Pedigree analysis of the 29 families was consistent with autosomal dominant inheritance in 72.4%, autosomal recessive inheritance in 17.2% and X-linked recessive inheritance in 10.4%. CONCLUSIONS Familial DCM affects at least a quarter of African patients with DCM, presents at a young age, is associated with peripartum cardiomyopathy, and follows an autosomal dominant pattern of inheritance in the majority of families. Family screening for familial DCM is indicated in all cases of unexplained DCM, including patients with peripartum cardiomyopathy.

Automated signal quality assessment of mobile phone-recorded heart sound signals

Abstract Mobile phones, due to their audio processing capabilities, have the potential to facilitate the diagnosis of heart disease through automated auscultation. However, such a platform is likely to be used by non-experts, and hence, it is essential that such a device is able to automatically differentiate poor quality from diagnostically useful recordings since non-experts are more likely to make poor-quality recordings. This paper investigates the automated signal quality assessment of heart sound recordings performed using both mobile phone-based and commercial medical-grade electronic stethoscopes. The recordings, each 60 s long, were taken from 151 random adult individuals with varying diagnoses referred to a cardiac clinic and were professionally annotated by five experts. A mean voting procedure was used to compute a final quality label for each recording. Nine signal quality indices were defined and calculated for each recording. A logistic regression model for classifying binary quality was then trained and tested. The inter-rater agreement level for the stethoscope and mobile phone recordings was measured using Conger’s kappa for multiclass sets and found to be 0.24 and 0.54, respectively. One-third of all the mobile phone-recorded phonocardiogram (PCG) signals were found to be of sufficient quality for analysis. The classifier was able to distinguish good- and poor-quality mobile phone recordings with 82.2% accuracy, and those made with the electronic stethoscope with an accuracy of 86.5%. We conclude that our classification approach provides a mechanism for substantially improving auscultation recordings by non-experts. This work is the first systematic evaluation of a PCG signal quality classification algorithm (using a separate test dataset) and assessment of the quality of PCG recordings captured by non-experts, using both a medical-grade digital stethoscope and a mobile phone.

Advancing global health and strengthening the HIV response in the era of the Sustainable Development Goals: the International AIDS Society—Lancet Commission

Author(s): Bekker, Linda-Gail; Alleyne, George; Baral, Stefan; Cepeda, Javier; Daskalakis, Demetre; Dowdy, David; Dybul, Mark; Eholie, Serge; Esom, Kene; Garnett, Geoff; Grimsrud, Anna; Hakim, James; Havlir, Diane; Isbell, Michael T; Johnson, Leigh; Kamarulzaman, Adeeba; Kasaie, Parastu; Kazatchkine, Michel; Kilonzo, Nduku; Klag, Michael; Klein, Marina; Lewin, Sharon R; Luo, Chewe; Makofane, Keletso; Martin, Natasha K; Mayer, Kenneth; Millett, Gregorio; Ntusi, Ntobeko; Pace, Loyce; Pike, Carey; Piot, Peter; Pozniak, Anton; Quinn, Thomas C; Rockstroh, Jurgen; Ratevosian, Jirair; Ryan, Owen; Sippel, Serra; Spire, Bruno; Soucat, Agnes; Starrs, Ann; Strathdee, Steffanie A; Thomson, Nicholas; Vella, Stefano; Schechter, Mauro; Vickerman, Peter; Weir, Brian; Beyrer, Chris