HIV-Associated pulmonary hypertension: case report

With the advent of highly active antiretroviral therapy, there has been a significant change in the epidemiology of pulmonary disease in HIV/AIDS. The relative prevalence of non-infectious manifestations is likely to rise. HIV associated pulmonary hypertension (HIV-PH), albeit low prevalence, is associated with significant morbidity and mortality. Presently, despite having scanty evidence on the management modalities of HIV-PH, evidence extrapolated from idiopathic pulmonary hypertension is being utilised to effectively manage some of these patients. Efforts should therefore be made to screen, diagnose and treat these patients. A case of a thirty year old female with HIV disease and severe pulmonary hypertension is presented

Novel multi-marker proteomics in phenotypically matched patients with ST-segment myocardial infarction:association with clinical outcomes

Early prediction of significant morbidity or mortality in patients with acute ST-segment elevation myocardial infarction (STEMI) represents an unmet clinical need. In phenotypically matched population of 139 STEMI patients (72 cases, 67 controls) treated with primary percutaneous coronary intervention, we explored associations between a 24-h relative change from baseline in the concentration of 91 novel biomarkers and the composite outcome of death, heart failure, or shock within 90 days. Additionally, we used random forest models to predict the 90-day outcomes. After adjustment for false discovery rate, the 90-day composite was significantly associated with concentration changes in 14 biomarkers involved in various pathophysiologic processes including: myocardial fibrosis/remodeling (collagen alpha-1, cathepsin Z, metalloproteinase inhibitor 4, protein tyrosine phosphatase subunits), inflammation, angiogenesis and signaling (interleukin 1 and 2 subunits, growth differentiation factor 15, galectin 4, trefoil factor 3), bone/mineral metabolism (osteoprotegerin, matrix extracellular phosphoglycoprotein and tartrate-resistant acid phosphatase), thrombosis (tissue factor pathway inhibitor) and cholesterol metabolism (LDL-receptor). Random forest models suggested an independent association when inflammatory markers are included in models predicting the outcomes within 90 days. Substantial heterogeneity is apparent in the early proteomic responses among patients with acutely reperfused STEMI patients who develop death, heart failure or shock within 90 days. These findings suggest the need to consider synergistic multi-biomarker strategies for risk stratification and to inform future development of novel post-myocardial infarction therapies

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

The influence of antiretroviral therapy on QTc interval amongst HIV patients at Aga Khan University Hospital, Nairobi

Aim: To determine the influence of antiretroviral (ARV) therapy on the QTC interval amongst HIV-infected patients. Design: Prospective Comparative survey of two population samples Patients and Setting: One hundred and thirty ARV naïve and one hundred and thirty treated HIV-positive patients selected from in and out patient departments of Aga Khan University Hospital underwent clinical evaluation and 12 lead resting ECG between August 2008 and March 2009. Methodology: Eligible HIV-positive patients were conveniently sampled and had a 12-lead electrocardiogram (ECG) performed to determine the QTinterval, corrected for the heart rate by the Bazzet formula. Analysis was then performed to determine the odds of development of a prolonged QTC interval (QTC ≥ 440ms) in the ARV-experienced arm compared to the ARV-naïve arm. Results: One hundred and thirty patients in each of the two study arms’ had ECG assessment of the QTC interval. 16.2% of the patients in the ARV-experienced arm had QTC prolongation compared to 6.9% in the ARV-naïve arm (chi square 5.43, p= 0.01) giving rise to an odds ratio of 2.5 (95% CI 1.01-6.67). Conclusion: ARV use significantly increases the risk of development of an acquired long QTC syndrome by two-and-a-half times

A prospective review of acute coronary syndromes in an urban hospital in sub-Saharan Africa

Objectives: To determine the epidemiology of acute coronary syndromes (ACS) in sub-Saharan Africa. Methods: A prospective survey was carried out of all patients with a diagnosis of ACS who were admitted to the critical care unit of a tertiary teaching hospital over a 25-month period. Demographics, presentation, management and outcomes were subsequently recorded. Results: A total of 111 (5.1% of all hospitalisations) patients were recruited, with 56% presenting with ST-elevation myocardial infarction (STEMI) and the rest non-ST-elevation myocardial infarction (NSTEMI) or unstable angina (UA). Chest pain was the most common presenting symptom, and up to one-third of all STEMI patients did not receive any form of reperfusion therapy, primarily due to late presentation. As in the developed world, diabetes, hypertension and cigarette smoking still account for the most common predisposing risk-factor profile, and the mortality associated with ACS is about six to 10% in our unit. Conclusions: ACS, contrary to common belief, is increasingly more prevalent in sub-Saharan Africa, with similar risk profiles to that in the developed world. Late presentation to hospital is common and accounts for the increased mortality associated with this condition

Disseminated cryptococcosis, an unusual cause of gross proteinuria in an HIV-infected patient

The laboratory diagnosis of renal tuberculosis is difficult, because identification of the organisms in the urine is hard and clinical and radiological presentations vary. However, ultrasound examination of the urinary tract reveals features of tuberculosis in over 50% of the cases [8]. A recent work published 152 cases of correctly diagnosed renal tuberculosis classified into six types. This classification takes the variability of the ultrasonographic appearance of renal tuberculosis into account, whereas nephrectasia, distension of renal pelvis and calyces, empyema or calcification were the most prominent visible signs [8]. In the case presented here, ultrasonographic findings and kidney biopsy results are primarily compatible with renal tuberculosis. Renal insufficiency accompanied by wasting should lead physicians to take tuberculosis into account

Clinical characteristics and outcomes of atrial fibrillation and flutter at the Aga Khan University Hospital, Nairobi

Introduction: Scant data exist on the epidemiology and clinical characteristics of atrial fibrillation in Kenya. Traditionally, atrial fibrillation (AF) in sub-Saharan Africa is as a result of rheumatic valve disease. However, with the economic transition in sub-Saharan Africa, risk factors and associated complications of this arrhythmia are likely to change. Methods: A retrospective observational survey was carried out between January 2008 and December 2010. Patients with a discharge diagnosis of either atrial fibrillation or flutter were included for analysis. The data-collection tool included clinical presentation, risk factors and management strategy. Follow-up data were obtained from the patients\u27 medical records six months after the index presentation. Results: One hundred and sixty-two patients were recruited (mean age 67 ± 17 years, males 56%). The distribution was paroxysmal (40%), persistent (20%) and permanent AF (40%). Associated co-morbidities included hypertension (68%), heart failure (38%) diabetes mellitus (33%) and valvular abnormalities (12%). One-third presented with palpitations, dizziness or syncope and 15% with a thromboembolic complication as the index AF presentation. Ratecontrol strategies were administered to 78% of the patients, with beta-blockers and digoxin more commonly prescribed. Seventy-seven per cent had a CHA2DS2VASC score ≥ 2, but one-quarter did not receive any form of oral anticoagulation. At the six-month follow up, 6% had died and 12% had been re-admitted at least once. Of the high-stroke risk patients on anticoagulation, just over one-half were adequately anticoagulated. Conclusion: Hypertension and diabetes mellitus, not rheumatic valve disease were the more common co-morbidities. Stroke risk stratification and prevention needs to be emphasised and appropriately managed

Catheter-induced postextrasystolic potentiation in the assessment of severity of low-gradient aortic valve stenosis

Background: Deciphering which patients with low-gradient aortic valve disease have severe stenosis can be difficult. We aimed to correlate the postextrasystolic potentiation (PESP) with dobutamine stress echocardiography and multidetector computed tomography in patients with low-gradient aortic valve stenosis. Methods: Patients with an aortic valve area ≤1 cm2 and a mean gradient <40 mm Hg were included. Aortic valve stenosis severity was assessed by a core lab with dobutamine stress echocardiography, followed by a multidetector computed tomography aortic valve score if indeterminate. A premature ventricular contraction was induced by intentional catheter contact with the myocardium within the left ventricle. PESP was calculated as a percent change of pre-to-post mean gradient. Multidetector computed tomography was used to measure the aortic valve calcification score, and subsequently, aortic valve calcification density. Results: Twenty-eight patients (age, 77±10 years; 19 female) were included. Dobutamine stress echocardiography increased mean gradient from baseline of 25±7 mm Hg to 36±11 mm Hg; pre-premature ventricular contraction mean gradient was 25±7 mm Hg and increased to post-premature ventricular contraction mean gradient of 32±10 mm Hg, representing a PESP of 24±11%. A ≥20% in PESP resulted in 100% sensitivity, 77% specificity, 83% positive predictive value, and 100% negative predictive value for diagnosing severe aortic valve stenosis. There was a significant correlation between PESP and projected aortic valve area and aortic valve calcification density (R=−0.64, P=0.0003; R=0.057, P=0.014, respectively). Conclusions: In patients with low-gradient aortic valve stenosis, catheter-induced premature ventricular contractions during cardiac catheterization causing ≥20% PESP has a 100% sensitivity for severe aortic valve stenosis. Validation of this 20% cutoff in larger groups with correlation to clinical end points is required