Dyslipidaemia in patients with chronic kidney disease - a neglected cardiovascular risk factor.

BACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) is a major cause of morbidity and mortality in patients with chronic kidney disease (CKD). In addition, CKD itself is a coronary artery disease equivalent due to its atherogenic potential. Despite the role of CKD in ASCVD and recommendations to control lipid levels aggressively, landmark lipid studies have often excluded patients with advanced CKD. Furthermore, there is a scarcity of data on the use and efficacy of lipid-lowering therapy (LLT) in those with CKD in South Africa (SA). OBJECTIVES: To determine the prevalence and control of dyslipidaemia in a cohort of SA patients with CKD. METHODS: A retrospective, cross-sectional observational study of 250 patients with CKD attending the Charlotte Maxeke Johannesburg Academic Hospital renal clinic from 1 July 2019 to 31 July 2020 was carried out. Lipograms, the use of LLT and achievement of target lipid levels were examined. RESULTS: The median (interquartile range) age of this cohort was 58 (46 - 69) years; 50.4% were males and 64.4% black African. Dyslipidaemia was prevalent in 83.6% (n=209) of patients. A total of 169 (67.6%) patients were on LLT, and of these only 28 (16.6%) achieved the recommended low-density lipoprotein cholesterol (LDL-C) target. Of those not on LLT, 51 (63%) were eligible for LLT and almost all were classified as either very high risk (64.2%) or high risk (28.4%) for ASCVD. Of those on LLT, all were on statin therapy, of which simvastatin at a mean dose of 20 mg daily was the most commonly prescribed LLT. CONCLUSION: This cohort comprised a large proportion of patients classified as high or very high risk for ASCVD. Despite this, the use of LLT was inadequate, and <20% of patients were at target LDL-C levels. These data suggest a greater need for awareness of initiating LLT to achieve recommended target LDL-C levels in patients with CKD.

Striking increase in the incidence of infective endocarditis associated with recreational drug abuse in urban South Africa.

BACKGROUND: We have recently noted a dramatic rise in the number of patients with infective endocarditis (IE) related to intravenous (IV) nyaope (a mixture of heroin, cocaine and antiretroviral drugs) presenting to Chris Hani Baragwanath Academic Hospital in Johannesburg, South Africa. OBJECTIVES: To document the clinical and echocardiographic characteristics of these patients. METHODS: Clinical and echocardiographic characteristics of all patients (N=68) with IE due to IV nyaope use were retrospectively extracted from hospital records (December 2014 - February 2017). RESULTS: The mean (standard deviation) age of the patients was 25.8 (4.5) years (97.1% were male). Withdrawal symptoms were noted in 25.1% of cases, fever in 58.8%, dyspnoea in 86.7% and right ventricular failure in 42.6%. Most patients were HIV-positive (76.1%), with CD4+ cell counts of <200 cells/µL in 8.8% of the total, 58.1% had hepatitis C infection, and only three were on antiretrovirals. Septic pulmonary emboli were noted in 61.8%. Blood cultures revealed Staphylococcus aureus in 61.2%, Enterococcus faecalis in 8.8% and Pseudomonas aeruginosa in 1 patient; 29.2% had sterile cultures and 8.8% polymicrobial infection. Severe right ventricular systolic dysfunction (RVS' Doppler velocity <10 cm/s) and pulmonary hypertension were noted in 19.1% and 62.2% of patients, respectively. Pericardial effusion was noted in 37.8%. The most commonly involved valve was the tricuspid (60.1%), followed by the mitral (17.2%), aortic (2.9%) and pulmonary (1 patient) valves. Combined valve lesions were noted in 19.1% of patients. Ten patients (14.7%) died. The main predictor of in-hospital mortality was S. aureus infection (odds ratio 5.0; p=0.042). CONCLUSIONS: We have documented the common clinical and echocardiographic characteristics of patients with IE secondary to IV nyaope use. IE due to IV drug use is responsible for considerable morbidity and mortality in a predominantly young male population.

Management of pulmonary hypertension.

Pulmonary arterial hypertension (PAH) is a potentially lethal disease mainly affecting young females. Although the precise mechanism of PAH is unknown, the past decade has seen the advent of many new classes of drugs with improvement in the overall prognosis of the disease. Unfortunately the therapeutic options for PAH in South Africa are severely limited. The Working Group on PAH is a joint effort by the South African Heart Association and the South African Thoracic Society tasked with improving the recognition and management of patients with PAH. This article provides a brief summary of the disease and the recommendations of the first meeting of the Working Group.

Tricuspid valve endocarditis associated with intravenous nyoape use: a report of 3 cases.

We report three cases of tricuspid valve infective endocarditis associated with intravenous nyoape use. Nyoape is a variable drug combination of an antiretroviral (efavirenz or ritonavir), heroin, metamphetamines and cannabis. Its use is becoming increasingly common among poor communities in South Africa. All our patients were young HIV-positive men from disadvantaged backgrounds. They all presented with tricuspid regurgitation and septic pulmonary emboli. They were treated with prolonged intravenous antibiotic courses, and one required referral for surgery.

Recommendations for the management of sickle cell disease in South Africa.

The spectrum of sickle cell disease (SCD) encompasses a heterogeneous group of disorders that include: (I) homozygous SCD (HbSS), also referred to as sickle cell anaemia; (ii) heterozygous SCD (HbAS), also referred to as sickle cell trait; and (iii) compound heterozygous states such as HbSC disease, HbSß thalassaemia, etc. Homozygous or compound heterozygous SCD patients manifest with clinical disease of varying severity that is influenced by biological and environmental factors, whereas subject with sickle cell trait are largely asymptomatic. SCD is characterized by vaso-occlusive episodes that result in tissue ischaemia and pain in the affected region. Repeated infarctive episodes cause organ damage and may eventually lead to organ failure. For effective management, regular follow-up with support from a multidisciplinary healthcare team is necessary. The chronic nature of the disease, the steady increase in patient numbers, and relapsing acute episodes have cost implications that are likely to impact on provincial and national health budgets. Limited resources mandate local management protocols for the purposes of consistency and standardisation, which could also facilitate sharing of resources between centres for maximal utility. These recommendations have been developed for the South African setting, and it is intended to update them regularly to meet new demands and challenges.

The thrombotic profile of treatment-naive HIV-positive Black South Africans with acute coronary syndromes.

BACKGROUND: Patients with human immunodeficiency virus (HIV) infection on protease inhibitors (PIs) have a heightened risk of arterial thrombosis but little is known about treatment-naive patients. METHODS/RESULTS: Prospective study from South Africa comparing thrombotic profiles of HIV-positive and -negative patients with acute coronary syndrome (ACS). A total of 30 treatment-naive HIV-positive patients with ACS were compared to 30 HIV-negative patients with ACS. Patients with HIV were younger; and besides smoking (73% vs 33%) and low high-density lipoprotein (HDL; 0.8 ± 0.3 vs 1.1 ± 0.4), they had fewer risk factors. Thrombophilia was more common in HIV-positive patients with lower protein C (PC; 82 ± 22 vs 108 ± 20) and higher factor VIII levels (201 ± 87 vs 136 ± 45). Patients with HIV had higher frequencies of anticardiolipin (aCL; 47% vs 10%) and antiprothrombin antibodies (87% vs 21%). CONCLUSION: Treatment-naive HIV-positive patients with ACS are younger, with fewer traditional risk factors but a greater degree of thrombophilia compared with HIV-negative patients.

Contemporary insights into the pathogenesis, diagnosis and therapy of pulmonary arterial hypertension.

Current data challenge the concept that pulmonary arterial hypertension (PAH) is purely a disorder of impaired vasomotor tone. Instead, we recognise today that the phenotype of PAH represents the complex and disordered regulation of expression of key signalling molecules and abnormal molecular trafficking. Discovery of mutations of the ubiquitous receptors of the transforming growth factor beta (TGF-ß) superfamily in many patients with PAH has been instrumental in unravelling the pathobiology of this otherwise fatal disorder. Much still needs to be learnt before we are able to substantially alter the natural history of PAH. Until such time, therapies that fundamentally attempt to restore vasomotor tone continue to be developed and tested. Current clinical research in the therapeutic arena is focused on defining the best permutation of the three major groups of drugs - prostacyclin analogues, phosphodiesterase type-five inhibitors and the endothelin receptor antagonists. However, if we are to make any significant impact on the otherwise dismal outcome of PAH, we have to recognise that even more important than the challenge of new therapies, is the challenge in diagnosing the condition early in the course of its relentless progression to right heart failure and eventual death.

Acute coronary syndromes in treatment-naïve black South africans with human immunodeficiency virus infection.

BACKGROUND: HIV patients on protease inhibitors have greater risk of acute coronary syndromes (ACS) but little is known about treatment-naïve patients. METHODS AND RESULTS: Authors conducted a prospective single-center study from Soweto, South Africa, comparing the clinical and angiographic features of treatment-naïve HIV positive and negative patients with ACS. Between March 2004 and February 2008, 30 consecutive treatment-naïve HIV patients with ACS were compared to the next HIV-negative patient as a 1:1 control. HIV patients were younger (43 +/- 7 vs. 54 +/- 13, P = 0.004) and, besides smoking (73% vs. 33%, P = 0.002), had fewer risk factors than the control group with less hypertension (23% vs. 77%, P = 0.0001), diabetes (3% vs. 23%, P = 0.05), LDL hyperlipidemia (2.2 +/- 0.9 vs. 3.0 +/- 1.2, P = 0.006), and other coronary risk factors (7% vs. 53%, P = 0.0001). HDL was lower in the HIV group (0.8 +/- 0.3 vs. 1.1 +/- 0.4, P = 0.001). Atherosclerotic burden was lower in the HIV group with more normal infarct-related arteries (47% vs. 13%, P = 0.005) but a higher degree of large thrombus burden (43% vs. 17%, P = 0.02). Stents were used to a similar degree in HIV and control patients (30% vs. 37%, P = 0.78) with more target lesion revascularization in the HIV group (56% vs. 0%, P = 0.008). CONCLUSION: Treatment-naïve HIV patients with ACS are younger and have fewer traditional risk factors than HIV-negative patients. HIV patients have less atherosclerotic but higher thrombotic burden which may imply a prothrombotic state in the pathogenesis of ACS in these patients.

Surgery for Infective Endocarditis

The last decade has seen many changes in the landscape of infective endocarditis (IE) - ranging from the epidemiology; microbiology; diagnostic techniques and indication for antibiotic prophylaxis. Unfortunately; the role of surgery in the patient with endocarditis; including the indication; timing and type of surgery continues to be plagued by controversy. Although surgery has an important and established role in critically ill patients with endocarditis; the choice between medical therapy and surgery is often less clear cut and poses a major challenge to the physician treating this condition. The following article summarises some of these controversies including indications for surgery in native and prosthetic valve endocarditis; the timing of surgery; the choice of prostheses and issues surrounding anti-coagulation

Coronary artery disease and risk factors in Black South Africans--a comparative study.

OBJECTIVE: The purpose of this study was to identify and compare coronary risk factors in different South African ethnic groups with angiographically documented significant coronary artery disease (CAD). DESIGN: An observational retrospective analysis. METHODS: Hospital records of 500 consecutive patients with no previous coronary interventions who underwent coronary angiography at Chris Hani Baragwanath Hospital, Soweto over a 2-year period were reviewed. Patients with significant CAD were selected for this study. Data analyzed included demographics, presenting diagnoses, coronary risk factors, number of coronary arteries significantly affected and extent of CAD, left ventricular ejection fraction (LVEF), and the main treatment modality for CAD. RESULTS: Of the 206 patients with significant CAD, 85 were Africans and 121 were non-Africans. There were significantly more females in the African group (31% vs 12%, P=.0023) and hypertension was more prevalent in the same group (78% vs 55%, P=.0006). Serum total (TC) and low-density lipoprotein (LDL) cholesterol were significantly lower in African than in non-African patients [189.5 (96.67-313.2) vs 228.2 (127.6-464) mg/dL; P=.0006 and 100.5 (34.8-282.3) vs 146.9 (42.54-313.2) mg/dL; P=.0001, respectively]. CONCLUSION: Cholesterol levels in this group of African patients with angiographically significant CAD are within the target range recommended by the adult treatment panel III (ATP III) guidelines of the National Cholesterol Education Program (NCEP). These data have implications for risk assessment using cholesterol and the role of cholesterol lowering treatment in populations of developing countries.

Preoperative left ventricular systolic dysfunction correlates with the adverse postoperative consequences of annular-papillary disconnection in the course of mitral valve replacement for stenosis.

BACKGROUND AND AIMS OF THE STUDY: Preservation of chordae tendineae helps maintain ventricular performance in patients having surgery for mitral regurgitation. The importance of chordal integrity in patients with rheumatic mitral stenosis is unknown. The purpose of this study was to determine the influence of chordal preservation on left ventricular function following relief of rheumatic mitral stenosis. METHODS: A total of 142 patients with mitral stenosis had balloon valvulotomy (group 1, n = 63), surgical commissurotomy (group 2, n = 33) or mitral valve replacement (group 3, n = 46). Chordae were resected in all group 3 patients. Left ventricular dimension in end-diastole (LVEDD), end-systole (LVESD) and fractional shortening (FS) were measured at baseline and at a mean interval of 11 +/- months post intervention. RESULTS: At one year, FS increased in groups 1 and 2, but decreased in group 3 (+11.5%, +9%, -6.1%, p < 0.005 for group 3 versus groups 1 and 2). a borderline significant increase LVEDD was seen in group 1 compared with groups 2 and 3 (11%, 5%, 4% respectively, p = 0.05). Differences in FS at follow up were due mainly to diametrically opposite changes in LVESD in the subgroup of patients with baseline left ventricular dysfunction (-1.9%, 0%, +9.8%, p < 0.005 for group 3 versus groups 1 and 2). CONCLUSIONS: Deterioration of left ventricular function only in patients having mitral valve replacement indicates chordal resection as a putative mechanism. The result of this study suggest that chordal preservation is particularly important in patients with mitral stenosis who have depressed preoperative left ventricular systolic function.

Anterior mitral leaflet retraction--a new echocardiographic predictor of severe mitral regurgitation following balloon valvuloplasty by the Inoue technique.

Echocardiographic quantification of the severity of anterior mitral leaflet retraction aids prediction of severe mitral regurgitation after balloon valvuloplasty.

Time-related changes in left ventricular function after double valve replacement for combined aortic and mitral regurgitation in a young rheumatic population. Predictors of postoperative left ventricular performance and role of chordal preservation.

BACKGROUND: The long-term effects of double valve replacement on left ventricular function in patients with combined severe rheumatic aortic and mitral regurgitation have not been reported previously. Furthermore, the importance of chordal preservation in this group of patients is unknown. METHODS AND RESULTS: Serial clinical and echocardiographic evaluations were performed prospectively in 44 patients who underwent double valve replacement for combined aortic and mitral regurgitation. Chordae to the posterior mitral leaflet were preserved in 27 patients. Mean follow-up was 40 +/- 19 months. Left ventricular end-diastolic diameter decreased significantly 3 months after surgery (from 66 +/- 10 to 52 +/- 11 mm; P < .001) without a substantial change in end-systolic diameter, resulting in a significant decline in ejection fraction (from 60 +/- 9% to 48 +/- 15%; P < .001). At 1 year, a significant reduction in end-systolic dimension was observed without a concomitant decline in end-diastolic diameter, thus normalizing the ejection fraction (55 +/- 12%; P = .17 versus baseline). No further changes were seen at latest follow-up. Multivariate regression analysis identified baseline end-systolic diameter and ejection fraction as independent predictors of postoperative systolic performance. Chordal preservation did not emerge as a univariate or multivariate predictor. CONCLUSIONS: After an initial postoperative decline in ejection fraction, normalization in left ventricular systolic function may be expected 1 year after double valve replacement for combined rheumatic mitral and aortic regurgitation. End-systolic diameter and ejection fraction are the only independent predictors of postoperative left ventricular performance.

Cyanosis and clubbing in a patient with iatrogenic Lutembacher syndrome.

A patient with rheumatic mitral and aortic stenosis is described in whom balloon dilatation of the mitral valve was complicated by an iatrogenic atrial septal defect with a small left to right shunt. Over the course of 4 years, the patient became progressively cyanosed and clubbed and was found to have reversed the shunt across the atrial septal defect due to the occurrence of severe tricuspid stenosis. The tricuspid valve was successfully dilated with re-establishment of a net left to right shunt. This syndrome, the first of its kind, should be appropriately termed the reversed Lutembacher syndrome.

Frequency of prosthetic valve-related complications with very low level warfarin anticoagulation combined with dipyridamole after valve replacement using St. Jude Medical prostheses.

The safety of a very low level of anticoagulation combined with dipyridamole in a rheumatic population (mean age 31 +/- 13 years) with the St. Jude Medical (SJM) prosthesis has not yet been tested. Furthermore, no data are available on the safety of relatively infrequent monitoring of anticoagulation levels and of the necessity for different therapeutic targets according to valve position, number of risk factors, and other baseline risk factors for thromboembolism. In this study, the performance of the SJM prosthesis was tested using a target international normalized ratio (INR) of 2.0 to 2.5 combined with dipyridamole 300 mg/day applied uniformly to all patients. Clinical, biochemical, and echocardiographic data were acquired prospectively in 200 consecutive patients at 3-month intervals. Follow-up (mean 27 +/- 13 months) was complete in 95% of patients. Thirteen patients died (2.9%/patient year). Severe left ventricular dysfunction was the cause of death in 10 of 13 patients. Probability of survival (Kaplan-Meier) was 0.92 at 36 months and of event-free survival 0.84 at 36 months. The median INR was 2.0 +/- 0.9. Valve obstruction did not occur, and there were 3 thromboembolic events (0.6%/patient year). Incidence of bleeding was 1.6%/patient year (n = 7) and was major (hemorrhagic stroke) in 1 (0.2%/patient year). Thus, the SJM prosthesis performs very well despite the use of very low level warfarin anticoagulation combined with dipyridamole. A 3-month assessment of the anticoagulation level is safe. Left ventricular dysfunction rather than valve-related complications is the leading cause of mortality in this population.