SA Heart consensus statement on closure of patent foramen ovale 2021.

A patent foramen ovale (PFO) is associated with numerous clinical conditions. The most severe of these is cryptogenic stroke. This consensus statement aims to provide a clinical guideline on which patients should be offered PFO closure.

2020 Heart Failure Society of South Africa perspective on the 2016 European Society of Cardiology Chronic Heart Failure Guidelines.

Heart failure with a reduced ejection fraction (HFrEF) is a condition frequently encountered by healthcare professionals and, in order to achieve the best outcomes for patients, needs to be managed optimally. This guideline document is based on the European Society of Cardiology Guidelines for the treatment of acute and chronic heart failure published in 2016, and summarises what is considered the best current management of patients with the condition. It provides information on the definition, diagnosis and epidemiology of HFrEF in the African context. The best evidence-based treatments for HFrEF are discussed, including established therapies (beta-blockers, ACE-i/ARBs, mineralocorticoid receptor antagonists (MRAs), diuretics) that form the cornerstone of heart failure management as well as therapies that have only recently entered clinical use (angiotensin receptor-neprilysin inhibitor (ARNI), sodium/glucose cotransporter-2 (SGLT2) inhibitors). Guidance is offered in terms of more invasive therapies (revascularisation, implantable cardioverter defibrillators (ICDs) and cardiac resynchronisation therapy (CRT) by implantation of a biventricular pacemaker with (CRT-D) or without (CRT-P) an ICD, left ventricular assist device (LVAD) use and heart transplantation) in order to ensure efficient use of these expensive treatment modalities in a resource-limited environment. Furthermore, additional therapies (digoxin, hydralazine and nitrates, ivabradine, iron supplementation) are discussed and advice is provided on general preventive strategies (vaccinations). Sections to discuss conditions that are particularly prevalent in sub-Saharan Africa (HIV-associated cardiomyopathy (CMO), peripartum CMO, rheumatic heart disease, atrial fibrillation) have been added to further improve clinical care for these commonly encountered disease processes. You are encouraged to read the complete 2016 ESC Heart Failure guideline: Ponikowski P, Voors AA, Anker SD, et al.; on behalf of the European Society of Cardiology. 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2016,37:2129-2200.

Beta-blocker target dosing and tolerability in a dedicated heart failure clinic in Johannesburg.

BACKGROUND: Despite the significant clinical benefits of beta-blockers in heart failure with reduced ejection fraction (HFrEF), prescription for and adherence to these agents is reported to be poor. There are few data on the use and tolerance of beta-blocker therapy in patients with HFrEF in South Africa and it is unknown whether these patients would benefit from further heart rate-lowering therapy. METHODS: Data from all patients with HFrEF attending the heart failure clinic of Charlotte Maxeke Johannesburg Academic Hospital from January 2000 to December 2014 were retrospectively collected. We first determined the rates of beta-blocker intolerance in this population and then categorised the patients according to their most recent dose of beta-blocker (low, moderate or target dose) in order to identify factors associated with beta-blocker intolerance. Lastly, we used the data to identify patients who would be suitable for further treatment with heart rate-lowering therapy. RESULTS: Five hundred patients, with a median follow up of 58.7 months, were identified during the study period. Black South Africans constituted the majority (66.4%) and most patients had HFrEF due to hypertension (32.8%). At the last recorded clinic visit at the end of the study period, 489 patients (97.8%) were taking a beta-blocker with 59.8% prescribed a beta-blocker at target dose. Consistent with previous data, bradycardia was the commonest cause for failing to reach target beta-blocker dose. Only 61 (12%) patients were on no (n = 11) or low (n = 50) dose of beta-blocker at final clinic visit. As per current guidelines, only 10.6% (n = 53) of this cohort of patients would qualify for further treatment with heart rate-lowering therapy. CONCLUSIONS: In a dedicated heart failure clinic in South Africa, beta-blockers were well-tolerated in the treatment of HFrEF. The potential role of specific heart rate-lowering therapy in patients treated adequately with heart failure medication and proper up-titration of beta-blockers is relatively small.

South African dyslipidaemia guideline consensus statement: 2018 update A joint statement from the South African Heart Association (SA Heart) and the Lipid and Atherosclerosis Society of Southern Africa (LASSA).

South Africa (SA) is home to a heterogeneous population with a wide range of cardiovascular risk factors. Cholesterol reduction in combination with aggressive management of modifiable risk factors, including nutrition, physical activity, blood pressure and smoking, can help to reduce and prevent morbidity and mortality in individuals who are at increased risk of cardiovascular events. This updated consensus guide to management of dyslipidaemia in SA is based on the updated European Society of Cardiology and European Atherosclerosis Society dyslipidaemia guidelines published in 2016. For individuals who are not considered to be at high or very high cardiovascular risk, the decision whether to treat and which interventional strategy to use is based on a cardiovascular risk score calculated using total cholesterol, high-density lipoprotein cholesterol (HDL-C), gender, age and smoking status. The cardiovascular risk score refers to the 10-year risk of any cardiovascular event and includes 4 categories of risk (low, moderate, high and very high). People with established cardiovascular disease, diabetes mellitus, chronic kidney disease and genetic or severe dyslipidaemias are considered to already be at high or very high risk and do not require risk scoring. Therapeutic lifestyle change is the mainstay of management for all patients. The need for and intensity of drug therapy is determined according to baseline low-density lipoprotein (LDL-C) levels and the target LDL-C concentration appropriate to the individual. LDL-C treatment targets are based on pre-treatment risk and are as follows: <3 mmol/L in low- and moderate risk cases; <2.5 mmol/L and a reduction of at least 50% if the baseline concentration is 2.5 - 5.2 mmol/L in high-risk cases; and <1.8 mmol/L and a reduction of at least 50% if the baseline concentration is 1.8 - 3.5 mmol/L in very high-risk cases. A statin is usually recommended first-line; the specific agent is based on the required degree of cholesterol reduction, comorbidities and co-prescribed medication. Special attention should be paid to children with a family history of genetic or severe dyslipidaemia, who should be screened for dyslipidaemia from 8 years of age. In SA, HIV infection is not considered to be a significant cardiovascular risk factor and treatment recommendations for HIV-positive individuals are the same as for the general population, with careful choice of pharmacotherapy to avoid potential adverse drug-drug interactions. The benefit of statins in individuals older than 70 years is uncertain and clinical judgement should be used to guide treatment decisions and to avoid side-effects and overmedication in this group.

Effects of an anabolic steroid (Durateston) on testicular angiogenesis in peripubertal stallions.

The aim of this study was to determine the effect of the anabolic steroid testosterone on the testicular vascularization, angiogenesis and expression of angiogenic factors, and their receptors in testes of peripubertal stallions. Seven peripubertal stallions were treated with Durateston and castrated either 4 (treatment group 1 [TG1]) or 12 weeks (TG2) after the last injection. The castration of seven untreated control stallions (control group [CG]) took place within the same time. In the testicular specimens, volume density (VD), numerical density (ND), and area of vessels were determined morphometrically. Immunohistochemically, the expression of vascular endothelial growth factor (VEGF) and its receptor VEGF-R2; angiopoietin 2 (Ang2) and its receptor Tie2 as well as of transforming growth factor α (TGF-α) was investigated. Morphometrically, the VD of TG1 (P = 0.000) and TG2 (P = 0.001) vessels and the ND of arterioles and venules and capillaries were higher (TG1, TG2: P < 0.05), and the area of capillary cross sections was smaller (TG1, TG2: P < 0.05) than that in the CG. Compared to TG2 horses, TG1 animals showed a higher (P < 0.05) VD and ND of vascular structures and a smaller (P < 0.05) area of capillary cross sections. In numerous vascular structures, especially of TG1, the TGF-α and, to a less extent, the Ang2 and VEGF-R2 expression was significantly higher (P < 0.05) than that in the CG. Sertoli cells in TG2 were characterized by a significantly higher expression (P < 0.05) of VEGF-R2 than in the CG. In summary, the most and smallest vessels could be detected in the testes of TG1. Most likely this is explainable by the highest expression of some angiogenic factors (TGF-α, Ang2) and receptors (VEGF-R2) investigated. This expression behavior may be stimulated by testosterone. As a significant decrease of morphometric parameters could be detected in TG2 compared to TG1, the stimulatory effect of testosterone seems to be temporary.

First trimester markers of preeclampsia in twins: maternal mean arterial pressure and uterine artery Doppler pulsatility index.

OBJECTIVE: This study aims to evaluate the distribution of mean arterial pressure (MAP) and uterine artery Doppler pulsatility index (PI) in first trimester twins with and without preeclampsia. METHOD: A total of 147 twins were recruited from a specialist clinic and 110 unaffected singleton pregnancies attending the same institution served as controls. MAP and Doppler PI values were expressed in multiples of the gestation-specific median using published equations. RESULTS: Among the twins, 12 had preeclampsia and two had pregnancy-induced hypertension. Among unaffected pregnancies, there was no significant difference in MAP levels between twins and singletons (P = 0.17, Wilcoxon rank sum test, two-tail). However, the Doppler PI levels were highly statistically significantly lower than in singletons (P < 0.0005). MAP was unrelated to chorionicity (P = 0.46), but there was a statistically significant increase in Doppler PI among monochorionic compared with dichorionic twins (P < 0.01). In twins with preeclampsia, MAP was significantly higher than in unaffected twins (P < 0.02, one-tail), whereas Doppler PI levels were significantly reduced (P < 0.01, two-tail). CONCLUSION: If first trimester screening for preeclampsia is extended to twins, a different normal median Doppler PI equation will be needed. Contrary to expectations, Doppler PI levels may not be raised in affected twins, although this needs confirmation in a larger study.

Heart Failure Society of South Africa (HeFSSA) perspective on the European Society of Cardiology (ESC) 2012 chronic heart failure guideline.

BACKGROUND: The South African Heart Association (SA Heart) is an affiliate of the European Society of Cardiology (ESC). SA Heart endorses ESC treatment guidelines with modification to suit local circumstances. The Heart Failure Society of South Africa (HeFSSA) is a special interest group of SA Heart. This guideline has been compiled on behalf of the HeFSSA and is based on the ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012. The focus is on heart failure with reduced ejection fraction (HF-REF) (i.e. ejection fraction <50%). We have recommended interventions in symptomatic patients with HF-REF in general to clarify the 'grey area' between the ESC guidelines definition of REF (<50%) and the predefined ejection fraction used in randomised heart failure trials (<35%). OBJECTIVE: To highlight new changes in the diagnosis and treatment of chronic heart failure with particular emphasis on areas that are relevant to SA. CONCLUSIONS: Randomised clinical trials are a crucial, but not the only, guide in treating HF-REF patients. There always remain questions that are unanswered and groups of patients not studied, so prudent clinical decisions are required.

The EndoPredict score provides prognostic information on late distant metastases in ER+/HER2- breast cancer patients.

BACKGROUND: ER+/HER2- breast cancers have a proclivity for late recurrence. A personalised estimate of relapse risk after 5 years of endocrine treatment can improve patient selection for extended hormonal therapy. METHODS: A total of 1702 postmenopausal ER+/HER2- breast cancer patients from two adjuvant phase III trials (ABCSG6, ABCSG8) treated with 5 years of endocrine therapy participated in this study. The multigene test EndoPredict (EP) and the EPclin score (which combines EP with tumour size and nodal status) were predefined in independent training cohorts. All patients were retrospectively assigned to risk categories based on gene expression and on clinical parameters. The primary end point was distant metastasis (DM). Kaplan-Meier method and Cox regression analysis were used in an early (0-5 years) and late time interval (>5 years post diagnosis). RESULTS: EP is a significant, independent, prognostic parameter in the early and late time interval. The expression levels of proliferative and ER signalling genes contribute differentially to the underlying biology of early and late DM. The EPclin stratified 64% of patients at risk after 5 years into a low-risk subgroup with an absolute 1.8% of late DM at 10 years of follow-up. CONCLUSION: The EP test provides additional prognostic information for the identification of early and late DM beyond what can be achieved by combining the commonly used clinical parameters. The EPclin reliably identified a subgroup of patients who have an excellent long-term prognosis after 5 years of endocrine therapy. The side effects of extended therapy should be weighed against this projected outcome.

EndoPredict improves the prognostic classification derived from common clinical guidelines in ER-positive, HER2-negative early breast cancer.

BACKGROUND: In early estrogen receptor (ER)-positive/HER2-negative breast cancer, the decision to administer chemotherapy is largely based on prognostic criteria. The combined molecular/clinical EndoPredict test (EPclin) has been validated to accurately assess prognosis in this population. In this study, the clinical relevance of EPclin in relation to well-established clinical guidelines is assessed. PATIENTS AND METHODS: We assigned risk groups to 1702 ER-positive/HER2-negative postmenopausal women from two large phase III trials treated only with endocrine therapy. Prognosis was assigned according to National Comprehensive Cancer Center Network-, German S3-, St Gallen guidelines and the EPclin. Prognostic groups were compared using the Kaplan-Meier survival analysis. RESULTS: After 10 years, absolute risk reductions (ARR) between the high- and low-risk groups ranged from 6.9% to 11.2% if assigned according to guidelines. It was at 18.7% for EPclin. EPclin reassigned 58%-61% of women classified as high-/intermediate-risk (according to clinical guidelines) to low risk. Women reclassified to low risk showed a 5% rate of distant metastasis at 10 years. CONCLUSION: The EPclin score is able to predict favorable prognosis in a majority of patients that clinical guidelines would assign to intermediate or high risk. EPclin may reduce the indications for chemotherapy in ER-positive postmenopausal women with a limited number of clinical risk factors.

Cultural differences in child delivery: comparisons between Jewish and Arab women in Israel.

OBJECTIVE: To compare Jewish and Arab women characteristics regarding pregnancy follow-up, compliance to a health regime and behavioural expressions during labour, delivery and the post-partum period. DESIGN: The participants answered a 45-item questionnaire designed for the current research. SETTING: The first three post-partum days in the delivery ward at one of the biggest hospitals in Israel. PARTICIPANTS: A total of 126 Jewish and Arab-Muslim parturients. RESULTS: Significant differences were found (P < 0.01) concerning pregnancy follow-up attendance and participation in a prenatal course, which were lower among Arab women. Several differences were found regarding delivery room attendance, type and number of companions, and behavioural expressions of pain, which were demonstrated more among Arab women. Epidural anaesthesia was highly prevalent among Jewish women, in comparison with the Arab women. While all Arab women decided to breastfeed their babies, only 71% of Jewish women expressed a wish to breastfeed. No significant differences were found between weight gains during pregnancy, reasons for delivery room attendance, number of pregnancy weeks prior to delivery and newborn weight. CONCLUSIONS: Cultural differences exist between Jewish and Arab women attending delivery rooms in Israel. Understanding these cultural differences may assist caregivers in providing culturally sensitive treatment that is suited to the parturients' needs.

[Evaluation of immunoglobulin G concentration in colostrum of mares by ELISA, refractometry and colostrometry]. / Postpartale Immunglobulin-G-Konzentrationen im equinen Kolostrum mittels ELISA-Methode, Kolostrometrie und Refraktometrie.

In 360 samples of colostrum and 36 samples of blood of warmblood mares, the concentration of immunoglobulin G (IgG) was evaluated in the post partal period with an ELISA and the results were compared to values obtained with 2 field methods--refractometry and colostrometry. A significant correlation (p < 0.0001) was determined between ELISA and colostrometry (r = +0.88) and between ELISA and refractometry (r = +0.93). So both field-methods seem suitable for evaluation of the colostral IgG-concentration in mares. Further the kinetic of the IgG concentration in colostrum, the volume of colostrum and the total amount of IgG was measured in the 12 hours post partum (p.p.) in each half udder of 36 mares of different parity. Immediately p.p. primiparous mares have a greater mean concentration of IgG (68 mg/ml) than multiparous mares (51 mg/ml). However, multiparous mares have a mean colostral volume of 1020 ml whereas, in primiparous mares, a mean volume of 527 ml was determined within the first three hours p.p. As a result of this the total amount of IgG was lower in primiparous (31.5 g) than in multiparous mares (48.5 g). A significant decrease of IgG concentration was measured in multiparous mares in the 1.5 hours following partum versus 3 hours in primiparous mares. The mean IgG concentration in the blood serum of the 36 mares immediately p.p. was 13.4 +/- 3.6 mg/ml. No significant correlation was observed between values of IgG concentration in the blood and in the colostrum of the mares.

Histomorphological and immunohistochemical characterization of equine granulosa cell tumours.

Benign (n=33) and malignant metastasizing (n=1) granulosa cell tumours (GCTs) from 34 mares aged 3-21 years, and normal (control) ovaries from nine mares aged 3-10 years, were examined histologically and immunohistochemically (for inhibin alpha, glutathione S-transferase alpha [GSTalpha], c-erbB-2 oncoprotein [cerb], cytokeratin, vimentin, desmin and alpha-actin), the results being related where appropriate to clinical signs and endocrinological data. Availability permitting, serum samples from GCT-affected mares before and several weeks after ovariectomy were examined for the following hormones: oestradiol, progesterone and testosterone (by radioimmunoassay); and inhibin B (by a cross-reactive ELISA). Histological examination revealed that the GCTs were predominantly well differentiated neoplasms. The metastasizing GCT differed immunohistochemically from the benign GCTs in respect of the expression patterns of vimentin, cerb and GSTalpha in the granulosa cells. A notable feature was the presence of Leydig-like cells in mares with stallion-like behaviour or elevated serum testosterone, or both. GSTalpha immunolabelling indicated that the Leydig-like cells were potential producers of steroid hormone. From the immunohistochemical and endocrinological findings it was concluded that GCTs produce abnormally high concentrations of inhibin, which reduce the release of follicle-stimulating hormone, leading to atrophy of the contralateral ovary-a finding in 27 of the mares.