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.

Diagnostic performance of dobutamine stress echocardiography: A South African experience.

BACKGROUND: Dobutamine stress echocardiography (DSE) is a well-established modality for the diagnosis of coronary artery disease, but there are no reported diagnostic data in southern Africa. Objectives. To compare the safety, sensitivity and specificity of a South African (SA) DSE programme with larger, international series. Methods. All patients undergoing DSE from 2019 to 2021 at a single SA centre were included. A new wall motion abnormality (≥2 segments) signified inducible ischaemia. Results. A total of 106 patients (mean (standard deviation) age 61 (11) years, 68% male) were analysed. Six patients (6%) experienced chest pain during DSE and 4 (4%) developed an atrial arrhythmia. The sensitivity and specificity for epicardial coronary stenosis were 77% and 74%, respectively, changing to 82% and 72% when excluding those who had previous coronary artery bypass surgery. Conclusion. The sensitivity, specificity and safety of an SA DSE programme were comparable to international series. A DSE programme is feasible in a resource-constrained environment.

Percutaneous left atrial appendage occlusion: A South African experience.

BACKGROUND: Atrial fibrillation (AF) is associated with all-cause mortality, heart failure and non-fatal stroke, and thromboprophylaxis is traditionally provided with oral anticoagulants (OACs). Percutaneous left atrial appendage occlusion (LAAO) with a dedicated device is an alternative approach to thromboprophylaxis in patients with AF who are: (i) intolerant to OACs (e.g. life-threatening haemorrhage); (ii) non-adherent to OACs; or (iii) at a high bleeding risk with OACs. Non-inferiority of LAAO compared with OACs was demonstrated in e.g. the WATCHMAN Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation (PROTECT AF) trial. Only very limited data are available on percutaneous LAAO in South Africa (SA), and no local outcome data have been reported. OBJECTIVES: To compare the safety and efficacy outcomes of an SA percutaneous LAAO programme with larger international series. METHODS: All patients undergoing percutaneous LAAO from 2013 to 2020 at a single centre (SAEndovascular, Kuils River Netcare Hospital, SA) were included from an ongoing registry. Survival analysis was performed with the Kaplan-Meier method. RESULTS: Of 101 LAAO recipients (mean (standard deviation) age 77 (10) years, 64% male) analysed, 90 (90%) had permanent AF, 1 (1%) persistent AF and 9 (9%) paroxysmal AF. The most common indication for LAAO was previous severe bleeding (n=23; 23%). The mean device size was 23 (3) mm and the procedural success rate was 98%. After a median (interquartile range) follow-up of 21 (5 - 41) months, 6 patients (6%) experienced stroke or all-cause mortality. Four patients (4%) had a life-threatening procedural complication (tamponade n=2 (2%) and device embolisation n=2 (2%)). These outcomes are comparable to large international series, e.g. PROTECT AF. CONCLUSIONS: The safety and efficacy outcomes of an SA percutaneous LAAO programme were comparable to large international series. A successful percutaneous LAAO programme is feasible in a southern African context.

Renal function in patients with significant tricuspid regurgitation: pathophysiological mechanisms and prognostic implications.

BACKGROUND: The pathophysiological mechanisms linking tricuspid regurgitation (TR) and chronic kidney disease (CKD) remain unknown. This study aimed to determine which pathophysiological mechanisms related to TR are independently associated with renal dysfunction and to evaluate the impact of renal impairment on long-term prognosis in patients with significant (≥ moderate) secondary TR. METHODS: A total of 1234 individuals (72 [IQR 63-78] years, 50% male) with significant secondary TR were followed up for the occurrence of all-cause mortality and the presence of significant renal impairment (eGFR of <60 mL min-1  1.73 m-2 ) at the time of baseline echocardiography. RESULTS: Multivariable analysis demonstrated that severe right ventricular (RV) dysfunction (TAPSE < 14 mm) was independently associated with the presence of significant renal impairment (OR 1.49, 95% CI 1.11 to 1.99, P = 0.008). Worse renal function was associated with a significant reduction in survival at 1 and 5 years (85% vs. 87% vs. 68% vs. 58% at 1 year, and 72% vs. 64% vs. 39% vs. 19% at 5 years, for stage 1, 2, 3 and 4-5 CKD groups, respectively, P < 0.001). The presence of severe RV dysfunction was associated with reduced overall survival in stage 1-3 CKD groups, but not in stage 4-5 CKD groups. CONCLUSIONS: Of the pathophysiological mechanisms identified by echocardiography that are associated with significant secondary TR, only severe RV dysfunction was independently associated with the presence of significant renal impairment. In addition, worse renal function according to CKD group was associated with a significant reduction in survival.

The potential beneficial role of isoflavones in type 2 diabetes mellitus.

Diabetes is a chronic global disease afflicting a substantial number of people worldwide. Different mechanisms have been highlighted in the progression of this disease such as dysfunction of pancreatic ß-cells, insulin resistance, elevated levels of free fatty acids which result in overproduction of reactive oxygen species, as well as pancreatic ß-cell failure and apoptosis. Isoflavones, are polyphenolic phytochemicals found in most leguminous plants, and have been identified as potentially useful antidiabetic agents. The pleiotropic effects of isoflavones include the targeting of numerous cell signaling pathways involved in the pathogenesis of diabetes. Several observational studies have supported the direct relationship between isoflavones intake and a lowered risk of diabetes. The aim of this review was to summarize relevant findings on the effects of isoflavone intake and risk of type II diabetes mellitus (T2DM), and to highlight some of the possible anti-diabetic molecular mechanisms of these polyphenols. Despite the promising therapeutic effects of isoflavones to moderate risk of T2DM, the underlying mechanisms for their preventive effects are still largely unknown. The acceptable human dosage levels of these polyphenols remain a debatable topic as these have a profound influence on the observed benefits. Considerable numbers of well-controlled, long-term human clinical studies of these phytochemicals are highly recommended. Furthermore, combinations of isoflavones and their derivatives in combination with other naturally isolated compounds, and perhaps even those drugs currently used therapeutically to control diabetes mellitus in clinical practice, may be worth exploring in the future.

Dietary supplements containing prohibited substances.

Dietary supplement use among athletes to enhance performance is proliferating as more individuals strive for obtaining that chemical competitive edge. As a result the concomitant use of dietary supplements containing performance-enhancing substances of those falling in the categories outlined in the current review, can also be expected to rise. This despite ever-increasing sophisticated analytical methodology techniques being used to assay dietary supplement and urine samples in doping laboratories. The reasons for this include that a variety of these chemical entities, many of them on the prohibited drug list of the WADA, are being produced on commercial scales in factories around the world (ephedrine and pseudoephedrine, sibutramine, methylhexaneamine, prohormones, 'classic' anabolic steroids, clenbuterol, peptide hormones etc.), aggressive marketing strategies are being employed by companies and these supplements can be easily ordered via e.g. the internet. It can also be anticipated that there will be an increase in the number of supplements containing 'designer' steroids and other 'newer' molecules. Chromatographic techniques combined with mass spectrometry leading to identification of molecular fragments and productions will assist in determining these substances. To prevent accidental doping, information regarding dietary supplements must be provided to athletes, coaches and sports doctors at all levels of competition. The risks of accidental doping via dietary supplement ingestion can be minimized by using 'safe' products listed on databases, e.g. such as those available in The Netherlands and Germany.

QTc prolongation prior to angiography predicts poor outcome and associates significantly with lower left ventricular ejection fractions and higher left ventricular end-diastolic pressures.

BACKGROUND: QT prolongation on the surface ECG is associated with sudden cardiac death. The cause of QT prolongation in ischaemic heart disease (IHD) patients remains unknown, but may be due to a complex interplay between genetic factors and impaired systolic and/or diastolic function through as yet unexplained mechanisms. It was hypothesised that QT prolongation before elective coronary angiography is associated with an increased mortality at six months. METHODS: Complete records of 321 patients who underwent coronary angiography were examined for QT interval corrected for heart rate (QTc), left ventricular ejection fraction (LVEF), left ventricular end-diastolic pressure (LVEDP) and known ischaemic heart disease risk factors. Patients were designated long QTc (LQTc) when they had prolonged QTc intervals or normal QTc (NQTc) when the QTc interval was normal. Patients with atrial fibrillation, bundle branch blocks, no ECG in the 24 hours before angiography, or a creatinine level > 200 µmol/l were excluded. Survival was determined telephonically at six months. RESULTS: Twenty-eight per cent of the total population had LQTc. During follow up, 15 patients (4.7%) died suddenly, 73% of whom had a LQTc. LQTc was significantly associated with mortality (LQTc 12% vs NQTc 1.7%; p < 0.01), and with lower but normal LVEF (LQTc 52.9 ± 15.4% vs NQTc 61.6 ± 13.6%; p < 0.01), higher LVEDP at LVEF > 45% (LQTc 19.2 ± 9.0 mmHg vs NQTc 15.95 ± 7.5 mmHg; p < 0.05), hypercholesterolaemia and a negative family history of IHD. CONCLUSION: In patients with sinus rhythm and normal QRS width, QTc prolongation before coronary angiography predicted increased mortality at six months. QTc also associated strongly with left ventricular systolic and diastolic dysfunction, hypercholesterolaemia and a negative family history of IHD.

Efficacy, safety and potential clinical roles of the COX-2-specific inhibitors.

About three decades ago, the primary mechanism of action of the non-steroidal anti-inflammatory drugs (NSAIDs) was elucidated when their inhibitory action on the production of prostaglandins was discovered. It was found that their action is centred on the inhibition of the cyclooxygenase (COX) enzyme responsible for converting arachidonic acid to prostaglandins. More recently, it was discovered that at least two isoforms of the enzyme exist. While the COX-1 isoenzyme is mainly constitutive, the COX-2 form is inducible. The constitutive form is principally associated with physiological/homeostatic functions while the inducible form is involved in inflammatory responses. Because many of the unwanted effects of the NSAIDs have been associated with COX-1 inhibition, specific drugs with a high inhibitory activity toward the COX-2 isoenzyme have been developed in recent years. The efficacy, safety and potential clinical roles of these COX-2-specific inhibitors are addressed in this review article.

Enhancing effect of temperature on the transmucosal penetration kinetics of 17 beta-estradiol.

Human vaginal mucosa may be used as a model of buccal mucosa for in vitro permeability studies using various chemical compounds. Rectilinear temperature dependence of water flux across vaginal mucosa between 25 degrees C and 41 degrees C has been shown. The objective of this study was to examine the behaviour of the above barrier on fluxes of 17 beta-estradiol at various temperatures. Frozen vaginal mucosa specimens from a single patient were used (snap-frozen in liquid nitrogen and stored at -85 degrees C). The permeability to tritiated 17 beta-estradiol was determined using a continous flow-through perfusion system at temperatures of 20 degrees C, 25 degrees C, 30 degrees C, 37 degrees C and 41 degrees C. Histological examinations were performed before and after permeability experiments. Estimated steady state flux values were used at 20 degrees C, 25 degrees C and 30 degrees C. Estimated and true mean 17 beta-estradiol steady state flux rates (20-24 h) were found to be 415 +/- 27 standard error of the Mean (SEM), 848 +/- 60 SEM, 1355 +/- 77 SEM, 1436 +/- 37 SEM and 1482 +/- 35 SEM cpm.cm-2.min-1, at temperatures of 20 degrees C, 25 degrees C, 30 degrees C, 37 degrees C and 41 degrees C, respectively. A non-linear regression analysis and plot (R2 = 0.9941) displayed a curvilinear flux-temperature relationship. The results from this study showed that, notwithstanding cellular damage, the principal physical permeability barrier governing permeation kinetics was non-linearly temperature-dependent between the temperatures studied, providing further support for the concept that this barrier is lipoidal in nature.

Enhancement of transmucosal permeation of cyclosporine by benzalkonium chloride.

OBJECTIVES: Permeation of cyclosporin A (CsA) through intact and de-epithelialized human vaginal mucosa in the presence and absence of benzalkonium chloride (BZCl) was tested. MATERIALS AND METHODS: Human vaginal mucosa (snap-frozen in liquid nitrogen, stored at -85 degrees C) had been used for permeability experiments. CsA permeation through thawed frozen intact and de-epithelialized vaginal mucosa was determined using a flow-through diffusion apparatus (20 degrees C, 24 h). Flux rates for CsA across these two mucosae were determined in the presence and absence of 0.01% BZCl. ANOVA and Duncan's multiple range test were used to test for steady-state and an unpaired t-test with Welch's correction was used to test for differences between the mean flux values at each time point (significance level of 5%). A piece of thawed tissue from each patient, before and after de-epithelialization, was placed in formalin and histologically examined. RESULTS: Flux rates of CsA across intact vaginal mucosa tended to increase by 28-46% in the presence of 0.01% BZCl, and CsA across de-epithelialized mucosa by approximately 28%. The latter differences were statistically significantly higher after 10 h. Flux rates across de-epithelialized mucosa were 52-140% higher in the presence of 0.01% BZCl (statistically significantly higher after 12 h). CONCLUSIONS: The permeation of CsA through intact and de-epithelialized human vaginal mucosa can be enhanced by 0.01% BZCl.

The effect of radiation on the permeability of human saphenous vein to 17 beta-oestradiol.

Radiation therapy is an effective way of treating many forms of cancer, however, there are some indications that it may facilitate the development of metastasis. The question arises whether radiation therapy during cancer treatment might result in an alteration of the permeability of the tissues being treated. This alteration in the permeability might lead to metastatic cells escaping from the irradiated tissue, leading to the spread of cancer to other sites in the body. Because of the above implication, we determined the diffusion kinetics of a radioactive marker, 17 beta-oestradiol, through human saphenous vein before and after a single half hour exposure to 60 Gy of 60Co gamma-irradiation. Six clinically healthy saphenous vein specimens (mean patient age +/- standard deviation 57 +/- 13 years; age range 41-77 years) were obtained during cardiac surgery. In vitro flux rates of 17 beta-oestradiol were determined through use of a flow-through diffusion apparatus immediately after irradiation for a period of 24 hours. No statistically significant differences could be demonstrated for the flux rates of 17 beta-oestradiol through the non-irradiated and 60 Gy irradiated saphenous vein tissue. These findings strongly suggest that irradiation at 2 Gy/min and a total dose of 60 Gy would not alter the permeability of the venous wall. We have demonstrated that the in vitro flow-through diffusion method is capable of measuring permeability aspects of endothelial cell layers in saphenous vein biopsies under conditions resembling clinical reality.

The effect of betel nut extract on cell growth and prostaglandin endoperoxide synthase in human epidermoid carcinoma cells.

The objective of this study was to find out whether prostaglandin endoperoxide synthase (PHS) involves the action of betel nut extract (BNE) on the growth of oral cancers. Therefore, growth and PHS activity were examined in two human oral carcinoma cell lines (OEC-M1 and KB) and one normal fibroblast cell line (NF) in the presence of increasing BNE concentration. BNE at concentrations above 50 microg/ml significantly inhibited the cell growth of OEC-M1 after 72 h in culture, of KB and NF after 48 h in culture. The IC50 of BNE in OEC-M1, KB and NF at 24 h in culture was about 406, 37.5 and 140 microg/ml respectively. PHS activity in OEC-M1 was significantly increased by low BNE concentrations (50 microg/ml, 114%; 100 microg/ml, 33%; 150 microg/ml, 30%) but significantly reduced at higher BNE concentrations (300 microg/ml, 33%; 500 microg/ml, 61%). The PHS activity in KB was significantly inhibited by BNE and this effect was intensified as concentrations increased (50 microg/ml, 31%; 100 microg/ml, 24%; 150 microg/ml, 43%; 300 microg/ml, 60%; 500 microg/ml, 92%). Similar to that in OEC-M1, the PHS activity in NF was significantly increased at low BNE concentrations (50 microg/ml, 139%; 100 microg/ml, 87%;150 microg/ml, 77%) but reduced at higher concentrations (300 microg/ml, 55%; 500 microg/ml, 72%). The PHS activity in all cell lines was almost completely blocked by indomethacin (5 x 10(-6) M). We conclude that these findings suggest that PHS may be an important biochemical mediator of the effect of BNE on the growth of two human oral carcinoma cell lines.