Spitting cobra (Naja nigricincta nigricincta) bites complicated by rhabdomyolysis, possible intravascular haemolysis, and coagulopathy

Zebra snake (Naja nigricincta nigricincta) bite is a significant health problem in Namibia. Although fatalities are thought to be rare, the severe cytotoxic effects and debilitating consequences of neglected bites are well documented. The focus of our treatment has always been the urgent treatment of necrosis. Although there have been a few reports of infant fatalities, acute renal failure and mild coagulation problems, systemic effects after envenomation were not well documented. Three case reports of patients with rhabdomyolysis, intravascular haemolysis and coagulopathy following N. n. nigricincta bites are presented

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 contex

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

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Evacetrapib and Cardiovascular Outcomes in High-Risk Vascular Disease

BACKGROUND: The cholesteryl ester transfer protein inhibitor evacetrapib substantially raises the high-density lipoprotein (HDL) cholesterol level, reduces the low-density lipoprotein (LDL) cholesterol level, and enhances cellular cholesterol efflux capacity. We sought to determine the effect of evacetrapib on major adverse cardiovascular outcomes in patients with high-risk vascular disease. METHODS: In a multicenter, randomized, double-blind, placebo-controlled phase 3 trial, we enrolled 12,092 patients who had at least one of the following conditions: an acute coronary syndrome within the previous 30 to 365 days, cerebrovascular atherosclerotic disease, peripheral vascular arterial disease, or diabetes mellitus with coronary artery disease. Patients were randomly assigned to receive either evacetrapib at a dose of 130 mg or matching placebo, administered daily, in addition to standard medical therapy. The primary efficacy end point was the first occurrence of any component of the composite of death from cardiovascular causes, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina. RESULTS: At 3 months, a 31.1% decrease in the mean LDL cholesterol level was observed with evacetrapib versus a 6.0% increase with placebo, and a 133.2% increase in the mean HDL cholesterol level was seen with evacetrapib versus a 1.6% increase with placebo. After 1363 of the planned 1670 primary end-point events had occurred, the data and safety monitoring board recommended that the trial be terminated early because of a lack of efficacy. After a median of 26 months of evacetrapib or placebo, a primary end-point event occurred in 12.9% of the patients in the evacetrapib group and in 12.8% of those in the placebo group (hazard ratio, 1.01; 95% confidence interval, 0.91 to 1.11; P=0.91). CONCLUSIONS: Although the cholesteryl ester transfer protein inhibitor evacetrapib had favorable effects on established lipid biomarkers, treatment with evacetrapib did not result in a lower rate of cardiovascular events than placebo among patients with high-risk vascular disease. (Funded by Eli Lilly; ACCELERATE ClinicalTrials.gov number, NCT01687998 .)

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402

Endovascular aortic aneurysm repair by a multidisciplinary team : lessons learned and six-year clinical update

The original publication is available at http://www,cvja.co.za/Includes bibliography.Background: Endovascular aneurysm repair (EVAR) (using an Federal Drug Association-approved AneuRx® device) compared to conventional surgical repair of abdom inal aortic aneurysm (AAA) previously rendered favourable outcomes regarding post-operative pain, avoidence of laparotomy, and rapid rehabilitation and hospital discharge in high-risk patients, including octagenarians. Objectives: To assess the safety, reduction in aneurysmrelated deaths, and interim survival data up to 72 months after AAA exclusion by endoluminal endografts (EVAR). Design: We carried out an open, controlled, prospective, multidisciplinary EVAR study for the period 1998 to 2003 (six years). In the earlier part of the study, EVAR was compared with previously published results of conventional open aneurysmectomy surgery. Setting: Heart Unit, Panorama Medi-Clinic, Parow, South Africa. Participants: We recruited adult male and female patients presenting with AAA and fulfilling the inclusion criteria for endovascular repair, as recommended by the consensus 2003 meeting of the Vascular Association of South Africa (VASSA). All patients were offered open surgery as an alternative and were entered into the VASSA EVAR trial registry. Pre-operatively, AAA anatomy was assessed by spiral-computed tomography (CT), and selectively with conventional angiography and intravascular ultrasound (IVUS). Informed consent was obtained in accordance with the recommendations of the Senate of Surgery Paper 2, Ethical Guidelines, Great Britain and Ireland. Patients underwent EVAR by a multidisciplinary interventional team. Interventions: Two hundred and seven adult patients with AAA were assessed. Forty-four of the 207 (21.2%) were excluded from EVAR because of irreversible comorbid factors and complex aneurysm morphology. One hundred and sixty-three patients (78%), with a mean age of 70.7 years (range 60−91 years), underwent EVAR (1998−2003). Five patients were lost to follow-up (3%). Median AAA diameter was 56.9 mm and ASA ratings were I, 1.2%; II, 15.9%; III, 57%; IV, 22.6%; and V, 2.4%. EVAR was performed in high- and low-risk categories of both sexes. Most patients were in ASA groups III and IV. Devices deployed: EVAR was performed using a selection of endografts over 72 months − AneuRx® (Medtronic) 47; Talent® (Medtronic) 49; Vanguard® three; Zenith® (Cook) one; Powerlink® (Endologix) 62; and other, one. Results: Thirty-day outcome: successful deployment 99%, primary stent patency 97%, surgical conversion 0.6%, procedural or intra-operative mortality 1.2%, 30-day mortality 4.3%, endoleaks 1.84%, and secondary intraprocedural endovascular interventions 24.5%. Perioperative mortality was 3.1% (one aneurysm related). One patient had suspected endograft infection. Late mortality was 21.4% (35 patients due to co-morbidities, and one was aneurysm related). Follow-up was a median of 28.3 months (range 1−69 months). In 163 patients, two persisting endoleaks (1.2%) were detected. Endotension was detected in 3/163 (1.8%) with average sac increase of 0.8 cm. Conversion to open surgery was needed in one patient (0.6%). Co-morbidities that contributed to late mortality included multi-organ failure, ischaemic heart disease (IHD), cardiomyopathy, renal failure, stroke and cancer. One procedural rupture was fatal (0.6%). Two late ruptures occurred; one was successfully endostented and the other patient died after a failed surgical intervention (0.6%). Endovascular repair of AAA is more expensive than conventional surgery. Introduction of the Endologix stent has reduced operative time from 120 to 60 minutes in un complicated patients. Newer-generation aortic stents allow better control of negative remodeling and stent migration. Conclusion: A multidisciplinary team can safely perform EVAR, with a low 30-day mortality rate in selected patients graded ASA II−IV and with favourable aortic aneurysm morphology. About 22% of patients with AAA are not suited for EVAR. Persisting late endoleaks occurred in 1.2% of the cohort study and were not device specific. Life-long follow-up post EVAR is a prerequisite to detect late device failure, endoleaks and aneurysm-sac enlargement, and to assure the durability of these midterm results. Short-term aneurysm rupture prevention is a predictable outcome in high-risk groups.Publishers' versio

EVAR : critical applied aortic morphology relevant to type-II endoleaks following device enhancement in patients with abdominal aortic aneurysms

The original publication is available at http://www.cvja.co.za/Endovascular repair (EVAR) of abdominal aortic aneurysms (AAA) is an established alternative option to conventional surgery for AAA, provided optimal anatomical morphology of the aneurysm sac, neck and outflow exists. In most documented series of EVAR, type-II endoleak occurrence is a universal procedural drawback. This is referred to as the Achilles heel of EVAR. This morphological study, addressing predominantly non-aneurysmal aortic anatomy, reveals the dyssynchronous origins of the renal ostia, ectopia of the superior mesenteric artery and median sacral artery, variations in the length of the infrarenal abdominal aorta, multiple mainstem renal arteries, and the presence of accessory renal arteries (in 13% of cadavers). Such potential vascular anomalies need careful consideration pre-operatively prior to EVAR. In a prospective, clinical study of EVAR in 163 patients over 60 months, using four different aortic stent devices, we demonstrated an intraprocedural type-II endoleak rate, before exclusion, of 3% (5/163). Most were related to patent lumbar arteries. An active policy of intraprocedural aneurysm pressure sac measurement and angiography was used to demonstrate type-I and type-II endoleaks, focusing on the applied anatomy of aortic side branches and variations. Selective intraprocedural coil embolisation and thrombin injection into the sac was utilised to thrombose persisting and large lumbar arteries that predisposed to retroleaks. We recorded a low incidence of persisting type-II endoleaks using this proactive treatment strategy by addressing variant aortic morphology and patent lumbar arteries during EVAR. One aneurysm-related death (0.6%) was observed due to late rupture after EVAR, and a single intraprocedural death was related to unpredictable aneurysm rupture. In conclusion, comprehensive anatomical knowledge of the abdominal aorta and its main collateral side branches, including variations, is a fundamental prerequisite if satisfactory and predictable results are to be achieved after EVAR, especially regarding prevention, diagnosis and treatment of type-II endoleaks. Intraprocedural aneurysm sac pressure monitoring, coil embolisation and the use of injection of thrombin into the aneurysm sac of selected patients is useful in reducing the incidence of post-EVAR type-II persisting endoleaks.Publishers' versio