Predictors of 1-year survival in South African transcatheter aortic valve implant candidates.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) has undergone rapid expansion internationally over the past 15 years. In view of resource constraints in developing countries, a major challenge in applying this technology lies in identifying patients most likely to benefit. The development of a risk prediction model for TAVI has proved elusive, with a reported area under the curve (AUC) of 0.6 - 0.65. The available models were developed in a First-World setting and may not be applicable to South Africa (SA). OBJECTIVES: To evaluate novel indicators and to develop a TAVI risk prediction model unique to the SA context. The current work represents the important initial steps of derivation cohort risk model development and internal validation. METHODS: Seven-year experience with 244 successive TAVI implants in three centres in Western Cape Province, SA, was used to derive risk parameters. All outcomes are reported in accordance with the Valve Academic Research Consortium definitions. Multiple preprocedural variables were assessed for their impact on 1-year survival using univariate and multivariate models. RESULTS: Factors found not to correlate with 1-year survival included age, renal function and aortic valve gradients. The commonly used surgical risk prediction models (Society of Thoracic Surgeons score and EuroSCORE) showed no correlation with outcomes. Factors found to correlate best with 1-year survival on multivariate analysis were preprocedural body mass index (BMI) (favouring higher BMI), preprocedural left ventricular end-diastolic dimension (LVED) and ejection fraction (EF) (favouring smaller LVED and higher EF), absence of atrial fibrillation, and three novel parameters: independent living, ability to drive a car, and independent food acquisition/cooking. Discriminant analysis of these factors yielded an AUC of 0.8 (95% confidence interval 0.7 - 0.9) to predict 1-year survival, with resubstitution sensitivities and specificities of 72% and 71%, respectively. CONCLUSIONS: Apart from existing predictors, we identified three novel risk predictors (independent living, ability to drive a car, and independent food acquisition/cooking) for 1-year survival in TAVI candidates. These novel parameters performed well in this early evaluation, with an AUC for predicting 1-year survival higher than the AUCs for many of the internationally derived parameters. The parameters are inexpensive and easy to obtain at the initial patient visit. If validated prospectively in external cohorts, they may be applicable to other resource-constrained environments.

Anti-inflammatory mechanisms of cannabinoids: an immunometabolic perspective.

A number of studies have implicated cannabinoids as potent anti-inflammatory mediators. However, the exact mechanism by which cannabinoids exert these effects remains to be fully explained. The recent resurgence in interest regarding the metabolic adaptations undergone by activated immune cells has highlighted the intricate connection between metabolism and an inflammatory phenotype. In this regard, evidence suggests that cannabinoids may alter cell metabolism by increasing AMPK activity. In turn, emerging evidence suggests that the activation of AMPK by cannabinoids may mediate an anti-inflammatory effect through a range of processes. First, AMPK may promote oxidative metabolism, which have been shown to play a central role in immune cell polarisation towards a tolerogenic phenotype. AMPK activation may also attenuate anabolic processes which in turn may antagonise immune cell function. Furthermore, AMPK activity promotes the induction of autophagy, which in turn may promote anti-inflammatory effects through various well-described processes. Taken together, these observations implicate cannabinoids to mediate part of their anti-inflammatory effects through alterations in immune cell metabolism and the induction of autophagy.

Takotsubo Cardiomyopathy : an Acute and Reversible Cardiomyopathy Mimicking Acute Myocardial Infarction

Takotsubo cardiomyopathy is an acute; reversible form of left ventricular dysfunction precipitated by emotional or physical stress. The condition is important to recognise as it mimics acute myocardial infarction and acute coronary syndrome. Most patients are female and postmenopausal. Presenting symptoms include severe chest pain; acute dyspnoea; hypotension or even cardiogenic shock. The ECG changes are suggestive of an acute coronary syndrome with T-wave inversion with / without ST elevation; most often in the precordial leads. The syndrome is characterised by a sudden onset of transient extensive akinesia of the left ventricle; often involving all three major coronary artery territories; in the absence of significant coronary artery stenosis. The wall motion typically involves the apex of the left ventricle with hyperkinesis of the base of the heart. Variant forms have recently been described where the wall motion abnormality involves the mid-ventricular wall with hyperkinesis of the base and apex; or the base of the heart with hyperkinesis of the apex. Characteristically; there is only a limited release of cardiac enzymes disproportionate to the extent of regional wall motion abnormality. Transient right ventricular dysfunction may occur and is associated with more complications; longer hospitalisation and worse left ventricular systolic dysfunction. Serial echocardiography is useful to document improvement in cardiac function. The pathogenesis is unclear. Transient mid-cavity obstruction has been invoked with subsequent myocardial stunning in the akinetic segments. Treatment is supportive. The most effective long-term management remains to be defined. Although the prognosis is good with recovery of ventricular function at about three weeks; some patients have died. The syndrome may recur

Beta-blockade by sotalol in early myocardial infarction decreases ventricular arrhythmias without increasing left ventricular volume.

Although early beta-blockade in acute myocardial infarction (AMI) may have potential benefits owing to an anti-arrhythmic effect and limitation of infarct size, the haemodynamic effects are not well characterised. Accordingly, we studied the effects of intravenous beta-blockade by sotalol in AMI, commencing a mean of 6 hours after the onset of chest pain, with particular reference to systemic haemodynamic changes and left ventricular (LV) volumes. Thirty patients were randomised to a control group or to sotalol therapy starting with 40 mg and increasing to 120 mg, followed by the maximal dose tolerated every 6 hours for 72 hours. Sotalol reduced heart rate and mean blood pressure without elevating pulmonary wedge pressure or increasing enzymatic infarct size. Sotalol also decreased the incidence of ventricular tachycardia (P less than 0.001). An important new finding was that there was no increase in the LV volume measured by radionuclide techniques. Therefore intravenous sotalol safely achieved its beneficial effects without causing LV dilatation.

Beta-blockade in acute myocardial infarction: is Swan-Ganz catheterization required before treatment?

Beta-blockade is used increasingly in early acute myocardial infarction (AMI) but may cause congestive heart failure (CHF). It is not known whether Swan-Ganz catheterization is necessary before beta-blockade in AMI. We made a retrospective analysis of 213 patients who underwent Swan-Ganz catheterization within 24 hours of AMI and compared precatheter CHF signs (dyspnoea, lung crepitations and x-ray appearance) with initial pulmonary artery wedge pressure (PAWP). One hundred nine of these patients received beta-blockade after catheterization, 31 did not tolerate beta-blockade. Absence of clinical CHF signs predicted a normal PAWP (less than or equal to 18 mmHg) in 86% of patients (42 of 49) and considerable safety in giving beta-blockade. Beta-blockade had to be stopped because of PAWP increase (greater than 5 mmHg) in 25 of 74 patients with CHF signs vs. 3 of 35 patients without CHF signs (p less than 0.005), and in 9 of 15 patients with high PAWP vs. 19 of 91 patients with normal PAWP (p less than 0.01). Only 2/28 patients (7%) intolerant to beta-blockade had a high PAWP but no clinical CHF. In conclusion hemodynamic intolerance to beta-blockade could have been predicted clinically without prior Swan-Ganz catheterization in 25/28 patients. Patients with CHF signs require catheterization if beta-blockade therapy is to be considered.

Tiapamil--a new calcium antagonist.

Calcium antagonists are an important new modality in cardiovascular therapy. Tiapamil, a congener of verapamil, is undergoing clinical and laboratory evaluation. We have undertaken experimental studies on the anti-arrhythmic properties of tiapamil, and on the intravenous use of this agent in patients with acute myocardial infarction. Reasons are given for suggesting that tiapamil warrants further clinical evaluation, after which it may join the more established calcium antagonists as a valuable therapeutic agent.

Follow-up clinical results in patients undergoing percutaneous transluminal coronary angioplasty.

Complete follow-up data were obtained from 229 consecutive patients who underwent percutaneous transluminal coronary angioplasty (PTCA) between 1979 and 1982 (mean follow-up 14 months, range 6 to 37). Single-vessel disease was present in 143 and multivessel disease in 86. PTCA was successful in 153 patients (67%). Failure was followed initially by bypass surgery in 59 and by continued medical therapy in 17. After successful PTCA, 90% of patients were improved subjectively and 74% were asymptomatic at follow-up. After unsuccessful PTCA but prompt bypass, 90% were improved subjectively and 85% were asymptomatic. Among the 229 patients, 39 (17%) required an additional intervention because of angina during follow-up; 15 of these had repeat PTCA and 18 had bypass surgery. Among patients with successful PTCA, revascularization was complete in 77% and partial in 23%. The completeness of revascularization with PTCA had a significant impact on follow-up. The follow-up data of patients with successful single-vessel PTCA and of those with multivessel disease with complete revascularization were similar. When the patients with complete revascularization were compared with those with multivessel disease but incomplete revascularization, the follow-up data were characterized by a higher incidence of angina or need for bypass surgery in the latter group (63%) than in the former group (29%); those with incomplete revascularization also had a significantly reduced event-free survival.

Tiapamil, a new calcium antagonist: hemodynamic effects in patients with acute myocardial infarction.

The afterload reduction and myocardial oxygen sparing that results after administration of calcium antagonists suggests a possible role for these drugs in intervention after onset of acute myocardial infarction, but their use in this setting is limited by the possibility that left ventricular failure will develop. Tiapamil is a new verapamil congener. The hemodynamic effects of this drug (1 mg/kg followed by 25 micrograms/kg/min over 36 hr) were studied in 30 patients randomly assigned in a double-blind manner to a tiapamil or control group within 12 hr of the onset of acute myocardial infarction as diagnosed by Swan-Ganz catheterization and gated blood pool scans. Tiapamil reduced heart rate from 83 +/- 20 beats/min (mean +/- SD) before to 74 +/- 19 beats/min after drug (over an average 36 hr), arterial pressure from 128 +/- 22/87 +/- 14 to 118 +/- 16/74 +/- 11 mm Hg, rate-pressure product from 10,695 +/- 3492 to 8800 +/- 2550 units, and systemic vascular resistance from 1732 +/- 351 to 1400 +/- 350 dynes X sec X cm-5. Tiapamil also increased stroke volume index from 34.7 +/- 12.1 to 41.6 +/- 12.0 ml/m2, left ventricular ejection fraction from 50.1 +/- 14.8% to 56.4 +/- 17.4% (at 24 hr), left ventricular end-diastolic volume index from 71.3 +/- 23.1 to 80.5 +/- 23.7 ml/m2, and peak diastolic filling rate (an index of diastolic relaxation) from 2.1 +/- 0.9 to 2.6 +/- 0.8 end-diastolic volumes/sec (p less than .05 for all changes). Cardiac index, wedge pressure, left ventricular end-systolic volume, and PR interval remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Intracoronary thrombus: role in coronary occlusion complicating percutaneous transluminal coronary angioplasty.

Angiograms from 238 consecutive patients who underwent percutaneous transluminal coronary angioplasty at the Mayo Clinic were reviewed to determine the presence of intracoronary thrombus before dilation. Patients with previously occluded vessels and those receiving streptokinase therapy were excluded. Intracoronary thrombus before dilation was present in 15 patients (6%); complete occlusion occurred in 11 (73%) of these during or immediately after dilation. None of these patients had angiographic evidence of major intimal dissection. In contrast, among the 223 patients in whom no intracoronary thrombus was present before dilation, complete occlusion occurred in 18 (8%) and in 12 was associated with major intimal dissection. The difference between the complete occlusion rates for patients with and without prior intracoronary thrombus was highly significant (73 versus 8%, respectively, p less than 0.001). Therefore, the presence of intracoronary thrombus identifies a group of patients who are at increased risk of developing complete occlusion during or after attempted coronary artery dilation.

Pseudoxanthoma elasticum in South Africa--genetic and clinical implications.

After investigation by a multidisciplinary team, 19 cases of biopsy-proven pseudoxanthoma elasticum are described. Evidence for an increased gene frequency in the Afrikaner population was found, as was support for the claim of genetic heterogeneity in the disorder. The well-described clinical manifestations involving the eyes, skin and cardiovascular system were seen, as were more rarely reported features such as acne, telangiectasia of the lips and bilateral cataracts. Mitral valve prolapse and gastro-intestinal haemorrhage were not found in our patients, although there are several reports in the literature.

Hemodynamic effects of sublingual nifedipine in acute myocardial infarction.

Twenty-six patients with acute myocardial infarction (mean delay time 6 hours after onset of symptoms) were randomized to control or nifedipine treatment (10 mg sublingually, followed by 10 mg every 6 hours for a total of 24 hours). Nifedipine reduced arterial blood pressure from 127/78 to 115/70 mm Hg at 30 minutes (p less than 0.001) and continued to reduce the blood pressure significantly for 12 to 18 hours. Nifedipine also reduced systemic vascular resistance and the rate-pressure product. Cardiac output increased from 4.9 liters/min before nifedipine to 5.4 liters/min at 60 minutes (p less than 0.05 vs controls). In patients with high initial pulmonary wedge pressures, sublingual nifedipine decreased the wedge pressure (p less than 0.001) more effectively than did 80 mg of furosemide given intravenously. Thus, nifedipine may be useful in patients with early myocardial infarction and left ventricular failure.

Aspects of the value of continuous ambulatory ECG monitoring in the detection and management of ischaemic heart disease. Case reports.

In 2 patients admitted for evaluation of chest pain occurring mainly at rest, organic disease of the nondominant circumflex artery only, with normal left anterior descending and right coronary arteries, was demonstrated in each case. Continuous ambulatory ECG monitoring by the Holter system revealed episodes of ST-segment elevation probably due to coronary artery spasm, allowing specific treatment to be instituted. Some aspects of the value of continuous ambulatory Holter monitoring in patients with ischaemic heart disease are discussed.

Induction of labour in pregnancy complicated by heart disease.

Thirty-seven patients whose pregnancies were complicated by heart disease and who required induction of labour were given 4 mg of prostaglandin E2 (PGE2) oral tablets per vaginam. Thirty-one patients (84%) went into labour and delivered within 24 hours, 28 of them vaginally. Although 3 infants had an Agpar score of less than 7 at birth, 2 having been delivered vaginally, all were discharged from hospital thriving and in good condition. No side-effects of PGE2 were observed and although these women had a wide range of functional disabilities, none developed deterioration in cardiac status. Vaginal administration of PGE2 for induction of labour is a safe and simple method of achieving elective delivery in patients with pregnancies complicated by heart disease.

Amiodarone in the treatment of patients with refractory symptomatic ventricular and supraventricular arrhythmias. A long-term follow-up study.

Fifty-two patients with refractory symptomatic supraventricular and ventricular arrhythmias were treated with amiodarone (Cordarone-X; Reckitt & Colman) and followed up for a mean period of 36,4 months (range 3-54 months). Amiodarone was effective in controlling supraventricular arrhythmias in 18 of 22 patients (82%) and ventricular arrhythmias in 18 of 30 (60%), giving an overall success rate of 72%. The incidence of sudden death in the patients with ventricular arrhythmias was significantly higher (P less than 0,01) in patients whose symptoms were not controlled by amiodarone than in those in whom control was achieved. Although side-effects occurred in 50 of the 52 patients they seldom necessitated withdrawal of the drug. This is the first report in which a substantial number of patients have been closely followed up for a mean period exceeding 22 months. The results described here demonstrate that the potent antiarrhythmic properties of amiodarone, previously observed for shorter periods of time, are maintained for up to 4 1/2 years, and that there is neither an increased incidence nor progression of side-effects in patients exposed to the drug for these longer periods of time.

Evaluation of lorcainide, a new anti-arrhythmic agent.

A new anti-arrhythmic agent, lorcainide, has been compared with lignocaine in patients with acute myocardial infarction. Lorcainide has been shown to be as effective as lignocaine in suppressing ventricular ectopy. Lorcainide is unusually free of side-effects and has the great advantage over lignocaine of being effective when given orally.