Avraham Shotan

Brain and Atrial Natriuretic Peptides in Patients with Ischemic Heart Disease with and without Heart Failure

The objective of the study was the evaluation of natriuretic peptides in ischemic heart disease. Atrial and brain peptides (ANP, BNP) were elevated in patients with ischemic heart failure, as compared with patients with angina without over failure, and controls (p < 0.01). BNP/ANP ratio was higher in NYHA class IV than in class III patients (2.67 +/- 0.87 vs. 1.52 +/- 0.59, respectively). Patients in the angina group, in whom elevated BNP or ANP was found, had subclinical systolic or diastolic dysfunction. There was inverse correlation between BNP, ANP and the left-ventricular ejection fraction (each r = 0.78, p < 0.001). We conclude that BNP is elevated as a result of myocardial dysfunction, but not of ischemia and seems to be a better index of disease stage and prognosis than ANP.

Abciximab in Carotid Stenting for Postsurgical Carotid Restenosis: Intermediate Results

Purpose: To report intermediate results of a pilot study in which the glycoprotein IIb/IIIa receptor antagonist abciximab was given to patients during percutaneous carotid stenting for recurrent internal carotid artery (ICA) stenosis. The objective was to prevent procedure-related cerebral embolic events and decrease the incidence of recurrent stenosis. Methods: Sixteen patients (9 women; mean age 66.5 years, range 39–78) with severe ICA recurrent stenosis (>80%) underwent balloon angioplasty and stenting. Before the procedure, abciximab was administered intravenously as a bolus (0.25 mg/kg) followed by a 12-hour continuous infusion (10 µg/min). Results: Fifteen patients received stents (14 Wallstent and 1 Strecker); 1 vessel was dilated with only 50% improvement in luminal diameter. Two stented arteries had residual stenosis (<30%) but satisfactory luminal diameter was achieved in the remaining 13 (81%) arteries. There were no neurological ischemic events during or following the procedure, nor were there any bleeding or peripheral vascular complications. Duplex surveillance studies up to 12 months revealed no significant recurrent stenosis in the treated vessels. Conclusions: The administration of abciximab in conjunction with percutaneous revascularization procedures for postsurgical carotid artery stenosis may reduce cerebral ischemic episodes. It may also attenuate restenosis in the treated artery.

Prevalence and prognostic significance of unrecognized systemic hypertension in patients with diabetes mellitus and healed myocardial Infarction and/or stable angina pectoris

Few data are available regarding the prevalence and prognostic significance of the triple coexistence of undiagnosed systemic hypertension, diabetes mellitus, and coronary heart disease. This study aimed to evaluate the prevalence and prognostic significance of unrecognized hypertension in cardiac diabetic patients previously defined as normotensives over a 5-year follow-up period. The study sample comprised 11,515 patients aged 45 to 74 years with a previous myocardial infarction and/or anginal syndrome who were screened but not included in the Bezafibrate Infarction Prevention study. Among them, 9,033 were nondiabetics and 2,482, diabetics. The diabetics were divided into 3 groups: (1) 1,272 normotensives, (2) 152 patients without history of hypertension but with elevated blood pressure (unrecognized hypertensives), and (3) 1,058 hypertensives with established diagnosis. The prevalence of both diagnosed and unrecognized hypertension in diabetics pooled together increased from 49% to 69% when World Health Organization and new Joint National Committee-VI criteria were compared. Crude all-cause mortality was lower in nondiabetics than in diabetics (11.2% vs 22.0%; p <0.001). Among diabetics the lowest all-cause mortality was documented for normotensives (19.3%), whereas the highest mortality was observed in unrecognized hypertensives (26.3%, p = 0.003). Both unrecognized and established hypertensives demonstrated a significant stroke-related mortality excess: about four- and threefold increases in cerebrovascular accident-related death, respectively, were observed (p = 0.002). On multivariate analysis, both unrecognized and diagnosed hypertension were consistent predictors of increased all-cause mortality, with a hazard ratio of 1.28 (95% confidence interval 0.90 to 1.82) and 1.24 (95% confidence interval 1.03 to 1.49), respectively. Our findings demonstrate widespread undiagnosed hypertension in diabetic coronary patients; their 5-year mortality was significantly increased compared with normotensives, and tended to be even higher than in diabetics previously identified as hypertensives.

Hypertension in Diet Versus Pharmacologically Treated Diabetics Mortality Over a 5-Year Follow-Up

The natural history of non-insulin-dependent diabetes mellitus (NIDDM) differs markedly between patients with diet treated and pharmacologically treated disease. However, the interrelationship between hypertension and these common diabetes types has not been specifically addressed in previous studies. This study was designed to evaluate the prognostic significance and prevalence of hypertension in coronary patients with diet versus pharmacologically treated NIDDM over a 5-year follow-up period. The study sample comprised 11 515 patients aged 45 to 74 years with a previous myocardial infarction and/or anginal syndrome who had been screened but were not included in the Bezafibrate Infarction Prevention study. Among them, 9033 were nondiabetics and 2482, diabetics (987 diet treated and 1495 pharmacologically treated). The prevalence of hypertension among nondiabetics, diet-treated diabetics, and pharmacologically treated diabetics was 31%, 42%, and 43%, respectively. Crude all-cause mortality (CM) was lower in the nondiabetic patients (11.2% versus 22.0%; P<0.001). Among diabetics, 548 patients died: 81 diet treated normotensives (CM 14%); 100 diet-treated hypertensives (CM 24.4%); 205 pharmacologically treated normotensives (CM 24.2%); and 162 pharmacologically treated hypertensive patients (CM 25.0%). Age-adjusted mortality was lowest for the normotensive patients in the diet-treated group and highest for the hypertensive pharmacologically treated patients. Multivariate analysis shows that hypertension is a strong and independent predictor of increased CM in diet-treated but not in pharmacologically treated NIDDM: hazard ratio (HR) was 1.68 (95% confidence interval [CI] 1.24 to 2.29) for the diet-treated versus 1. 01 (95% CI 0.82 to 1.26) for the pharmacologically treated diabetics. The contribution of hypertension to stroke mortality was substantial for both diet treated and pharmacologically treated NIDDM: hazard ratios were 3.17 (95% CI 1.12 to 8.98) and 2.21 (95% CI 0.72 to 6.77), respectively. The increased risk of mortality associated with hypertension in relatively mild diet-treated NIDDM strongly supports the clinical benefit of early blood pressure control among diabetic patients with ischemic heart disease.

Prognostic significance of cerebrovascular disease in 11,526 chronic coronary artery disease patients

Patients with chronic CAD and a history of cerebrovascular events were compared with patients without prior cerebrovascular events to assess the effect of these events on 5-year prognosis. Despite adjustment for older age and higher comorbidity among patients who had experienced a cerebrovascular event, a history of such an event was associated with an increased risk of 1.86 for total mortality.

Plasma Atrial Natriuretic Peptide Levels for Predicting the Outcome of Atrial Fibrillation

The predictive value of plasma atrial natriuretic peptide (ANP) on the cardioversion outcome was evaluated in 46 hospitalized patients with recent-onset atrial fibrillation (AF). Cardioversion was successful in 42 (91%) patients, 7 (15%) of them regained sinus rhythm spontaneously. After 12 months, 14 (33%) cardioverted patients were in chronic AF. There were no differences in plasma ANP levels between groups where cardioversion failed, those who cardioverted but later developed chronic AF or those who remained in sinus rhythm. However, among patients who were on antiarrhythmic therapy, ANP levels obtained after cardioversion were lower in those who later remained in sinus rhythm. We conclude that lower ANP after cardioversion may be associated with increased chances of long-term preservation of sinus rhythm.

Effect of Beta-Blocker Therapy in Patients With Coronary Artery Disease in New York Heart Association Classes II and III

The aim of the study was to investigate the effect of beta-blocker treatment on a large cohort of patients with coronary artery disease in functional classes II and III according to the New York Heart Association (NYHA) classification. Among 11,575 patients with coronary artery disease screened for participation, but not included in the Bezafibrate Infarction Prevention (BIP) study, 3,225 (28%) were in NYHA classes II and III. In the latter group of patients we compared the prognosis of 1,109 (34%) treated with beta blockers with 2,116 counterparts not receiving beta-blocker therapy. After a mean follow-up of 4 years, all-cause and cardiac mortality rates were significantly lower among beta-blocker users, 9% and 5%, respectively, than among beta-blocker nonusers, 17% and 11%, respectively (p <0.01 for both). After multivariate adjustment, treatment with beta blockers was associated with a lower all-cause mortality risk (hazards ratio [HR] 0.62, 95% confidence interval [CI] 0.49 to 0.78), and a lower cardiac mortality risk (HR = 0.61, 95% CI 0.45 to 0.83) than was no treatment with a beta blocker. Lower total mortality risk was noted among patients in NYHA class II (HR 0.63, 95% CI 0.48 to 0.82) and in NYHA class III (HR 0.57, 95% CI 0.37 to 0.87) as well as in patients with (HR 0.62, 95% CI 0.48 to 0.81) or without (HR 0.70, 95% CI 0.45 to 1.09) a previous myocardial infarction. We conclude that beta-blocker therapy in coronary patients in NYHA classes II or III is safe and associated with a lower risk for all-cause and cardiac mortality.

Are coronary patients at higher risk with digoxin therapy? An ongoing controversy

Previous reports have yielded contradictory conclusions regarding the safety of digoxin therapy in patients with acute myocardial infarction. The purpose of our study was to determine whether digoxin therapy is associated with increased mortality in patients with chronic coronary artery disease. We analyzed data from 8173 patients who were screened for participation in the Bezafibrate Infarction Prevention (BIP) trial and who survived an acute myocardial infarction at least 6 months prior to the study. Three-year overall mortality of the 451 (15.5%) patients receiving digoxin (according to the judgement of their treating physician) at the time of screening for BIP participation, was 22.4% compared to 8.3% in the patients who did not receive digoxin. Cardiac mortality was 16.2% in the digoxin-treated group, compared to 4.9% in the non-treated patients. The increased risk associated with digoxin remained statistically significant when patients were stratified according to sex, age groups, functional capacity and the presence of hypertension, diabetes or angina. The administration of digoxin to survivors of an acute myocardial infarction in the chronic phase of their disease, is statistically associated with a 30-50% increase in the risk of overall and cardiac mortality during long-term follow-up. A propensity of increased risk of arrhythmias in ischemic coronary patients may explain this finding.

Does participation in a long-term clinical trial lead to survival gain for patients with coronary artery disease?

PURPOSEnLittle is known about the advantages and disadvantages of participation in a clinical trial for patients with coronary heart disease. We hypothesized that participation itself in a long-term clinical trial with regular clinical evaluation and adjustment of treatments might lead to survival gain among patients with coronary artery disease who agreed or refused to participate in the Bezafibrate Infarction Prevention study.nnnSUBJECTS AND METHODSnThe study was performed in 18 university hospitals. There were 3502 patients who fulfilled the inclusion criteria. Among them, 3122 patients signed informed consent and were included in the study (participants), whereas 380 declined to participate (nonparticipants). For all participants, routine visits to the clinics were scheduled bimonthly for study medication distribution and compliance assessment, and every 4 months for clinical evaluation and management. Nonparticipants continued with community-based treatment and were followed only for mortality.nnnRESULTSnThe two groups were similar with regard to age, sex, and the prevalence of most cardiovascular diseases, risk factors, and medications, except that participants were more likely to have presented with an anginal syndrome (1788 [57%] vs. 190 [50%]) and to have symptomatic heart failure (754 [25%] vs. 66 [18%]). During follow-up (mean [+/- SD], 7.7 +/- 0.8 years), 475 patients died. All-cause mortality was similar in participants (n = 423 [13.6%]) and nonparticipants (n = 52 [13.7%]). In a multivariate analysis, participation in the clinical trial was not associated with all-cause mortality (hazard ratio [HR] = 0.96; 95% confidence interval [CI]: 0.70 to 1.30) or cardiac mortality (HR = 1.12; 95% CI: 0.72 to 1.74).nnnCONCLUSIONnParticipation in a long-term clinical trial in a country with readily accessible community-based medicine may not lead to survival gain in patients with coronary artery disease.

In vivo assessment of the inotropic and toxic effects of oxidized ouabain

SummaryOxidized ouabain, a product of the oxidative cleavage of the rhamnose ring in ouabain has been found to have a higher inotropic toxic ratio in cultured cardiac myocytes.The purpose of our study was to evaluate the efficacy and toxicity of oxidized ouabain in comparison with ouabain in intact animals. Drugs were infused to healthy cats; the positive inotropic effect, and the time-course of development of arrhythmia were followed and recorded until death. Oxidized ouabain was associated with a higher increase in arterial blood pressure, a mean increase of 41±19% as compared with 21±8% in the ouabain group (p<0.10). There were no significant differences in maximal increases of dP/dt or dP/dt/P (65±29%, 28±10% for oxidized ouabain and 49±16%, 27±11% for ouabain, respectively). The mean doses causing persistent arrhythmia (toxic dose) were 93±23 μg/kg of oxidized ouabain vs 39±14 μg/kg of ouabain. Lethal arrhythmias were produced by 215±46 μg/kg of oxidized ouabain and 62±16 μg/kg of ouabain. The radio of toxic to lethal doses was 0.62±0.11 for ouabain vs 0.45±0.09 for oxidized ouabain (p<0.05), but the inotropic to toxic dose ratios were not different.We conclude that oxidized ouabain acts similarly to the known cardiac glycosides in doses which produce inotropic effects in cats, has a lower potency as compared to ouabain, and appears to have a more benign course of intoxication.