Pregnancy in women with hypertrophic cardiomyopathy: data from the European Society of Cardiology initiated Registry of Pregnancy and Cardiac disease (ROPAC).

AIMS: We report the maternal and foetal outcomes at birth and after 6 months in a cohort of pregnant women with hypertrophic cardiomyopathy (HCM). Although most women with HCM tolerate pregnancy well, there is an increased risk of obstetric and cardiovascular complications. METHODS AND RESULTS: All pregnant women with HCM entered into the prospective worldwide Registry of Pregnancy and Cardiac disease (ROPAC) were included in this analysis. The primary endpoint was a major adverse cardiovascular event (MACE), which included death, heart failure (HF), thrombo-embolic event, and arrhythmia. Baseline and outcome data were analysed and compared for patients with MACE vs. without MACE and for patients with obstructive HCM vs. non-obstructive HCM. Sixty pregnant women (mean age 30.4 ± 6.0 years) with HCM (41.7% obstructive) were included. No maternal mortality occurred in this cohort. In 14 (23%) patients at least one MACE occurred: 9 (15.0%) HF and 7 (12%) an arrhythmia (6 ventricular and 1 atrial fibrillation). MACE occurred most commonly during the 3rd trimester and postpartum period. In total, 3 (5.0%) women experienced foetal loss. Women with MACE had a higher rate of emergency Caesarean delivery for cardiac reasons (21.4% vs. 0%, P = 0.01). No significant differences in pregnancy outcome were found between women with obstructive and non-obstructive HCM. NYHA functional class of ≥II and signs of HF before pregnancy, were associated with MACE. CONCLUSION: Although most women with HCM tolerated pregnancy well, cardiovascular complications were not uncommon and predicted by pre-pregnancy status facilitating pre-pregnancy counselling and targeted antenatal care.

Utilization of low-profile intra-aortic balloon catheters inserted by the sheathless technique in acute cardiac patients: clinical efficacy with a very low complication rate.

UNLABELLED: Initial intra-aortic balloon pump (IABP) catheters were of large caliber and their utilization resulted in a high incidence of complications, including limb ischemia, bleeding and thrombosis, peripheral neurologic sequelae, and infection. Despite eventual decrease in the size of IABP catheters, the complication rate has remained high. HYPOTHESIS: The study was undertaken to determine whether use of recently available low-profile IABP catheters would result in a lower incidence of vascular and bleeding complications. METHODS: We prospectively evaluated the incidence of complications when consecutively using the low-profile (8F) IABP catheter inserted mostly sheathlessly in 161 acute cardiac patients between January 1, 2000 and April, 2003. RESULTS: Complications encountered included mild transient limb ischemia in two patients (1.2%), minor bleeding episodes in four patients (2.4%), one major puncture site bleeding (0.6%), and a pseudoaneurysm treated percutaneously in two patients (1.2%). Two patients (1.2%) suffered limb ischemia due to embolization or local thrombosis requiring vascular intervention. These complications were milder and their incidence remarkably lower than those reported previously when IABP catheters larger than 8F were used. CONCLUSION: Utilization of low-profile IABP 8F catheters in a sheathless technique entails an exceedingly low complication rate despite an acute presentation, intense anticoagulant and antiaggregant therapy, frequent comorbidity, advanced age, severe coronary disease, and reduced cardiac function in a large proportion of treated patients.

A prospective study of plasma fibrinogen levels and the risk of stroke among participants in the bezafibrate infarction prevention study.

PURPOSE: Plasma fibrinogen has emerged as an important predictor of cardiovascular disease, but few data are available on its association with stroke. We sought to determine if plasma fibrinogen is a marker of increased risk or a direct causative risk factor for stroke. SUBJECTS AND METHODS: Patients from the Bezafibrate Infarction Prevention Study, a placebo-controlled, randomized clinical trial of secondary prevention of coronary heart disease by lipid modification with bezafibrate retard (400 mg daily), were studied. Plasma fibrinogen levels were measured at baseline and yearly thereafter. Stroke, a prospectively monitored endpoint, was systematically assessed regarding stroke type, subtype, and functional outcome. RESULTS: Mean baseline fibrinogen levels were significantly higher in patients subsequently having a cerebrovascular event (140 strokes, 36 transient ischemic attacks; mean follow-up, 6.2 years) than in patients who did not (375 vs. 349 mg/dL, P <0.0001). Fibrinogen levels did not differ significantly by the type, subtype, or severity of the cerebrovascular event. Risk of ischemic stroke increased from 3.3% in the lowest tertile (baseline fibrinogen <314 mg/dL) to 7.% in the middle tertile (fibrinogen 314 to 373 mg/dL) to 10% in the upper tertile (fibrinogen >373 mg/dL, P <0.001). Adjusting for age, blood pressure, and other covariates, fibrinogen levels in the upper tertile were associated with more than a twofold increase in risk of ischemic stroke compared with in the lowest tertile (hazard ratio = 2.6; 95% confidence interval: 1.5 to 4.3). We did not find fibrinogen change from baseline to be related to subsequent ischemic stroke events. CONCLUSION: Plasma fibrinogen is a strong predictor of, rather than a direct causative factor for, subsequent stroke among patients at increased risk owing to manifest coronary heart disease.

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.

Maternal and fetal outcomes of subsequent pregnancies in women with peripartum cardiomyopathy.

BACKGROUND: Peripartum cardiomyopathy is a rare and sometimes fatal form of heart failure. Little is known about the outcomes of subsequent pregnancies in women who have had the disorder. METHODS: Through a survey of members of the American College of Cardiology, we identified 44 women who had had peripartum cardiomyopathy and had a total of 60 subsequent pregnancies. We then reviewed the medical records of these women and interviewed the women or their physicians. RESULTS: Among the first subsequent pregnancies in the 44 women, 28 occurred in women in whom left ventricular function had returned to normal (group 1) and 16 occurred in women with persistent left ventricular dysfunction (group 2). The pregnancies were associated with a reduction in the mean (+/-SD) left ventricular ejection fraction both in the total cohort (from 49+/-12 percent to 42+/-13 percent, P<0.001) and in each group separately (from 56+/-7 percent to 49+/-10 percent in group 1, P=0.002; and from 36+/-9 percent to 32+/-11 percent in group 2, P=0.08). During these pregnancies, a decrease of more than 20 percent in the left ventricular ejection fraction occurred in 21 percent of the women in group 1 and 25 percent of those in group 2, and symptoms of heart failure occurred in 21 percent of the women in group 1 and 44 percent of those in group 2. The mortality rate was 0 percent in group 1 and 19 percent in group 2 (P=0.06). In addition, the frequency of premature delivery was higher in group 2 (37 percent vs. 11 percent), as was that of therapeutic abortions (25 percent vs. 4 percent). CONCLUSIONS: Subsequent pregnancy in women with a history of peripartum cardiomyopathy is associated with a significant decrease in left ventricular function and can result in clinical deterioration and even death.

Prognosis of patients with a recurrent acute myocardial infarction before and in the reperfusion era--a national study.

BACKGROUND: Patients with recurrent acute myocardial infarction (AMI) are at increased risk for morbidity and mortality. We compared the outcome of patients with recurrent AMI hospitalized in coronary care units in the prereperfusion and reperfusion eras. METHODS: The study population comprised 2 large-scale cohorts with recurrent AMI: (1) 1415 (24%) of 5839 consecutive patients with AMI hospitalized in 1981 to 1983 (Secondary Prevention Reinfarction Israeli Nifedipine Trial [SPRINT] Registry) and (2) 1093 (25%) of 4317 patients with AMI from three national surveys performed in 1992 to 1996. RESULTS: Patients in the 1990s had significantly lower rates of heart failure and cardiogenic shock. The 7-day mortality declined from 18% in 1981-1983 to 10% in 1992-1996 (adjusted odds ratio [OR] 0.57 [0.44-0.75]), the 30-day mortality rate from 26% to 16% (OR 0.56 [0.44-0.71]), and the 1-year mortality rate from 39% to 26% (adjusted hazard ratio [HR] 0.64 [0.54-0.75]), respectively. In the 1992-1996 cohort, the adjusted risk of 7-day, 30-day, and 1-year mortality for patients with recurrent AMI treated with thrombolysis in comparison to patients without thrombolysis was OR 1.69 (1.07-2.65), 1.52 (1.03-2.23), and HR 1.18 (0.90-1.55), respectively. The mortality rate among patients treated with early percutaneous transluminal coronary angioplasty/coronary artery bypass grafting was 3% versus 12% at 7 days (OR 0.36 [0.16-0.73]), 7% versus 18% at 30 days (OR 0.45 [0.25-0.77]), and 16% versus 29% at 1 year (HR 0.64 [0.46-0.96]), in comparison to patients without revascularization. CONCLUSION: The prognosis of patients with recurrent AMI improved significantly during the reperfusion era. Although thrombolysis may have a limited therapeutic effect among patients with recurrent AMI, an interventional approach seems more appropriate when indicated. A randomized trial of thrombolysis versus early revascularization is needed in patients with recurrent AMI.

Sex differences in management and outcome after acute myocardial infarction in the 1990s: A prospective observational community-based study. Israeli Thrombolytic Survey Group.

BACKGROUND: Previous studies have suggested that women with acute myocardial infarction (AMI) are less aggressively managed than are men. The aim of this study was to assess sex differences in medical and invasive coronary procedures (angiography, PTCA, and CABG) in AMI patients admitted to cardiac care units (CCUs) in Israel in the mid 1990s and their association with early and 1-year prognosis. METHODS AND RESULTS: We studied 2867 consecutive AMI patients (2125 men, 74%) hospitalized in all 25 CCUs in Israel from 3 prospective nationwide surveys conducted in 1992, 1994, and 1996. Women were, on average, older than men (69 versus 61 years, P:<0.0001) and had a higher prevalence of hypertension, diabetes, Killip class >/=II on admission, and in-hospital complications. Women received aspirin and beta-blockers less often than did men, but these differences were not significant after age adjustment. The unadjusted rates of thrombolysis, angiography, and PTCA/CABG use were lower in women than in men but not after covariate adjustment: 42% versus 48% (adjusted odds ratio [OR] 0.92, 95% CI 0.77 to 1.11), 23% versus 31% (OR 0.88, 95% CI 0.70 to 1.09), and 15% versus 19% (OR 0.93, 95% CI 0.72 to 1.19), respectively. The 30-day mortality was higher in women than in men (17.6% versus 9.6%, respectively; OR 1.39, 95% CI 1.06 to 1.82), but the 30-day to 1-year mortality rate was not (9.1% versus 5.6%, respectively; hazard ratio 1.18, 95% CI 0.84 to 1.66). CONCLUSIONS: This prospective nationwide observational community-based study of consecutive AMI patients hospitalized in the CCUs in the mid 1990s indicates that women fare significantly worse than do men at 30 days but not thereafter at 1-year. The difference in 30-day outcome was not influenced by the use of different therapeutic modalities, including thrombolysis and invasive coronary procedures, but was rather due to the older age and greater comorbidity of women; these findings seem also to explain the less frequent use of invasive procedures in women.

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 microg/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.

Double-blind, placebo-controlled study to evaluate the effect of organic nitrates in patients with chronic heart failure treated with angiotensin-converting enzyme inhibition.

BACKGROUND: Organic nitrates are widely used in the treatment of chronic heart failure (CHF). No information, however, is available regarding their effect in patients already treated with ACE inhibitors. METHODS AND RESULTS: In a randomized, double-blind, crossover design, we studied the effects of high-dose (50 to 100 mg) transdermal nitroglycerin (NTG) and placebo given daily for 12 hours in 29 patients with CHF (NYHA functional classes II to III). Exercise time (4 hours after patch application) showed a progressive improvement during NTG administration, with an increase of 38+/-35 seconds (9+/-7%) at the end of the first month (P=NS), 76+/-28 seconds (16+/-6%) at the end of the second month (P=0.01), and 117+/-34 seconds (27+/-6%) at the end of the third month (P=0.003). No significant change was seen during placebo administration (12+/-20, 5+/-26, and 19+/-28 seconds, all P=NS). Exercise time 8 hours after NTG application measured at 3 months was also significantly longer, with a difference of 87+/-28 seconds (P=0.006), but not with placebo (23+/-36 seconds, P=0.53). Assessment of quality of life and need for additional diuretics or hospitalizations for CHF failed to demonstrate a significant difference between the 2 treatment periods. In contrast, NTG decreased left ventricular end-diastolic (-2.1+/-0.1%, P<0.05) and end-systolic (-3.2+/-1.3%, P<0.05) dimensions and augmented LV fractional shortening (24.7+/-10.5%, P<0.03). The effect of placebo on these parameters was not statistically significant. CONCLUSION: High-dose nitrate therapy significantly improves exercise tolerance and left ventricular size and systolic function in patients with chronic, mild to moderate CHF already treated with ACE inhibitors. These findings support the role of organic nitrates as an adjunctive therapy to ACE inhibitors in patients with chronic CHF.

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.

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.

Pharmacokinetic and pharmacodynamic evaluation of atenolol during and after pregnancy.

STUDY OBJECTIVE: To evaluate changes due to pregnancy on atenolol's pharmacokinetics, response of maternal heart rate to atenolol, and the drug's effect on fetal heart rate. DESIGN: Prospective study. SETTING: Large university teaching hospital. PATIENTS: Fourteen pregnant women who were receiving oral atenolol for cardiac disease were enrolled and 10 completed the study. INTERVENTIONS: Patients were studied for 12 hours during the third trimester (TT) and again 6 weeks postpartum (PP). MEASUREMENTS AND MAIN RESULTS: Fetal heart rates, and maternal heart rates at rest and during exercise were recorded. Maternal plasma and urine atenolol concentrations were measured. Average resting heart rates (TT 68+/-10, PP 62+/-9 beats/min) and maximum heart rate during exercise (TT 100+/-6, PP 87+/-7 beats/min) were significantly higher in the third trimester than postpartum (p<0.05). The 12-hour atenolol area under the curve (TT 0.208+/-0.061, PP 0.215+/-0.089 ng/ml/day) and maximum plasma concentrations during the time of exercise tests (TT 1.07+/-0.39, PP 1.14+/-0.53 mmol/L) were not significantly different. Individual and population pharmacokinetics did not differ significantly between study periods. The fetal heart rate did not correlate with maternal atenolol concentration. CONCLUSION: Constant dosages of atenolol result in higher heart rates during pregnancy compared with the postpartum period. This lack of heart rate control is not due to significant changes in atenolol's pharmacokinetics or plasma concentrations.

Effect of beta-blocker therapy in patients with coronary artery disease in New York Heart Association classes II and III. The Bezafibrate Infarction Prevention (BIP) Study Group.

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.

Pain scoring--a method for assessing acute antianginal therapy comparison of the response to acute sublingual administration of an isosorbide dinitrate tablet, isosorbide dinitrate spray and nitroglycerin spray in unstable angina.

It is difficult to assess acute therapeutic intervention therapy, particularly in patients with unstable angina. Our aim was to evaluate the feasibility of a pain-scoring method and to compare the response to sublingual administration of an isosorbide dinitrate (ISDN) tablet, ISDN spray or nitroglycerin (NTG) spray. Pain scoring was assessed by the subjective grading of the patients' pain severity from 1 to 10. We studied 205 patients (mean age 66 +/- 13 years). Pain attenuation, defined as at least 50% reduction in pain intensity, occurred in the ISDN tablet, ISDN spray and NTG spray groups after 360 +/- 290, 318 +/- 289 and 233 +/- 271 s, respectively (p = 0.0005). In conclusion, pain scoring is a feasible and useful clinical method to assess antianginal therapy in unstable angina patients. Sublingual nitrate sprays, particularly NTG, seem to alleviate anginal pain faster than ISDN tablets in this patient population.

Prognostic significance of cerebrovascular disease in 11,526 chronic coronary artery disease patients. Bezafibrate Infarction Prevention (BIP) Study Group.

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.

Incidence of arrhythmias in normal pregnancy and relation to palpitations, dizziness, and syncope.

We assessed the relation between symptoms and cardiac arrhythmias in 110 consecutive pregnant patients without evidence of heart disease referred for evaluation of palpitations, dizziness, and syncope (study group) and in 52 consecutive patients referred for evaluation of an asymptomatic functional precordial murmur (control group). Both groups had a high incidence of arrhythmias on Holter monitoring with atrial premature complexes (APCs) of 56% in the study group and 58% in the control group, > 100 APCs in 7% and 4% of the patients, respectively, and isolated ventricular premature complexes (VPCs) in 59% and 50%, respectively. The number of isolated VPCs was higher and > 50 VPCs/hour were seen in more patients in the study group (3,235 +/- 6,397 vs 678 +/- 3,358 beats/24 hours p < 0.05 and 22% vs 2% p = 0.03). Similarly, the incidence of multifocal VPCs was higher in the study patients (12% vs 2%, p < 0.05). There was no correlation between the incidence of both VPCs or APCs and symptoms, and only 10% of symptomatic episodes were accompanied by the presence of arrhythmias. Repeated Holter monitoring 6 weeks postpartum in 9 women with multiple premature contractions during pregnancy (9,073 +/- 9,210/24 hours) showed a substantial reduction to 1,345 +/- 1,997/24 hours (p < 0.05). Thus, this study confirms an increased incidence of arrhythmias during normal pregnancy. These arrhythmias consist mostly of APCs and VPCs. The number of simple and multifocal VPCs is higher in patients presenting with symptoms of palpitations, dizziness, or syncope; however, there is no correlation between the incidence of arrhythmias and symptoms, and only 10% of symptomatic episodes were accompanied by the presence of arrhythmias.

Low total cholesterol is associated with high total mortality in patients with coronary heart disease. The Bezafibrate Infarction Prevention (BIP) Study Group.

The present non-intervention screening study was undertaken to explore the relationships between pre-existing low total cholesterol and all-cause mortality. Eleven thousand, five hundred and sixty-three patients with coronary heart disease who attended a screening visit but were not included in the Bezafibrate Infarction Prevention study were followed-up for a mean of 3.3 years after determination of baseline total cholesterol. Five hundred and ninety-five (5%) of this largely unselected population who had total cholesterol levels < or = 160 mg.dl-1 formed the study population. The remaining 10968 patients acted as controls. The relative risk of all-cause mortality among patients with low cholesterol compared to others was 1.49 (95% CI: 1.16-1.91). The relative risk of non-cardiac death was 2.27 times higher in the low cholesterol group than in the controls (95% CI: 1.49-3.45), whereas the risk of cardiac death was the same in both groups (relative risk 1.09; 95% CI: 0.76-1.56). The most frequent cause of non-cardiac death associated with low total cholesterol was cancer. These results in patients with coronary heart disease add weight to previous studies associating low total cholesterol with an increased risk of non-cardiac death. However, a longer follow-up of this cohort of patients is necessary in order to clarify this association.

Calcium antagonists and mortality in patients with coronary artery disease: a cohort study of 11,575 patients.

OBJECTIVES: This study sought to establish the risk ratio for mortality associated with calcium antagonists in a large population of patients with chronic coronary artery disease. BACKGROUND: Recent reports have suggested that the use of short-acting nifedipine may cause an increase in overall mortality in patients with coronary artery disease and that a similar effect may be produced by other calcium antagonists, in particular those of the dihydropyridine type. METHODS: Mortality data were obtained for 11,575 patients screened for the Bezafibrate Infarction Prevention study (5,843 with and 5,732 without calcium antagonists) after a mean follow-up period of 3.2 years. RESULTS: There were 495 deaths (8.5%) in the calcium antagonist group compared with 410 in the control group (7.2%). The age-adjusted risk ratio for mortality was 1.08 (95% confidence interval [CI] 0.95 to 1.24). After adjustment for the differences between the groups in age and gender and the prevalence of previous myocardial infarction, angina pectoris, hypertension, New York Heart Association functional class, peripheral vascular disease, chronic obstructive pulmonary disease, diabetes and current smoking, the adjusted risk ratio declined to 0.97 (95% CI 0.84 to 1.11). After further adjustment for concomitant medication, the risk ratio was estimated at 0.94 (95% CI 0.82 to 1.08). CONCLUSIONS: The current analysis does not support the claim that calcium antagonist therapy in patients with chronic coronary artery disease, whether myocardial infarction survivors or others harbors an increased risk of mortality.

Usefulness of beta-blocker therapy in patients with non-insulin-dependent diabetes mellitus and coronary artery disease. Bezafibrate Infarction Prevention (BIP) Study Group.

The benefit of beta-blocker therapy in patients after myocardial infarction is well established. The use of beta blockers in the high-risk subgroup of patients with combined diabetes mellitus (DM) and coronary artery disease (CAD) remains controversial. From a database of 14,417 patients with chronic CAD who had been screened for participation in the Bezafibrate Infarction Prevention (BIP) study, 2,723 (19%) had non-insulin-dependent DM. Baseline characteristics and 3-year mortality were analyzed in patients with DM receiving (n = 911; 33%) and not receiving (n = 1,812; 67%) beta blockers. Total mortality during a 3-year follow-up was 7.8% in those receiving beta blockers compared with 14.0% in those who were not (a 44% reduction). A reduction in cardiac mortality of 42% between the 2 groups was also noted. Three-year survival curves showed significant differences in mortality with increasing divergence (p = 0.0001). After multiple adjustment, multivariate analysis identified beta-blocker therapy as a significant independent contributor to improved survival (relative risk = 0.58; 90% confidence interval 0.46 to 0.74). Within the diabetic population, the main benefit associated with beta-blocker therapy was observed in older patients, in those with a history of myocardial infarction, those with limited functional capacity, and those at lower risk. Thus, therapy with beta blockers appears to be associated with improved long-term survival in the high-risk subpopulation of patients with DM and CAD.