Effectiveness of nifedipine GITS in combination with atenolol in chronic stable angina.

Nifedipine gastrointestinal therapeutic system (GITS) is a once-daily formulation of nifedipine that provides stable plasma concentrations over the entire 24 h dosing interval. Two-hundred and one patients with Canadian Cardiovascular Society class II to III angina who were on 50 mg of atenolol yet still experiencing angina symptoms were randomized to receive either placebo or nifedipine GITS 30, 60 or 90 mg/day. After four weeks of treatment, the changes in time from baseline to onset of 1 mm ST segment depression in the 183 eligible patients were 26.7+/-10.2 s, 40.9+/-11.3 s, 63.2+/-12.9 s and 70.3+/-12.6 for the placebo, and 30, 60 and 90 mg/day groups, respectively. These differences were significant (P<0.05) for the 60 and 90 mg/day groups compared with placebo and for the 60 mg/day group compared with the 30 mg/day group. The times to onset of pain and termination of exercise showed similar prolongation but did not achieve statistical significance. During the one-year open label phase of the study, patients exhibited statistically significant improvements in the time to onset of ST segment depression, time to anginal pain and time to termination of exercise at a mean dose of 52.3 mg/day of nifedipine GITS. Adverse events were primarily vasodilatory in nature. This study supports the use of nifedipine GITS in patients with chronic stable angina inadequately controlled on beta-blocker alone.

Generalized linear least squares method for fast generation of myocardial blood flow parametric images with N-13 ammonia PET.

In this paper, we developed and tested strategies for estimating myocardial blood flow (MBF) and generating MBF parametric images using positron emission tomography (PET), N-13 ammonia, and the generalized linear least square (GLLS) method. GLLS was generalized to the general linear compartment model, modified for the correction of spillover, validated using simulated N-13 ammonia data, and examined using PET data from several patient studies. In comparison to the standard model-fitting procedure, the GLLS method provided similar accuracy and superior computational speed.

Noninvasive quantification of the cerebral metabolic rate for glucose using positron emission tomography, 18F-fluoro-2-deoxyglucose, the Patlak method, and an image-derived input function.

The authors developed and tested a method for the noninvasive quantification of the cerebral metabolic rate for glucose (CMRglc) using positron emission tomography (PET), 18F-fluoro-2-deoxyglucose, the Patlak method, and an image-derived input function. Dynamic PET data acquired 12 to 48 seconds after rapid tracer injection were summed to identify carotid artery regions of interest (ROIs). The input function then was generated from the carotid artery ROIs. To correct spillover, the early summed image was superimposed over the last PET frame, a tissue ROI was drawn around the carotid arteries, and a tissue time activity curve (TAC) was generated. Three venous samples were drawn from the tracer injection site at a later time and used for the spillover and partial volume correction by non-negative least squares method. Twenty-six patient data sets were studied. It was found that the image-derived input function was comparable in shape and magnitude to the one obtained by arterial blood sampling. Moreover, no significant difference was found between CMRglc estimated by the Patlak method using either the arterial blood sampling data or the image-derived input function.

Treatment and outcome of patients with acute myocardial infarction and prior cerebrovascular events in the thrombolytic era: the Israeli Thrombolytic National Survey.

BACKGROUND: Patients with a history of stroke presenting with acute myocardial infarction (MI) are often excluded from thrombolytic therapy owing to fear of intracranial hemorrhage. Few data, however, are available on the risks vs the benefits of thrombolysis in patients with an acute MI and a prior cerebrovascular event (PCE). METHODS: Data were derived from 2 nationwide surveys of 2012 consecutive patients with acute MI admitted to all 25 coronary care units in Israel during 1992 and 1994. Thrombolytic therapy was given to patients with a PCE at the discretion of the treating physicians. Outcomes were compared between patients with an acute MI with and without a PCE and between patients with a PCE treated with or excluded from thrombolysis. RESULTS: Patients with a PCE (n = 115 [6%]) were older, with higher rates of atherosclerotic risk factors and in-hospital complications than their counterparts without a prior event (n = 1897). They were treated less often with thrombolysis or mechanical reperfusion. The 1-year mortality rates were higher among patients with a PCE (28% vs 19%, P<.01), but not after multivariate adjustments for clinical characteristics (adjusted hazard ratio, 1.08; 95% confidence interval, 0.75-1.55). Patients with an acute MI and a PCE who were treated with thrombolysis (n = 29 [25%]) were compared with 46 patients found ineligible for thrombolysis primarily because of their PCE. The timing of the PCE was comparable in both groups (one fifth in the preceding year), while prior transient ischemic attacks were more prevalent among patients who had undergone thrombolysis. The patients who were treated with thrombolysis (n = 29) were older, had a higher rate of anterior infarction, and, while in the hospital, received aspirin, anticoagulants, and beta-blockers more often than their counterparts (n= 46). In-hospital intracranial hemorrhage did not occur in either group. The 1-year mortality rates were 2-fold higher among patients who had not undergone thrombolysis compared with those who had (33% vs 18%; adjusted hazard ratio, 2.44; 95% confidence interval, 0.78-7.64). CONCLUSIONS: These findings, derived from 2 nationwide surveys of consecutive patients with acute MI, suggest that patients with PCEs have an adverse outcome attributed to their older age and less favorable risk profile. Thrombolytic therapy, however, based on our preliminary data, may be beneficial in selected patients with an acute MI with a nonrecent PCE.

Plasma lipid oxidation and susceptibility of low-density lipoproteins to oxidation in male patients with stable coronary artery disease.

OBJECTIVES: Oxidative modifications of low-density lipoproteins (LDL) are considered to be important in the pathogenesis of atherosclerosis. However, the data on the association between LDL oxidation and severity of clinical manifestations of coronary artery disease (CAD) are contradictory. Previous reports were concerned mostly with unstable angina patients. The present study was undertaken to evaluate plasma lipid oxidation status in patients with stable CAD. DESIGN AND METHODS: 37 male patients with angiographically confirmed CAD (asymptomatic or suffering from stable angina pectoris) and 32 control subjects were used in the study. Plasma levels of vitamin E and products of lipid peroxidation, as well as parameters of the test for oxidizability of LDL in vitro were measured. RESULTS: We did not find differences between 2 groups of individuals regarding the levels of products of lipid peroxidation, vitamin E levels, lag time, maximal rate of oxidation, and total amount of conjugated dienes in the test for oxidizability of LDL. CONCLUSION: The results of our study challenge, but do not disprove, the oxidative hypothesis of atherosclerosis. Real atherosclerotic modifications of plasma LDL occur apparently in the vascular wall after trapping of LDL by the interstitial matrix. The rise in oxidative parameters in unstable angina reported in the literature may not be the cause of the disease but, rather, the consequence of the multiple brief episodes of ischemia-reperfusion.

Long-term prognosis of patients after a Q wave compared with a non-Q wave first acute myocardial infarction. Data from the SPRINT Registry.

UNLABELLED: OBJECTIVE, DESIGN AND PATIENTS: Between August 1981 and July 1983, 5839 consecutive myocardial infarction patients were hospitalized in 13 coronary care units in Israel. The present study examines 10 year survival among 4037 consecutive patients with a first myocardial infarction with either Q or non-Q waves. Demographic and medical data were collected from hospital records, and 1 year clinical follow-up was complete for 99% of hospital survivors. Mortality follow-up was extended to June 1992 (mean 10 years of follow-up). RESULTS: Five hundred and eighty patients (14%) had first myocardial infarctions of the non-Q wave type and 3457 of the Q wave type. Hospital mortality was significantly higher in patients with a Q wave (10%) than those with a non-Q wave myocardial infarction (7%) (P < 0.05). One year post-discharge, non-fatal reinfarction and mortality rates were comparable in patients with Q wave (4% and 7%) and non-Q wave myocardial infarctions (4% and 7% respectively). Similarly, 5 to 10 year post-discharge mortality rates were equally high in patients with a non-Q wave (26% and 44%) as in those with a first episode of a Q wave myocardial infarction (22% and 40% respectively). CONCLUSIONS: Patients with a first non-Q wave acute myocardial infarction exhibited relatively better in-hospital survival than counterparts with a first Q wave infarction, but the advantage did not persist after discharge. Patients with a non-Q wave infarction deserve particular attention as their post-discharge mortality risk is similar to counterparts with a first Q wave myocardial infarction.

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.

Lysine-binding species of lipoprotein(a) in coronary artery disease.

Elevated levels of plasma lipoprotein(a) [Lp(a)] have frequently been associated with coronary artery disease (CAD). Recently Lp(a) was fractionated into two species with different affinities for Lysine-Sepharose. The influence of lysine-binding heterogeneity of Lp(a) on its cardiovascular pathogenicity has not previously been studied. The authors have determined plasma levels of total Lp(a), its lysine-binding [lys+] and unretained [lys-] species in 67 male CAD patients undergoing cardiac catheterization. Forty-three patients have severe CAD (two- or three-vessel disease) and 24 patients have less pronounced CAD (one-vessel disease or less than 50% narrowing of coronary vessels). All patients were ranked in order of their Lp(a) levels and then grouped into quartiles. The prevalence of severe CAD was significantly higher in the upper Lp(a) quartile as compared with the other three quartiles (odds ratio 10-5; chi-square 11.2; P = 0.0008). Similar results were obtained when the same analysis was carried out for [lys+] and [lys-] species of Lp(a) (odds ratio 11.52 and 3.3, respectively; chi-square 12.3 and 4.34, respectively; P = 0.0004 and 0.037, respectively). Thus, measurement of either species of Lp(a) does not provide any additional improvement in the prediction of CAD as compared to the estimation of total Lp(a) levels.

Immediate and long-term prognostic significance of a first anterior versus first inferior wall Q-wave acute myocardial infarction. Secondary Prevention Reinfarction Israeli Nifedipine Trial (SPRINT) Study Group.

Of 3,981 patients with a first Q-wave acute myocardial infarction (AMI), 1,929 (48%) had an anterior and 1,724 (43%) an inferior wall AMI. These 2 groups were well-matched with respect to age, gender and relevant history. The in-hospital mortality rate was 18%, and the 1- and 5-year post-discharge mortality rates were 9 and 25%, respectively, in patients with anterior wall AMI compared with the corresponding rates of 11, 6 and 19% in those with inferior wall AMI (p < 0.0001 for each category). The frequency of recurrent nonfatal AMI in the year after the index AMI was 8% in the patients with anterior wall AMI compared with 4% in those with inferior wall AMI (p < 0.0001). By multiple logistic regression analysis of events, anterior wall AMI was an independent predictor of in-hospital mortality only. The findings indicate that the anatomic location of a Q-wave AMI influences immediate and short-term survival of patients with a first Q-wave AMI.

The prognostic significance of angina pectoris preceding the occurrence of a first acute myocardial infarction in 4166 consecutive hospitalized patients.

We examined the role of chronic (greater than 1 month) angina pectoris (AP) before acute myocardial infarction (AMI) in predicting hospital and long-term mortality rates among 4166 patients with first AMIs. The prevalence of AP in these patients was 43%. Chronic AP was more common in women (49%), patients with hypertension (49%), and diabetic patients (49%) than in men and counterparts free of the former conditions (p less than 0.005). In patients with AP the hospital course was more complicated and non-Q-wave AMI was more common than in counterparts without AP. In-hospital (16%), as well as 1 (8%)- and 5-year postdischarge (26%), mortality rates in hospital survivors were higher among patients with previous AP than in patients without previous AP (12%, 6%, and 19%, respectively) (p less than 0.01). After adjustment for age and all other predictors of increased hospital mortality rates in this cohort of patients, AP preceding AMI emerged as an independent predictor of increased hospital mortality rates (odds ratio 1.30; 90% confidence interval 1.10 to 1.53). For postdischarge mortality rates (mean follow-up 5 1/2 years), the covariate-adjusted relative risk of death in patients with AP was similar at 1.29 (p less than 0.0001; 90% confidence interval 1.16 to 1.44), according to estimation by Cox proportional hazards model. These data support the notion that preexisting AP identifies a group of patients at increased risk of death.

Long-term prognosis after acute myocardial infarction in patients with left ventricular hypertrophy on the electrocardiogram. SPRINT Study Group.

Among 4,720 consecutive hospital survivors from acute myocardial infarction (AMI) treated in 13 coronary care units between July 1981 and August 1983, the estimated prevalence of electrocardiographic left ventricular (LV) hypertrophy was 6.1%. The prevalence of electrocardiographic LV hypertrophy increased with age and was higher in patients with previous myocardial infarction, angina and systemic hypertension. Mean age of patients with electrocardiographic LV hypertrophy was 67.2 vs 61.4 years in counterparts free of electrocardiographic LV hypertrophy. Patients with electrocardiographic LV hypertrophy had a higher rate of congestive heart failure on admission, or developing during their stay in coronary care units. The 1- and 5-year mortality rates were 19.7 and 46.6% among patients with electrocardiographic LV hypertrophy versus 8.7 and 26.2%, respectively (p less than 0.001) in patients without this finding. The covariate-adjusted odds ratio of 1-year mortality was 1.88 for the presence of electrocardiographic LV hypertrophy when age alone was adjusted for, and 1.51 (90% confidence interval, 1.09 to 2.10) when multiple covariate adjustment was undertaken. After multiple covariate adjustment for 5-year mortality after discharge, the relative risk associated with electrocardiographic LV hypertrophy was 1.51 (90% confidence interval, 1.26 to 1.80). The results of the present study showed that the presence of electrocardiographic LV hypertrophy on the discharge electrocardiogram of survivors from AMI is associated with a 1.5-fold increase of short- and long-term mortality. Patients with electrocardiographic LV hypertrophy, potentially at an increased post-discharge risk, may be candidates for early noninvasive testing and more intensive follow-up after recovering from AMI.

Cerebrovascular accident complicating acute myocardial infarction: incidence, clinical significance and short- and long-term mortality rates. The SPRINT Study Group.

PURPOSE: The purpose of this study was to report the incidence, the antecedents, and the clinical significance of clinically recognized cerebrovascular accidents or transient ischemic attacks (CVA-TIA) complicating acute myocardial infarction. PATIENTS AND METHODS: During 1981 to 1983, a secondary prevention study with nifedipine (SPRINT) was conducted in 14 hospitals in Israel among 2,276 survivors of acute myocardial infarction. During the study, demographic, historical, and medical data were collected on special forms for all patients with diagnosed acute myocardial infarction in 13 of these 14 hospitals (the SPRINT registry, n = 5,839). Mortality follow-up was completed for 99% of hospital survivors for a mean follow-up of 5.5 years (range: 4.5 to 7 years). RESULTS: The incidence of CVA-TIA was 0.9% (54 of 5,839). The latter rate increased significantly only with age, from 0.4% among patients up to 59 years old to 1.6% among those aged greater than or equal to 70 years. Multivariate analysis identified age, congestive heart failure, and history of stroke as predictors of CVA-TIA during the acute phase of myocardial infarction. Patients with CVA-TIA exhibited a complicated hospital course, with a 15-day mortality rate of 41%. Subsequent mortality rates in survivors at 1 and 5 years were 34% and 59%, respectively. Rates at the same time points in patients without CVA-TIA were 16%, 11%, and 29% (p less than 0.01). In a multivariate analysis that included age, gender, congestive heart failure, history of previous myocardial infarction, and hypertension, CVA-TIA was independently associated with increased 15-day mortality (covariate-adjusted odds ratio [OR] = 2.62; 90% confidence interval [CI], 1.59 to 4.32), as well as subsequent 1-year (OR = 3.29; 90% CI, 1.70 to 6.36) and long-term (mean follow-up = 5.5 years) mortality (OR = 2.46; 90% CI, 1.30 to 4.69). CONCLUSION: In this large cohort of consecutive patients with myocardial infarction, CVA-TIA was a relatively infrequent complication of acute myocardial infarction. Factors independently favoring the occurrence of CVA-TIA were old age, previous CVA, and congestive heart failure. CVA-TIA occurring during acute myocardial infarction independently increased the risk of early death threefold as well as the risk of long-term mortality in early-phase survivors. (2.5-fold).

Monotherapy of stable angina pectoris with bopindolol in comparison with diltiazem.

The efficiency of bopindolol (B) in the treatment of moderate stable angina pectoris was compared with that of diltiazem (D) by clinical evaluation and exercise tolerance. Following washout of previous treatment, patients were randomly assigned to either medication: 16 to D and 15 to B. The initial dose of B was 1 mg once daily, increased after 4 weeks to 2 mg once daily; the respective doses of D were 120 and 240 mg, given in 4 divided doses. Therapy resulted in an average decrease of 22 pain episodes and 256 min of pain time per month in the B group, whereas the respective reductions in the D group were 1.65 episodes and 129 min. Improvement in the exercise test indices following 8 weeks of treatment was more marked in the B group than in the D group. The average double product at peak exercise decreased markedly in the B group and more moderately in the D group. Thus, 2 mg B given once daily effectively blocked B receptors and relieved angina more efficiently than 240 mg D given in 4 divided doses.

[Echocardiographic diagnosis of anomalous origin of left coronary artery].

Cross sectional and M-mode echocardiography is a well-established noninvasive technique in the diagnosis of dilated cardiomyopathy and is essential in the evaluation of its severity and progress. However, in most cases of dilated cardiomyopathy in children, it does not provide data suggestive of the etiology of the disease. In the rare congenital malformation, anomalous origin of the left coronary artery from the pulmonary artery, the echocardiographic techniques may suggest the diagnosis when the left coronary artery cannot be demonstrated to arise from its usual site, the left coronary sinus (as visualized in the short axis of the aortic root). A firm diagnosis can be made if the anomalous origin of the left coronary artery is identified in a cross-sectional view of the main pulmonary artery (left parasternal long axis view of the main pulmonary artery, Fig. 1). This was demonstrated in a 9-year-old girl by coronary and aortic angiography (Fig. 2a, b). Anatomical confirmation was made during corrective surgery 3 months later. The origin of the left coronary artery was at the left posterior aspect of the main pulmonary artery, just proximal to its bifurcation. This is an unusual origin in this anomaly in which the coronary artery has been reported to arise close to the pulmonary valve, but not distal, as in this case.

Von Willebrand factor and mitral valve prolapse.

The levels of von Willebrand factor (vWF:Ag) were measured in 27 patients with mitral valve prolapse (MVP) and compared to 27 age matched controls. Decreased levels of vWF:Ag (less than 80%) were found in 59% (16/27) of those with MVP compared to only 7% (2/27) of the controls (p less than 0.001). Mean vWF: Ag levels were also significantly lower in those with MVP (68 +/- 30% versus 100 +/- 23%, p less than 0.001). In those with MVP and congestive heart failure secondary to rupture chordae tendineae, however, the mean level of vWF: Ag was not significantly different from control values (95 +/- 32). There was an increased incidence of recurrent nose bleeds in those with MVP and low levels of vWF:Ag. We conclude that there is a relationship between MVP and low levels of vWF:Ag which may explain the increased incidence of epistaxis in such patients. Increased release of vWF:Ag in those with MVP and concomitant congestive heart failure may account for the normal levels found in this subgroup.

The scale of myocardial involvement in varicella myocarditis.

Two patients with varicella myocarditis are described. An arrhythmia associated with complete recovery occurred in the first patient whereas intractable congestive heart failure complicated by hemiplegia resulted in a fatal outcome in the other case. We stress the extent of myocardial involvement produced by the herpes zoster virus in the setting of varicella.