scispace - formally typeset
Search or ask a question

Showing papers in "Circulation in 1992"


Journal ArticleDOI
TL;DR: The relation between the heart period variability measures and all-cause mortality, cardiac death, and arrhythmic death before and after adjusting for five previously established postinfarction risk predictors is explored.
Abstract: BACKGROUNDWe studied 715 patients 2 weeks after myocardial infarction to establish the associations between six frequency domain measures of heart period variability (HPV) and mortality during 4 ye...

1,708 citations


Journal ArticleDOI
TL;DR: Serum triglyceride concentration has prognostic value, both for assessing coronary heart disease risk and in predicting the effect of gemfibrozil treatment, especially when used in combination with HDL-C and LDL-C.
Abstract: BACKGROUND We studied the joint effect of baseline triglyceride and lipoprotein cholesterol levels on the incidence of cardiac end points in the trial group (n = 4,081) of the Helsinki Heart Study, a 5-year randomized coronary primary prevention trial among dyslipidemic middle-aged men. The relative risks (RR) were calculated using Cox proportional hazards models with a dummy variable technique that allows simultaneous study of subgroup combinations from the placebo and treatment groups. METHODS AND RESULTS In the placebo group (n = 2,045), the low density lipoprotein cholesterol (LDL-C)/high density lipoprotein cholesterol (HDL-C) ratio was the best single predictor of cardiac events. This ratio in combination with the serum triglyceride level revealed a high-risk subgroup: subjects with LDL-C/HDL-C ratio greater than 5 and triglycerides greater than 2.3 mmol/l had a RR of 3.8 (95% CI, 2.2-6.6) compared with those with LDL-C/HDL-C ratio less than or equal to 5 and triglyceride concentration less than or equal to 2.3 mmol/l. In subjects with triglyceride concentration greater than 2.3 mmol/l and LDL-C/HDL-C ratio less than or equal to 5, RR was close to unity (1.1), whereas in those with triglyceride level less than or equal to 2.3 mmol/l and LDL-C/HDL-C ratio greater than 5, RR was 1.2. The high-risk group with LDL-C/HDL-C ratio greater than 5 and triglyceride level greater than 2.3 mmol/l profited most from treatment with gemfibrozil, with a 71% lower incidence of coronary heart disease events than the corresponding placebo subgroup. In all other subgroups, the reduction in CHD incidence was substantially smaller. CONCLUSIONS Serum triglyceride concentration has prognostic value, both for assessing coronary heart disease risk and in predicting the effect of gemfibrozil treatment, especially when used in combination with HDL-C and LDL-C.

1,358 citations


Journal ArticleDOI
TL;DR: In patients participating in regular physical exercise and low-fat diet, coronary artery disease progresses at a slower pace compared with a control group on usual care.
Abstract: BACKGROUNDSignificant regression of coronary and femoral atherosclerotic lesions has been documented by angiographic studies using aggressive lipid-lowering treatment. This study tested the applicability and effects of intensive physical exercise and low-fat diet on coronary morphology and myocardial perfusion in nonselected patients with stable angina pectoris.METHODS AND RESULTSPatients were recruited after routine coronary angiography for stable angina pectoris; they were randomized to an intervention group (n = 56) and a control group on "usual care" (n = 57). Treatment comprised intensive physical exercise in group training sessions (minimum, 2 hr/wk), daily home exercise periods (20 min/d), and low-fat, low-cholesterol diet (American Heart Association recommendation, phase 3). No lipid-lowering agents were prescribed. After 12 months of participation, repeat coronary angiography was performed; relative and minimal diameter reductions of coronary lesions were measured by digital image processing. Cha...

1,289 citations


Journal ArticleDOI
TL;DR: The known benefits of regular aerobic exercise and current recommendations for implementation of exercise programs are described in a revised report as discussed by the authors, and the potential risk of physical activity can be reduced by medical evaluation, risk stratification, supervision, and education.
Abstract: Physical inactivity is recognized as a risk factor for coronary artery disease. Regular aerobic physical activity increases exercise capacity and plays a role in both primary and secondary prevention of cardiovascular disease.1 2 3 4 5 The known benefits of regular aerobic exercise and current recommendations for implementation of exercise programs are described in this revised report.6 Exercise training increases cardiovascular functional capacity and decreases myocardial oxygen demand at any level of physical activity in apparently healthy persons as well as in most subjects with cardiovascular disease. Regular physical activity is required to maintain these training effects. The potential risk of physical activity can be reduced by medical evaluation, risk stratification, supervision, and education.4 Exercise can help control blood lipid abnormalities, diabetes, and obesity. In addition, aerobic exercise adds an independent blood pressure–lowering effect in certain hypertensive groups with a decrease of 8 to 10 mm Hg in both systolic and diastolic blood pressure measurements.7 8 9 10 There is a direct relation between physical inactivity and cardiovascular mortality, and physical inactivity is an independent risk factor for the development of coronary artery disease.11 12 13 14 There is a dose-response relation between the amount of exercise performed from approximately 700 to 2000 kcal of energy expenditure per week and all-cause mortality and cardiovascular disease mortality in middle-aged and elderly populations.14 15 The greatest potential for reduced mortality is in the sedentary who become moderately active.15 Most beneficial effects of physical activity on cardiovascular disease mortality can be attained through moderate-intensity activity (40% to 60% of maximal oxygen uptake, depending on age).14 15 16 The activity can be accrued through formal training programs or leisure-time physical activities. Although most of the supporting data are based on studies in men, more recent findings …

1,231 citations


Journal ArticleDOI
TL;DR: The data suggest that a high stored iron level, as assessed by elevated serum ferritin concentration, is a risk factor for coronary heart disease.
Abstract: BACKGROUNDIron can induce lipid peroxidation in vitro and in vivo in humans and has promoted ischemic myocardial injury in experimental animals. We tested the hypothesis that high serum ferritin concentration and high dietary iron intake are associated with an excess risk of acute myocardial infarction.METHODS AND RESULTSRandomly selected men (n = 1,931), aged 42, 48, 54, or 60 years, who had no symptomatic coronary heart disease at entry, were examined in the Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) in Eastern Finland between 1984 and 1989. Fifty-one of these men experienced an acute myocardial infarction during an average follow-up of 3 years. On the basis of a Cox proportional hazards model adjusting for age, examination year, cigarette pack-years, ischemic ECG in exercise test, maximal oxygen uptake, systolic blood pressure, blood glucose, serum copper, blood leukocyte count, and serum high density lipoprotein cholesterol, apolipoprotein B, and triglyceride concentrations, men with seru...

1,165 citations


Journal ArticleDOI
TL;DR: MCE demonstrates that angiographically successful reflow cannot be used as an indicator of successful myocardial reperfusion in AMI patients and the residual contrast defect in the risk area demonstrated immediately after reflow is a predictor of poor functional recovery of the postischemic myocardium.
Abstract: BACKGROUNDWe investigated myocardial perfusion dynamics after thrombolysis and its clinical implications.METHODS AND RESULTSWe studied 39 patients with acute anterior myocardial infarction (AMI). Myocardial contrast echocardiography (MCE) was performed before and immediately after successful reflow with intracoronary injection of sonicated Ioxaglate. The average segmental score by two-dimensional echocardiography (graded 0, normal, to 3, akinetic/dyskinetic) and global ejection fraction (left ventricular ejection fraction, LVEF%) by left ventriculography were measured at 1 day and at 4 weeks after reflow. Hypokinesis in the infarct region was assessed by the centerline method and expressed in terms of standard deviations (regional wall motion [RWM]: SD/chord) of normal. Immediately after reflow, 30 of 39 patients (group A) showed significant contrast enhancement within the risk area. The other nine patients (23%, group B), however, showed the residual contrast defect in the risk area (myocardial no reflow...

1,056 citations


Journal ArticleDOI
TL;DR: The Doppler guide wire measures phasic flow velocity patterns and linearly tracks changes in flow rate in small, straight coronary arteries and should facilitate measurement ofphasic coronary flow velocity during coronary angiography and angioplasty.
Abstract: BACKGROUNDAn improved intravascular ultrasonic Doppler device could aid the clinical assessment of coronary hemodynamics. We evaluated a new device consisting of a 12-MHz piezoelectric transducer integrated onto the tip of a 0.018-in. flexible, steerable angioplasty guide wire.METHODS AND RESULTSDoppler spectra were recorded in model tubes with pulsatile blood flow and in-line electromagnetic flowmeter. In four straight tubes (i.d., 0.79-4.76 mm), the time average of spectral peak velocity (APV) was linearly related to blood flow (QEMF) (r2 greater than or equal to 0.98 for each tube). A Doppler-derived quantitative flow estimate (QD) was calculated as the product of vessel cross-sectional area and mean velocity, with mean velocity estimated as 0.5 x APV. The slope of QD versus QEMF for the four tubes was near unity. APV was less accurate in a 7.94-mm straight tube and in tortuous segments. In four dogs, the left circumflex coronary artery (LCx) was perfused from the femoral artery via a cannula with in-l...

1,024 citations


Journal ArticleDOI
TL;DR: Carefully selected patients with moderate to severe CHF can achieve significant, worthwhile improvements with exercise training, and autonomic balance was altered by physical training when assessed by three methods.
Abstract: BACKGROUNDMany secondary abnormalities in chronic heart failure (CHF) may reflect physical deconditioning. There has been no prospective, controlled study of the effects of physical training on hemodynamics and autonomic function in CHF.METHODS AND RESULTSIn a controlled crossover trial of 8 weeks of exercise training, 17 men with stable moderate to severe CHF (age, 61.8 +/- 1.5 years; left ventricular ejection fraction, 19.6 +/- 2.3%), increased exercise tolerance (13.9 +/- 1.0 to 16.5 +/- 1.0 minutes, p less than 0.001), and peak oxygen uptake (13.2 +/- 0.9 to 15.6 +/- 1.0 ml/kg/min, p less than 0.01) significantly compared with controls. Training increased cardiac output at submaximal (5.9-6.7 l/min, p less than 0.05) and peak exercise (6.3-7.1 l/min, p less than 0.05), with a significant reduction in systemic vascular resistance. Training reduced minute ventilation and the slope relating minute ventilation to carbon dioxide production (-10.5%, p less than 0.05). Sympathovagal balance was altered by ph...

956 citations


Journal ArticleDOI
TL;DR: These results constitute the initial demonstration at the cellular level that adrenergic stimulation leads to cyclic AMP-mediated calcium overload of the cell, with a resultant decrease in synthetic activity and/or viability.
Abstract: BACKGROUNDTo delineate the mechanism(s) of catecholamine-mediated cardiac toxicity, we exposed cultures of adult cardiac muscle cells, or cardiocytes, to a broad range of norepinephrine concentrations.METHODS AND RESULTSNorepinephrine stimulation resulted in a concentration-dependent decrease in cardiocyte viability, as demonstrated by a significant decrease in viable rod-shaped cells and a significant release of creatine kinase from cells in norepinephrine-treated cultures. Norepinephrine-mediated cell toxicity was attenuated significantly by beta-adrenoceptor blockade and mimicked by selective stimulation of the beta-adrenoceptor, whereas the effects mediated by the alpha-adrenoceptor were relatively less apparent. When norepinephrine stimulation was examined in terms of cardiocyte anabolic activity, there was a concentration-dependent decrease in the incorporation of [3H]phenylalanine and [3H]uridine into cytoplasmic protein and nuclear RNA, respectively. The decrease in cytoplasmic labeling was largel...

858 citations


Journal ArticleDOI
TL;DR: Lumen diameter was not affected by age or by vessel tortuosity but was significantly increased among men with left ventricular hypertrophy or dilated cardiomyopathy, and should be of particular value in the investigation of diffuse atherosclerotic disease.
Abstract: BACKGROUND Precise knowledge of the expected "normal" lumen diameter at a given coronary anatomic location is a first step toward developing a quantitative estimate of coronary disease severity that could be more useful than the traditional "percent stenosis." METHODS AND RESULTS Eighty-three arteriograms were carefully selected from among 9,160 consecutive studies for their smooth lumen borders indicating freedom from atherosclerotic disease. Of these, 60 men and 10 women had no abnormalities of cardiac function, seven men had idiopathic dilated cardiomyopathy, and six men had left ventricular hypertrophy associated with significant aortic stenosis. Lumen diameter was measured at 96 points in 32 defined coronary segments or major branches. Measurements were scaled to the catheter, corrected for imaging distortion, and had a mean repeat measurement error of 0.12 mm. When sex, anatomic dominance, and branch length were accounted for, normal lumen diameter at each of the standard anatomic points could usually be specified with a population variance of +/- 0.6 mm or less (SD) and coefficient of variation of less than 0.25 (SD/mean). For example, the left main artery measured 4.5 +/- 0.5 mm, the proximal left anterior descending coronary artery (LAD) 3.7 +/- 0.4 mm, and the distal LAD 1.9 +/- 0.4 mm. For the LAD, lumen diameter was not affected by anatomic dominance (right versus left), but for the right coronary artery, proximal diameter varied between 3.9 +/- 0.6 and 2.8 +/- 0.5 mm (p less than 0.01) and for the left circumflex, between 3.4 +/- 0.5 and 4.2 +/- 0.6 mm (p less than 0.01). Women had smaller epicardial arterial diameter than men (-9%; p less than 0.001), even after normalization for body surface area (p less than 0.01). Branch artery caliber was unaffected by the anatomic dominance but increased with branch length, expressed as a fraction of the origin-to-apex distance (p less than 0.001). Lumen diameter was not affected by age or by vessel tortuosity but was significantly increased among men with left ventricular hypertrophy (+ 17%; p less than 0.001) or dilated cardiomyopathy (+ 12%; p less than 0.001). CONCLUSIONS This is a reference normal data set against which to compare lumen dimensions in various pathological states. It should be of particular value in the investigation of diffuse atherosclerotic disease.

840 citations


Journal ArticleDOI
TL;DR: These results may partly explain the alterations of contractility in vivo in patients with heart failure.
Abstract: BACKGROUNDExperiments were performed in human ventricular myocytes to investigate properties of excitation-contraction coupling in patients with terminal heart failure. Myocytes were isolated from left ventricular myocardium of patients with cardiac failure caused by dilated or ischemic cardiomyopathy undergoing transplantation. These results were compared with those obtained from cells of healthy donor hearts that for technical reasons were not suitable for transplantation.METHODS AND RESULTS[Ca2+]i transients and Ca2+ currents were recorded from isolated cells under voltage clamp perfused internally with the Ca2+ indicator fura 2. In cells that were stimulated externally, the cell-permeant form of the indicator, fura 2-AM, was used. When action potentials were to be recorded, cells were stimulated in current clamp mode. Unstimulated Ca2+ current densities were not significantly different in myopathic and control cells. In diseased myocytes, resting [Ca2+]i levels were 165 +/- 61 nmol/l, compared with 95...

Journal ArticleDOI
TL;DR: The main purpose of the review is to delineate normal arterial intima from atherosclerotic lesions and, in particular, to distinguish physiological adaptations from atheosclerotic increases in intimal thickness.
Abstract: This report is a concise review of current knowledge of the structure and function of the intima of the aorta and the major distributing arteries. The main purpose of the review is to delineate normal arterial intima from atherosclerotic lesions and, in particular, to distinguish physiological adaptations from atherosclerotic increases in intimal thickness. To characterize normal intima, including the adaptive intimal thickenings, some of which represent locations in which atherosclerotic lesions are prone to develop, the structure, composition, and functions of the arterial intima in young people as well as in laboratory animals not subjected to known atherogenic stimuli are reviewed. This report on arterial intima is the first in a series of four. The second report will review and define initial, fatty streak, and intermediate types of atherosclerotic lesions, and the third report will review all types of advanced (i.e., potentially clinical and clinical) lesions. The overall objective is to define arterial intima and all types of atherosclerotic lesions, and then to postulate, in a fourth and final report, a valid and up-to-date pathobiologicaJ nomenclature and classification of atherosclerotic lesions.

Journal ArticleDOI
Helmut Drexler1, Urs Riede1, Thomas Münzel1, H König1, E Funke1, Hanjörg Just1 
TL;DR: It appears that alterations of skeletal muscle contribute to the decreased exercise capacity of patients with chronic heart failure but are, in principle, reversible by an effective treatment regimen.
Abstract: BACKGROUNDThe present study was designed to define the prevalence and characteristics of skeletal muscle alterations in patients with chronic heart failure (CHF) and their relation to exercise capacity.METHODS AND RESULTSThe ultrastructure of skeletal muscle was analyzed by ultrastructural morphometry in 57 patients with CHF and 18 healthy controls. The volume density of mitochondria (Vvm) and the surface density (Svmc) of mitochondrial cristae were evaluated as a structural correlate of oxidative capacity of skeletal muscle. Vvm and Svmc were reduced by approximately 20% in patients with severe CHF irrespective of age and etiology. The cytochrome oxidase activity in mitochondria as determined by cytochemistry and subsequent morphometry in a subset of patients (n = 10) was significantly decreased in heart failure (p less than 0.01). The capillary length density of skeletal muscle was reduced in CHF (n = 12, p less than 0.05), and the fiber type distribution was shifted to type II fibers (n = 15, p less th...

Journal ArticleDOI
TL;DR: Findings indicate that patients with chronic HF frequently develop significant skeletal muscle atrophy and metabolic abnormalities, which is consistent with intrinsic oxidative abnormalities.
Abstract: BACKGROUNDThe purpose of this study was to investigate the prevalence of skeletal muscle atrophy and its relation to exercise intolerance and abnormal muscle metabolism in patients with heart failure (HF).METHODS AND RESULTSPeak VO2, percent ideal body weight (% IBW), 24-hour urine creatinine (Cr), and anthropometrics were measured in 62 ambulatory patients with HF. 31P magnetic resonance spectroscopy (MRS) and imaging (MRI) of the calf were performed in 15 patients with HF and 10 control subjects. Inorganic phosphorus (Pi), phosphocreatine (PCr), and intracellular pH were measured at rest and during exercise. Calf muscle volume was determined from the sum of the integrated area of muscle in 1-cm-thick contiguous axial images from the patella to the calcaneus. A reduced skeletal muscle mass was noted in 68% of patients, as evidenced by a decrease in Cr-to-height ratio of less than 7.4 mg/cm and/or upper arm circumference of less than 5% of normal. Calf muscle volume (MRI) was also reduced in the patients ...

Journal Article
TL;DR: A definitive answer on the role that the analysis of markers of cardiac vagal activity may play in risk stratification of patients with coronary artery disease should be provided by Autonomic Tone and Reflexes After Myocardial Infarction (ATRAMI), an ongoing prospective study.
Abstract: The analysis of the autonomic control of the heart, by means of indirect markers, may represent a new approach for identifying patients at higher risk for sudden cardiac death after a myocardial infarction. This possibility is based on the evidence that autonomic responses during acute myocardial ischemia are a major determinant of the outcome (i.e., occurrence of ventricular fibrillation or survival). Specifically, sympathetic activation can trigger malignant arrhythmias, whereas vagal activity may exert a protective effect. Several experimental observations have provided new insights on the relation between sympatho-vagal interactions and the likelihood for the occurrence of ventricular fibrillation. In an established experimental model for sudden death involving conscious dogs with a healed myocardial infarction, either depressed reflex chronotropic responses during a blood pressure rise or reduced variability of heart rate (respectively, markers of reflex and tonic cardiac vagal activity) identify dogs at greater risk to develop malignant arrhythmias during a new ischemic episode. In anesthetized cats, direct neural recording of vagal activity to the heart confirmed that vigorous reflex vagal activation during acute myocardial ischemia is associated with protection from ventricular fibrillation. Furthermore, in these experiments the reflex neural response to acute myocardial ischemia was predicted by the analysis of baroreflex sensitivity. The antifibrillatory effect of vagal activation is confirmed by the prevention of ventricular fibrillation during acute ischemia in dogs susceptible to sudden cardiac death by direct electrical stimulation of the right vagus. The clinical counterpart of these experimental data lies in three separate prospective studies showing a higher cardiac mortality in patients who after a myocardial infarction have a depressed baroreflex sensitivity or a decreased heart rate variability. A definitive answer on the role that the analysis of markers of cardiac vagal activity may play in risk stratification of patients with coronary artery disease should be provided by Autonomic Tone and Reflexes After Myocardial Infarction (ATRAMI), an ongoing prospective study. In ATRAMI, baroreflex sensitivity and heart rate variability will be assessed within 20 days after a myocardial infarction in 1,200 patients enrolled in Europe, U.S.A., and Japan with a minimum follow up of one year.

Journal ArticleDOI
TL;DR: These results highlight effects of increased pulsatile load caused by aging or hypertension on the pressure-volume loop and indicate that this load and its effects on cardiac performance are often underestimated by mean arterial resistance but are better accounted for by Ea.
Abstract: BACKGROUNDThis study tested whether the simple ratio of ventricular end-systolic pressure to stroke volume, known as the effective arterial elastance (Ea), provides a valid measure of arterial load in humans with normal and aged hypertensive vasculatures.METHODS AND RESULTSVentricular pressure-volume and invasive aortic pressure and flow were simultaneously determined in 10 subjects (four young normotensive and six older hypertensive). Measurements were obtained at rest, during mechanically reduced preload, and after pharmacological interventions. Two measures of arterial load were compared: One was derived from aortic input impedance and arterial compliance data using an algebraic expression based on a three-element Windkessel model of the arterial system [Ea(Z)], and the other was more simply measured as the ratio of ventricular end-systolic pressure to stroke volume [Ea(PV)]. Although derived from completely different data sources and despite the simplifying assumptions of Ea(PV), both Ea(Z) and Ea(PV)...

Journal ArticleDOI
TL;DR: Elevated immunoreactive endothelin-1 specifically correlated with the extent of pulmonary hypertension in congestive heart failure patients, suggesting it is a regional mediator ofmonary hypertension or a marker for its occurrence requires additional evaluation.
Abstract: BACKGROUNDEndothelin is a family of potent vasoconstrictor peptides of vascular endothelial origin. Although it has been proposed that the vasoconstrictor effects of endothelin are produced at the ...

Journal ArticleDOI
TL;DR: It is indicated that more than half of patients with premature CAD have a familial lipoprotein disorder, with Lp(a) excess, hypertriglyceridemia with hypoalphalipoproteinemia, and combined hyperlipidemia and apolipoprotein levels are in part genetically determined.
Abstract: The prevalence of familial lipoprotein disorders was assessed in 102 kindreds with — total of 603 subjects in whom the proband had angiographically documented significant (>50% narrowing) coronary artery disease. Kindreds were classified as abnormal if the proband and at least one first degree relative had fasting triglyceride, low density lipoprotein (LDL) cholesterol, apolipoprotein (apo) B, or lipoprotein (a) values >90th percentile or their high density lipoprotein (HDL) cholesterol or apoA-I value were <10th percentile of age and gender adjusted control values. The following prevalence of familial disorders was noted: Lp(a) excess 18.6%, dyslipidemia (elevated triglycerides and low HDL cholesterol) 14.7%, combined hyperlipidemia (11.7% with low HDL cholesterol) 13.7%, hyperapobetalipoproteinemia 5%, hypoalphalipoproteinemia 4%, and hypercholesterolemia 3%.

Journal ArticleDOI
TL;DR: A lower stroke volume, heart rate, and arteriovenous oxygen difference at maximal exercise all contribute to the age-related decline in V˙o2max.
Abstract: BACKGROUND The relative contributions of decreases in maximal heart rate, stroke volume, and oxygen extraction and of changes in body weight and composition to the age-related decline in maximal oxygen uptake (VO2max) are unclear and may be influenced by sex and level of physical activity. METHODS AND RESULTS To investigate mechanisms by which aging, sex, and physical activity influence VO2max, we quantified VO2, cardiac output, and heart rate during submaximal and maximal treadmill exercise and assessed weight and fat-free mass in healthy younger and older sedentary and endurance exercise-trained men and women. For results expressed in milliliters per kilogram per minute, a three-to-four-decade greater age was associated with a 40-41% lower VO2max in sedentary subjects and a 25-32% lower VO2max in trained individuals (p less than 0.001). A smaller stroke volume accounted for nearly 50% of these age-related differences, and the remainder was explained by a lower maximal heart rate and reduced oxygen extraction (all p less than 0.001). Age-related effects on maximal heart rate and oxygen extraction were attenuated in trained subjects (p less than 0.05). After normalization of VO2max and maximal cardiac output to fat-free mass, age- and training-related differences were reduced by 24-47% but remained significant (p less than 0.05). For trained but not sedentary subjects, maximal cardiac output and stroke volume normalized to fat-free mass were greater in men than in women (p less than 0.05). CONCLUSIONS A lower stroke volume, heart rate, and arteriovenous oxygen difference at maximal exercise all contribute to the age-related decline in VO2max. Effects of age and training on VO2max, maximal cardiac output, and stroke volume cannot be fully explained by differences in body composition. In sedentary subjects, however, the sex difference in maximal cardiac output and stroke volume can be accounted for by the greater percentage of body fat in women than in men.

Journal ArticleDOI
TL;DR: The risks of pulmonary angiography were sufficiently low to justify it as a diagnostic tool in the appropriate clinical setting and clinical judgment is probably the most important consideration in the assessment of risk.
Abstract: BACKGROUNDThe Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) addressed the value of ventilation/perfusion scans in acute pulmonary embolism (PE). The present study evaluates the risks and diagnostic validity of pulmonary angiography in 1,111 patients who underwent angiography in PIOPED:METHODS AND RESULTSComplications were death in five (0.5%), major nonfatal complications in nine (1%), and less significant or minor in 60 (5%). More fatal or major nonfatal complications occurred in patients from the medical intensive care unit than elsewhere: five of 122 (4%) versus nine of 989 (1%) (p less than 0.02). Pulmonary artery pressure, volume of contrast material, and presence of PE did not significantly affect the frequency of complications. Renal dysfunction, either major (requiring dialysis) or less severe, occurred in 13 of 1,111 (1%). Patients who developed renal dysfunction after angiography were older than those who did not have renal dysfunction: 74 +/- 13 years versus 57 +/- 17 years...

Journal ArticleDOI
TL;DR: An area showing slow potentials is present at the perinodal region in humans and application of radiofrequency energy renders tachycardia noninducible through the preferential modification of the anterograde slow pathway in patients with AVNRT.
Abstract: BACKGROUNDAblation of the slow pathway has been performed to eliminate atrioventricular (AV) nodal reentrant tachycardia (AVNRT) either by a surgical approach or by using radiofrequency catheter technique guided by retrograde slow pathway activation mapping. From previous experience of midseptal and posteroseptal mapping, we were aware of the existence of peculiar slow potentials in most humans. Postulating their role in AVNRT, we studied these potentials and the effects of radiofrequency energy.METHODS AND RESULTSSixty-four patients (mean age, 48 +/- 19 years) with the usual form of AVNRT were studied. Slow, low-amplitude potentials were recorded when using the anterograde AV conducting system. Slow potentials occupied all (giving a continuum of electrograms) or some of the time between the atrial and ventricular electrograms. Their most specific patterns were their progressive response to increasing atrial rates, which resulted in a dramatic decline in amplitude and slope, a corresponding increase in du...

Journal Article
TL;DR: The U-shaped relation between total mortality in men and the flat relation in women resulted largely from a positive relation of TC with coronary heart disease death and an inverse relation with deaths caused by some cancers (e.g., lung but not colon), respiratory disease, digestive disease, trauma, and residual deaths.
Abstract: BackgroundA National Heart, Lung, and Blood Institute (NHLBI) Conference was held October 9–10, 1990, to review and discuss existing data on U-shaped relations found between mortality rates and blood total cholesterol levels (TC) in some but not other studies. Presentations were given from 19 cohort studies from the United States, Europe, Israel, and Japan. A representative of each study presented its findings and also submitted tables of proportional hazards regression coefficients for entry TC levels in regard to death, and these were incorporated into a formal statistical overview adjusted for age, diastolic blood pressure, cigarette smoking, body mass index, and alcohol intake, as available. Methods and ResultsThe U-shape for total mortality in men and the flat relation in women resulted largely from a positive relation of TC with coronary heart disease death and an inverse relation with deaths caused by some cancers (e.g., lung but not colon), respiratory disease, digestive disease, trauma, and residual deaths. Risk for combined noncardiovascular, noncancer causes of death decreased steadily across the range of TC. The conference considered possible explanations for the statistical associations found between low TC levels or active TC lowering and certain causes of death. One is that TC is lowered by some disease conditions themselves, such as wasting in chronic pulmonary disease or reduced production and secretion of cholesterol-bearing lipoproteins with liver disease. In this sort of situation, the TC: mortality association found in observational studies may be due to preexisting disease. This was addressed by excluding early deaths from the analysis, which did not change the results. The conference considered as well the biological function of cholesterol, which, if seriously deranged, might hypothetically cause a wide variety of diseases and dysfunction. The conference also considered the biological functions that might provide plausible mechanisms for the associations found. ConclusionsDefinitive interpretation of the associations observed was not possible, although most participants considered it likely that many of the statistical associations of low or lowered TC level are explainable by confounding in one form or another. The conference focused on the apparent existence and nature of these associations and on the need to understand their source rather than on any pertinence of the findings for public health policy. Further research is recommended to explain the observed associations of low TC levels (and TC lowering) with certain noncardiovascular diseases. This includes studies of the time course of TC change in disease, the relation of TC to morbidity, further studies of possible epidemiological confounding, monitoring of population trends in TC and mortality, further studies of the relations in women, auditing of noncardiovascular events in trials, studies of cell membrane, genetic and molecular links to cholesterol metabolism, TC level and disease, studies of disease manifestations in specific lipid disorders, and further study of the proposed causal mechanisms linking low TC and hemorrhagic stroke.

Journal ArticleDOI
TL;DR: In patients with heart failure and reduced LVEF, chronic ACE inhibition with enalapril prevents progressive LV dilatation and systolic dysfunction (increased ESV).
Abstract: BACKGROUND In patients with heart failure, activation of the renin-angiotensin system is common and has been postulated to provide a stimulus for further left ventricular (LV) structural and functional derangement. We tested the hypothesis that chronic administration of the angiotensin converting enzyme (ACE) inhibitor enalapril prevents or reverses LV dilatation and systolic dysfunction among patients with depressed ejection fraction (EF) and symptomatic heart failure. METHODS AND RESULTS We examined subsets of patients enrolled in the Treatment Trial of Studies of Left Ventricular Dysfunction (SOLVD). Fifty-six patients with mild to moderate heart failure underwent serial radionuclide ventriculograms, and 16 underwent serial left heart catheterizations, before and after randomization to enalapril (2.5-20 mg/day) or placebo. At 1 year, there were significant treatment differences in LV end-diastolic volume (EDV; p less than 0.01), end-systolic volume (ESV; p less than 0.005), and EF (p less than 0.05). These effects resulted from increases in EDV (mean +/- SD, 136 +/- 27 to 151 +/- 38 ml/m2) and ESV (103 +/- 24 to 116 +/- 24 ml/m2) in the placebo group and decreases in EDV (140 +/- 44 to 127 +/- 37 ml/m2) and ESV (106 +/- 42 to 93 +/- 37 ml/m2) in the enalapril group. Mean LVEF increased in enalapril patients from 0.25 +/- 0.07 to 0.29 +/- 0.08 (p less than 0.01). There was a significant treatment difference in LV end-diastolic pressure at 1 year (p less than 0.05), with changes paralleling those of EDV. The time constant of LV relaxation changed only in the placebo group (p less than 0.01 versus enalapril), increasing from 59.2 +/- 8.0 to 67.8 +/- 7.2 msec. Serial radionuclide studies over a period of 33 months showed increases in LV volumes only in the placebo group. Two weeks after withdrawal of enalapril, EDV and ESV increased to baseline levels but not to the higher levels observed with placebo. CONCLUSIONS In patients with heart failure and reduced LVEF, chronic ACE inhibition with enalapril prevents progressive LV dilatation and systolic dysfunction (increased ESV). These effects probably result from a combination of altered remodeling and sustained reduction in preload and afterload.

Journal ArticleDOI
TL;DR: This stent may be a useful adjunct to balloon dilatation in acute or threatened closure and presents the early clinical results.
Abstract: BACKGROUND. Acute closure remains a significant limitation of percutaneous transluminal coronary angioplasty (PTCA) and underlies the majority of ischemic complications. This study details the clinical and angiographic characteristics of a series of patients receiving an intracoronary stent device to manage acute and threatened closure and presents the early clinical results. METHODS AND RESULTS. From October 1989 through June 1991, 115 patients undergoing PTCA received intracoronary stents to treat acute or threatened closure in 119 vessels. Sixty-three percent had multivessel coronary disease, 33 (29%) had undergone prior coronary artery bypass grafting (CABG), and 52 (45%) had had previous PTCA. Using the American College of Cardiology/American Heart Association (ACC/AHA) classification, 15% of lesions were class A, 55% were class B, and 30% were class C. Eight patients were referred with severe coronary dissection and unstable angina after PTCA at other institutions. Acute closure was defined as occlusion of the vessel with TIMI (Thrombolysis in Myocardial Infarction) 0 or 1 flow immediately before stent placement. Threatened closure required two or more of the following criteria: 1) a residual stenosis greater than 50%, 2) TIMI grade 2 flow, 3) angiographic dissection comprising extraluminal dye extravasation and/or a length of greater than 15 mm, 4) evidence of clinical ischemia (either typical angina or ECG changes). Twelve vessels (10%) met the criteria for acute closure, and 87 vessels (73%) satisfied the criteria for threatened closure. Twenty vessels (17%) failed to meet two criteria. Stenting produced optimal angiographic results in 111 vessels (93%), with mean diameter stenosis (+/- 1 SD) reduced from 83 +/- 12% before to 18 +/- 29% after stenting. Overall, in-hospital mortality was 1.7% and CABG was required in 4.2%; Q wave myocardial infarction (MI) occurred in 7% and non-Q wave MI in 9%. Stent thrombosis occurred in nine patients (7.6%). For the 108 patients who presented to the catheterization laboratory without evolving MI, Q wave MI occurred in 4% and non-Q wave MI occurred in 7%. Angiographic follow-up has been performed in 81 eligible patients (76%), and 34 patients (41%) had a lesion of greater than or equal to 50%. CONCLUSIONS. This stent may be a useful adjunct to balloon dilatation in acute or threatened closure. Randomized studies comparing this stent with alternative technologies are required.

Journal ArticleDOI
TL;DR: The U-shape for total mortality in men and the flat relation in women resulted largely from a positive relation of TC with coronary heart disease death and an inverse relation with deaths caused by some cancers, which decreased steadily across the range of TC.
Abstract: BACKGROUNDA National Heart, Lung, and Blood Institute (NHLBI) Conference was held October 9-10, 1990, to review and discuss existing data on U-shaped relations found between mortality rates and blood total cholesterol levels (TC) in some but not other studies. Presentations were given from 19 cohort studies from the United States, Europe, Israel, and Japan. A representative of each study presented its findings and also submitted tables of proportional hazards regression coefficients for entry TC levels in regard to death, and these were incorporated into a formal statistical overview adjusted for age, diastolic blood pressure, cigarette smoking, body mass index, and alcohol intake, as available.METHODS AND RESULTSThe U-shape for total mortality in men and the flat relation in women resulted largely from a positive relation of TC with coronary heart disease death and an inverse relation with deaths caused by some cancers (e.g., lung but not colon), respiratory disease, digestive disease, trauma, and residu...

Journal ArticleDOI
TL;DR: Radiofrequency energy applied to a critical area in the atrial flutter reentrant circuit, inferior or posterior to the coronary sinus ostium, will terminate and prevent arrhythmia reinduction.
Abstract: BACKGROUND Recent studies of human type 1 atrial flutter demonstrated reentry in the right atrium and an area of slow conduction in the low posteroseptal right atrium. Direct-current catheter ablation of this area has been only moderately successful in preventing recurrence. Therefore, we performed endocardial activation mapping and entrainment pace mapping during atrial flutter to determine the critical site for radiofrequency ablation of this arrhythmia. METHODS AND RESULTS Twelve consecutive patients (seven men and five women; age, 21-73 years) with type 1 atrial flutter (mean cycle length, 253 +/- 39 msec) underwent right atrial endocardial activation and entrainment pace mapping using standard transvenous catheter techniques to localize the atrial flutter reentrant circuit, the area of slow conduction, and the exit site from the area of slow conduction. Upon identifying appropriate sites, radiofrequency energy (16-29 W) was applied via a 4-mm tipped catheter. Activation mapping of atrial flutter revealed a counterclockwise reentrant wave front originating just inferior or posterior to the coronary sinus ostium, proceeding superiorly in the atrial septum to the right atrial free wall, then inferiorly toward the tricuspid annulus and finally medially between the inferior vena cava and the tricuspid annulus, where low-amplitude fragmented electrical activity was noted. Entrainment pace mapping from this area produced an exact P wave match to atrial flutter on 12-lead ECG with a long (greater than 40 msec) stimulus-to-P interval indicating slow conduction, whereas pacing just inferior or posterior to the coronary sinus ostium produced an exact P wave match with a short stimulus-to-P interval (less than 40 msec), presumably identifying the exit site from the area of slow conduction. Radiofrequency energy (one to 14 applications) was effective in terminating and preventing reinduction of atrial flutter in 10 patients. In two patients, atrial flutter was not terminated during radiofrequency energy application but during subsequent pacing attempts. Sites where ablation was successful, located just inferior or posterior to the coronary sinus ostium, were characterized by discrete electrograms with activation times of -20 to -50 msec before P wave onset and exact entrainment pace maps with a stimulus-to-P interval of 20 to 40 msec, consistent with the exit site from the area of slow conduction. Follow-up (mean, 16 +/- 9 weeks; range, 2-31 weeks) revealed recurrence of the original atrial flutter in two patients, one of whom underwent repeat ablation without further recurrence, self-limited infrequent recurrence of a new atrial flutter or atrial fibrillation in three suppressed by beta-blocker or digoxin, and no recurrence in seven. CONCLUSIONS 1) Radiofrequency energy applied to a critical area in the atrial flutter reentrant circuit, inferior or posterior to the coronary sinus ostium, will terminate and prevent arrhythmia reinduction. 2) Long-term follow-up in a larger series of patients will be required to confirm efficacy of this technique, although short-term results look promising.

Journal ArticleDOI
TL;DR: Long-term angiotensin converting enzyme inhibition with cilazapril in a dose of 5 mg b.i.d. does not prevent restenosis and does not favorably influence the overall clinical outcome after PTCA.
Abstract: BACKGROUND Cilazapril is a novel angiotensin converting enzyme inhibitor with antiproliferative effects in the rat model after balloon injury. METHODS AND RESULTS We conducted a randomized, double-blind placebo-controlled trial to assess the effect of cilazapril in angiographic restenosis prevention after percutaneous transluminal coronary angioplasty (PTCA). Patients received cilazapril 2.5 mg in the evening after successful PTCA and 5 mg b.i.d. for 6 months or matched placebo. In addition, all patients received aspirin for 6 months. Coronary angiograms before PTCA, after PTCA, and at 6-month follow-up were quantitatively analyzed. In 94% of 735 recruited patients, PTCA was successful and all inclusion and exclusion criteria were met. For the per-protocol analysis, quantitative angiography after PTCA and at follow-up was available in 595 patients who complied with the treatment regimen (309 control, 286 cilazapril). The mean difference in minimal coronary lumen diameter between post-PTCA and follow-up angiogram (primary end point) was -0.29 +/- 0.49 mm in the control group and -0.27 +/- 0.51 mm in the cilazapril group. Clinical events during 6-month follow-up, analyzed on an intention-to-treat basis, were ranked according to the most serious clinical event ranging from death (control, two; cilazapril, three), nonfatal myocardial infarction (control, eight; cilazapril, 5), coronary revascularization (control, 51; cilazapril, 53), or recurrent angina requiring medical therapy (control, 67; cilazapril, 68) to none of the above (control, 224; cilazapril, 212). There were no significant differences in ranking. CONCLUSIONS Long-term angiotensin converting enzyme inhibition with cilazapril in a dose of 5 mg b.i.d. does not prevent restenosis and does not favorably influence the overall clinical outcome after PTCA.

Journal ArticleDOI
TL;DR: In this paper, contractile function of isolated left ventricular myocardium from New York Heart Association class IV-failing and nonfailing human hearts at physiological temperature and heart rates was investigated.
Abstract: BACKGROUNDIn congestive heart failure (idiopathic dilated cardiomyopathy), exercise is accompanied by a smaller-than-normal decrease in end-diastolic left ventricular volume, depressed peak rates of left ventricular pressure rise and fall, and depressed heart-rate-dependent potentiation of contractility (bowditch treppe). We studied contractile function of isolated left ventricular myocardium from New York Heart Association class IV-failing and nonfailing hearts at physiological temperature and heart rates in order to identify and quantitate abnormalities in myocardial function that underlie abnormal ventricular function.METHODS AND RESULTSThe isometric tension-generating ability of isolated left ventricular strips from nonfailing and failing human hearts was investigated at 37 degrees C and contraction frequencies ranging from 12 to 240 per minute (min-1). Strips were dissected using a new method of protection against cutting injury with 2,3-butanedione monoxime (BDM) as a cardioplegic agent. In nonfaili...

Journal ArticleDOI
TL;DR: Clinicians must exclude from selection for Fontan operation patients known to be at high risk for death or poor outcome to assure good functional long-term outcome in addition to survival.
Abstract: BACKGROUNDThe purpose of this study was to estimate survival and quality of outcome and assess factors associated with outcome for patients out 5 to 15 years from their Fontan operation.METHODS AND RESULTSWe studied 352 patients who had the Fontan operation prior to 1985. The overall 1-, 5-, and 10-year survival was 77%, 70%, and 60%, respectively. The following factors were significantly associated with lower survival: univentricular heart or complex congenital anomalies other than tricuspid atresia, early calendar year of operation, heterotaxia syndromes, early age at operation, increased pulmonary artery pressure, atrioventricular valve dysfunction, and higher (worse) New York Heart Association class. Reoperations were necessary for 103 of the 352 patients. At least 20% of the survivors have or have had cardiac arrhythmias requiring antiarrhythmic medication or mechanical pacemaker insertion. Between 7% and 10% of the patients have had or had protein-losing enteropathy/hypoproteinemia. At 5 years posto...

Journal ArticleDOI
TL;DR: It is suggested that both fast and slow pathways can be selectively ablated for control of AVNRT and slow pathway ablation, by obviating the risk of AV block, appears to be safer and should be considered as the first approach.
Abstract: BACKGROUND The safety and efficacy of selective fast versus slow pathway ablation using radiofrequency energy and a transcatheter technique in patients with atrioventricular nodal reentrant tachycardia (AVNRT) were evaluated. METHODS AND RESULTS Forty-nine consecutive patients with symptomatic AVNRT were included. There were 37 women and 12 men (mean age, 43 +/- 20 years). The first 16 patients underwent a fast pathway ablation with radiofrequency current applied in the anterior/superior aspect of the tricuspid annulus. The remaining 33 patients initially had their slow pathway targeted at the posterior/inferior aspect of the right interatrial septum. The fast pathway was successfully ablated in the initial 16 patients and in three additional patients after an unsuccessful slow pathway ablation. A mean of 10 +/- 8 radiofrequency pulses were delivered; the last (successful) pulse was at a power of 24 +/- 7 W for a duration of 22 +/- 15 seconds. Four of these 19 patients developed complete atrioventricular (AV) block. In the remaining 15 patients, the post-ablation atrio-His intervals prolonged from 89 +/- 30 to 138 +/- 43 msec (p less than 0.001), whereas the shortest 1:1 AV conduction and effective refractory period of the AV node remained unchanged. Ten patients lost their ventriculoatrial (VA) conduction, and the other five had a significant prolongation of the shortest cycle length of 1:1 VA conduction (280 +/- 35 versus 468 +/- 30 msec, p less than 0.0001). Slow pathway ablation was attempted initially in 33 patients and in another two who developed uncommon AVNRT after successful fast pathway ablation. Of these 35 patients, 32 had no AVNRT inducible after 6 +/- 4 radiofrequency pulses with the last (successful) pulse given at a power of 36 +/- 12 W for a duration of 35 +/- 15 seconds. After successful slow pathway ablation, the shortest cycle length of 1:1 AV conduction prolonged from 295 +/- 44 to 332 +/- 66 msec (p less than 0.0005), the AV nodal effective refractory period increased from 232 +/- 36 to 281 +/- 61 msec (p less than 0.0001), and the atrio-His interval as well as the shortest cycle length of 1:1 VA conduction remained unchanged. No patients developed AV block. Among the last 33 patients who underwent a slow pathway ablation as the initial attempt and a fast pathway ablation only when the former failed, 32 (97%) had successful AVNRT abolition with intact AV conduction. During a mean follow-up of 6.5 +/- 3.0 months, none of the 49 patients had recurrent tachycardia. Forty patients had repeat electrophysiological studies 4-8 weeks after their successful ablation, and AVNRT could not be induced in 39 patients. CONCLUSIONS These data suggest that both fast and slow pathways can be selectively ablated for control of AVNRT: Slow pathway ablation, however, by obviating the risk of AV block, appears to be safer and should be considered as the first approach.