Acute cardiovascular responses to leg-press resistance exercise in heart transplant recipients.

BACKGROUND: Reduced skeletal muscle strength is characteristic of individuals following heart transplantation. Weight lifting exercise has been demonstrated as an effective means by which to increase muscular strength in other cardiac patients but the appropriateness of this form of exercise in heart transplant patients has not been investigated. The purpose of this study was to describe the cardiovascular responses of heart transplant patients to a single, prolonged bout of weight lifting training. METHODS: Twenty-three heart transplant recipients were stratified into early (Early; 3 months; n=6), intermediate (Intermediate; 1-3 years; n=7) and late (Late; 5-14 years; n=10) post transplant groups and studied in four experimental conditions: supine rest, upright rest, single leg-press exercise (28 repetitions over 2 min 20 s at 50% 1 repetition maximum) and recovery. Swan-Ganz catheterization allowed measurement of right heart pressures and cardiac output by thermodilution. Systemic arterial pressures and heart rate were measured continuously using a non-invasive finger cuff. RESULTS: Cardiac output increased by 30, 40 and 54% during exercise in Early, Intermediate and Late, respectively. Heart rate increased by 4.5% in Early compared to 11 and 16% increases in Intermediate and Late. At peak exercise, systolic blood pressures reached average values of 179+/-9, 180+/-14 and 176+/-8 mmHg in Early, Intermediate and Late, respectively. Average mean pulmonary artery pressure did not exceed 30 mmHg and average pulmonary wedge pressure did not exceed 15 mmHg in any group during the exercise. CONCLUSIONS: These observations indicate that a lengthened set of single leg-press exercise at a moderate lifting intensity can be performed within safe and acceptable physiological limits in patients following heart transplantation. To better address the specific rehabilitation needs of heart transplant recipients, future research should focus on developing training programs which include weight lifting exercise.

Increased circulating monocyte activation in patients with unstable coronary syndromes.

OBJECTIVES: The primary objective of this research was to assess the activation level of circulating monocytes in patients with unstable angina. BACKGROUND: Markers of systemic inflammatory responses are increased in patients with unstable coronary syndromes, but the activation state and invasive capacity of circulating monocytes have not been directly assessed. METHODS: Peripheral blood mononuclear cell (MC) activation in blood samples isolated from patients with stable and unstable coronary artery disease was measured in two studies. In study 1, a modified Boyden chamber assay was used to assess spontaneous cellular migration rates. In study 2, optical analysis of MC membrane fluidity was correlated with soluble CD14 (sCD14), a cellular activation marker. RESULTS: Increased rates of spontaneous monocyte migration (p < 0.01) were detected in patients with unstable angina (UA) (Canadian Cardiovascular Society [CCS] angina class IV) on comparison to patients with acute myocardial infarction (MI), stable angina (CCS angina classes I to III) or normal donors. No significant increase in lymphocyte migration was detected in any patient category. Baseline MC membrane fluidity measurements and sCD14 levels in patients with CCS class IV angina were significantly increased on comparison with MCs from normal volunteers (p < 0.001). A concomitant reduction in the MC response to activation was detected (p < 0.05). CONCLUSIONS: Using two complementary assays, activated monocytes with increased invasive capacity were detected in the circulation of patients with unstable angina. This is the first demonstration of increased monocyte invasive potential in unstable patients, raising the issue that systemic inflammation may both reflect and potentially drive plaque instability.

Fluorescence spectroscopic analysis of circulating platelet activation during coronary angioplasty.

BACKGROUND AND OBJECTIVE: Platelet activation during percutaneous transluminal coronary angioplasty (PTCA) initiates thrombus formation and plaque regrowth at sites of arterial injury, limiting procedure efficacy. We have developed a simple assay for circulating platelet activation based on fluorescence analysis of membrane fluidity and intracellular calcium concentration and light scattering analysis of platelet aggregation. STUDY DESIGN/MATERIALS AND METHODS: Platelet activation state was measured in 45 patients undergoing angioplasty, before and after treatment with platelet inhibitors. RESULTS: PTCA alone produced a decrease in pyrene dimer formation (P0.0083) and an increase in light scattering at 650 nm (P0.0128). Treatment with ADP and GPIIb/IIIa receptor antagonists reduced PTCA induced changes in pyrene dimer formation. An unexpected decrease in pyrene dimer formation (P0.05) was detected when the GPIIb/IIIa receptor antagonist was given together with an ADP receptor antagonist. CONCLUSIONS: 1) Analysis of membrane fluidity provides a sensitive marker for platelet activation state. 2) Reduced membrane fluidity after combined platelet inhibitor treatments suggests reduced antiplatelet efficacy.

Intracoronary ultrasound imaging: methods and clinical applications.

OBJECTIVE: To review the development of intracoronary ultrasound, its current utility and the impetus for its continued development as a coronary imaging modality. DATA SOURCES: English-language literature (1966 to 1999) was searched in the MEDLINE database with the key words 'ultra- sound', 'intravascular' and 'intracoronary', and limited to human studies. In addition, an online public access catalogue was searched using the subject headings 'cardiovascular diseases - therapy', 'heart diseases' and 'vascular diseases'. STUDY SELECTION AND DATA EXTRACTION: Articles relating to the history of intravascular or intracoronary ultrasound, methods and materials employed, advantages and disadvantages, safety issues and future directions of research in the area of intracoronary ultrasound were selected. DATA SYNTHESIS: Intracoronary ultrasound has been shown to improve upon demonstrated weaknesses of coronary angiography. This imaging technique, while invasive, has not been associated with significant, acute adverse effects and has proved to be useful in guiding interventions, and evaluating the mechanism and extent of their success. Technological limitations with respect to the equipment employed, and the acquisition, processing and display of images are the subject of intense research focus because they hinder more widespread clinical use of intracoronary ultrasound. CONCLUSIONS: Intracoronary ultrasound has emerged as a safe and useful tool in the visualization of the coronary vasculature. Technological limitations and questions about long term safety are a concern. Its ability to overcome the inherent limitations of coronary angiography, and to guide and evaluate coronary interventions supports the notion that this technique will continue to assume an ever-expanding role in interventional cardiology.

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.

The role of donor age and ischemic time on survival following orthotopic heart transplantation.

BACKGROUND: The advances in immunotherapy, along with a liberalization of eligibility criteria have contributed significantly to the ever increasing demand for donor organs. In an attempt to expand the donor pool, transplant programs are now accepting older donors as well as donors from more remote areas. The purpose of this study is to determine the effect of donor age and organ ischemic time on survival following orthotopic heart transplantation (OHT). METHODS: From April 1981 to December 1996 372 adult patients underwent OHT at the University of Western Ontario. Cox proportional hazards models were used to identify predictors of outcome. Variables affecting survival were then entered into a stepwise logistic regression model to develop probability models for 30-day- and 1-year-mortality. RESULTS: The mean age of the recipient population was 45.6 +/- 12.3 years (range 18-64 years: 54 < or = 30; 237 were 31-55; 91 > 56 years). The majority (329 patients, 86.1%) were male and the most common indications for OHT were ischemic (n = 180) and idiopathic (n = 171) cardiomyopathy. Total ischemic time (TIT) was 202.4 +/- 84.5 minutes (range 47-457 minutes). In 86 donors TIT was under 2 hours while it was between 2 and 4 hours in 168, and more than 4 hours in 128 donors. Actuarial survival was 80%, 73%, and 55% at 1, 5, and 10 years respectively. By Cox proportional hazards models, recipient status (Status I-II vs III-IV; risk ratio 1.75; p = 0.003) and donor age, examined as either a continuous or categorical variable ([age < 35 vs > or = 35; risk ratio 1.98; p < 0.001], [age < 50 vs > or = 50; risk ratio 2.20; p < 0.001], [age < 35 vs 35-49 versus > or = 50; risk ratio 1.83; p < 0.001]), were the only predictors of operative mortality. In this analysis, total graft ischemic time had no effect on survival. However, using the Kaplan-Meier method followed by Mantel-Cox logrank analysis, ischemic time did have a significant effect on survival if donor age was > 50 years (p = 0.009). By stepwise logistic regression analysis, a probability model for survival was then developed based on donor age, the interaction between donor age and ischemic time, and patient status. CONCLUSIONS: Improvements in myocardial preservation and peri-operative management may allow for the safe utilization of donor organs with prolonged ischemic times. Older donors are associated with decreased peri-operative and long-term survival following. OHT, particularly if graft ischemic time exceeds 240 minutes and if these donor hearts are transplanted into urgent (Status III-IV) recipients.

The Canadian Study of Cardiac Transplantation. Atherosclerosis. Investigators of the CASCADE Study.

OBJECTIVES: To describe risk factors associated with the development of transplantation coronary artery disease (TCAD). DESIGN: A retrospective study of the Canadian experience. PATIENTS: Seven hundred and nineteen patients with follow-up of at least 12 months following transplantation and a minimum of one coronary angiogram were analyzed. RESULTS: Two hundred and fourteen patients (30%) developed angiographic evidence of TCAD during an average follow-up of 50+/-25 months. Actuarial freedom rate from TCAD averaged 60%, and survival averaged 85% five years following transplantation. Abnormal coronary angiograms increased from 11% to 40% between the first and the fifth year following transplantation. The Cox multivariate final model showed that recipients of donor hearts of 50 years and older (RR 4.35, 95% CI 2.32 to 8.15), patients with two or more episodes of acute rejection (RR 1.56, 95% CI 1.11 to 2.21) and patients with a diagnosis of ischemic cardiomyopathy before transplantation (RR 1.38, 95% CI 1.03 to 1.84) were at higher risk of TCAD. The same risk factors also had a significant effect on survival, although patients who were administered a hepatic hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor during follow-up had a higher survival rate (95% versus 85%, P=0.01) five years following heart transplantation. CONCLUSIONS: Recipients of hearts from older donors, patients with an ischemic heart disease before transplantation and those with several episodes of acute rejection are at increased risk for TCAD. Patients who are administered an HMG-CoA reductase inhibitor during follow-up have a higher survival rate five years following transplantation.

Predictors of early mortality after heart transplantation: the Canadian transplant experience from 1981 to 1992. The CASCADE Investigators. Canadian Study of Cardiac Transplant Atherosclerosis Determinants.

OBJECTIVE: To determine risk factors for early death following transplantation in the Canadian heart transplant experience. METHODS: A retrospective multicentre study of the Canadian experience in heart transplantation was performed to evaluate the role of risk factors of early death within 30 days following transplantation. Eight hundred and thirty-three patients older than 15 years underwent cardiac transplantation between 1981 and 1992 in 10 centres across Canada. The association between risk factors and early mortality was analyzed with a multivariate logistic model to examine simultaneously the effect of all risk factors. RESULTS: Seventy-eight patients (9%) died during the first month following transplantation. Recipient age (P = 0.549), sex (P = 0.554) and body mass (P = 0.313) had no effect. Baseline pulmonary vascular resistance (P < 0.001) and systolic pulmonary pressure (P = 0.021) before transplantation were related to early death. Older donors (P = 0.027) were associated with a higher rate of early death but there was no relation with donor sex (P = 0.597), body mass (P = 0.413), blood group (P = 0.227) and ischemic time (P = 0.309). Patients with pulmonary vascular resistance of 6 or greater (Wood units) and donors older than 50 years had relative risks of early death five and two times, respectively, those of patients without these risk factors. CONCLUSION: Patient survival averaged 91% one month following transplantation in the Canadian experience between 1981 and 1992. The two predictors most strongly correlated with early death were elevated pulmonary vascular resistance at baseline and older donors.

Comparison of Tc-99m sestamibi perfusion imaging and echocardiography using an arbutamine infusion for the detection of coronary artery disease.

Arbutamine, a synthetic catecholamine, coupled with a closed-loop, computerized delivery system was evaluated in conjunction with technetium-99m sestamibi scintigraphy and echocardiography for the detection of coronary artery disease. Concordance between the imaging methods was 68%, with a similar sensitivity for coronary disease using echocardiography (78%) and technetium-99m sestamibi (76%), although more arbutamine-induced ischemia was noted with perfusion imaging.

Changes in skeletal muscle morphology and biochemistry after cardiac transplantation.

Skeletal muscle biopsies (vastus lateralis) were performed in 12 patients (mean age 47 +/- 11 years) before and at 3 and 12 months after cardiac transplantation. Fiber type analysis revealed a predominance of type II fibers before cardiac transplantation (66 +/- 10%); the ratio did not change after transplantation. Fiber cross-sectional area increased by 35% to 39% in all fiber types by 12 months after cardiac transplantation. Fiber cross-sectional area, however, remained below the reported normal values. The number of capillaries surrounding each fiber did not change after cardiac transplantation. Skeletal muscle enzyme activity of phosphofructokinase, citrate synthase, and beta-hydroxyacyl coenzyme A dehydrogenase increased by 26%, 47%, and 63%, respectively, after cardiac transplantation (p < 0.05). Peak oxygen uptake also increased significantly after cardiac transplantation (19.5 +/- 8.1 ml/kg/min at 12 months vs 9.8 +/- 1.4 ml/kg/min before transplant, p < 0.01); however, uptake remained 40% below that of predicted. Thus, significant improvement in skeletal muscle morphology and biochemistry occurs in the first year after cardiac transplantation in association with improved exercise capacity. Recovery, however, may be incomplete, which could explain residual impairment of exercise capacity in these patients.

Routine surveillance myocardial biopsies are unnecessary beyond one year after heart transplantation.

BACKGROUND: Myocardial rejection is most apt to occur in the first 90 days after heart transplantation. Nevertheless, surveillance endomyocardial biopsies are often performed on a regular basis, indefinitely. The benefit of this approach to patient management is uncertain. Our objective was to determine the frequency of abnormalities and the influence of a routine annual endomyocardial biopsy on patient management. METHODS: In a consecutive series of 235 transplant recipients who survived 1 year or more, the results of 1123 routine endomyocardial biopsies performed 1 year or more after transplantation were reviewed. The incidence of late rejection, presence of Quilty effect (focal endocardial or myocardial lymphocytic aggregates), and therapeutic reaction to the biopsy result were analyzed. RESULTS: Of 1123 biopsy specimens in 235 patients (1 to 12 years after transplantation), 1115 (99.3%) showed no evidence of significant rejection (grade 0 or 1). Only seven (0.6%) had evidence of rejection grade 2 or worse. Of the seven abnormal biopsy specimens in seven patients, two occurred at 1 year, two at 2 years, and one each at 4, 7, and 8 years. Of these, six were treated for rejection with an increase in the immunosuppressive therapy. One patient was identified as having a symptomatic condition at the time of biopsy. A focal endocardial or myocardial accumulation of lymphocytes (Quilty effect) was present in 311 biopsy specimens (27.6%). Beyond 1 year, 33 patients died, 14 because of graft vascular disease with or without rejection and 19 because of other causes. No deaths were predicted on the basis of a routine surveillance biopsy. CONCLUSIONS: Myocardial rejection is rare beyond 1 year after transplantation. The routine endomyocardial biopsy does not significantly impact patient management beyond 1 year. A selective approach to myocardial biopsies, on the basis of a change in clinical status or immunosuppressive medications, is justified.

Basis for aerobic impairment in patients after heart transplantation.

BACKGROUND AND METHODS: To evaluate the physiologic basis for the suboptimal peak oxygen uptake observed after heart transplantation, we calculated the functional aerobic impairment ([(peak predicted oxygen uptake-peak observed oxygen uptake)/peak predicted oxygen uptake] x 100) and related it to donor/recipient, operative, and maximal exercise variables. Fifty-seven heart transplant recipients (mean age 50 +/- 10 years, 1 to 9 years after transplantation) underwent maximal upright cycle exercise testing. Concomitant exercise central hemodynamic measurements were obtained in 36 patients (63%). RESULTS: The mean peak oxygen uptake was 21.7 +/- 6.5 ml/kg/min and functional aerobic impairment was 34% +/- 17%. Functional aerobic impairment correlated positively (p < 0.01) with peak systemic vascular resistance (r = 0.55) and negatively with peak cardiac index (r = -0.62) and peak systemic arteriovenous oxygen difference (r = -0.66). A weak correlation was found between functional aerobic impairment and the duration of cardiac disease (r = 0.35, p < 0.01) but not the origin of heart failure. No correlation was seen between functional aerobic impairment and donor age, total ischemic time, time since transplantation, recipient age, and resting and exercise right and left ventricular filling pressures. CONCLUSIONS: These results suggest that the decreased exercise capacity observed in heart transplant recipients is in part due to increased peripheral vascular resistance and decreased oxygen extraction possibly due to skeletal muscle atrophy. These factors may be the result of irreversible changes from long-standing heart disease, deconditioning, or the effect of cyclosporine and prednisone.

Stress testing with closed-loop arbutamine as an alternative to exercise. The International Arbutamine Study Group.

OBJECTIVES: This study compared exercise and pharmacologic stress testing using arbutamine delivered by a closed-loop device for the detection of coronary artery disease. BACKGROUND: Arbutamine, an agent designed to simulate exercise, has been developed in conjunction with a closed-loop delivery device that modulates the rate of administration on the basis of physiologic feedback. METHODS: Two hundred ten patients (180 men, 30 women) with symptoms and angiographic evidence of coronary artery disease were studied. Ischemia was categorized in three ways: 1) the presence of angina; 2) the occurrence of > or = 0.1-mV horizontal or downsloping ST segment depression or elevation at 60 ms after the J point; or 3) the presence of either condition 1 or 2. RESULTS: In the 210 patients, the mean increase in heart rate and systolic blood pressure evoked by arbutamine and exercise was 51 and 53 beats/min (p = NS) and 36 and 44 mm Hg (p < 0.0001), respectively. Arbutamine detected ischemia more often than exercise with each of the three ischemic end points. Sensitivity for detecting ischemia by either angina or ST segment change was 84% (95% confidence interval ¿ change was 84% (95% confidence interval [CI] 79% to 89%) for arbutamine and 75% (95% CI 69% to 81%) for exercise testing (p = 0.014). For angina alone, sensitivity was 73% (95% CI 67% to 79%) for arbutamine and 64% (95% CI 57% to 71%) for exercise (p = 0.026). For ST segment change alone, sensitivity was 47% (95% CI 40% to 54%) for arbutamine and 44% (95% CI 37% to 51%) for exercise (p = 0.426). Cardiac events occurred in five patients (1.8%) within 24 h of the arbutamine test. CONCLUSIONS: In detecting documented coronary artery disease, the sensitivity of arbutamine testing was equal to that of exercise for the electrocardiographic end point of ST segment change alone. Arbutamine testing was significantly superior to exercise testing for either ST change or angina or for angina alone.

Latissimus dorsi dynamic cardiomyoplasty: role of combined ICD implantation.

Latissimus dorsi cardiomyoplasty is a promising surgical therapy in some patients with congestive heart failure. Although the mortality in heart failure patients is attributable primarily to heart failure and ventricular arrhythmias, the mechanism of death after cardiomyoplasty is not well characterized. We describe the clinical course of a patient undergoing cardiomyoplasty and discuss the role of combined use with an implantable cardioverter defibrillator. A 39-year-old man with congestive heart failure due to a massive anterior wall myocardial infarction was evaluated for latissimus dorsi cardiomyoplasty. The patient was in NYHA Functional Class III due to heart failure. He did not have any significant exertional or rest angina. During a Naughton stress test, the patient could exercise for 10 minutes, achieving 4 METS. Pulmonary function study showed a peak V O2 of 22.1 mL/min per kg. Radionuclide angiography demonstrated that the anterior wall was akinetic with a left ventricular ejection fraction of 22%. Cardiac hemodynamic studies suggested moderate pulmonary hypertension, elevated wedge pressure, and suboptimal response to exercise. A Holter recording showed frequent ventricular extrasystoles. Cardiomyoplasty was preferred to heart transplantation because the patient did not have end-stage heart failure. Postoperatively, the patient required low doses of dopamine. He developed recurrent, sustained, and hemodynamically significant episodes of ventricular tachycardia. He was treated with a combination of amiodarone and procainamide. He died 2 days postoperatively with ventricular fibrillation. Ventricular arrhythmias are a major cause of death in patients with heart failure. Latissimus dorsi cardiomyoplasty appears to be a promising but unproven therapy in such patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Cholesterol-lowering therapy after heart transplantation: a 12-month randomized trial.

BACKGROUND: Hypercholesterolemia, a common problem after heart transplantation, may be important in the genesis and progression of allograft coronary artery disease. The current study was performed to compare the efficacy of gemfibrozil, simvastatin, and cholestyramine for cholesterol lowering in heart transplant recipients. METHODS: In this prospective 1-year study, 48 heart transplant recipients with moderate hypercholesterolemia were randomized to therapy with gemfibrozil 600 mg twice daily (n = 17), simvastatin 10 mg daily (n = 13), and cholestyramine 4 gm twice daily (n = 18). Detailed lipoprotein analysis was performed at baseline and after 3, 6, and 12 months of treatment. RESULTS: Total cholesterol and low-density lipoprotein cholesterol were reduced 19% and 29%, respectively, after 3 months of simvastatin therapy (p < 0.0001) with a sustained reduction in total cholesterol (25%) and low-density lipoprotein cholesterol (39%) at 1 year. Gemfibrozil and cholestyramine treatment did not result in a reduction in cholesterol levels. Apolipoprotein B levels were reduced by 29% at the end of 1 year with simvastatin but not with the other treatments. Serum triglyceride levels were reduced significantly by treatment with gemfibrozil (up to 36%, p < 0.01) but not by the other treatments. High-density lipoprotein cholesterol initially rose in patients treated with simvastatin and gemfibrozil; however, this effect did not persist to 12 months. However, the ratio of low-density lipoprotein/high-density lipoprotein was favorably affected by simvastatin, with a 38% reduction by 12 months (p < 0.0001) but not by the other treatments. Over the course of 1 year, 14 patients dropped out of the study: four from the gemfibrozil arm and ten from the cholestyramine arm. Gastrointestinal intolerance was the most common reason for study termination (8 of 14). All patients in the simvastatin treatment arm completed 12 months of therapy. No biochemical abnormalities resulted from any therapy, and no therapy caused significant alteration in cyclosporine blood levels. CONCLUSIONS: Of the three therapies studied, simvastatin was found to be the most efficacious and well tolerated for cholesterol lowering in patients after heart transplantation.

Evolution of resting lung function in the first year after cardiac transplantation.

The aim of our study was to characterize the time course and magnitude of the changes in lung function in the first year after cardiac transplantation. Resting pulmonary function tests (spirometry, lung volumes and transfer factor) were performed in 14 patients prior to and at 1, 3 and 12 months after surgery. Resting central haemodynamics were also measured serially in the first year post-transplantation. Before transplantation, patients had impaired resting lung function with marked decrease in transfer factor (TL,CO). Although resting central haemodynamics improved markedly within the first week after cardiac transplantation, lung function (forced expiratory volume in one second (FEV1)) was significantly improved only at three months post-transplantation. TL,CO, however, decreased further early after cardiac transplantation. By 12 months, FEV1 and forced vital capacity had increased significantly by 31 and 33%, respectively, while total lung capacity increased by 22%. On the other hand, TL,CO did not increase significantly and remained well below normal at 12 months after cardiac transplantation, at a value equal to 68% of predicted. We conclude that the resting abnormalities in lung function of most patients with heart failure are reversible after cardiac transplantation, except for TL,CO which remains below normal values. Recovery of lung function, however, lags behind the improvement in cardiac function.

Amlodipine in chronic stable angina: results of a multicenter double-blind crossover trial.

The efficacy and safety of amlodipine, 10 mg, a new long-acting calcium antagonist, was compared with placebo in 103 patients with stable angina pectoris in a multicenter double-blind crossover study. The trial consisted of an initial 2-week single-blind placebo period followed by a first period of 4 weeks of double-blind therapy, which was followed by a 1 week washout period and then a second 4-week double-blind period after treatments were crossed over. Twenty-four-hour Holter electrocardiographic monitoring was carried out in 12 patients at three centers. In the first double-blind period amlodipine produced a significantly greater increase in symptom-limited exercise duration (amlodipine 478.5 to 520.6 vs placebo 484.6 to 485.2 seconds; change +8.8% vs +0.1%, respectively; p = 0.0004) and total work (amldipine 2426 to 2984 vs placebo 2505 to 2548 kilopondmeters; change +24% vs +1.7%, respectively; p = 0.0006) and a decrease in angina attack frequency (from 3 to 1 per week; p = 0.016) and nitroglycerin consumption (from 2 to 0.5 tablets/wk; p = 0.01) compared with placebo. Holter monitoring revealed significant reductions in numbers (amlodipine 4.65 to 2.22 vs placebo 1.84 to 1.54; change -52% vs +84%, respectively; p = 0.06), absolute total area (amlodipine 87.66 to 11.43 vs placebo 5.76 to 35.24; change -87% vs +513%, respectively; p = 0.02), and duration (amlodipine 12.29 to 2.95 vs 1.66 to 7.74 seconds; change -76% vs +367%, respectively; p = 0.008) of ST-segment depressions after treatment with amlodipine compared with placebo. After the treatments were crossed over changes continued to favor amlodipine.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of cardiac filling pressures on the release of atrial natriuretic peptide during exercise in heart transplant recipients.

OBJECTIVE: To determine the influence of body posture and central hemodynamics on the plasma levels of immunoreactive atrial natriuretic peptide (irANP) during exercise in cardiac transplant patients. METHODS: Central hemodynamics, mixed expired gas and ventilatory measurements, and venous blood sampling (for irANP determination) were obtained in cardiac transplant patients at rest and during supine (n = 12) or upright (n = 12) graded cycle exercise. Cardiopulmonary and irANP responses to exercise were compared between the upright and supine postures. RESULTS: At rest (supine), irANP concentrations were similar in both groups (172 +/- 87 pg/mL supine and 182 +/- 72 pg/mL upright) and did not correlate with resting supine central hemodynamics. During exercise, central filling pressures increased in both groups but patients exercising in the supine position had a greater increase. Peak exercise right atrial pressure was 12 +/- 4 mmHg supine versus 7 +/- 5 mmHg upright (P < 0.005). Peak exercise pulmonary capillary wedge pressure was 22 +/- 6 mmHg supine versus 14 +/- 5 mmHg upright (P < 0.005). At peak exercise, irANP levels were greater in the supine than upright position (419 +/- 166 pg/mL supine versus 277 +/- 40 pg/mL upright, P < 0.05). The change in irANP from rest to peak exercise correlated (P < 0.05) with changes in pulmonary capillary wedge pressure (r = 0.67), systolic pulmonary artery pressure (r = 0.78) and right atrial pressure (r = 0.53). There was, however, no correlation between change in irANP and peak oxygen consumption, change in heart rate or change in mean arterial blood pressure. CONCLUSIONS: In cardiac transplant recipients, exercise is a stimulus for ANP secretion, and augmentation in plasma irANP levels during exercise is modulated by changes in central hemodynamics.