Exercise-induced increase in lipid peroxidation in patients with chronic heart failure: relation to exercise intolerance.

BACKGROUND: Little is known about the relationship between exercise intolerance and lipid peroxidation in chronic heart failure (CHF) patients. This study was designed to investigate the relationship between exercise-induced plasma malondialdehyde (MDA) changes in CHF patients and to determine whether there is any association between plasma MDA levels and exercise capacity assessed by cardiopulmonary exercise testing. METHODS: Cardiopulmonary exercise testing was applied to 31 CHF patients (16 ischemic, 15 idiopathic) and controls. Rest and peak exercise blood samples were analyzed for MDA. RESULTS: Patients with CHF had elevation of plasma MDA levels during exercise compared with controls (p < 0.001 vs. p = 0.588). MDA change remained significant both in ischemic and idiopathic cardiomyopathy groups (p < 0.05 and p < 0.01, respectively). Delta MDA (peak exercise MDA - rest MDA) showed significant inverse correlation with peak oxygen consumption in patients with CHF. CONCLUSION: Lipid peroxidation is increased in patients with CHF during exercise regardless of etiology, and this increase is inversely related to oxygen consumption.

Long-term combined therapy with losartan and an angiotensin-converting enzyme inhibitor improves functional capacity in patients with left ventricular dysfunction.

OBJECTIVE: The efficacy of angiotensin-converting enzyme (ACE) inhibitors in the treatment of heart failure (HF) is well documented. However, ACE inhibitors may provide incomplete blockade of the renin-angiotensin-aldosterone system due to the alternative pathways for the production of angiotensin II (Ang II). The aim of this study was to evaluate the efficacy of combined therapy of an ACE inhibitor and the Ang II receptor blocker losartan in patients with HF by using cardiopulmonary exercise testing (CPET) on a treadmill. METHODS AND RESULTS: Seventeen patients (ejection fraction < or = 40%) were included in the study group. At the start of the study, all participants were on chronic ACE inhibitors therapy. Fifty mg losartan was added to the treatment and CPET was performed before and 6-8 months after starting losartan therapy. Sixteen patients with HF were included in the control group. CPET was performed once at the beginning and repeated 6-8 months later without any change in the treatment protocol. The change in CPET values (walk-time (WT), peakVO2, anaerobic threshold (AT), minute ventilation (VE), VE/VO2, peak heart rate (HR),VO2/HR) was investigated. In the losartan-treated group a significant increase was noted in WT (393 +/- 157 vs. 507 +/- 155 sec, p < 0.01); peak VO2 (1205 +/- 240 vs. 1330 +/- 253 ml/min, p < 0.05); and AT (794 +/- 131 vs. 895 +/- 177 ml/min, p < 0.05). In the control group exercise parameters did not change significantly. The change from baseline to follow-up between the two groups is statistically significant for WT and peak VO2 (114 +/- 94 vs. -58 +/- 134 sec, p < 0.0 1 and 125 +/-183 vs. -116 +/- 221 ml/min, p <0.01). CONCLUSIONS: Addition of losartan to the ACE inhibitor therapy in patients with HF improves functional capacity in the long run.

Echocardiographic prediction of long-term response to biventricular pacemaker in severe heart failure.

BACKGROUND: Biventricular pacing substantially improves LV systolic function and symptom status in some patients with dilated cardiomyopathy. AIMS: To assess whether the long-term benefit could be predicted from the echocardiographic parameters. METHODS AND RESULTS: Sixteen patients with dilated cardiomyopathy who underwent atrio-biventricular pacemaker implantation were analyzed in two groups: the responders (n=11) were those with a symptomatic improvement of one or more NYHA functional class; the non-responders (n=5) failed to improve at follow-up (7.6+/-5 months). Echocardiography was performed at baseline, the day after the implantation and then every 3 months. Besides the conventional parameters, the following variables were included: LV diastolic filling time (DFT); the duration of mitral regurgitation (dMR); and LV dP/dt obtained from the continuous wave mitral regurgitation curve. While the baseline DFT and dP/dt were not significantly different between non-responders and responders (256+/-105 vs. 358+/-115, P=0.14 and 564+/-199 vs. 468+/-117, P=0.44, respectively), the QRS width (149+/-15 vs. 175+/-24 ms, P=0.05) and the dMR (343+/-70 vs. 443+/-49 ms, P=0.007) were higher in the responders. The changes of dMR, DFT and QRS width by pacing were not significantly different between groups (P=0.18, 0.30 and 0.77, respectively). However, the change of LV dP/dt by pacing in the responders was significantly different than for non-responders (from 468+/-117 to 676+/-216 mmHg/s vs. from 564+/-199 to 483+/-94, P=0.002). An acute increase in LV dP/dt over 22% by pacing yielded only two false negatives and no false positives in predicting the long-term responsiveness. CONCLUSION: Patients with longer QRS and dMR are more likely to benefit from atrio-biventricular stimulation. The acute changes of Doppler derived LV dP/dt may provide valuable information in predicting the long-term response to biventricular pacing.

[Assessment of the efficacy of bisoprolol administration by cardiopulmonary exercise testing in patients with heart failure]. / Kalp Yetersizliginde Bisoprolol Tedavi Etkinliginin Kardiyopulmoner Egzersiz Testi ile Degerlendirilmesi.

OBJECTIVE: It is well known that long-term therapy with beta-blockers reduces morbidity and mortality, improves left ventricular function in patients with heart failure. However the effect of beta-blockade on exercise tolerance in patients with heart failure remains unclear. In the present study we evaluated effects of the addition of bisoprolol to standart therapy with a diuretic and an angiotensin converting enzyme (ACE) inhibitor on exercise capacity in patients with chronic heart failure. METHODS: We enrolled 52 patients (mean age 59+/-11 years) with stable, mild to moderate chronic heart failure and left ventricular ejection fraction of 40% or less receiving standart therapy with diuretic and ACE inhibitor. We randomly assigned patients to bisoprolol 1.25 mg (n=28) or control (n=24) groups. The drug progressively increased to a maximum dose of 5 mg per day. Cardiopulmonary exercise testing (CPET) was performed in all patients of the bisoprolol and control groups before and after 3 months from the beginning of the study. RESULTS: We found a significant increase in exercise duration, maximal O2 uptake (pik VO2), the O2 uptake at the anaerobic threshold (VO2-AT) and O2-pulse (pik VO2/HR), and improved functional capacity (p<0.001). Bisoprolol produced significant reduction in heart rate at rest (p=0.01) and during maximal exercise (p=0.041). In the control group no significant changes were observed. CONCLUSION: The addition of bisoprolol to the standart therapy in patients with mild to moderate heart failure is well tolerated and improves functional capacity.

Tissue Doppler imaging adds incremental value in predicting exercise capacity in patients with congestive heart failure.

Left ventricular (LV) systolic and diastolic parameters derived from Doppler echocardiography have been used widely to predict functional capacity but diastolic filling is affected by various factors. Tissue Doppler imaging (TDI) that records systolic and diastolic velocities within the myocardium and at the corners of the mitral annulus, has been shown to provide additional information about regional and global LV function. The goal of this study was to examine whether TDI-derived parameters add incremental value to other standard Doppler echocardiographic measurements in predicting exercise capacity. The study enrolled 59 consecutive patients with stable congestive heart failure (CHF). The etiology of heart failure was coronary artery disease in 42 patients and dilated cardiomyopathy in 17. Twenty-three age-matched healthy subjects were recruited as controls. Conventional echocardiographs and TDI were obtained. Early (Ea) and late (Aa) diastolic and systolic (Sa) mitral annulus velocities, the Ea/Aa and E/Ea ratios, were measured by pulsed wave TDI placed at the septal side of the mitral annulus and results were compared with results of cardiopulmonary exercise testing. Systolic and early diastolic velocities of mitral annulus were decreased and the E/Ea ratio was increased in the restrictive group as compared to controls (P = 0.02, P = 0.03, P < 0.001, respectively) but there was no significant difference in late diastolic velocity and the Ea/Aa ratio between the restrictive group and controls. The average peak VO2 of the patients were 14.9 +/- 4.9 ml/min per kg. Achieved peak VO2 of the patients with E/Ea ratio 7.5 (P < 0.001). Interestingly, the patients with the nonrestrictive pattern and E/Ea ratio >7.5 had reduced exercise capacity, as did the group with restrictive LV filling patterns (12.8 +/- 3.3 vs 12.9 +/- 4.0 ml/min per kg, P = 0.9). Similarly, there was no significant difference in the mean exercise capacity between the patients with a nonrestrictive pattern vs restrictive pattern with E/Ea ratio 7.5 was used, 21 out of 24 patients in the reduced exercise capacity group were identified with 16 false positives in the preserved exercise capacity group (P = 0.001). Mitral annular systolic and diastolic velocities of TDI were associated with cardiopulmonary exercise capacity in patients with LV systolic dysfunction. Index of the E/Ea ratio was found to be the most powerful predictor of peak oxygen uptake.

Plasma homocysteine concentration in patients with poor or good coronary collaterals.

BACKGROUND: Elevated plasma homocysteine (Hcy) concentrations are associated with an increased risk of vascular disease. Hcy is known to inhibit endothelial cell proliferation in vitro. The purpose of the present study was to investigate the role of plasma Hcy concentrations on development of collateral circulation in single-vessel chronic total occlusion. METHODS AND RESULTS: Collateral status was determined by Rentrop's classification. Of 817 patients, 56 cases of pure single-vessel chronic total occlusion were studied. Plasma Hcy concentrations in patients with single-vessel total coronary occlusion were higher compared with controls (17.3 +/-12.6 micromol/L vs 10.9+/-4.9 micromol/L, p=0.015). There was no significant difference in plasma Hcy concentrations of the good and poor collateral groups (17.2+/-13.7 micromol/L vs 15.3+/-9.3 micromol/L, p=0.834). Plasma Hcy concentrations in individual Rentrop subclasses 0, 1, 2 and 3 were as follows: 15.9 +/-9.1, 16.3+/-12.4, 17.1+/-14.1 and 20.1+/-13.5 micromol/L (p=0.893). There was a positive linear correlation between Rentrop subclass and angina pectoris duration (r=0.41, p=0.003). Angina pectoris duration was the only independent variable affecting the development of coronary collaterals in the present study (odds ratio [confidence interval]: 1.85 [1.12-2.91], p=0.014). CONCLUSION: Patients with single-vessel chronic total occlusion had higher plasma Hcy concentrations than controls, but similar Hcy concentrations when compared according to the presence of poor or good coronary collaterals. There is a lack of association between plasma Hcy concentration and coronary collateral status in the current study.

Abnormal heart rate recovery immediately after cardiopulmonary exercise testing in heart failure patients.

An attenuated heart rate recovery (HRR) immediately after exercise has been shown to be predictive of mortality. It is not known whether HRR predicts mortality when measured in patients with heart failure. The present study was undertaken to evaluate the ability of HRR to predict mortality in patients with heart failure. We studied 84 NYHA class II or III chronic congestive heart failure patients who had a left ventricular ejection fraction < or = 40%. All patients underwent symptom limited cardiopulmonary exercise testing. The value for the HRR was defined as the difference in heart rate between peak exercise and one-minute later; a value < or = 18 beats per minute was considered abnormal. The patients were divided into 2 groups according to the value of HRR. Those with abnormal HRR were assigned to group I and those with normal HRR were assigned to group II. The 2 groups were compared with each other regarding baseline characteristics and exercise capacity assessed by peak VO2. There were 26 patients (31%) in group I and 58 patients (69%) in group II. Group II patients had better performance on treadmill exercise testing than group I patients. They had greater exercise duration (7.5 +/- 3.8 minutes versus 5 +/- 3.5 minutes, P = 0.006), better heart-rate reserve (79 +/- 25% versus 63 +/- 27%, P = 0.01), and higher values of maximal heart-rate (141 +/- 18 beats/min versus 132 +/- 17 beats/min, P = 0.04). Group II patients also had higher peak VO2 values (16.8 +/- 4.4 mL/kg/min versus 14.4 +/- 3.6 mL/kg/min, P = 0.01). When we separated the groups according to beta-blocker usage, beta-blockers had no prominent effect on HRR. In the follow-up period (mean 14.1 +/- 6.1 months), the presence of abnormal HRR and lower peak VO2 (< or = 14 mL/kg/min) were the only significant predictors of mortality in our patient population (adjusted hazard ratio [HR] 5.2, 95% CI, 1.3 to 24, P = 0.03 and adjusted HR 13, 95% CI, 2.1 to 25.6, P = 0.005, respectively). It seems that the attenuated HRR value one minute after peak exercise appears to be a reliable index of the severity of exercise intolerance in heart failure patients and this study supports the value of HRR as a prognostic marker among heart failure patients referred for cardiopulmonary exercise testing for prediction of prognosis.

Single high-dose bolus tirofiban with high-loading-dose clopidogrel in primary coronary angioplasty.

Glycoprotein IIb/IIIa inhibitor therapy during primary percutaneous coronary intervention (PCI) decreases the incidence of major adverse cardiac events. These effects directly result from the level of platelet inhibition. It was shown that standard dosing of tirofiban is insufficient for optimal platelet inhibition. We sought to determine the efficacy and safety of single high-dose bolus (HDB) tirofiban with high-dose clopidogrel loading in primary PCI in acute ST elevation myocardial infarction. A total of 100 patients (mean age 55.2 +/- 9.9 years, male/female = 86/14) undergoing primary PCI, pretreated with clopidogrel (450 mg) and aspirin (325 mg), were consecutively randomized into two groups. Group I (n = 50) received a standard dose bolus of tirofiban (10 microg/kg/3 min) with 24-h infusion at a rate of 0.15 microg/kg/min. Group II received single HDB tirofiban (25 microg/kg/3 min). The assessed angiographic, clinical, and echocardiographic endpoints were: initial and final Thrombolysis in Myocardial Infarction (TIMI) grade flow (TGF), corrected TIMI frame count (CTFC), ST-segment resolution (STR) at 90 min, in-hospital bleeding complications, echocardiographic left ventricular ejection fraction (LVEF), death, reinfarction, and repeat target vessel revascularization at 1 month. Platelet function inhibition was measured using PFA-100 (Behring-Dade, Liederbach, Germany) with a test cartridge unit containing a membrane coated with 2 microg of equine Type I collagen and 50 microg adenosine diphosphate before, and 10 min, 2, 4, 6, 12, and 24 h after the bolus of the tirofiban in the first 10 cases of each group. There were no significant differences in baseline characteristics between groups. Initial TGF III was more frequent (24% vs 8%, P = 0.029) and the value of CTFC was lower (75 +/- 34 vs 89 +/- 25, P = 0.03) in group II. Postprocedural TGF, CTFC, STR, bleeding complications, and LVEF at 1 month were not different between the two groups. There was a higher rate of reinfarction in group II (8%) compared with group I (2%), but this difference was not statistically significant (P > 0.05). The results of platelet function analyses showed that group II patients had significantly prolonged platelet function assay closure times (299 +/- 6 s) compared with group patients (236 +/- 97 s) at 10 min after the bolus dose (P = 0.04). However, after the first dose between 2 and 24 h, PFA closure times were significantly prolonged in patients with tirofiban infusion. High-dose bolus of tirofiban seems to be safe and more effective than conventional dose at the periprocedural time, whereas continuous infusion of tirofiban may be necessary in the first 24 h before stable and safe antiplatelet status is reached with clopidogrel. However, safety and efficacy of HDB tirofiban and high-loading-dose clopidogrel together with tirofiban infusion requires further studies with a larger population.

Impact of early tirofiban administration on myocardial salvage in patients with acute myocardial infarction undergoing infarct-related artery stenting.

BACKGROUND/AIMS: The timing of GpIIb/IIIa inhibitor administration may be important in achieving early epicardial and myocardial reperfusion. We evaluated the effect of early tirofiban on myocardial salvage and cardiovascular outcome in patients with acute myocardial infarction (AMI) undergoing infarct-related artery stenting. METHODS: Patients (n = 66) with a first AMI presenting <6 h from onset of symptoms were randomized to either early administration of tirofiban in the emergency room (n = 32) or later administration in the catheterization laboratory (n = 34) (tirofiban bolus dose of 10 microg/kg, followed by 0.15 microg/kg for 24 h). The primary end-point was the degree of myocardial salvage, determined by means of serial scintigraphic studies with technetium-99m sestamibi. Thirty-day major adverse cardiac events were also assessed. RESULTS: There were no significant differences in patient characteristics or in their presentation. The mean door-to-balloon time was similar in both groups (43 +/- 12 and 53 +/- 9 min, p = 0.08). The early and late treatment groups received tirofiban 18 +/- 4 and 52 +/- 10 min after admission, respectively. Angiographic analysis revealed a higher initial frequency of TIMI grade 3 flow in the early group (31% vs. 12%, p = 0.04). Procedural success was achieved in all patients. Myocardial risk area were comparable between early and late treatment groups (35.6 +/- 12.2% vs. 39.3 +/- 14.0%, p = 0.6). Scintigraphic outcomes demonstrated a significant reduction in the final infarction size (11.8 +/- 5.2% vs. 22.4 +/- 6.2%, p = 0.01), and improvement in salvage index (0.68 +/- 0.22 vs. 0.44 +/- 0.18, p = 0.003) in favor of the early tirofiban group. The thirty-day composite end-point of death, recurrent MI or rehospitalization also favored the early group (6% early, 15% late, p = 0.06). CONCLUSION: Early tirofiban administration enhanced the degree of myocardial salvage and clinical outcome in patients with AMI undergoing infarct-related artery stenting.

Metabolic syndrome as a predictor of non-dipping hypertension.

Metabolic syndrome (MS) and non-dipping hypertension both increase cardiovascular mortality. Although both clinical modalities share common pathophysiologic factors in their etiologies, previous studies did not find any association between them. We aimed to investigate the association between MS and non-dipping blood pressure by comparing different definitions of MS. One-hundred-thirty-two consecutive patients (58 men) who underwent 24-hour ambulatory blood pressure monitoring were analyzed. MS was evaluated according to the currently used Adult Treatment Panel (ATP) III definition criteria, named MS-ATP III. In order to reveal the weights of risk contributing to MS, a new diagnostic scoring method (MS-Score) was used in comparison with MS-ATP III. Nocturnal non-dipping refers to a reduction in average systolic and/or diastolic blood pressure at night (< or = 10%) compared with daytime average values. Non-dipping pattern was found in 61.4% of patients. The frequency of MS according to MS-Score, but not MS ATP III, was significantly higher in patients with non-dipping pattern than those without it (p = 0.009). Although more prominent in the nighttime, MS-Score showed positive correlation with all systolic blood pressure results (r = 0.27, p = 0.002). Adjusted for baseline characteristics, high (> or = 27.5) MS-Score remained as an independent predictor of non-dipping pattern (OR 2.64, p = 0.038). Finally, high MS-Score, but not MS-ATP III, is a predictor of non-dipping pattern. Nighttime systolic blood pressure is higher in patients with high MS-Score. Therefore, patients with high MS-Score may be more prone to cardiovascular events than those with low MS-Score.

Congenital coronary anomalies in adults: comparison of anatomic course visualization by catheter angiography and electron beam CT.

The objective of this study was to compare the anatomic course of anomalous coronary arteries by axial and three-dimensional volume-rendered electron beam computed tomography (EBCT) angiography and X-ray catheter angiography (CAG). We performed a blinded study where patients who previously underwent CAG with (n = 14) and without (n = 14; age- and gender-matched controls) anomalous coronary anatomy were studied with EBCT coronary angiography. Forty to 50 EKG-triggered 3 mm overlapping axial slices were acquired with 2 mm table movement within one breath hold during the i.v. injection of 140 cc of nonionic iodinated contrast (4 ml/sec). The axial source images and volume-rendered three-dimensional reconstructions were evaluated for the presence, type, and course of coronary anomalies and the results were compared to those of CAG. All normal and anomalous coronary arteries were identified by both modalities in all subjects. Identified anomalies include single coronary artery (n = 3), left-sided right coronary artery (n = 3), right-sided left main coronary artery (n = 3), anterior descending coronary artery (n = 2), circumflex coronary artery (n = 2), and separate left-sided ostia for left anterior descending and circumflex coronary arteries (n = 1). In five cases, there was discrepancy in the course of the anomalous vessels between the two modalities. Consensus reading among cardiologist and radiologists favored the interpretation of EBCT over catheter angiography. Noninvasive EBCT coronary angiography compares well with CAG in identifying anomalous coronary arteries and may provide confirmatory evaluation of their precise anatomic relationships to the heart and great vessels.

Neurofibromatosis as a cause of multiple coronary aneurysms.

Neurofibromatosis is a rare cause of coronary aneurysm. We present a case of multiple coronary artery aneurysms in a patient with neurofibromatosis. Coronary angiography was performed because of postmyocardial infarction angina. Coronary angiography revealed multiple coronary aneurysms in the left anterior descending and circumflex arteries, and diffuse irregularities in the right coronary artery. None of the coronary arteries showed critical stenosis. The patient was successfully managed with aspirin, clopidogrel, and beta-blocker therapy.

Single coronary artery with subsequent coursing of right coronary artery between aorta and pulmonary artery: fractional flow reserve of the anomalous artery guiding the treatment.

A single coronary artery with an anomalous origin between the pulmonary artery and aorta is an unusual congenital anomaly. We present a 60 year old female patient with stable angina pectoris. Her coronary angiogram revealed that the right coronary artery originated from the left main stem and coursed between the great vessels. There was 90% stenosis in the left anterior descending coronary artery. We performed a fractional flow reserve study of both the anomalous origin artery and stenosed vessel. Fractional flow reserve study of the anomalous RCA did not reveal functional ischemia. We did not refer the patient to coronary artery bypass grafting but instead performed percutaneous coronary revascularization of the LAD. The patient is alive and has been free of symptoms during the 1 year follow-up.

Value of left atrial function in predicting exercise capacity in heart failure with moderate to severe left ventricular systolic dysfunction.

Left atrial (LA) function is associated with left ventricular (LV) diastolic filling and cardiac output response to exercise. But the relation between LA function and exercise performance has not been adequately evaluated. The aim of this study was to investigate the relation between LA function and exercise capacity in dilated cardiomyopathy (DCM) with cardiopulmonary exercise testing. Forty-four patients with a left ventricular end-diastolic dimension (LVDd) > or = 60 mm and an ejection fraction (EF) < or = 40%, and in normal sinus rhythm were included in this study. Patients were divided into group 1 and group 2 according to their exercise peak oxygen uptake (VO2) (group 1: peak VO2 >14 mL/kg/min, group 2: peak VO2 < or = 14 mL/ kg/min). LA function indices were defined as follows: LA end-systolic diameter (LASd), end-diastolic diameter (LADd), LA systolic volume (LASV), LA diastolic volume (LADV), LA ejection volume (LAEV), and LA ejection fraction (LAEF). LASd, LADd, LASV, and LADV were significantly increased in group 2 (P < 0.001, P < 0.001, P < 0.05, P < 0.005). Group 1 had significantly higher LAEF (P < 0.001 ) and LVEF (P < 0.05). Group 2 had significantly shorter exercise duration, and decreased anaerobic threshold levels and minute ventilation volumes (P < 0.001, P < 0.001, P < 0.005 ). There was a positive correlation between peak VO2 and LVEF (r = 0.46, P = 0.002), and LAEF (r = 0.61, P < 0.001), peak A wave velocity (r = 0.39, P = 0.009), E wave deceleration time (r = 0.56, P < 0.001), and isovolumic relaxation time (IVRT) (r = 0.35, P = 0.04). There was a negative correlation between peak VO2 and LASd (r = -0.53, P < 0.001) LADd (r = -0.59, P < 0.001), LASVI (r = -0.34, P = 0.027), LADVI (r = -0.37, P = 0.001), and the E/A ratio (r = -0.41, P = 0.006), Decreased LAEF and increased LA sizes were associated with decreased peak VO2. The results clearly demonstrate that LA functions at rest are related to exercise performance in patients with heart failure.