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Biomedical subjects

T De Marco

Publications and source records attributed to T De Marco.

At least 19 recordsLinked to original sources

Impact of a home-based walking and resistance training program on quality of life in patients with heart failure.

Patients with heart failure (HF) often have profound activity limitations and diminished quality of life (QOL) due to symptoms of dyspnea and fatigue. Although recent studies demonstrate positive physiologic and psychological benefits of low to moderate intensity, supervised, aerobic exercise training performed 3 to 5 days/ week for 20 to 40 minutes' duration, in a monitored setting, the efficacy of a home-based exercise program combining endurance and resistance exercise on symptoms and QOL, are unknown. This randomized controlled study examined the efficacy, safety, and adherence rates of a 3-month home-based combined walking and resistance exercise program on symptoms and QOL in 40 women and men aged 30 to 76 years with New York Heart Association class II to III HF. Baseline and 3-month evaluations consisted of a chronic HF questionnaire to assess symptoms and QOL and exercise capacity by symptom-limited treadmill exercise test with respiratory gas analysis. The exercise intervention improved fatigue (p = 0.02), emotional function (p = 0.01), and mastery (p = 0.04). Overall exercise adherence was excellent (90%) and there were no reported adverse events. A moderate intensity home-based combined walking and resistance program for patients with class II to III HF is safe and effective in reducing symptoms and improving QOL.

Adult↗

Clinical insights on the use of highly sensitive cardiac troponin assays.

This review describes the pathophysiological and histopathological rationale for using the cardiac isoforms of troponin T and troponin I in congestive heart failure (CHF). It also focuses on the potential clinical usefulness of new generation highly sensitive and specific cardiac troponin assays with respect to histological monitoring, risk stratification and therapeutic follow-up of patients with CHF. The availability of more powerful analytical tools for these highly specific markers of myocardial injury offers a unique opportunity to expand the field of their application and to explore new disease processes. Because cardiac troponin T and cardiac troponin I provide useful clinical information unavailable through other diagnostic techniques, they appear as promising biochemical markers in patients with CHF.

Biomarkers↗

Biventricular pacing in patients with congestive heart failure: two prospective randomized trials. The VIGOR CHF and VENTAK CHF Investigators.

Epidemiologic studies suggest that 20-30% of patients diagnosed with symptomatic congestive heart failure (CHF) have intraventricular conduction disorders characterized by a discoordinate contraction pattern and wide QRS. Biventricular pacing is an emerging therapy allowing simultaneous electrical stimulation of the right and left ventricles with the use of an implantable pacing system. The aim of this article is to describe 2 prospective randomized multicenter trials examining the effects of biventricular pacing on functional capacity, quality of life, and hemodynamic status in patients with dilated cardiomyopathy and intraventricular delay. The VIGOR CHF Trial is designed to assess functional and symptomatic improvement in heart failure patients with biventricular pacing and without a concomitant indication for conventional bradycardia pacemaker therapy. To assess for potential placebo effects, patients are randomized to receive either biventricular pacemaker therapy or no pacing therapy for the first 6 weeks, after which both groups receive pacing therapy. The VENTAK CHF trial uses an implantable cardioverter defibrillator system (ICD) designed to provide chronic biventricular pacing therapy in addition to treating ventricular tachyarrhythmias. All patients receive conventional ICD and CHF therapy throughout the study and are randomized in a 2-period crossover design to receive either no pacing or biventricular pacing for 3-month intervals. Patient enrollment in both studies is ongoing, with a closed analysis. The unique designs of these trials provide the opportunity to study this therapy in high-risk patients who have been optimally treated for heart failure.

Adult↗

Influence of felodipine on left ventricular hypertrophy and systolic function in orthotopic heart transplant recipients: possible interaction with cyclosporine medication.

BACKGROUND: Concentric left ventricular (LV) hypertrophy develops early in orthotopic heart transplant (OHT) recipients. To compare the effects of a calcium channel blocker, felodipine, versus diuretics on LV hypertrophy and LV systolic function repeated magnetic resonance imaging studies were performed in OHT recipients. Cyclosporine levels and neurohormones were also measured to explore potential interactions with treatment. METHODS: Twenty-two patients were randomized at baseline (2 months after OHT) to receive felodipine or diuretic treatment. Before and after 4 months of treatment (n = 19), LV dimensions and LV mass (Simpson's rule) were measured. The relationship between circumferential fiber shortening (two-shell cylindrical model) and end-systolic wall stress was used as a measure of load-independent LV contractility. Neurohormones were measured at the beginning and end of the treatment period, and cyclosporine levels and blood pressures were additionally measured during treatment. RESULTS: At baseline, the felodipine and diuretic groups did not differ in LV mass, wall stress, and fiber shortening. During felodipine treatment LV mass decreased (p < 0.01) and tended to increase during diuretics treatment (p = 0.06). Afterload-corrected fiber shortening did not change during felodipine treatment, but decreased (p < 0.01) with diuretics. Changes in LV mass were positively correlated with cyclosporine levels (r = 0.70) in the diuretics group, but not in the felodipine group. CONCLUSIONS: In OHT recipients during diuretic treatment, progression of LV hypertrophy occurs in relation to cyclosporine plasma levels and is accompanied by impairment of systolic contractile function. Felodipine induces regression of LV hypertrophy, while systolic contractile function is preserved. During felodipine treatment, regression of LV hypertrophy is unrelated to cyclosporine levels. Thus, felodipine seems to attenuate the hypertrophic effect of cyclosporine on transplanted hearts.

Analysis of Variance↗

Successful immunomodulation with intravenous gamma globulin and cyclophosphamide in an alloimmunized heart transplant recipient.

A highly human leukocyte antigen-sensitized heart transplant candidate underwent immunomodulation with intravenous gamma globulin and cyclophosphamide. His panel reactive antibody screen fell from 64% to 14%. He underwent successful orthotopic heart transplantation with a histoincompatible, T-cell cross-match-negative heart without the development of hyperacute rejection. The combination of intravenous gamma globulin and cyclophosphamide may be a simple and effective means to overcome the human leukocyte antigen-barrier in sensitized heart transplant candidates.

Combined Modality Therapy↗

Assessment of early left ventricular remodeling in orthotopic heart transplant recipients with cine magnetic resonance imaging: potential mechanisms.

We performed short axis cine magnetic resonance imaging studies in 11 patients 2 months after they underwent orthotopic heart transplantation (OHT), and in 10 control subjects, to measure left ventricular (LV) volumes, mass, and end-systolic wall stress to assess ventricular remodeling after OHT. Although there were no significant differences in ventricular volumes and ejection fractions between heart transplant recipients and control subjects, heart transplant recipients had significantly higher LV mass (198 +/- 61 vs 132 +/- 27 gm, p = 0.001). As a consequence of myocardial hypertrophy, end-systolic wall stress was significantly reduced in heart transplant recipients compared with control subjects (34 +/- 16 vs 57 +/- 10 kdyne/cm2, p = 0.001). Moreover, heart transplant recipients had significantly reduced end-systolic wall stress/volume ratio when compared with control subjects (0.89 +/- 0.3 vs 1.26 +/- 0.3 kdyne/cm2/ml, p < 0.01), indicating an already reduced LV contractility 2 months after heart transplantation. Univariate regression analysis revealed a significant correlation between LV mass and averaged cyclosporine levels, but no correlation between LV mass and blood pressure, cold ischemic time, acute rejection, age, body mass, blood pressure, plasma catecholamine levels, or plasma renin activity. Magnetic resonance imaging demonstrates early LV remodeling after OHT with reduced myocardial contractility. Cyclosporine may be contributing to these changes.

Adult↗

Iodine-123 metaiodobenzylguanidine scintigraphic assessment of the transplanted human heart: evidence for late reinnervation.

OBJECTIVES: This study attempted to determine whether cardiac sympathetic reinnervation occurs late after orthotopic heart transplantation. BACKGROUND: Metaiodobenzylguanidine (MIBG) is taken up by myocardial sympathetic nerves. Iodine-123 (I-123) MIBG cardiac uptake reflects intact myocardial sympathetic innervation of the heart. Cardiac transplant recipients do not demonstrate I-123 MIBG cardiac uptake when studied < 6 months from transplantation. However, physiologic and biochemical studies suggest that sympathetic reinnervation of the heart can occur > 1 year after transplantation. METHODS: We performed serial cardiac I-123 MIBG imaging in 23 cardiac transplant recipients early (< or = 1 year) and late (> 1 year) after operation. In 16 subjects transmyocardial norepinephrine release was measured late after transplantation. RESULTS: No subject had visible I-123 MIBG uptake on imaging < 1 year after transplantation. However, 11 (48%) of 23 subjects developed visible cardiac I-123 MIBG uptake 1 to 2 years after transplantation. Only 3 (25%) of 12 subjects with a pretransplantation diagnosis of idiopathic cardiomyopathy demonstrated I-123 MIBG uptake compared with 8 (73%) of 11 with a pretransplantation diagnosis of ischemic or rheumatic heart disease (p = 0.04). All 10 subjects with a net myocardial release of norepinephrine had cardiac I-123 MIBG uptake; all 6 subjects without a net release of norepinephrine had no cardiac I-123 MIBG uptake. CONCLUSIONS: Sympathetic reinnervation of the transplanted human heart can occur > 1 year after operation, as assessed by I-123 MIBG imaging and the transmyocardial release of norepinephrine. Reinnervation is less likely to occur in patients with a pretransplantation diagnosis of idiopathic cardiomyopathy than in those with other etiologies of congestive heart failure.

3-Iodobenzylguanidine↗

Systemic and coronary hemodynamic effects of bepridil in patients with depressed left ventricular function.

To assess the effects of oral bepridil therapy (10-14 days) on cardiac performance and myocardial energetics in the presence of depressed left ventricular function, systemic and coronary hemodynamic effects and neurohumoral effects were evaluated in 7 patients with coronary artery disease and reduced ejection fraction at control, submaximal, and maximal pacing rates during atrial pacing stress. After bepridil therapy, arterial, right atrial, and left ventricular filling pressures as well as systemic vascular resistance and left ventricular stroke work index did not change, suggesting no deleterious effects of bepridil on cardiac performance in patients with reduced ejection fraction. Rate-pressure product, myocardial oxygen consumption, coronary sinus blood flow, myocardial lactate extraction, and catecholamine balance remained unchanged. Development of angina during pacing showed a variable response to bepridil. We conclude that despite its potential negative inotropic effect, bepridil does not exert deleterious effects on hemodynamics or left ventricular performance. The mechanism for its beneficial antianginal effect may be due to favorable redistribution of myocardial blood flow to ischemic zones; no clear effect on anginal threshold or sympathetic tone could be demonstrated in these patients.

Aged↗

Flosequinan, a new vasodilator: systemic and coronary hemodynamics and neuroendocrine effects in congestive heart failure.

OBJECTIVES: The aim of this study was to evaluate the immediate and long-term systemic and coronary hemodynamic, metabolic and neurohormonal effects of flosequinan in patients with congestive heart failure. BACKGROUND: Preliminary studies have shown that this new long-acting oral systemic vasodilator may have beneficial effects in patients with heart failure. METHODS: Thirteen patients with congestive heart failure were studied. Systemic and coronary hemodynamic, metabolic and neurohormonal effects of flosequinan were assessed acutely with repeat systemic hemodynamic studies after 6 weeks of treatment. RESULTS: The administration of flosequinan acutely and after long-term treatment, resulted in a significant increase in cardiac index, stroke work index and stroke volume index with a reduction in systemic and pulmonary vascular resistances. The improvement in ventricular function was associated with an improvement in left ventricular efficiency without a change in myocardial oxygen consumption or coronary sinus blood flow. Myocardial oxygen extraction and net myocardial lactate extraction also did not change significantly with flosequinan therapy. Systemic catecholamine levels and myocardial catecholamine balance did not change. Plasma arterial and coronary sinus atrial natriuretic factor concentrations were elevated at baseline; the latter concentrations at the level of the great cardiac vein were significantly higher than those of arterial concentrations, indicating increased left ventricular release of atrial natriuretic factor in congestive heart failure. Both arterial and coronary sinus atrial natriuretic factor levels were significantly reduced with the administration of flosequinan at peak effect in association with an improvement in systemic hemodynamics. CONCLUSIONS: Flosequinan therapy in patients with congestive heart failure results in a sustained beneficial hemodynamic action and improved cardiac performance without an increase in metabolic demand or activation of the sympathetic nervous system.

Aged↗

Scintigraphic assessment of MIBG uptake in globally denervated human and canine hearts--implications for clinical studies.

To further characterize the behavior of metaiodobenzylguanidine (MIBG) in the myocardium and to test the hypothesis that the denervated heart would show normal early uptake on MIBG due to non-neuronal localization, we examined the early and late distribution of 123I-labeled MIBG in normal and globally denervated canine and human hearts. Canine hearts were denervated by intravenous injections of 6-hydroxydopamine, while patients were studied a mean of 4.3 mo following cardiac transplantation. Results in denervated hearts were compared to normal controls. Normal hearts showed prominent MIBG uptake on initial 5-min and 3-hr delayed images. Globally denervated canine hearts showed prominent uptake on initial images and absence of localization on delayed images, indicating complete washout of non-neuronally bound radionuclide. The transplanted human hearts showed no localization of MIBG on either early or delayed images. These results suggest that the non-neuronal uptake mechanism (uptake 2) is not significant in human myocardium. This finding has significant implications for interpreting the myocardial behavior of MIBG in various pathologic situations such as dilated cardiomyopathy.

3-Iodobenzylguanidine↗

Decreased coronary sinus oxygen content: a predictor of adverse prognosis in patients with severe congestive heart failure.

Patients with congestive heart failure have abnormal coronary hemodynamics, characterized by decreased coronary sinus oxygen content, increased coronary sinus blood flow and increased myocardial oxygen consumption. To evaluate their prognostic importance, the clinical characteristics and systemic and coronary hemodynamics were related to survival in 91 patients with severe congestive heart failure and decreased ejection fraction (25.5 +/- 10% [mean +/- SD]). In 69 patients congestive heart failure was due to or secondary to coronary artery disease (group 1) and in 22 it was due to idiopathic dilated cardiomyopathy (group 2). Five patients were in functional class II, 48 in class III and 38 in class IV. The median survival time was 20.7 months. As assessed with the Cox proportional hazards model, coronary sinus oxygen content was most strongly associated with a poor prognosis. On the basis of a comparison between the lowest (coronary sinus oxygen content less than or equal to 4.44 vol%) and highest quintile (coronary sinus oxygen content greater than 4.44 vol%), a low coronary sinus oxygen content was associated with a 2.34-fold increased risk of dying (95% confidence interval, 1.31 to 4.08). A low systolic blood pressure and a high diastolic pulmonary artery pressure were also significantly associated with increased mortality. Patients in the subgroup with a low coronary sinus oxygen content had values for functional class, ejection fraction and systemic hemodynamics similar to those of patients in the subgroup with high coronary sinus oxygen content. It is concluded that a low coronary sinus oxygen content indicative of noncompensated metabolic demand suggests a poor prognosis in patients with severe congestive heart failure.

Aged↗

Systemic and coronary haemodynamics and pharmacodynamics of enalapril and enalaprilat in congestive heart failure.

Enalapril is an effective angiotensin-converting enzyme (ACE) inhibitor which produces salutary, beneficial haemodynamic effects in patients with congestive heart failure. Enalapril also produces beneficial neurohumoral changes, as well as improving abnormal coronary haemodynamics and myocardial energetics that are frequently encountered in these patients. Administration of enalapril once or twice daily appears to be quite effective during maintenance therapy in patients with chronic congestive heart failure.

Aldosterone↗

Central and peripheral adrenergic receptor agonists in heart failure.

The subtypes of alpha- and beta- and dopaminergic receptors have been identified along with specific agonists and antagonists. The effects of alpha-receptor agonists on haemodynamics results from the interaction of relative changes in vascular tone and increase in myocardial contractility. Predominantly, beta 1 agonists improve cardiac performance by increasing contractility which is usually accompanied by increased myocardial oxygen consumption. Dopaminergic receptor agonists improve left ventricular function primarily by reduction in systemic vascular resistance usually without a change in myocardial oxygen consumption. beta 2-receptor agonists improve cardiac function both by increasing contractility and by peripheral vasodilation usually without an increase in metabolic cost. The effects of various adrenoreceptor agonists such as dobutamine, dopamine, prenalterol, levodopa and dopexamine on systemic and coronary haemodynamics and on myocardial energetics in heart failure are reviewed.

Adrenergic alpha-Agonists↗

Systemic and coronary hemodynamic and neurohumoral effects of levodopa in chronic congestive heart failure.

Systemic and neurohumoral effects of oral levodopa were evaluated in 17 patients with severe chronic heart failure. The maximum mean dopamine level achieved after 1.5 g of oral levodopa was 19.6 +/- 16.4 ng/ml. At peak dopamine level, cardiac index increased by 14% from baseline (1.95 +/- 0.55 to 2.27 +/- 0.45 liters/min/m2, p less than 0.05), stroke volume index increased by 14% (22.4 +/- 6.0 to 25.9 +/- 5.8 ml/min/m2, p less than 0.01). There was a trend toward reduced systemic vascular resistance of 13% (1,773 +/- 769 to 1,535 +/- 432 dynes.s.cm-5, p = 0.08). There was no significant change from baseline in heart rate, mean arterial pressure, right atrial pressure, pulmonary capillary wedge pressure, pulmonary vascular resistance and rate-pressure product. In addition, as the arterial dopamine level increased there was a concomitant decrease in plasma norepinephrine level that was sustained for the period of observation. In a subgroup of 8 patients, there was no change in coronary sinus blood flow, myocardial oxygen consumption, myocardial oxygen extraction, lactate extraction and transmyocardial release of catecholamines after levodopa. These findings suggest that oral levodopa, 1.5 g, can improve left ventricular function without adversely affecting myocardial energetics and catecholamine balance.

Aged↗