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PubMed1994

Cardiovascular effects of inhaled nitric oxide in patients with left ventricular dysfunction.

BACKGROUND: Pulmonary vascular resistance (PVR) is frequently elevated in patients with advanced heart failure. Nitric oxide (NO), which contributes to the activity of endothelium-derived relaxing factor, causes relaxation of pulmonary arteries and veins in vitro. Inhalation of NO gas causes pulmonary vasodilation in patients with primary and secondary forms of pulmonary hypertension. METHODS AND RESULTS: To test the hypothesis that inhalation of NO gas lowers PVR in patients with heart failure, we studied the hemodynamic effects of a 10-minute inhalation of NO (80 ppm) in 19 patients with New York Heart Association class III (n = 5) and class IV (n = 14) heart failure due to left ventricular (LV) dysfunction. Although inhalation of NO had no effect on pulmonary artery pressures, the PVR decreased by 31 +/- 7% (P < .001) due to a 23 +/- 7% increase (P < .001) in pulmonary artery wedge pressure and despite a 4 +/- 2% (P < .05) decrease in cardiac index. The magnitude of the decrease in PVR with inhaled NO was inversely related (r = -.713; P < .001) to the baseline PVR. Inhaled NO had no effect on heart rate, systemic arterial pressure, systemic vascular resistance, or LV peak +dP/dt or -dP/dt. CONCLUSIONS: In patients with heart failure due to LV dysfunction, inhalation of NO causes a decrease in the PVR associated with an increase in LV filling pressure. These findings predict that inhaled NO, if used alone at this dose (80 ppm), may have adverse effects in patients with LV failure.

Administration, Inhalation↗
PubMed1990

hemofiltration reverses left ventricular dysfunction during sepsis in dogs.

Depressed left ventricular (LV) contractility in sepsis has been ascribed to the presence of circulating cardiodepressant substance (filterable cardiodepressant factor in sepsis [FCS]); however, this finding is controversial. The authors hypothesized that if a decrease in LV contractility indeed occurred due to a circulating depressant substance, then removal of this substance by hemofiltration would reverse by dysfunction. In this study, LV mechanics were examined before and after hemofiltration in anesthetized dogs during continuous intravenous infusion of live Escherichia coli. Left ventricular anterior-posterior and apex-base dimensions were measured by subendocardial ultrasonic crystal transducers implanted 4 weeks before the experiments. Left ventricular contractility was determined from the end-systolic pressure-dimension relationship. The slope of this relationship (Emax) is an index of contractility. After 4 h of sepsis, Emax was reduced by one half. Hemofiltration resulted in a return of Emax to control values. The FCS activity in the plasma was also assessed by the percent reduction in isometric contraction of electrically stimulated, isolated right ventricular trabeculae obtained from nonseptic dogs. The FCS activity reached a peak 4 h after sepsis and was reduced after 2 h of hemofiltration. The results show that during experimental sepsis, a circulating substance of less than 30,000 d produces a decrease in LV contractility and that this LV dysfunction may be improved by hemofiltration.

Animals↗
PubMed2006

Dysautonomia and ventricular dysfunction in the indeterminate form of Chagas disease.

BACKGROUND: The associations between autonomic function and biventricular function in patients with the indeterminate form of Chagas disease remains to be elucidated. METHODS: In 42 asymptomatic patients and 19 healthy volunteers, the autonomic function was assessed by time domain indices of heart rate variability (HRV), analyzed for 24 h; the right ventricular function was assessed by fraction area change, right ventricle shortening, and systolic excursion of the tricuspid valve; and the left ventricular function was assessed by ejection fraction and transmitral flow velocities. Data were expressed as mean+/-SD or medians (including the lower quartile and upper quartile). Groups were compared by Student's t or Mann-Whitney U test. Autonomic and ventricular function were correlated by Pearson's or Spearman's correlation coefficient. The level of significance was 5%. RESULTS: Right and left ventricular systolic function indexes were comparable between groups. Transmitral flow velocities were decreased in the Chagas disease group (p<0.05). The patients presented impaired HRV as indicated by the values of SDNN-day (80 (64-99) ms vs. 98 (78-127) ms; p=0.045), SDNNI-24 h (54 (43-71) vs. 65 (54-105) ms; p=0.027), SDNNI-day (49 (42-64) vs. 67 (48-76) ms; p=0.045), pNN50-day (2.2 (0.7-5)% vs. 10 (3-11)%; p=0.033); and pNN50-24 h (3 (1-7)% vs. 12 (8-19)%; p=0.013). There were no correlations between the left ventricular diastolic indices and autonomic dysfunctional indices (p>0.05). CONCLUSION: Patients with the indeterminate form of Chagas disease have both dysautonomia and left ventricular diastolic dysfunction. However, the right ventricular function is preserved. Importantly, ventricular diastolic dysfunction and dysautonomia are independent phenomena.

Adult↗
PubMed1999

Role of angiotensin II in sympathetic nervous system induced left ventricular dysfunction.

Experiments were undertaken to determine whether angiotensin (Ang) II concentration increases during massive sympathetic nervous system (SNS) activation and whether such an increase plays a role in the pathogenesis of SNS-induced left ventricular (LV) dysfunction. We also sought to determine whether excessive Ca2+ uptake through L-type channels due to intense adrenoceptor activation is responsible for the LV dysfunction. AngII concentration was measured in the plasma and myocardium before and after massively activating the SNS with an intracisternal injection of veratrine. In separate experiments, rabbits were given losartan, enalaprilat, enalaprilat plus HOE-140, nifedipine, -Bay K 4866, or saline before massively activating the SNS. LV function was evaluated 2.5 h later. The intense SNS activity caused plasma and myocardial AngII to increase by 400 and 437%, respectively. AngII receptor blockade did not prevent LV dysfunction. In contrast, enalaprilat reduced the degree of dysfunction, but its cardioprotection was abolished by HOE-140. Although nifedipine prevented SNS-induced LV dysfunction, administration of the Ca2+ channel opener, -Bay K 4866, did not increase its severity. Our results indicate that AngII is not involved in the pathogenesis of SNS-induced LV dysfunction and that the cardioprotection provided by angiotensin converting enzyme (ACE) inhibition is due to activation of a bradykinin pathway. Furthermore, the finding that the magnitude of the LV dysfunction was reduced by enalaprilat, and not increased by -Bay K 4866, suggests that intense adrenoceptor activation of L-type Ca2+ channels is not the primary pathogenetic mechanism.

Adrenergic beta-Antagonists↗
PubMed2006

Comparison of the prognostic value of SPECT after nitrate administration and metabolic imaging by PET in patients with ischaemic left ventricular dysfunction.

PURPOSE: We compared the prognostic value of 99mTc-tetrofosmin single-photon emission computed tomography (SPECT) after nitrate administration and positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) in patients with ischaemic left ventricular (LV) dysfunction. METHODS: Eighty-nine patients with previous myocardial infarction and LV dysfunction (LV ejection fraction 33 +/- 10%) underwent 99mTc-tetrofosmin SPECT under control conditions (baseline) and after sublingual administration of 10 mg of isosorbide dinitrate (nitrate). Within 1 week, all patients underwent PET imaging with 18F-FDG. Four patients were excluded because of inadequate FDG uptake caused by severe diabetes. Follow-up data were obtained by phone contact with patients and by review of hospital or physicians' records. Cardiac death, myocardial infarction and late revascularisation for unstable angina were considered as events. Follow-up data were not available in three patients. Follow-up was 96% complete at a mean period of 29 +/- 19 months. RESULTS: At baseline SPECT, 59 (72%) patients had evidence of viable myocardium, while 23 did not. Of these latter patients, 12 (52%) demonstrated viable myocardium after nitrate and 13 (56%) had preserved metabolic activity. Cardiac events (cardiac death, myocardial infarction and late revascularisation for unstable angina) occurred in 24 (29%) patients. Event-free survival was similar in patients with and patients without viable myocardium at baseline SPECT (p = 0.8). In contrast, event-free survival was lower in patients with viable myocardium at nitrate SPECT and PET compared to those without viable myocardium (both p<0.05). CONCLUSION: In patients with ischaemic LV dysfunction, the prognostic value of SPECT imaging after nitrate is comparable to that of PET metabolic imaging.

Female↗
PubMed1998

Left ventricular dysfunction after open repair of simple congenital heart defects in infants and children: quantitation with the use of a conductance catheter immediately after bypass.

OBJECTIVE: Quantification of myocardial injury after the simplest pediatric operations by load-independent indices of left ventricular function, using conductance and Mikro-Tip pressure catheters (Millar Instruments, Inc., Houston, Tex.) inserted through the left ventricular apex. METHODS: Sixteen infants and children with intact ventricular septum undergoing cardiac operations had left ventricular function measured, immediately before and after bypass. Real-time pressure-volume loops were generated by conductance and Mikro-Tip pressure catheters placed in the long-axis via the left ventricular apex, and preload was varied by transient snaring of the inferior vena cava. RESULTS: Good quality pressure-volume loops were generated in 13 patients (atrial septal defects, n = 11; double-chambered right ventricle, n = 1; supravalvular aortic stenosis, n = 1; age 0.25 to 14.4 years, weight 3.1 to 46.4 kg). Their mean bypass time was 41 +/- 14 minutes and mean aortic crossclamp time 27 +/- 11 minutes. End-systolic elastance decreased by 40.7% from 0.34 +/- 0.17 to 0.21 +/- 0.15 mm Hg-1.ml-1.kg-1 (p < 0.001). There were no significant changes in the slope of the stroke work-end-diastolic volume relationship, end-diastolic elastance, time constant of isovolumic relaxation, and normalized values of the maxima and minima of the first derivative of developed left ventricular pressure. CONCLUSION: Load-independent indices of left ventricular function can be derived from left ventricular pressure-volume loops generated by conductance and Mikro-Tip pressure catheters during the perioperative period in infants and children undergoing cardiac operations. Incomplete myocardial protection was demonstrated by a deterioration in systolic function after even short bypass and crossclamp times.

Adolescent↗
PubMed2005

Assessment of myocardial viability with dobutamine stress echocardiography in patients with ischemic left ventricular dysfunction.

The noninvasive assessment of myocardial viability has proved clinically useful for distinguishing hibernating and/or stunned myocardium from irreversibly injured myocardium in patients with chronic ischemic heart disease or recent myocardial infarction, with marked regional and/or global left ventricular (LV) dysfunction. Noninvasive techniques utilized for the detection of viability in asynergic myocardial regions include positron emission tomographic imaging of residual metabolic activity, single photon emission tomography (SPECT) of radioisotope uptake with thallium-201, low-dose dobutamine echocardiography assessment of inotropic reserve and myocardial contrast echocardiography for evaluation of microvascular integrity. Of these techniques, dobutamine stress echocardiography is a safe, widely available and relatively inexpensive modality for the identification of myocardial viability for risk stratification and prognosis. Low-dose dobutamine response can accurately predict improvement of dysfunctional yet viable myocardial regions, and thus identify a subset of patients whose LV function will improve following successful coronary revascularization.

Cardiotonic Agents↗
PubMed2000

Diabetes and outcomes of coronary artery bypass graft surgery in patients with severe left ventricular dysfunction: results from The CABG Patch Trial database. The CABG Patch Trial Investigators and Coordinators.

OBJECTIVES: We examined the relationship between diabetes mellitus and outcomes after coronary artery bypass graft (CABG) surgery in patients with severe left ventricular (LV) dysfunction. BACKGROUND: Although diabetes is associated with poor outcomes after CABG surgery among unselected patients, the relationship between diabetes and mortality after CABG surgery among patients with LV dysfunction is less certain. METHODS: Using data from The CABG Patch Trial, a study of implantable cardiac defibrillator therapy, we analyzed 900 patients with ejection fraction <0.36 who underwent CABG surgery from 1990 to 1996. RESULTS: Diabetics comprised 38% of the patients, and 48% of diabetics were prescribed insulin. Diabetes was associated with hypertension, peripheral vascular disease, history of stroke, clinical heart failure and rales on physical exam. Diabetics were at higher risk for postoperative superficial sternal wound infection and renal failure. With an average follow-up time of 32 +/-16 months, actuarial all-cause mortality 48 months after CABG surgery was 26% in diabetics and 24% in nondiabetics (p = 0.66, log-rank test). Diabetes was not associated with long-term mortality in Cox multiple regression analyses. Actuarial re-hospitalization rates 48 months after CABG surgery were 85% in diabetics and 69% in nondiabetics (p = 0.0001, log-rank test). Diabetics had a 44% higher risk of re-hospitalization for any cause (p = 0.0001) and a 24% higher risk of re-admission for cardiac causes (p < 0.05). Unexpectedly, fewer arrhythmic events were found in diabetics. CONCLUSIONS: Diabetes was not a predictor of mortality after CABG surgery among patients with LV dysfunction despite associated comorbidities. However, diabetes was associated with increased postoperative complications and re-hospitalization.

Aged↗
PubMed2001

Long-term results of coronary artery bypass grafting procedure in the presence of left ventricular dysfunction and hibernating myocardium.

OBJECTIVE: Long-term left ventricular (LV) performance and patient outcome after coronary artery bypass grafting (CABG) procedure in the presence of depressed LV function and hibernating myocardium (HM) have been poorly determined. Therefore, we prospectively evaluated patients undergoing CABG with severe LV dysfunction and HM to elucidate postoperative prognosis. METHODS: We enrolled 120 consecutive patients undergoing CABG with severe LV dysfunction and HM as assessed by dobutamine echocardiography and by rest-redistribution radionuclide (Thallium-201) study. Mean patient age was 60+/-9 years (range 31-77 years). Mean preoperative LVEF was 28%+/-9 (range 10-40%). All patients underwent echocardiographic study to assess LV recovery of function intraoperatively, prior to hospital discharge, at 3 months, at 1 year, and yearly during the follow-up. Univariate and multivariate analysis were performed to to evaluate predictors of postoperative survival. RESULTS: There were 2 hospital (1.6%) and 15 late (12.5%) deaths, mainly for heart failure, leading to an actuarial survival of 80+/-6% and 60+/-9% at 5 and 8 years, respectively. LVEF significantly improved perioperatively (from 28+/-9% to 40+/-2%, P<0.01). Increase in LVEF, however, was gradually offset over the time (EF of 33+/-9%, 32+/-8%, and 30+/-9% at 3 months, and 12 months, and 8 years after surgery, respectively). Furthermore, patients who experienced limited LV functional recovery perioperatively had a more remarkable decline of LVEF thereafter, and suffered from recurrence of heart failure symptoms (freedom from heart failure 82+/-5% and 60+/-8% at 4 and 8 years respectively). Advanced preoperative NYHA Class, and age were independent risks factors for reduced postoperative survival. Preoperative angina and use of arterial conduits apparently did not influence patient morbidity and mortality at long term. CONCLUSION: CABG procedure in the presence of HM enhances LV recovery of function and has a favourable prognosis. Functional benefit of the left ventricle, however, appears to be time-limited, despite remarkable improvement in patient functional capacity. Advanced preoperative heart failure, minimal perioperative improvement of LVEF, and age account for a poor long-term prognosis.

Adult↗
PubMed2002

End-systolic wall stress is a major determinant of postoperative left ventricular dysfunction in patients with congenital mitral regurgitation.

To clarify the contribution of afterload to left ventricular performance after repair of mitral regurgitation, we evaluated echocardiographically 8 children who had undergone surgical repair for isolated congenital mitral regurgitation. We examined the relationship between left ventricular systolic function and preload, afterload, and contractility. The left ventricular systolic function was strongly correlated with the afterload after the surgical repair. In the postoperative state, reducing afterload by vasodilators could be a useful means of treating cardiac failure, in addition to using catecholamines to increase the contractility.

Adolescent↗
PubMed2003

Heterozygous deficiency of hypoxia-inducible factor-2alpha protects mice against pulmonary hypertension and right ventricular dysfunction during prolonged hypoxia.

Chronic hypoxia induces pulmonary vascular remodeling, leading to pulmonary hypertension, right ventricular hypertrophy, and heart failure. Heterozygous deficiency of hypoxia-inducible factor-1alpha (HIF-1alpha), which mediates the cellular response to hypoxia by increasing expression of genes involved in erythropoiesis and angiogenesis, has been previously shown to delay hypoxia-induced pulmonary hypertension. HIF-2alpha is a homologue of HIF-1alpha and is abundantly expressed in the lung, but its role in pulmonary hypertension remains unknown. Therefore, we analyzed the pulmonary response of WT and viable heterozygous HIF-2alpha-deficient (Hif2alpha(+/-)) mice after exposure to 10% O(2) for 4 weeks. In contrast to WT mice, Hif2alpha(+/-) mice were fully protected against pulmonary hypertension and right ventricular hypertrophy, unveiling a critical role of HIF-2alpha in hypoxia-induced pulmonary vascular remodeling. Pulmonary expression levels of endothelin-1 and plasma catecholamine levels were increased threefold and 12-fold respectively in WT but not in Hif2alpha(+/-) mice after hypoxia, suggesting that HIF-2alpha-mediated upregulation of these vasoconstrictors contributes to the development of hypoxic pulmonary vascular remodeling.

Animals↗
PubMed1998

The short-term effects of digoxin in patients with right ventricular dysfunction from pulmonary hypertension.

OBJECTIVE: Studies on the effects of digoxin in patients with right ventricular failure and normal left ventricular function have not been performed. We evaluated the short-term effects of digoxin administration in patients with primary pulmonary hypertension on hemodynamics, neurohormones, and baroreceptor responsiveness. DESIGN: This was a prospective study with patients serving as their own controls. SETTING: University Hospital Intensive Care Unit with central monitoring. PATIENTS: Seventeen patients with primary pulmonary hypertension and symptomatic heart failure were enrolled. INTERVENTIONS: Following baseline hemodynamics, neurohormonal samples were drawn and the heart rate response to change in blood pressure following a challenge of phenylephrine and nitroprusside were recorded. One mg of intravenous digoxin was given and the measurements repeated after 2 hours. RESULTS: Following digoxin there was a significant increase in cardiac output (3.49+/-1.2 to 3.81+/-1.2 L/min., p=0.028), a significant fall in norepinephrine (680+/-89 to 580+/-85 pg/ml, p=.013), and a significant increase in atrial natriuretic peptide (311+/-44 to 421+/-9 pg/ml, p=0.01). All of the patients had changes in heart rate and blood pressure following phenylephrine and nitroprusside challenge, but there was no significant difference in the change in heart rate response to change in blood pressure when rechallenged after digoxin treatment. CONCLUSION: Digoxin produces a modest increase in cardiac output in patients with pulmonary hypertension and right ventricular failure, as well as a significant reduction in circulating norepinephrine. No detectable effects of digoxin on baroreceptor responsiveness were apparent. The use of digoxin in pulmonary hypertension is warranted.

Adult↗
PubMed2003

Complete revascularization in patients with severe left ventricular dysfunction.

OBJECTIVE: This study evaluates whether patients with coronary artery disease and severely depressed left ventricular ejection fraction (LVEF) benefit from complete revascularization by multivessel coronary artery bypass. METHODS: From April 1994 to May 2002, 42 patients who underwent coronary artery bypass grafting (CABG) at our institution had impaired left ventricular (LV) function [an ejection fraction (EF) of 30% or less]. The average preoperative LVEF was 23.8%. The mean number of grafts was 4.6. Complete revascularization by multivessel bypass grafting was the goal for all patients. RESULTS: Thirty days mortality was 0 and hospital mortality was 2.4%. The mean graft patency rate for 35 (83%) patients at one month was 98.8%. The mean postoperative LVEF improved significantly, from 23.8% to 35.2% (p<0.05), and the New York Heart Association (NYHA) classification was improved in most patients. The Kaplan-Meier estimate of survival at 5 years was 83.1%, and that of the cardiac event-free rate at 5 years was 77.5%. CONCLUSION: For patients with poor LV function, complete surgical revascularization by multivessel bypass grafting can be performed safely, with satisfactory hospital mortality and long-term results.

Adult↗
PubMed2004

[Correction of baroreflex sensitivity impairment and efficacy of prevention of sudden arrhythmic death in patients with postinfarction left ventricular dysfunction].

Baroreflex sensitivity was assessed in 287 patients with history of myocardial infarction and left ventricular ejection fraction < or =40% by phenylephrine test and was found to be depressed (4.44+/-0.38 ms/mm Hg). Repeat study in 3, 6 and 12 months revealed substantial improvement of baroreflex sensitivity in patients treated with perindopril especially when it was combined with amiodarone, metoprolol, bisoprolol and carvedilol but not with atenolol. Combined therapy with amiodarone and carvedilol provided greatest reduction of sudden arrhythmic and total mortality. Superiority of combination of amiodarone with lipophilic beta-adrenoblocker over monotherapy had been anticipate but was not confirmed in any of large prospective studies.

Adrenergic beta-Antagonists↗
PubMed2005

Right ventricular dysfunction in advanced heart failure.

For many years cardiologists were not interested in studying right ventricular function and the role of the right ventricle in heart failure and in other disease states has therefore been largely underestimated. More recently a consensus has grown on the critical role of right ventricular function in patients with advanced congestive heart failure. The estimation of right ventricular function is nowadays warranted in the standard evaluation of patients with heart failure either due to ischemic heart disease or to primary dilated cardiomyopathy, since it is helpful in the clinical assessment and in the prognostic stratification of such patients. Most information may be obtained non-invasively using sound but simple and reproducible echocardiographic indicators of right ventricular function.

Disease Progression↗
PubMed1990

Coronary atherosclerosis is associated with left ventricular dysfunction and dilatation in aortic stenosis.

Patients with aortic stenosis develop widely variable patterns of left ventricular hypertrophy and dysfunction. We postulated that coronary atherosclerosis (CAD) may be associated with impaired left ventricular function and chamber dilatation in patients with aortic stenosis. Left ventricular mass and volumes were quantified from two-dimensional echocardiography and correlated with coronary angiography in 78 patients with severe aortic stenosis and no previous myocardial infarction or regional wall motion abnormalities. Eighteen patients (group 1) had smooth coronary arteries, 25 patients had irregular coronary arteries with 50% or less stenosis (group 2), and 35 patients had obstructive CAD (group 3). Even though the calculated valve area was similar in all three study groups, group 1 patients had higher values for ejection fraction (65 +/- 9%, 51 +/- 17%, and 48 +/- 13%; p = 0.0002), systolic mass-to-volume ratio (9.2 +/- 3.9, 5.6 +/- 2.8, and 5.2 +/- 2.2; p = 0.0001), and cardiac index (2.9 +/- 0.7, 2.5 +/- 0.7, and 2.3 +/- 0.6 l/min.min2; p = 0.015) than patients in groups 2 and 3, respectively (mean +/- SD). Mean circumferential wall stress was inversely related to severity of CAD. Multivariate analysis showed that CAD is an independent predictor of ejection fraction and mass-to-volume ratio in this group of patients. Thus, in an elderly population with severe aortic stenosis, patients with both obstructive and nonobstructive CAD have an increased incidence of left ventricular enlargement and systolic dysfunction.

Aged↗