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[Identification of viable myocardium in patients with chronic ischemic disease and left ventricular dysfunction: correlations between blood flow, metabolic activity and regional function].

To identify the presence of viable myocardium in areas of severe systolic dysfunction, we studied 22 patients (age 45 to 78 years) with chronic coronary artery disease and left ventricular dysfunction (mean ejection fraction 29 +/- 9%). All subjects underwent thallium-201 single photon emission computed tomography (SPECT), using the reinjection technique, positron emission tomography (PET) with H2(15)O and 18-fluorodeoxyglucose (FDG) to measure regional blood flow and exogenous glucose uptake, respectively, and nuclear magnetic resonance imaging (MRI). From matched transaxial PET, SPECT and MRI tomograms, a total of 290 left ventricular myocardial regions were analyzed. According to the regional wall thickening, measured from MRI, 3 groups of myocardial regions were identified: akinetic-dyskinetic (n = 60), showing either absence of systolic thickening or systolic thinning; hypokinetic (n = 97), showing an absolute wall thickening less than or equal to 2 mm; normal (n = 133), showing an absolute wall thickening greater than 2 mm. Of the 60 akinetic or dyskinetic regions, 3 were normal by SPECT and 37 corresponded to either a total or partially reversible thallium defect: 34 of these 40 regions also showed presence of FDG uptake by PET. The remaining 20 akinetic or dyskinetic regions showed a thallium defect that remained irreversible after reinjection: in 7 of these 20 regions, however, there was evidence of metabolic activity, as expressed by FDG uptake. Thus, 47 (78%) of the myocardial akinetic or dyskinetic regions showed presence of viable tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Prevalence and prognostic value of left ventricular dysfunction in non-Q-wave myocardial infarction.

Forty-two consecutive patients with non-Q-wave acute myocardial infarction (AMI) and 40 consecutive patients with transmural AMI were comparatively examined by equilibrium gated radionuclide angiography (ERNA) to assess prevalence and prognostic value of left ventricular dysfunction in non-Q-wave AMI. Left ventricular ejection (LVEF) was generally preserved both in anterior and inferior non-Q-wave infarctions and sharply reduced only in anterior transmural infarctions. ERNA cannot assist in identifying any subgroup of patients with non-Q-wave AMI at risk of major complications other than left ventricular failure because they may develop such complications in spite of a normal LVEF.

Adult

Serial evaluation of right ventricular dysfunction associated with acute inferior myocardial infarction.

Right ventricular (RV) function was evaluated serially by multigated blood pool imaging in 18 patients with RV dysfunction associated with acute inferior myocardial infarction. Radionuclide ventriculograms were performed on all patients within 18 hours of chest pain and again at 10 days. In addition, 15 of 18 patients had rest and exercise radionuclide ventriculograms at 3 months. The mean resting right ventricular ejection fractions (RVEF) at admission, 10 days, and 3 months in these patients was 31.8 +/- 12.6% (SD), 46.9 +/- 11.2% (p less than 0.05), and 44.5 +/- 10.2% (p less than 0.05), while the left ventricular ejection fractions were 55.9 +/- 10.6%, 57.9 +/- 13.3%, and 53.1 +/- 11.2% (p = ns). The 3-month exercise radionuclide ventriculogram demonstrated an increase in RVEF greater than 5% in 6 of 15 patients. In eight catheterized patients, neither the location nor the severity of coronary artery narrowing nor the presence of collaterals correlated with the RV exercise response. Improvement in RV function over a 10-day interval following acute inferior myocardial infarction suggests the presence of significant reversible right ventricular dysfunction during the acute phase.

Cardiac Catheterization

Cardiovascular and neurohormonal effects of atrial natriuretic peptide in conscious dogs with and without chronic left ventricular dysfunction.

Atrial natriuretic peptide (hANP 4-28) was infused for 1 h (0.3 microgram/kg/min) in 11 normal awake dogs and seven awake dogs with chronic left ventricular dysfunction, induced 16 weeks earlier by repetitive DC shock. The responses were similar in the two groups and included decreases in arterial pressure (107-99 mm Hg), heart rate (83-72 beats/min), and cardiac output (3.6-2.8 L/min), without changes in right or left ventricular filling pressures. Systemic vascular resistance (SVR) tended to rise during the infusion and was significantly increased (2,847-3,442 dyn s cm-5, p less than .05) during the postinfusion recovery period. Regional blood flows (microspheres) during infusion revealed a decrease in skin and splanchnic flow. Despite the apparent vasoconstrictor effect, plasma norepinephrine (PNE), renin activity (PRA), and arginine vasopressin (AVP) levels all fell during ANP infusion. These data suggest that ANP exerts a cardioinhibitory effect, possibly similar to that of arginine vasopressin (AVP), and that the net systemic vasoconstrictor effect of ANP in these dogs is mediated by a complex interrelationship between direct vascular effects, neurohormonal inhibition, and central reflex activation.

Animals

Effect of indecainide in patients with left ventricular dysfunction.

Indecainide, a new antiarrhythmic agent classified as type Ic was evaluated in 11 patients with heart disease who had greater than or equal to 30 ventricular premature complexes/hour, moderate-to-marked left ventricular dysfunction, and mean ejection fraction 34% +/- 8%. Patients received indecainide, 50 mg by mouth, every 6 hours and the dose was increased until greater than or equal to 80% suppression was noted, adverse effects occurred, or a maximum dose of 100 mg indecainide was given every 6 hours. Ventricular premature complexes were suppressed greater than or equal to 80% in nine patients (p less than 0.05) and ventricular tachycardia episodes were completely suppressed in five of eight patients. The effective or maximal mean daily indecainide dose was 191 +/- 32 mg; half of the responders achieved achieved efficacy at serum drug concentration greater than or equal to 600 ng/ml. Serum drug concentration was directly related to gender (r = 0.78, p less than 0.04) and inversely related to creatinine clearance (r = 0.74, p less than 0.05) and ejection fraction (r = 0.71, p less than 0.02). Indecainide prolonged mean PR and QRS intervals (p less than 0.05) but not QT or QTc. There was a linear relation between percent change in PR (r = 0.80, p less than 0.001) and QRS (r = 0.66, p less than 0.001) intervals and serum drug concentration. After starting or increasing the dose, careful observation of patients with decreased renal function or reduced ejection fraction should be exercised because they attain higher drug concentration than normal subjects.

Adult

"Escape" of aldosterone production in patients with left ventricular dysfunction treated with an angiotensin converting enzyme inhibitor: implications for therapy.

Despite the findings in randomized trials of a significant effect of angiotensin-converting enzyme (ACE) inhibitors in reducing morbidity and mortality of patients with symptomatic left ventricular dysfunction, the morbidity and mortality of these patients remains relatively high. One potential strategy to further improve morbidity and mortality in these patients is blockade of a aldosterone. Many clinicians have assumed that ACE inhibitors would block both angiotensin II and aldosterone. However, there are data to suggest that aldosterone production may "escape" despite the use of an ACE inhibitor. An escape of aldosterone production has several important consequences, including: sodium retention, potassium and magnesium loss, myocardial collagen production, ventricular hypertrophy, myocardial norepinephrine release, endothelial dysfunction, and a decrease in serum high density lipoprotein cholesterol. Due to the potential importance of these mechanisms, the finding that there is a significant correlation between aldosterone production and mortality in patients with heart failure, as well as evidence that an aldosterone antagonist, spironolactone, when administered to patients with heart failure treated with conventional therapy including an ACE inhibitor results in increased diuresis and symptomatic improvement, an international prospective multicenter study has been organized, the Randomized Aldactone Evaluation Study (RALES Pilot Study), to evaluate the safety of blocking the effects of aldosterone in patients with heart failure treated with an ACE inhibitor.

Aldosterone

Acute haemodynamic effects of the beta 1-adrenoceptor partial agonist xamoterol at rest and during supine exercise in patients with left ventricular dysfunction due to ischaemic heart disease: a double-blind randomized trial.

The effects of xamoterol 0.2 mg kg-1 i.v. and placebo on left ventricular function at rest and on exercise were compared in patients with left ventricular dysfunction due to ischaemic heart disease. Improvements were seen in systolic and diastolic function at rest, and at up to 50% of maximal exercise, without evidence of worsening myocardial ischaemia.

Adrenergic beta-Agonists

Left ventricular dysfunction after acute myocardial infarction: results of a prospective multicenter study.

In a multicenter prospective study of 866 patients who survived the coronary care unit phase of an acute myocardial infarction, variables reflecting left ventricular function were examined to assess their impact on 2 year survival. Single variables that reflected left ventricular dysfunction before infarction and in the acute and recovery phases were, respectively, history of prior myocardial infarction, rales in the coronary care unit dichotomized at greater than bibasilar and predischarge radionuclide ejection fraction dichotomized at less than 0.40. When combined in a stepwise fashion, patients lacking these three risk characteristics had a 2 year 4.2% mortality rate, whereas patients possessing all three characteristics had a 45% mortality rate. Rales in the coronary care unit and predischarge ejection fraction act independently, and each contributes to mortality. Fifty-two patients with advanced rales but an ejection fraction of 0.40 or greater had a 21% mortality rate. Similarly, 208 patients with few rales but an ejection fraction of less than 0.40 had a 15% mortality rate. These data suggest that the mortality risk imposed by those factors that assess permanent left ventricular damage is independent of and additive to the mortality risk contributed by dynamic, acute phase dysfunction. These data fit the hypothesis that acute phase dysfunction is, in part, due to transient ischemia that, on reversal, can restore function toward normal. The results suggest 1) that assessment of left ventricular function during the acute and recovery phases of myocardial infarction is necessary to define prognostic characteristics of an individual patient, and 2) that of particular importance is the identification of patients whose postinfarction course is consistent with reversible ischemia.

Cardiac Output

Comparative hemodynamic effects of mexiletine and quinidine in patients with severe left ventricular dysfunction.

Mexiletine and quinidine are often administered to patients with severe congestive heart failure, but their hemodynamic effects have not been adequately studied in these individuals. In a randomized, crossover study, the hemodynamic responses to single oral doses of quinidine (600 mg) and mexiletine (400 mg) were compared in 20 patients with marked left ventricular dysfunction. Quinidine predominantly caused vasodilation, with mean arterial, left ventricular filling, and right atrial pressures all decreasing (-7 +/- 2, -2.3 +/- 1.0, and -1.1 +/- 0.5 mm Hg, respectively) and the systemic vascular resistance also declining (-308 +/- 84 dynes.sec.cm5). In contrast, the systemic vascular resistance increased (314 +/- 84 dynes.sec.cm-5) and the mean arterial, left ventricular filling, and right atrial pressures also increased (+2 +/- 2, +6.1 +/- 1.8, and +1.8 +/- 0.6 mm Hg, respectively) after mexiletine. Cardiac performance declined with mexiletine (cardiac and stroke work indexes decreasing -0.3 +/- 0.1 L/min/m2 and -5 +/- 1 gm.m/m2, respectively), but there was no significant change in cardiac or stroke work indexes with quinidine (+0.1 L/min/m2 and -0.3 +/- 0.9 gm.m/m2, respectively). The response to the two agents significantly differed for all parameters measured (p less than 0.005). These hemodynamic changes were accompanied by clinical effects. Mexiletine induced increased dyspnea in five patients and quinidine led to symptomatic hypotension in two patients. Plasma concentrations of mexiletine and serum concentrations of quinidine were within or below the therapeutic range in all patients. In conclusion, mexiletine and quinidine exert different hemodynamic effects when given to patients with severe congestive heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral

Detection of regional left ventricular dysfunction in early pacing-induced heart failure using ultrasonic integrated backscatter.

BACKGROUND: It has been demonstrated that cyclic variation of ultrasonic integrated backscatter (CVIBS) may be useful in detecting altered physical conditions in the heart. However, no previous study has examined serial changes of CVIBS in the myocardium during the development of left ventricular dysfunction. METHODS AND RESULTS: We examined alterations of CVIBS in pacing-induced cardiac dysfunction. Eight pigs (36 +/- 2 kg) were studied before and sequentially during sustained rapid ventricular pacing (225 +/- 9 beats per minute). CVIBS was measured in the IVS and left ventricular PLW before pacing and daily for 4 days after onset of pacing. Five additional pigs (35 +/- 10 kg) were examined after 14 days of pacing. Regional function and CVIBS were assessed with pacemakers inactivated. A quantitative integrated backscatter imaging system (two-dimensional format) was used. Over 4 days of pacing, the magnitude of CVIBS progressively decreased in the PLW but was unchanged in the IVS, findings that persisted at 14 days. Percent wall thickening in the PLW progressively decreased to a greater degree than percent wall thickening in the IVS. A linear relation between the magnitude of CVIBS and percent wall thickening was found. At 14 days, blood flow to the two regions was similar but regional differences in CVIBS persisted. CONCLUSIONS: Rapid left ventricular pacing produces abnormalities of regional myocardial function within 48 hours of pacing. Regional myocardial dysfunction is accompanied by a reduction in CVIBS in the same region.

Animals

Acute hemodynamic and arrhythmogenic effects of high-dose intravenous salbutamol in patients with chronic left ventricular dysfunction.

The short-term hemodynamic and possible arrhythmogenic effects of intravenous salbutamol at a dose of 30 or 60 micrograms/min were evaluated in 14 patients with severe chronic left ventricular dysfunction using equilibrium radionuclide angiocardiography and electrocardiographic monitoring. Salbutamol infusions at a dose of 30 micrograms/min did not cause significant hemodynamic changes; however, at a dose of 60 micrograms/min there was a significant increase in stroke volume, cardiac output, and left ventricular ejection fraction. Heart rate increased significantly while systemic peripheral resistance decreased significantly. Two patients developed ventricular premature beats and another two supraventricular tachycardia, but none were associated with adverse consequences. Thus, high-dose intravenous salbutamol is effective and safe, and may be used in the acute management of patients with poor left ventricular function.

Adult

Intravascular and extravascular pulmonary fluid volumes during chronic experimental left ventricular dysfunction.

To assess the effects of chronic left ventricular (LV) dysfunction on intravascular pulmonary blood volume (PBV) and extravascular lung water (EVLW) lung fluid volumes, 56 dogs were evaluated by means of double-indicator dilution techniques. PBV and EVLW were measured in seven control dogs, in eight dogs 4 hours after the production of left heart dysfunction, and then in three additional groups of dogs (n = seven in each group) 7, 14, and 30 days after the production of LV dysfunction. Twenty dogs were excluded because we were unable to produce elevations in LV end-diastolic volume greater than 25 mm Hg. EVLW was measured using heat as the diffusible indicator, and electric shock was used to create heart block and myocardial scarring in order to produce LV dysfunction. Plasma volume was calculated prior to death by means of radioiodinated albumin. In the remaining animals, electric shock acutely and chronically elevated LV end-diastolic pressure (control 2.3 +/- 1.0 mm Hg; postshock pressures greater than 25 mm Hg). PBV increased initially after cardiac failure and remained so as time progressed, although it represented a smaller fraction of the plasma volume as time passed (11.2 +/- 2.1% control, 15.9 +/- 3.4% at 4 hours after failure, and 12.6 +/- 2.0% at 7 days; the former p less than 0.005 vs control, the latter p less than 0.01 vs control). EVLW increased as time progressed, in consort with small but progressive increases in left atrial pressure. Thus, we conclude that the effects of acute and chronic LV dysfunction on pulmonary circulation are significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Effects of oral hydralazine on rest and exercise hemodynamics in patients with aortic or mitral regurgitation and left ventricular dysfunction.

The hemodynamic effects of afterload reduction were studied at rest and during two levels of upright exercise in patients with aortic or mitral regurgitation and left ventricular dysfunction. Eleven patients underwent invasive hemodynamic monitoring before and after 50-70 mg of oral hydralazine was given ever 6 h for 48 h. At rest, heart rate and mean arterial pressure after hydralazine were unchanged from control. During exercise, there was no significant change in heart rate, but mean arterial pressure fell significantly during the first level of exercise. Systemic vascular resistance was elevated before hydralazine and was significantly reduced after treatment at both exercise levels. After hydralazine, the resting oxygen consumption was significantly elevated at rest but was unchanged during exercise, the arteriovenous oxygen difference was significantly narrowed at both rest and exercise, and the pulmonary capillary wedge pressure was also significantly lower at both rest and exercise. In this select group of patients who are not candidates for surgical valve replacement, chronic afterload reduction with oral hydralazine may result in increased cardiac performance, decreased pulmonary congestion, reduced myocardial oxygen demands, and improvement in resting and/or exertional symptoms.

Administration, Oral

Short-term haemodynamic evolution and late follow-up of post-infarct patients with left ventricular dysfunction undergoing a physical training programme.

The aims of this study were to investigate the short-term haemodynamic changes occurring in post-infarct patients with left ventricular dysfunction undergoing a physical training programme and the prognostic implications of such changes. Ninety-five male patients with no evidence of congestive heart failure, consecutively admitted for exercise testing with haemodynamic monitoring in the supine position, in whom exercise pulmonary artery diastolic pressure (PAdP) exceeded 20 mmHg were enrolled in an in-hospital one-month physical training programme. After training all patients' exercise capacity increased by 24% (P less than 0.001) with no change of PAdP. At matched work load, heart rate decreased (126 +/- 21 vs 120 +/- 19 bt min-1, P less than 0.05) as did PAdP (27 +/- 5 vs 25 +/- 6 mmHg, P less than 0.05) and A-VO2 difference increased (9.5 +/- 1.7 vs 10 +/- 1.6 ml%, P less than 0.01). Similar results were observed in a subset of patients with exercise PAdP greater than 30 mmHg (30 patients). In 11 patients with inadequate cardiac output neither heart rate nor PAdP decreased after training and a disproportionate increase in blood pressure was noted. Clinical follow-up ranged from 1 to 8 years (62 +/- 32 months). Seven deaths, 12 reinfarctions and 14 coronary artery bypass graftings occurred. The modifications, after training in work capacity, heart rate and PAdP, were not predictive of events.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Long-term treatment of ventricular tachycardia with amiodarone in presence of severe left ventricular dysfunction.

A group of 34 consecutive patients with coronary artery disease (n = 29) or dilated cardiomyopathy (n = 5) (3 women, 31 men, age 38-80 yr) who had severely impaired left ventricular function (left ventricular ejection fraction less than or equal to 40%) and high-grade ventricular ectopic activity (sustained or nonsustained ventricular tachycardia or ventricular fibrillation) were treated with amiodarone (mean dose: 206 mg/d) and followed for 1-117 (mean: 49) months. In the total group, there were seven sudden deaths, five deaths due to pump failure, one non-cardiac death, and two successful heart transplantations during follow-up. Thus the annual cardiac mortality in these carefully selected and followed patients was 8, 6%, the annual cardiac event rate was 10, 1%. The cumulative cardiac survival-rate was 62% after 5 years and 41% after 10 years. In five patients, treatment was interrupted after 10 to 43 months, three of the patients were alive at follow-up and two suffered cardiac death, resulting in an annual cardiac death rate of 12% in this subgroup of treatment. Based on the results of this retrospective analysis we conclude that in patients with low left ventricular ejection fraction and nonsustained or sustained ventricular tachycardia treated with low dose amiodarone, mortality was unexpectedly low. Thus, it may be the antiarrhythmic treatment to be considered in patients with ventricular tachycardia and severe left ventricular dysfunction.

Adult

Prognostic importance of the immediate hemodynamic response to nifedipine in patients with severe left ventricular dysfunction.

To determine the clinical significance of the occurrence of hemodynamic deterioration after the administration of calcium channel blocking drugs, nifedipine (20 mg orally) was administered to 29 patients with severe left ventricular dysfunction. Thirteen patients showed hemodynamic improvement with the drug (Group 1), as shown by a notable increase in cardiac index associated with a modest decrease in mean arterial pressure. The other 16 patients exhibited hemodynamic deterioration after nifedipine (Group 2), as reflected by a decline in right and left ventricular stroke work indexes accompanied by a marked hypotensive response. These differences were not related to differences in the peripheral vascular response to nifedipine, because both groups showed similar decreases in systemic and pulmonary vascular resistances. Groups 1 (hemodynamic improvement) and 2 (hemodynamic deterioration) were similar with respect to all demographic variables and pretreatment left ventricular performance (cardiac index, left ventricular filling pressure and systemic vascular resistance). Yet, the 1 year actuarial survival in patients in Group 1 was substantially better than that in patients in Group 2 (67 versus 23%, p = 0.009). Group 2, however, had higher values for plasma renin activity (17.7 +/- 6.0 versus 4.3 +/- 1.4 mg/ml per h, p less than 0.05), lower values for serum sodium concentration (134.6 +/- 1.2 versus 139.2 +/- 0.6 mEq/liter, p less than 0.05) and higher values for mean right atrial pressure (15.8 +/- 2.0 versus 7.9 +/- 1.4 mm Hg, p less than 0.01) than did patients in Group 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Haemodynamic dose-response actions of cicloprolol in left ventricular dysfunction due to ischaemic heart disease.

Cicloprolol is a cardioselective beta-1 partial agonist; its haemodynamic and radionuclide (nuclear stethoscope) effects were determined in 22 patients with impaired left ventricular function due to coronary artery disease. Following a 20 min stable control period, the effects of four doses of cicloprolol (0.025, 0.025, 0.05 and 0.1 mg/kg at 10 min intervals) were measured at rest 5-10 min after each intravenous injection. The effects of the cumulative 0.2 mg/kg dosage were assessed during supine bicycle exercise and compared with a control exercise period. At rest there were significant increases in systolic arterial without change in mean blood pressure. The heart rate and cardiac index were unchanged. There was a significant increase in left ventricular ejection fraction with a reduction in filling pressure and volume. Patients with resting heart rate below 75 beats/min and with ejection fraction greater than 35% showed the greatest improvement. During supine bicycle exercise, ejection fraction was increased compared to control (31 +/- 2 to 36 +/- 2; P less than 0.01), cardiac volume reduced and exercise tachycardia attenuated. These data suggest that cicloprolol may be of value where beta-blockade is considered in the presence of underlying left ventricular dysfunction due to ischaemic heart disease.

Adrenergic beta-Antagonists