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[The accuracy of echocardiography during the infusion of low-dose dobutamine in identifying vital myocardium in patients with obstructive coronary disease and chronic left ventricular dysfunction].

The identification of viable myocardium has important therapeutic implications in patients with coronary artery disease (CAD) and chronic left ventricular dysfunction. To assess the accuracy of transthoracic echocardiography (TTE) during dobutamine infusion for identification of viable myocardium, we have analyzed 14 patients affected by CAD and chronic abnormalities of left ventricular wall motion (RWM), present at rest, referred for coronary artery bypass grafting (CABG): 8 of 14 patients had a history of myocardial infarction with evidence of Q waves at the surface ECG. All patients had a clinical stable CAD. RWM response to dobutamine (5 mcg/kg/min and 10 mcg/kg/min) was evaluated using TTE and compared to RWM changes after CABG analyzed by intraoperative epicardial echocardiography (EE). RWM was analyzed qualitatively by dividing the left ventricle into 16 segments and a score index was assigned to each region (0: normal; 1: hypokinetic; 2: akinetic; 3: dyskinetic). Of 125 akinetic segments present at rest before CABG, 93 showed functional improvement after CABG at intraoperative EE. The RWM response to dobutamine infusion predicted intraoperative improvement after CABG in 85 of 93 segments (sensitivity: 91.3%) and identified 25 of the 32 segments which did not exhibit intraoperative improvement (specificity: 78.1%). The TTE performed 15 days after CABG showed no worsening or further improvement in RWM when compared with intraoperative EE study. Summed segment scores in 14 patients showed significantly improvement from 17.9 +/- 7, medium values at rest, to 5.1 +/- 4 after dobutamine infusion (p less than 0.001) and 5 +/- 7 after CABG (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[Respiratory changes of superior vena cava flow velocity in old myocardial infarction with severe left ventricular dysfunction].

The clinical significance of the flow velocity of the superior vena cava (SVC) in old myocardial infarction (OMI) with severe left ventricular dysfunction were evaluated using pulsed Doppler echocardiography. The subjects consisted of 10 patients with OMI (averaged left ventricular ejection fraction: 0.37 +/- 0.11) and 10 age-matched normal controls. Among the patients, eight had extensive anterior infarction and two had both anterior and inferior infarctions. During normal respiration, the peak SVC flow velocities in systole (S) and diastole (D), and the D/S ratio were measured. To evaluate right ventricular diastolic function, we measured the peak velocity across the tricuspid orifice in early diastole (rapid inflow: T-R) and the atrial contraction phase (T-A), and the ratio T-A/T-R during quiet expiration. In the normal controls, S was greater than D, both during expiration and inspiration. During inspiration, S, D and the D/S in the normal controls increased, with a greater increase in D than in S. In the patients, however, D and the D/S did not increase during inspiration. T-R was less and the T-A/T-R was greater in the patients with OMI than in the normal controls. These findings of tricuspid flow velocity revealed impaired diastolic filling of the right ventricle in patients with OMI. In conclusion, the impaired diastolic filling of the right ventricle in patients with OMI might be one of the causes of the abnormal response of the SVC flow velocity during normal spontaneous respiration.

Blood Flow Velocity

Myocardial enterovirus infection with left ventricular dysfunction: a benign disease compared with idiopathic dilated cardiomyopathy.

OBJECTIVES: Endomyocardial biopsy samples from patients with idiopathic dilated cardiomyopathy were screened for the presence of enterovirus genome. Patients with enterovirus-positive samples were further studied with regard to disease course, histologic variables and response to interferon-alpha treatment. BACKGROUND: Studies of patients with idiopathic dilated cardiomyopathy have reported widely divergent clinical outcomes, suggesting that there is no unique underlying pathogenetic mechanism. METHODS: Five left ventricular endomyocardial biopsy samples were screened for the presence of the enterovirus genome by an established in situ hybridization technique in combination with a histologic, histomorphometric and immunohistologic workup. The course of the disease was then prospectively followed for up to 50 months. Virus-positive patients whose condition deteriorated were treated with interferon-alpha. RESULTS: Of 77 patients, 20 (26%) had enterovirus-positive and 57 (74%) enterovirus-negative biopsy samples. During a mean follow-up period of 25.8 +/- 13.7 months, 1 patient in the enterovirus-positive group and 11 in the enterovirus-negative group died. Four patients in the enterovirus-negative group underwent heart transplantation (p < 0.05). The surviving 19 enterovirus-positive patients had a decrease in mean left ventricular end-diastolic diameter from 66 to 61 mm (p < 0.05) and a mean increase in left ventricular ejection fraction from 0.35 to 0.43 (p < 0.05). In contrast, enterovirus-negative patients had no significant change in end-diastolic diameter or left ventricular ejection fraction. Four patients in the enterovirus-positive group whose condition deteriorated were treated with a 6-month course of subcutaneous interferon-alpha (3 x 10(6) U every second day). This treatment induced hemodynamic improvement in all four patients and eliminated the persistent enteroviral infection in two. CONCLUSIONS: Enterovirus-positive patients have a better heart transplantation-free survival rate and hemodynamic course, with fewer histologic changes, than do enterovirus-negative patients. In addition, enterovirus-positive patients respond favorably to interferon-alpha treatment. These observations indicate that myocardial enteroviral infection with associated left ventricular dysfunction is a distinct disease entity with a benign course.

Cardiac Catheterization

Left ventricular dysfunction in acute myocardial infarction due to isolated left circumflex coronary artery stenosis.

The characteristics of regional and global left ventricular dysfunction due to isolated left circumflex (LC) artery stenosis were determined from the contrast ventriculograms of 52 patients studied during acute myocardial infarction. In patients with a left dominant coronary circulation (35%), the severity, circumferential extent and location of hypokinesia resembled those of right coronary artery stenosis. However, in patients with a right dominant or balanced circulation (65%), the location of LC artery-related hypokinesia varied over the entire left ventricular contour, overlapping with the territories of the left anterior descending and right coronary arteries. The method for measuring the severity of hypokinesia was adjusted to take into account the wide territory of the LC artery. This enhanced the sensitivity of the method, particularly in the right anterior oblique view, as indicated by the greater severity of hypokinesia measured (-2.5 +/- 0.9 vs -1.8 +/- 1.1 standard deviations by our previously published method, p less than 0.001). However, the overlap of the artery territories may make it difficult to selectively measure the dysfunction due to stenosis of an artery of interest in patients with multiple infarctions. The circumferential extent of hypokinesia due to LC artery thrombosis was greater in the left than the right anterior oblique view. When averaged over both views, the size of the dysfunctional segment approached that due to left anterior descending coronary artery thrombosis, exceeding the size previously reported. These results suggest that current eligibility criteria for thrombolytic therapy select patients with extensive LC artery beds.

Cineradiography

Effect of long-term enalapril therapy on neurohormones in patients with left ventricular dysfunction. SOLVD Investigators.

The aim of this study was to compare the long-term effects of treatment with enalapril or placebo on plasma neurohormones in patients with left ventricular (LV) dysfunction. Elevated neurohormonal levels are associated with increased mortality in patients with congestive heart failure. Multiple studies have shown that angiotensin-converting enzyme inhibitors decrease mortality and morbidity in these patients. In Studies of Left Ventricular Dysfunction (SOLVD), enalapril significantly reduced mortality in patients with symptomatic LV dysfunction (treatment trial). In contrast, in patients with asymptomatic LV dysfunction (prevention trial), there was no significant reduction in mortality with enalapril therapy. The effect of enalapril was examined in 333 prevention trial and 129 treatment trial patients. Plasma norepinephrine (NE) and plasma renin activity were measured in these patients at baseline, and at 4 and 12 months of follow-up. In a subset of these patients, atrial natriuretic peptide (ANP) and arginine vasopressin were also measured. Analysis of covariance models were used to determine the effect of enalapril on each neurohormone. Participants in the treatment trial had significantly higher neurohormonal levels when compared with those in the prevention trial or normal control subjects. In the treatment trial, patients taking enalapril had a greater decrease in plasma NE levels than patients taking placebo (p < 0.08).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

The distribution and severity of coronary artery disease and left ventricular dysfunction among patients with single coronary artery disease and angina pectoris.

The distribution and severity of coronary artery disease and left ventricular dysfunction were evaluated in 103 patients with single coronary artery disease and angina pectoris. The coronary arterial patterns were separated into right (76), mixed (18), and left (9) systems depending upon the blood supply to the inferior surface of the left ventricle. The following relationships were noted: (1) In patients with single coronary artery disease and angina pectoris, coronary arterial lesions are similar among right, mixed, and left systems. (2) In order of frequency, single coronary artery disease occurred most commonly in the left anterior descending coronary artery (55), next most commonly in the right coronary artery (36), and least commonly in the circumflex/obtuse marginal coronary artery (12). (3) Left ventricular wall motion abnormalities were seen in descending order of frequency: patients with right coronary artery (50%), left anterior descending coronary artery (36%), and circumflex/obtuse marginal coronary artery (25%) disease.

Adult

Exercise training in patients with severe left ventricular dysfunction. Hemodynamic and metabolic effects.

We studied the effects of exercise training in patients with chronic heart failure attributed to left ventricular dysfunction (ejection fraction, 24 +/- 10%). Twelve ambulatory patients with stable symptoms underwent 4-6 months of conditioning by exercising 4.1 +/- 0.6 hr/wk at a heart rate corresponding to 75% of peak oxygen consumption. Before and after training, patients underwent maximal bicycle exercise testing with direct measurement of central hemodynamic, leg blood flow, and metabolic responses. Exercise training resulted in a decrease in heart rate at rest and submaximal exercise and a 23% increase in peak oxygen consumption from 16.8 +/- 3.8 to 20.6 +/- 4.7 ml/kg/min (p less than 0.01). Heart rate, arterial lactate, and respiratory exchange ratio were unchanged at peak exercise after training. Maximal cardiac output tended to increase from 8.9 +/- 2.7 to 9.9 +/- 3.2 1/min and contributed to improved peak oxygen consumption in some patients, although this change did not reach statistical significance (p = 0.13). Rest and exercise measurements of left ventricular ejection fraction, left ventricular end-diastolic volume, and left ventricular end-systolic volume were unchanged. Right atrial, pulmonary arterial, pulmonary capillary wedge, and systemic arterial pressures were not different after training. Training induced several important peripheral adaptations that contributed to improved exercise performance. At peak exercise, systemic arteriovenous oxygen difference increased from 13.1 +/- 1.4 to 14.6 +/- 2.3 ml/dl (p less than 0.05). This increase was associated with an increase in peak-exercise leg blood flow from 2.5 +/- 0.7 to 3.0 +/- 0.8 l/min (p less than 0.01) and an increase in leg arteriovenous oxygen difference from 14.5 +/- 1.3 to 16.1 +/- 1.9 ml/dl (p = 0.07). Arterial and femoral venous lactate levels were markedly reduced during submaximal exercise after training, even though cardiac output and leg blood flow were unchanged at these workloads. Thus, ambulatory patients with chronic heart failure can achieve a significant training effect from long-term exercise. Peripheral adaptations, including an increase in peak blood flow to the exercising leg, played an important role in improving exercise tolerance.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult

Left ventricular filling pattern and pulmonary wedge pressure are closely related in patients with recent anterior myocardial infarction and left ventricular dysfunction.

To determine whether mitral flow velocity can be used to estimate mean pulmonary wedge pressure (PWP) in patients with left ventricular dysfunction, 50 patients with recent Q-wave anterior infarction and a reduced ejection fraction (less than 40%) underwent simultaneous pulsed-wave Doppler measurements of mitral flow and right heart catheterization. Doppler tracings and PWP were recorded at rest, after passive leg lifting (45 degrees) and (in 15 patients with increased PWP) after 5 mg sublingual ISDN. Significant correlations were found between the ratio of peak early to peak late diastolic velocity (E/A) and PWP (r = 0.83). Early diastolic deceleration and the ratio of the time velocity integral of atrial contribution to the total time velocity integral were also correlated to PWP (r = 0.80 and r = 0.79 (respectively). The E/A ratio was less than 1 in 25 patients and more than 1 in the remaining 25. An E/A ratio of at least 1 predicted a PWP of more than 20 mmHg with a sensitivity of 100% and a specificity of 86%. In all five patients, in whom the PWP was less than 20 mmHg at baseline and became greater with leg lifting, the E/A ratio changed from less than 1 to more than 1. After ISDN, changes in E/A ratio from more than 1 to less than 1 identified all 12 patients with a PWP falling below 20 mmHg. In conclusion, patients with recent Q-wave anterior infarction and a reduced ejection fraction mitral flow velocity-derived variables correlate with PWP representing a reliable index for the diagnosis of markedly increased PWP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Comparison of rest-redistribution thallium-201 imaging and reinjection after stress-redistribution for the assessment of myocardial viability in patients with left ventricular dysfunction secondary to coronary artery disease.

Thallium (Tl)-201 reinjection after stress-redistribution (RI) imaging has been proven to accurately identify ischemic and viable myocardium. Quantitative Tl-201 analysis after stress has also shown viable myocardium in most mild to moderate (51% to 85% of normal uptake) irreversible Tl-201 defects. However, if the main clinical question is whether a region is viable, and not whether there is inducible ischemia, a resting protocol may be more appropriate. The aim of this study was to determine whether rest-redistribution (RD) quantitative Tl-201 single-photon emission tomographic imaging provides the same information on viable myocardium as Tl-201 RI. Thus, 15 patients (mean age 58 +/- 9 years) with chronic coronary artery disease and left ventricular dysfunction (ejection fraction 35 +/- 8%) were studied by both RI and RD Tl-201 single-photon emission tomography. Regional Tl-201 uptake was assessed quantitatively using a 16-segment model. When Tl-201 images were classified as normal/reversible (viable) or irreversible (nonviable), RI showed viable myocardium in 145 of 240 myocardial regions (60%), whereas RD showed it in 103 of 240 myocardial regions (43%). The 2 imaging protocols provided concordant information in 176 of 240 myocardial regions (73%). Among the 64 (27%) discordant regions, 53 (22%) were viable by RI and nonviable by RD, whereas 11 (5%) were viable by RD and nonviable by RI (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Scintigraphically detected predominant right ventricular dysfunction in acute myocardial infarction: clinical and hemodynamic correlates and implications for therapy and prognosis.

To determine the clinical and hemodynamic correlates as well as therapeutic and prognostic implications of predominant right ventricular dysfunction complicating acute myocardial infarction, 43 consecutive patients with scintigraphic evidence of right ventricular dyssynergy and a depressed right ventricular ejection fraction (less than 0.39) in association with normal or near normal left ventricular ejection fraction (greater than or equal to 0.45) were prospectively evaluated. All 43 patients had acute inferior infarction, forming 40% of patients with acute inferior infarction, and only eight (24%) had elevated jugular venous pressure on admission. On hemodynamic monitoring, 74% of patients had a depressed cardiac index (less than or equal to 2.5 liters/min per m2), averaging 2.0 +/- 0.05 for the group. Of these, 30% did not demonstrate previously described hemodynamic criteria of predominant right ventricular infarction (right atrial pressure greater than or equal to 10 mm Hg or right atrial to pulmonary capillary wedge pressure ratio greater than or equal to 0.8, or both). The left ventricular end-diastolic volume was reduced to 49 +/- 11 ml/m2 (n = 22) and correlated significantly with the stroke volume index (r = 0.82; p less than 0.0001) and cardiac index (r = 0.57; p = 0.005). The follow-up right ventricular ejection fraction, determined in 33 patients, showed an increase of 10% or greater in 26 (79%), increasing from a mean value of 0.30 +/- 0.06 to 0.40 +/- 0.09 (p less than 0.0001) without a significant overall change in the mean left ventricular ejection fraction (0.56 +/- 0.10 to 0.56 +/- 0.11, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease

[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

Current and ongoing randomized trials in heart failure and left ventricular dysfunction.

Several large randomized trials have been completed recently and provided valuable information on the effects of various interventions in heart failure and left ventricular dysfunction. A review of ongoing randomized trials showed that there were 19 major trials addressing the effect of treatments on exercise tolerance, morbidity or mortality. Although it is hoped that these trials will answer many questions, they will also raise additional questions. Therefore, these remaining questions will need to be answered by future clinical trials.

Adrenergic beta-Antagonists

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