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PubMed1993

Temporary leukocyte depletion reduces ventricular dysfunction during prolonged postischemic reperfusion.

Leukocyte depletion improves early postischemic ventricular performance in neonatal models of global myocardial ischemia. However, the rate of leukocyte reaccumulation after cardiopulmonary bypass and its subsequent impact on myocardial function is not known. This laboratory study examined the effect of leukocyte depletion on myocardial performance during the initial 6-hour period after bypass in an in situ, in vivo porcine model of neonatal cardiac surgery. Fifteen 3- to 5-day-old piglets (eight control and seven leukocyte depleted animals) were instrumented by placement of left ventricular short-axis sonomicrometry crystals and an intraventricular micromanometer catheter. Mechanical leukocyte depletion was achieved with Pall RC100 filters (Pall Biomedical, Inc., Fajardo, Puerto Rico) in the cardiopulmonary bypass circuit. Neonatal hearts were subjected to 90 minutes of hypothermic ischemia after a single dose of cold crystalloid cardioplegia. Two control animals died after the operation and were excluded from data analysis. Leukocyte filtration reduced the granulocyte count during initial myocardial reperfusion to 0.8% of control values. However, circulating granulocyte counts increased in leukocyte depleted animals throughout the postoperative period, reaching 68% of control values by 6 hours. Despite this rapid return of circulating granulocytes, animals subjected to leukocyte depletion had significantly better preservation of left ventricular performance (measured by preload recruitable stroke work, p < or = 0.02), left ventricular systolic function (measured by end-systolic pressure-volume relationship, p < or = 0.05), and ventricular compliance (p < or = 0.04) during the experiment. These changes in ventricular function were associated with a significant increase in left ventricular water content (p < or = 0.02) and tissue myeloperoxidase activity (p < or = 0.005) in control animals compared with leukocyte depleted animals. This study demonstrates that leukocyte depletion during initial reperfusion results in sustained improvement in postischemic left ventricular function despite the rapid return of granulocytes to the circulation.

Animals↗
PubMed1997

Lack of left ventricular dysfunction associated with sustained exposure to hyperlipidemia following lung transplantation.

OBJECTIVES: Hyperlipidemia due to standard immunosuppressive agents occurs commonly following solid organ transplantation. A decision to treat hyperlipidemias would be based on the assumption that such disorders lead to accelerated atherogenesis and ultimately to cardiac dysfunction. We therefore sought to examine whether hyperlipidemias following lung transplantation were associated with a decline in left ventricular (LV) function. STUDY DESIGN: We retrospectively reviewed serial echocardiograms, radionucleotide angiograms (RNAs), and serum lipid levels following lung transplantation. Results of cardiac studies were defined as abnormal if a decline in LV grade occurred from the best result at any time postoperatively to the most recent study. PATIENTS: A total of 184 patients with transplants between November 1983 and June 1995 were reviewed. Eighty patients were excluded owing to incomplete data. One patient was excluded because of severe perioperative myocardial dysfunction. RESULTS: Approximately 80% of patients had elevated cholesterol levels and 60% had elevated low-density lipoprotein levels. Triglyceride levels were raised in 34% of patients while only 4% had an abnormal serum high-density lipoprotein level. More than 80% of patients had no evidence of LV abnormalities in either RNA or echocardiographic studies (group 1). One patient had a change in echocardiographic LV function but no change in grade of RNA (group 2). Twenty patients had a decline in grade based on RNA but no change in the echocardiogram (group 3). There were no patients with changes in both RNA and echocardiogram (group 4). All changes in LV function were from grade I to II. The mean period of follow-up exceeded 30 months for patients in groups 1 to 3. Follow-up data at 3, 4, and 5 years were available on 47, 23, and 12 patients, respectively. There were no differences between the proportions of subjects with normal and abnormal serum lipid levels in each group. CONCLUSIONS: In the initial 5 years after lung transplantation, dyslipidemias affect the majority of patients but are not associated with evidence of deteriorating LV function.

Anticholesteremic Agents↗
PubMed2002

Effects of long-term monotherapy with eplerenone, a novel aldosterone blocker, on progression of left ventricular dysfunction and remodeling in dogs with heart failure.

BACKGROUND: In heart failure (HF), aldosterone has been implicated in the formation of reactive interstitial fibrosis, a maladaptation that contributes to left ventricular (LV) remodeling. Eplerenone is a novel selective aldosterone blocker. The present study examined the effects of long-term monotherapy with eplerenone on the progression of LV dysfunction and remodeling in dogs with chronic HF. METHODS AND RESULTS: HF was produced in 14 dogs by intracoronary microembolizations that were discontinued when LV ejection fraction (EF) was between 30% and 40%. Two weeks after the last embolization, dogs were randomized to 3 months of oral therapy with eplerenone (10 mg/kg twice daily, n=7) or no therapy at all (control, n=7). Hemodynamic measurements were made just before randomization and were repeated at the end of 3 months of therapy. In control dogs, LV end-diastolic and end-systolic volume increased significantly (62+/-4 versus 68+/-4 mL, P<0.001, and 38+/-3 versus 47+/-3 mL, P<0.001, respectively), and EF decreased significantly (38+/-1% versus 31+/-2%, P<0.001). In contrast, end-diastolic volume, end-systolic volume, and EF remained unchanged during the 3 months of treatment in eplerenone-treated dogs. LV end-diastolic wall stress increased significantly in control dogs but decreased significantly in eplerenone-treated dogs. Compared with control, eplerenone was associated with a 28% reduction in cardiomyocyte cross-sectional area, a 37% reduction of volume fraction of reactive interstitial fibrosis, and a 34% reduction of volume fraction of replacement fibrosis. CONCLUSIONS: Our results indicate that long-term therapy with eplerenone prevents progressive LV dysfunction and attenuates LV remodeling in dogs with chronic HF.

Administration, Oral↗
PubMed2005

Early EPS/ICD strategy in survivors of acute myocardial infarction with severe left ventricular dysfunction on optimal beta-blocker treatment. The BEta-blocker STrategy plus ICD trial.

AIMS: This multicentre prospective randomised trial was undertaken to evaluate the usefulness of an electrophysiological study (EPS)-guided/implantable cardioverter defibrillator (ICD) strategy in patients at high risk of sudden death (SD) early after myocardial infarction (MI). Previous studies have shown the benefits of such a strategy only in high-risk patients late after MI. METHODS AND RESULTS: We enrolled 143 survivors of acute MI (<1 month) with left ventricular ejection fraction < or = 35% and either frequent (> or =10/h) premature ventricular complexes (PVCs), or depressed heart rate variability (SDNN < 70 ms) or abnormal signal-averaged ECG, who were able to tolerate optimised beta-blocker therapy (68 +/- 40 mg/day of metoprolol). Of these, 138 were randomised, in a 2:3 ratio, to two therapeutic strategies: conventional (CONV) strategy (n = 59) or EPS-guided/ICD strategy (n = 79). The latter resulted in ICD implantation in 24 inducible patients and in CONV therapy in the remaining 55. During a mean follow-up of 540 +/- 378 days, 26 patients (19%) died: nine (6.5%) SD, nine (6.5%) non-SD, and four (3%) non-cardiac death; in four patients (3%) the cause of death was unknown. The actuarial overall mortality for the CONV and EPS-guided/ICD arms was 18% vs 14% after 1 year and 29.5% vs 20% after 2 years, respectively (P = 0.3 and 0.2). CONCLUSIONS: Despite optimal therapy, mortality remains significant in high-risk patients following MI. Although there is a trend in favour of EPS-guided/ICD, our data are insufficient to demonstrate a survival benefit of this strategy early after MI.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Brain injury and ventricular dysfunction: insights into reversible heart failure.

The unique syndrome of brain death is associated with cardiac dysfunction; however, if such a heart is removed from this environment and transplanted, the cardiac dysfunction often resolves. This scenario offers insight into the mechanisms of reversible forms of cardiac injury and suggests that treatment of the extra-cardiac milieu by removing the initiating insult can often result in recovery. The mechanisms leading to reversible cardiac dysfunction are discussed in this review, with concentration on the implications of such injury in determining outcomes following transplantation.

Biomarkers↗
PubMed2006

Dosage dependent hormonal counter regulation to combination therapy in patients with left ventricular dysfunction.

UNLABELLED: The present study attempts to assess the efficacy combination therapy for heart failure. Genuine dose-response studies on combination therapy are not available and published studies involved adding one drug on top of 'usual treatment'. Sixteen different dosage combinations of trandolapril and bumetanide was tested in a double blind, double placebo-controlled, randomized, multiple cross-over study in a 16 times six balanced incomplete Latin square design. Patients reported optimal quality of life on the sub maximal dose bumetanide. Bumetanide decreased left ventricular function and increased heart rate and plasma noradrenaline in a dose dependent manner. Doses of bumetanide of more than 0.5 mg, given twice daily significantly decreased the quality of life and increased diuresis. Weight loss was maximal on 0.5 mg bumetanide twice daily. Trandolapril significantly reduced systolic blood pressure with the maximal effect at 0.5 mg daily. Both drugs significantly increased renin concentration with a significant potentiating interaction. It was not possible to detect beneficial effects of combination therapies. The optimal dosage of Bumetanide appeared to be 0.5 mg twice daily based on its effect on quality of life and weight loss. Estimated by the reduction in systolic blood pressure the optimal dosage of Trandolapril appeared to be 0.5 mg once daily. CONCLUSIONS: It appears that patients should be given less than the usually recommended dosages. Patients may be treated with a low dose loop diuretic, if signs of water retention are present or if symptomatic relief is desired.

Aged↗
PubMed2006

Comparison of regional versus global assessment of left ventricular function in patients with left ventricular dysfunction, heart failure, or both after myocardial infarction: the valsartan in acute myocardial infarction echocardiographic study.

BACKGROUND: Left ventricular (LV) ejection fraction (EF) and wall-motion index (WMI) have both been shown to be independent predictors of outcome after myocardial infarction (MI). OBJECTIVES: We sought to determine whether these two measurements of LV systolic function provide similar or complementary information about prognosis after MI. METHODS: Echocardiography was performed in 610 patients with LV dysfunction, heart failure, or both after MI enrolled in the Valsartan in Acute MI trial. LVEF was estimated by biplane Simpson's rule, and WMI was assessed using a 16-segment model in 502 patients with echocardiograms of sufficient quality for wall-motion assessment. RESULTS: Both LVEF and WMI were independent predictors of adverse outcome after MI. LVEF conferred no additional prognostic information in multivariable analysis including WMI (P = .39) or number of affected segments (P = .53), whereas WMI (P = .02) and total number of affected segments (P = .006) remained significant even when adjusting for LVEF. CONCLUSIONS: Assessment of regional dysfunction by WMI or the number of affected segments has slightly more prognostic value than LVEF in patients with LV dysfunction, heart failure, or both after MI. Regional assessment might be a more sensitive predictor of outcome than global assessment in patients with acute MI.

Aged↗
PubMed2005

Left ventricular dysfunction in patients with subclinical hypothyroidism and its reversibility after hormone therapy.

AIM: To ascertain the presence of LV dysfunction in patients of subclinical hypothyroidism and its reversibility after hormone therapy. METHODS AND METERIAL: Thirty two patients with subclinical hypothyroidism (SH) were included in the study, along with thirty two age and sex matched individuals serving as controls. The patients with SH had normal serum T3 and T4 with an elevated TSH value. All patients and the controls were subjected to detailed echocardiographic examination for assessment of LV systolic and diastolic function before and one year after hormone (thyroxine) therapy. RESULTS: The systolic function of LV was normal in patients with SH. There was significant diastolic dysfunction in the SH patients as compared with controls. There was prolongation of deceleration above time (169 +/- 6.1 msec. vs. 148.1 +/- 5.4 msec in controls, p < 0.05), isovolumic relaxation time (89.1 +/- 7.3 msec vs. 79.4 +/- 5.9 msec., p<0.05), increased A wave (0.63 +/- 0.6 m/sec. vs. 0.54 +/- 0.05 m/sec) and reduced E/A ratio (0.7 +/- 0.09 vs. 1.4 +/- 0.3, p < 0.05). Echocardiography at the end of one year of hormone therapy revealed considerable improvement in diastolic function of the LV. There was significant improvement in DT (from 169 +/- 6.1 msec. to 151 +/- 5.2 msec, p < 0.05), IVRT (from 89.1 +/- 7.3 msec. to 80.2 +/- 6.5 msec, p < 0.05) and increased E/A ratio (from 0.7 +/- 0.09 to 1.3 +/- 0.1, p < 0.05). CONCLUSION: Hypothyroidism, even in subclinical stage, can cause diastolic dysfunction of the LV. These abnormalities in diastolic function can be reversed by thyroxine therapy.

Adult↗
PubMed2006

Transient ischemic dilatation of the left ventricle with severe post stress left ventricular dysfunction in the setting of severe aortic stenosis and normal coronary arteries.

Transient ischemic dilatation (TID) of the left ventricle observed during single photon myocardial perfusion emission computed tomography (SPECT) is an important non-perfusion finding that may not only suggest underlying significant (usually multi-vessel) coronary artery disease (CAD) but also an independent prognostic factor of adverse outcomes regardless of abnormal or normal perfusion finding. We present a patient with no significant epicardial coronary disease who had significant TID and considerable decrease in the left ventricular ejection fraction with left ventricular dilatation after a rest-stress Tc-99 tetrofosmin SPECT study in the setting of severe aortic stenosis. With the advent of gated SPECT imaging the additive value of determining rest and post stress EF, as demonstrated in this case, aided in the recognition of TID and transient decrease in the left ventricular ejection fraction. These are not necessarily related to obstructive epicardial coronary disease, but are a result of severe aortic valve disease causing subendocardial ischemia in the setting of multilple other non-ischemic etiologies of TID such as left ventricular hypertrophy and diabetes mellitus.

Adenosine↗