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PubMed1995

[Transluminal coronary angioplasty in patients with left ventricular dysfunction; immediate and long term results].

Transluminal coronary angioplasty is increasingly performed in patients with left ventricular dysfunction. However, there is little data available concerning the outcome of these patients. The aim of this retrospective study was to assess the immediate and long-term results in 90 patients (76 men and 14 women) with left ventricular ejection fractions < or = 35% (average 29 +/- 5%) undergoing angioplasty between 1980 and December 1992. Eighty-seven patients (96%) had a history of infarction, 27 (30%) had already at least one episode of left ventricular failure and 34 (38%) had unstable angina at the time of angioplasty. The coronary disease was usually multi-vessel. A total of 118 lesions were dilated with a primary success rate of 77% (91/118): 86% (82/95) in non-occlusive stenoses and 39% (9/23) in complete obstructions. The total success rate per procedure was 72% (65/90) with a hospital mortality rate of 5.5% (5 cases). The mean follow-up period was 53 +/- 47 months. Twelve patients died during this period and two were lost to follow-up. The total and cardiovascular mortality at the end of the study was 19% (17/88). Eight of the 71 survivors underwent another revascularisation procedure (4 bypasses and 4 angioplasties); 21 (29%) have stable angina, 50 (71%) have no anginal pain and 61 (86%) have antianginal treatment. The probability of survival at one and four years was 81 +/- 4% and 79 +/- 5%, respectively. A multivariate analysis using the Cox model showed three independent prognostic factors for long-term mortality: triple coronary vessel disease, the best predictive factor, left ventricular ejection fraction and female gender.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMedDate not supplied

Prognostic value of tomographic rest-redistribution thallium 201 imaging in medically treated patients with coronary artery disease and left ventricular dysfunction.

BACKGROUND: Previous studies show that rest-redistribution thallium imaging is useful in the assessment of myocardial viability. The impact of such studies on patient outcome is not well defined. This study examined the prognostic value of tomographic rest-redistribution 201T1 imaging in 81 medically treated patients with coronary artery disease and left ventricular dysfunction. METHODS AND RESULTS: Rest-redistribution single-photon emission computed tomographic images were obtained and analyzed quantitatively. The segmental thallium uptake (20 segments per patient) was interpreted as normal, reversible defect, mild to moderate fixed defect, or severe fixed defect. The thallium images were abnormal in 80 patients, with no redistribution (no ischemia) in 43 patients and redistribution (ischemia) in 38 patients. The left ventricular ejection fraction was 27% +/- 8% in patients with no redistribution and 26% +/- 7% in patients with redistribution (difference not significant). In patients with no ischemia, there were 7 +/- 5 severe fixed defects and 5 +/- 4 mild to moderate fixed defects per patient. In patients with ischemia there were 7 +/- 4 reversible defects, 3 +/- 3 mild to moderate fixed defects, and 5 +/- 4 severe fixed defects per patient. The number of any abnormal segments was 11 +/- 5 in patients with no ischemia and 14 +/- 4 in patients with ischemia (p = 0.03). During a mean follow-up of 31 +/- 24 months, there were 11 cardiac deaths in patients with no ischemia (26%) and 22 in patients with ischemia (58%); the survival rate was worse in patients with than without ischemia (p < 0.05). Multivariate Cox survival analysis on important clinical, angiographic, and thallium variables showed that the presence of redistribution was an independent predictor of death (x2 = 5; p = 0.03). CONCLUSIONS: Patients with left ventricular dysfunction and redistribution on rest thallium imaging, a marker of hibernating myocardium, have a higher mortality rate with medical therapy than do patients with a comparable degree of left ventricular dysfunction but with fixed defects only. Thus observations similar to those made with positron emission tomography can be made in a much more straightforward, simple, and probably cost-effective manner with single-photon emission computed tomography.

Aged↗

PubMed2007

Persistent atrial fibrillation is associated with appropriate shocks and heart failure in patients with left ventricular dysfunction treated with an implantable cardioverter defibrillator.

AIM: The objective of this study was to investigate whether persistent atrial fibrillation (AF) and new-onset AF are associated with appropriate shocks, cardiovascular mortality, chronic heart failure (CHF), and inappropriate shocks in implantable cardioverter defibrillator (ICD) patients with left ventricular dysfunction. METHODS: We included 290 consecutive ICD patients with a documented left ventricular ejection fraction < or = 0.35 and compared outcomes between patients without AF (n = 207), those with persistent AF (n = 64), and those with new-onset AF (n = 19). RESULTS: The patients with persistent AF were older, more frequently had valve disease and cardiac surgery, and less frequently had coronary artery disease as compared with the patients without AF. Patients with persistent AF had a higher New York Heart Association class, however, left ventricular ejection fraction rates between these 2 groups were comparable (0.28 +/- 0.07 vs 0.29 +/- 0.08, P = not significant). No difference was found between patients with new-onset AF and those without AF. During follow-up (2.6 +/- 1.9 years), more patients with persistent AF received appropriate ICD shocks as compared with those without AF (24 [38%] vs 49 [24%], P = .04). Deterioration of CHF occurred more often in patients with persistent AF (19 [30%], P = .001) and those with new-onset AF (9 [47%], P < .001) as compared with patients without AF (31 [14%]). Multivariate analysis revealed that patients with persistent AF had an increased risk for appropriate ICD shocks (adjusted hazard ratio [HR] 1.9, 95% CI 1.2-3.2, P = .009). Persistent AF (adjusted HR 2.1, 95% CI 1.1-3.9, P = .03) and new-onset AF (adjusted HR 2.5, 95% CI 1.1-5.7, P = .02) were found to be independent risk indicators of CHF deterioration. CONCLUSIONS: In ICD patients with left ventricular dysfunction, persistent AF is associated with appropriate ICD shocks and deterioration of CHF. New-onset AF is related to deterioration of CHF.

Aged↗

PubMed1998

Antiplatelet agents and survival: a cohort analysis from the Studies of Left Ventricular Dysfunction (SOLVD) trial.

OBJECTIVES: This study sought to evaluate the relation between antiplatelet agent (APA) use and survival and morbidity from cardiac disease in patients with left ventricular (LV) systolic dysfunction. BACKGROUND: APAs play an important role in the prevention and treatment of coronary disease. Their effects in patients with LV systolic dysfunction are unknown. METHODS: We reviewed data on APA use in 6,797 patients enrolled in the Studies of Left Ventricular Dysfunction (SOLVD) trial and analyzed the relation between their use and all-cause mortality as well as the combined end point of death or hospital admission for heart failure (HF). We used Cox regression to adjust for differences in baseline characteristics and to test for the interaction between APA use and selected patient variables in relation to outcome. RESULTS: APA use (46.3% of patients) was associated with significantly reduced mortality from all causes (adjusted hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.73 to 0.92, p = 0.0005) and reduced risk of death or hospital admission for HF (adjusted HR 0.81, 95% CI 0.74 to 0.89, p < 0.0001) but was not influenced by trial assignment, gender, LV ejection fraction, New York Heart Association class or etiology. A strong interaction was observed among APA use, randomization group and all-cause mortality. The association between APA use and survival was not observed in the enalapril group, nor was an enalapril benefit on survival detectable in patients receiving APAs at baseline. However, randomization to enalapril therapy significantly reduced the combined end point of death or hospital admission for HF in APA users. CONCLUSIONS: In patients with LV systolic dysfunction, use of APAs is associated with improved survival and reduced morbidity. This association is retained after adjustment for baseline characteristics. APA use is associated with retained but reduced benefit from enalapril.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1998

Left ventricular dysfunction in human immunodeficiency virus (HIV)-infected patients.

We evaluated left ventricular function by echocardiography in a prospective study that included 98 consecutive human immunodeficiency virus (HIV)-infected patients and 40 HIV-seronegative normal controls. When compared with controls, HIV patients showed increased isovolumic relaxation time (101+/-18 ms versus 71+/-10 ms; p<0.0001) and left ventricular diastolic diameters (51+/-6 mm versus 47+/-3 mm; p<0.0005), and decreased fractional shortening (31+/-6% versus 37+/-2%; p<0.0001). Diastolic dysfunction was the most frequent finding (63% of the patients). We found depressed ejection fraction in 31 (32%) patients. Only 8 (8%) patients had symptomatic congestive heart failure. Left ventricular dysfunction was not attributable to intravenous drug abuse or to therapy. It was less severe in earlier stages of the infection (fractional shortening: acquired immunodeficiency syndrome=30%+/-6%, asymptomatic HIV-seropositives 34%+/-5%; p<0.005) and in HIV-2-infected patients. Patients with opportunistic infections (all aetiologies mixed) had more frequent congestive heart failure than those without infections (16% of the patients with versus 4% of the patients without infections; p<0.05). The fact that even asymptomatic HIV-seropositives had signs of left ventricular dysfunction (fractional shortening: asymptomatic HIV-seropositives=34%+/-5%; controls=37%+/-2%; p<0.05) favours the hypothesis of the HIV being one of the causes of these abnormalities.

AIDS-Related Opportunistic Infections↗

PubMed2004

Enalapril prevents perpetuation of atrial fibrillation by suppressing atrial fibrosis and over-expression of connexin43 in a canine model of atrial pacing-induced left ventricular dysfunction.

UNLABELLED: Effects of enalapril on a canine model of atrial pacing-induced atrial fibrillation (AF) with rapid ventricular responses were determined. METHODS: Four weeks of atrial rapid pacing was performed on twenty-four beagles pretreated with placebo (Group I, n = 14) or enalapril 1 mg/kg (Group II, n = 10). Atrial effective refractory period (ERP), P-wave width, duration of AF, and left ventricular ejection fraction (LVEF) were evaluated every week. AF cycle length was determined by spectral analyses of fibrillation waves. Quantitative analysis of histology was added. RESULTS: After 4 weeks of pacing, P-wave width was longer in Group I than in Group II, and the duration of induced AF was significantly longer in Group I (59.6 +/- 66.3 seconds) than in Group II (3.6 +/- 3.4 seconds, P < 0.05). AF cycle length was longer in Group I than in Group II despite similar shortening of atrial ERP. Mean ventricular rate during rapid atrial pacing was not different between the two groups. LVEF similarly decreased in both groups. Interstitial fibrosis and expression of connexin43 was greater in Group I than in Group II (interstitial fibrosis, 9.2 +/- 8.4 versus 1.9 +/- 2.1%, P < 0.05; connexin43, 5.3 +/- 2.2 versus 1.1 +/- 1.1%, P < 0.05). CONCLUSIONS: Enalapril suppressed atrial pacing-induced AF with tachycardia-mediated cardiomyopathy by suppressing interstitial fibrosis, connexin43 over-expression and conduction delay.

Animals↗

PubMed1998

Marked elevation of brain natriuretic peptide levels in pericardial fluid is closely associated with left ventricular dysfunction.

OBJECTIVES: The purpose of this study was to investigate whether atrial and brain natriuretic peptides (ANP and BNP, respectively) represent autocrine/paracrine factors and are accumulated in pericardial fluid. BACKGROUND: ANP and BNP, systemic hormones produced by the heart, have elevated circulating levels in patients with heart failure. Recent evidence suggests that the heart itself is one of the target organs for these peptides. METHODS: With an immunoreactive radiometric assay, we measured the concentrations of these peptides in plasma and pericardial fluid simultaneously in 28 patients during coronary artery bypass graft surgery. RESULTS: The pericardial levels of BNP were markedly elevated in patients with impaired left ventricular function. We investigated the correlation of ANP and BNP levels in plasma or pericardial fluid with left ventricular hemodynamic variables. None of the hemodynamic variables correlated with ANP levels in plasma or pericardial fluid. Both plasma and pericardial fluid levels of BNP were significantly related to left ventricular end-diastolic and systolic volume indexes (LVEDVI and LVESVI, respectively). In addition, BNP pericardial fluid levels had closer relations with LVEDVI (r = 0.679, p < 0.0001) and LVESVI (r = 0.686, p < 0.0001) than did BNP plasma levels (LVEDVI: r = 0.567, p = 0.0017; LVESVI: r = 0.607, p = 0.0010). BNP levels in pericardial fluid but not in plasma correlated with left ventricular end-diastolic pressure (r = 0.495, p = 0.0074). CONCLUSIONS: BNP levels in pericardial fluid served as more sensitive and accurate indicators of left ventricular dysfunction than did BNP levels in plasma. Thus, BNP may be secreted from the heart into the pericardial space in response to left ventricular dysfunction, and it may have a pathophysiologic role in heart failure as an autocrine/paracrine factor.

Aged↗

PubMed1999

Plasma vasoactive peptides after acute myocardial infarction in relation to left ventricular dysfunction.

We measured plasma concentrations of vasoactive peptides in 32 patients with acute myocardial infarction and evaluated their value as markers of left ventricular dysfunction. Plasma levels of atrial natriuretic peptide (ANP), the N-terminal fragment of proANP (NT-proANP), B-type natriuretic peptide (BNP) and endothelin-1 were measured serially by radioimmunoassays. The infarct size was estimated from the creatine kinase MB release curve. Coronary angiography and left ventricular cineangiography were performed in all patients during hospitalization and 6 months later in 15 patients. Myocardial infarction caused an increase in vasoactive peptides, the highest values for ANP (36.5+/-6.79 pmol/l), NT-proANP (1130+/-170 pmol/l) and endothelin-1 (9.72+/-0.68 pmol/l) being found on admission and those for BNP (56.0+/-7.13 pmol/l) on Day 2. Plasma levels of natriuretic peptides were dependent on infarct size, its location and degree of myocardial dysfunction and that of BNP also on infarct artery patency. Plasma endothelin-1 level was higher in patients with TIMI 3 than TIMI 0-2 flow. Plasma vasoactive peptides remained elevated during the 6-month follow-up period and they were dependent on the degree of myocardial dysfunction. BNP measured on any day of hospitalization showed the best correlation with ejection fraction measured during the acute phase of infarction or at 6 months. The results show that BNP is the best indicator of left ventricular dysfunction after myocardial infarction and its reliability is not dependent on the time point of measurement.

Analysis of Variance↗

PubMed2002

Evidence for left ventricular dysfunction in patients with obstructive sleep apnoea syndrome.

There is limited information on the development of left ventricular (LV) dysfunction in patients with obstructive sleep apnoea (OSA) in the absence of lung and cardiac comorbidity. This study aimed to investigate whether OSA patients without heart morbidity develop LV dysfunction, and to assess the effect of continuous positive airway pressure (CPAP) on LV function. Twenty-nine OSA patients and 12 control subjects were studied using technetium-99m ventriculography to estimate LV ejection fraction (LVEF), LV peak emptying rate (LVPER), time to peak emptying rate (TPER), peak filling rate (LVPFR) and time to peak filling rate (TPFR) before and after 6 months of treatment with CPAP. A significantly lower LVEF was found in OSA patients, compared to control subjects, (53+/-7 versus 61+/-6%) along with a reduced LVPER (2.82+/-0.58 versus 3.82+/-0.77 end-diastolic volumes x s(-1)). Furthermore, OSA patients had significantly lower LVPFR (2.67+/-0.71 versus 3.93+/-0.58 end-diastolic volumes x s(-1)) and delayed TPFR (0.19+/-0.04 versus 0.15+/-0.03 s) in comparison with the control group. Six-months of CPAP treatment was effective in significantly improving LVEF, LVPER, LVPFR and TPFR. In conclusion, obstructive sleep apnoea patients without any cardiovascular disease seem to develop left ventricular systolic and diastolic dysfunction, which may be reversed, either partially or completely, after 6 months of continuous positive airway pressure treatment.

Female↗

PubMed2001

[Serum copper levels in patients with chronic heart failure associated with systolic left ventricular dysfunction and its relation to the severity of cardiac failure].

UNLABELLED: The authors examined the serum copper concentrations in a group of 40 patients with chronic heart failure and significant systolic left ventricular dysfunction with an ejection fraction of less than 35%. In 21 patients the examination was made on admission to hospital on account of deterioration of cardiac insufficiency (group A), in 19 patients with stable chronic cardiac failure the examination was made at the out-patient department (group B). Assessment of serum copper concentrations was made by the method of absorption spectrophotometry under standard conditions. Assessment of the ejection fraction of the left ventricle and dimensions of the cardiac compartments was made by two-dimensional echocardiography. The heart rate was assessed from the electrocardiogram at rest. RESULTS: The authors found statistically significantly higher copper concentrations in patients of group A (19.78 +/- 1.67 mumol/l) as compared with group B (14.80 +/- 1.54 mumol/l, p < 0.001). The correlation between copper concentrations, the left ventricular ejection fraction, dimensions of the cardiac compartments and heart rate are not significant. CONCLUSION: Serum copper concentrations in patients with chronic heart failure and significant systolic left ventricular dysfunction are related to the severity of the disease and are higher in patients admitted on account of cardiac insufficiency than in patients with stable cardiac failure.

Aged↗

PubMedDate not supplied

Severe left ventricular dysfunction and arrhythmias as complications of gram-positive sepsis: rapid recovery in children.

Severe left ventricular dilatation and dysfunction in children may be associated with poor outcome in as many as 45% of cases. The prognosis for children with poor left ventricular function or arrhythmias associated with septic shock may be better, however, this has been inadequately studied. We report the favorable outcome of three children who presented with Gram-positive sepsis and significant cardiovascular compromise-two with severely dilated, poorly contractile left ventricle, and one with mild left ventricular dysfunction and incessant, malignant, and rapid atrial and ventricular arrhythmias. Our experience with these patients shows that complete and rapid resolution of these complications may be achieved with aggressive therapy.

Adolescent↗

PubMed1986

Left ventricular dysfunction versus paravalvular leak in patients with mitral disc prostheses.

UNLABELLED: Left ventricular dysfunction and prosthesis malfunction are the main causes of hemodynamic deterioration following prosthetic mitral valve replacement. The aim of this study is to reassess the usefulness of a combined echo-phonocardiographic technique to differentiate these different situations in order to select medical or surgical treatment in patients with a mitral disc prosthesis. Two patient groups were studied. The first group consists of five patients with paravalvular leak (PL), surgically or pathologically verified. Second group: nine patients with left ventricular failure (LVF) and normal functioning prosthesis. The diastolic diameter of the left ventricle (LV) was significantly increased in the LVF group compared with the PL group. A protodiastolic hump was present in four cases of PL. The variability of the interval between A2 and the mitral valve opening (delta A2-MVO) was less than 30 msec in the LVF group and greater than 30 msec in the PL group. The interval between A2 and maximal LV posterior wall (A2-PW) exceeded 60 msec in the PL group and was shorter than 60 msec in the LVF group. IN CONCLUSION: the echo-phonocardiographic technique, especially when by using two newly proposed parameters, seems to be very useful to discriminate between PL and LVF.

Adult↗

PubMed1999

Dobutamine-atropine stress echocardiography for risk stratification in patients with chronic left ventricular dysfunction.

OBJECTIVE: To assess the prognostic value of sustained improvement, scar and inducible ischemia with or without viability in patients with chronic left ventricular dysfunction (LVD). BACKGROUND: Dobutamine-atropine stress echocardiography (DASE) accurately detects scar, reversible dysfunction and the extent of coronary artery disease in LVD. METHODS: Three hundred fifty consecutive patients (age 62+/-13 years, mean+/-SD, 215 men/135 women) with moderate to severe LVD (LVEF < 40%, mean 30+/-8%) underwent DASE and were followed for > or =18 months. Dobutamine-atropine stress echocardiographic findings were classified according to sustained improvement in all vascular territories, scar, inducible ischemia (worsening wall motion at peak dose only or biphasic responses) and their extent. RESULTS: Sustained improvement occurred in 83 patients (24%), scar alone in 99 (28%) and inducible ischemia in 168 (48%, with biphasic responses in 104). Ischemia was induced in all vascular territories in 26 patients. Patients with sustained improvement or scar alone were treated medically, whereas 46% (78/168) with inducible ischemia were revascularized (coronary bypass surgery, n = 67 or angioplasty, n = 11). There were 76 hard events including cardiac death in 59, nonfatal myocardial infarction in 11, and resuscitated sudden death in 6. Hard events were rare in sustained improvement (5%, 4/83), uncommon in scar (13%, 13/99) and common (p < 0.01) in medically treated patients with inducible ischemia (59%, 53/90). Cardiac deaths were especially common (p < 0.01) in patients with biphasic responses (55%, 28/51). Inducible ischemia independently predicted hard events (chi2 = 75.35, p < 0.001) along with reduced LVEF at peak dose (chi2 = 8.38, p = 0.004). Hard cardiac events were uncommon (8%, 6/78, p < 0.001) in patients with inducible ischemia who underwent early revascularization. CONCLUSIONS: Inducible ischemia during DASE was the major determinant of outcome in LVD and independent of clinical data and left ventricular function. Improved wall thickening alone and scar alone predicted good outcome. Survival of patients with inducible ischemia was better after revascularization.

Adult↗

PubMed1999

Assessment of the stability of N-terminal pro-brain natriuretic peptide in vitro: implications for assessment of left ventricular dysfunction.

Plasma concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) are raised in patients with left ventricular dysfunction. Measurement of this peptide has a potential diagnostic role in the identification and assessment of patients with heart failure. The stability of this peptide over time periods and conditions pertaining to routine clinical practice has not been reported previously. Blood samples were obtained from 15 subjects. One aliquot was processed immediately, and the remaining portions of the blood samples were stored for 24 h or 48 h at room temperature or on ice prior to processing. Plasma concentrations of NT-proBNP were measured with a novel immunoluminometric assay developed within our laboratory. Mean plasma concentrations of NT-proBNP were not significantly different whether blood samples were centrifuged immediately and stored at -70 degrees C or kept at room temperature or on ice for 24 h or 48 h. The mean percentage differences from baseline (reference standard) were +5.2% (95% confidence interval +18.2 to -7.8%) and +0.8% (+15.2 to -13.7%) after storage for 24 h at room temperature or on ice respectively, and +8.9% (+24.2 to -6. 5%) and +3.2% (+15.1 to -0.9%) for storage for 48 h at room temperature or on ice respectively. Pearson correlation coefficients for baseline NT-proBNP concentrations compared with levels at 48 h at room temperature or on ice were r=0.89 and r=0.83 respectively (both P<0.0001). Thus NT-proBNP extracted from plasma samples treated with EDTA and aprotinin is stable under conditions relevant to clinical practice.

Adult↗

PubMed2005

[Impaired endothelium-dependent forearm vasodilation in idiopathic dilated cardiomyopathy is related to severe left ventricular dysfunction and elevated serum tumor necrosis factor levels].

INTRODUCTION AND OBJECTIVES: Endothelial dysfunction has been found in patients with idiopathic dilated cardiomyopathy (IDC), but its mechanism remains unknown. Our aim was to investigate whether forearm endothelium-dependent vasoreactivity correlates with cardiac disease severity or neurohormonal activation. PATIENTS AND METHOD: We studied 23 patients with IDC and 10 healthy sex- and age-matched controls using brachial artery ultrasound to assess flow-mediated dilation (FMD) and nitroglycerin-induced vasodilation (NIV). In the IDC group, we determined plasma neurohormone and cytokine levels at the same time. RESULTS: FMD was significantly less in the IDC group compared with the control group [--0.06 (2.8)% vs 4.4 (4.6)%, respectively; P<.01], whereas NIV was similar in both groups [15.0 (6.4)% vs 14.0 (7.4)%, respectively; P=NS]. FMD was significantly less in patients with poorer left ventricular (LV) function and more severe LV dilatation, and in those with a higher tumor necrosis factor-alpha (TNF-alpha) level. NIV was similar in all patient subgroups. There was a significant inverse correlation between the TNF-alpha plasma level and FMD (r=-0.75; P<.01). No correlation was found between the plasma levels of other neurohormones and FMD. CONCLUSIONS: FMD, but not NIV, was impaired in patients with IDC compared with control subjects. In patients, there were significant associations between FMD impairment and the severity of LV dilatation, the severity of LV systolic dysfunction, and the plasma TNF-alpha level. The strongest correlation was observed between TNF-alpha plasma level and FMD. These data suggest that TNF-alpha may be implicated in endothelial dysfunction in patients with IDC.

Arm↗

PubMed1998

Comparative efficacy of a DA2/alpha2 agonist and a beta-blocker in reducing adrenergic drive and cardiac fibrosis in an experimental model of left ventricular dysfunction after coronary artery occlusion.

Attenuation of neuroendocrine activation may be beneficial in congestive heart failure. Sympathetic nervous system overactivity can be reduced by receptors blockade or by reducing norepinephrine (NE) spillover. This study evaluated and compared the effects of a DA2-dopaminergic receptor/alpha2-adrenoceptor agonist (CHF-1024) and a beta1-adrenoreceptor antagonist in terms of hemodynamics, ventricular remodeling, beta-adrenergic drive, and cardiac fibrosis after myocardial infarction (MI) in rats. MI was induced by left coronary artery ligation in 213 rats, whereas 12 were left unoperated on. After 2 months, the operated-on animals were treated for 1 more month with CHF-1024 at either 0.33 mg/kg/day (low dose) or 1 mg/kg/day (high dose) or with metoprolol (10 mg/kg/day), delivered through implanted osmotic minipumps. Plasma concentration and urinary excretion of NE were measured before the rats were killed. Hemodynamic variables were measured and morphometric analysis was done on the diastole-arrested hearts to quantify left ventricular remodeling and interstitial collagen density. Metoprolol treatment tended to normalize LV end-diastolic pressure (LVEDP). CHF-1024 at either dose, and metoprolol, significantly reduced collagen deposition in LV of infarcted animals (from 8.8 +/- 0.5% LV area in vehicle-treated rats to 6.6 +/- 0.2% or 6.4 +/- 0.2% after the low or high dose of CHF-1024, respectively; p < 0.05). Similarly, CHF-1024 at either dose reduced the plasma concentration of NE (from 224 +/- 53 pg/ml to 60 +/- 7 pg/ml or 87 +/- 13 pg/ml; p < 0.05) and urinary excretion of NE in rats with MI, whereas beta-blockade did not affect these variables. In conclusion, CHF-1024 infused for 1 month to rats with LV dysfunction reduced heart rate, NE spillover, and collagen deposition, without unwanted effects, only appearing at the higher dose. Effective beta-blockade with metoprotol reduced LVEDP with no effects on heart function. Neither DA2/alpha2 stimulation nor beta-blockade altered LV remodeling after coronary artery ligation.

Adrenergic alpha-2 Receptor Agonists↗

PubMed1995

Results of revascularization in patients with severe left ventricular dysfunction.

BACKGROUND: In patients with coronary artery disease and poor ventricular function (ejection fraction, < 20%), bypass grafting remains a surgical challenge. This study evaluates experience with isolated revascularization in such patients. METHODS AND RESULTS: In 79 consecutive patients (69 men, 10 women; average age, 59 +/- 9 years), preoperative ejection fraction was 18 +/- 5%. Indications for surgery were congestive heart failure (CHF) in 5 of 79 patients (6%), CHF and angina in 19 (24%), angina in 41 (52%), ventricular arrhythmias (VAs) in 8 (10%), and critical anatomy in 6 (8%). Some patients had prior VAs (23 of 79; 29%) or mitral regurgitation (18; 23%) and required emergent surgery (25; 32%). At surgery, temperature mapping ensured adequate distribution of antegrade cold cardioplegia, with 3.6 +/- 0.7 grafts per patient, including left internal mammary artery graft in 60 of 79 (76%) and endarterectomy in 14 (18%). Hospital mortality was 3.8%. Perioperative support included intra-aortic balloon pump in 18 of 79 (23%) and drugs for VAs in 28 (35%). Morbidity included myocardial infarction in 2 of 79 (2.5%) and stroke in 2 (2.5%). During follow-up, there were 19 late deaths. Actuarial survival was 94%, 82%, and 68% at 1, 2, and 5 years, respectively, and was similar in patients with severe angina, CHF, mitral regurgitation, or VAs. Freedom from sudden death was 100%, 98%, and 91% at 1, 2, and 5 years, respectively. Among survivors, angina improved in 84% and heart failure improved in 26%. CONCLUSIONS: These data support bypass graft surgery in patients with severe LV dysfunction. With careful cardioplegic techniques, hospital mortality was low (3.8%). Long-term survival is encouraging, with good relief of symptoms in most patients. Perioperative VAs are frequent but respond to medical treatment, with only 23% of patients discharged on antiarrhythmic drugs. Five-year freedom from sudden death is 91%, with only 3 late sudden deaths in this series.

Actuarial Analysis↗

PubMed2004

A common variant of the AMPD1 gene predicts improved survival in patients with ischemic left ventricular dysfunction.

BACKGROUND: A recent retrospective study suggested that the adenosine monophosphate deaminase (AMPD)-1 gene variant C34T predicts outcome in heart failure patients. This variant might lead to ischemic preconditioning by increasing tissue adenosine. We tested whether the survival benefit of C34T occurs preferentially in the setting of ischemic left ventricular dysfunction. METHODS AND RESULTS: A consecutive cohort of patients (n=390) with left ventricular ejection fraction <40% was evaluated. In the ischemic patient subgroup (n=210) multivariate analysis identified AMPD1 T allele carriage (hazard ratio=0.43, confidence interval=0.20-0.94, P=.035) as an independent predictor of transplant-free cardiovascular survival. No benefit was found in the nonischemic group although the number of events was too small to reliably exclude a benefit by genotype. CONCLUSION: The AMPD1 C34T polymorphism influences transplant-free cardiovascular survival in the setting of ischemic left ventricular dysfunction.

AMP Deaminase↗