Effects of oral amino acid supplementation on myocardial function in patients with type 2 diabetes mellitus

Background

Diabetes mellitus is associated with an increased rate of cardiac amino acid catabolism that could interfere with cardiac function.

Methods

We assessed the effects of an oral amino acids mixture (AAM) on myocardial function in patients with type 2 diabetes mellitus (DM2). We studied 65 consecutive patients with DM2 who had normal resting left ventricular ejection fraction (LVEF) and did not have obstructive coronary artery disease (CAD). After baseline evaluations, patients were randomized to receive, in a single-blinded fashion, AAM (12 grams/day) or placebo for 12 weeks, after which, treatment was crossed over for another similar period. At baseline and at the end of each treatment, 2-dimensional ecocardiography at rest and during isometric exercise (handgrip) was performed, as were biochemical assays. Twenty adults, matched for age, sex, and body mass index served as control subjects.

Results

At baseline and during AAM or placebo treatment, resting left ventricular dimensions and LVEF in patients with DM2 did not differ from those of control subjects. In patients with DM2, at baseline and during placebo treatment, peak handgrip LVEF decreased significantly in comparison with the resting value (63% ± 9% vs 56% ± 9%, P <.001; and 62% ± 6% vs 55% ± 8%, P <.001). During AAM treatment, peak handgrip LVEF did not differ from resting value (66% ± 11% vs 64% ± 9%, P = not significant). Thus, exercise LVEF was higher during AAM treatment than both baseline and placebo treatment (66% ± 11% vs 56% ± 9% and vs 55% ± 8%, P <.001). In contrast to placebo treatment, after the AAM supply, a decreased glycated hemoglobin level was observed (7.0% ± 1.3% vs 7.6% ± 1.8%, P <.05).

Conclusions

Myocardial dysfunction is easily inducible with isometric exercise in patients with DM2 who have normal resting LV function and do not have CAD. An increased amino acid supply prevents this phenomenon and improves metabolic control.     

Improvement of P wave dispersion after cardiac resynchronization therapy for heart failure

Objective

The purpose of this study is to investigate the effect of cardiac resynchronization therapy (CRT) on P wave maximum duration (PWM) and P wave dispersion (PWD) in patients with advanced heart failure.

Methods

Forty-six patients (33 men; mean age, 60 ± 11 years) with CRT were enrolled in the present study. PWM and PWD were measured using 12-lead surface electrocardiography (ECG) at a paper speed of 50 mm/s and 20 mm/mV. Serial ECG, echocardiography, clinical assessment, and device interrogations were performed at baseline and 3 months after CRT.

Results

After 3 months of follow-up, PWM and PWD values were significantly decreased (129.6 ± 11.3 to 120.7 ± 10.7 milliseconds, P < .001; 42.6 ± 8.0 to 32.3 ± 10.1 milliseconds; P < .001, respectively). It showed a significant reduction in left atrial diameter (LAD) (46.5 ± 5.2 to 44.9 ± 5.6 mm, P = .021) and an improvement in left ventricular ejection fraction (LVEF) (29.0% ± 7.5% to 36.2% ± 8.0%, P < .001). The decrease of PWM and PWD was positively correlated with the reduction of LAD and negatively correlated with the improvement of LVEF. The reduction in atrial fibrillation burden was observed after 3 months of follow-up.

Conclusions

Cardiac resynchronization therapy decreases PWM and PWD along with an improvement of LVEF and a reduction of LAD. Further studies are needed to evaluate the clinical implications of decrease of PWD on prevention of atrial fibrillation.     

Rehabilitation: Periodic somatosensory stimulation increases arterial baroreflex sensitivity in chronic heart failure patients

Background

One of the beneficial effects of exercise training in chronic heart failure (CHF) is an improvement in baroreflex sensitivity (BRS), a prognostic index in CHF. In our hypothesis-generating study we propose that at least part of this effect is mediated by neural afferent information, and more specifically, by exercise-induced somatosensory nerve traffic.

Objective

To compare the effects of periodic electrical somatosensory stimulation on BRS in patients with CHF with the effects of exercise training and with usual care.

Methods

We compared in stable CHF patients the effect of transcutaneous electrical nerve stimulation (TENS, N = 23, LVEF 30 ± 9%) with the effects of bicycle exercise training (EXTR, N = 20, LVEF 32 ± 7%). To mimic exercise-associated somatosensory ergoreceptor stimulation, we applied periodic (2/s, marching pace) burst TENS to both feet. TENS and EXTR sessions were held during two successive days.

Results

BRS, measured prior to the first intervention session and one day after the second intervention session, increased by 28% from 3.07 ± 2.06 to 4.24 ± 2.61 ms/mm Hg in the TENS group, but did not change in the EXTR group (baseline: 3.37 ± 2.53 ms/mm Hg; effect: 3.26 ± 2.54 ms/mm Hg) (P(TENS vs EXTR) = 0.02). Heart rate and systolic blood pressure did not change in either group.

Conclusions

We demonstrated that periodic somatosensory input alone is sufficient and efficient in increasing BRS in CHF patients. This concept constitutes a basis for studies towards more effective exercise training regimens in the diseased/impaired, in whom training aimed at BRS improvement should possibly focus more on the somatosensory aspect.     

Limited predictive value of cardiopulmonary exercise indices in patients with moderate chronic heart failure treated with carvedilol

Background

Peak oxygen consumption (VO2) is traditionally used for risk stratification in chronic heart failure (CHF); however, its predictive value is unknown with carvedilol treatment. Therefore, we sought to investigate the prognostic role of gas-exchange parameters obtained from symptom-limited cardiopulmonary exercise testing (CPX) in patients with CHF that is treated with carvedilol.

Methods

A total of 508 consecutive patients (443 men, mean age [± SD] 59 ± 9 years) with a mean left ventricular ejection fraction (LVEF) of 25% ± 7% underwent CPX. The peak VO2 was 13.9 ± 3 mL/kg/min; the rate of increase of minute ventilation per unit of increase of carbon dioxide production (VE/VCO2 slope) was 32 ± 2. Outcomes (cardiovascular death or urgent heart transplantation) were determined when all patients who survived had been observed for a minimum of 6 months.

Results

Patients were divided into groups according to treatment (carvedilol and non-carvedilol); 236 patients were treated with carvedilol (46%), at a mean dose of 25 ±13 mg. The VE/CO2 slope, LVEF, peak VO2, and carvedilol treatment were revealed by means of multivariate analysis to be independent and additional predictors in the total population; VE/VCO2 slope, LVEF, and peak VO2 were revealed to be independent and additional predictors in the patients in the noncarvedilol group (all P <.001); and only peak VO2 was revealed to be an independent and additional predictor in the patients in the carvedilol group (P <.01). In the carvedilol group, mortality rates were 26%, 11%, 10%, and 4% (P <.05) in patients with peak VO2 ≤10 mL/kg/min, >10 to ≤14 mL/kg/min, >14 to18 mL/kg/min, and ≥18 mL/kg/min, respectively. No difference in mortality rates according to peak VO2 or additional outcome indices were identified in the 212 patients with peak VO2 >10 mL/kg/min.

Conclusions

Peak VO2 provides limited predictive information in patients with CHF that is treated with carvedilol, and no additional gas exchange parameter yields supplementary advice.     

Acute effects of β-endorphin on cardiovascular function in patients with mild to moderate chronic heart failure

Background

Cardiomyocytes produce opioid peptides and receptors. β-Endorphin is increased in the plasma of patients with congestive heart failure (CHF). We evaluated whether an intravenous infusion of β-endorphin exerted any effect on cardiovascular function and on the neurohormonal milieu in patients with mild to moderate CHF.

Methods

According to a double-blind, placebo-controlled design, 10 patients (5 men, age 46.9 ± 8.2 years [mean ± SD]) with CHF and New York Heart Association functional class II to III received, in random order, 1-hour intravenous infusion of β-endorphin (500 μg/h) and, on a separate occasion, received placebo and underwent echocardiographic and laboratory measurements at baseline and during infusions.

Results

β-Endorphin significantly increased left ventricular ejection fraction (LVEF) (P = .0001) and stroke volume (P = .0001), and reduced systemic vascular resistance (P = .031) in patients with CHF. These changes were paralleled by a significant increase in plasma levels of glucagon (P = .0001), GH (P = .0001), and IGF-1 (P = .0001), and a significant decrease in plasma levels of endothelin (P = .0001) and catecholamines (P = .01). No hemodynamic and neurohormonal changes were observed during the placebo study in any patient.

Conclusions

We conclude that a short-term, high dose infusion of β-endorphin improves LVEF, reduces systemic vascular resistance, blunts the neurohormonal activation, and stimulates the GH/IGF-1 axis in patients with mild to moderate CHF.     

Regression of significant tricuspid regurgitation after mitral balloon valvotomy for severe mitral stenosis

Background

Significant tricuspid regurgitation (TR) is occasionally associated with severe mitral stenosis and has an adverse impact on morbidity and mortality in patients undergoing mitral valve surgery. However, the effect of successful mitral balloon valvotomy (MBV) on significant TR is not fully elucidated. The aim of this study was to investigate TR after MBV in patients with severe mitral stenosis.

Methods

We analyzed the data of 53 patients with significant TR (grade ≥2, on a 1 to 3 scale) from the mitral balloon valvotomy database at our hospital. Patients were evaluated by Doppler echocardiography before valvotomy and at follow-up 1 to 13 years after MBV. Patients were divided into group A (27 patients), in whom TR regressed by ≥1 scale, and group B (26 patients), in whom TR did not regress.

Results

The Doppler-determined pulmonary artery systolic pressure was initially higher and decreased at follow-up more in group A (from 70.7 ± 23.8 to 36.5 ± 8.3 mm Hg; P < .0001) than in group B (from 48.7 ± 17.8 to 41.6 ± 13.1 mm Hg; P = NS). Compared with patients in group B, patients in group A were younger (25 ±10 vs 35 ± 11 years; P < .005), had higher prevalence of functional TR (85% vs 8%; P < .0001), and had lower incidence of atrial fibrillation (7% vs 38%; P < .005). Significant decrease in right ventricular end-diastolic dimension after MBV was noted in group A but not in group B. The mitral valve area at late follow-up was larger in group A than in group B (1.8 ± 0.3 vs 1.6 ± 0.3 cm²; P < .05).

Conclusions

Regression of significant TR after successful MBV in patients with severe mitral stenosis was observed in patients who had severe pulmonary hypertension. This improvement in TR occurred even in the presence of organic tricuspid valve disease.     

Cardiorenal anemia syndrome in chronic heart failure contributes to increased sympathetic nerve activity

Background

We sought to assess whether cardiorenal anemia syndrome (CRAS) in chronic heart failure (CHF) patients contributes to sympathetic overactivity through modulation of sympathetic reflexes.

Methods and results

We prospectively studied 15 patients with CRAS and CHF and 15 control CHF patients, matched for age, gender distribution, type of cardiomyopathy, left ventricular ejection fraction (LVEF) and BMI. We compared muscle sympathetic nerve activity (MSNA) and the effect of peripheral chemoreflex deactivation on MSNA in both groups. We also compared sympathetic baroreflex function, assessed by the slope of the relationship between MSNA and diastolic blood pressure in both groups and while peripheral chemoreflexes were (by breathing 100% oxygen for 15 min) or not deactivated. Baseline MSNA was significantly elevated in CHF patients with CRAS compared with control CHF patients (83.1 ± 4.6 versus 64.9 ± 2.9 bursts/100 heart beats; P < 0.05) and sympathetic baroreflex impaired (2.69 ± 0.44 vs 5.25 ± 0.60% bursts/mm Hg; P < 0.01). Chemoreflex deactivation with administration of 100% oxygen led to a significant decrease in muscle sympathetic nerve activity (77.8 ± 4.7 versus 82.1 ± 4.9 bursts/100 heart beats; P < 0.01) and to an increase in sympathetic baroreflex function (2.77 ± 0.45 vs 5.63 ± 0.73% bursts/mm Hg; P < 0.01) in patients with CRAS and CHF. In contrast, neither room air nor 100% oxygen changed MSNA, hemodynamic or sympathetic baroreflex function in control CHF patients.

Conclusions

CRAS in CHF patients is associated with elevated sympathetic activity mediated by both tonic activation of peripheral chemoreflex and baroreflex impairment.     

Expression of miR-126 and miR-508-5p in endothelial progenitor cells is associated with the prognosis of chronic heart failure patients

Background

MicroRNA (miRNA) expression profiles in endothelial progenitor cells (EPCs) contribute to EPC dysfunction in patients suffering from coronary artery disease. However, it remains unclear whether miRNA expression in EPCs is associated with the prognosis of chronic heart failure (CHF) secondary to ischemic cardiomyopathy (ICM) or non-ischemic cardiomyopathy (NICM).

Methods and results

One hundred six patients with CHF (55 ICM and 51 NICM) and 30 healthy controls were followed until the end of 24 months or when the end point was obtained (cardiovascular death). The miRNA expression profile was analyzed by TaqMan Human MicroRNA Array Set v2.0 in 30 randomly assigned samples (ICM = 10, NICM = 10, and healthy controls = 10). During the 24-month follow-up, 26 patients died from cardiovascular disease. Sixteen miRNAs (miR-126, miR-508-5p, miR-34a, miR-210, miR-490-3p, miR-513-5p, miR-517c, miR-518e, miR-589, miR-220c, miR-200a*, miR-186*, miR-7i*, miR-200b*, miR-595, and miR-662) were found to be differentially expressed between ICM and NICM patients. Survival analysis showed that miR-126 and miR-508-5p levels in EPCs were independent prognostic factors (P = 0.003; HR (hazard ratio): 0.19; 95% CI (confidence intervals): 0.06–0.58, P = 0.002; HR: 2.292; 95% CI: 1.37–3.84) for the outcome of ICM or NICM patients with CHF. Pathway enrichment analysis showed that the angiogenesis pathway was the most likely pathway regulated by miR-126 and miR-508-5p.

Conclusions

The miRNAs miR-126 and miR-508-5p are associated with the outcome of ICM and NICM patients with CHF. These two miRNAs could be useful in the diagnosis of CHF patients, and might provide novel targets for prevention and treatment of CHF.     

Role of oral amiodarone in patients with atrial fibrillation and congestive heart failure

Background

Amiodarone is recognized as the most effective therapy for maintaining sinus rhythm (SR) post cardioversion in patients with atrial fibrillation (AF). It is also recommended for controlling AF in patients with congestive heart failure (CHF). We retrospectively examined the efficacy and safety of oral amiodarone in patients with AF and CHF.

Methods

Forty-eight consecutive AF patients whose left ventricular ejection fraction (LVEF) was less than 50% and B-type natriuretic peptide (BNP) was higher than 100 pg/ml were investigated retrospectively, and divided into 3 groups: paroxysmal AF, 16 patients; persistent AF, 9 patients; and permanent AF, 23 patients.

Results

The permanent AF group had a longer history of AF, larger left ventricular end-diastolic diameter (LVDd) and left atrial diameter (LAD) than paroxysmal and persistent AF groups (p < 0.05). After median follow-up of 265 days, amiodarone suppressed paroxysms in 88% of paroxysmal AF patients, while SR was maintained in all persistent AF patients, and 35% of permanent AF patients. Of the 32 persistent and permanent AF patients, 12 (71%) out of 17 maintained SR after successful electrical cardioversion, and conversion to SR occurred spontaneously in 5 (33%) out of 15. The effective group had significantly smaller LVDd and LAD than the ineffective group. In the effective group, BNP decreased significantly from 723 ± 566 pg/ml to 248 ± 252 pg/ml, (p < 0.0005) and LVEF increased significantly from 33 ± 7% to 50 ± 13% (p < 0.0005) during follow up, while no changes were observed in the ineffective group. The patients with low LVEF (≤30%) benefited comparably from amiodarone to the patients with LVEF >30%. Complications occurred in 24 (50%) patients leading to discontinuation of amiodarone in 11 (23%).

Conclusions

Oral amiodarone helped restore SR in paroxysmal and persistent AF patients with CHF. The successful rhythm control by amiodarone resulted in the improvement of LV function and the decrease of BNP levels.     

Impact of short-term intermittent intravenous dobutamine therapy on endothelial function in patients with severe chronic heart failure

Background

Intermittent intravenous dobutamine therapy is used to treat patients with decompensated end-stage chronic heart failure (CHF), in whom the vascular endothelium is usually impaired. Although it has been suggested that modification or reversal of endothelial dysfunction may be of significant therapeutic benefit, the impact of short-term intermittent intravenous dobutamine therapy on flow-mediated dilation (FMD) in patients with severe decompensated end-stage chronic CHF has not been assessed.

Methods

We prospectively assessed the impact of intermittent intravenous low-dose dobutamine therapy on endothelium-dependent brachial artery FMD and endothelium-independent nitroglycerin (NTG)-mediated vasodilation using high resolution ultrasound scanning in 20 consecutive male patients with severe CHF and ischemic cardiomyopathy (New York Heart Association functional class IV), at baseline and after 4 months, and compared them to 20 age- and sex-matched control subjects. The cardiac index (CI), stroke index (SI), and systemic vascular resistance (SVR) were assessed non-invasively with a thoracic electrical bioimpedance device before and after intravenous dobutamine therapy.

Results

Intermittent intravenous dobutamine therapy resulted in significant improvement in post-intervention FMD compared with baseline (7.7% ± 2.4% vs 1.1% ± 2.6%; P = .001), a finding not evident in control subjects (1.3% ± 2.6% vs 1.2% ± 2.1%; P = .78). There was no significant effect of dobutamine treatment compared with control subjects on NTG-induced vasodilation (7.6% ± 5.5% vs 7.5% ± 8.8%, P = .979). Short-term dobutamine therapy also significantly improved SVR (1797 ± 926 dyne sec/cm⁵ vs 2172 ± 1133 dyne sec/cm⁵, P = .05), CI (2. 4± 0.6 L/min/m² vs 1.9 ± 0.6 L/min/m², P = .01), and SI (33.5 ± 11.7 mL/m² vs 27.2 ± 12.4 mL/m², P = .02).

Conclusions

Short-term intermittent intravenous low-dose dobutamine therapy significantly improved vascular endothelial function, perhaps demonstrating an additional mechanism for improved SVR, CI, and SI in patients with severe CHF.     

Association of Lp-PLA2 with digital reactive hyperemia,coronary flow reserve,carotid atherosclerosis and arterial stiffness in coronary artery disease

Background

Lipoprotein-associated Phospholipase A2 (Lp-PLA2), has a powerful inflammatory and atherogenic action in the vascular wall and is an independent marker of poor prognosis in coronary artery disease (CAD). We investigate the association of Lp-PLA2 with markers of vascular dysfunction and atherosclerosis with proven prognostic value in CAD.

Methods

In 111 patients with angiographically documented chronic CAD, we measured 1) carotid intima-media thickness (CIMT), 2) reactive hyperemia using fingertip peripheral arterial tonometry (RH-PAT), 3) coronary flow reserve (CFR), by Doppler echocardiography 4) pulse wave velocity (PWV) and 5) blood levels of Lp-PLA2.

Results

Patients with Lp-PLA2 concentration >234.5 ng/ml (50th percentile) had higher CIMT (1.44 ± 0.07 vs. 1.06 ± 0.06 mm), PWV (11.0 ± 2.36 vs. 9.7 ± 2.38 m/s) and lower RH-PAT(1.24 ± 0.25 vs. 1.51 ± 0.53) and CFR (2.39 ± 0.75 vs. 2.9 ± 0.86) compared to those with lower Lp-PLA (p < 0.05 for all comparisons). Lp-PLA2 was positively associated with CIMT (regression coefficient b: 0.30 per unit of Lp-PLA2, p = 0.02), PWV (b:0.201, p = 0.04) and inversely with RHI-PAT (b: −0.371, p < 0.001) and CFR (b:−0.32, p = 0.002). In multivariate analysis, Lp-PLA2 was an independent determinant of RHI-PAT, CFR, CIMT and PWV in a model including age, sex, smoking, diabetes, dyslipidemia and hypertension (p < 0.05 for all vascular markers). Lp-PLA2, RHI-PAT and CFR were independent predictors of cardiac events during a 3-year follow-up.

Conclusions

Elevated Lp-PLA2 concentration is related with endothelial dysfunction, carotid atherosclerosis, impaired coronary flow reserve and increased arterial stiffness and adverse outcome in CAD patients. These findings suggest that the prognostic role of Lp-PLA2 in chronic CAD may be explained by a generalized detrimental effect of this lipase on endothelial function and arterial wall properties.     

Screening for left ventricular systolic dysfunction among patients with risk factors for heart failure

Background

The prevalence of left ventricular systolic dysfunction (LVSD) among individuals at risk for heart failure (HF) and the feasibility of screening have not been clearly defined. This study determined the prevalence of LVSD with the use of a limited screening echocardiogram among patients with risk factors for HF but no prior HF.

Methods

General medicine patients ≥60 years of age with hypertension, diabetes, coronary artery disease, or previous myocardial infarction (MI) but no history of HF or reduced left ventricular ejection fraction (LVEF) were eligible. Medical history and symptoms of breathlessness were determined by interview and chart review; consenting patients underwent electrocardiography and echocardiography. The outcome was LVEF ≤45%, based on visual estimation from the echocardiogram.

Results

Of the 482 patients who completed the study, only 1 patient could not have the LVEF visually estimated. A total of 7.9% of patients had LVEF ≤45%. The prevalence was 15.4% among those with a prior MI and 6.7% among those without prior MI. In multivariate analysis, prior MI (adjusted odds ratio, 2.75; 95% CI, 1.14 to 6.64) and probable or definite left ventricular hypertrophy by electrocardiography (adjusted odds ratio, 3.57; 95% CI, 1.22 to 10.48) were the strongest predictors of LVEF ≤45%.

Conclusions

Screening for LVSD among high-risk patients is feasible and has substantial yield, even among patients without prior MI. In light of the low cost of screening and the available therapies to prevent progression of LVSD to overt HF, controlled clinical trials of screening high-risk subgroups appear to be justified.     

Comparison of cardiopulmonary exercise testing variables in COPD patients with and without coronary artery disease

Background

Coronary artery disease (CAD) is a common concomitant condition and an important cause of morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD). Since COPD and CAD can both independently cause reduced exercise capacity, it is reasonable to hypothesize that the combination of these diseases may compound the abnormalities observed during cardiopulmonary exercise testing (CPET). However, little is known about the impact of CAD on the CPET response in COPD patients. The aim of this study is to compare exercise capacity and gas exchange variables in COPD patients with and without CAD.

Methods

Fifty-four COPD subjects without CAD (COPDnoCAD) were matched to 54 COPD subjects diagnosed with CAD (COPD/CAD) according to age, gender, body mass index and severity of COPD. All subjects underwent resting pulmonary function and symptom-limited CPET.

Results

Comparing COPDnoCAD patients with COPD/CAD patients revealed that exercise capacity, as measured by % peak oxygen consumption (42 ± 16% vs 53 ± 19%, p = 0.002) and % peak wattage (23 ± 13% vs 32 ± 16%, p = 0.001), was significantly lower in COPD/CAD. Ventilatory response, as measured by VE/VCO₂ nadir (36 ± 9 vs 32 ± 5, p = 0.001), was significantly higher in COPD/CAD, with % peak VO₂ and VE/VCO₂ nadir correlating to % FEV₁ and inversely correlating with %DLCO.

Conclusion

COPD patients with CAD have significantly impaired CPET responses with lower exercise capacity and impaired gas exchange compared to COPD patients without CAD. These findings may affect the clinical interpretation of CPET data in COPD patients who have concomitant CAD.     

Myocardial alterations and clinical implications associated with recovery of cardiac function in dilated cardiomyopathy with obesity

Background

Obesity is associated with an increased risk of heart failure (HF) but the relationship between changes in cardiac function and the specific pathological features of dilated cardiomyopathy (DCM) with obesity, remains unknown.

Methods

Endomyocardial biopsies from the left ventricle (LV) were obtained from 50 patients with DCM, at the first-onset of decompensated HF. Thirty patients were obese (obese-group: body mass index > 30 kg/m²) and 20 were non-obese (lean-group). Clinical data were acquired at the admission, after one month and one year.

Results

The obese-group had higher systolic blood pressure (142.8 ± 33.9 vs 113.6 ± 18.7 mm Hg; p < 0.001) and serum troponin-T level (0.049 ± 0.07 vs 0.020 ± 0.03 ng/mL; p = 0.022) than the lean-group. LV ejection fraction (LVEF) was not significantly different between groups, but after one year the obese-group had an improved LVEF (57.0 ± 11.4 vs 44.3 ± 17.1; p = 0.003). Light microscopy revealed that the obese-group had larger cardiomyocytes (17.2 ± 1.7 vs 16.4 ± 1.4 μm; p = 0.033) and less myofilament lysis (37 vs 75%; p = 0.008) with a higher density of lipid droplets (1.93 ± 0.8 vs 0.94 ± 0.7 /μm²; p < 0.001). Multivariate regression analysis revealed that independent predictors of LVEF improvement after 12 months were diuretics use, nuclear diameter, and absence of myofilament lysis (p = 0.024, 0.012 and 0.028, respectively).

Conclusions

Cardiac function in most patients with DCM with obesity is reversible and myocardial structural changes are trivial even at the ultrastructural level.     

Impact of acute hyperglycemia on left ventricular function after reperfusion therapy in patients with a first anterior wall acute myocardial infarction

Objective

This study was undertaken to assess the relationship between acute hyperglycemia and left ventricular function after reperfusion therapy for acute myocardial infarction (AMI).

Methods

This study consisted of 529 patients with a first anterior wall AMI who underwent coronary angiography followed by coronary angioplasty or thrombolysis within 12 hours after the onset of chest pain. Plasma glucose was measured at the time of hospital admission. Acute hyperglycemia was defined as plasma glucose >10 mmol/L.

Results

Although acute hyperglycemia was associated with both lower acute left ventricular ejection fraction (LVEF) (46% ± 12% vs 48% ± 10%, P = .026) and lower predischarge LVEF (51% ± 15% vs 56% ± 15%, P = .001), the difference was more pronounced in the latter and the change in LVEF was significantly smaller in patients with acute hyperglycemia (4.8% ± 11.2% vs 8.0% ± 13.8%, P = .022). Multivariable analysis showed that there was a significant correlation between plasma glucose and impaired predischarge LVEF, even after adjustment of acute LVEF (r = −0.13, P = .005). Thirty-day mortality tended to be higher in patients with acute hyperglycemia than in patients without (7.1% vs 3.5%, P = .06). Multivariable analysis showed that plasma glucose (per 1 mmol/L increase) was an independent predictor of 30-day mortality after AMI (odds ratio 1.12, 95% CI 1.03-1.22, P = .009).

Conclusion

Acute hyperglycemia was independently associated with impaired left ventricular function and higher 30-day mortality after AMI. These results may provide a potential explanation for poor outcomes of patients with AMI and acute hyperglycemia.     

Heart failure after myocardial infarction: prevalence of preserved left ventricular systolic function in the community

Background Studies have reported that a large proportion of the cases of congestive heart failure (CHF) with mixed etiologies have preserved left ventricular systolic function. Whether this is the case in subjects with CHF after myocardial infarction (MI) is not known. This study was undertaken to examine the prevalence and characteristics associated with CHF in patients who had preserved ejection fraction (LVEF) after MI. Methods Clinical characteristics and LVEF were ascertained in a population-based cohort of patients with CHF after incident MI in Olmsted County, Minn. All MIs were validated by use of standardized epidemiological criteria, and all episodes of CHF were validated by use of Framingham criteria. Results Between 1979 and 1994, 1658 patients had an MI, and 644 of these patients (38%) had CHF during 7.4 ± 5.4 years of follow-up. Of these patients, 395 (61%) underwent LVEF assessment. Preserved LVEF (ie, ≥50%) was present in 30% of cases, and this proportion did not change with time. The proportion of women with CHF and preserved LVEF (37%) was greater than the proportion of men (23%, P = .002). The positive association between female sex and preserved LVEF remained significant after adjustment (odds ratio 1.97, 95% CI 1.26-3.07, P = .003). The highest tertile of peak creatinine phosphokinase level was negatively associated with preserved LVEF (odds ratio 0.51, 95% CI 0.29-0.89). Conclusion A notable proportion of cases of CHF after MI have preserved LVEF. This underscores the burden of CHF with preserved LVEF in a well-defined group of patients with documented coronary disease. CHF with preserved LVEF after MI is associated with female sex and smaller MI size. (Am Heart J 2003;145:742-8.)     

Electrocardiographic findings in cardiogenic shock, risk prediction, and the effects of emergency revascularization: results from the SHOCK trial

Objectives

To evaluate electrocardiographic (ECG) parameters as predictors of 1-year mortality in patients developing cardiogenic shock after acute myocardial infarction (AMI), and to document associations between these ECG parameters and the survival benefit of emergency revascularization versus initial medical stabilization.

Background

Emergency revascularization reduces the risk of mortality in patients developing cardiogenic shock after AMI. The prognostic value of ECG parameters in such patients is unclear, and it is uncertain whether emergency revascularization reduces the mortality risk denoted by ECG parameters.

Methods

In a prospective substudy of 198 SHOCK (SHould we emergently revascularize Occluded Coronaries for cardiogenic shocK) trial patients, ECGs recorded within 12 hours of shock were interpreted by personnel blinded to the patients' treatment assignment and outcome.

Results

The baseline heart rate was higher in non-survivors than in survivors (106 ± 20 versus 95 ± 24 beats/minute, P = .001). There was a significant association between the QRS duration and 1-year mortality in medically stabilized patients (115 ± 28 ms in non-survivors versus 99 ± 23 ms in survivors, P = .012), but not in emergently revascularized patients (110 ± 31 versus 116 ± 27 ms respectively, P = .343). The interaction between the QRS duration, mortality and treatment assignment was significant (P = .009). Among patients with inferior AMI, a greater sum of ST depression was associated with higher 1-year mortality in medically stabilized patients (P = .029), but not in emergently revascularized patients (P = .613, treatment interaction P = .025). On multivariate analysis, the independent mortality predictors were increasing age, elevated pulmonary capillary wedge pressure, heart rate, sum of ST depression in medically stabilized patients, and interaction (P = .016) between a prolonged QRS duration and treatment assignment. The adjusted hazard ratio for 1-year mortality per 20 ms increase in the QRS duration was 1.19 (95% CI 0.98-1.46) in medically stabilized patients and 0.81 (95% CI 0.63-1.03) in emergently revascularized patients.

Conclusion

ECG parameters identified patients with cardiogenic shock who were at high risk. Emergency revascularization eliminated the incremental mortality risk associated with cardiogenic shock in patients with a prolonged QRS duration, or inferior AMI accompanied by precordial ST depression. Prospective assessments of the magnitude of the treatment effect based on ECG parameters are required.     

Endothelial function and cardiovascular events in chronic kidney disease

Background

As patients with chronic kidney disease (CKD) are at high risk of developing coronary artery disease (CAD), it is important to stratify their cardiovascular risk. We investigated whether peripheral endothelial dysfunction is associated with the presence of CAD in patients with CKD and is a predictor of cardiovascular events.

Methods

We enrolled 383 CKD patients with at least one coronary risk factor. Peripheral endothelial function was assessed by reactive hyperemia peripheral arterial tonometry index (RHI). The presence of CAD was determined by coronary angiography. Cardiovascular events were assessed during follow-up.

Results

Ln-RHI was significantly lower in risk factor-matched CKD patients (n = 323) than risk factor-matched non-CKD patients (n = 323) (0.527 ± 0.192 vs. 0.580 ± 0.218, p = 0.001). In CKD patients (n = 383), Ln-RHI was significantly lower in CAD (0.499 ± 0.183, n = 262) than non-CAD (0.582 ± 0.206, n = 121) (p < 0.001) patients. Multivariate logistic regression analysis identified Ln-RHI as an independent factor associated with the presence of CAD (p = 0.001). During a mean follow-up period of 30 months, 90 cardiovascular events were recorded in CKD patients. Multivariate Cox hazard analysis identified low-Ln-RHI as an independent predictor of cardiovascular events (hazard ratio = 2.70, 95% confidence interval = 1.62–4.51, p < 0.001). The predictive value of combined Ln-RHI and Framingham risk score (FRS) was evaluated by net reclassification index (NRI) and C-statistics, which showed significant improvement (NRI = 22%, p < 0.001) (C-statistics: FRS = 0.49, FRS + Ln-RHI = 0.62, p = 0.005).

Conclusions

Endothelial function was significantly impaired in CKD patients and correlated with the presence of CAD. Severe endothelial dysfunction was an independent and incremental predictor of cardiovascular events in CKD.     

Comparison of ventricular tachyarrhythmia characteristics in patients with idiopathic dilated or ischemic cardiomyopathy and defibrillators implanted for primary prevention

Background:

Implantable cardioverter‐defibrillator (ICD) therapy for primary prevention is well established in ischemic cardiomyopathy (ICM). Data on the role of ICDs in patients with dilated cardiomyopathy (DCM) and no history of ventricular tachyarrhythmia (VT/VF) are more limited.

Hypothesis:

DCM patients with an impaired left ventricular ejection fraction (LVEF) still represent a low arrhythmic risk subgroup in clinical practice.

Methods:

ICD stored data of DCM patients with an LVEF ≤35% was compared to data of ICM patients meeting Multicenter Automatic Defibrillator Implantation Trial (MADIT) eligibility criteria. VT/VF occurrences and electrical storm (ES) events were analyzed.

Results:

There were 652 patients followed for 50.9 ± 33.9 months. There were 1978 VT and 241 VF episodes analyzed in 66 out of 203 patients (32.5%) with DCM and in 118 out of 449 patients (26.3%, P = 0.209) with ICM. Freedom of appropriate ICD treatment due to VT/VF or ES events did not differ in both patient populations (log‐rank, P>0.05). In patients presenting with VT/VF episodes, mean event rates were comparable in both patient populations (3.2 ± 14.1 for DCM and VT vs 3 ± 13.9 for ICM and VT [P = 0.855], 0.4 ± 1.3 for DCM and VF vs 0.4 ± 1.8 for ICM and VF [P = 0.763], and 0.2 ± 0.7 for DCM and ES vs 0.2 ± 1 for ICM and ES [P = 0.666]).

Conclusions:

DCM patients with prophylactic ICDs implanted due to heart failure and patients fulfilling MADIT criteria reveal comparable patterns of VT/VF/ES events during long‐term follow‐up. Incidence, mean number of events, and time to first event did not differ significantly. Findings support the current guidelines for prophylactic ICD therapy in DCM patients with heart failure. © 2011 Wiley Periodicals, Inc. The authors have no funding, financial relationships, or conflicts of interest to disclose.     

Comparative long term effects of nebivolol and carvedilol in hypertensive heart failure patients

Background

Beta-blockers improve left ventricular (LV) systolic function and prognosis in patients with chronic heart failure (CHF), but their different pleiotropic properties may influence their cardiovascular effects. This open-label study compared the effects of long-term treatment with nebivolol versus carvedilol on LV ejection fraction (LVEF), in hypertensive CHF patients. Secondary end points were to assess the effect of the 2 beta-blockers on exercise capacity and clinical outcome.

Methods and Results

A total of 160 hypertensive CHF patients, with LVEF <40% and in New York Heart Association (NYHA) functional class I, II, or III, were randomly assigned to receive nebivolol or carvedilol for 24 months. At baseline and at the end of treatment, all patients underwent clinical evaluation, echocardiography, and 6-minute walking test. The target doses were 10 mg/d for nebivolol and 50 mg/d for carvedilol. Compared with baseline values, LVEF increased by a similar extent in the carvedilol (C) and nebivolol (N) groups (C from 36.1% (SD 1.5%) to 40.9% (SD 1.9%), P < .001; N from 34.1% (SD 1.8%) to 38.5% (SF 2.2%), P < .001). Heart rate and NYHA functional class decreased significantly in both groups, and the 6-minute walking distance increased (C from 420 m (SD 104 m) to 490 m (SD 115 m), P < .001; N from 421 m (SD 118 m) to 487 m (SD 138 m), P < .001). During 24 months, 21 carvedilol recipients (26%) and 18 nebivolol recipients (22%) had cardiac events, including 3 and 4 deaths, respectively.

Conclusion

In the long term, nebivolol and carvedilol appear to be similarly effective in the treatment of hypertensive patients with CHF.