Heart Failure Of Nonischemic Origin Research Articles

Relationship between left ventricular mechanical dyssynchrony and accelerated 99mTc-MIBI clearance in patients with heart failure

Aim. To evaluate 99mTc-methoxy-isobutyl-isonitrile (99mTc-MIBI) washout rate and its relationship with contractility and left ventricular (LV) mechanical dyssynchrony in patients with heart failure (HF) of non-ischemic origin.Material and methods. The study included 20 patients with HF of non-ischemic origin with indications for cardiac resynchronization therapy (CRT). Ten patients without HF were included in the comparison group. All patients underwent 99mTc-MIBI myocardial perfusion scintigraphy (MPS). We assessed the 99mTc-MIBI washout rate, as well as LV perfusion, contractility, and mechanical dyssynchrony using phase analysis data (phase standard deviation, histogram bandwidth (HBW), asymmetry, and gradient). Six months after CRT, all patients with HF underwent MPS to assess the changes of studied parameters.Results. According to MPS, patients with HF had a higher 99mTc-MIBI washout rate from the LV myocardium compared with the comparison group (10,9 (8,49-13,8) vs 3,98 (0,9-9,8)%, p=0,0001), as well as severe LV mechanical dyssynchrony (standard deviation: 66 (55,11-73,24) vs 13,1 (10,1-19,6), p<0,0001; HBW: 207 (165-246) vs 40 (33-66), p<0,0001). The 99mTc-MIBI washout rate was positively correlated with LV end-diastolic (r=0,46, p<0,001) and LV end-systolic volumes (r=0,44, p<0,001) and negatively correlated with LV ejection fraction (r=0,41, p<0,001). A moderate correlation was found between the 99mTc-MIBI washout rate and following LV mechanical dyssynchrony and contractility parameters: HBW (r=0,412, p<0,001), asymmetry (r=-0,41, p<0,001), gradient (r=-0,44, p<0,001), wall motion (r=-0,45, p=0,001), wall thickening (r=-0,54, p<0,001). Six months after CRT, all patients showed a significant decrease in the 99mTc-MIBI washout rate from 12,4 (10,3-14,9) to 8,14 (3,37-8,88)%, p=0,0006.Conclusion. In patients with HF of non-ischemic origin, an increase in the 99mTc-MIBI washout rate from the LV myocardium is associated with the severity of impaired cardiac contractility and mechanical dyssynchrony.

AntimiR-132 Attenuates Myocardial Hypertrophy in an Animal Model of Percutaneous Aortic Constriction

BackgroundPathological cardiac hypertrophy is a result of afterload-increasing pathologies including untreated hypertension and aortic stenosis. It features progressive adverse cardiac remodeling, myocardial dysfunction, capillary rarefaction, and interstitial fibrosis often leading to heart failure. ObjectivesThis study aimed to establish a novel porcine model of pressure-overload–induced heart failure and to determine the effect of inhibition of microribonucleic acid 132 (miR-132) on heart failure development in this model. MethodsThis study developed a novel porcine model of percutaneous aortic constriction by implantation of a percutaneous reduction stent in the thoracic aorta, inducing progressive remodeling at day 56 (d56) after pressure-overload induction. In this study, an antisense oligonucleotide specifically inhibiting miR-132 (antimiR-132), was regionally applied via intracoronary injection at d0 (percutaneous transverse aortic constriction induction) and d28. ResultsAt d56, antimiR-132 treatment diminished cardiomyocyte cross-sectional area (188.9 ± 2.8 vs. 258.4 ± 9.0 μm2 in untreated hypertrophic hearts) and improved global cardiac function (ejection fraction 48.9 ± 1.0% vs. 36.1 ± 1.7% in control hearts). Moreover, at d56 antimiR-132-treated hearts displayed less increase of interstitial fibrosis compared with sham-operated hearts (Δsham 1.8 ± 0.5%) than control hearts (Δsham 10.8 ± 0.6%). Of note, cardiac platelet and endothelial cell adhesion molecule 1+ capillary density was higher in the antimiR-132–treated hearts (647 ± 20 cells/mm2) compared with in the control group (485 ± 23 cells/mm2). ConclusionsThe inhibition of miR-132 is a valid strategy in prevention of heart failure progression in hypertrophic heart disease and may be developed as a treatment for heart failure of nonischemic origin.

Heart failure patients unresponsive to implantable cardioverter-defibrillator therapy: a neglected problem.

Heart failure patients unresponsive to implantable cardioverter-defibrillator therapy: a neglected problem.

Dynamic Trajectories of Left Ventricular Ejection Fraction in Heart Failure

BackgroundLong-term trajectories of left ventricular ejection fraction (LVEF) in heart failure (HF) are incompletely characterized. ObjectivesThis study sought to examine LVEF trajectories in HF with reduced LVEF (<40%) and mid-range LVEF (40% to 49%) and the prognostic impact of LVEF dynamic changes over 15-year follow-up. MethodsIn this prospective, consecutive, observational registry of real-life HF outpatients, the authors performed 2-dimensional echocardiography at baseline and on a structured schedule after 1 year and then every 2 years up to 15 years. ResultsThe mean number of LVEF measurements in the 1,160 included patients was 3.6 ± 1.7. As a whole, Loess curves of long-term LVEF trajectories showed an inverted U shape with a marked rise in LVEF during the first year, maintained up to a decade, and a slow LVEF decline thereafter (p for trajectory <0.001). This pattern was more pronounced in HF of nonischemic origin and in women. Patients with new-onset HF (≤12 months) had a higher early increase in LVEF, whereas patients with ischemic HF showed a lower LVEF increase at 1 year; both groups had a relative plateau thereafter. Patients with HF with mid-range LVEF had less of an increase (3 ± 9%) than those with HF with reduced LVEF (9 ± 12%) during the first year (p < 0.001), but the groups overlapped after 15 years. Patients who died had lower final LVEF and worse LVEF dynamics in the immediately preceding period than survivors. ConclusionsLVEF trajectories vary in HF depending on a number of disease modifiers, but an inverted U-shaped pattern with lower LVEF at both ends of the distribution emerged. A declining LVEF in the preceding period was associated with higher mortality.

Effect of atorvastatin therapy on the clinical course of chronic heart failure of non-ischemic origin

Изучено влияние 24-недельного приема аторвастатина в дополнение к основной терапии у 52 больных хроническим миокардитом с сердечной недостаточностью I-II функциональных классов с сохранной систолической функцией левого желудочка сердца.Показано, что применение аторвастатина в суточной дозе 5-20 мг ведет к снижению активности иммунного воспаления и сопровождается положительной динамикой клинической симптоматики. Библиогр. 10 назв. Ил. 2. Табл. 2.

Dose-response relationship of total and leisure time physical activity to risk of heart failure: a prospective cohort study.

The nature of the association between levels of physical activity and risk of heart failure is little known. We investigated nonlinear associations of total and leisure time physical activity with risk of heart failure. In 1997, 39 805 persons without heart failure completed a questionnaire of lifestyle factors and medical history. We used Cox regression models to investigate total (adjusting for education and previous myocardial infarction) and direct (multivariable-adjusted) effects of self-reported total and leisure time physical activity on risk of heart failure of any cause and heart failure of nonischemic origin. Heart failure diagnoses were obtained until December 31, 2010. Higher leisure time physical activity was associated with lower risk of heart failure of any cause; hazard ratio of the total effect of leisure time physical activity was for fifth versus first quintile 0.54; 95% confidence interval was 0.44 to 0.66. The direct effect was similar. High total daily physical activity level was associated with lower risk of heart failure, although the effect was less pronounced than for leisure time physical activity (total effect hazard ratio, 0.81; 95% confidence interval, 0.69-0.95; fifth versus first quintile). A similar direct effect observed. Leisure time physical activity was inversely related to risk of developing heart failure in a dose-response fashion. This was reflected in a similar but less pronounced association of total physical activity with risk of heart failure. Only part of the effects appeared to be mediated by traditional risk factors.

Monoamine metabolism in the brain of rats with chronic heart failure of non-ischemic origin

Chronic heart failure (CHF) modulates the activity of monoaminergic systems in the central nervous system (CNS). An increased dioxyphenylacetic acid/dopamine ratio and 5-oxyindoleacetic acid/serotonin ratio in the majority of the brain structures studied during CHF indicate the high activity of the dopamine and serotonin systems and their functional stress during the development of hypoxia-compensative processes aimed at the maintenance of the normal cerebral blood flow. However, if a convulsive seizure develops during CHF, it may result in the failure of compensatory and adaptive mechanisms, thus, leading to decreased levels of dopamine, serotonin, and their metabolites in most brain regions studied. These animals are also characterized by increased seizure readiness, which is not usually found in the postictal period in rats without heart pathologies. Hence, CHF prolongs the postictal changes in the brain, limits its capacity to recovery, which, in turn, builds a basis for further seizure development.

Dose-dependent effects of omega-3-polyunsaturated fatty acids on systolic left ventricular function, endothelial function, and markers of inflammation in chronic heart failure of nonischemic origin: A double-blind, placebo-controlled, 3-arm study

Supplementation with 1 g/d omega-3-polyunsaturated fatty acids (n3-PUFAs) demonstrated a small survival advantage in patients with chronic heart failure (CHF) in the GISSI-HF trial. However, a dose-efficacy relationship was postulated for the beneficial effects of n3-PUFA before. Therefore, we evaluated dose-dependent effects of n3-PUFA in patients with severe CHF.In a double-blind, randomized, controlled pilot trial, 43 patients with severe, nonischemic heart failure received 1 g/d n3-PUFA (n = 14), 4 g/d n3-PUFA (n = 13), or placebo (n = 16) for 3 months. Changes in left ventricular ejection fraction (LVEF), flow-mediated vasodilation, plasma high-sensitive interleukin 6 and high-sensitive tumor necrosis factor α, and exercise peak oxygen consumption were assessed.Left ventricular ejection fraction increased in a dose-dependent manner (P = .01 for linear trend) in the 4 (baseline vs 3 months [mean ± SD]: 24% ± 7% vs 29% ± 8%, P = .005) and 1 g/d treatment groups (24% ± 8% vs 27% ± 8%, P = .02). Flow-mediated vasodilation increased significantly with high-dose 4 g/d n3-PUFA (8.4% ± 4.8% vs 11.6% ± 7.0%, P = .01) but only trendwise with low-dose 1 g/d (8.3% ± 5.3% vs 10.2% ± 4.3%, P = .07). Interleukin 6 significantly decreased with 4 g/d n3-PUFA (3.0 ± 2.9 pg/mL vs 0.7 ± 0.8 pg/mL, P = .03) but only trendwise with 1 g/d (4.5 ± 6.6 pg/mL to 1.6 ± 2.1 pg/mL, P = .1). High-sensitive tumor necrosis factor α decreased trendwise with 4 g/d n3-PUFA but remained unchanged with 1 g/d. In patients with maximal exercise effort, only 4 g/d increased the peak oxygen consumption. No changes in any investigated parameters were noted with placebo.Treatment with n3-PUFA for 3 months exerts a dose-dependent increase of LVEF in patients with CHF. In parallel, a significant improvement of endothelial function and decrease of interleukin 6 is found with high-dose n3-PUFA intervention.

Cell distribution after intracoronary bone marrow stem cell delivery in damaged and undamaged myocardium: implications for clinical trials

IntroductionEarly randomized clinical trials of autologous bone marrow cardiac stem cell therapy have reported contradictory results highlighting the need for a better evaluation of protocol designs. This study was designed to quantify and compare whole body and heart cell distribution after intracoronary or peripheral intravenous injection of autologous bone marrow mononuclear cells in a porcine acute myocardial infarction model with late reperfusion.MethodsMyocardial infarction was induced using balloon inflation in the left coronary artery in domestic pigs. At seven days post-myocardial infarction, 1 × 10(8) autologous bone marrow mononuclear cells were labeled with fluorescent marker and/or 99mTc radiotracer, and delivered using intracoronary or peripheral intravenous injection (leg vein).ResultsScintigraphic analyses and Υ-emission radioactivity counting of harvested organs showed a significant cell fraction retained within the heart after intracoronary injection (6 ± 1.7% of injected radioactivity at 24 hours), whereas following peripheral intravenous cell injection, no cardiac homing was observed at 24 hours and cells were mainly detected within the lungs. Importantly, no difference was observed in the percentage of retained cells within the myocardium in the presence or absence of myocardial infarction. Histological evaluation did not show arterial occlusion in both animal groups and confirmed the presence of bone marrow mononuclear cells within the injected myocardium area.ConclusionsIntravenous bone marrow mononuclear cell injection was ineffective to target myocardium. Myocardial cell distribution following intracoronary injection did not depend on myocardial infarction presence, a factor that could be useful for cardiac cell therapy in patients with chronic heart failure of non-ischemic origin or with ischemic myocardium without myocardial infarction.

Endothelial Function and Arterial Compliance are not Impaired in Subjects With Heart Failure of Non-Ischemic Origin

BackgroundPatients with heart failure and underlying ischemic heart disease (IHD) exhibit both endothelial dysfunction and increased arterial stiffness. We investigated whether this is also the case in heart failure of nonischemic etiology. Methods and ResultsEleven patients with heart failure and IHD, 12 patients with heart failure from angiographically verified idiopathic nonischemic dilated cardiomyopathy (DCM), and 16 healthy subjects of similar age and sex were compared. Endothelium-dependent and independent function were evaluated by ultrasonic measurement of flow-mediated dilatation (FMD) and glyceryl trinitrate (GTN)-induced dilatation of the brachial artery respectively. Vascular compliance was assessed by carotid-femoral pulse wave velocity (PWV) and augmentation index (AIx). Heart failure severity was similar in IHD and DCM patients. FMD was impaired in the subjects with IHD as compared with control subjects (4.8 ± 0.3 vs. 8.0 ± 3.6 %, P < .01), but not in those with DCM. GTN-induced vasodilatation was not different in patients and controls. PWV was also increased in IHD patients compared with controls (12.1 ± 3.6 vs. 8.0 ± 1.6 m/s, P < .01), but not in DCM patients. AIx was similar in patients and controls. ConclusionHeart failure of nonischemic etiology is not associated with abnormalities of endothelium-mediated dilatation or of arterial compliance. The findings of our study now need to be confirmed in larger studies.

Left ventricular dysfunction: which role for calcium antagonists?

Left ventricular dysfunction is the most common cause of congestive heart failure. Thus, treating or preventing left ventricular dysfunction represents an important therapeutic goal. The use of calcium antagonists in the treatment of left ventricular dysfunction or congestive heart failure has been proposed for many years now, mainly because of their potent vasodilatory effect. However, despite the theoretical basis, the results of studies exploring the possible use of calcium antagonists in this setting have not been at all encouraging. It has been suggested that this is because calcium antagonists have important additional effects: they depress cardiac contractility and activate the neurohormonal system. The various calcium antagonists have different characteristics and can be potentially useful in a variety of clinical conditions. Amlodipine (a calcium antagonist with a minimal cardiodepressant effect, long half-life and minimal activity on the neurohormonal system) has been shown to be clinically useful in congestive heart failure of nonischaemic origin. Calcium antagonists capable of limiting heart rate increment are useful in limiting ischaemia-induced left ventricular dysfunction. Verapamil exerts a potent protective effect on both microvascular damage and mechanical recovery during prolonged ischaemia followed by reperfusion. Lastly, nisoldipine is capable of ameliorating left ventricular function in patients with left ventricular diastolic dysfunction and has, therefore, potential in the treatment of congestive heart failure of left ventricular diastolic dysfunction origin. Thus, calcium antagonists may have a role in the treatment of left ventricular dysfunction provided that patient characteristics, the underlying mechanisms of the left ventricular dysfunction and the various calcium antagonist characteristics are well understood and carefully considered.