Clinical predictors of outcome in survivors of out-of-hospital cardiac arrest treated with hypothermia

AbstractBackgroundOut-of-hospital cardiac arrest (OHCA) is a leading cause of death and severe neurological disability. The objective of this study was to identify clinical predictors of early neurological outcome in survivors of OHCA managed according to recent recommendations for OHCA care.MethodsData from survivors of OHCA, admitted to a tertiary cardiac intensive care unit and treated with hypothermia in a 22 months period (n=46, age 60±13 years, 74% males) were retrospectively evaluated. At 1-month follow-up, patients were classified according to the best achieved Glasgow–Pittsburgh cerebral performance categories (CPC 1–5) and factors affecting the outcome were analysed.ResultsAt 1-month follow-up, 23 patients (50%) had favourable outcome (CPC 1–2), while 23 patients (50%) had poor outcome (CPC 3–5), including 19 with in-hospital death (41% of total). Patients with good outcome were younger (55±13 years vs. 66±10 years; P=0.003), had more often myocardial infarction as the cause of arrest (63% vs. 30%; P=0.018) and ventricular fibrillation/tachycardia as an initial rhythm (78% vs. 39%; P=0.007). Both groups differed by lactate level on admission (4.0±4.6 vs. 7.3±4.1mmol/l, P=0.02), after 12h (2.5±1.1 vs. 4.3±3.2mmol/l, P=0.04) and after 24h (1.9±1.2 vs. 3.2±1.9mmol/l, P=0.04). Logistic regression revealed the following independent outcome predictors: age, acute myocardial infarction and admission lactate level.ConclusionFavourable outcome was observed in a half of OHCA survivors. Young age, acute myocardial infarction as underlying aetiology of cardiac arrest, and low lactate level on admission were the best predictors of favourable outcome

Pulse wave analysis during supine rest may identify subjects with recurrent vasovagal syncope A B S T R A C T

In the present study, we studied whether analysis of the FAP (finger arterial pressure) waveform during supine rest discriminates subjects with recurrent VVS (vasovagal syncope) from healthy controls. Signal-averaged FAP waveforms (Finapres) were obtained in 32 head-up tilt-test-positive subjects with recurrent VVS (35 + − 13 years) and in 32 sex-and age-matched healthy controls. The DT (time delay) between the systolic and diastolic peaks of the FAP waveform was measured and large artery SI (stiffness index) was calculated as a ratio of body height and DT. VVS patients had significantly shorter DT compared with controls (303 + − 31 compared with 329 + − 18 ms; P < 0.001) and higher SI (5.79 + − 0.70 compared with 5.20 + − 0.36 m/s; P < 0.001). The differences were independent of heart rate and blood pressure. SI > 5.45 m/s identified subjects with syncope with a sensitivity of 72 % and a specificity of 84 %. Age-corrected DT (cDT = DT + age − 350) identified subjects with syncope with a sensitivity of 75 % and a specificity of 84 %. Combined use of cDT < 0 ms and SI > 5.45 m/s increased sensitivity and specificity to 81 % and 96 % respectively. The discriminative power of FAP descriptors improved further when younger subjects were excluded. In subjects aged > 30 years (median age), the combination of cDT and SI identified subjects with syncope with a sensitivity of 93 % and a specificity of 100 %. These results suggest that FAP descriptors during supine rest might be useful in the diagnosis of VVS in middle-aged subjects

B-type natriuretic peptide: powerful predictor of endstage chronic heart failure in individuals with systolic dysfunction of the systemic right ventricle

Aim To assess whether B-type natriuretic peptide (BNP) can serve as a predictor of end-stage chronic heart failure (CHF) in patients with severe systolic dysfunction of the systemic right ventricle (SRV). Methods We performed a retrospective analysis in 28 patients with severe systolic dysfunction of the SRV (ejection fraction 23 ± 6%) who were evaluated as heart transplant (HTx) candidates between May 2007 and October 2014. The primary endpoints of the study (end-stage CHF) were progressive CHF, urgent HTx, and ventricular assist device (VAD) implantation. Plasma BNP levels were measured using a chemiluminescent immunoassay. Results During median follow-up of 29 months (interquartile range, 9-50), 3 patients died of progressive CHF, 5 patients required an urgent HTx, and 6 patients underwent VAD implantation. BNP was a strong predictor of end-stage CHF (hazard ratio per 100 ng/L: 1.079, 95% confidence interval, 1.042-1.117, P<0.001). The following variables with corresponding areas under the curve (AUC) were identified as the most significant predictors of end-stage CHF: BNP (AUC 1.00), New York Heart Association functional class class III or IV (AUC 0.98), decompensated CHF in the last year (AUC 0.96), and systolic dysfunction of the subpulmonal ventricle (AUC 0.96). Conclusion BNP is a powerful predictor of end-stage CHF in individuals with systolic dysfunction of the SRV

Proteomic and transcriptomic analysis of heart failure due to volume overload in a rat aorto-caval fistula model provides support for new potential therapeutic targets - monoamine oxidase A and transglutaminase 2

<p>Abstract</p> <p>Background</p> <p>Chronic hemodynamic overloading leads to heart failure (HF) due to incompletely understood mechanisms. To gain deeper insight into the molecular pathophysiology of volume overload-induced HF and to identify potential markers and targets for novel therapies, we performed proteomic and mRNA expression analysis comparing myocardium from Wistar rats with HF induced by a chronic aorto-caval fistula (ACF) and sham-operated rats harvested at the advanced, decompensated stage of HF.</p> <p>Methods</p> <p>We analyzed control and failing myocardium employing iTRAQ labeling, two-dimensional peptide separation combining peptide IEF and nano-HPLC with MALDI-MS/MS. For the transcriptomic analysis we employed Illumina RatRef-12v1 Expression BeadChip.</p> <p>Results</p> <p>In the proteomic analysis we identified 2030 myocardial proteins, of which 66 proteins were differentially expressed. The mRNA expression analysis identified 851 differentially expressed mRNAs.</p> <p>Conclusions</p> <p>The differentially expressed proteins confirm a switch in the substrate preference from fatty acids to other sources in the failing heart. Failing hearts showed downregulation of the major calcium transporters SERCA2 and ryanodine receptor 2 and altered expression of creatine kinases. Decreased expression of two NADPH producing proteins suggests a decreased redox reserve. Overexpression of annexins supports their possible potential as HF biomarkers. Most importantly, among the most up-regulated proteins in ACF hearts were monoamine oxidase A and transglutaminase 2 that are both potential attractive targets of low molecular weight inhibitors in future HF therapy.</p

Vliv hypolipidemik na endotelialni dysfunkci a nelipidove rizikove faktory aterosklerozy.

Lipid-lowering therapy represents one from the most efficient modalities in primary or secondary prevention of coronary heart disease (CAD). Besides their effects on blood lipid levels, lipid-lowering drugs have the ability to influence several recently identified factors, associated with the increased risk of CAD like C-reactive protein, fibrinogen, insulin, homocysteine and others. The changes of these non-lipid risk factors during lipid-lowering therapy can be relevant for progression of atherosclerosis and should be therefore studied. The sum of the effects of various risk factors might be useful for selection of optimal treatment strategies according to individual risk. To compare the main groups of lipid-lowering drugs - statins and fibrates, a randomised cross-over open-label trial has been proposed.Summary in EnglishAvailable from STL, Prague, CZ / NTK - National Technical LibrarySIGLECZCzech Republi

Sodium Nitrite Improves Exercise Hemodynamics and Ventricular Performance in Heart Failure With Preserved Ejection Fraction

AbstractBackgroundThere is no effective medical treatment for heart failure with preserved ejection fraction (HFpEF). Increases in pulmonary capillary wedge pressure (PCWP) develop in patients with HFpEF during exercise coupled with impaired nitric oxide (NO) signaling. Nitrite can be reduced to bioactive NO in vivo, particularly under conditions of tissue hypoxia, as with exercise.ObjectivesThis study sought to determine whether acute nitrite administration improves exercise hemodynamics and cardiac reserve in HFpEF.MethodsIn a double-blind, randomized, placebo-controlled, parallel-group trial, subjects with HFpEF (N = 28) underwent invasive cardiac catheterization with simultaneous expired gas analysis at rest and during exercise, before and 15 min after treatment with either sodium nitrite or matching placebo.ResultsBefore the study drug infusion, HFpEF subjects displayed an increase in PCWP with exercise from 16 ± 5 mm Hg to 30 ± 7 mm Hg (p < 0.0001). After study drug infusion, the primary endpoint of exercise PCWP was substantially improved by nitrite compared with placebo (adjusted mean: 19 ± 5 mm Hg vs. 28 ± 6 mm Hg; p = 0.0003). Nitrite-enhanced cardiac output reserve improved with exercise (+0.5 ± 0.7 l/min vs. −0.4 ± 0.7 l/min; p = 0.002) and normalized the increase in cardiac output relative to oxygen consumption. Nitrite improved pulmonary artery pressure-flow relationships in HFpEF and increased left ventricular stroke work with exercise versus placebo, indicating an improvement in ventricular performance with stress.ConclusionsAcute sodium nitrite infusion favorably attenuates hemodynamic derangements of cardiac failure that develop during exercise in individuals with HFpEF. Prospective trials testing long-term nitrite therapy in this population are warranted. (Acute Effects of Inorganic Nitrite on Cardiovascular Hemodynamics in Heart Failure With Preserved Ejection Fraction; NCT01932606

Exercise unmasks distinct pathophysiologic features in heart failure with preserved ejection fraction and pulmonary vascular disease

Aims Pulmonary hypertension (PH) and pulmonary vascular disease (PVD) are common and associated with adverse out- comes in heart failure with preserved ejection fraction (HFpEF). Little is known about the impact of PVD on the pathophysiology of exercise intolerance. Methods and results Heart failure with preserved ejection fraction patients (n= 161) with elevated pulmonary capillary wedge pressure (>= 15 mmHg) at rest were classified into three groups: non-PH-HFpEF (n = 21); PH but no PVD (isolated post-capillary PH, IpcPH; n = 95); and PH with PVD (combined post- and pre-capillary PH, CpcPH; n = 45). At rest, CpcPH-HFpEF patients had more right ventricular (RV) dysfunction and lower pulmonary arterial (PA) compliance compared to all other groups. While right atrial pressure (RAP) and left ventricular transmural pressure (LVTMP) were similar in HFpEF with and without PH or PVD at rest, CpcPH-HFpEF patients demonstrated greater increase in RAP, enhanced ventricular interdependence, and paradoxical reduction in LVTMP during exercise, differing from all other groups (P <0.05). Lower PA compliance was correlated with greater increase in RAP with exercise. During exercise, CpcPH-HFpEF patients displayed an inability to enhance cardiac output, reduction in forward stroke volume, and blunted augmentation in RV systolic performance, changes that were coupled with marked limitation in aerobic capacity. Conclusion Heart failure with preserved ejection fraction patients with PVD demonstrate unique haemodynamic limitations during exercise that constrain aerobic capacity, including impaired recruitment of LV preload due to excessive right heart congestion and blunted RV systolic reserve. Interventions targeted to this distinct pathophysiology require testing in patients with HFpEF and PVD

The impact of phosphodiesterase‐5 inhibition or angiotensin‐converting enzyme inhibition on right and left ventricular remodeling in heart failure due to chronic volume overload

Abstract While phosphodiesterase‐5 inhibition (PED5i) may prevent hypertrophy and failure in pressure‐overloaded heart in an experimental model, the impact of PDE5i on volume‐overload (VO)‐induced hypertrophy is unknown. It is also unclear whether the hypertrophied right ventricle (RV) and left ventricle (LV) differ in their responsiveness to long‐term PDE5i and if this therapy affects renal function. The goal of this study was to elucidate the effect of PDE5i treatment in VO due to aorto‐caval fistula (ACF) and to compare PDE5i treatment with standard heart failure (HF) therapy with angiotensin‐converting enzyme inhibitor (ACEi). ACF/sham procedure was performed on male HanSD rats aged 8 weeks. ACF animals were randomized for PDE5i sildenafil, ACEi trandolapril, or placebo treatments. After 20 weeks, RV and LV function (echocardiography, pressure‐volume analysis), myocardial gene expression, and renal function were studied. Separate rat cohorts served for survival analysis. ACF led to biventricular eccentric hypertrophy (LV: +68%, RV: +145%), increased stroke work (LV: 3.6‐fold, RV: 6.7‐fold), and reduced load‐independent systolic function (PRSW, LV: −54%, RV: −51%). Both ACF ventricles exhibited upregulation of the genes of myocardial stress and glucose metabolism. ACEi but not PDE5i attenuated pulmonary congestion, LV remodeling, albuminuria, and improved survival (median survival in ACF/ACEi was 41 weeks vs. 35 weeks in ACF/placebo, p = .02). PDE5i increased cyclic guanosine monophosphate levels in the lungs, but not in the RV, LV, or kidney. PDE5i did not improve survival rate and cardiac and renal function in ACF rats, in contrast to ACEi. VO‐induced HF is not responsive to PDE5i therapy