Nonischemic Heart Failure Etiology Research Articles

Women are More Likely to be Physically Frail Compared with Men in Heart Failure

Introduction Physical frailty is highly prevalent in heart failure (HF); however, little is known about the role of age, gender, ejection fraction phenotype (HF with reduced ejection fraction (HFrEF) vs. HF with preserved ejection fraction (HFpEF)), and HF etiology (ischemic vs. non-ischemic) in explaining physical frailty in HF. Hypothesis There is a higher prevalence of physical frailty in adults with HF who are ≥ 65 years, are women, have HFpEF, and have non-ischemic HF etiology. Methods This was an analysis of data collected from a study of adults with HF. Physical frailty was measured with the Frailty Phenotype Criteria: unintentional weight loss, weakness, slowness, physical exhaustion, and low physical activity. Physical frailty was determined by the number of criteria met; those who met 0-2 criteria were not physically frail, and those who met 3-5 were considered physically frail. Comparative statistics were used to compare prevalence of physical frailty between adults ≥ 65 years vs. Results The average age of the sample (n = 65) was 62.0±16.6 years, and 35.3% were female. A majority (84.6%) had HFrEF, and most (76.9%) had non-ischemic etiology. Physical frailty was identified in 43% of the sample. Adults ≥ 65 years were more likely to be physically frail than those Conclusions In HF, women have higher rates of physical frailty compared with men, irrespective of age, ejection fraction phenotype, and etiology, indicating that women with HF may be at increased risk for poor outcomes related to physical frailty.

Abstract P170: Etiologies and Characteristics of Heart Failure for Human Immunodeficiency Virus (HIV)-Infected Persons and Uninfected Controls

Background: Human immunodeficiency virus (HIV) is associated with elevated risks for heart failure (HF). No studies to our knowledge have evaluated physician-adjudicated etiologies of HF (e.g., ischemic vs. non-ischemic) for HIV-infected persons in the modern ART era. Hypothesis: We hypothesize that non-ischemic etiologies of HF will comprise a greater proportion of overall HF for HIV-infected than uninfected persons. Methods: We performed a nested study of a cohort of HIV-infected and uninfected persons frequency-matched on age, sex, race, zip code of residence, and clinic location receiving care at an urban medical center between 1/1/2000 and 1/1/2018. Two trained MDs independently reviewed clinical notes, imaging and laboratory studies to determine contributing etiologies of HF for 128 patients (75 HIV-infected, 53 uninfected) with physician-adjudicated HF. Laboratory and imaging data as well as clinical notes from clinical care were used to classify etiologies of HF. HF was considered ischemic in etiology based on any prior angiogram demonstrating ≥70% epicardial coronary stenosis, stress testing consistent with ischemia, and/or documented previous myocardial infarction. Non-ischemic heart failure etiologies were subtyped based on pre-specified criteria as valvular, inflammatory, drug induced, hypertensive, infiltrative, hypertrophic, dilated, tachycardia induced, pulmonary hypertension, acute pulmonary embolism, stress cardiomyopathy (Takotsubo), renal volume overload, cirrhotic volume overload, or unspecified. More than one etiology of HF was possible if criteria were met for multiple etiologies. Results: Age at HF onset, sex, and race of HIV-infected vs. uninfected persons with HF were similar. Diabetes was less common among HIV-infected (30.7%) vs. uninfected (54.7%; p = 0.01) persons with HF. There were no significant differences in the proportion of HIV-infected vs. uninfected persons with ischemic vs. non-ischemic etiology of HF. Within non-ischemic HF, drug/toxin-induced cardiomyopathy was more common among HIV-infected (17.3%) than uninfected (5.7%) persons (p= 0.049). The left ventricular ejection fraction (LVEF) at HF diagnosis was significantly lower for HIV-infected (37.6% ± 16.4%) than uninfected (44.9% ± 18.3%; p =0.02) persons. The difference was apparent among persons with non-ischemic etiologies (38.0% ± 16.7% vs. 47.9% ± 17.8% for HIV-infected vs. uninfected; p=0.01), but not for those with ischemic etiologies of HF (37.1% ± 15.9% vs. 38.3% ± 18.3% for HIV-infected vs. uninfected; p=0.83). Conclusions: HIV-infected persons with HF had lower LVEF at HF diagnosis and were more likely to have toxin/drug-induced HF etiology than uninfected persons with HF. Future studies are needed to understand etiologies of and prognosis HF among HIV-infected persons to inform prevention and treatment.

In-Hospital Initiation of Sacubitril/Valsartan in Stabilised Patients with Heart Failure and Reduced Ejection Fraction Naïve to Renin-Angiotensin System Blocker: An Analysis of the Transition Study

Background: In the PIONEER-HF study, in-hospital initiation of sacubitril/valsartan (S/V) versus enalapril in patients with heart failure (HF) and reduced ejection fraction (HFrEF), stabilised after acute decompensation, was associated with superior reduction of NT-proBNP, irrespective of prior use of angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB). Methods: In TRANSITION (NCT02661217), 1002 patients with HFrEF, hospitalised for acute decompensated HF after haemodynamic stabilisation, were randomised 1:1 and initiated open-label S/V either pre- or post-discharge (1–14 days). Primary endpoint was the proportion of patients achieving the target dose (97/103 mg, bid) at 10 weeks post-randomisation. Endpoints, adverse events (AEs) and serious AEs (SAEs) were compared by ACEi/ARB status in the combined pre- and post-discharge arms. Results: ACEi/ARB-naïve group [326 (32.9%)] had lower systolic blood pressure, serum creatinine, higher heart rate, and more often had non-ischaemic HF aetiology. Similar proportions of ACEi/ARB-naïve and non-naïve patients achieved the target dose of S/V (48.3% vs 47.9%, RRR 1.01 [0.88–1.16]) (Figure) and 88% patients from both groups were maintained on any S/V dose at Week 10. The rate of permanent discontinuation of S/V due to AEs was low and comparable. Overall incidence of AEs was 65.3% in ACEi/ARB-naïve and 68.3% in non-naïve patients (RRR 0.96 [0.87–1.05]) and incidence of SAEs was 16.3% and 19.4% respectively (RRR 0.83 [0.63–1.12]) (Table). Conclusion: In hospitalised patients with HFrEF naïve to ACEi/ARB, S/V can be safely initiated pre-discharge or shortly after discharge, and up-titration is well tolerated.

Reduction of Sympathetic Innervation Following Transition to Sacubitril/Valsartan in the Remodel (Reverse Remodeling Effects of Entresto) Study

Background Increased sympathetic nervous system activity is commonly observed in heart failure with reduced ejection fraction and is one cause of pathological structural remodeling of the left ventricle. Sacubitril/valsartan reduces mortality and heart failure hospitalizations, but its effect on sympathetic nervous system activity is unknown. Methods Patients enrolled in the prospective, longitudinal REMODEL study underwent 123-meta-iodobenzylguanidine scintigraphy prior to and three months following conversion from angiotensin converting enzyme inhibitor or angiotensin receptor blocker therapy to sacubitril/valsartan. The early heart-to-mediastinum (H/M) ratio, late H/M ratio and washout rate were calculated. Baseline and on-therapy values were compared using a paired t-test analysis. Results 40 patients were enrolled in this study. The mean age was 55 ± 12 years, 25 (63%) were male, and 30 (75%) had a non-ischemic heart failure etiology. Following transition to sacubitril/valsartan therapy, the late H/M ratio increased from 1.39 ± 0.19 to 1.52 ± 0.19 (p Conclusions Addition of sacubitril/valsartan to baseline heart failure therapy resulted in a decrease in cardiac sympathetic activity, as shown by a decrease in both the early and late H/M ratio and an increase in the washout rate on MIBG imaging. The decrease in sympathetic nervous system activity may underlie the improvement in survival seen with sacubitril/valsartan and can serve as a good measure of medication response.

Gender Differences in Utilization of Specialized Heart Failure Clinics.

Although heart failure (HF) prevalence is equally high among men and women, observed differences in the provision of care are still not fully understood. We sought to evaluate gender differences in patient profiles, diagnostic testing, medication prescription, and referrals in specialized multidisciplinary ambulatory HF clinics in Ontario. Medical chart abstraction was conducted first by randomly selecting 9 (out of 34) HF clinics in Ontario, and then by randomly selecting 100 patient records in each clinic. Data on patient demographics, comorbidities, diagnostic tests, medication use, and referrals were abstracted, covering a period from the first clinic visit up to 1 year. Descriptive statistics and regression analysis were used to assess gender differences. Of the 884 patients, only 314 were women (35.5%). At the first clinic visit, women were older, had better systolic function but worse functional status, and had a lower prevalence of hyperlipidemia, diabetes, and smoking than men. There were more women with non-ischemic HF etiology than men (63.9% vs. 43.3%, p < 0.001). Adjusted analysis did not reveal gender differences in the average number of echocardiographic assessments and in the prescription rates of evidence-based medications. Men were twice more likely to be referred to electrophysiology studies than women (18.6% vs. 7.8%, p < 0.001). The rates of dietary counseling and cardiac rehabilitation referrals were similarly low in both groups. More men than women are treated in specialized ambulatory HF clinics. Although women differ from men in selected clinical characteristics, no major differences were observed in patient management. The reasons for low enrollment rates of women into the HF ambulatory clinics need further investigation.

Effect of Omecamtiv Mecarbil in Patients with Ischemic and Non-Ischemic Heart Failure with Reduced Ejection Fraction: Results From COSMIC-HF

Introduction: LV systolic dysfunction is a final common pathway of multiple etiologies in the pathogenesis of chronic heart failure (HF). We evaluated the influence of HF etiology (ischemic vs. non-ischemic) on the response to the selective cardiac myosin activator, omecamtiv mecarbil (OM), in patients with HFrEF. Hypothesis: OM would have similar effects in patients with HFrEF regardless of HF etiology. Methods: COSMIC-HF (NCT 01786512) was a Phase 2 multicenter, randomized, double-blind, placebo-controlled trial in outpatients (n = 448) with a history of optimally-treated chronic HF, LVEF ≤40%, and NT-proBNP ≥200 pg/mL (≥1200 pg/mL with atrial fibrillation). In the expansion phase, patients were randomized 1:1:1 to receive placebo (n = 149), OM at 25 mg BID (n = 150), or 25 mg twice daily with pharmacokinetic-guided increases to 50 mg twice daily (n = 149; OM PK-group) for 20 weeks. Interaction terms were used to assess for a differential effect of OM in the OM PK-group by etiology on various study endpoints. Results: In COSMIC-HF, 287 (64%) had ischemic etiology of HF and 161 (36%) had non-ischemic HF etiology. Previous COSMIC-HF results demonstrated nominally statistically significant changes in all pre-specified secondary efficacy endpoints compared to placebo in the OM PK-group at 20 weeks. The current analyses demonstrate similar findings of efficacy in patients regardless of HF etiology (Table). There was no difference in the change from baseline in troponin after 20 weeks of therapy between the ischemic and non-ischemic OM PK-groups. HF etiology did not modify the effectiveness of OM; there were no significant interaction effects of treatment group with HF etiology for any of these variables (Table). Overall and cardiac adverse events were similar between the placebo and PK-titration groups for patients with ischemic (Subject incidence; Overall: Placebo, 58.4% vs. OM, 62.0%; Cardiac: Placebo, 20.2% vs. OM 20.0%) or non-ischemic (Overall: Placebo, 65.0% vs. OM, 71.7%; Cardiac: Placebo, 30.0% vs. OM 23.9%) etiologies. Conclusion: These data from COSMIC-HF suggest that OM produced similar findings with regard to pharmacodynamic response, cardiac function, heart rate, biomarkers, and adverse events in patients with ischemic and non-ischemic etiology of HF.

Hospitalization for Recently Diagnosed Versus Worsening Chronic Heart Failure: From the ASCEND-HF Trial

BackgroundIt is unclear how patients hospitalized for acute heart failure (HF) who are long-term chronic HF survivors differ from those with more recent HF diagnoses. ObjectivesThe goal of this study was to evaluate the influence of HF chronicity on acute HF patient profiles and outcomes. MethodsThe ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) trial randomized 7,141 hospitalized patients with acute HF with reduced or preserved ejection fraction (EF) to receive nesiritide or placebo in addition to standard care. The present analysis compared patients according to duration of HF diagnosis before index hospitalization by using pre-specified cutoffs (0 to 1 month [i.e., “recently diagnosed”], >1 to 12 months, >12 to 60 months, and >60 months). ResultsOverall, 5,741 (80.4%) patients had documentation of duration of HF diagnosis (recently diagnosed, n = 1,536; >1 to 12 months, n = 1,020; >12 to 60 months, n = 1,653; and >60 months, n = 1,532). Across HF duration groups, mean age ranged from 64 to 66 years, and mean ejection fraction ranged from 29% to 32%. Compared with patients with longer HF duration, recently diagnosed patients were more likely to be women with nonischemic HF etiology, higher baseline blood pressure, better baseline renal function, and fewer comorbidities. After adjustment, compared with recently diagnosed patients, patients with longer HF duration were associated with more persistent dyspnea at 24 h (>1 to 12 months, odds ratio [OR]: 1.20; 95% confidence interval [CI]: 0.97 to 1.48; >12 to 60 months, OR: 1.34; 95% CI: 1.11 to 1.62; and >60 months, OR: 1.31; 95% CI: 1.08 to 1.60) and increased 180-day mortality (>1 to 12 months, hazard ratio [HR]: 1.89; 95% CI: 1.35 to 2.65; >12 to 60 months, HR: 1.82; 95% CI: 1.33 to 2.48; and >60 months, HR: 2.02; 95% CI: 1.47 to 2.77). The influence of HF duration on mortality was potentially more pronounced among female patients (interaction p = 0.05), but did not differ according to age, race, prior ischemic heart disease, or ejection fraction (all interactions, p ≥ 0.23). ConclusionsIn this acute HF trial, patient profile differed according to duration of the HF diagnosis. A diagnosis of HF for ≤1 month before hospitalization was independently associated with greater early dyspnea relief and improved post-discharge survival compared to patients with chronic HF diagnoses. The distinction between de novo or recently diagnosed HF and worsening chronic HF should be considered in the design of future acute HF trials. (A Study Testing the Effectiveness of Nesiritide in Patients With Acute Decompensated Heart Failure; NCT00475852)

Is ICD effective in primary prevention od Sudden Cardiac Death in patients with heart failure of nonischemic etiology?

In DANISH trial, published in 2016, beneficial effect of implantation of cardioverter-defibrillator on mortality in population of patients with heart failure of nonischemic etiology was not demonstrated. It should be pointed out that up to 58% of patients in both arms received cardiac resynchronization therapy, so there were not two but four arms of the trial: optimal medical therapy, ICD, CRTP, CRTD with respective mortality: 27; 25; 20 and 19% (p=0,08). In the trial 50% relative risk reduction of arrhythmic death was observed and beneficial effect on mortality was demonstrated in population under 59 years treated with ICD. Twenty four patients in non-ICD group were implanted during the trial because of arrhythmia. If composite end point would be defined as total mortality and necessity to implant ICD because of arrhythmia the difference between groups would reach statistical significance (p=0,0181). In metaanalysis of AMIOVIRT, CAT COMPANION, DEFINITE SCD-HeFT and DANISH 24% reduction in total mortality was demonstrated. Even if COMPANION will be removed from the analysis still 20% beneficial effect of ICD will be present. In large analysis of 45 trials on risk factors of arrhythmic events in the population of dilated cardiomyopathy the following had impact on this risk: LVEDD, LVEF, EPS results, presence of nsVT, QRS prolongation, LBBB, results of SAECG, fragmented QRS, QRS-T angle and TWA. DANISH trial, despite its importance, does not justify discontinuing ICD therapy in patients with nonischemic heart failure.

Abstract 13158: Hospitalization for De Novo versus Worsening Chronic Heart Failure: Insights From the ASCEND-HF Trial

Introduction: Heart failure (HF) is a heterogeneous syndrome and individual patient survival varies widely. It is unclear how hospitalized acute HF (AHF) patients who are long-term chronic HF survivors differ from those with more recent HF diagnoses. Methods: The ASCEND-HF trial randomized 7,141 hospitalized AHF patients with reduced or preserved ejection fraction (EF) to nesiritide or placebo in addition to standard care. The present analysis compared patients by duration of HF diagnosis prior to index hospitalization using pre-specified cutpoints (0-1 month [i.e. “ de novo ”], &gt;1-12 months, &gt;12-60 months, &gt;60 months). Results: Overall, 5,741 (80.4%) patients had documentation of duration of HF diagnosis ( de novo , N=1536; &gt;1-12 months, N=1020; &gt;12-60 months, N=1653; &gt;60 months, N=1532). Mean age ranged from 64-66 years and mean EF from 29-32% across all HF duration groups. Compared to patients with longer HF duration, de novo patients were more likely to have non-ischemic HF etiology, fewer comorbidities, lower natriuretic peptide levels, and better baseline functional status (all P-value &lt;0.01). After adjustment, compared to de novo patients, longer HF duration was associated with more persistent dyspnea at 24 hours and increased 180-day mortality (Table). The influence of HF duration on mortality did not differ by age, gender, race, etiology of HF, or EF (all P-value for interaction ≥0.05). Conclusion: In this large AHF trial cohort, patient profile differed by duration of the HF diagnosis. De novo HF diagnosis was independently associated with greater early dyspnea relief and improved post-discharge survival compared to those with chronic HF diagnoses.

Heart failure and orthostatic hypotension.

Orthostatic hypotension (OH) is traditionally defined as a fall of ≥20mmHg in systolic and/or ≥10mmHg in diastolic blood pressure within 3min of active standing. OH is a common comorbidity among patients with heart failure (HF). A comprehensive review regarding the relationship between OH and HF has not been published in the English literature. Here we provide current information about concomitant HF and OH, including: pathophysiology, methods of evaluation, prevalence, risk factors, prognosis and management of OH in HF patients, as well as the incidence of HF among patients with OH. The prevalence of OH in HF ranges from 8% among community-living individuals to 83% in elderly hospitalized patients. Dizziness and palpitations are the most frequent OH symptoms. Main predisposing factors for OH are HF severity, non-ischemic HF etiology, prolonged bed rest, hypertension and polypharmacy. OH in HF is generally managed according to recommendations for treatment of OH in the non-HF population. However, since acceptable pharmacotherapy with fludrocortisone and midodrine is problematic in HF due to adverse effects, the management of OH is based mainly on non-pharmacologic interventions. Several prospective epidemiological studies reported that OH is independently associated with an increased risk of developing HF. Since OH is a common and frequently symptomatic condition in HF patients, its clinical implications should be emphasized. Longitudinal studies should be conducted to investigate the prognostic significance and optimal management of OH in the HF population.

Strain-time curve analysis by speckle tracking echocardiography in cardiac resynchronization therapy: Insight into the pathophysiology of responders vs. non-responders.

BackgroundPatients with non-ischemic heart failure etiology and left bundle branch block (LBBB) show better response to cardiac resynchronization therapy (CRT). While these patients have the most pronounced left ventricular (LV) dyssynchrony, LV dyssynchrony assessment often fails to predict outcome. We hypothesized that patients with favorable outcome from CRT can be identified by a characteristic strain distribution pattern.MethodsFrom 313 patients who underwent CRT between 2003 and 2006, we identified 10 patients who were CRT non-responders (no LV end-systolic volume [LVESV] reduction) with non-ischemic cardiomyopathy and LBBB and compared with randomly selected CRT responders (n = 10; LVESV reduction ≥15 %). Longitudinal strain (εlong) data were obtained by speckle tracking echocardiography before and after (9 ± 5 months) CRT implantation and standardized segmental εlong-time curves were obtained by averaging individual patients.ResultsIn responders, ejection fraction (EF) increased from 25 ± 9 to 40 ± 11 % (p = 0.002), while in non-responders, EF was unchanged (20 ± 8 to 21 ± 5 %, p = 0.57). Global εlong was significantly lower in non-responders at pre CRT (p = 0.02) and only improved in responders (p = 0.04) after CRT. Pre CRT septal εlong -time curves in both groups showed early septal contraction with mid-systolic decrease, while lateral εlong showed early stretch followed by vigorous mid to late contraction. Restoration of contraction synchrony was observed in both groups, though non-responder remained low amplitude of εlong.ConclusionsCRT non-responders with LBBB and non-ischemic etiology showed a similar improvement of εlong pattern with responders after CRT implantation, while amplitude of εlong remained unchanged. Lower εlong in the non-responders may account for their poor response to CRT.

Heterogenous haemodynamic effects of adaptive servoventilation therapy in sleeping patients with heart failure and Cheyne-Stokes respiration compared to healthy volunteers.

This study investigated the haemodynamic effects of adaptive servoventilation (ASV) in heart failure (HF) patients with Cheyne-Stokes respiration (CSR) versus healthy controls. Twenty-seven HF patients with CSR and 15 volunteers were ventilated for 1h using a new ASV device (PaceWave™). Haemodynamics were continuously and non-invasively recorded at baseline, during ASV and after ventilation. Prior to the actual study, a small validation study was performed to validate non-invasive measurement of Stroke volume index (SVI). Non-invasive measurement of SVI showed a marginal overall difference of -0.03±0.41 L/min/m(2) compared to the current gold standard (Thermodilution-based measurement). Stroke volume index (SVI) increased during ASV in HF patients (29.7±5 to 30.4±6 to 28.7±5mL/m(2), p<0.05) and decreased slightly in volunteers (50.7±12 to 48.6±11 to 47.9±12mL/m(2)). Simultaneously, 1h of ASV was associated with a trend towards an increase in parasympathetic nervous activity (PNA) in HF patients and a trend towards an increase in sympathetic nervous activity (SNA) in healthy volunteers. Blood pressure (BP) and total peripheral resistance response increased significantly in both groups, despite marked inter-individual variation. Effects were independent of vigilance. Predictors of increased SVI during ASV in HF patients included preserved right ventricular function, normal resting BP, non-ischaemic HF aetiology, mitral regurgitation and increased left ventricular filling pressures. This study confirms favourable haemodynamic effects of ASV in HF patients with CSR presenting with mitral regurgitation and/or increased left ventricular filling pressures, but also identified a number of new predictors. This might be mediated by a shift towards more parasympathetic nervous activity in those patients.

Biomarker-assist score for reverse remodeling prediction in heart failure: The ST2-R2 score

BackgroundLimited data exists regarding biomarker use to predict left ventricular (LV) reverse remodeling (R2). Our aim was to examine the value of soluble ST2 (ST2), N-terminal-pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), and galectin-3 relative to LV-R2 in systolic heart failure (HF), and to develop a clinical score for LV-R2 prediction. MethodsR2 was defined as a) LV ejection fraction (LVEF) increase ≥15%, or b) LVEF increase ≥10% plus reduction of LV end-systolic diameter index ≥20% or LV end-systolic volume ≥40%, for 12months. ResultsWe studied 304 patients (79.6% men, mean age 66.1±12.3years) with baseline LVEF <40%. R2 was observed in 104 patients (34.2%). In univariable logistic regression, factors associated with R2 were age (p=0.02), non-ischemic etiology of HF (p<0.001), NYHA functional class (p=0.02), baseline LVEF (p=0.005), absence of left bundle branch block (LBBB; p=0.002), ST2 (p=0.004), NT-proBNP (p=0.005), and hs-cTnT (p<0.001); HF duration achieved borderline significance (p=0.08). In multivariable analysis, ST2 remained the only biomarker associated with LV-R2. We developed the ST2-R2 score for use in clinical practice for predicting R2; variables included were ST2 <48ng/mL, non-ischemic etiology, absence of LBBB, HF duration <12months, baseline LVEF <24%, and β-blocker treatment. The score had an area under the curve of 0.79 in the derivation cohort and 0.73 in a separate validation cohort. ConclusionsThe ST2-R2 score, which includes the novel biomarker ST2 and five clinical variables, reasonably predicts LV-R2 in systolic HF patients. ST2 was the only studied biomarker that was independently associated with R2.

Abstract 12899: A New Prognostic Marker for Functional Deterioration in Heart Failure: Coronary Vascular Resistance

Introduction: Heart failure (HF) is a challenging clinical syndrome with complex pathophysiology. Previous studies demonstrated that coronary flow reserve assessed by PET technique was impaired in HF. Transthoracic echocardiography (TTE) can provide reliable data for myocardial blood flow (MBF) which can be measured from coronary sinus (CS). In relation with MBF, coronary vascular resistance (CVR) can be evaluated. In this study, we aimed to evaluate the association of MBF and CVR with clinical data in HF. Methods: The MBF was measured in 100 patients (80 patients with HF (LVEF&lt;30%) and 20 healthy control subjects. MBF was measured from anterograde CS flow TVI at PLAX RV inflow view and CS diameter at A2C view (2Πr2*TVI*heart rate) and indexed to left ventricular mass index. Patient group was categorized based on NYHA functional classes (NYHA FCs). Results: There was an incremental trend for MBF with advancing NYHA FCs (β=0.253, p=0.015). MBF was similar among HF patients due to NYHA FCs. However, MBF was higher in NYHA FC 4 group compared to healthy subjects (p=0.029). Also, CVR was lower in HF patients than the control group (11.15±6.54 vs.24.84±7.29, p&lt;0.001). In the subgroup analysis, CVR was not statistically different between non-ischemic and ischemic etiology of HF (6.91±1.38 vs. 6.31±0.89, p=0.249). Additionally, CVR was significantly lower in NYHA FC 4 compared to other study groups. CVR was positively correlated with peak VO2 (β=0.596, p&lt;0.001), and Seattle Heart Failure Model derived life expectancy (β=0.476, p&lt;0.001) and negatively correlated with serum BNP level (β=-0.450, p=0.001), troponin I (β=-0.366, p=0.001) and serum uric acid level (β=-0.503, p&lt;0.001). In multivariate analysis, CVR is an independent predictor of mortality (HR:0.763 95%CI:0.624-0.933 P=0.008). In ROC analysis, a cut of value 6.73 for CVR has a 74% sensitivity and 66.7 % specifity for prediction of mortality in HF(AUC 0.825 P&lt;0.001). Conclusion: Our results showed that CVR was reduced with advancing FC in HF patients, despite MBF was similar among different FCs. In addition, CVR was significantly correlated with various prognostic markers in HF patients. Therefore, evaluation of MBF hemodynamics, particularly CVR, with TTE may utilize prognostic assessment of HF patients.

Endothelial dysfunction expressed as endothelial microparticles in patients with end-stage heart failure.

Left ventricular assist devices (LVAD), currently used in treatment of terminal heart failure, are working on principle of rotary pump, which generates continuous blood flow. Non-pulsatile flow is supposed to expose endothelial cells to high stress and potential damage. Therefore, we investigated longitudinal changes in concentration of circulating endothelial microparticles (EMP) as a possible marker of endothelial damage before and after implantation of LVAD. Study population comprised 30 patients with end-stage heart failure indicated for implantation of the Heart Mate II LVAD. Concentrations of microparticles were measured as nanomoles per liter relative to phosphatidylserine before and 3 months after implantation. At 3 months after implantation we observed significant decrease in concentration of EMP [5.89 (95 % CI 4.31-8.03) vs. 3.69 (95 % CI 2.70-5.03), p=0.03] in the whole group; there was no difference observed between patients with ischemic etiology of heart failure (n=18) and with heart failure of non-ischemic etiology (n=12). In addition, heart failure etiology had no effect on the rate of EMP concentration decrease with time. These results indicate possibility that LVAD do not cause vascular damage 3 months after implantation. Whether these results suggest improvement of vascular wall function and of endothelium is to be proved in long-term studies.

Inotrope Use and Outcomes Among Patients Hospitalized for Heart Failure: Impact of Systolic Blood Pressure, Cardiac Index, and Etiology

BackgroundInotropes are widely used in hospitalized systolic heart failure (HF) patients, especially those with low systolic blood pressure (SBP) or cardiac index. In addition, inotropes are considered to be harmful in nonischemic HF. Methods and ResultsWe examined the association of in-hospital inotrope use with (1) major events (death, ventricular assist device, or heart transplant) and (2) study days alive and out of hospital during the first 6 months in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness, which excluded patients with immediate need for inotropic therapy. Predefined subgroups of interest were baseline SBP <100 versus ≥100 mm Hg, cardiac index <1.8 vs ≥1.8 L min−1 m−2, and ischemic versus nonischemic HF etiology. Inotropes were frequently used in both the <100 mm Hg (88/165 [53.3%]) and the ≥100 mm Hg (106/262 [40.5%]) SBP subgroups and were associated with higher risk for major events in both subgroups (adjusted hazard ratio [HR] 2.85, 95% confidence interval [CI] 1.59–5.12 [P < .001]; and HR 1.86, 95% CI 1.02–3.37 [P = .042]; respectively). Risk with inotropes was more pronounced among those with cardiac index ≥1.8 L min−1 m−2 (n = 114; HR 4.65, 95% CI 1.98–10.9; P < .001) vs <1.8 L min−1 m−2 (n = 82; HR 1.48, 95% CI 0.61–3.58; P = .39). Event rates were higher with inotropes in both ischemic (n = 215; HR 2.64, 95% CI 1.49–4.68; P = .001) and nonischemic (n = 216; HR 2.19, 95% CI 1.18–4.07; P = .012) patients. Across all subgroups, patients who received inotropes spent fewer study days alive and out of hospital. ConclusionsIn the absence of cardiogenic shock or end-organ hypoperfusion, inotrope use during hospitalization for HF was associated with unfavorable 6-month outcomes, regardless of admission SBP, cardiac index, or HF etiology.

Using Growth Mixture Modeling to Identify Classes of Sodium Adherence in Adults With Heart Failure

The prevention of fluid retention is important to reduce hospitalizations in patients with heart failure (HF). Following a low-sodium diet helps to reduce fluid retention. The primary objective of this study was to use growth mixture modeling to identify distinct classes of sodium adherence-characterized by shared growth trajectories of objectively measured dietary sodium. The secondary objective was to identify patient-level determinants of the nonadherent trajectory. This was a secondary analysis of data collected from a prospective longitudinal study of 279 community-dwelling adults with previously or currently symptomatic HF. Growth mixture modeling was used to identify distinct trajectories of change in 24-hour urinary sodium excretion measured at 3 time points over 6 months. Logistic modeling was used to predict membership in observed trajectories. The sample was predominantly male (64%), had a mean age of 62 years, was functionally compromised (59% New York Heart Association class III), and had nonischemic HF etiology. Two distinct trajectories of sodium intake were identified and labeled adherent (66%) and nonadherent (34%) to low-sodium diet recommendations. Three predictors of the nonadherent trajectory were identified, confirming our previous mixed-effect analysis. Compared with being normal weight (body mass index <25 kg/m2), being overweight and obese was associated with a 4-fold incremental increase in the likelihood of being in the nonadherent trajectory (odds ratio [OR], 4.63; 95% confidence interval [CI], 1.66-12.91; P < .002). Being younger than 65 years (OR, 4.66; 95% CI, 1.04-20.81; P = .044) or having diabetes (OR, 4.15; 95% CI, 1.29-13.40; P = .016) were both associated with more than 4 times the odds of being in the nonadherent urine sodium trajectory compared with being older than 65 years or not having diabetes, respectively. Two distinct trajectories of sodium intake were identified in patients with HF. The nonadherent trajectory was characterized by an elevated pattern of dietary sodium intake shown by others to be associated with adverse outcomes in HF. Predictors of the nonadherent trajectory included higher body mass index, younger age, and diabetes.

Predictors of positive response to cardiac resynchronization therapy

BackgroundApproximately 30% of patients treated with cardiac resynchronization therapy (CRT) do not achieve favourable response. The purpose of the present study was to identify echocardiographic and clinical predictors of a positive response to CRT.MethodsThe study included 82 consecutive heart failure (HF) patients in New York Heart Association (NYHA) functional class III or IV with left bundle branch block (LBBB), QRS duration ≥ 120 ms and left ventricular ejection fraction (LVEF) ≤ 35%. Statistical analysis was performed using IBM SPSS statistical software (SPSS v.21.0 for Mac OS X). A p value < 0.05 was considered statistically significant.ResultsEchocardiographic response was established in 81.6% and clinical response was achieved in 82.9% of patients. Significant univariate predictors of favourable echocardiographic response after 12 months were smaller left ventricular end-diastolic diameter (LVEDD) (odds ratio [OR] 0.89; 95% confidence interval [CI] 0.82 - 0.97, p = 0.01), and smaller left ventricular end-systolic diameter (LVESD) (OR 0.91; 95% CI 0.85 - 0.98, p = 0.01). Lower uric acid concentration was associated with better echocardiographic response (OR 0.99; 95% CI 0.99 - 1.0, p = 0.01). Non-ischemic HF etiology (OR 4.89; 95% CI 1.39 - 17.15, p = 0.01) independently predicted positive clinical response. Multiple stepwise regression analysis demonstrated that LVEDD lower than 75 mm (OR 5.60; 95% confidence interval [CI] 1.36 - 18.61, p = 0.01) was the strongest independent predictor of favourable echocardiographic response.ConclusionsSmaller left ventricular end-diastolic and end-systolic diameters and lower serum uric acid concentration were associated with better response to CRT. Left ventricular end-diastolic diameter and non-ischemic heart failure etiology were the strongest independent predictors of positive response to CRT.

Five-year survival of patients with chronic systolic heart failure of ischemic and non-ischemic etiology: analysis of prognostic factors.

IntroductionDespite advances in pharmacotherapy, electrotherapy and interventional treatment, chronic heart failure (HF) is still associated with poor long-term outcome.Aim of the studyTo determine the death rate and risk factors in patients with HF of ischemic and non-ischemic etiology in five-year follow-up.Material and methodsConsecutive patients with chronic systolic HF hospitalized in the period 2006-2008 were analyzed retrospectively. Study exclusion criteria were: infections (< 3 months before hospitalization), hemodynamically significant valve disease, advanced chronic kidney disease, liver cirrhosis and neoplastic diseases (< 5 years before hospitalization).ResultsThe analysis encompassed 266 patients divided into two groups: Group A, with HF of ischemic etiology (n = 157), and Group B, with HF of non-ischemic etiology (n = 109). Mortality was significantly higher in Group A than in Group B (49% vs. 28.4%, p = 0.001). The independent risk factors for death in Group A were: New York Heart Association (NYHA) class (HR = 1.81; p < 0.001); concentrations of high-sensitivity C-reactive protein (hs-CRP) (HR = 1.01; p < 0.05), fibrinogen (HR = 1.04; p < 0.001) and N-terminal prohormone brain natriuretic peptide (NT-proBNP) (HR = 1.02; p < 0.001); and right ventricular end-diastolic diameter (RVEDd) (HR = 1.07; p < 0.01). In Group B they were age (HR = 1.07; p < 0.05) and NT-proBNP concentration (HR = 1.03; p < 0.001).ConclusionsMortality was significantly lower in Group B than in Group A. The independent risk factors for death in Group B were age and NT-proBNP serum concentration, whilst in Group A they were NYHA class, serum concentrations of hs-CRP, NT-proBNP and fibrinogen, and RVEDd.

Identification of clinical risk factors of atrial fibrillation in congestive heart failure

Factors associated with the development of atrial fibrillation (AF) in general population have been described, but it is still unknown whether the same risk factors apply to heart failure (HF) patients. The aim of this study was to identify clinical factors related to various forms of AF in HF patients. The clinical and echocardiographic characteristics were assessed in 155 HF patients: 50 with sinus rhythm, 52 with non-permanent AF, and 53 with permanent AF. Multivariate logistic regression analysis showed that the increase in the NYHA class was an independent risk factor for both forms of AF. The occurrence of permanent AF in comparison to sinus rhythm group was independently associated with hs-C-reactive protein (CRP) elevation above 1 mg/dL (OR 1.87, 95% CI 1.05-3.35), left atrial dimension above 4 cm (OR 3.78, 95% CI 1.29-11.06) and tricuspid maximal pressure gradient elevation above 35 mm Hg (OR 5.01, 95% CI 1.38-18.27). The presence of coronary disease was independently associated with less frequent occurrence of permanent AF in comparison to sinus rhythm group (OR 0.21, 95% CI 0.06-0.67). More advanced congestive HF was associated with presence of both types of AF. Non-ischemic etiology of HF and elevated CRP are independently associated with permanent AF compared to sinus rhythm. Left ventricular diastolic dysfunction indicators (increased tricuspid maximal pressure gradient and left artial dimension) are independently associated with permanent AF.