Nonischemic Heart Failure Etiology Research Articles

Implantable Cardioverter Defibrillator Tachycardia Therapies: Past, Present and Future Directions.

Implantable cardioverter defibrillators (ICDs) have a long history and have progressed significantly since the 1980s. They have become an essential part of the prevention of sudden cardiac death, with a proven survival benefit in selected patient groups. However, with more recent trials and with the introduction of contemporary heart failure therapy, there is a renewed interest and new questions regarding the role of a primary prevention ICD, especially in patients with heart failure of non-ischaemic aetiology. This review looks at the history and evolution of ICDs, appraises the traditional evidence for ICDs and looks at issues relating to patient selection, risk stratification, competing risk, future directions and a proposed contemporary ICD decision framework.

Assessing physical activity in heart failure with the CHAMPS physical activity questionnaire

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Office of Research on Women’s Health and the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health Background It is difficult to quantify physical activity among adults with heart failure (HF) in the context of many disease-driven limitations. The Community Healthy Activities Model Program for Seniors (CHAMPS) Physical Activity Questionnaire, designed to measure physical activity among older adults, may be helpful in quantifying physical activity in HF. Purpose To quantify physical activity levels among adults with HF using the CHAMPS Physical Activity Questionnaire and to compare physical activity expenditure and frequency between adults ≥ 65 years vs. < 65 years, women and men, and those physically frail vs. non-physically frail. Methods This was an analysis of data collected from a cohort study of adults with New York Heart Association Functional Class I-IV HF. Using the CHAMPS Questionnaire, we calculated caloric expenditure (kcal) and frequency per week in all activities and moderate intensity activities. Physical frailty was measured with the Frailty Phenotype Criteria. Comparative statistics were used to compare physical activity between groups. Results The average age of the sample (n = 117) was 63.6±15.6 years, 48.7% were female, and most (76.9%) had non-ischemic HF etiology. Median caloric expenditure from all physical activities was 1827 kcal/week [Interquartile Range 735-3943] and moderate intensity activities was 397 kcal/week [Interquartile Range 0-1886]. For caloric expenditure from all physical activities, there was no significant difference between adults ≥ 65 years vs. < 65 years (p = 0.894), but women and those physically frail had significantly lower caloric expenditure (both p < 0.001). For caloric expenditure from moderate intensity physical activities, there was no significant difference between adults ≥ 65 years vs. < 65 years (p = 0.346), but women had significantly lower caloric expenditure (p < 0.001) as well as those physically frail (p < 0.001). Median frequency of all physical activities was 13 times per week [Interquartile Range 8-21] and of all moderate intensity activities was 3 times per week [Interquartile Range 0-8]. Conclusions Many adults with HF, regardless of age, report low physical activity using the CHAMPS Physical Activity Questionnaire; however, women and those physically frail report considerably lower physical activity than men and those non-physically frail, respectively. Capturing physical activity levels across multiple activities is necessary for the design and implementation of physical activity interventions in HF, and the CHAMPS measure may be one tool to do this.

Prognostic value of mitral regurgitation in patients with heart failure undergoing cardiac resynchronization therapy

Abstract Funding Acknowledgements Type of funding sources: None. Background Cardiac resynchronization therapy (CRT) is a well-established treatment for specific groups of heart failure (HF) patients. CRT improves outcomes in ischemic and non-ischemic HF patients, depending on different predictors. Mitral regurgitation (MR) is a common echocardiographic finding with uncertain reported impact on prognosis. Purpose We sought to investigate clinical outcomes in HF patient undergoing CRT according to MR severity, for both ischemic and non-ischemic HF etiology. A transthoracic echocardiogram was performed before and 1-year after device-based therapy to all patients (in doubtful cases, a cardiac magnetic resonance imaging was also performed to evaluate the mitral regurgitant volume). Methods Single-center retrospective study of consecutive patients submitted to CRT implantation. Patients were stratified attending to MR at baseline and after CRT, as having significant (moderate and severe MR) or non-significant MR. The primary endpoint was a composite of major adverse cardiac events (MACE), including HF hospitalization or all-cause mortality. Sustained ventricular arrhythmic events were the secondary endpoint. Results 117 HF patients (mean age 71.1 ± 10.6 years, males 67.5%) were enrolled, 31.6% had an ischemic HF etiology and 23.9% were included in the baseline significant MR (SMR) group. Regarding baseline characteristics, 40.2% had atrial fibrillation (AF), 23.9% obstructive pulmonary disease (COPD) and 9% peripheral artery disease (PAD). Patients in SMR group had more dyslipidemia (p = 0.026) and lower left ventricular ejection fraction (median 25% vs 32%, p = 0.001). At 1-year of follow-up, 11.1% had significant MR, most (61.5%) with the same MR baseline degree and presented with higher NYHA class (p = 0.032). During the follow-up, 15.4% reached the primary endpoint while 8.5% the secondary endpoint. Ischemic etiology (p = 0.204, p = 0.191) and the severity of baseline MR (p = 0.106, p = 0.213) did not predict any of the endpoints. On the contrary, male gender (p = 0.033), alcohol consumption (p = 0.003), PAD (p = 0.004) and COPD (p = 0.005) were independent predictors for MACE endpoint at a multivariable analysis. For the secondary endpoint, PAD (p = 0.020) and AF (p = 0.001) were both significant predictors. Significant MR after CRT implantation was an independent strong predictor only for MACE outcome (HR 4.37, p = 0.014). Conclusions Baseline significant MR was not associated with clinical outcomes after CRT implantation. However, MR at follow-up was a strong determinant of higher mortality and HF hospitalizations in more symptomatic patients, regardless of HF etiology.

Effects of CRT on atrial and ventricular arrhythmias in patients with HF

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Cardiac resynchronization therapy (CRT) is an accepted treatment for patients with heart failure (HF). Cardiac arrhythmias present a significant and complex issue in this patient group. Evidence exploring the influence of CRT on cardiac arrhythmias rate variations is limited. Purpose Our research investigates the effectiveness of CRT in the treatment of existing and newly diagnosed atrial and ventricular arrhythmias, and impact of epicardial lead position on these arrhythmias rate variations, as well as on the CRT response. Methods This single-center, prospective, observational study included 75 consecutive patients admitted for CRT implantation over a 12-month period. All included patients had episodes of atrial and/or ventricular arrhythmias, diagnosed by 12-lead ECG or 24-hour Holter monitoring. Pre-procedural demographic characteristics were collected for all patients, including ECG records, NYHA functional class, echocardiographic assessment of left ventricular ejection function and questionnaire for quality-of-life. During device follow up atrial and ventricular arrhythmias appearance was monitored. Additional assessment of echocardiographic parameters, NYHA - functional class, quality of life and rate of major cardiovascular complications and rehospitalizations was performed. Results The mean age of the patients was 62.4 ± 10.3 years, with 74.6% male and 25.3% females. 72% had a non-ischemic HF etiology. Pre-procedural paroxysmal AF was present in 34.7%, persistent AF in 36%, PVCs in 32%, NSVT 16%, and VT in 18,7% patients. 55% of the included patients were responders to CRT. Our results showed decrease in rate of all ventricular arrhythmias, with significant reduction in the percentage of VT (p=0.003), regardless of CRT response. Significant reduction of PVCs and NSVT rate (p=0.012 & p=0.024) was found in the responder group of patients. Regarding AF, our results showed a decrease in the number of AF events in both patient groups, however this was most visible in the responder patients with paroxysmal AF (p=0.057). In CRT responders, left ventricular pacing lead was most commonly located in a lateral branch vein of the CS with middle and mid/lateral position. In terms of quality of life and general condition of the patients, we noticed a significant improvement in the NYHA - functional class (p <0.001), as well as in both parts of the quality-of-life assessment questionnaire (p=0.0135, p<0.001). Conclusion CRT is an effective treatment for atrial and ventricular arrhythmias in HF patients, especially in responders to this therapy. LV epicardial lead position proved to be very important influence in the process of LV reverse remodeling, which is in direct correlation of the CRT responders and its effectiveness in reducing the rate of cardiac arrhythmias.

The burden of heart failure in cardiac intensive care unit: a prospective 7years analysis.

The profiles of patients at cardiac intensive care units (CICU) have evolved towards a patient population with an increasing number of co-morbid medical conditions and acute heart failure (HF). The current study was designed to illustrate the burden of HF patients admitted to CICU, and evaluate patient characteristics, in-hospital course and outcomes of CICU patients with HF compared with patients with acute coronary syndrome (ACS). A prospective study including all consecutive patients admitted to the CICU at a tertiary medical centre between 2014 and 2020. The main outcome was a direct comparison between HF and ACS patients in processes of care, resource use, and outcomes during CICU hospitalization. A secondary analysis compared ischaemic versus non-ischaemic HF aetiology. Adjusted analysis evaluated parameters associated with prolonged hospitalization. The cohort included 7674 patients with a total annual CICU admissions of 1028-1145 patients. HF diagnosis patients represented 13-18% of the annual CICU admissions and were significantly older with higher incidence of multiple co-morbidities compared with patients with ACS. HF patients also required more intensive therapies and demonstrated higher incidence of acute complications as compared with ACS patients. Length of stay at the CICU was significantly longer among HF patients compared with patients with ACS (either STEMI or NSTEMI) (6.2±4.3 vs. 4.1±2.5 vs. 3.5±2.1, respectively, P<0.001). HF patients represented a disproportionately higher amount of total CICU patient days during the study period, as the total length of hospitalization of HF patients was 44-56% out of the total cumulative days in CICU of patients with ACS every year. In hospital mortality rates were also significantly higher among patients with HF compared with STEMI or NSTEMI (4.2% vs. 3.1% vs. 0.7%, respectively, P<0.001). Despite several differences in baseline characteristics between patients with ischaemic versus non-ischaemic HF, which can be attributed mainly to disease aetiology, hospitalization length and outcomes were similar among the groups regardless of HF aetiology. In multivariable analysis for the risk of prolonged hospitalization in the CICU adjusted to potential significant co-morbidities associated with poor outcomes, HF was found to be an independent and significant parameter associated with the risk of prolonged hospitalization with an OR of 3.5 (95% CI 2.9-4.1, P<0.001). Patients with HF in CICU have higher severity of illness with a prolonged and complicated hospital course, all of which can substantially increase the burden on clinical resources.

Impact of ischaemic aetiology on the efficacy of intravenous ferric carboxymaltose in patients with iron deficiency and acute heart failure: insights from the AFFIRM-AHF trial.

In AFFIRM-AHF, intravenous ferric carboxymaltose (FCM) reduced heart failure (HF) hospitalisations and improved quality of life versus placebo in iron-deficient patients stabilised after an acute HF episode. This analysis explored the effects of FCM versus placebo in patients with ischaemic and non-ischaemic HF aetiology. We included 1082 patients from AFFIRM-AHF: 590 with ischaemic HF (defined as investigator-reported ischaemic HF aetiology and/or prior acute myocardial infarction and/or prior coronary revascularisation) and 492 with non-ischaemic HF. The prevalences of male sex, comorbidities, and history of HF were higher in the ischaemic versus non-ischaemic HF subgroup. Annualised event rates for the primary composite outcome of total HF hospitalisations and cardiovascular death with FCM versus placebo were 65.3 versus 100.6 per 100 patient-years in the ischaemic HF subgroup (rate ratio [RR] 0.65, 95% confidence interval [CI] 0.47-0.89, p=0.007) and 58.3 versus 52.5 in the non-ischaemic HF subgroup (RR 1.11, 95% CI 0.75-1.66, p=0.60) (pinteraction =0.039). An interaction between HF aetiology and treatment effect was also observed for the secondary outcome of total HF hospitalisations (pinteraction =0.038). A nominal increase in quality of life, assessed using the 12-item Kansas City Cardiomyopathy Questionnaire, was observed with FCM versus placebo, within each subgroup. Heart failure hospitalisations and cardiovascular deaths occurred at a higher rate in patients with ishaemic versus those with non-ischaemic HF and were reduced by FCM versus placebo only in ischaemic patients. Further studies are needed to assess the role of aetiology in FCM efficacy.

Prevention of sudden death in heart failure with reduced ejection fraction: do we still needan implantable cardioverter-defibrillator for primary prevention?

Sudden death is a devastating complication of heart failure (HF). Current guidelines recommend an implantable cardioverter-defibrillator (ICD) for prevention of sudden death in patients with HF and reduced ejection fraction (HFrEF) specifically those with a left ventricular ejection fraction ≤35% after at least 3 months of optimized HF treatment. The benefit of ICD in patients with symptomatic HFrEF caused by coronary artery disease has been well documented; however, the evidence for a benefit of prophylactic ICD implantation in patients with HFrEF of non-ischaemic aetiology is less strong. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, beta-blockers (BB), and mineralocorticoid receptor antagonists (MRA) block the deleterious actions of angiotensin II, norepinephrine, and aldosterone, respectively. Neprilysin inhibition potentiates the actions of endogenous natriuretic peptides that mitigate adverse ventricular remodelling. BB, MRA, angiotensin receptor-neprilysin inhibitor (ARNI) have a favourable effect on reduction of sudden cardiac death in HFrEF. Recent data suggest a beneficial effect of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in reducing serious ventricular arrhythmias and sudden cardiac death in patients with HFrEF. So, in the current era of new drugs for HFrEF and with the optimal use of disease-modifying therapies (BB, MRA, ARNI and SGLT2i), we might need to reconsider the need and timing for use of ICD as primary prevention of sudden death, especially in HF of non-ischaemic aetiology.

Evaluation of Right Ventricular Myocardial Mechanics by 2- and 3-Dimensional Speckle-Tracking Echocardiography in Patients With an Ischemic or Non-ischemic Etiology of End-Stage Heart Failure

BackgroundThe aims of our study were (1) to assess the right ventricular (RV) myocardial mechanics by two-dimensional (2D) and three-dimensional (3D) speckle-tracking echocardiography (STE) in patients with an ischemic or non-ischemic etiology of end-stage heart failure (HF) and (2) to explore which RV index evaluated by 2D- and 3D-STE was the most powerful indicator for identifying the ischemic and non-ischemic etiologies of end-stage HF.MethodsA total of 96 patients with left ventricular ejection fraction (LVEF) < 30% were enrolled in our study: 42 patients (mean age, 52 ± 10 years; 9.5% female) with ischemic cardiomyopathy and 54 patients (mean age, 46 ± 14 years; 16.7% female) with non-ischemic cardiomyopathy. A total of 45 healthy subjects (mean age, 46 ± 13 years; 24.4% female) served as controls. The longitudinal strain of the RV free wall (RVFWLS) was determined by both 2D- and 3D-STE.ResultsCompared to controls, patients with an ischemic or non-ischemic etiology of end-stage HF had lower 2D-RVFWLS, 3D-RVFWLS and RV ejection fraction (RVEF) values (P < 0.05). Patients with non-ischemic cardiomyopathies (NICMs) had significantly lower 3D-RVFWLS and RVEF values than in those with ischemic cardiomyopathies (ICMs), whereas 2D-RVFWLS and conventional RV function parameters did not differ between the two subgroups. RVEF was highly related to 3D-RVFWLS (r = 0.72, P < 0.001), modestly related to 2D-RVFWLS (r = 0.51, P < 0.001), and weakly related to conventional RV function indices (r = –0.26 to 0.46, P < 0.05). Receiver operating characteristic curve analysis revealed that the optimal 3D-RVFWLS cut-off value to distinguish NICM from ICM patients was –14.78% (area under the curve: 0.73, P < 0.001), while 2D-RVFWLS and conventional RV echocardiographic parameters did not.ConclusionOur study demonstrated the superiority of 3D-RVFWLS over 2D-RVFWLS and conventional RV function indices in identifying the ischemic and non-ischemic etiologies of end-stage HF. These findings support the idea that 3D-RVFWLS may be a promising non-invasive imaging marker for distinguishing NICM from ICM.

Abstract 10895: Biomarkers of Physical Frailty in Heart Failure

Introduction: Physical frailty is highly prevalent and associated with worse outcomes among adults with heart failure (HF). However, the biological mechanisms underlying physical frailty in HF are poorly understood. The aim was to identify biomarkers associated with physical frailty in HF using a multimarker strategy to reflect multiple physiological processes. Hypothesis: We hypothesized that biomarkers of neurohormonal activation, inflammation, insulin resistance, and adipose and skeletal muscle dysfunction would differentiate physically frail from non-physically frail adults with HF. Methods: We collected data and plasma samples from adults with New York Heart Association Functional Class I-IV HF. Physical frailty was measured with the Frailty Phenotype Criteria. Plasma biomarkers assayed were: N-terminal pro-B-type natriuretic peptide, norepinephrine, dihydroxyphenolglycol, soluble tumor necrosis factor alpha receptor 1, adiponectin, insulin, glucose, insulin-like growth factor-1, and myostatin. Comparative statistics and multivariate linear regression were used. Results: The average age of the participants (n = 113) was 63.5±15.7 years, half (48%) were women, and most had a non-ischemic etiology of HF (73%). Physical frailty was identified in 42% of the sample and associated with female gender, higher body mass index, more comorbidities, and HF with preserved ejection fraction. After adjusting for Seattle HF Model projected survival scores, comorbidities, body mass index, and gender, those physically frail had significantly lower plasma adiponectin, lower insulin-like growth factor-1, and lower myostatin compared with those non-physically frail (all p &lt; 0.05). There were no significant differences in other biomarkers between physical frailty groups. Conclusions: Biomarkers involved in adipose tissue and skeletal muscle development, maintenance, and function were significantly different between those physically frail and non-physically frail. Physical frailty in HF may be, in part, underpinned by dysfunctional peripheral processes involving the adipose tissue and skeletal muscle.

Sodium-glucose co-transporter-2 inhibitors improve cardiovascular outcomes in heart failure with reduced ejection fraction regardless of ischemic etiology

Abstract Background Coronary artery disease remains the main underlying cause of heart failure (HF), despite the progress in prevention, diagnosis and treatment. Sodium-glucose co-transporter-2 inhibitors have been shown to improve surrogate cardiovascular outcomes in patients with HF with reduced ejection fraction (HFrEF), regardless of diabetes status. Purpose We sought to determine the effect of SGLT-2 inhibitors on the primary composite endpoint (cardiovascular death or hospitalization for HF) across the two hallmark trials in the HFrEF population (EMPEROR Reduced and DAPA-HF), according to ischemic or non-ischemic etiology of HF. Methods We pooled data from EMPEROR reduced and DAPA-HF trials in a total of 8,474 patients with HFrEF, performing a sub-analysis according to the presence of ischemic cardiomyopathy as the underlying cause of HFrEF. Results Treatment with SGLT-2 inhibitors resulted in a significant decrease in the risk for the primary composite outcome in patients with HFrEF of ischemic etiology, equal to 18% (RR=0.82, 95% CI: 0.73–0.92, I2=0%). In patients with HFrEF of non-ischemic etiology, SGLT-2 inhibitors produced a significant decrease in the risk for the primary composite outcome equal to 18% (RR=0.72, 95% CI: 0.63–0.82, I2=0%). Despite the greater effect in patients with non-ischemic HFrEF, no subgroup difference was detected (p=0.16). Generated results are summarized in Figure 1. Conclusions SGLT-2 inhibitors improve surrogate cardiovascular outcomes both in patients with ischemic and non-ischemic HFrEF. Funding Acknowledgement Type of funding sources: None. Figure 1

An aetiology-based subanalysis of the Telerehabilitation in Heart Failure Patients (TELEREH-HF) trial.

AimsThe aim of our study was to analyse the benefits of a 9 week hybrid comprehensive telerehabilitation (HCTR) programme in heart failure (HF) patients according to aetiology, as a subanalysis of the Telerehabilitation in Heart Failure Patients (TELEREH‐HF) trial.Methods and resultsOverall, 555 (65.3%) patients with ischaemic (IS) and 295 (34.7%) patients with non‐ischaemic (NIS) HF aetiology were randomized. There were no differences between the effect of HCTR and usual care (UC) on the primary outcome of number of days alive and out of the hospital in 26 months from the time of randomization in either aetiology (Wilcoxon–Mann–Whitney test), and no heterogeneity of effect between the aetiologies was noted (van Elteren test, P = 0.746). In Cox proportional hazards regression analysis, treatment was not independently associated with the secondary outcomes. For all‐cause mortality, the adjusted hazard ratio for HCTR vs. UC was 0.90 (95% confidence interval, 0.54–1.51) in IS and 1.42 (95% confidence interval, 0.69–2.94) in NIS (P interaction = 0.316). Differences between HCTR and UC in terms of change in the 6 min walk test distance and cardiopulmonary exercise test time after 9 weeks reached statistical significance in the IS arm (P = 0.015 and P < 0.001, respectively), but not in the NIS arm; however, tests of heterogeneity indicated no statistically significant differences.ConclusionsThe trial showed no difference between HCTR and UC in the primary outcome of percentage of days alive and out of the hospital for either IS or NIS aetiology. Moreover, the magnitude of changes in the clinical and functional statuses of the HF patients did not differ by aetiology. HCTR might have had beneficial effects on the 6 min walk test distance and cardiopulmonary exercise test time after 9 weeks in the IS patients; however, the effect was not statistically significantly different from that observed in the NIS patients.

Validation of Heart Failure Discharge Coding Utilising the PEOPLE Study and ADHF Registry

The accuracy of hospital discharge coding is important for quality improvement and research. The aim of this validation study was to evaluate the accuracy of heart failure (HF) coding in national hospitalisation data. HF hospitalisations identified from the Prospective Evaluation of Outcome in Patients with Heart Failure with Preserved Left Ventricular Ejection Fraction (PEOPLE) study and Acute Decompensated Heart Failure (ADHF) registry were linked to hospitalisation records. Index hospitalisations were reviewed for International Classification of Diseases 10th Revision (ICD10) coding for HF as the first (primary) or subsequent (secondary) diagnosis. The coding-definition of ischaemic HF aetiology (myocardial infarction or coronary revascularisation in the prior 10 years) was compared with HF aetiology recorded in PEOPLE/ADHF. Of 2,546 patients (22% from PEOPLE, 78% from ADHF), mean age was 65 years, 63% were male and 55% had reduced left ventricular ejection fraction. At the index admission, HF was coded as the primary diagnosis in 60%, secondary diagnosis in 30% and neither in 10%. All patients from PEOPLE had HF as either the primary (71%) or secondary (29%) diagnosis. 36% had ischaemic and 51% had non-ischaemic HF aetiology defined in PEOPLE/ADHF. After excluding those with unknown aetiology in the ADHF registry (14%), the proposed coding-definition for HF aetiology had a sensitivity of 80% (95% CI, 77%-82%) and specificity of 87% (95% CI, 85%-89%). Studies that utilise ICD10 coding should include both primary and secondary HF diagnoses. HF aetiology can be identified with modest accuracy using diagnostic/procedural coding.

Mid and Later Life Reproductive Factors Are Not Associated with Physical Frailty Among Women with Heart Failure

Background In heart failure (HF), the prevalence of physical frailty is high, and women are more likely to be frail than men; however, the reasons for gender differences in physical frailty in HF are unknown. Frailty has been associated with younger age at menopause and a history of hysterectomy, possibly reflecting accelerated aging. The relationship between physical frailty and later life reproductive factors might elucidate mechanisms of physical frailty among women with HF. Hypothesis : We hypothesized that, among women with HF, physical frailty will be associated with history of hysterectomy, post-menopause, and reproductive cancer. Methods : This was an analysis of data collected from a study of gender differences in physical frailty in HF. We examined reproductive factors of hysterectomy, post-menopause, and reproductive cancer history among women in the sample. Physical frailty was measured using the Frailty Phenotype Criteria: unintentional weight loss, weakness, slowness, physical exhaustion, and low physical activity. Comparative statistics were used to compare reproductive factors with physical frailty. Logistic regression was used to quantify associations between reproductive factors and physical frailty, accounting for age, etiology, HF type (reduced or preserved ejection fraction), and Charlson Comorbidity Index. Results The average age of women in our sample (n = 56) was 65.0±16.3 years and 83.9% had non-ischemic etiology of HF. The majority (82%) were in menopause transition or post-menopause. Physical frailty was identified in 58.9% of women. There was no significant association between physical frailty and history of a hysterectomy (χ2 = 1.52, p = 0.22), post-menopause (χ2 = 0.87, p = 0.65), or reproductive cancer (χ2 = 0.19, p = 0.67). In separate multivariate logistic regression models, history of hysterectomy (OR 1.75, 95% CI [0.48, 6.34]), post-menopause (OR 0.38, 95% CI [0.03, 5.07]), or reproductive cancer (OR 0.35, 95% CI [0.04, 2.95]) were not significantly associated with physical frailty in women. Conclusions Mid and later life reproductive factors, as well as age, do not appear to be significantly associated with physical frailty among women with HF, indicating that physical frailty affects women across the lifespan. However, future studies should explore a comprehensive reproductive history, including age of menarche, pregnancy, breastfeeding, and other reproductive life events, as variables that may impact physical frailty among women with HF.

Atrial arrhythmias in heart failure with a reduced ejection fraction.

Atrial arrhythmias are common among individuals with heart failure with a reduced ejection fraction (HFrEF). This review describes management options for these arrhythmias and discusses emerging clinical data supporting catheter ablation. Several recent clinical trials indicate that catheter ablation is superior to pharmacologic therapy for management of symptomatic atrial fibrillation in the setting of HFrEF. Restoration and maintenance of sinus rhythm appears to have the greatest benefit with regard to ejection fraction improvement among individuals with a nonischemic heart failure etiology and minimal left ventricular fibrosis. A rhythm control strategy should be strongly considered in patients with HFrEF, especially when the atrial arrhythmia is symptomatic or is present at the time of a heart failure diagnosis. Catheter ablation may be the preferred strategy for maintenance of sinus rhythm in this patient population.

Adherence to ESC cardiac resynchronization therapy guidelines: findings from the ESC CRT Survey II

Cardiac resynchronization therapy (CRT) reduces morbidity and mortality in patients with heart failure (HF) and electrical dyssynchrony. The European Society of Cardiology (ESC) Guidelines provide evidence-based recommendations indicating optimal patient selection for CRT implantation in both the 2013 European Heart Rhythm Association (EHRA) and the 2016 Heart Failure Association (HFA) Guidelines. We assessed the adherence to guidelines and identified factors associated with guideline adherence. In 2016, the HFA and EHRA conducted the CRT Survey II in 42 ESC countries. The data collected were sufficient to evaluate adherence to guidelines in 8021 patients. Of these, 67% had a Class I guideline indication for CRT implantation, which was significantly correlated with female gender (1.70, P < 0.0001), age <75 years (1.55, P < 0.0001), non-ischaemic HF aetiology (1.22, P < 0.0001), and elective admission (1.87, P < 0.0001). A further 26% of implants had a Class IIa indication, 5% IIb and only 2% a contraindication to CRT-a Class III indication. Patients implanted under Level IIa indications were much more likely to have more comorbidities than patients implanted under Level I indications. However, there were large variations in guideline adherence between ESC countries. Implanters in ESC member states demonstrate a high degree of adherence to ESC guidelines with 98% of implants having a documented Class I, IIa or IIb indication. Cardiac resynchronization therapy implantation without a Class I indication was more likely in men, patients age ≥75 years, with HF of ischaemic origin and in patients admitted to hospital acutely.

Relation of Pretransplant Peak Oxygen Consumption to Outcomes After Heart Transplantation

Peak exercise oxygen consumption (pVO2) is an important predictor of prognosis in patients with heart failure (HF). The association between pretransplant pVO2 and post-transplantation outcomes in HF patients has not been previously studied. We identified adult OHT recipients with available pVO2 in the United Network for Organ Sharing registry (2000 to 2015). Patients were divided into 3 categories using Weber classification: class B (pVO2 16 to 20 ml/kg/min), class C (pVO2 10 to 16 ml/kg/min), and class D (pVO2 <10 ml/kg/min). Postoperative outcomes (mortality, renal failure, rejection) were compared between the groups. A total of 9,623 patients were included in this analysis; the mean age was 54 ± 11 years, 74% were male, 75% were white and 59% had nonischemic etiology of HF. The mean pVO2 was 11.7 ± 3.6 ml/kg/min: 1,202 (12.5%) in class B, 6,055 (62.9%) in class C, and 2,366 (24.6%) were in class D. At a median follow-up of 6.1 years, 2,730 (28.4%) died. Post-transplantation survival decreased with decreasing pVO2; 1 and 5-year survival: B (92%, 80%), C (90%, 79%), and D (87%, 75%), p <0.001 by log-rank. After multiple adjustments, patients in class D had significantly higher post-transplantation mortality compared with class C (Hazard Ratio (HR) 1.21 [1.03 to 1.43], p = 0.02). When analyzed as a continuous variable, each 1 ml/kg/min increase in pVO2 was associated with 2% decrease in mortality during follow-up (adjusted HR 0.98 [0.96 to 0.99], p <0.001). Patients in class D had significantly prolonged (>14 days) hospitalization (adjusted Odds Ratio (OR) 1.42 [1.20 to 1.68], p <0.001) and a trend toward increased need for dialysis (adjusted OR 1.36 [1.00 to 1.84], p = 0.05) compared with patients in class B. In this large cohort, lower pretransplant pVO2 was associated with greater mortality and morbidity after OHT. These results suggest that earlier transplantation might improve post-transplantation outcomes in advanced HF patients.

Effectiveness of catheter ablation of atrial fibrillation according to heart failure etiology.

BackgroundCatheter ablation is an important rhythm control therapy in patients with atrial fibrillation (AF) with concomitant heart failure (HF). The objective of this study was to assess the comparative efficacy of AF ablation patients with ischemic vs nonischemic heart failure.MethodsWe conducted a retrospective, observational cohort study of patients with HF who underwent AF ablation. Outcomes were compared based on HF etiology and included in‐hospital events, symptoms (Mayo AF Symptom Inventory [MAFSI]), and functional status (New York Heart Association class) and freedom from atrial arrhythmias at 12 months.ResultsAmong 242 patients (n = 70 [29%] ischemic, n = 172 [71%] nonischemic), patients with nonischemic cardiomyopathy were younger (mean age 64 ± 11.5 vs 69 ± 9.1, P = .002), more often female (36% vs 17%, P = .004), and had higher mean left‐ventricular ejection fraction (47% vs 42%, P = .0007). There were no significant differences in periprocedural characteristics, including mean procedure time (243 ± 74.2 vs 259 ± 81.8 minutes, P = .1) and nonleft atrial ablation (17% vs 20%, P = .6). All‐cause adverse events were similar in each group (15% vs 17%, P = .7). NYHA and MAFSI scores improved significantly at follow‐up and did not differ according to HF etiology (P = .5; P = .10‐1.00 after Bonferroni correction). There were no significant differences in freedom from recurrent atrial arrhythmia at 12‐months between ischemic (74%) and nonischemic patients (78%): adjusted RR 0.63, 95% confidence interval 0.33‐1.19.ConclusionsCatheter ablation in patients with AF and concomitant heart failure leads to significant improvements in functional and symptom status without significant differences between patients with ischemic vs nonischemic HF etiology.

1037 Differences in reverse remodelling between ischemic and non-ischemic left ventricular segments as assessed by myocardial work after sacubitril-valsartan therapy

Abstract Introduction Myocardial work (MW) is a new transthoracic echocardiographic (TTE) parameter that enhances the information provided through left ventricular (LV) global longitudinal strain (GLS), allowing to investigate LV performance even in cases of changes in afterload. None is known about the effects of Sacubitril-Valsartan (LCZ696) therapy in MW parameters. Purpose Compare the changes in MW parameters between ischemic and non-ischemic segments after LCZ696 therapy. Methods The study was a prospective evaluation of chronic Heart Failure (HF) patients with optimized standard of care therapy and LV ejection fraction ≤40%, in which LCZ696 therapy was started and no other HF treatment was expected to change. A TTE study was performed before and 6 months after LCZ696 therapy, using the GE Vivid E95 ultrasound system. A semiautomated analysis of GLS was performed after two-dimensional images were acquired in the standard apical 4-, 3- and 2 chamber views. MW and related indices were estimated using custom software. Two groups were created according to the 17 segment model TTE study before LCZ696 therapy: G1 (ischemic group): dyskinesia/akinesia/hypokinesia segments in patients with ischemic HF etiology; G2 (non-ischemic group): normokinesia segments in patients with ischemic and all segments in patients with non-ischemic HF etiology; Results Of the 42 patients, 35 (83.3%) completed the six-months follow-up with LCZ696, since 2 patients (4.8%) died and 5 patients (11.9%) discontinued treatment for adverse events. Mean age was 58.6 ± 11.1 years, with ischemic etiology in 15 (42.9%), resulting in a total of 26.5% segments for G1. Baseline global MW index (GWI) had no statistical difference between G1 and G2 (566.1 VS 584.8mmHg%, p = 0.257), but baseline MW efficiency (GWE) were significantly lower in G1 (71.9 VS 78.8%, p &amp;lt; 0.001). The table represents the mean values for MW parameters in G1 and G2 before and 6 months after LCZ696 therapy, with a significantly increase in GWI and GWE values in both groups. Despite no difference in the increase in GWE (p = 0.872), the increase in GWI were higher in G2 than G1 (p &amp;lt; 0.001). Conclusion MW seems to be a new tool providing signs of reverse remodelling and better cardiac performance in ischemic and non-ischemic segments after LCZ696 therapy. Table 1 Time 0 6 months p GWI in ischemic segments (mmHg%) 566.1 ± 364.0 696.5 ± 445.2 &amp;lt;0.001 GWE in ischemic segments (%) 71.9 ± 25.0 78.9 ± 19.1 0.009 GWI in non-ischemic segments (mmHg%) 584.8 ± 434.3 812.3 ± 442.0 &amp;lt;0.001 GWE in non-ischemic segments (%) 78.8 ± 21.2 85.7 ± 15.8 0.004 MW data before and after six months of LCZ696 therapy

Cardiac Strains As a Tool for Optimization of Cardiac Resynchronization Therapy in Non-responders: a Pilot Study.

BackgroundApproximately 30% of patients do not respond to implantation of Cardiac Resynchronization Therapy – Defibrillators (CRT-D). The aim of this study was to investigate the potential for cardiac strain speckle tracking to optimize the performance of CRT-D in non-responding patients.Methods30 patients not responding to Cardiac Resynchronization Therapy-Defibrillators after 3 months were randomly divided into control and intervention groups. Atrioventricular interval was adjusted so that E and A waves did not overlap, the interventricular interval was subsequently optimized to yield maximum improvement of the sum of longitudinal+radial+circumferential strains. The left ventricular ejection fraction (LVEF) and NYHA improvement 3 months after optimization were evaluated and use of other strain combinations assessed.ResultsA significant correlation between the (combined) strain change and LVEF improvement was detected (p<0.01). 75% of patients with non-ischemic etiology of heart failure who did not respond to the original CRT-D reacted favorably with significant LVEF and NYHA improvement. The area strain was the best predictor of LVEF/NYHA improvement in those patients. No significant improvement was recorded in patients with ischemic etiology.ConclusionsAV and VV optimization based on speckle tracking is a very promising method potentially leading to a significant improvement of the outcome of CRT-D, especially in patients with non-ischemic etiology of heart failure.

Recovery of left ventricular dysfunction after sacubitril/valsartan: predictors and management

BackgroundLiterature describing recovery of left ventricular (LV) function post sacubitril/valsartan treatment and the optimal management of heart failure (HF) patients receiving sacubitril/valsartan remain sparse. MethodsWe recruited 437 consecutive chronic HF patients with baseline left ventricular ejection fraction (LVEF) less than 40%, who were treated with sacubitril/valsartan. All patients underwent routine echocardiographic measurement. ResultsDuring treatment period, recovery of LVEF to 50% or greater was observed in 77 (17.6%) patients. After multivariate analysis, recovery of LV dysfunction was associated with non-ischemic etiology of HF, smaller baseline LV end-diastolic diameter (LVEDD), and higher initial dosage of sacubitril/valsartan. Compared to those without recovery of LV dysfunction, death from cardiovascular causes or first unplanned hospitalization for HF (CVD/HFH) were significantly lower in patients with LVEF recovery [11.7% vs. 24.4%, hazard ratio (HR) 0.42, p = 0.014]. Among patients with recovery of LVEF, 51 patients continued to receive the same dosage of sacubitril/valsartan had higher LVEF and were less likely to have deterioration of LVEF than the other 26 patients who received either tapering dose of sacubitril/valsartan or switching from sacubitril/valsartan to renin-angiotensin-system blockers (LVEF 56.4 ± 5.3% vs. 45.0 ± 12.8%, p < 0.001; ΔLVEF 1.2 ± 5.1% vs. −9.3 ± 12.0%, p < 0.001). CVD/HFH occurred more frequently in the taper group than the maintenance group (23.1% vs. 5.9%, HR 0.22, p = 0.035). ConclusionsNon-ischemic etiology of HF, smaller baseline LVEDD, and higher initial dosage of sacubitril/valsartan could predict better recovery of LV function. Among patients with functional recovery, tapering sacubitril/valsartan dose was associated with deterioration of recovered heart function and had less favorable prognosis during follow-up.