Lower Kansas City Cardiomyopathy Questionnaire Research Articles

Proteomics Identify Clinical Phenotypes and Predict Functional Outcomes in Heart Failure With Preserved Ejection Fraction: Insights From VITALITY-HFpEF.

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome that may emerge from overlapping systemic processes associated with comorbidities. We assessed whether unique clusters of circulating proteins are associated with specific clinical characteristics and functional status at baseline and follow-up in a well-phenotyped cohort of patients with HFpEF. We evaluated 368 proteins associated with cardiovascular disease and inflammation in prerandomization blood samples from 763 VITALITY-HFpEF (Vericiguat to Improve Physical Functioning in Daily Living Activities of Patients With HFpEF) participants who had a left ventricular ejection fraction ≥45% and a heart failure decompensation event within 6 months. Proteins were clustered, and their associations with clinical characteristics, baseline, and 24-week functional outcomes (Kansas City Cardiomyopathy Questionnaire Physical Limitation Score, 6-minute walk distance [6MWD], and Fried frailty phenotype) were estimated with linear regression. Elastic net regression was used to derive a proteomic summary composite to predict changes in 24-week functional outcomes. Four unique protein clusters were identified, containing 24, 66, 197, and 81 proteins. At baseline, 2 protein clusters with the hub proteins caspase-3 and Dickkopf-related protein 1 were associated with increased frailty, whereas the cluster with tumor necrosis factor receptor 1 as a hub protein was associated with lower Kansas City Cardiomyopathy Questionnaire Physical Limitation Score and shorter 6MWD. By contrast, the cluster with protein C as a hub protein was associated with less frailty and longer a 6MWD. The 24-week increase in 6MWD was negatively correlated with the protein cluster with caspase-3; the protein C cluster was correlated with less frailty at 24 weeks. The baseline proteomic summary composite predicted observed changes in Kansas City Cardiomyopathy Questionnaire Physical Limitation Score and 6MWD at 24 weeks (r=0.42 and 0.30; P<0.001 for both). Proteomics differentiate specific baseline functional traits associated with HFpEF and may facilitate phenotyping in a heterogeneous disease. These proteins also provide insights into the diverse pathophysiology of HFpEF and which patients may improve functional status during follow-up. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03547583.

Impact of Persistent Versus Paroxysmal Preoperative Atrial Fibrillation on In-Hospital, One-Year, and Late Clinical Outcomes Following Transcatheter Aortic Valve Implantation

Previous reports on the impact of preexisting atrial fibrillation (AF) on clinical outcomes after transcatheter aortic valve implantation (TAVI) have presented limited data on the relative impact of paroxysmal versus persistent AF subtypes. We compared in-hospital, 1-year, and late clinical outcomes in 1,098 patients who underwent TAVI with preoperative AF (556 paroxysmal, 542 persistent) versus 1,787 patients without AF. The propensity-matched cohorts with AF (n = 643) and without AF (n = 686) did not differ with respect to baseline clinical characteristics, operative technique, or in-hospital TAVI complications. At 1-year, patients with AF had higher all-cause mortality (9.0% vs 6.1%, p = 0.046) and readmission rates (13.1 vs 8.8%, p = 0.014), with lower Kansas City cardiomyopathy questionnaire scores (77.8 ± 21.8 vs 84.3 ± 17.1, p <0.001). Echocardiographic follow-up (mean time 455 ± 285 days) demonstrated no significant intergroup differences in hemodynamic findings other than a progressive increase in left atrial volume index in patient subgroups (without AF: 37.4 ± 14.7 ml/m2 vs paroxysmal AF: 46.4 ± 21.4 ml/m2 vs persistent AF: 60.5 ± 26.3 ml/m2, p <0.001). On late follow-up (mean time 49.0 [45.1 to 52.9] months), patients with persistent AF had worse all-cause mortality than patients without AF (hazard ratio 1.55, 95% confidence interval 1.17 to 2.06, p = 0.003), with no significant survival differences between the paroxysmal AF and without AF subgroups. In conclusion, patients with preexisting AF and patients without AF who underwent TAVI had similar in-hospital outcomes but worse 1-year mortality, hospital readmission, and quality of life outcomes. Compared with patients without AF, patients with persistent but not paroxysmal preexisting AF have higher late all-cause mortality at a mean follow-up of 49 months. Patients with persistent AF have higher levels of left atrial volume index than patients with paroxysmal AF and patients without AF on intermediate echocardiographic follow-up.

Efficacy of empagliflozin in heart failure with preserved ejection fraction according to frailty status in EMPEROR-Preserved.

Frailty is a severe, common co-morbidity associated with heart failure (HF) with preserved ejection fraction (HFpEF). The impact of frailty on HFpEF outcomes may affect treatment choices in HFpEF. The impact of frailty on HFpEF patients and any impact on the clinical benefits of sodium glucose co-transporter 2 (SGLT2) inhibition in HFpEF have been described in only a limited number of trials. Whether the SGLT2 inhibitor empagliflozin would improve or worsen frailty status when given to HFpEF patients is also not known. The aims of this study were, therefore, to evaluate, in HFpEF patients enrolled in the EMPEROR-Preserved trial (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction), the impact of frailty on clinical outcomes, and on the effects of empagliflozin, as well as the effect of empagliflozin on frailty status during treatment period. We calculated a cumulative deficit-derived frailty index (FI) using 44 variables including clinical, laboratory and quality of life parameters recorded in EMPEROR-Preserved. Patients were classified into four groups: non-frail (FI<0.21), mild frailty (0.21 to <0.30), moderate frailty (0.30 to <0.40) and severe frailty (≥0.40). Clinical outcomes and health-related quality of life were evaluated according to baseline FI along with the effect of empagliflozin on chronological changes in FI (at 12, 32 and 52weeks). The patient distribution was 1514 (25.3%), 2100 (35.1%), 1501 (25.1%) and 873 (14.6%) in non-frail, mild frailty, moderate frailty and severe frailty, respectively. Severe frailty patients tended to be female and have low Kansas City Cardiomyopathy Questionnaire (KCCQ) scores, more co-morbidities and more polypharmacy. Incidence rates of the primary outcome of cardiovascular death or HF hospitalization increased as frailty worsened (hazard ratio [HR] of each FI category compared with the non-frail group: 1.10 [95% confidence interval, CI, 0.89-1.35], 2.00 [1.63-2.47] and 2.61 [2.08-3.27] in the mild frailty, moderate frailty and severe frailty groups, respectively; P trend<0.001). Compared with placebo, empagliflozin reduced the risk for the primary outcome across the four FI categories, HR: 0.59 [95% CI 0.42-0.83], 0.79 [0.61-1.01], 0.77 [0.61-0.96] and 0.90 [0.69-1.16] in non-frail to severe frailty categories, respectively (P value for trend=0.097). Empagliflozin also improved other clinical outcomes and KCCQ score across frailty categories. Compared with placebo, empagliflozin-treated patients had a higher likelihood of being in a lower FI category at Weeks 12, 32 and 52 (P<0.05), odds ratio: 1.12 [95% CI 1.01-1.24] at Week 12, 1.21 [1.09-1.34] at Week 32 and 1.20 [1.09-1.33] at Week 52. Empagliflozin improved key efficacy outcomes with a possible diminution of effect in very frail patients. Empagliflozin also improved frailty status during follow-up.

Sex Differences in Heart Failure With Reduced Ejection Fraction in the GALACTIC-HF Trial

BackgroundWomen with heart failure with reduced ejection fraction (HFrEF) receive less guideline-recommended therapy and experience worse quality of life than men. ObjectivesThe authors sought to assess differences in baseline characteristics, outcomes, efficacy, and safety of omecamtiv mecarbil between men and women enrolled in the GALACTIC-HF (Registrational Study With Omecamtiv Mecarbil [AMG 423] to Treat Chronic Heart Failure With Reduced Ejection Fraction) study. MethodsIn GALACTIC-HF, patients with symptomatic heart failure with EF of 35% or less, recent heart failure event, and elevated natriuretic peptides were randomized to omecamtiv mecarbil or placebo. The current analysis investigated differences in baseline characteristics, clinical outcomes, and efficacy and safety of omecamtiv mecarbil between men and women. ResultsOf 8,232 patients analyzed, 21.2% were women. Women more likely self-identified as being Black, had worse symptoms (lower Kansas City Cardiomyopathy Questionnaire Total Symptom Score [KCCQ-TSS]), and were less likely to be treated with angiotensin receptor/neprilysin inhibitor and devices at baseline. Compared with men, women had lower rates of the primary endpoint (adjusted HR: 0.80, 95% CI: 0.73-0.88). Sex did not significantly modify omecamtiv mecarbil’s treatment effect (P interaction = 0.68). Women also had 20% less risk of cardiovascular death, heart failure event, and all-cause death. Women participants had lower rates of serious adverse events. ConclusionsWomen participants of the GALACTIC-HF trial had worse quality of life and were less likely to be treated with guideline-based therapies at baseline. Despite KCCQ-TSS being predictive of poor outcomes in this population, women had a 20% lower risk of an HF event or cardiovascular death compared with men. The beneficial effect of omecamtiv mecarbil did not significantly differ by sex. (Registrational Study With Omecamtiv Mecarbil [AMG 423] to Treat Chronic Heart Failure With Reduced Ejection Fraction [GALACTIC-HF]; NCT02929329)

Outcomes of transcatheter aortic valve replacement in patients with cardiogenic shock.

The safety and efficacy of transcatheter aortic valve replacement (TAVR) with contemporary balloon expandable transcatheter valves in patients with cardiogenic shock (CS) remain largely unknown. In this study, the TAVRs performed for CS between June 2015 and September 2022 using SAPIEN 3 and SAPIEN 3 Ultra bioprosthesis from the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry were analysed. CS was defined as: (i) coding of CS within 24 h on Transcatheter Valve Therapy Registry form; and/or (ii) pre-procedural use of inotropes or mechanical circulatory support devices and/or (iii) cardiac arrest within 24 h prior to TAVR. The control group was comprised of all the other patients undergoing TAVR. Baseline characteristics, all-cause mortality, and major complications at 30-day and 1-year outcomes were reported. Landmark analysis was performed at 30 days post-TAVR. Cox-proportional multivariable analysis was performed to determine the predictors of all-cause mortality at 1 year. A total of 309 505 patients underwent TAVR with balloon-expandable valves during the study period. Of these, 5006 patients presented with CS prior to TAVR (1.6%). The mean Society of Thoracic Surgeons score was 10.76 ± 10.4. The valve was successfully implanted in 97.9% of patients. Technical success according to Valve Academic Research Consortium-3 criteria was 94.5%. In a propensity-matched analysis, CS was associated with higher in-hospital (9.9% vs. 2.7%), 30-day (12.9% vs. 4.9%), and 1-year (29.7% vs. 22.6%) mortality compared to the patients undergoing TAVR without CS. In the landmark analysis after 30 days, the risk of 1-year mortality was similar between the two groups [hazard ratio (HR) 1.07, 95% confidence interval (CI) 0.95-1.21]. Patients who were alive at 1 year noted significant improvements in functional class (Class I/II 89%) and quality of life (ΔKCCQ score +50). In the multivariable analysis, older age (HR 1.02, 95% CI 1.02-1.03), peripheral artery disease (HR 1.25, 95% CI 1.06-1.47), prior implantation of an implantable cardioverter-defibrillator (HR 1.37, 95% CI 1.07-1.77), patients on dialysis (HR 2.07, 95% CI 1.69-2.53), immunocompromised status (HR 1.33, 95% CI 1.05-1.69), New York Heart Association class III/IV symptoms (HR 1.50, 95% CI 1.06-2.12), lower aortic valve mean gradient, lower albumin levels, lower haemoglobin levels, and lower Kansas City Cardiomyopathy Questionnaire scores were independently associated with 1-year mortality. This large observational real-world study demonstrates that the TAVR is a safe and effective treatment for aortic stenosis patients presenting with CS. Patients who survived the first 30 days after TAVR had similar mortality rates to those who were not in CS.

Quality of Life, Procedural Success, and Clinical Outcomes following Transcatheter Mitral Valve Repair.

Limited data exist regarding the association between the quality of life (QoL) and clinical outcomes following transcatheter mitral valve repair (TMVr). We aimed to evaluate the prognostic significance of QoL assessment following TMVr and to characterize those who had procedural success, yet reported a low Kansas City Cardiomyopathy Questionnaire (KCCQ-12) score. We reported the experience of Cedars-Sinai Medical Center patients between 2013 and 2020. Patients were allocated into four groups according to the 30-day KCCQ: <25, 25-49, 50-74, and ≥75. Primary outcome included 1-year all-cause death or heart failure (HF) hospitalizations. We also examined the association between QoL and the primary outcome in those with procedural success. A total of 555 patients were included in our analysis, median follow-up of 650 days (IQR 243-1113). The lower KCCQ groups had a higher prevalence of functional mitral regurgitation (65%, 60%, 56%, and 43%, p = 0.001), as well as a higher Society of Thoracic Surgeon (STS) score. These groups had a significantly higher occurrence of 1-year all-cause death or HF hospitalizations in a stepwise fashion (40%, 22%, 16%, and 10%, p < 0.001). Multivariable Cox regression analysis revealed 30-day KCCQ as the strongest predictor of the 1-year primary outcome (HR 0.98, 95%CI (0.97-0.99), p = 0.006). Approximately a quarter of patients with procedural success had a low KCCQ score. These patients had a higher rate of the combined 1-year outcome regardless of procedural success or failure. QoL following TMVr is a powerful prognostic factor. KCCQ assessment is an important indicator for identifying patients prone to adverse outcomes even after procedural success.

The clinical and biochemical effects of atrial fibrillation on heart failure with reduced ejection fraction; a sub-saharan African perspective

Abstract Background Sub Saharan Africa (SSA) has seen one of the sharpest increases in cardiovascular disease-related mortality. This increase is evidenced by a growing burden of heart failure and atrial fibrillation (AF) risk factors. Atrial fibrillation is a common comorbidity of heart failure with reduced ejection fraction (HFrEF) which predisposes to an increased risk of morbidity and mortality. Studies done in high income countries (HIC) suggest that there may be an essential role for ethnic differences. However, in the absence of accurate epidemiological data in Sub-Saharan Africa, this cannot be proven. To date, there has never been a prospective systematic description of patients with HFrEF/AF and HFrEF/sinus rhythm (SR). Aim Our study aimed to describe the clinical and biochemical profile of patients with HFrEF/AF and HFrEF/SR in a Sub-Saharan African cohort. Methods The study was conducted inthe division of our Academic Hospital in South Africa. We enrolled 141 patients, consecutively, with HFrEF. Baseline clinical characteristics and exploratory biomarkers were recorded. All participants underwent comprehensive echocardiography. Novel left atrial strain was measured using 2D-speckle tracking echocardiography. These values were compared between patients in SR and in AF. Results The prevalence of AF was 21.38%. Hypertensive heart disease was the leading cause of HFrEF (36%). HFrEF/AF patients were significantly older (66.7±11.9) than those in SR (53.7±14.4) (p=0.000) with significantly different racial proportions (p=0.001). Coronary artery disease was prevalent in patients with HFrEF/AF. Patients with HFrEF/AF had significantly lower Kansas City Cardiomyopathy Questionnaire scores (29.83±15.27) compared to those in SR (44.26±16.30) (p=0.000) as well as worsening functional class (NYHA III–IV; 64.3% vs 22.7%, p=0.000). Measured levels of sST2 were greater in HFrEF/AF patients 40.45ng/mL (17.6–68.6) vs 20.8 (7.9–44.0) in HFrEF/SR (p=0.031). Patients with HFrEF/AF had a significantly greater left atrial volume (ml) (83.9 [64–99.9]) than those with HFrEF/SR (61.53±25.46) (p=0.038). Left atrial strain reservoir function (%) was significantly lower in patients with HFrEF/AF (29.00±13.60) compared to those with HFrEF/SR (41.56±15.46) (p=0.0004) Conclusion Our findings demonstrate that patients with HFrEF/AF are older than those in SR but much younger compared to patients in HICs. Hypertensive heart disease is a major cause of HFrEF in South Africa. We demonstrate that patients with HFrEF/AF are clinically worse off than those with HFrEF/SR. Atrial fibrillation is a marker of fibrosis and disease severity in HFrEF. Patients with HFrEF/AF had elevated sST2 levels a more deformed left atrium morphologically and poor tissue doppler function. On strain imaging, HFrEF/AF patients had poor left atrial reservoir function. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): The South African Medical Research Council

Impact of Non-cardiac Comorbidities on Long-Term Clinical Outcomes and Health Status After Acute Heart Failure in China.

BackgroundIndividual non-cardiac comorbidities are prevalent in HF; however, few studies reported how the aggregate burden of non-cardiac comorbidities affects long-term outcomes, and it is unknown whether this burden is associated with changes in health status.AimsTo assess the association of the overall burden of non-cardiac comorbidities with clinical outcomes and quality of life (QoL) in patients hospitalized for heart failure (HF).MethodsWe prospectively enrolled patients hospitalized for HF from 52 hospitals in China. Eight key non-cardiac comorbidities [diabetes, chronic renal disease, chronic obstructive pulmonary disease (COPD), anemia, stroke, cancer, peripheral arterial disease (PAD), and liver cirrhosis] were included, and patients were categorized into four groups: none, one, two, and three or more comorbidities. We fitted Cox proportional hazards models to assess the burden of comorbidities on 1-year death and rehospitalization.ResultsOf the 4,866 patients, 25.3% had no non-cardiac comorbidity, 32.2% had one, 22.9% had two, and 19.6% had three or more in China. Compared with those without non-cardiac comorbidities, patients with three or more comorbidities had higher risks of 1-year all-cause death [heart rate, HR 1.89; 95% confidence interval (CI) 1.48–2.39] and all-rehospitalization (HR 1.35; 95%CI 1.15–1.58) after adjustment. Although all patients with HF experienced a longitudinal improvement in QoL in the 180 days after discharge, those with three or more non-cardiac comorbidities had an unadjusted 11.4 (95%CI −13.4 to −9.4) lower Kansas City Cardiomyopathy Questionnaire (KCCQ) scores than patients without comorbidities. This difference decreased to −6.4 (95%CI −8.6 to −4.2) after adjustment for covariates.ConclusionAmong patients hospitalized with HF in this study, a higher burden of non-cardiac comorbidities was significantly associated with worse health-related QoL (HRQoL), increased risks of death, and rehospitalization post-discharge. The findings highlight the need to address the management of comorbidities effectively in standardized HF care.

Impaired health status is independently associated with persistently elevated NT-proBNP levels despite medical therapy for heart failure with reduced ejection fraction

Abstract Background Impaired health status as measured by standardized tools such as Kansas City Cardiomyopathy Questionnaire (KCCQ), Duke Activity Status Index (DASI) and six-minute walk test (6MWT) has been shown to predict hospitalization and mortality in patients with chronic heart failure. However, prognostic implications of these measurements in response to guideline-directed medical therapy for heart failure with reduced ejection fraction (HFrEF) remained to be elucidated. Purpose We hypothesized that impaired health status were predictive of persistently elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) after 6 and 12 months of therapeutic optimization in HFrEF. Methods Data on the GUIDE-IT trial that included protocolized HFrEF drug titration were analyzed. Patients who did not have NT-proBNP at 12 months were excluded. KCCQ overall and clinical summary scores, and DASI scores at baseline and 6 months were calculated. Six-minute walk test (6MWT) distance at baseline were also available. Response to medical therapy was defined as having NT-proBNP at 12 months of less than 1,000 pg/mL. Median value of each measurement was used as a cutoff. Multivariate logistic regression analysis was used to determine independent associations between different QOL scores and NT-proBNP response after adjustment for age, comorbidities, baseline EF, NYHA functional class, and NT-proBNP. Results There were 193 (43%) responders. Compared with those who responded to the medical therapy, non-responders were older, and more likely to have comorbidities including coronary artery disease, stroke, PAD, AF, hypertension, COPD, DM, CKD, and dyslipidemia, as well as lower EF, NHYA functional class and higher baseline NT-proBNP. After adjustment for baseline characteristics, lower KCCQ (either overall or summary) scores at baseline and 6 months, and lower DASI scores at 6 months (but not baseline) were independently associated with lower likelihood of response to GDMT (Table). In contrast, baseline 6MWT distance did not predict non-response to GDMT after adjustments. Conclusions Only impaired baseline KCCQ scores were predictive of persistently elevated NT-proBNP, while lower KCCQ and DASI scores at 6 month were predictive of persistently elevated NT-proBNP. Funding Acknowledgement Type of funding sources: None. Health Status Score below Median and ORs

The relationship of dehydration and body mass index with the occurrence of atrial fibrillation in heart failure patients

Abstract Background/Introduction Heart failure (HF) and atrial fibrillation (AF) are two conditions that are likely to dominate the next years of cardiovascular (CV) care. These diseases frequently coexist and they can beget one another due to similar risk factors and similar pathophysiology. Purpose The aim of the study was to assess the relationship of dehydration, body mass index (BMI) and other indices with the occurrence of AF in HF patients. Methods The study included 113 patients [median age 64 years; 57.52% male] hospitalized due to HF. Baseline demographics, body mass analysis, echocardiographic results, key cardiopulmonary exercise test (CPET) parameters, six minute walk distance (6MWD) and Kansas City Cardiomyopathy Questionnaire (KCCQ) score were assessed. Results Of all patients, 23 (20.35%) had AF, and 90 (79.65%) had sinus rhythm (SR). Patients with AF were older (med. 66 vs 64 years; p=0.039), with higher BMI (32.02 vs. 28.51 kg/m2; p=0.017) and percentage of fat content (37.0 vs. 27.9%, p=0.014). They were more dehydrated, with a lower percentage of total body water (TBW%) (45.7 vs 50.0%; p=0.022). Clinically, patients with AF had more often higher New York Heart Association (NYHA) class (III vs II; p&amp;lt;0.001), shorter 6MWD (median 292.35 vs 378.4 m; p=0.001) and a lower KCCQ overall summary score (52.60 vs 73.96 points; p=0.002). Patients with AF had significantly lower exercise capacity as measured by peak oxygen consumption (peak VO2) (0.92 vs 1.26 mL/min, p=0.016), peak VO2/kg (11 vs. 15 mL/kg/min; p&amp;lt;0.001), and percentage of predicted VO2max (pp-peak VO2) (62.5 vs 70.0; p=0.010). We also found VE/VCO2 (med.33.85 vs 32.20; p=0.049) to be higher and peak oxygen pulse (8.5 vs 11 mL/beat; p=0.038) to be lower in patients with AF than in patients without AF. In a multiple logistic regression model higher BMI (OR 1.23 per unit increase, p&amp;lt;0.001) and higher left atrial volume index (LAVI) (OR 1.07 per unit increase, p=0.03), lower tricuspid annular plane systolic excursion (TAPSE) (OR 0.74 per unit increase, p=0.03) and lower TBW% in body mass analysis (OR 0.90 per unit increase, p=0.03) were independently related to AF in patients with HF. Conclusions Increased volume of left atrium and right ventricular systolic dysfunction are well-known predictors of AF occurrence in patients with HF, but hydration status and increased body mass also seem to be important factors of AF in HF patients. Funding Acknowledgement Type of funding sources: None. Figure 1

The Relationship of Dehydration and Body Mass Index With the Occurrence of Atrial Fibrillation in Heart Failure Patients.

Purpose: The aim of the study was to assess the relationship of dehydration, body mass index (BMI) and other indices with the occurrence of atrial fibrillation (AF) in heart failure (HF) patients.Methods: The study included 113 patients [median age 64 years; 57.52% male] hospitalized due to HF. Baseline demographics, body mass analysis, echocardiographic results, key cardiopulmonary exercise test (CPET) parameters, 6 min walk distance (6MWD) and Kansas City Cardiomyopathy Questionnaire (KCCQ) score were assessed.Results: Of all patients, 23 (20.35%) had AF, and 90 (79.65%) had sinus rhythm (SR). Patients with AF were older (med. 66 vs. 64 years; p = 0.039), with higher BMI (32.02 vs. 28.51 kg/m2; p = 0.017) and percentage of fat content (37.0 vs. 27.9%, p = 0.014). They were more dehydrated, with a lower percentage of total body water (TBW%) (45.7 vs. 50.0%; p = 0.022). Clinically, patients with AF had more often higher New York Heart Association (NYHA) class (III vs. II; p < 0.001), shorter 6MWD (median 292.35 vs. 378.4 m; p = 0.001) and a lower KCCQ overall summary score (52.60 vs. 73.96 points; p = 0.002). Patients with AF had significantly lower exercise capacity as measured by peak oxygen consumption (peak VO2) (0.92 vs. 1.26 mL/min, p = 0.016), peak VO2/kg (11 vs. 15 mL/kg/min; p < 0.001), and percentage of predicted VO2max (pp-peak VO2) (62.5 vs 70.0; p=0.010). We also found VE/VCO2 (med. 33.85 vs. 32.20; p = 0.049) to be higher and peak oxygen pulse (8.5 vs. 11 mL/beat; p = 0.038) to be lower in patients with AF than in patients without AF. In a multiple logistic regression model higher BMI (OR 1.23 per unit increase, p < 0.001) and higher left atrial volume index (LAVI) (OR 1.07 per unit increase, p = 0.03), lower tricuspid annular plane systolic excursion (TAPSE) (OR 0.74 per unit increase, p =0.03) and lower TBW% in body mass analysis (OR 0.90 per unit increase, p =0.03) were independently related to AF in patients with HF.Conclusion: Increased volume of left atrium and right ventricular systolic dysfunction are well-known predictors of AF occurrence in patients with HF, but hydration status and increased body mass also seem to be important factors of AF in HF patients.

Evaluating Out-of-Hospital 30-Day Mortality After Transfemoral Transcatheter Aortic Valve Replacement

This study sought to better understand out-of-hospital 30-day mortality following transfemoral transcatheter aortic valve replacement (TAVR) and identify factors associated with poor outcomes. Despite improvements in outcomes with TAVR for severe aortic stenosis, out-of-hospital 30-day mortality has not been evaluated. This study examined patients in the Society of Thoracic Surgeons/American College of Cardiology TVT (Transcatheter Valve Therapy) Registry undergoing TAVR for severe aortic stenosis from January 2015 to March 2018. Primary and secondary endpoints were 30-day out-of-hospital all-cause mortality and out-of-hospital cardiovascular mortality, respectively. Logistic regression models were used to assess association between pre-specified factors and endpoints. A total of 106,749 patients underwent TAVR and were eligible for analysis. Transfemoral TAVR was performed in 92.3% of patients. A total of 2,137 (2.2%) transfemoral patients died within 30days of the procedure, and 623 (29%) patients of these patients experienced out-of-hospital 30-day mortality. Cardiovascular and pulmonary etiologies accounted for the majority of observed mortality. Multivariable regression analysis identified older age, gender, lower body surface area, lower left ventricular ejection fraction, lower hemoglobin, atrial fibrillation or flutter, severe lung disease, home oxygen use, lack of moderate-to-severe aortic insufficiency, urgent TAVR, lower Kansas City Cardiomyopathy Questionnaire score, longer hospital length of stay, and in-hospital complications as being independently associated with the primary endpoint. New onset or pre-existent atrial fibrillation or flutter was also independently associated with 30-day out-of-hospital cardiovascular mortality in the transfemoral population. We identified 30-day all-cause mortality rate for TAVR of 2.2%. Approximately one-third of patients experienced out-of-hospital mortality at 30days. Several factors were identified as being independently associated with30-day out-of-hospital all-cause and cardiovascular mortality. Further work is needed to understand how besttoimprove out-of-hospital mortality following TAVR.

Differences in clinical characteristics and reported quality of life of men and women undergoing cardiac resynchronization therapy.

AimsResponse to cardiac resynchronization therapy (CRT) is known to be associated with a number of clinical characteristics, including QRS duration and morphology, gender, height, and the aetiology of heart failure (HF). We assessed the relation of gender and baseline characteristics with QRS duration and Kansas City Cardiomyopathy Questionnaire.Methods and resultsAdaptResponse is a global randomized trial. The trial enrolled CRT‐indicated patients with New York Heart Association classes II–IV HF, left bundle branch block (QRS ≥ 140 ms in men, ≥130 ms in women), and baseline PR interval ≤200 ms. In total, 3620 patients were randomized, including 1569 women (43.3%) approaching the actual proportion of women in the HF population. Women were older and more often New York Heart Association class III or IV than men (55.6% vs. 48.7%), had less frequent ischaemic cardiomyopathy (21.2% vs. 39.5%), and had a 5.1 ms shorter QRS duration than men. Women were more often depressed (18.5% vs. 9.7%), had a significantly lower Kansas City Cardiomyopathy Questionnaire score, and had differences in medication prescriptions.ConclusionsAdaptResponse is the largest randomized CRT trial and enrolled more women than any other landmark CRT trial. Women differed from men with regard to baseline characteristics and quality of life. Whether these differences translate into clinical outcome differences will be examined further in the AdaptResponse trial.

Transcatheter aortic valve replacement in patients with severe comorbidities: A retrospective cohort study.

To investigate the long-term outcomes of patients with severe comorbidities (sCM) undergoing transcatheter aortic valve replacement (TAVR). The benefit of TAVR may be limited among patients with sCM due to a lack of mortality- or quality-of-life-benefit. All TAVR patients in the Allina Health System between January 1, 2011 and August 7, 2018 were included (n = 890, 82 ± 8 years, 55% men). sCM included: severe lung disease, severe liver disease, end-stage renal disease, severe, severe dementia, severe dilated cardiomyopathy, and frailty. Outcomes between patients with (n = 215, 24%) and without (n = 675, 76%) sCM were compared. At baseline, patients with sCM had worse symptoms, higher STS-PROM and a lower Kansas City Cardiomyopathy Questionnaire (KCCQ) score compared to those without. During a median follow-up of 15 months (IQR, 7-29 months), there were 208 (23%) deaths. Patients with sCM had a lower 3-year survival free from all-cause mortality (40% vs. 79%, p < .001), and lower 3-year survival free from the composite endpoint of all-cause mortality, re-hospitalization for heart failure, myocardial infarction or stroke (31% vs. 64%, p < .001) compared to those without sCM. The estimated monthly increase in KCCQ scores following TAVR was 1.5, 95%CI (1.3, 1.7), p < .001 irrespective of sCM grouping. From Cox regression analysis, severe comorbidities, with the exception of liver disease, were associated with an increased risk of all-cause mortality and any additional comorbidity was associated with a multiplicative increase in risk of mortality of 2.8 (95%CI 2.3, 3.6), p < .001. TAVR patients with sCM have poor 3-year outcomes but may experience improvements in their quality of life.

Health-related quality of life in patients with heart failure eligible for treatment with sacubitril-valsartan.

AimTo describe and compare self‐reported health‐related quality of life between younger and older patients with severe heart failure eligible for treatment with sacubitril–valsartan and to explore the association between health‐related quality of life and age, NYHA classification, systolic blood pressure and NT‐proBNP level.DesignCross‐sectional study.MethodsA total of 59 patients, eligible for treatment with sacubitril–valsartan were consecutively included and divided into a younger (≤75 years) and older group (>75 years). Health‐related quality of life was assessed using the Kansas City Cardiomyopathy Questionnaire and the EuroQol 5‐dimensions. Data were collected between June 2016 and January 2018. The STROBE checklist was used.ResultsThere were no differences in overall health‐related quality of life between the age groups. The older patients reported lower scores in two domains measured with the Kansas City Cardiomyopathy Questionnaire, namely self‐efficacy (67.0 SD 22.1 vs. 78.8 SD 19.7) and physical limitation (75.6 SD 19.0 vs. 86.3 SD 14.4). Higher NYHA class was independently associated with lower Kansas City Cardiomyopathy Questionnaire Overall Summary Score.

Transcatheter Aortic-Valve Replacement with a Balloon-Expandable Valve in Low-Risk Patients

BackgroundAmong patients with aortic stenosis who are at intermediate or high risk for death with surgery, major outcomes are similar with transcatheter aortic-valve replacement (TAVR) and surgical aortic-valve replacement. There is insufficient evidence regarding the comparison of the two procedures in patients who are at low risk.MethodsWe randomly assigned patients with severe aortic stenosis and low surgical risk to undergo either TAVR with transfemoral placement of a balloon-expandable valve or surgery. The primary end point was a composite of death, stroke, or rehospitalization at 1 year. Both noninferiority testing (with a prespecified margin of 6 percentage points) and superiority testing were performed in the as-treated population.ResultsAt 71 centers, 1000 patients underwent randomization. The mean age of the patients was 73 years, and the mean Society of Thoracic Surgeons risk score was 1.9% (with scores ranging from 0 to 100% and higher scores indicating a greater risk of death within 30 days after the procedure). The Kaplan–Meier estimate of the rate of the primary composite end point at 1 year was significantly lower in the TAVR group than in the surgery group (8.5% vs. 15.1%; absolute difference, −6.6 percentage points; 95% confidence interval [CI], −10.8 to −2.5; P<0.001 for noninferiority; hazard ratio, 0.54; 95% CI, 0.37 to 0.79; P=0.001 for superiority). At 30 days, TAVR resulted in a lower rate of stroke than surgery (P=0.02) and in lower rates of death or stroke (P=0.01) and new-onset atrial fibrillation (P<0.001). TAVR also resulted in a shorter index hospitalization than surgery (P<0.001) and in a lower risk of a poor treatment outcome (death or a low Kansas City Cardiomyopathy Questionnaire score) at 30 days (P<0.001). There were no significant between-group differences in major vascular complications, new permanent pacemaker insertions, or moderate or severe paravalvular regurgitation.ConclusionsAmong patients with severe aortic stenosis who were at low surgical risk, the rate of the composite of death, stroke, or rehospitalization at 1 year was significantly lower with TAVR than with surgery. (Funded by Edwards Lifesciences; PARTNER 3 ClinicalTrials.gov number, NCT02675114.)

Which patients with heart failure should receive specialist palliative care?

AimsWe investigated which patients with heart failure (HF) should receive specialist palliative care (SPC) by first creating a definition of need for SPC in patients hospitalised with HF using patient‐reported outcome measures (PROMs) and then testing this definition using the outcome of days alive and out of hospital (DAOH). We also evaluated which baseline variables predicted need for SPC and whether those with this need received SPC.Methods and resultsPROMs assessing quality of life (QoL), symptoms, and mood were administered at baseline and every 4 months. SPC need was defined as persistently severe impairment of any PROM without improvement (or severe impairment immediately preceding death). We then tested whether need for SPC, so defined, was reflected in DAOH, a measure which combines length of stay, days of hospital re‐admission, and days lost due to death. Of 272 patients recruited, 74 (27%) met the definition of SPC needs. These patients lived one third fewer DAOH than those without SPC need (and less than a quarter of QoL‐adjusted DAOH). A Kansas City Cardiomyopathy Questionnaire (KCCQ) summary score of <29 identified patients who subsequently had SPC needs (area under receiver operating characteristic curve 0.78). Twenty‐four per cent of patients with SPC needs actually received SPC (n = 18).ConclusionsA quarter of patients hospitalised with HF had a need for SPC and were identified by a low KCCQ score on admission. Those with SPC need spent many fewer DAOH and their DAOH were of significantly worse quality. Very few patients with SPC needs accessed SPC services.

Abstract 055: Changes in Disease-specific versus Generic Health Status Measures After Left Ventricular Assist Device Implantation: Insights From INTERMACS

Background: The effects of left ventricular assist device (LVAD) therapy on quality of life (QoL) are typically assessed with a combination of heart failure (HF)-specific and generic QoL measures. A generic QoL measure is believed to be necessary to fully capture the QoL effects of LVADs, as non-cardiac factors, such as comorbidities or LVAD complications, may limit generic QoL despite improvement in HF QoL after LVAD. However, the frequency and drivers of this expected discrepancy between HF-specific and generic QoL measures after LVAD implant are not known. Methods: Patients who underwent LVAD implantation as part of the INTERMACS registry from 2012-14 were assessed prior to and 6 months after LVAD with the Kansas City Cardiomyopathy Questionnaire (KCCQ) and EQ-5D Visual Analog Scale (VAS) to measure HF-specific and generic QoL, respectively. Scores range from 0-100, and ~5 points indicates a clinically relevant change for both measures. Changes in scores were standardized by dividing by the standard deviation of the corresponding baseline score and were categorized as: &lt;0 (worsening), 0 to &lt;0.5 (small improvement), 0.5 to &lt;1 (moderate improvement), and ≥1 (large improvement). Discordance was defined as a ≥2-category difference in standardized changes. Among patients who reported improvement in HF-QoL, multivariable logistic regression was used to examine factors associated with KCCQ-VAS discordance. Results: Among 1888 patients, the majority reported improvement in both HF-specific and generic QoL after LVAD, with mean changes in the KCCQ of 32.7 ± 25.0 and in the VAS of 27.6 ± 27.4. Among the 1539 patients (81.5%) with moderate/large improvement in KCCQ, 334 (21.7%) had discordant changes in generic QoL (i.e., VAS did not substantially increase despite improvement in KCCQ). In multivariable modeling, baseline VAS scores were the strongest predictor of future KCCQ-VAS discordance (OR 2.17 per +10 VAS, 95% CI 1.98-2.38). Post-LVAD complications were not associated with discordance. Conclusion: In a multicenter cohort of patients undergoing LVAD implant, most patients had substantial improvements in both CHF-specific and generic QoL. Discordance occurred in only ~1/5 of patients and was primarily observed among patients who reported good generic QoL prior to their LVAD (despite low KCCQ). Contrary to our expectations, non-cardiac comorbidities and LVAD complications were not associated with discordance. These results support the continued use of the KCCQ to monitor QoL before and after LVAD implantation but also highlight potential limitations of the VAS in fully capturing the QoL effects from LVADs.

Current evidence-based therapy does not restore plasma apelin level in phenotypically diverse chronic heart failure patients

Background: Apelin, endogenous peptide acting through its receptor (APJ), is the most potent inotropic agent known to man. Plasma apelin and cardiac APJ mRNA levels rise in early stages of chronic heart failure (CHF) but fall later in decompensated CHF. The effect of current evidence-based management of CHF on plasma apelin level is not known. We estimated change in plasma apelin level in CHF patients of diverse phenotypes treated with standard pharmacotherapy and compared it with the corresponding change in left ventricular ejection fraction (LVEF), plasma brain natriuretic peptide (BNP) level and quality of life (QoL).Methods: With ethical approval and written informed consent, venous blood samples were collected from 39 CHF [dilated cardiomyopathy (DCM) (n=21), restrictive cardiomyopathy (RCM) (n=9) and chronic constrictive pericarditis (CCP) (n=9)] patients and 10 age-matched healthy controls, at baseline and after 12 weeks. Plasma apelin and BNP were estimated by competitive ELISA (RayBiotech Inc.) and an auto-analyzer (Triage, Allere Inc.), respectively. QoL was assessed using Kansas City Cardiomyopathy Questionnaire (KCCQ). Nonparametric tests were applied and p-value &lt;0.05 was considered significant.Results: Low LVEF, KCCQ score and high BNP levels were observed in all CHF patients compared to controls. Plasma apelin level was depressed in RCM and CCP patients compared to controls but not in DCM patients. These parameters did not change in any group after 3 months of standard pharmacotherapy.Conclusions: Current evidence-based management of CHF does not restore the depressed apelin-APJ axis. New drugs are required for specifically modulating this promising therapeutic target in CHF.

Abstract 12580: Does Sex Influence the Effect of Surgical Revascularization in Patients in Ischemic Left Ventricular Dysfunction? Results From the STICH Trial

Introduction: Studies have shown sex-specific differences regarding CAD and heart failure with left ventricular (LV) dysfunction. Whether these differences impact the benefit of CABG in patients with ischemic LV dysfunction has not been studied prospectively. Female sex is conventionally considered a risk factor for open-heart surgery, and has been included as a poor prognostic factor in multiple cardiac operative risk evaluation scores. We investigated the impact of sex on the long-term benefit of CABG in patients enrolled in the prospective Surgical Treatment for Ischemic Heart Failure Study (STICH) trial. Method: The STICH trial randomized 1212 patients [148 (12%) women and 1064 (88%) men] with CAD and EF≤ 35% to medical therapy alone (MED) versus MED plus CABG. Long-term (10-year) outcomes with each treatment were compared according to sex. Results: At baseline, women were older with higher BMI and more CAD risk factors (e.g. diabetes) except for smoking, and had lower rates of prior CABG than men (all p&lt;0.05). Moreover, women had higher NYHA class, lower 6-min walk capacity and lower Kansas City Cardiomyopathy Questionnaire scores (all p&lt;0.05). At 10-year follow up, the all-cause mortality rate (HR 0.70, CI 0.55-0.89, adjusted p=0.002) and CV mortality rate (HR 0.64, CI 0.48-0.86, adjusted p=0.006) were significantly lower in women than men. Furthermore, with randomization to CABG vs. MED treatment, there was no significant interaction between sex and treatment group in all-cause mortality, CV mortality, mortality or CV hospitalization (all p&gt;0.05, Figure 1). In addition, surgical deaths were similar for both sexes among patients randomized to CABG. Conclusion: Sex does not impact the effect of CABG on all-cause mortality, CV mortality, CV hospitalization or surgical deaths in patients with ischemic LV dysfunction. Thus, sex should not influence treatment decisions regarding CABG in these patients.