KCCQ Score Research Articles

Questionable Value of Concomitant Tricuspid Valve Procedure with Left Ventricular Assist Device Implantation

Tricuspid regurgitation (TR) is common in end stage heart failure patients receiving left ventricular assist devices (LVADs), but the value of intervention is uncertain. This study examined the impact of tricuspid valve procedures (TVP) at time of LVAD implantation on clinical outcomes and quality of life metrics. We included patients in the INTERMACS database with TR who received continuous-flow LVADs from the 2008 to 2017. TR was stratified by severity. Patients receiving concomitant TVP were compared to those without intervention in a stratified analysis. Survival analyses and Andersen-Gill hazard models were used to examine associations with clinical outcomes. Our analysis included 8263 (53.1%) mild, 4252 (33.3%) moderate, and 2100 (13.5%) severe TR cases. TVP rate increased with severity: 13.0% of mild cases underwent TVP versus 55.2% of severe cases. TVP was not associated with survival difference for mild (median 57.8 months for TVP vs. 55.6 months for non-TVP, P=0.69, HR 1.10 [95%: 0.87-1.50]), moderate (47.5 vs. 51.1 months, P=0.23, HR 1.20 [0.99-1.50]), or severe TR (43.3 vs 46.3 months, P=0.09, HR 1.30 [0.99-1.60]). TVP was associated with increased risk of bleeding, arrhythmia, stroke, renal failure, and respiratory failure (P<0.01 for each) and not with Kansas City Cardiomyopathy Questionnaire (KCCQ) differences at 12- or 24-months follow-up. TVP at time of LVAD implantation was not associated with differences in survival or KCCQ scores. However, there were associations with increased risk of adverse events. Further studies are needed to understand appropriateness criteria for TVP with LVAD implantation.

4291Six-month outcomes from the multicenter, prospective study with the novel PASCAL transcatheter valve repair system for patients with mitral regurgitation in the CLASP study

Abstract Background Severe mitral regurgitation may lead to an impaired prognosis if left untreated. Transcatheter treatment options have emerged as an alternative to surgery and an adjunct to medical therapy. We report the six-month results of the PASCAL transcatheter valve repair system in treating patients with mitral regurgitation enrolled in the multicenter, prospective, single arm CLASP study. Methods The PASCAL Transcatheter Valve Repair System is a leaflet repair therapy that uses clasps and paddles to place a woven Nitinol spacer between the native valve leaflets to fill the regurgitant orifice via a transseptal approach. Eligible patients had clinically significant MR despite optimal medical therapy and were deemed candidates for transcatheter mitral repair by the local Heart Team. Safety, performance, and clinical outcomes were prospectively assessed at baseline, discharge, 30 days, and 6 months post-procedure. All major adverse events (MAE) were adjudicated by an independent clinical events committee and echocardiographic images were assessed by a core lab. The MAE rate was the primary safety endpoint, defined as the composite of cardiovascular mortality, stroke, MI, new need for renal replacement therapy, severe bleeding, and re-intervention for study device-related complications. Results Between June 2017 and September 2018, 62 patients were enrolled at 14 sites worldwide for transcatheter mitral valve reconstruction using the PASCAL system. The mean age was 76.5 years (62.9% male). All patients had MR grade ≥3+, with 59% functional, 34% degenerative, and 7% mixed etiology, and 51.6% of patients were in NYHA Class III/IV. Successful implantation of the PASCAL device was achieved in 95% of patients. At discharge, 95% of patients had MR grade ≤2+ with 81% grade ≤1+. There was one cardiovascular mortality and the MAE rate was 4.8%. At 30-day follow-up, paired analyses shows that 98% of patients had MR grade ≤2+ with 81% grade ≤1+ and 88% were in NYHA Class I/II (p&lt;0.0001). The 6MWD improved by 38.9 m (p=0.0015) and was accompanied by average improvements in KCCQ and EQ5D scores by 14.1 points (p&lt;0.0001) and 8.3 points (p=0.0028), respectively. The six-month data will be available for presentation. Conclusions In this early device experience, the PASCAL transcatheter valve repair system showed an acceptable safety profile and performed as intended in treating patients with mitral regurgitation. The PASCAL device resulted in significant MR grade reduction, which was associated with clinically and statistically significant improvements in functional status, exercise capacity, and quality of life. Continued follow-up is warranted to validate these initial promising results. Acknowledgement/Funding Edwards Lifesciences

1409Use of phenomapping to determine response of treatment by sacubitril/valsartan in patients with heart failure with reduced ejection fraction

Abstract Background Treatment by sacubitril/valsartan decreases mortality, improves KCCQ score and ejection fraction in patients with heart failure with reduced ejection fraction (HF REF), but there is currently no data to predict response to treatment. Purpose The purpose of our work was to assess whether unbiased clustering analysis, using dense phenotypic data, could identify phenotypically distinct HF-REF subtypes with good or no response after 6 months of sacubitril/valsartan administration. Methods A total of 78 patients in NYHA functional class 2–3 and treated by ACE inhibitor or AAR2, were prospectively assigned to equimolar sacubitril/valsartan replacement. We collected demographic, clinical, biological and imaging continuous variables. Phenotypic domains were imputed with 5 eigenvectors for missing value, then filtered if the Pearson correlation coefficient was &gt;0.6 and standardized to mean±SD of 0±1. Thereafter, we used agglomerative hierarchical clustering for grouping phenotypic variables and patients, then generate a heat map (figure 1). Subsequently, participants were categorized using Penalized Model-Based Clustering. P&lt;0,05 was considered significant. Results Mean age was 60.4±13.4 yo and 79.0% patients were males. Mean ejection fraction was 29.3±7.0%. Overall, 16 phenotypic domains were isolated (figure 1) and 3 phenogroups were identified (Table 1). Phenogroup 1 was remarkable by isolated left ventricular involvement (LVTDD 64.3±5.9mm vs 73.9±8.7 in group 2 and 63.8±5.7 in group3, p&lt;0.001) with moderate diastolic dysfunction (DD), no mitral regurgitation (MR) and no pulmonary hypertension (PH). Phenogroups 2 and 3 corresponded to patients with severe PH (TRMV: 2.93±0.47m/s in group 2 and 3.15±0.61m/s in groupe 3 vs 2.16±0.32m/s in group 1), related to severe DD (phenogroup 2) or MR (phenogroup 3). In both phenogroups, the left atrium was significantly enlarged and the right ventricle was remodeled, compared with phenogroup 1. Despite more severe remodeling and more compromised hemodynamic in phenogroups 2 and 3, the echocardiographic response to sacubitril/valsartan was comparable in all groups with similar improvement of EF and reduction of cardiac chambers dimensions (response of treatment, defined by improvement of FE +15% and/or decreased of indexed left ventricule diastolic volume −15% = group 2: 22 (76%); group 3: 18 (60%); group 1: 9 (50%); p=0.17; OR group 2 vs 1: OR=3.14; IC95% [0.9–11.03]; p=0.074; OR group 3 vs 1: OR=1.5; IC95% [0.46–4.87]; p=0.5)). The clinical response was even better in phenogroups 2 and 3 (Group 2: 19 (66%); group 3: 21 (78%) vs group 1: 9 (50%); p=0.05). Heat map Conclusion HF-REF patients with severe diastolic dysfunction, significant mitral regurgitation and elevated pulmonary hypertension by echocardiographic had similar reverse remodeling but better clinical improvement than patients with isolated left ventricular systolic dysfunction.

Impact of diastolic dysfunction on long-term mortality and quality of life after transcatheter aortic valve replacement.

There is conflicting data as to whether diastolic dysfunction (DD) affects the prognosis of patients with aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). Consecutive patients undergoing TAVR underwent assessment of DD with preoperative echocardiography and NT-pro BNP. Long-term survival was ascertained every 6 months by clinic visits or phone. DD was graded according to the new American Society of Echocardiography recommendations. Health status was assessed at baseline and 30 days post-procedure using the KCCQ-12 questionnaire. Long-term survival was displayed using Kaplan-Meier curves according to NT-pro BNP levels and DD grades. We included 222 patients, mean age 78 (±8) years, median STS score 4 (interquartile range = 3-7), median follow-up time 385 days (IQR = 180-640). DD was absent in 25, Grade I in 13, Grade II in 74, Grade III in 24, and indeterminate in 86 patients. Advanced (Grades II-III) DD was associated with higher pre-procedural NT-pro BNP levels (p < .001), worse quality of life (p < .001) but similar surgical risk (p = .43). Advanced and indeterminate DD were associated with increased long-term mortality (25-28% vs. 5%, p = .02) and elevated NT-pro BNP levels (26.4% vs. 9.8%, p = .05). Improvements in quality of life measures were seen in all DD groups (median change in KCCQ score no or Grade I DD:14 [3-21] vs. Grades II-III DD: 15 [16-26; p = .37]). Preoperative NT-pro BNP levels and echocardiographic indices of indeterminate or advanced DD are associated with increased long-term mortality after TAVR but similar improvements in quality of life.

Effect of Left Atrial Volume on Short Term Outcomes Including Functional Status after Transcatheter Mitral Valve Repair

Background Transcatheter mitral valve repair has been increasingly used in patients with high surgical risk with severe degenerative mitral regurgitation (MR). Increased left atrial volume index (LAVI) has been associated with poor long-term prognosis in these patients. Methods We evaluated 43 consecutive patients undergoing mitral valve repair with MitraClip device (Abbott) from 2015 to 2018. Echocardiographic parameters and Kansas City Cardiomyopathy Questionnaire score (KCCQ - a validated patient reported quality of life measure) were analyzed. Patients were divided into 2 groups with either LAVI 48ml/cm2 (severely enlarged). Results Forty-three patients were evaluated with a mean age of 78. There was no difference in baseline comorbidities between the two groups. There was 95.3% procedural success overall. There was no significant difference in procedural duration, length of stay, residual MR and in-hospital adverse events. KCCQ score at 30 days had improved significantly in both groups but there was no difference in magnitude of improvement among the two groups. There was no difference in overall 30 day readmissions/adverse events including heart failure readmissions in the two groups. Conclusion In this single center study, severely enlarged LAVI was not associated with any significant difference in short term outcomes including functional and quality of life outcomes in patients undergoing valve repair.

Associations of perceived stress and state anger with symptom burden and functional status in patients with heart failure

Background: Psychosocial stress and anger trigger cardiovascular events, but their relationship to heart failure (HF) exacerbations is unclear. We investigated perceived stress and anger associations with HF functional status and symptoms.Methods and Results: In a prospective cohort study (BETRHEART), 144 patients with HF (77% male; 57.5 ± 11.5 years) were evaluated for perceived stress (Perceived Stress Scale; PSS) and state anger (STAXI) at baseline and every 2 weeks for 3 months. Objective functional status (6-min walk test; 6MWT) and health status (Kansas City Cardiomyopathy Questionnaire; KCCQ) were also measured biweekly. Linear mixed model analyses indicated that average PSS and greater than usual increases in PSS were associated with worsened KCCQ scores. Greater than usual increases in PSS were associated with worsened 6MWT. Average anger levels were associated with worsened KCCQ, and increases in anger were associated with worsened 6MWT. Adjusting for PSS, anger associations were no longer statistically significant. Adjusting for anger, PSS associations with KCCQ and 6MWT remained significant.Conclusion: In patients with HF, both perceived stress and anger are associated with poorer functional and health status, but perceived stress is a stronger predictor. Negative effects of anger on HF functional status and health status may partly operate through psychological stress.

Discrepancy between patient-reported quality of life and the prognostic assessment of Japanese patients hospitalized with acute heart failure.

Patient-reported quality of life (PRQL) is a primary therapeutic target for patients with chronic heart failure (HF) and is associated with long-term prognosis. However, its utility in hospitalized HF (HHF) patients in the acute setting remains unclear. We aimed to assess the utility of PRQL (the Kansas City Cardiomyopathy Questionnaire [KCCQ]) in HHF patients and its association with long-term prognosis as well as with the clinical risk score (Get With The Guidelines-Heart Failure [GWTG-HF] risk score). PRQL was evaluated using the KCCQ in consecutive 114 HHF patients. Its association with the composite outcome of all-cause mortality or HF readmission within the first year after discharge was analyzed. Furthermore, its distribution by the clinical risk score (GWTG-HF) was evaluated using Pearson's correlation coefficient. The median KCCQ was 34.9, but was widely distributed (interquartile range 23.7-56.8). After adjustment for known prognostic indicators, the KCCQ was not an independent predictor of the composite outcome within the first year (group with high vs. low KCCQ scores: hazard ratio, 0.67; 95% confidence interval 0.26-1.71). There was no significant correlation between the KCCQ and the GWTG-HF risk score. In conclusion, PRQL during the acute phase of HF was significantly impaired and also varied widely, irrespective of patient characteristics or severity. PRQL assessment and risk prediction for HHF patients in the acute setting seemed to provide two distinct types of information for health care providers.

Digoxin is Associated with Higher Quality of Life in LVAD Recipients

Purpose To examine the effects of digoxin on functional capacity and quality of life as measured by the 6-minute walk test (6MWT) and Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ) in patients receiving the Heartware HVAD system. Methods HVAD patients who remained alive on device support at 6 months from the ADVANCE + CAP, ENDURANCE + Supplemental trials were eligible. Pts were separated by digoxin use: those who were discharged from the index hospitalization on digoxin and remained on digoxin through 6 months (DIG, n=161) and those discharged from the index hospitalization not on digoxin and remained off through 6 months (NO DIG, n=533). Differences in 6MWT and KCCQ were compared between groups at baseline, 6, and 12 months. Adverse events were compared between groups from baseline through 6 months. Results Baseline characteristics were similar: Mean age was 59 years and 23% of patients were female. Serum creatinine was 0.9mg/dL ± 0.7. History of atrial fibrillation was more common in the DIG group (57.8% vs 42.9%, p = 0.001). Compared to the NO DIG group, the DIG group had greater improvements in KCCQ score at 6 months (+ 36.8 vs. + 27.7, p=0.0001) and at 12 months (+35.9 vs +29.5, p=0.01). 6MWT was similar between groups (Table 1). Device malfunction within 6 months was more common in the DIG group [18% (0.42 EPPY) vs 9.2% (0.21 EPPY), p = 0.002]. Rates of other adverse events including 6-month re-hospitalization [47.8% (2.21 EPPY) vs 42.9% (1.8 EPPY), p=0.10] were similar. Conclusion LVAD recipients maintained on chronic digoxin for at least 6 mo had greater improvements in QOL scores compared to those not treated with digoxin despite having higher rates of device malfunction and similar improvements in functional capacity. Prospective study is warranted.

Does heart failure-specific health status identify patients with bothersome symptoms, depression, anxiety, and/or poorer spiritual well-being?

Patients with heart failure often have under-recognized symptoms, depression, anxiety, and poorer spiritual well-being ('QoL domains'). Ideally all patients should have heart failure-specific health status and quality of life (QoL) domains routinely evaluated; however, lack of time and resources are limiting in most clinical settings. Therefore, we aimed to evaluate whether heart failure-specific health status was associated with QoL domains and to identify a score warranting further evaluation of QoL domain deficits. Participants (N = 314) enrolled in the Collaborative Care to Alleviate Symptoms and Adjust to Illness trial completed measures of heart failure-specific health status [Kansas City Cardiomyopathy Questionnaire, KCCQ (score 0-100, 0 = worst health status)], additional symptoms (Memorial Symptom Assessment Scale), depression (Patient Health Questionnaire-9), anxiety (Generalized Anxiety Disorder-7), and spiritual well-being (Facit-Sp) at baseline. Mean ± standard deviation (SD) KCCQ score was 46.9 ± 19.3, mean age was 65.5 ± 11.4, and 79% were male. Prevalence of QoL domain deficits ranged from 11% (nausea) to 47% (depression). Sensitivity/specificity of KCCQ for each QoL domain ranged from 20-40%/80-96% for KCCQ ≤ 25, 61-84%/48-62% for KCCQ ≤ 50, 84-97%/26-40% for KCCQ ≤ 60, and 96-100%/8-13% for KCCQ ≤ 75. Patients with KCCQ ≤ 60 had mean ± SD 4.5 ± 2.5 QoL domain deficits (maximum 12), vs. 1.6 ± 1.6 for KCCQ > 60 (P < 0.001). Similar results were seen for KCCQ ≤25 (6.6 ± 2.4 vs. 3.3 ± 2.4), KCCQ ≤ 50 (4.8 ± 2.6 vs. 2.5 ± 2) and KCCQ ≤ 75 (4.0 ± 2.6 vs. 1.0 ± 1.2) (all P < 00001). KCCQ ≤ 60 had good sensitivity for each QoL domain deficit and for patients with at least one QoL domain deficit. Screening for QoL domain deficits should target patients with lower KCCQ scores based on a clinic's KCCQ score distribution and clinical resources for addressing QoL domain deficits.

Association of Renin-Angiotensin Inhibitor Treatment With Mortality and Heart Failure Readmission in Patients With Transcatheter Aortic Valve Replacement

Data are lacking on the effect of a renin-angiotensin system (RAS) inhibitor prescribed after transcatheter aortic valve replacement (TAVR). Treatment with a RAS inhibitor may reverse left ventricular remodeling and improve function. To investigate the association of prescription of a RAS inhibitor and outcomes after TAVR. Retrospective cohort study of TAVR procedures performed in the United States (using the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapies Registry) between July 2014 and January 2016 that were linked to Medicare claims data (final date of follow-up: March 31, 2017). To account for differences in demographics, echocardiographic findings, and in-hospital complications, 1:1 propensity matching was performed. Initial hospital discharge prescription of a RAS inhibitor after TAVR. Primary outcomes were all-cause death and readmission due to heart failure at 1 year after discharge, which were considered separately. The secondary outcome was health status assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ; score range: 0-100, with a higher score indicating less symptom burden and better quality of life; a small effect size was defined as 5 points) at 1 year. Among 21 312 patients who underwent TAVR at 417 US sites, 8468 patients (39.7%) were prescribed a RAS inhibitor at hospital discharge. After propensity matching, 15 896 patients were included (mean [SD] age, 82.4 [6.8] years; 48.1% were women; mean [SD] left ventricular ejection fraction [LVEF], 51.9% [11.5%]). Patients with a prescription for a RAS inhibitor vs those with no prescription had lower mortality rates at 1 year (12.5% vs 14.9%, respectively; absolute risk difference [ARD], -2.4% [95% CI, -3.5% to -1.4%]; hazard ratio [HR], 0.82 [95% CI, 0.76 to 0.90]) and lower heart failure readmission rates at 1 year (12.0% vs 13.8%; ARD, -1.8% [95% CI, -2.8% to -0.7%]; HR, 0.86 [95% CI, 0.79 to 0.95]). When stratified by LVEF, having a prescription for a RAS inhibitor vs no prescription was associated with lower 1-year mortality among patients with preserved LVEF (11.1% vs 13.9%, respectively; ARD, -2.81% [95% CI, -3.95% to -1.67%]; HR, 0.78 [95% CI, 0.71 to 0.86]), but not among those with reduced LVEF (18.8% vs 19.5%; ARD, -0.68% [95% CI, -3.52% to 2.20%]; HR, 0.95 [95% CI, 0.81 to 1.12]) (P = .04 for interaction). Of 15 896 matched patients, 4837 (30.4%) were included in the KCCQ score analysis and improvements at 1 year were greater in patients with a prescription for a RAS inhibitor vs those with no prescription (median, 33.3 [interquartile range, 14.2 to 51.0] vs 31.3 [interquartile range, 13.5 to 51.1], respectively; difference in improvement, 2.10 [95% CI, 0.10 to 4.06]; P < .001), but the effect size was not clinically meaningful. Among patients who underwent TAVR, receiving a prescription for a RAS inhibitor at hospital discharge compared with no prescription was significantly associated with a lower risk of mortality and heart failure readmission. However, due to potential selection bias, this finding requires further investigation in randomized trials.

Association of Transcatheter Mitral Valve Repair With Quality of Life Outcomes at 30 Days and 1 Year

Improvements in symptoms, functional capacity, and quality of life are among the key goals of edge-to-edge transcatheter mitral valve repair (TMVR) for mitral regurgitation. To examine health status outcomes among patients undergoing TMVR in clinical practice and the factors associated with improvement. This cohort study used the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry, which contains data on patients with severe mitral regurgitation treated with TMVR from 2013 through 2017 in 217 US hospitals. Change in disease-specific health status (Kansas City Cardiomyopathy Questionnaire-Overall Summary score [KCCQ-OS]; range 0-100 points, with higher scores indicating better health status) at 30 days and 1 year after TMVR. We also examined factors associated with health status at 30 days after TMVR, by means of multivariable linear regression using a generalized estimating equations approach to account for clustering of patients within sites. The KCCQ data were available in 81.2% at baseline, 69.3% of survivors at 30 days, and 47.4% of survivors at 1 year. Among 4226 patients who underwent TMVR, survived 30 days, and completed the KCCQ at baseline and follow-up, the KCCQ-OS increased from 41.9 before TMVR to 66.7 at 30 days (mean change 24.8 [95% CI, 24.0-25.6] points; P < .001), representing a large clinical improvement. The KCCQ scores remained stable from 30 days to 1 year after TMVR, with no further significant increase or decline. On multivariable analysis, atrial fibrillation (-2.2 [95% CI, -3.7 to -0.6] points; P = .01), permanent pacemaker (-2.1 [95% CI, -3.7 to -0.4] points; P = .01), severe lung disease (-3.9 [95% CI, -6.2 to -1.5] points; P = .001), home oxygen (-2.7 [95% CI, -4.9 to -0.4] points; P = .02), and lower KCCQ scores at baseline (3.9 points for each 10-point increase [95% CI, 3.6-4.2]; P < .001) were independently associated with lower 30-day KCCQ-OS scores. In-hospital renal failure was uncommon but was also associated with significant reductions in 30-day KCCQ-OS scores (-7.3 [95% CI -13.3 to -1.2] points). In estimates calculated with inverse probability weighting, after 1 year after TMVR, 54.2% (95% CI 52.2%-56.1%) of patients were alive and well; 23.0% had died, 21.9% had persistently poor health status (KCCQ-OS <60 points), 5.5% had a health status decline from baseline, and 4.6% had both poor health status and health status decline. In a national cohort of US patients undergoing edge-to-edge TMVR in clinical practice, health status was impaired prior to the procedure, improved within 30 days, and remained stable through 1 year among surviving patients with available data. While long-term mortality remains high, most surviving patients demonstrate improvements in symptoms, functional status, and quality of life, with only modest differences by patient-level factors.

Percutaneous Repair for Recurrent Mitral Regurgitation After Surgical Repair: A Mitraclip Experience

ABSTRACTBackground: The aim of our study was to evaluate the acute feasibility and short-term efficacy of mitral valve repair using the MitraClip device in patients with prior surgical repair. Mitral regurgitation (MR) may recur after surgical repair. Because reoperation is associated with significant mortality and morbidity, a transcatheter approach appears appealing.Methods: Between April 2015 and December 2016, 12 patients with MR after a previous surgical repair underwent the MitraClip procedure. Procedural details, intraoperative echocardiographic features, and baseline and 30-day clinical follow-up data were analyzed and compared to those of patients undergoing MitraClip therapy with no prior surgical repair (n = 54) within the same timeframe.Results: Past medical history, MR severity, and NYHA class did not differ between the two groups. A MitraClip was deployed in all 12 patients in the surgical repair (SR) group and in 51 patients in the no surgical repair (NR) group. Induction of mitral stenosis precluding final device deployment occurred in one and two cases, respectively. The procedure was associated with successful reduction of MR to ≤ moderate in all SR patients and in 47 (96%) NR patients. Total procedural time, fluoroscopy time, time from transseptal access to first MitraClip release, and final diastolic gradients were not different between the groups. Clinical outcomes—NYHA class and KCCQ scores—were not different at 30 days.Conclusions: In selected patients with recurrent MR after surgical repair, the MitraClip procedure is feasible and effective without significant increase in procedural time, fluoroscopy time, diastolic mitral gradient compared to MitraClip therapy in patients without prior surgical repair.

183 - AWAKE-HF: Rationale and Design of a Study Using a Wearable Biosensor to Objectively Evaluate the Effect of Sacubitril/Valsartan Initiation on Measures of Physical Activity, Symptoms, and Sleep, as Health-Related Quality of Life Functions in Subjects with Heart Failure

Background: Clinical experience suggests that patients with heart failure with reduced ejection fraction (HFrEF) report improved health-related quality of life (HRQoL) shortly after beginning sacubitril/valsartan (S/V). This study explores early changes in objective HRQoL measures (physical activity, sleep) in HFrEF subjects initiating S/V versus enalapril. Methods: AWAKE-HF is a prospective, multicenter, double-blind, randomized trial assessing physical activity during waking and sleeping hours, subjective sleep quality, and HRQoL of approximately 140 HFrEF subjects (LVEF ≤40%, NYHA functional class II-III) in their unrestricted home environment. The 18-week study consists of 3 phases: a 2-week baseline phase during which subjects continue current HF therapy, an 8-week blinded treatment phase (1:1 S/V vs enalapril, uptitrated to target doses), and an 8-week S/V open-label (OL) extension phase. Subjects will wear a wrist-worn actigraphy device continuously during five 7-day assessment periods: baseline phase (2nd week), blinded treatment phase (1st and 8th weeks) and the OL extension (1st and 8th weeks). During each assessment period, subjects also will complete a daily symptom assessment tool and a sleep questionnaire (e-diary), reporting every 24 hours. KCCQ assessments and a home sleep test will be taken during the baseline phase and prior to the end of the randomized and OL phases. The difference between mean activity counts (baseline vs blinded treatment phase) during the most active 30 minutes of the subject's waking hours and mean activity during sleep will be the primary and key secondary endpoints. Additional endpoints include relationships between the initiation of study treatment and various activity measurements, activity temporal distribution, KCCQ scores, sleep disturbances, and apnea-hypopnea index (AHI) during different study periods. Conclusion: AWAKE-HF is an evaluation of the early impact of S/V treatment on HRQoL in the home environment in HFrEF subjects. Clinical implications: The AWAKE-HF study will objectively assess the impact of sacubitril/valsartan treatment initiation vs enalapril on health related quality of life in subjects with HFrEF. This may provide insight and perspective into the early real-world clinical experience with sacubitril/valsartan.

319 - Improvements in Cardiac Biomarkers are Associated with Better Health-Related Quality of Life in Patients with Light Chain Amyloidosis

Introduction: Light chain (AL) amyloidosis is a rare, complex disease associated with significant morbidity and mortality. B-type natriuretic peptide (BNP) or N-terminal proB-type natriuretic peptide (NT-proBNP) is used to monitor disease progression and response to treatment among patients with cardiac involvement from AL amyloidosis. The relationships between these cardiac biomarkers and health-related quality of life (HRQoL) are poorly understood in this condition. Hypothesis: Patterns of HRQoL in patients with cardiac AL amyloidosis will differ significantly by changes in BNP or NT-proBNP. Methods: We obtained cardiac biomarker and HRQoL data from patients with AL amyloidosis from two data sources. A subsample of patients with cardiac involvement was drawn from a community-based study of AL amyloidosis patients (n = 108). HRQoL scores (based on the SF-36® Health Survey [SF-36] and the Kansas City Cardiomyopathy Short Form [KCCQ-12]) were examined by patients with and without a history of ≥30% decrease in NT-proBNP. Bivariate analyses were conducted using analysis of variance. HRQoL scores were reported relative to existing benchmarks, including: 1) mean SF-36 scores from both a general population sample and patients with congestive heart failure (CHF); and 2) mean KCCQ scores according to New York Heart Association (NYHA) functional classes. Analysis of variance was used to compare SF-36 scores to age- and sex- adjusted benchmarks. Data were obtained from a subsample of patients with AL amyloidosis seen at the Amyloidosis Center at Boston University between 1994 and 2014 who had pre- and post- assessments (n = 95). Associations between changes in HRQoL and changes in BNP were assessed longitudinally with generalized linear models that controlled for baseline HRQoL scores. Results: In the community-based sample, HRQoL scores differed significantly by NT-proBNP response for all SF-36 and KCCQ scales and summary scores (P < .05 for all) (Fig. 1). Patients without a NT-proBNP response had SF-36 scores that were comparable to CHF benchmarks. Longitudinal analyses based on BNP further supported associations between changes in cardiac biomarkers and changes in HRQoL. Conclusions: Although these cardiac biomarkers have been clinically validated as surrogate treatment measures for survival in AL amyloidosis, these data further support that they may also be useful surrogates for clinical measures such as HRQoL and NYHA status.

Multinational and multiethnic variations in health-related quality of life in patients with chronic heart failure

Assessing health-related quality of life (HRQoL) in patients with heart failure (HF) is an important goal of clinical care and HF research. We sought to investigate ethnic differences in perceived HRQoL and its association with mortality among patients with HF and left ventricular ejection fraction ≤35%, controlling for demographic characteristics and HF severity. We compared 5697 chronic HF patients of Indian (26%), white (23%), Chinese (17%), Japanese/Koreans (12%), black (12%), and Malay (10%) ethnicities from the HF-ACTION and ASIAN-HF multinational studies using the Kansas City Cardiomyopathy Questionnaire (KCCQ; range 0-100; higher scores reflect better health status). KCCQ scores were lowest in Malay (58±22) and Chinese (60±23), intermediate in black (64±21) and Indian (65±23), and highest in white (67±20) and Japanese or Korean patients (67±22) after adjusting for age, sex, educational status, HF severity, and risk factors. Self-efficacy, which measures confidence in the ability to manage symptoms, was lower in all Asian ethnicities (especially Japanese/Koreans [60±26], Malay [66±23], and Chinese [64±28]) compared to black (80±21) and white (82±19) patients, even after multivariable adjustment (P<.001). In all ethnicities, KCCQ strongly predicted 1-year mortality (HR 0.45, 95% CI 0.30-0.67 for highest vs lowest quintile of KCCQ; P for interaction by ethnicity .101). Overall, HRQoL is inversely and independently related to mortality in chronic HF but is not modified by ethnicity. Nevertheless, ethnic differences exist independent of HF severity and comorbidities. These data may have important implications for future global clinical HF trials that use patient-reported outcomes as endpoints.

Effect of Oral Iron Repletion on Exercise Capacity in Patients With Heart Failure With Reduced Ejection Fraction and Iron Deficiency

Iron deficiency is present in approximately 50% of patients with heart failure with reduced left ventricular ejection fraction (HFrEF) and is an independent predictor of reduced functional capacity and mortality. However, the efficacy of inexpensive readily available oral iron supplementation in heart failure is unknown. To test whether therapy with oral iron improves peak exercise capacity in patients with HFrEF and iron deficiency. Phase 2, double-blind, placebo-controlled randomized clinical trial of patients with HFrEF (<40%) and iron deficiency, defined as a serum ferritin level of 15 to 100 ng/mL or a serum ferritin level of 101 to 299 ng/mL with transferrin saturation of less than 20%. Participants were enrolled between September 2014 and November 2015 at 23 US sites. Oral iron polysaccharide (n = 111) or placebo (n = 114), 150 mg twice daily for 16 weeks. The primary end point was a change in peak oxygen uptake (V̇o2) from baseline to 16 weeks. Secondary end points were change in 6-minute walk distance, plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, and health status as assessed by Kansas City Cardiomyopathy Questionnaire (KCCQ, range 0-100, higher scores reflect better quality of life). Among 225 randomized participants (median age, 63 years; 36% women) 203 completed the study. The median baseline peak V̇o2 was 1196 mL/min (interquartile range [IQR], 887-1448 mL/min) in the oral iron group and 1167 mL/min (IQR, 887-1449 mL/min) in the placebo group. The primary end point, change in peak V̇o2 at 16 weeks, did not significantly differ between the oral iron and placebo groups (+23 mL/min vs -2 mL/min; difference, 21 mL/min [95% CI, -34 to +76 mL/min]; P = .46). Similarly, at 16 weeks, there were no significant differences between treatment groups in changes in 6-minute walk distance (-13 m; 95% CI, -32 to 6 m), NT-proBNP levels (159; 95% CI, -280 to 599 pg/mL), or KCCQ score (1; 95% CI, -2.4 to 4.4), all P > .05. Among participants with HFrEF with iron deficiency, high-dose oral iron did not improve exercise capacity over 16 weeks. These results do not support use of oral iron supplementation in patients with HFrEF. clinicaltrials.gov Identifier: NCT02188784.

Burdensome Physical and Depressive Symptoms Predict Heart Failure–Specific Health Status Over One Year

ContextHeart failure (HF)-specific health status (symptom burden, functional status, and health-related quality of life) is an important patient-reported outcome that is associated with palliative care needs, hospitalizations, and death. ObjectivesTo identify potentially modifiable patient-reported factors that predict HF-specific health status over one year. MethodsThis was a prospective cohort study using data from the Patient-Centered Disease Management trial. Participants were identified using population-based sampling of all patients with an HF diagnosis at four VA Medical Centers. Patients were enrolled with reduced HF-specific health status (i.e., significant HF symptoms, limited functional status, and poor quality of life, defined by a Kansas City Cardiomyopathy Questionnaire [KCCQ] score <60). Patient-reported factors at baseline were chest pain, other noncardiac pain, dry mouth, numbness/tingling, constipation, nausea, cough, dizziness, depressive symptoms (Patient Health Questionnaire–9), and spiritual well-being (validated, single-item measure). Patients reported HF-specific health status (KCCQ) at 3, 6, and 12 months. ResultsOf 384 U.S. veterans, 42% screened positive for depression and 76% described burdensome physical symptoms at baseline. In bivariate analyses, all patient-reported factors were correlated with KCCQ score over one year. Multivariable mixed-effect modeling showed that baseline chest pain, numbness/tingling, depressive symptoms, and higher comorbidity count predicted HF-specific health status over the following year. ConclusionBurdensome physical and depressive symptoms independently predicted subsequent HF-specific health status in patients with symptomatic HF. Whether addressing these aspects of the patient experience can improve health status and well-being in symptomatic HF should be studied further.

Abstract 17912: Health-related Quality of Life Outcomes in PARADIGM-HF

Introduction: Heart failure with reduced ejection fraction (HF) patients have impaired health-related quality of life (HRQL) with variable responses to therapies that target mortality and HF hospitalizations. In PARADIGM-HF, LCZ696 reduced morbidity and mortality compared with enalapril. Prior analysis demonstrated a significant difference in 8-month Kansas City Cardiomyopathy-Clinical Summary score (KCCQ-CSS) when imputing 0 for death (-2.99 vs. -4.63, p=0.0014). Given improvements in mortality with LCZ696, this analysis provides impact of therapy on all domains of HRQL in survivors only. Hypothesis: LCZ696 will improve HRQL Methods: Patients (after run-in phase) completed disease-specific KCCQ at randomization, 4 month, 8 month, and annual visits. Changes in KCCQ scores were calculated using repeated measures ANCOVA model adjusting for treatment, region, &amp; baseline values (primary efficacy pre-specified at 8 months), and association of KCCQ with mortality was assessed. Results: Among 8442 patients enrolled in PARADIGM-HF, 7623 (90%) completed KCCQ scores at randomization with complete data at 8 months on 7281 (86%). Baseline KCCQ scores were similar in LCZ696 and enalapril groups (73.5±20 vs. 72.3±19). Death increased with every 10 point decrement of baseline KCCQ-CSS [HR 1.11 (1.09, 1.14)]. At 8 months, LCZ696 group noted improvements in both KCCQ-CSS (+0.61 vs. -0.28, p=0.010) and KCCQ-Overall summary score (+1.10 vs. -0.15, p&lt;0.001) in comparison to enalapril group with consistent trends in most KCCQ domains (Table). Adjusted change scores demonstrated consistent improvements in LCZ696 compared with enalapril through 36 months. Conclusions: Disease-specific HRQL is associated with survival. Changes in HRQL were better in patients treated with LCZ696 compared with enalapril with consistency in most domains. These findings suggest that LCZ696 leads to better HRQL in addition to morbidity &amp; mortality in HF-reduced ejection fraction patients.

Volumetric Response beyond Six Months of Cardiac Resynchronization Therapy and Clinical Outcome.

AimsResponse to cardiac resynchronization therapy (CRT) is often assessed six months after implantation. Our objective was to assess the number of patients changing from responder to non-responder between six and 14 months, so-called late non-responders, and compare them to patients who were responder both at six and 14 months, so-called stable responders. Furthermore, we assessed predictive values of six and 14-month response concerning clinical outcome.Methods105 patients eligible for CRT were enrolled. Clinical, laboratory, ECG, and echocardiographic parameters and patient-reported health status (Kansas City Cardiomyopathy Questionnaire [KCCQ]) were assessed before, and six and 14 months after implantation. Response was defined as ≥15% LVESV decrease as compared to baseline. Major adverse cardiac events (MACE) were registered until 24 months after implantation. Predictive values of six and 14-month response for MACE were examined.ResultsIn total, 75 (71%) patients were six-month responders of which 12 (16%) patients became late non-responder. At baseline, late non-responders more often had ischemic cardiomyopathy and atrial fibrillation, higher BNP and less dyssynchrony compared to stable responders. At six months, late non-responders showed significantly less LVESV decrease, and higher creatinine levels. Mean KCCQ scores of late non-responders were lower than those of stable responders at every time point, with the difference being significant at 14 months. The 14 months response was a better predictor of MACE than six months response.ConclusionsThe assessment of treatment outcomes after six months of CRT could be premature and response rates beyond might better correlate to long-term clinical outcome.

Abstract 225: Frequency and Assessment of Poor Global Outcome in Patients with Left Ventricular Assist Devices

Background: Left ventricular assist device (LVAD) therapy can improve survival and quality of life in advanced heart failure (HF), but some patients may still do poorly after LVAD. Understanding the likelihood of experiencing poorer outcomes after LVAD can better inform patients and calibrate their expectations. Methods: We analyzed patients receiving LVAD therapy from January 2012 to October 2013 at a single, high-volume, high-acuity center. We defined a poor global outcome at 1 year after LVAD as the occurrence of death, disabling stroke (precluding transplant), poor patient-reported health status (most recent KCCQ at 3, 6, or 12 months &lt; 45, corresponding to NYHA class IV), or recurrent HF (≥2 HF readmissions post-implant). We compared characteristics of those with and without poor global outcome. Results: Among 164 LVAD recipients who had 1-year outcomes data, mean age was 56, 76.7% were white, 20.9% were female, and 85.9% were INTERMACS Profile 1 or 2 (cardiogenic shock or declining despite inotropes). Poor global outcome occurred in 58 (35.4%) patients at 1 year, of whom 37 (63.8%) died, 17 (29.3%) had a most recent KCCQ score &lt; 45, 3 (5.2%) had ≥2 HF readmissions, and 1 (1.7%) had a disabling stroke (Figure). Eight of the patients who died also experienced one of the three other poor outcomes prior to death. Patients who experienced a poor global outcome were more likely to be designated for destination therapy (46.4% vs. 23.6%, p=0.01) than bridge to transplant, have longer index admissions (median [IQR]: 39 [24, 57] days vs. 25 [18, 35] days, p=0.003), and have major GI bleeding (44.2% vs. 27.7%, p=0.056), and were less likely to undergo LVAD exchange (0% vs. 12.3%, p=0.004). Conclusion: In this large, single-center study assessing global outcome after LVAD implantation, we found that about a third of all patients had experienced a poor global outcome at 1 year. While LVAD therapy remains life-saving and the standard of care for many patients with advanced heart failure, these findings could help guide discussions with eligible patients and families. Future work should compare patients’ pre-LVAD expectations with likely outcomes and create risk models to estimate the probability of poorer outcomes for individual patients using pre-procedural factors.