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Background: Heart failure (HF) with improved ejection fraction (HFiEF) is defined as a new subset in addition to the subsets of HF with reduced EF (≤40%; HFrEF) and HF with preserved EF (>40%). The characteristics and outcomes of patients with ischemic HFiEF after coronary revascularization are unknown. Methods and Results: We identified 1,816 patients with coronary artery diseases and reduced EF (≤40%) in a large hospital in China, who underwent either coronary artery bypass graft surgery (n=1,126) or percutaneous coronary intervention with drug eluting stent (n=687) from January 2005 to December 2014. All patients had EF reassessment during follow-up. The improvement of EF peaked at 3 months and persisted for more than one year after revascularization. Thus, 589 patients who had EF reassessment between 3 to 12 months after revascularization were included in the definitions of HFiEF and HFrEF patient cohort and subsequent survival analysis. 367 (62.3%) patients had EF >40% which constituted HFiEF cohort while 222 (37.7%) patients with EF≤40% constituted HFrEF cohort. Using stepwise logistic regression, we identified preoperative EF (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.02-1.11; P =0.006), left ventricular end-systolic diameter (OR, 0.93; 95% CI, 0.91-0.95; P =0.000) and history of myocardial infarction (OR, 0.61; 95% CI, 0.42-0.88; P =0.008) were associated with being in HFiEF group. Using Cox proportional hazard models, HFiEF patients had lower risk of all-cause mortality (hazard ratios [HR], 0.39; 95% CI, 0.23-0.68; P =0.001), sudden cardiac death (HR, 0.32; 95% CI, 0.14-0.75; P =0.009) and death due to HF (HR, 0.13; 95% CI, 0.03-0.52; P =0.004) compared to HFrEF patients. Nonproportional outcome of composite end points (i.e., combination of all-cause mortality, HF hospitalization and repeat revascularization) between HFiEF and HFrEF groups was detected by using the Schoenfeld residuals. By using flexible parametric model, patients with HFiEF had similar risk of composite end points in the first 5 years (HR, 0.84; 95% CI, 0.53-1.31; P =0.433), but significantly lower risk during years 6 to 11(HR, 0.12; 95% CI, 0.03-0.56; P =0.007). In the HFiEF group, the risk of death were age (HR, 1.07; 95% CI, 1.02-1.12; P =0.008), current smoking (HR, 5.62; 95% CI, 1.93-18.18; P =0.002) and history of myocardial infarction (HR, 2.89; 95% CI, 1.05-7.93; P =0.039). By contrast, in the HFrEF group, the risk factors were moderate or severe mitral regurgitation (HR, 1.81; 95% CI, 1.06-3.11; P =0.031) and estimated glomerular filtration rate (HR, 0.97; 95% CI, 0.95-0.99; P=0.014). Conclusions: Patients with ischemic HFiEF have distinct clinical characteristics and favorable outcomes. Our data support HFiEF as a distinct HF category in ischemic HF patients after revascularization therapy.

Introduction: Some patients with heart failure (HF) will go on to develop advanced HF, characterized by severe HF symptoms despite attempts to optimize medical therapy. Our understanding of advanced HF at a population level remains limited. The goals of this study were to determine the risk of developing advanced HF in patients with newly diagnosed HF, identify risk factors for developing advanced HF, and evaluate the impact of advanced HF on outcomes. Methods: This was a population-based, retrospective cohort study of Olmsted County, Minnesota residents with a new clinical diagnosis of HF between 2007-2017. The primary outcome was development of advanced HF, defined using the 2018 European Society of Cardiology Criteria. Risk factors for development of advanced HF from the time of incident HF diagnosis were examined using cause-specific Cox proportional hazard regression models. The associations of development of advanced HF with risks of hospitalization and mortality were examined using Andersen-Gill and Cox models, respectively, with advanced HF treated as a time dependent covariate. Results: There were 4597 residents with incident HF from 2007 to 2017. The cumulative incidence of advanced HF was 6.0%, 9.1%, and 11.5% at 2, 4, and 6 years after incident HF diagnosis. Characteristics independently associated with development of advanced HF included older age, male sex, diabetes, chronic obstructive pulmonary disease, peripheral vascular disease, lower serum sodium, worse right ventricular function, left atrial enlargement, higher estimated filling pressures, and higher right ventricular systolic pressure (p<0.05 for each). Development of advanced HF was associated with increased risks of all-cause hospitalization (adjusted HR 3.00; 95% CI 2.65-3.41, p<0.001), HF hospitalization (HR 10.24, 95% CI 8.67-12.10), all-cause mortality (HR 5.00, 95% CI 4.46-5.59, p<0.001), and cardiovascular mortality (HR 7.84, 95% CI 6.74-9.12). Conclusions: In this population-based study, clinical, laboratory and echocardiographic characteristics at the time of incident HF diagnosis were associated with future risk of advanced HF. Development of advanced HF was associated with markedly increased morbidity and mortality.

Introduction: Guideline-directed medical therapy (GDMT) dramatically improves outcomes in heart failure with reduced ejection fraction (HFrEF). Our goal was to examine GDMT use in community patients with newly diagnosed HFrEF. Methods: We performed a population-based, retrospective cohort study of all Olmsted County, Minnesota residents with newly diagnosed HFrEF (EF≤40%) 2007-2017. We excluded patients with contraindications to medication initiation (allergy, intolerance, heart rate<50 for beta blockers, SBP <80mm Hg for beta blockers, ACEi/ARB/ARNI; high creatinine (>3 mg/dL ACEi/ARB/ARNI, >2.5 men or >2.0 mg/dL women for mineralocorticoid receptor antagonists, MRAs) or hyperkalemia (potassium >5 meQ/L for ACEi/ARB/ARNI, MRA). We examined use and peak dose achieved for beta blockers, HF beta blockers (metoprolol succinate, carvedilol, bisoprolol), ACEi/ARB/ARNI, and MRA in the first year after HFrEF diagnosis. We used logistic regression to evaluate predictors of GDMT use. Results: From 2007-2017, 1160 patients were diagnosed with HFrEF (mean age 69.7 years, 65.6% men). Most eligible patients received beta blockers (92.1%) and ACEi/ARB/ARNI (86.5%) in the first year after HFrEF. However, only 63.6% of patients were treated with a HF beta blocker, and most did not receive MRAs (82.6%). The percentage of treated patients reaching medication target doses was 20.5% for HF beta blockers, 25.3% for ACEi/ARB/ARNI, and 11.2% for MRA. Compared to patients not seen in an HF clinic, patients seen in an HF clinic (n=380, 32.8%) were at greater odds of receiving beta blockers (OR 3.85, 95% CI 1.79-8.33); HF beta blockers (OR 3.85, 95% CI 2.63-5.26); ACEi/ARB/ARNIs (OR 3.85, 95% CI 2.17-6.67); and MRAs (OR 3.03, 95% CI 2.08-4.35). Other independent predictors of GDMT use included younger age (beta blockers, ACEi/ARB/ARNI), male gender (MRAs), higher SBP (beta blockers, ACEi/ARB/ARNI), lower EF (HF beta blockers), higher BMI (MRAs), and diabetes (ACEi/ARB/ARNI, p<0.05 for each). Conclusions: In this population-based study, most patients with newly diagnosed HFrEF received beta blockers and ACEi/ARB/ARNIs, but goal doses were usually not achieved. GDMT use was much higher in patients referred to an HF clinic.

Introduction: Advanced or “Stage D” heart failure (Adv HF) patients are at high risk of poor outcomes. However, recognition of Adv HF is limited as diagnostic criteria are complex. Administrative algorithms to identify Adv HF could enable better understanding of who has advanced HF and lead to enhanced therapeutics development, dissemination, and outcomes. Methods: In a population-based cohort of all Olmsted County, Minnesota residents with ≥1 HF billing code 2007-2017 (n=9881), we identified all patients with Adv HF (n=753) by applying the gold standard European Society of Cardiology Adv HF criteria via manual medical review by a HF cardiologist. The Adv HF index date was the date the patient first met all ESC criteria. We then developed candidate algorithms to identify Adv HF using only administrative data (billing codes and HF prescriptions or comorbidities known to affect HF outcomes), applied them to the entire HF cohort and assessed their ability to identify patients with Adv HF on or after their Adv HF index date. Results: A single hospitalization (Hsp) for HF or ventricular arrhythmias (VA, 2007-2017) identified all patients with Adv HF (sensitivity 100%), but the PPV was low (36.4%). Requiring more Hsp, other signs of Adv HF such as hyponatremia, acute kidney injury, hypotension or high-dose diuretic use decreased the sensitivity but improved specificity and PPV. As Adv HF was relatively uncommon, negative predictive values (NPV) were high regardless of algorithm characteristics. Conclusions: Algorithms using administrative data can identify patients with Adv HF with clinically useful accuracy.

Introduction: Various risk models have been used to predict mortality after implantation of continuous-flow ventricular assist devices (CF-VADs). Discriminatory power and predictive accuracy vary, and there is a need to develop and validate a contemporary risk score in a large multicenter patient cohort. Hypothesis: We sought to develop an early mortality risk score utilizing a large voluntary research registry of patients implanted with CF-VADs, with the focus on increased discriminatory power. Methods: From May 2004 to May 2015, 1150 patients in the Mechanical Circulatory Support Research Network (MCSRN) registry were randomly divided into equal-sized derivation and validation samples (n=575, each group). Candidate predictors from the derivation sample were subjected to backward stepwise logistic regression until the model with lowest Akaike information criterion value was identified for predicting 90-day mortality. A risk score was developed based on the variables and their respective regression coefficients in the final model. Discriminatory power of the risk score was evaluated using receiver operating characteristic analysis, and calibration was assessed using Hosmer-Lemeshow goodness of fit test. Results: Overall 90-day mortality was 9.4% (n=99). The final logistic regression model consisted of 9 predictors: Age at implant, preoperative mechanical ventilation, serum total bilirubin, hemoglobin, tricuspid valve regurgitation severity, left ventricular end-diastolic diameter, cardiac index, pulmonary capillary wedge pressure, and destination therapy (DT) as an indication for pump placement. The area under the curve was 0.86 in the derivation sample (95% CI, 0.75-0.97) and 0.75 in the validation sample (95% CI, 0.63-0.86). Hosmer-Lemeshow goodness of fit test yielded insignificant values in both samples (p=0.75, p=0.58) consistent with good calibration. Conclusions: The proposed 90-day mortality MCSRN risk score provides highest-to-date discriminatory power when compared to already published models. The risk score is applicable to a contemporary large cohort of patients implanted with CF-VADs for either indication (bridge or DT).

Background The epidemiology of ventricular arrhythmias (VAs) in patients with advanced heart failure (HF) is not well defined. Methods and Results Residents of Olmsted County, Minnesota, with advanced HF from 2007 to 2017 were identified using the 2018 European Society of Cardiology criteria. Billing codes were used to capture VAs; severe VAs requiring emergency care were defined as events associated with emergency department visits or hospitalizations. The cumulative incidence of VAs postadvanced HF was estimated with the Kaplan–Meier method. Multivariable Cox analyses were used to determine the following: (1) Predictors of severe VAs postadvanced HF; and (2) Impact of severe VAs on mortality. Of 936 patients with advanced HF, 261 (27.9%) had a history of VA. The 1‐year cumulative incidence of severe VAs postadvanced HF was 5.4%. Prior VAs (hazard ratio [HR] 2.22 [95% CI, 1.26–3.89], P =0.006) and left ventricular ejection fraction <40% (HR, 3.79 [95% CI, 1.72–8.39], P <0.001) were independently associated with increased severe VA risk postadvanced HF. New‐onset severe VAs were associated with increased mortality (HR, 4.41 [95% CI, 2.80–6.94]; P <0.001), whereas severe VAs in patients with prior VAs had no significant association with mortality risk (HR, 1.08 [95% CI, 0.65–1.78]; P =0.77). Severe VAs were associated with increased mortality in patients without implantable cardioverter defibrillators (HR, 4.89 [95% CI, 2.89–8.26]; P <0.001), but not in patients with implantable cardioverter defibrillators (HR, 1.42 [95% CI, 0.92–2.19]; P =0.11). Conclusions Patients with left ventricular ejection fraction <40% and prior VAs have increased risk of severe VA postadvanced HF. New‐onset severe VAs or severe VAs without implantable cardioverter defibrillators postadvanced HF are associated with increased mortality.

Background: The Kansas City Cardiomyopathy Questionnaire (KCCQ) has been psychometrically evaluated in multiple heart failure (HF) populations, but the comparability of its psychometric properties between men and women is unknown. Methods: Data from 3 clinical trials (1 in stable HF with preserved ejection fraction, 1 each in stable and acute HF with reduced ejection fraction) and 1 prospective cohort study (stable HF with reduced ejection fraction), incorporating 6773 men and 3612 women with HF, were used to compare the construct validity, internal and test-retest reliability, ability to detect change, predict mortality and hospitalizations and minimally important differences between the 2 sexes. Interactions of the KCCQ overall summary and subdomain scores by sex were independently examined. Results: The KCCQ-Overall Summary score correlated well with New York Heart Association functional class in both sexes across patients with stable (correlation coefficient: −0.40 in men versus −0.49 in women) and acute (−0.37 in men versus −0.34 in women) HF. All KCCQ subdomains demonstrated concordant relationships with relevant comparison standards with no significant interactions by sex in 19 of 21 of these construct validity analyses. All KCCQ scores were equally predictive and other psychometric evaluations showed similar results by sex: test-retest reliability (intraclass correlation coefficient 0.94 in men versus 0.92 in women), responsive to change (standardized response mean 1.01 in both sexes), as were the minimally important differences and internal reliability. Conclusions: The psychometric properties of the KCCQ, in terms of validity, prognosis, reliability, and sensitivity to change, are comparable in men and women with HF with preserved ejection fraction and HF with reduced ejection fraction.

Background: Left ventricular assist devices as destination therapy (DT-LVAD) have been shown to decrease mortality compared with medical management, and can improve quality of life for many patients with advanced heart failure. However, while most patients live longer with DT-LVAD than they would have with medical therapy, deaths still occur. We sought to systematically examine the end-of-life care of patients who died with a DT-LVAD at a single center. Methods: All patients undergoing DT-LVAD at the Mayo Clinic in Rochester, Minnesota from January 1, 2007 through September 30, 2014 who subsequently died prior to July 1, 2015 were included. The cause of death was determined based on review of documentation in the electronic medical record, including autopsy reports, death certificates and clinical notes. Details about palliative care consultations, hospice enrollment, hospitalizations, and device deactivation at the end-of-life were obtained from the electronic medical record. Results: Of 89 patients that died with a DT-LVAD (84 HeartMate II, 3 HeartWare, 2 Heartmate XVE, mean age at death 66.1 years), the mean (standard deviation) time from LVAD implantation to death was 2.0 (1.9) years. The most common causes of death were multiorgan failure (25.9%), hemorrhagic stroke (24.7%), and progressive heart failure (20.0%). Nearly half (45.6%) of patients saw palliative care in consultation within a month prior to death. However, only 13 (15.5%) patients enrolled in hospice a median of 11 (range 1-315) days prior to death, including 4 patients with concurrent cancer, 2 with stroke, and 7 with multiorgan failure. The vast majority of patients (78.6%) died in the hospital, and of those hospitalized at death, 87.7% died in the intensive care unit. Most patients hospitalized at death transitioned to a comfort-directed approach to care within 24 hours of dying. In total, 43 (48.3%) patients had their LVAD deactivated prior to death, with all but 3 undergoing deactivation in the hospital. The vast majority of patients died within an hour of LVAD deactivation, and all within 26 hours. Conclusions: In contrast to the general heart failure population, most patients with DT-LVAD die in the hospital and very few enroll in hospice. A significant body of research has demonstrated that patients who die in the intensive care unit and the hospital, as opposed to home or with hospice assistance, experience worse quality of life, quality of death and caregiver outcomes. Potential reasons that patients with DT-LVAD may experience different end-of-life care than other patients with heart failure exist, including that they often experience sudden changes in health status prior to death from acute events such as hemorrhagic stroke. However, further work is needed to understand these differences and to determine whether patients with DT-LVAD are receiving optimal end-of-life care.

Background: Destination therapy left ventricular assist devices (DT-LVADs) have become a treatment option for carefully selected patients with end-stage heart failure. Death is inevitable despite DT-LVAD, with 1-year mortality approximately 20% and median survival 5 years. However, end-of-life processes for LVAD patients vary significantly by institution, provider, and patient preference. Palliative care has played an increasing role in the care of this patient population, yet there remains little data on the most effective way to integrate palliative care and hospice in the DT-LVAD population. Therefore, we aimed to understand the end-of-life perspectives regarding LVADs among both cardiology and palliative care/hospice providers. Methods: Using internet-based, secure methods, we administered a 41-item survey via electronic mail to members of the American Academy of Hospice and Palliative Medicine, European Society of Cardiology-Heart Failure Association, the International Society for Heart and Lung Transplantation, and the Heart Failure Society of America to assess their perspectives on end-of-life care in patients with LVADs. Descriptive statistics were used to analyze data. Fisher’s exact test was used to compare categorical data. Results: From October to November 2011, there were a total of 440 respondents (palliative care/hospice=137; cardiology=303). Most were physicians (80%; n=320) and male (59%; n=232). The majority of providers in both groups viewed an LVAD as a life-sustaining treatment. The groups differed in their attitudes, beliefs, and comfort with end-of-life care in patients with an LVAD. Few palliative care/hospice providers believed a patient needed to be imminently dying to turn off an LVAD; whereas most cardiology providers noted patients should be imminently dying in order to consider LVAD deactivation (2% vs 60%; p=<0.001). Most palliative care/hospice providers believed requests for turning off an LVAD in a patient who is not nearing death should be honored. In contrast, just over half of cardiology providers contended the request should be honored (88% vs 57%; p=<0.001). The provider groups also disagreed on requiring ethics consultation, with most cardiology providers stating it was necessary prior to turning off an LVAD near the end of life (67% vs 24%; p=<0.001). Conclusion: Cardiology providers and palliative care/hospice providers collectively have different perceptions on management of end of life in patients with an LVAD. Bridging the gaps between these two disciplines is a critical first step in creating a more cohesive approach to end-of-life care for these patients—one that honors autonomy but respects individual provider comfort levels.