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Background The Acute Decompensated Heart Failure National Registry (ADHERE) and Get With The Guidelines (GWTG) registries have developed simple heart failure (HF) in-hospital mortality risk scores. We hypothesized that HF scores predictive of in-hospital mortality would perform as well for early postdischarge mortality risk stratification. Methods and Results In this single-center, community-based, retrospective study of all consecutive primary HF hospitalizations (6203 hospitalizations in 3745 patients) from 2000 to 2013, the ADHERE and GWTG risk scores were calculated from admission data. There were 176 (3.0%) and 399 (6.7%), 869 (14.7%), and 1272 (21.5%) deaths in-hospital and at 30, 90, and 180 days postdischarge, respectively. The GWTG but not ADHERE risk score was well calibrated for in-hospital mortality. Both the ADHERE (C statistic 0.66 and 0.67, 0.64, and 0.64) and GWTG (C statistic 0.74 and 0.73, 0.71, and 0.70) HF risk scores were similarly predictive of in-hospital and 30-, 90-, and 180-day postdischarge mortality. The ADHERE risk score identified 10% and the GWTG risk score identified 20% of hospitalizations where 180-day postdischarge mortality was 50%, a prognostic bench mark for hospice referral. In contrast, hospitalizations characterized as lowest risk by the ADHERE (57% of hospitalizations; 180-day mortality 16.2%) or GWTG score (20% of hospitalizations; 180-day mortality 8.0%) had substantially lower mortality (odds ratios high versus low risk of 5–8 [ADHERE] and 11–18 [GWTG] across time points; P <0.0001 for all). Conclusions The simple ADHERE and GWTG scores stratify hospitalized HF patients for both inpatient and early postdischarge mortality risk, allowing comprehensive risk assessment on admission.

Background Soluble ST2 is a biomarker that is elevated in certain systemic inflammatory diseases. Comorbidity‐driven microvascular inflammation is postulated to play a key role in heart failure with preserved ejection fraction ( HF p EF ) pathophysiology, but data on how sST 2 relates to clinical characteristics or inflammatory conditions or biomarkers in HF p EF are limited. We sought to determine circulating levels and clinical correlates of sST 2 in HF pEF. Methods and Results At enrollment, patients (n=174) from the Phosphodiesterase‐5 Inhibition to Improve Clinical Status And Exercise Capacity in Diastolic Heart Failure (RELAX) trial of sildenafil in HF p EF had sST 2 levels measured. Clinical characteristics; cardiac structure and function; exercise performance; and biomarkers of neurohumoral activation, systemic inflammation and fibrosis, and myocardial necrosis were assessed in relation to sST 2 levels. Median sST 2 levels in male and female HFpEF patients were 36.7 ng/mL (range 30.9–49.2 ng/mL; reference range 4–31 ng/mL) and 30.8 ng/mL (range 25.3–39.3 ng/mL; reference range 2–21 ng/mL), respectively. Among HF p EF patients, higher sST 2 levels were associated with the presence of diabetes mellitus; atrial fibrillation; renal dysfunction; right ventricular pressure overload and dysfunction; systemic congestion; exercise intolerance; and biomarkers of systemic inflammation and fibrosis, neurohumoral activation, and myocardial necrosis ( P <0.05 for all). sST 2 was not associated with left ventricular structure or left ventricular systolic or diastolic function. Conclusions In HF p EF , sST 2 levels were associated with proinflammatory comorbidities, right ventricular pressure overload and dysfunction, and systemic congestion but not with left ventricular geometry or function. These data suggest that sST2 may be a marker of systemic inflammation in HF p EF and potentially of extracardiac origin. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 00763867.

Background: Cardiomyocytes are resistant to radiation. However, cardiac radiation exposure causes coronary microvascular endothelial inflammation, a perturbation implicated in the pathogenesis of heart failure (HF) and particularly HF with preserved ejection fraction (HFpEF). Radiotherapy for breast cancer results in variable cardiac radiation exposure and may increase the risk of HF. Methods: We conducted a population-based case-control study of incident HF in 170 female residents of Olmsted County, Minnesota (59 cases and 111 controls), who underwent contemporary (1998–2013) radiotherapy for breast cancer with computed tomography–assisted radiotherapy planning. Controls were matched to cases for age, tumor side, chemotherapy use, diabetes mellitus, and hypertension. Mean cardiac radiation dose (MCRD) in each patient was calculated from the patient’s computed tomography images and radiotherapy plan. Results: Mean age at radiotherapy was 69±9 years. Of HF cases, 38 (64%) had EF≥50% (HFpEF), 18 (31%) had EF<50% (HF with reduced EF), and 3 (5%) did not have EF measured. The EF was ≥40% in 50 of the 56 HF cases (89%) with an EF measurement. The mean interval from radiotherapy to HF was 5.8±3.4 years. The odds of HF was higher in patients with a history of ischemic heart disease or atrial fibrillation. The MCRD was 2.5 Gy (range, 0.2–13.1 Gy) and higher in cases (3.3±2.7 Gy) than controls (2.1±2.0 Gy; P =0.004). The odds ratio (95% confidence interval) for HF per log MCRD was 9.1 (3.4–24.4) for any HF, 16.9 (3.9–73.7) for HFpEF, and 3.17 (0.8–13.0) for HF with reduced EF. The increased odds of any HF or HFpEF with increasing MCRD remained significant after adjustment for HF risk factors and in sensitivity analyses matching by cancer stage rather than tumor side. Only 18.6% of patients experienced new or recurrent ischemic events between radiotherapy and the onset of HF. Conclusions: The relative risk of HFpEF increases with increasing cardiac radiation exposure during contemporary conformal breast cancer radiotherapy. These data emphasize the importance of radiotherapy techniques that limit MCRD during breast cancer treatment. Moreover, these data provide further support for the importance of coronary microvascular compromise in the pathophysiology of HFpEF.

VT Ablation in LVAD RecipientsBackgroundPatients with advanced heart failure (HF) are predisposed to ventricular arrhythmias (VAs), particularly following implantation of a left ventricular assist device (LVAD). There is minimal evidence for appropriate management strategies.ObjectivesThis study aimed to compare the burden of VA and response to ablation performed either before or following LVAD implantation.MethodsWe created a retrospective cohort of patients who underwent both VA ablation and Heart Mate II (Thoratec, Pleasanton, CA, USA) LVAD implantation at Mayo Clinic (Rochester, MN, USA). Patients were stratified based on whether they underwent VA ablation before (pre‐LVAD) or after LVAD (post‐LVAD) implantation. Descriptive analyses assessed 6‐month arrhythmia burden in relation to LVAD implantation and VA ablation.ResultsA total of 9 patients underwent both LVAD implantation and VA ablation. There were 3 and 6 patients, respectively, in the pre‐LVAD and post‐LVAD cohorts. Among patients in the pre‐LVAD cohort, the median number of VAs tended to increase after ablation (9 vs. 72) and decreased after LVAD implantation (72 vs. 63). Similarly among patients in the post‐LVAD cohort, the median burden of VAs increased after LVAD implantation (1 vs. 22) and the median burden decreased after ablation (22 vs. 13). Two of 6 patients had substrate related to the LVAD inflow cannula site, while other substrate was not related directly to the cannula.ConclusionsIn patients with progressive HF and LVAD implantation, ablation is associated with reduced VA rates. In LVAD patients, most VAs arise from substrate unrelated to the inflow cannula site.

Background— Despite the ability of left ventricular assist device as destination therapy (DT-LVAD) to prolong survival for many patients with advanced heart failure, little is known about the eventual end-of-life care that patients with DT-LVAD receive. Methods and Results— All patients undergoing DT-LVAD at the Mayo Clinic in Rochester, Minnesota, from January 1, 2007, to September 30, 2014, who subsequently died before July 1, 2015, were included. Information about end-of-life care was obtained from documentation in the electronic medical record. Of 89 patients who died with a DT-LVAD, the median (25th–75th percentile) time from left ventricular assist device implantation to death was 14 (4–31) months. The most common causes of death were multiorgan failure (26%), hemorrhagic stroke (24%), and progressive heart failure (21%). Nearly half (46%) of the patients saw palliative care within 1 month before death; however, only 13 (15%) patients enrolled in hospice a median 11 (range 1–315) days before death. Most patients (78%) died in the hospital, of which 88% died in the intensive care unit. In total, 49 patients had their left ventricular assist device deactivated before death, with all but 3 undergoing deactivation in the hospital. Most patients died within an hour of left ventricular assist device 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 few use hospice. Further work is needed to understand these differences and to determine whether patients with DT-LVAD are receiving optimal end-of-life care.

Objectives To investigate the effect of the number and type of comorbid conditions on death and hospitalizations in individuals with incident heart failure ( HF ). Design Population‐based cohort study. Setting Olmsted County, Minnesota. Participants Olmsted County, Minnesota, residents with incident HF from 2000 to 2010 (mean age 76 ± 14, 56% female) (N = 1,714). Measurements The prevalence of 16 chronic conditions obtained at HF diagnosis classified into three groups: cardiovascular ( CV ) related, other physical, and mental. Results The mean number of conditions per participant was 2.6 ± 1.5 for CV ‐related conditions, 1.3 ± 1.1 for other physical conditions, and 0.30 ± 0.61 for mental conditions. After a mean follow‐up of 4.2 years, 1,073 deaths and 6,306 hospitalizations had occurred. After adjustment for age, sex, ejection fraction, in‐ or outpatient status, and number of other conditions, an increase of one other physical condition was associated with a 14% ( HR = 1.14, 95% CI = 1.08–1.20) greater risk of death and a 26% ( HR = 1.26, 95% CI = 1.20–1.32) greater risk of hospitalization, and an increase of one mental condition was associated with a 31% ( HR = 1.31, 95% CI = 1.19–1.44) greater risk of death and an 18% ( HR = 1.18, 95% CI = 1.07–1.29) greater risk of hospitalization. In contrast, an increase of one CV ‐related condition was not associated with greater risk of death and was associated with a 10% ( HR = 1.10, 95% CI = 1.06–1.15) greater risk of hospitalization. Conclusion CV ‐related conditions are the most common type of comorbid conditions in individuals with HF , but other physical and mental conditions are more strongly associated with death and hospitalizations. This underscores the effect of non‐ CV conditions on outcomes in HF .

Guidelines for performing concomitant procedures (CPs) in patients undergoing continuous flow-left ventricular assist device (CF-LVAD) implantation are unclear. The impact of an increased surgical complexity outside the constraint of landmark clinical trials has not been reported. From May 2004 to December 2013, 614 patients (499 males, 81%) underwent CF-LVAD implant at our institutions. Median age was 57 ± 13 years and 364 (59%) were bridge to transplantation (BTT). Survival and device-related complications were analyzed and stratified based on the surgical intervention. A total of 398 patients (65%) underwent CF-LVAD implantation without CPs. The remaining patients (35%, n = 216) were grouped according to various CPs. Survival was comparable between groups and not influenced by the CP, device type, or indication for implant. Time-to-first device-related adverse event was shorter in patients with CPs. Regression analysis revealed only increased age (p = 0.03), increase in baseline creatinine (p = 0.002), cardiopulmonary bypass time (p = 0.03), and decreased body mass index (p = 0.03) were predictors of mortality, whereas only age (p = 0.006) and prior sternotomy (p = 0.02) were related to adverse device-related events. Performing CPs leads to comparable survival and device-related outcomes after implant. The decision to perform CPs should be balanced with age, preoperative renal dysfunction, and projected complexity of surgery.

Background— Contemporary data are lacking on the prognostic importance of heart failure (HF) after myocardial infarction (MI). We evaluated the prognostic impact of HF post MI according to preserved/reduced ejection fraction and the timing of its occurrence. Methods and Results— All Olmsted County, Minnesota, residents (n=2596) with incident MI diagnosed in 1990 to 2010 and no prior HF were followed through March 2013. Cox models were used to examine (1) the hazard ratios for death associated with HF type and timing and (2) secular trends in survival by HF status. During a mean follow-up of 7.6 years, there were 1116 deaths, 634 in the 902 patients who developed HF (70%) and 482 in the 1694 patients who did not develop HF (28%). After adjustment for age and sex, HF as a time-dependent variable was strongly associated with mortality (hazard ratio =3.31, 95% confidence interval: 2.93–3.75), particularly from cardiovascular causes (hazard ratio =4.20, 95% confidence interval: 3.50–5.03). Further adjustment for MI severity and comorbidity, acute treatment, and recurrent MI moderately attenuated these associations (hazard ratio =2.49 and 2.94 for all-cause and cardiovascular mortality, respectively). Mortality did not differ by ejection fraction, but was higher for delayed- versus early-onset HF ( P for heterogeneity =0.002). The age- and sex-adjusted 5-year survival estimates in 2001 to 2010 versus 1990 to 2000 were 82% and 81% among HF-free and 61% and 54% among HF patients, respectively ( P for heterogeneity of trends =0.05). Conclusions— HF markedly increases the risk of death after MI. This excess risk is similar regardless of ejection fraction but greater for delayed- versus early-onset HF. Mortality after MI declined over time, primarily as a result of improved HF survival.