Dunlay, Shannon M.

Background To investigate heart failure ( HF ) hospitalization trends in the United States and change in trends after publication of management guidelines. Methods and Results Using data from the National Inpatient Sample and the US Census Bureau, annual national estimates in HF admissions and in‐hospital mortality were estimated for years 2001 to 2014, during which an estimated 57.4 million HF ‐associated admissions occurred. Rates (95% confidence intervals) of admissions and in‐hospital mortality among primary HF hospitalizations declined by an average annual rate of 3% (2.5%–3.5%) and 3.5% (2.9%–4.0%), respectively. Compared with 2001 to 2005, the average annual rate of decline in primary HF admissions was more in 2006 to 2009 (ie, 3.4% versus 1.1%; P =0.02). In 2010 to 2014, primary HF admission continued to decline by an average annual rate of 4.3% (95% confidence interval, 3.9%–5.1%), but this was not significantly different from 2006 to 2009 ( P =0.14). In contrast, there was no further decline in in‐hospital mortality trend after the guideline‐release years. For hospitalizations with HF as the secondary diagnosis, there was an upward trend in admissions in 2001 to 2005. However, the trend began to decline in 2006 to 2009, with an average annual rate of 2.4% (95% confidence interval, 0.8%–4%). Meanwhile, there was a consistent decline in in‐hospital mortality by an average annual rate of 3.7% (95% confidence interval, 3.3%–4.2%) during the study period, but the decline was more in 2006 to 2009 compared with 2001 to 2005 (ie, 5.4% versus 3.4%; P <0.001). Beyond 2009, admission and in‐hospital mortality rates continued to decline, although this was not significantly better than the preceding interval. Conclusions From 2001 to 2014, HF admission and in‐hospital mortality rates declined significantly in the United States; the greatest improvements coincided with the publication of the 2005 American College of Cardiology/American Heart Association HF guidelines.

Highly specialized left ventricular assist device care is not readily available in many areas, potentially limiting access to therapy. This retrospective analysis examines the relationship of outcomes by patient distance from implanting left ventricular assist device center within the Mechanical Circulatory Support Research Network. Zip codes were used to calculate patient distance, with the primary outcome of interest being 3-year survival by distance from the surgical center. Secondary outcomes included 90-day survival and incident event rates for the following: gastrointestinal bleeding, infection, cerebral event, and pump thrombosis. Across the four centers, there were 1184 patients supported for a median of 486 days. Overall survival was 91 ± 0.8% at 90 days and 61 ± 1.9% at 3 years, with worse 3-year survival in those living >90 vs . ≤90 miles from the ventricular assist device implant center (55 ± 3.0% vs . 64 ± 2.5, p = 0.019). Patients living >90 miles from an implant center were older, more likely to be implanted for destination therapy support, had a prior sternotomy, and had worse renal function than those living closer ( p <0.05 for all). After adjusting for these factors, albumin and center of implant, the hazard ratio did not reach statistical significance (hazard ratio = 1.2; p = 0.14). Except for gastrointestinal bleeding, the event rates for the secondary outcomes were higher for those living closer to the implanting center. Protocols should be designed for more frequent follow-up and increased shared care opportunities to ensure optimal outcomes are achieved in distant patients.

Continuous-flow left ventricular assist devices (CF-LVADs) have revolutionized the management of patients with advanced heart failure. Alternative implant strategies are increasingly used for device placement. We reviewed our experience from the Mechanical Circulatory Support Research Network registry with the HeartWare centrifugal CF-LVAD (HVAD). From May 2004 to August 2015, 1,150 patients underwent primary CF-LVAD implantation at our institutions. Within this group, a total of 283 patients (25%) were implanted with the HVAD. A minimally invasive left lateral thoracotomy (MILT) implant strategy was used in 53 patients (20%), of which 22 (42%) were implanted off-pump. Median age at implant was 59 years and 183 patients (65%) were implanted as bridge-to-transplantation. Follow-up was 100% complete for a total of 302 patient-years of support. In-hospital mortality was 4.9% (14 patients), and was comparable between the conventional sternotomy (CS) and MILT cohorts (p = 0.15). Patients in the MILT cohort had a shorter median length of stay (p < 0.01) and had a lower incidence of postimplant pump thrombus (p = 0.02). Cumulative survival at the end of follow-up reached 84%, and was comparable between the two groups (p = 0.298). Multivariate analysis identified preoperative bilirubin level as the only independent predictor of survival. Surgical technique had no impact on survival. In this large, multicenter experience, data demonstrate excellent survival and adverse event profiles for patients supported with the HVAD technology, regardless of surgical implant technique. With constant advancements in device technology along with our increasing clinical experience with the newer techniques, minimally invasive LVAD implantation continues to evolve as a valuable alternative to CS in selected patients.

Although improvement in cardiac output and hemodynamic parameters is routinely demonstrated in patients implanted with continuous-flow left ventricular assist devices (CF-LVADs), improvement in exercise capacity is inconsistently seen. Our purpose was to determine whether native cardiac factors, LVAD factors, or comorbid factors were associated with lack of improvement. Review of all patients undergoing preimplant cardiopulmonary exercise testing (CPET) and CPET on LVAD therapy at one institution was performed between 2007 and 2014 (n = 49). Comprehensive assessment of echocardiographic parameters, right heart catheterization data, medications, and comorbid illness was undertaken. There was no mean improvement in peak oxygen consumption (VO2; 11.8–12.4 ml/kg/min; p = 0.26), although exercise time (5.1 [46% predicted] to 5.8 min [56% predicted]; p = 0.02) and nadir of the ratio of minute ventilation to carbon dioxide production slope (VE/VCO2; 39–36; p = 0.001) improved. Factors most strongly associated with improvement in VO2 were Heartmate II pulsatility index (PI; R = 0.48; p = 0.001), power (R = −0.40; p = 0.009), pump flow (R = −0.40; p = 0.008), and pump speed (R = −0.32; p = 0.04). Peak heart rate (HR) was also associated with improvement in VO2 (R = 0.41; p = 0.004). Left ventricular ejection fraction (LVEF; R = 0.004; p = 0.77), right ventricular (RV) function (R = 0.22; p = 0.28), and aortic valve opening (R = 0.20; p = 0.57) were not associated with improvement in VO2. Our data suggest that less reliance on LVAD support was modestly associated with improvement in exercise capacity. Further studies should seek to determine the optimal level of device support prospectively in relation to exercise capacity.

Background: A diagnosis of heart failure (HF) often requires a comprehensive lifestyle change to maintain disease stability. When patients with HF are married, the spouse frequently assumes the caregiving role. Our objectives were to describe the health of spouses of married patients with HF, and examine whether the health of a spouse impacts patient outcomes. Methods and Results: We identified 905 patients that were married at the time of incident HF diagnosis in Olmsted County, MN, from 2000 to 2012. Using Rochester Epidemiology Project resources, the patient and their spouse’s comprehensive longitudinal health histories were linked. Spousal health at patient HF diagnosis was assessed by comorbidity burden, self-reported difficulty with activities of daily living and prior hospitalizations. The associations of spousal health with patient outcomes and patient death with spousal outcomes were examined using Cox and Andersen–Gill models. Spouses of patients with HF were elderly (mean age, 71 years), often had comorbid conditions, and 16% had difficulty with ≥1 activities of daily living. After adjustment for patient age, sex, and comorbidity, there were no independent associations of spousal health and patient risk of death or hospitalization after HF diagnosis. However, the risk of hospitalization (adjusted hazard ratio, 1.34; 95% confidence interval, 1.11–1.60; P =0.002) and death (hazard ratio, 2.10; 95% confidence interval, 1.60–2.75; P <0.001) increased in the surviving spouse after patient death. Conclusions: We found no evidence that the health of a spouse impacts patient outcomes after HF diagnosis. However, after a patient with HF dies, their surviving spouse’s risk of hospitalization and death increases.

Background There are few data describing the longitudinal use of and adherence to heart failure medications following left ventricular assist device (LVAD) implantation. Methods and Results Using a large US commercial insurance database, patients who received an LVAD ( International Classification of Diseases, 9th Revision, Clinical Modification code 37.66) and survived to hospital discharge without heart transplantation between January 1, 2006, and March 31, 2015, were identified. Heart failure medication use from 3 months before 1‐year post‐ LVAD was examined using linked pharmacy claims. Differences in the proportion of patients taking heart failure medications post LVAD compared with pre LVAD were examined using McNemar test. Predictors of post‐ LVAD medication use and poor medication adherence (proportion of days covered <0.8) were identified via logistic regression. Among 362 patients (mean age, 57.4 years; 75.1% men), compared with pre LVAD , the proportion of patients taking anticoagulants and antiarrhythmics following LVAD increased; mineralocorticoid receptor antagonists, thiazide diuretics, and digoxin decreased; and β‐blockers, angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers, and loop diuretics did not change. Pre‐ LVAD medication use was associated with post‐ LVAD use across all medication classes. The proportion of patients with poor medication adherence was 28.8%, 39.0%, and 36.0% for β‐blockers, angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers, and anticoagulants, respectively. Many patients with poor adherence completely discontinued use of the medication. Conclusions Neurohormonal antagonist use after LVAD was inconsistent, perhaps reflecting uncertainty of therapeutic benefit in this population. Medication adherence post‐ LVAD was poor in many patients. Further work is needed to delineate the reasons for nonadherence after LVAD .

Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurologic disorder with predictable challenges regarding disease progression and end-of-life care. These include need for respiratory and nutritional support. Little is known about how such choices impact end-of-life health service utilization for these patients. Using OptumLabs Data Warehouse, a large administrative claims database with more than 150 million privately insured, geographically diverse enrollees, we sought to explore outcomes associated with the use of enteral nutrition (EN). Patients were of age ≥18 years, with first ALS diagnosis during calendar years 2006-2012, and 6 months of continuous health plan coverage before first diagnosis. EN use was identified using procedure codes. Data were summarized descriptively. Among 1974 patients with ALS, mean age was 60.0 ± 12.5 years, 41.8% were women, and 9.7% demonstrated use of EN. Median time from ALS diagnosis to evidence of EN was 211 days (interquartile range [IQR]: 70-426). Those receiving EN had greater aggregate comorbidity (47% with Charlson-Deyo Comorbidity Index ≥ 3 vs only 27% in non-EN subset). In total, 38.1% of patients had at least 1 hospitalization, with median time to hospitalization of 162 days. Unfortunately, the EN group ended coverage a median of 155 days after EN started (IQR: 63.5-388), thereby limiting ability to capture outcomes. Although many ALS patients were identified, EN use was lower than expected, due to being earlier in disease trajectory and lost to follow-up with transition from private insurance. As such, databases exclusively including privately insured patients may be suboptimal for detecting late complications of protracted illnesses.

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.