Objective To determine among community patients with heart failure (HF), whether pulmonary artery systolic pressure (PASP) assessed by Doppler echocardiography was associated with death and improved risk prediction over established factors, using the integrated discrimination improvement (IDI) and net reclassification improvement (NRI). Background While several studies have focused on idiopathic pulmonary arterial hypertension, less is known about pulmonary hypertension among patients with HF, particularly on its prognostic value in the community. Methods Olmsted County residents with HF between 2003 and 2010 prospectively underwent assessment of ejection fraction (EF), diastolic function, and PASP by Doppler echocardiography. Results PASP was recorded in 1049 of 1153 patients (mean age 76±13, 51% women). Median PASP was 48 mmHg (25th-75th percentile, 37.0-58.0). There were 489 deaths after a follow-up of 2.7±1.9 years. There was a strong positive graded association between PASP and mortality. Increasing PASP was associated with an increased risk of death (HR 1.45, 95%CI 1.13-1.85 for tertile 2; HR 2.07, 95%CI 1.62-2.64 for tertile 3, versus tertile 1), independently of age, sex, comorbidities, EF and diastolic function. Adding PASP to models including these clinical characteristics resulted in an increase in the c-statistic from 0.704 to 0.742 (p=0.007), an IDI gain of 4.2% (p<0.001), and an NRI of 14.1% (p=0.002), indicating that PASP improved prediction of death over traditional prognostic factors. All results were similar for CV death. Conclusion Among community patients with HF, PASP strongly predicts death and provides incremental and clinically relevant prognostic information independently of known predictors of outcomes.

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Objective To evaluate the risk of cancer in patients with heart failure (HF) compared to community controls and its impact on outcome. Background HF is associated with excess morbidity and mortality. Non-cardiac causes of adverse outcomes in HF are increasingly recognized but not fully characterized. Methods In a case-control study, we compared history of cancer among community subjects newly diagnosed with HF from 1979–2002 to age-, sex-, and date-matched community controls without HF (961 pairs). Individuals without cancer at index (596 pairs) were followed for cancer in a cohort design, and the survival of HF patients who developed cancer was assessed. Results Before index, 22% of HF cases and 23% of controls had a history of cancer (odds ratio 0.94; 95% CI 0.75–1.17). During 9,203 person-years of follow-up [mean (SD), 7.7 (6.4) years], 244 new cancer cases were identified; HF patients had a 68% higher risk of developing cancer [hazard ratio (HR) 1.68; 95% CI 1.13–2.50] adjusted for body mass index, smoking and comorbidities. The HRs were similar for men and women with a trend toward a stronger association among subjects ≤75 years (P=0.22) and during the most recent time period (P=0.075). Among HF cases, incident cancer increased the risk of death (HR 1.56; 95% CI 1.22–1.99) adjusted for age, sex, year and comorbidities. Conclusions HF patients are at increased risk of cancer, which appears to have increased over time. Cancer increases mortality in HF underscoring the importance of non-cardiac morbidity and of cancer surveillance in the management of HF patients.

Objectives The aim of this study was to determine the prevalence of frailty in a community cohort of patients with heart failure (HF) and to determine whether frailty is associated with healthcare utilization. Background Frailty is associated with death in patients with HF, but its prevalence and impact on healthcare utilization in patients with HF are poorly characterized. Methods Residents of Olmsted, Dodge, and Fillmore counties in Minnesota with HF between October 2007 and March 2011 were prospectively recruited to undergo frailty assessment. Frailty was defined as 3 or more of the following: unintentional weight loss, exhaustion, weak grip strength, and slowness and low physical activity measured by the SF-12 physical component score. Intermediate frailty was defined as 1 or 2 components. Negative binomial regression was used to examine the association between outpatient visits and frailty; Andersen-Gill models were used to determine if frailty predicted emergency department (ED) visits or hospitalizations. Results Among 448 patients (mean age 73 ± 13 years, 57% men), 74% had some degree of frailty (19% frail, 55% intermediate frail). Over a mean follow-up period of 2.0 ± 1.1 years, 20,164 outpatient visits, 1,440 ED visits, and 1,057 hospitalizations occurred. After adjustment for potential confounders, frailty was associated with a 92% increased risk for ED visits and a 65% increased risk for hospitalizations. The population-attributable risk associated with any degree of frailty was 35% for ED visits and 19% for hospitalizations. Conclusions Frailty is common among community patients with HF and is a strong and independent predictor of ED visits and hospitalizations. Because frailty is potentially modifiable, it should be incorporated in the clinical evaluation of patients with HF.

Background Frailty is recognized as an important prognostic indicator in heart failure. There has been interest in understanding whether pre-operative frailty is associated with worse outcomes after destination left ventricular assist device (LVAD). Methods Patients undergoing destination LVAD at the Mayo Clinic in Rochester, Minnesota from February 2007 to June 2012 were included. Frailty was assessed using the Deficit Index (31 impairments, disabilities, and comorbidities) and defined as the proportion of deficits present. We divided patients based on tertiles of the Deficit Index (>0.32= frail, 0.23–0.32= intermediate frail, <0.23= not frail). Cox proportional hazard regression models were used to examine the association between frailty and death. Patients were censored at death or last follow-up through October 2013. Results Among 99 patients (mean age 65 years, 18% female, 55% ischemic HF), the Deficit Index ranged from 0.10 to 0.65 (mean 0.29). After a mean follow-up of 1.9 ±1.6 years, 79% had been rehospitalized (range 0–17 hospitalizations, median 1 per person) and 45% had died. Compared to those who were not frail, patients who were intermediate frail (adjusted HR 1.70, 95% CI 0.71–4.31) and frail (HR 3.08, 95% CI 1.40–7.48) were at increased risk for death (p for trend=0.004). The mean (SD) days alive out of hospital the first year after LVAD was 293 (107), 266 (134), and 250 (132) in those who were not frail, intermediate frail, and frail, respectively. Conclusions Frailty pre-destination LVAD is associated with increased risk of death, and may represent an important patient selection consideration.

Background The increasing prevalence of heart failure (HF) and high associated costs have spurred investigation of factors leading to adverse outcomes in HF patients. Studies to date report inconsistent evidence regarding the link between depression and outcomes with only limited data on emergency department (ED) and outpatient visits. Methods and Results Olmsted, Dodge, and Fillmore county, MN residents with HF were prospectively recruited between October 2007 and December 2010, and completed a one-time 9-item Patient Health Questionnaire (PHQ-9) for depression categorized as: none-minimal (PHQ-9 score 0–4), mild (5–9), or moderate-severe (≥10). Andersen-Gill models were used to determine if depression predicted hospitalizations and ED visits while negative binomial regression models explored the association of depression with outpatient visits. Cox proportional hazards regression characterized the relationship between depression and all-cause mortality. Among 402 HF patients (mean age 73±13, 58% male), 15% had moderate-severe depression, 26% mild, and 59% none-minimal. Over a mean follow-up of 1.6 years, 781 hospitalizations, 1000 ED visits, 15,515 outpatient visits, and 74 deaths occurred. After adjustment, moderate-severe depression was associated with nearly a 2-fold increased risk of hospitalization (HR 1.79, 95% CI 1.30–2.47) and ED visits (HR 1.83, 95% CI 1.34–2.50), a modest increase in outpatient visits (RR 1.20, 95% CI 1.00–1.45), and a 4-fold increase in all-cause mortality (HR 4.06, 95% CI 2.35–7.01). Conclusions In this prospective cohort study, depression independently predicted an increase in the use of healthcare resources and mortality. Greater recognition and management of depression in HF may optimize clinical outcomes and resource utilization.

While the association between exposure to secondhand smoke and lung cancer risk is well established, few studies with sufficient power have examined the association by histological type. In this study, we evaluated the secondhand smoke-lung cancer relationship by histological type based on pooled data from 18 case-control studies in the International Lung Cancer Consortium (ILCCO), including 2,504 cases and 7,276 controls who were never smokers and 10,184 cases and 7,176 controls who were ever smokers. We used multivariable logistic regression, adjusting for age, sex, race/ethnicity, smoking status, pack-years of smoking, and study. Among never smokers, the odds ratios (OR) comparing those ever exposed to secondhand smoke with those never exposed were 1.31 (95% CI: 1.17–1.45) for all histological types combined, 1.26 (95% CI: 1.10–1.44) for adenocarcinoma, 1.41 (95% CI: 0.99–1.99) for squamous cell carcinoma, 1.48 (95% CI: 0.89–2.45) for large cell lung cancer, and 3.09 (95% CI: 1.62–5.89) for small cell lung cancer. The estimated association with secondhand smoke exposure was greater for small cell lung cancer than for non-small cell lung cancers (OR=2.11, 95% CI: 1.11–4.04). This analysis is the largest to date investigating the relation between exposure to secondhand smoke and lung cancer. Our study provides more precise estimates of the impact of secondhand smoke on the major histological types of lung cancer, indicates the association with secondhand smoke is stronger for small cell lung cancer than for the other histological types, and suggests the importance of intervention against exposure to secondhand smoke in lung cancer prevention.

Background Frailty, an important prognostic indicator in heart failure (HF), may be defined as a biological phenotype or an accumulation of deficits. Each method has strengths and limitations, but their utility has never been evaluated in the same community HF cohort. Methods Southeastern Minnesota residents with HF were recruited from 2007–2011. Frailty according to the biological phenotype was defined as 3 or more of: weak grip strength, physical exhaustion, slowness, low activity and unintentional weight loss >10 lbs. in 1 year. Intermediate frailty was defined as 1–2. The deficit index was defined as the proportion of deficits present out of 32 deficits. Results Among 223 patients (mean age 71±14, 61% male), 21% were frail and 48% intermediate frail according to the biological phenotype. The deficit index ranged from 0.02–0.75, with a mean (SD) of 0.25 (0.13). Over a mean follow-up of 2.4 years, 63 patients died. After adjustment for age, sex and ejection fraction, patients categorized as frail by the biological phenotype had a 2-fold increased risk of death compared to those with no frailty, whereas a 0.1 unit increase in the deficit index was associated with a 44% increased risk of death. Both measures predicted death equally (C-statistics: 0.687 for biological phenotype and 0.700 for deficit index). Conclusion The deficit index and the biological phenotype equally predict mortality. As the biological phenotype is not routinely assessed clinically, the deficit index, which can be ascertained from medical records, is a feasible alternative to ascertain frailty.