Frailty and outcomes after implantation of left ventricular assist device as destination therapy.

BACKGROUND: Frailty is recognized as a major prognostic indicator in heart failure. There has been interest in understanding whether pre-operative frailty is associated with worse outcomes after implantation of a left ventricular assist device (LVAD) as destination therapy. METHODS: Patients undergoing LVAD implantation as destination therapy at the Mayo Clinic, Rochester, Minnesota, from February 2007 to June 2012, were included in this study. 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 to 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% with ischemic heart failure), 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% of the patients had been rehospitalized (range 0 to 17 hospitalizations, median 1 per person) and 45% had died. Compared with those who were not frail, patients who were intermediate frail (adjusted HR 1.70, 95% CI 0.71 to 4.31) and frail (HR 3.08, 95% CI 1.40 to 7.48) were at increased risk for death (p for trend = 0.004). The mean (SD) number of days alive out of hospital the first year after LVAD was 293 (107) for not frail, 266 (134) for intermediate frail and 250 (132) for frail patients. CONCLUSIONS: Frailty before destination LVAD implantation is associated with increased risk of death and may represent a significant patient selection consideration.

Measuring frailty in heart failure: a community perspective.

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 to 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 lb in 1 year. Intermediate frailty was defined as 1 to 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.

Contemporary trends in heart failure with reduced and preserved ejection fraction after myocardial infarction: a community study.

Major changes have recently occurred in the epidemiology of myocardial infarction (MI) that could possibly affect outcomes such as heart failure (HF). Data describing trends in HF after MI are scarce and conflicting and do not distinguish between preserved and reduced ejection fraction (EF). We evaluated temporal trends in HF after MI. All residents of Olmsted County, Minnesota (n = 2,596) who had a first-ever MI diagnosed in 1990-2010 and no prior HF were followed-up through 2012. Framingham Heart Study criteria were used to define HF, which was further classified according to EF. Both early-onset (0-7 days after MI) and late-onset (8 days to 5 years after MI) HF were examined. Changes in patient presentation were noted, including fewer ST-segment-elevation MIs, lower Killip class, and more comorbid conditions. Over the 5-year follow-up period, 715 patients developed HF, 475 of whom developed it during the first week. The age- and sex-adjusted risk declined from 1990-1996 to 2004-2010, with hazard ratios of 0.67 (95% confidence interval (CI): 0.54, 0.85) for early-onset HF and 0.63 (95% CI: 0.45, 0.86) for late-onset HF. Further adjustment for patient and MI characteristics yielded hazard ratios of 0.86 (95% CI: 0.66, 1.11) and 0.63 (95% CI: 0.45, 0.88) for early- and late-onset HF, respectively. Declines in early-onset and late-onset HF were observed for HF with reduced EF (<50%) but not for HF with preserved EF, indicating a change in the case mix of HF after MI that requires new prevention strategies.

Frailty and healthcare utilization among patients with heart failure in the community.

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.

Heart failure performance measures: eligibility and implementation in the community.

BACKGROUND: The goal of heart failure (HF) performance measures is to improve quality of care by assessing the implementation of guidelines in eligible patients. Little is known about the proportion of eligible patients and how performance measures are implemented in the community. METHODS: We determined the eligibility for and adherence to performance measures and ß-blocker therapy in a community-based cohort of hospitalized HF patients from January 2005 to June 2011. RESULTS: All of the 465 HF inpatients (median age 76 years, 48% men) included in the study received an ejection fraction assessment. Only 164 had an ejection fraction <40% thus were candidates for ß-blocker and angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blocker (ARB) therapy. Considering absolute contraindications, 99 patients were eligible to receive ACE inhibitors/ARB, and 162 to receive ß-blockers. Among these, 85% received ACE inhibitors/ARBs and 91% received ß-blockers. Among the 261 individuals with atrial fibrillation, 89 were eligible for warfarin and 54% received it. Of 52 current smokers, 69% received cessation counseling during hospitalization. CONCLUSION: In the community, among eligible hospitalized HF patients, the implementation of performance measures can be improved. However, as most patients are not candidates for current performance measures, other approaches are needed to improve care and outcomes.

Patients with heart failure have an increased risk of incident cancer.

OBJECTIVES: This study sought to evaluate the risk of cancer in patients with heart failure (HF) compared with community controls and to determine the impact of cancer post-HF on outcomes. BACKGROUND: HF is associated with excess morbidity and mortality. Noncardiac causes of adverse outcomes in HF are increasingly recognized, but not fully characterized. METHODS: In a case-control study, we compared the history of cancer among community subjects newly diagnosed with HF from 1979 to 2002 to age-, sex-, and date-matched community controls without HF (961 pairs). Individuals without cancer at the index date (596 pairs) were followed for cancer in a cohort design, and the survival of HF patients who developed cancer was assessed. RESULTS: Before the index date, 22% of HF cases and 23% of controls had a history of cancer (odds ratio [OR]: 0.94; 95% confidence interval [CI]: 0.75 to 1.17). During 9,203 person-years of follow-up (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 to 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 of age (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 to 1.99) adjusted for age, sex, index 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 noncardiac morbidity and of cancer surveillance in the management of HF patients.

Frailty and health-related quality of life among residents of long-term care facilities.

OBJECTIVE: To determine the prevalence and relationship of frailty and health-related quality of life (HRQOL) among residents of long-term care [nursing homes (NH) and assisted living (AL)] facilities. METHODS: Residents of NH and AL facilities in La Crosse County, Wisconsin, were recruited 1/2009-6/2010 and assessed for frailty (gait speed, unintended weight loss, grip strength), comorbidity (Charlson index), and HRQOL [Short Form (SF)-36]. RESULTS: Among 137 participants, 85% were frail. Frail residents were older, had more comorbidities (2.0 vs. 0, p < .001) and lower mean SF-36 Physical Component Score (PCS, 32 vs. 48, p < .001). Following adjustments for age, sex, and comorbidities, compared to nonfrail residents, frail residents had lower SF-36 PCS (mean difference -14.7, 95% CI. -19.3,-10.1, p < .001). Frailty, comorbidity, and HRQOL did not differ between NH and AL facilities. DISCUSSION: Frail residents had lower HRQOL, suggesting that preventing frailty may lead to better HRQOL among residents of long-term care facilities.

Physical health status measures predict all-cause mortality in patients with heart failure.

BACKGROUND: Physical health status measures have been shown to predict death in heart failure (HF); however, few studies found significant associations after adjustment for confounders, and most were not representative of all HF patients. METHODS AND RESULTS: HF patients from southeastern MN were prospectively enrolled between 10/2007 and 12/2010, completed a 12-item Short Form Health Survey (SF-12) and a 6-minute walk, and were followed through 2011 for death from any cause. Scores ≤ 25 on the SF-12 physical component indicated low self-reported physical functioning, and the first question of the SF-12 measured self-rated general health. Low functional exercise capacity was defined as ≤ 300 m walked during a 6-minute walk. Over a mean follow-up of 2.3 years, 86 deaths occurred among the 352 participants. A 1.6-fold (95% confidence interval, 1.0-2.7) and 1.8-fold (95% confidence interval, 1.1-2.9) increased risk of death was observed among patients with low self-reported physical functioning and low functional exercise capacity, respectively. Poor self-rated general health corresponded to a 2.7-fold (95% confidence interval, 1.5-4.9) increased risk of death compared with good to excellent general health. All measures equally discriminated between who would die and who would survive (C-statistics: 0.729, 0.750, and 0.740 for self-reported physical functioning, self-rated general health, and functional exercise capacity, respectively). CONCLUSIONS: Three physical health status measures, captured by the SF-12 and a 6-minute walk, equally predict death among community HF patients. Therefore, the first question of the SF-12, which is the least burdensome to administer, may be sufficient to identify HF patients at greatest risk of death.

Depression, healthcare utilization, and death in heart failure: a community study.

BACKGROUND: The increasing prevalence of heart failure (HF) and high associated costs have spurred investigation of factors leading to adverse outcomes in patients with HF. Studies to date report inconsistent evidence on the link between depression and outcomes with only limited data on emergency department and outpatient visits. METHODS AND RESULTS: Olmsted, Dodge, and Fillmore county, Minnesota residents with HF were prospectively recruited between October 2007 and December 2010 and completed a 1-time 9-item Patient Health Questionnaire for depression categorized as: none to minimal (Patient Health Questionnaire score, 0-4), mild (5-9), or moderate to severe (≥10). Andersen-Gill models were used to determine whether depression predicted hospitalizations and emergency department visits, whereas 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 patients with HF (mean age, 73±13 years; 58% men), 15% had moderate to severe depression, 26% mild, and 59% none to minimal depression. During a mean follow-up of 1.6 years, 781 hospitalizations, 1000 emergency department visits, 15 515 outpatient visits, and 74 deaths occurred. After adjustment, moderate to severe depression was associated with nearly a 2-fold increased risk of hospitalization (hazard ratio, 1.79; 95% confidence interval, 1.30-2.47) and emergency department visits (hazard ratio, 1.83; 95% confidence interval, 1.34-2.50), a modest increase in outpatient visits (rate ratio, 1.20; 95% confidence interval, 1.00-1.45), and a 4-fold increase in all-cause mortality (hazard ratio, 4.06; 95% confidence interval, 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.

Cardiovascular and noncardiovascular disease associations with hip fractures.

BACKGROUND: There is growing awareness of an association between cardiovascular disease and fractures, and a temporal increase in fracture risk after myocardial infarction has been identified. To further explore the nature of this relationship, we systematically examined the association of hip fracture with all disease categories and assessed related secular trends. METHODS: By using resources of the Rochester Epidemiology Project, a population-based incident case-control study was conducted. Disease history was compared among all Olmsted County, Minnesota, residents aged 50 years or more with a first radiographically confirmed hip fracture in 1985-2006 and community control subjects individually matched (1:1) to cases on age, sex, and index year (n = 3808; mean age, 82 years; standard deviation, 9 years; 76% were women). RESULTS: All cardiovascular and numerous non-cardiovascular disease categories (eg, infectious diseases, nutritional and metabolic diseases, mental disorders, diseases of the nervous system and sense organs, and diseases of the respiratory system) were associated with fracture risk. However, increasing temporal trends were detected almost exclusively in cardiovascular disease categories. The largest increases in association were observed for ischemic heart disease, other forms of heart disease (including heart failure), hypertension, and diabetes, and were more pronounced among elderly women than other demographic subgroups. CONCLUSIONS: Although the association with hip fracture was not specific to cardiovascular disease, temporal increases were mainly detected in cardiometabolic diseases, all of which have been linked previously to frailty. This mechanism and others warrant further investigation.

Myocardial infarction and sudden cardiac death in Olmsted County, Minnesota, before and after smoke-free workplace laws.

BACKGROUND: Reductions in admissions for myocardial infarction (MI) have been reported in locales where smoke-free workplace laws have been implemented, but no study has assessed sudden cardiac death in that setting. In 2002, a smoke-free restaurant ordinance was implemented in Olmsted County, Minnesota, and in 2007, all workplaces, including bars, became smoke free. METHODS: To evaluate the population impact of smoke-free laws, we measured, through the Rochester Epidemiology Project, the incidence of MI and sudden cardiac death in Olmsted County during the 18-month period before and after implementation of each smoke-free ordinance. All MIs were continuously abstracted and validated, using rigorous standardized criteria relying on biomarkers, cardiac pain, and Minnesota coding of the electrocardiogram. Sudden cardiac death was defined as out-of-hospital deaths associated with coronary disease. RESULTS: Comparing the 18 months before implementation of the smoke-free restaurant ordinance with the 18 months after implementation of the smoke-free workplace law, the incidence of MI declined by 33% (P < .001), from 150.8 to 100.7 per 100,000 population, and the incidence of sudden cardiac death declined by 17% (P = .13), from 109.1 to 92.0 per 100,000 population. During the same period, the prevalence of smoking declined and that of hypertension, diabetes mellitus, hypercholesterolemia, and obesity either remained constant or increased. CONCLUSIONS: A substantial decline in the incidence of MI was observed after smoke-free laws were implemented, the magnitude of which is not explained by community cointerventions or changes in cardiovascular risk factors with the exception of smoking prevalence. As trends in other risk factors do not appear explanatory, smoke-free workplace laws seem to be ecologically related to these favorable trends. Secondhand smoke exposure should be considered a modifiable risk factor for MI. All people should avoid secondhand smoke to the extent possible, and people with coronary heart disease should have no exposure to secondhand smoke.

Pulmonary pressures and death in heart failure: a community study.

OBJECTIVES: The purpose of this study was 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 and net reclassification improvement. BACKGROUND: Although several studies have focused on idiopathic pulmonary arterial hypertension, less is known about pulmonary hypertension among patients with HF, particularly about its prognostic value in the community. METHODS: Between 2003 and 2010, Olmsted County residents with HF prospectively underwent assessment of ejection fraction, diastolic function, and PASP by Doppler echocardiography. RESULTS: PASP was recorded in 1,049 of 1,153 patients (mean age 76 ± 13; 51% women). Median PASP was 48 mm Hg (25th to 75th percentile: 37.0 to 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 (hazard ratio [HR]: 1.45, 95% confidence interval [CI]: 1.13 to 1.85 for tertile 2; HR: 2.07, 95% CI: 1.62 to 2.64 for tertile 3 vs. tertile 1), independently of age, sex, comorbidities, ejection fraction, 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 integrated discrimination improvement gain of 4.2% (p < 0.001), and a net reclassification improvement of 14.1% (p = 0.002), indicating that PASP improved prediction of death over traditional prognostic factors. All results were similar for cardiovascular death. CONCLUSIONS: Among community patients with HF, PASP strongly predicts death and provides incremental and clinically relevant prognostic information independently of known predictors of outcomes.

Medication adherence among community-dwelling patients with heart failure.

OBJECTIVE: To determine medication use and adherence among community-dwelling patients with heart failure (HF). PATIENTS AND METHODS: Residents of Olmsted County, Minnesota, with HF were recruited from October 10, 2007, through February 25, 2009. Pharmacy records were obtained for the 6 months after enrollment. Medication adherence was measured by the proportion of days covered (PDC). A PDC of less than 80% was classified as poor adherence. Factors associated with medication adherence were investigated. RESULTS: Among the 209 study patients with HF, 123 (59%) were male, and the mean ± SD age was 73.7 ± 13.5 years. The median (interquartile range) number of unique medications filled during the 6-month study period was 11 (8-17). Patients with a documented medication allergy were excluded from eligibility for medication use within that medication class. Most patients received conventional HF therapy: 70% (147/209) were treated with ß-blockers and 75% (149/200) with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers. Most patients (62%; 127/205) also took statins. After exclusion of patients with missing dosage information, the proportion of those with poor adherence was 19% (27/140), 19% (28/144), and 13% (16/121) for ß-blockers, angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, and statins, respectively. Self-reported data indicated that those with poor adherence experienced more cost-related medication issues. For example, those who adhered poorly to statin therapy more frequently reported stopping a prescription because of cost than those with good adherence (46% vs 6%; P < .001), skipping doses to save money (23% vs 3%; P = .03), and not filling a new prescription because of cost (46% vs 6%; P < .001). CONCLUSION: Community-dwelling patients with HF take a large number of medications. Medication adherence was suboptimal in many patients, often because of cost.