Roger, Véronique L.

Thais Coutinho, 2011 Finalist and Presenting Author

Background: Pulmonary hypertension is common in HFpEF and is associated with increased mortality. Pulmonary hypertension can lead to right ventricular systolic dysfunction. However, the magnitude and prognostic significance of RV dysfunction in the HFpEF population are unclear. Hypothesis: RV systolic dysfunction is common in HFpEF and is associated with increased mortality. Methods: RV size and systolic function were assessed qualitatively (as normal or abnormal) and pulmonary artery systolic pressure (PASP) was estimated using echocardiography in 548 consecutive HFpEF subjects (Framingham criteria and EF ≥50%) from a prospective population based study (Olmsted County, Minnesota). Control group was a retrospectively identified random sample of age and sex matched hypertensive (N=360) and normotensive subjects (N=168) from Olmsted County. HFpEF group was followed for up to 5 years (median follow up 4.4 years). Results: See table and figure. RV enlargement and systolic dysfunction were more prevalent in HFpEF compared with age and sex matched hypertensive and normotensive controls. In HFpEF subjects with PASP above the median, RV systolic dysfunction was associated with poor survival compared with normal RV function. RV systolic dysfunction was a significant predictor of mortality even after adjustment for age and PASP in a Cox regression model (Hazard Ratio=1.4, p=0.02). Conclusions: In the community, RV systolic dysfunction is common in HFpEF and is associated with higher mortality. Although quantitative assessment of RV function is difficult owing to its complex geometry, qualitative assessment is feasible on the majority of subjects and provides significant prognostic information.

Objective : Practice analysis of cardiac surgical service lines suggested that, for patients having routine cardiac surgery, standardization of care processes in the ICU could reduce cost and improve outcomes. We tested this hypothesis in a large surgical practice. Methods : Patients eligible for a standardized care pathway were prospectively identified preoperatively. ICU protocol development and practice redesign occurred in 2009 with implementation in 2010. In the ICU, all major process steps to recovery were managed by tiered and integrated protocols whereby care advancement is the default if clinical criteria are met. We compared outcomes of patients managed by protocol to those managed by standard care. ICU metrics (time intubated, drip weaning, length of stay) were benchmarked against a sample of 65 CABG patients from 2008. Return to ICU and to OR for standardized care patients were compared to concurrent patients under routine care. We report on all patients having cardiac surgery for 12 months beginning March 2010. Findings : Over 12 months, the ICU care of 1289 patients followed standardized tiered protocols, while 1309 patients were managed by standard care. After implementation of standardized protocols, ICU metrics improved in protocol patients relative to 2008 (2010 versus 2008): mean intubation time in hours (7.4 vs 11.6), mean time on hemodynamic drips in hours (16.2 vs 25.3), average ICU length of stay in hours (25.1 vs 35.9). The safety of protocol based care is demonstrated by lower rates of return to ICU and to OR among patients under protocol vs non-protocol: return to OR (1.8% vs 8.9%), return to ICU (1.6% vs 6.2%). Conclusions: With proper patient selection and rigorous protocols that make care advancement the default, cardiac surgical care in the ICU can be standardized and clinical metrics improved. The safety of this strategy is demonstrated by very low rates of return to OR or ICU. This practice model is translatable to other ICU practices.

Objective: To determine if the implementation of smoke-free workplace laws reduced the incidence of the acute coronary events including myocardial infarction (MI) and sudden cardiac death (SCD). Background: Nonsmokers chronically exposed to second-hand smoke (SHS) are at increased risk of death from heart disease. However, a nonlinear dose relationship exists between SHS exposure and coronary heart disease (CHD) such that the relative risk of CHD is 1.31 for nonsmokers and 1.78 for smokers. Reductions in admissions for MI in locales where smoke-free workplace laws have been implemented have been observed, but none have assessed SCD. On January 1, 2002, a smoke-free restaurant law (Ordinance #1) was implemented in Olmsted County, Minnesota, and on October 1, 2007, all workplaces became smoke-free (Ordinance #2). Methods: Under the auspices of the Rochester Epidemiology Project, we measured the incidence of MI and SCD during the 18-month calendar period before and after implementation of each smoke-free ordinance. All MI were validated using biomarkers, cardiac pain, and Minnesota coding of the ECG. SCD was defined as out-of-hospital deaths assigned to CHD (ICD-9 codes 410 through 414). Results: For the overall study period of the 18 months before the implementation of the smoke-free restaurant ordinance and 18 months after the implementation of the smoke-free workplace ordinance, we observed a 45% decline in the incidence for MI (p <0.01) and a 50% decline in the incidence for SCD (p <0.01). See Table. During this same period, the prevalence of hypertension, diabetes, hypercholesterolemia, and obesity either remained constant or increased while the prevalence of smoking among adults declined by 23% (22% to 17%). Conclusion: In the Olmsted County population, substantial declines in the incidence of MI and SCD were observed after smoke-free laws were implemented. Smoke-free workplace laws may not only be associated with a decrease in MI but SCD as well.

Abstract Background Multimorbidity and functional limitation are associated with poor outcomes in heart failure (HF). However, the individual and combined effect of these on health‐related quality of life in patients with HF is not well understood. Methods Patients aged ≥30 years with two or more HF diagnostic codes and one or more HF‐related prescription drugs from four U.S. institutions were mailed a survey to measure patient‐centric factors including functional status (activities of daily living [ADLs]) and health‐related quality of life (PROMIS‐29 Health Profile). Patients with HF from January 1, 2013 to February 1, 2018 were included. Multimorbidity was defined as ≥2 non‐cardiovascular comorbidities; functional limitation as any limitation in at least one of eight ADLs. Patients were categorized into four groups by multimorbidity (Yes/No) and functional limitation (Yes/No). We dichotomized the PROMIS‐29 sub‐scale scores at the median and calculated odd ratios for the four multimorbidity/functional limitation groups. Results A total of 3330 patients with HF returned the survey (response rate 31%); 3020 completed the questions of interest and were retained. Among these patients (45% female; mean age 73 [standard deviation: 12] years), 29% had neither multimorbidity nor functional limitation, 24% had multimorbidity only, 22% had functional limitation only, and 25% had both. After adjustment, having functional limitation only was associated with higher anxiety (odds ratio [OR]: 3.44, 95% confidence interval [CI]: 2.66–4.45), depression (OR: 3.11, 95% CI: 2.39–4.06), and fatigue (OR: 4.19, 95% CI: 3.25–5.40); worse sleep (OR: 2.14, 95% CI: 1.69–2.72) and pain (OR: 6.73, 95% CI: 5.15–8.78); and greater difficulty with social activities (OR: 9.40, 95% CI: 7.19–12.28) compared with having neither. Results were similar for having both multimorbidity and functional limitation. Conclusion Patients with only functional limitation have similar poor health‐related quality of life scores as those with both multimorbidity and functional limitation, underscoring the important role that physical functioning plays in the well‐being of patients with HF.

Background Clinical risk scores are used to identify those at high risk of atherosclerotic cardiovascular disease (ASCVD). Despite preventative efforts, residual risk remains for many individuals. Very low‐density lipoprotein cholesterol (VLDL‐C) and lipid discordance could be contributors to the residual risk of ASCVD. Methods and Results Cardiovascular disease–free residents, aged ≥40 years, living in Olmsted County, Minnesota, were identified through the Rochester Epidemiology Project. Low‐density lipoprotein cholesterol (LDL‐C) and VLDL‐C were estimated from clinically ordered lipid panels using the Sampson equation. Participants were categorized into concordant and discordant lipid pairings based on clinical cut points. Rates of incident ASCVD, including percutaneous coronary intervention, coronary artery bypass grafting, stroke, or myocardial infarction, were calculated during follow‐up. The association of LDL‐C and VLDL‐C with ASCVD was assessed using Cox proportional hazards regression. Interaction between LDL‐C and VLDL‐C was assessed. The study population (n=39 098) was primarily White race (94%) and female sex (57%), with a mean age of 54 years. VLDL‐C (per 10‐mg/dL increase) was significantly associated with an increased risk of incident ASCVD (hazard ratio, 1.07 [95% CI, 1.05–1.09]; P <0.001]) after adjustment for traditional risk factors. The interaction between LDL‐C and VLDL‐C was not statistically significant ( P =0.11). Discordant individuals with high VLDL‐C and low LDL‐C experienced the highest rate of incident ASCVD events, 16.9 per 1000 person‐years, during follow‐up. Conclusions VLDL‐C and lipid discordance are associated with a greater risk of ASCVD and can be estimated from clinically ordered lipid panels to improve ASCVD risk assessment.

Background Frailty is common in heart failure (HF) and is associated with death but not routinely captured clinically. Frailty is linked with inflammation and malnutrition, which can be assessed by a novel plasma multimarker score: the metabolic vulnerability index (MVX). We sought to evaluate the associations between frailty and MVX and their prognostic impact. Methods and Results In an HF community cohort (2003–2012), we measured frailty as a proportion of deficits present out of 32 physical limitations and comorbidities, MVX by nuclear magnetic resonance spectroscopy, and collected extensive longitudinal clinical data. Patients were categorized by frailty score (≤0.14, >0.14 and ≤0.27, >0.27) and MVX score (≤50, >50 and ≤60, >60 and ≤70, >70). Cox models estimated associations of frailty and MVX with death, adjusted for Meta‐Analysis Global Group in Chronic Heart Failure (MAGGIC) score and NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide). Uno's C‐statistic measured the incremental value of MVX beyond frailty and clinical factors. Weibull's accelerated failure time regression assessed whether MVX mediated the association between frailty and death. We studied 985 patients (median age, 77; 48% women). Frailty and MVX were weakly correlated (Spearman's ρ=0.21). The highest frailty group experienced an increased rate of death, independent of MVX, MAGGIC score, and NT‐proBNP (hazard ratio, 3.3 [95% CI, 2.5–4.2]). Frailty improved Uno's c‐statistic beyond MAGGIC score and NT‐proBNP (0.69–0.73). MVX only mediated 3.3% and 4.5% of the association between high and medium frailty groups and death, respectively. Conclusions In this HF cohort, frailty and MVX are weakly correlated. Both independently contribute to stratifying the risk of death, suggesting that they capture distinct domains of vulnerability in HF.

BACKGROUND: Heart failure is heterogeneous syndrome with persistently high mortality. Nuclear magnetic resonance spectroscopy enables high-throughput metabolomics, suitable for precision phenotyping. We aimed to use targeted metabolomics to derive a metabolic risk score (MRS) that improved mortality risk stratification in heart failure. METHODS: Nuclear magnetic resonance was used to measure 21 metabolites (lipoprotein subspecies, branched-chain amino acids, alanine, GlycA (glycoprotein acetylation), ketone bodies, glucose, and citrate) in plasma collected from a heart failure community cohort. The MRS was derived using least absolute shrinkage and selection operator penalized Cox regression and temporal validation. The association between the MRS and mortality and whether risk stratification was improved over the Meta-Analysis Global Group in Chronic Heart Failure clinical risk score and NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels were assessed. RESULTS: The study included 1382 patients (median age, 78 years, 52% men, 43% reduced ejection fraction) with a 5-year survival rate of 48% (95% CI, 46%–51%). The MRS included 9 metabolites measured. In the validation data set, a 1 standard deviation increase in the MRS was associated with a large increased rate of death (hazard ratio, 2.2 [95% CI, 1.9–2.5]) that remained after adjustment for Meta-Analysis Global Group in Chronic Heart Failure score and NT-proBNP (hazard ratio, 1.6 [95% CI, 1.3–1.9]). These associations did not differ by ejection fraction. The integrated discrimination and net reclassification indices, and Uno’s C statistic, indicated that the addition of the MRS improved discrimination over Meta-Analysis Global Group in Chronic Heart Failure and NT-proBNP. CONCLUSIONS: This MRS developed in a heart failure community cohort was associated with a large excess risk of death and improved risk stratification beyond an established risk score and clinical markers.

Background Heart failure (HF) is a complex disease that contributes to a high number of hospitalizations, deaths, and economic health care costs each year. However, among patients with HF, there is a lack of awareness of their HF diagnosis that has not been fully examined. Methods and Results Residents from 3 counties of southeast Minnesota with a first‐ever International Classification of Diseases, Ninth Revision ( ICD‐9 ) code 428 or Tenth Revision ( ICD‐10 ) code I50 between January 1, 2013 and March 31, 2016 (N=2461) were prospectively surveyed to measure HF self‐awareness. A total of 1114 patients returned the survey (response rate, 45%), and 787 had validated HF upon medical record review. Among these 787 patients with HF (mean age, 76 years; 53% men), 37% (n=293) were aware of their HF diagnosis. After adjustment, being a woman (odds ratio [OR], 1.56 [95% CI, 1.10–2.22]), having HF with reduced ejection fraction (OR, 1.58 [95% CI, 1.13–2.22]), attending the HF clinic (OR, 4.07 [95% CI, 2.25–7.36]), and having coronary artery disease (OR, 1.65 [95% CI, 1.16–2.37]) were all associated with increased awareness of an HF diagnosis. Conversely, having diabetes was associated with decreased awareness of an HF diagnosis (adjusted OR, 0.69 [95% CI, 0.50–0.95]). Conclusions Awareness of an HF diagnosis is low in a community population of patients with HF. Strategies to improve patient awareness of their diagnosis should be implemented to improve self‐care behaviors and outcomes in patients with HF.