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1.  Calcium-Channel Blockers and Outcomes in Older Patients With Heart Failure and Preserved Ejection Fraction 
Circulation. Heart failure  2014;7(6):945-952.
Little is known about associations of calcium channel blockers (CCBs) with outcomes in patients with heart failure and preserved ejection fraction (HFpEF).
Methods and Results
Of the 10,570 hospitalized HFpEF patients, ≥65 years, EF ≥40%, in the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF; 2003–2004), linked to Medicare data (through December 31, 2008), 7514 had no prior history of CCB use. Of these, 815 (11%) patients received new discharge prescriptions for CCBs. Propensity scores for CCB initiation, calculated for each of the 7514 patients, were used to assemble a matched cohort of 1620 (810 pairs) patients (mean age, 80 years; mean EF, 56%; 65% women; 10% African American) receiving and not receiving CCBs, balanced on 114 baseline characteristics. The primary composite endpoint of all-cause mortality or HF hospitalization occurred in 82% and 81% of patients receiving and not receiving CCBs (hazard ratio {HR} for CCBs, 1.03; 95% confidence interval {CI}, 0.92–1.14). HRs (95% CIs) for all-cause mortality, HF hospitalization and all-cause hospitalization were 1.05 (0.94–1.18), 1.05 (0.91–1.21), and 1.03 (0.93–1.14), respectively. Similar associations were observed when we categorized patients into those receiving amlodipine and non-amlodipine CCBs. Among 7514 pre-match patients, multivariable-adjusted and propensity-adjusted HRs (95% CI) for primary composite endpoint were 1.03 (0.95–1.12) and 1.02 (0.94–1.11), respectively.
In hospitalized older HFpEF patients, new discharge prescriptions for CCBs had no associations with composite or individual endpoints of mortality or HF hospitalization, regardless of the class of CCBs.
PMCID: PMC4997614  PMID: 25296862
calcium channel blocker; heart failure; preserved ejection fraction
2.  Factors associated with variations in hospital expenditures for acute heart failure in the United States 
American heart journal  2014;169(2):282-289.e15.
Relatively little contemporary data are available that describe differences in acute heart failure (AHF) hospitalization expenditures as a function of patient and hospital characteristics, especially from a population-based investigation. This study aimed to evaluate factors associated with variations in hospital expenditures for AHF in the United States.
A cross-sectional analysis using discharge data from the 2011 Nationwide Inpatient Sample, Healthcare Cost and Utilization Project, was conducted. Discharges with primary International Classification of Diseases, Ninth Revision, Clinical Modification, diagnosis codes for AHF in adults were included. Costs were estimated by converting Nationwide Inpatient Sample charge data using the Healthcare Cost and Utilization Project Cost-to-Charge Ratio File. Discharges with highest (≥80th percentile) versus lowest (≤20th percentile) costs were compared for patient characteristics, hospital characteristics, utilization of procedures, and outcomes.
Of the estimated 1 million AHF hospital discharges, the mean cost estimates were $10,775 per episode. Younger age, higher percentage of obesity, atrial fibrillation, pulmonary disease, fluid/electrolyte disturbances, renal insufficiency, and greater number of cardiac/noncardiac procedures were observed in stays with highest versus lowest costs. Highest-cost discharges were more likely to be observed in urban and teaching hospitals. Highest-cost AHF discharges also had 5 times longer length of stay, were 9 times more costly, and had higher in-hospital mortality (5.6% vs 3.5%) compared with discharges with lowest costs (all P < .001).
Acute heart failure hospitalizations are costly. Expenditures vary markedly among AHF hospitalizations in the United States, with substantial differences in patient and hospital characteristics, procedures, and in-hospital outcomes among discharges with highest compared with lowest costs.
PMCID: PMC4316377  PMID: 25641538
3.  Differences in Health Care Use and Outcomes by the Timing of In-Hospital Worsening Heart Failure 
American heart journal  2015;170(6):1124-1132.
Patients hospitalized with acute heart failure may experience worsening symptoms requiring escalation of therapy. In-hospital worsening heart failure is associated with worse in-hospital and postdischarge outcomes, but associations between the timing of worsening heart failure and outcomes is unknown.
Using data from a large clinical registry linked to Medicare claims, we examined characteristics, outcomes, and costs of patients hospitalized for acute heart failure. We defined in-hospital worsening heart failure by the use of inotropes or intravenous vasodilators, or initiation of mechanical circulatory support, hemodialysis, or ventilation. The study groups were early worsening heart failure (n = 1990), late worsening heart failure (n = 4223), complicated presentation (n = 15,361), and uncomplicated hospital course (n = 41,334).
Among 62,908 patients, those with late in-hospital worsening heart failure had higher in-hospital and postdischarge mortality than patients with early worsening heart failure or complicated presentation. Those with early or late worsening heart failure had more frequent all-cause and heart failure readmissions at 30 days and 1 year, with resultant higher costs, compared with patients with an uncomplicated hospital course.
Although late worsening heart failure was associated with the highest mortality, both early and late worsening heart failure were associated with more frequent readmissions and higher health care costs compared to uncomplicated hospital course. Prevention of worsening heart failure may be an important focus in the care of hospitalized patients with acute heart failure.
PMCID: PMC4684593  PMID: 26678634
Disease Progression; Heart Failure; Hospitalization; Outcome Assessment (Health Care)
4.  Cost‐Effectiveness of LDL‐C Lowering With Evolocumab in Patients With High Cardiovascular Risk in the United States 
Clinical Cardiology  2016;39(6):313-320.
Randomized trials have shown marked reductions in low‐density lipoprotein cholesterol (LDL‐C), a risk factor for cardiovascular disease (CVD), when evolocumab is administered. We hypothesized that evolocumab added to standard of care (SOC) vs SOC alone is cost‐effective in the treatment of patients with heterozygous familial hypercholesterolemia (HeFH) or atherosclerotic CVD (ASCVD) with or without statin intolerance and LDL‐C >100 mg/dL. Using a Markov cohort state transition model, primary and recurrent CVD event rates were predicted considering population‐specific trial‐based mean risk factors and calibrated against observed rates in the real world. The LDL‐C–lowering effect from population‐specific phase 3 randomized studies for evolocumab was used together with estimated LDL‐C–lowering effect on CVD event rates per 38.67‐mg/dL LDL‐C lowering from a statin‐trial meta‐analysis. Costs and utilities were included from published sources. Evolocumab treatment was associated with both increased cost and improved quality‐adjusted life‐years (QALY): HeFH (incremental cost: US$153 289, incremental QALY: 2.02, incremental cost‐effectiveness ratio: US$75 863/QALY); ASCVD (US$158 307, 1.12, US$141 699/QALY); and ASCVD with statin intolerance (US$136 903, 1.36, US$100 309/QALY). Evolocumab met both the American College of Cardiology/American Heart Association (ACC/AHA) and World Health Organization (WHO) thresholds in each population evaluated. Sensitivity and scenario analyses confirmed that model results were robust to changes in model parameters. Among patients with HeFH and ASCVD with or without statin intolerance, evolocumab added to SOC may provide a cost‐effective treatment option for lowering LDL‐C using ACC/AHA intermediate/high value and WHO cost‐effectiveness thresholds. More definitive information on the clinical and economic value of evolocumab will be available from the forthcoming CVD outcomes study.
PMCID: PMC5074319  PMID: 27092712
5.  Medication Initiation Burden Required to Comply with Heart Failure Guideline Recommendations and Hospital Quality Measures 
Circulation  2015;132(14):1347-1353.
Guidelines for heart failure (HF) recommend prescription of guideline-directed medical therapy before hospital discharge; some of these therapies are included in publicly reported performance measures. The burden of new medications for individual patients has not been described.
Methods and Results
Get With The Guidelines-HF registry 2008–2013 collected prescribing, indications, and contraindications for angiotensin converting enzyme inhibitors or angiotensin receptor blockers (ACEI/ARB), beta-blockers (BB), aldosterone antagonists (AldA), hydralazine/isosorbide dinitrate (H/ISDN), and anticoagulants. The difference between a patient’s medication regimen at hospital admission and that recommended by HF quality measures at discharge was calculated. Among 158,922 patients from 271 hospitals with a primary discharge diagnosis of HF, initiation of ACEI/ARB was indicated in 18.1% of all patients (55.5% of those eligible at discharge were not receiving ACEI/ARB at admission), BB in 20.3% (50.5% of eligible), AldA in 24.1% (87.4% of eligible), H/ISDN in 8.6% (93.1% of eligible), and anticoagulant in 18.0% (58.0% of eligible). Cumulatively, 0.4% of patients were eligible for 5 new medication groups, 4.1% for 4, 9.4% for 3, 10.1% for 2, and 22.7% for 1; 15.0% were not eligible for new medications because of adequate prescribing at admission; and 38.4% were not eligible for any medications recommended by HF quality measures. Compared with newly indicated medications (mean 1.45±1.23), actual new prescriptions were lower (mean 1.16±1.00).
A quarter of patients hospitalized with HF need to start more than 1 medication to meet HF quality measures. Systems for addressing medication initiation and managing polypharmacy are central to HF transitional care.
PMCID: PMC4941099  PMID: 26316616
Heart Failure; Quality of Health Care; Prescribing Patterns; Physician; Medication Therapy Management; Medication Adherence
6.  Temporal Trends in Care and Outcomes of Patients Receiving Fibrinolytic Therapy Compared to Primary Percutaneous Coronary Intervention: Insights From the Get With The Guidelines Coronary Artery Disease (GWTG‐CAD) Registry 
Timely reperfusion after ST‐elevation myocardial infarction (STEMI) improves survival. Guidelines recommend primary percutaneous coronary intervention (PPCI) within 90 minutes of arrival at a PCI‐capable hospital. The alternative is fibrinolysis within 30 minutes for those in those for whom timely transfer to a PCI‐capable hospital is not feasible.
Methods and Results
We identified STEMI patients receiving reperfusion therapy at 229 hospitals participating in the Get With the Guidelines—Coronary Artery Disease (GWTG‐CAD) database (January 1, 2003 through December 31, 2008). Temporal trends in the use of fibrinolysis and PPCI, its timeliness, and in‐hospital mortality outcomes were assessed. We also assessed predictors of fibrinolysis versus PPCI and compliance with performance measures. Defect‐free care was defined as 100% compliance with all performance measures. We identified 29 190 STEMI patients, of whom 2441 (8.4%) received fibrinolysis; 38.2% of these patients achieved door‐to‐needle times ≤30 minutes. Median door‐to‐needle times increased from 36 to 60 minutes (P=0.005) over the study period. Among PPCI patients, median door‐to‐balloon times decreased from 94 to 64 minutes (P<0.0001) over the same period. In‐hospital mortality was higher with fibrinolysis than with PPCI (4.6% vs 3.3%, P=0.001) and did not change significantly over time. Patients receiving fibrinolysis were less likely to receive defect‐free care compared with their PPCI counterparts.
Use of fibrinolysis for STEMI has decreased over time with concomitant worsening of door‐to‐needle times. Over the same time period, use of PPCI increased with improvement in door‐to‐balloon times. In‐hospital mortality was higher with fibrinolysis than with PPCI. As reperfusion for STEMI continues to shift from fibrinolysis to PPCI, it will be critical to ensure that door‐to‐needle times and outcomes do not worsen.
PMCID: PMC5121508  PMID: 27792640
fibrinolysis; myocardial infarction; outcome and process assessment; primary percutaneous coronary intervention; Myocardial Infarction; Percutaneous Coronary Intervention; Quality and Outcomes; Epidemiology; Secondary Prevention
7.  ACC/AHA/AACVPR/AAFP/ANA Concepts for Clinician–Patient Shared Accountability in Performance Measures 
Circulation  2014;130(22):1984-1994.
PMCID: PMC4500543  PMID: 25366994
AHA Scientific Statements; quality indicators; quality measurement; shared accountability
8.  Higher risk for incident heart failure and cardiovascular mortality among community‐dwelling octogenarians without pneumococcal vaccination 
Esc Heart Failure  2015;3(1):11-17.
Octogenarians have the highest incidence of heart failure (HF) that is not fully explained by traditional risk factors. We explored whether lack of pneumococcal vaccination is associated with higher risk of incident HF among octogenarians.
Methods and results
In the Cardiovascular Health Study (CHS), 5290 community‐dwelling adults, ≥65 years of age, were free of baseline HF and had data on pneumococcal vaccination. Of these, 851 were octogenarians, of whom, 593 did not receive pneumococcal vaccination. Multivariable‐adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for associations of lack of pneumococcal vaccination with incident HF and other outcomes during 13 years of follow‐up were estimated using Cox regression models, adjusting for demographics and other HF risk factors including influenza vaccination. Octogenarians had a mean (±SD) age of 83 (±3) years; 52% were women and 17% African American. Overall, 258 participants developed HF and 662 died. Lack of pneumococcal vaccination was associated with higher relative risk of incident HF (aHR, 1.37; 95% CI, 1.01–1.85; P = 0.044). There was also higher risk for all‐cause mortality (aHR, 1.23; 95% CI, 1.02–1.49; P = 0.028), which was mostly driven by cardiovascular mortality (aHR, 1.45; 95% CI, 1.06–1.98; P = 0.019). Octogenarians without pneumococcal vaccination had a trend toward higher risk of hospitalization due to pneumonia (aHR, 1.34; 95% CI, 0.99–1.81; P = 0.059). These associations were not observed among those 65–79 years of age.
Among community‐dwelling octogenarians, lack of pneumococcal vaccination was associated with a significantly higher independent risk of incident HF and mortality, and trend for higher pneumonia hospitalization.
PMCID: PMC5019269  PMID: 27668089
Octogenarians; Pneumococcal vaccination; Heart failure; Mortality
9.  ACC/AHA/AACVPR/AAFP/ANA Concepts for Clinician–Patient Shared Accountability in Performance Measures 
Developed in collaboration with the National Committee for Quality Assurance, the American Society of Health-System Pharmacists, and the American Medical Association–Physician Consortium for Performance Improvement
Endorsed by the American Society of Health-System Pharmacists
PMCID: PMC4476791  PMID: 25439761
ACC/AHA performance measure; quality indicators; quality measurement; shared accountability
10.  Relationship of physical activity and healthy eating with mortality and incident heart failure among community‐dwelling older adults with normal body mass index 
Esc Heart Failure  2015;2(1):20-24.
Normal body mass index (BMI) is associated with lower mortality and may be achieved by physical activity (PA), healthy eating (HE), or both. We examined the association of PA and HE with mortality and incident heart failure (HF) among 2040 community‐dwelling older adults aged ≥ 65 years with baseline BMI 18.5 to 24.99 kg/m2 during 13 years of follow‐up in the Cardiovascular Health Study.
Methods and results
Baseline PA was defined as ≥500 weekly metabolic equivalent task‐minutes and HE as ≥5 daily servings of vegetable and fruit intake. Participants were categorized into four groups: (i) PA−/HE− (n = 384); (ii) PA−/HE+ (n = 162); (iii) PA+/HE− (n = 992); and (iv) PA+/HE+ (n = 502). Participants had a mean age of 74 (±6) years, mean BMI of 22.6 (±1.5) kg/m2, 61% were women, and 4% African American. Compared with PA−/HE−, age‐sex‐race‐adjusted hazard ratios and 95% confidence intervals for all‐cause mortality for PA−/HE+, PA+/HE−, and PA+/HE+ groups were 0.96 (0.76–1.21), 0.61 (0.52–0.71), and 0.62 (0.52–0.75), respectively. These associations remained unchanged after multivariable adjustment and were similar for cardiovascular and non‐cardiovascular mortalities. Respective demographic‐adjusted hazard ratios (95% confidence intervals) for incident HF among 1954 participants without baseline HF were 1.21 (0.81–1.81), 0.71 (0.54–0.94), and 0.71 (0.51–0.98). These latter associations lost significance after multivariable adjustment.
Among community‐dwelling older adults with normal BMI, physical activity, regardless of healthy eating, was associated with lower risk of mortality and incident HF, but healthy eating had no similar protective association in this cohort.
PMCID: PMC4973627  PMID: 27499885
Physical activity; Healthy eating; Incident heart failure; Older adults
11.  Payment Source, Quality of Care, and Outcomes in Patients Hospitalized with Heart Failure 
This study analyzed the relationship between payment source and quality of care and outcomes in heart failure (HF).
HF is a major cause of morbidity and mortality. There is a lack of studies assessing the association of payment source on HF quality of care and outcomes.
We analyzed 99,508 HF admissions from 244 sites between January 2005 and September 2009. Patients were grouped based on payer status (private/HMO; no insurance; Medicare; Medicaid) with the private/HMO group as reference.
The no insurance group was less likely to receive evidence-based beta-blockers (EBBB; adjusted odds ratio [OR] 0.73, 95% confidence intervals [CI] 0.62 to 0.86), an implantable cardioverter defibrillator (ICD; OR 0.59, 95% CI 0.50 to 0.70) or anticoagulation for atrial fibrillation (OR 0.73, 95% CI 0.61 to 0.87). Similarly, the Medicaid group was less likely to receive EBBB (OR 0.86, 95% CI 0.78 to 0.95) or ICD (OR 0.86, 95% CI 0.78 to 0.96). ACEI/ARB and beta-blockers were prescribed less frequently in the Medicare group (OR 0.89, 95% CI 0.81 to 0.98). Medicare, Medicaid, and no insurance groups had longer hospital stays. Higher adjusted rates of in-hospital mortality were seen in patients with Medicaid (OR 1.22, 95% CI 1.06 to 1.41) and in reduced systolic function patients with no insurance.
Decreased quality of care and outcomes for patients with HF was observed in no insurance, Medicaid and Medicare groups compared to the private/HMO group.
PMCID: PMC4603423  PMID: 21939830
payment source; quality; outcomes
12.  Factors Associated With Initial Prasugrel Versus Clopidogrel Selection for Patients With Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention: Insights From the Treatment With ADP Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome (TRANSLATE‐ACS) Study 
Few studies have examined how antiplatelet therapies are selected during the routine care of acute myocardial infarction patients, particularly relative to the patient's estimated mortality and bleeding risks.
Methods and Results
We examined patients presenting with acute myocardial infarction treated with percutaneous coronary intervention at 233 US hospitals in the TRANSLATE‐ACS observational study from April 2010 to October 2012. We developed a multivariable logistic regression model to identify factors associated with prasugrel selection. Prasugrel use rates and associated 1‐year risk‐adjusted major adverse cardiovascular events and Global Utilization of Streptokinase and t‐PA for Occluded Coronary Arteries (GUSTO) moderate/severe bleeding outcomes were also examined in relation to predicted mortality and bleeding using the validated Acute Coronary Treatment and Intervention Outcomes (ACTION) risk prediction scores. Among 11 969 patients, 3123 (26%) received prasugrel at the time of percutaneous coronary intervention. The strongest factors associated with prasugrel use included cardiogenic shock (odds ratio [OR] 1.68, 95% CI 1.25–2.26), drug‐eluting stent use (OR 1.45, 95% CI 1.31–1.62), and ST‐segment elevation myocardial infarction presentation (OR 1.23, 95% CI 1.12–1.35). Older age (OR 0.57, 95% CI 0.0.53–0.61), dialysis (OR 0.56, 95% CI 0.32–0.96), prior history of stroke/transient ischemic attack (OR 0.52, 95% CI 0.38–0.73), and interhospital transfer (OR 0.50, 95% CI 0.46–0.55) were associated with lowest prasugrel selection. Prasugrel was used less often than clopidogrel in patients at higher predicted bleeding risk (21.9% versus 29.7%, P<0.001). Yet paradoxically, prasugrel was also less likely than clopidogrel to be used in patients with higher predicted mortality risk (21.1% versus 30.2%, P<0.001). Adjusted bleeding and outcomes events were similar among those receiving prasugrel and clopidogrel in the 4 subgroups of patients based on bleeding risk and ischemic benefits.
In community practice, prasugrel use may be driven more by bleeding risk rather than ischemic benefit. This may result in underutilization of higher potency ADP receptor inhibitor among patients more likely to derive ischemic benefit.
PMCID: PMC5079042  PMID: 27663414
acute coronary syndrome; clopidogrel; prasugrel; risk prediction; Acute Coronary Syndromes; Coronary Artery Disease
13.  Relationship of Physical Activity and Healthy Eating with Mortality and Incident Heart Failure among Community-Dwelling Older Adults with Normal Body Mass Index 
ESC heart failure  2015;2(1):20-24.
Normal body mass index (BMI) is associated with lower mortality and may be achieved by physical activity (PA), healthy eating (HE), or both. We examined the association of PA and HE with mortality and incident heart failure (HF) among 2040 community-dwelling older adults aged ≥ 65 years with baseline BMI 18.5 to 24.99 kg/m2 during 13 years of follow-up in Cardiovascular Health Study.
Methods and results
Baseline PA was defined as ≥500 weekly metabolic equivalent task-minutes (MET-minutes) and HE as ≥5 daily servings of vegetable and fruit intake. Participants were categorized into 4 groups: (1) PA−/HE− (n=384); (2) PA+/HE− (n=992); (3) PA−/HE+ (n=162); and (4) PA+/HE+ (n=502). Participants had a mean age of 74 (±6) years, mean BMI of 22.6 (±1.5) kg/m2, 61% were women, and 4% African American. Compared with PA−/HE−, age-sex-race-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality for PA−/HE+, PA+/HE−, and PA+/HE+ groups were 0.96 (0.76–1.21), 0.61 (0.52–0.71) and 0.62 (0.52–0.75), respectively. These associations remained unchanged after multivariable adjustment and were similar for cardiovascular and non-cardiovascular mortalities. Respective demographic-adjusted HRs (95% Cis) for incident HF among 1954 participants without baseline HF were 1.21 (0.81–1.81), 0.71 (0.54–0.94) and 0.71 (0.51–0.98). These later associations lost significance after multivariable-adjustment.
Among community-dwelling older adults with normal BMI, physical activity, regardless of healthy eating, was associated with lower risk of mortality and incident HF, but healthy eating had no similar protective association in this cohort.
PMCID: PMC4973627  PMID: 27499885
Physical activity; healthy eating; incident heart failure; older adults
14.  Discharge Hospice Referral and Lower 30-Day All-Cause Readmission in Medicare Beneficiaries Hospitalized for Heart Failure 
Circulation. Heart failure  2015;8(4):733-740.
Heart failure (HF) is the leading cause for hospital readmission. Hospice care may help palliate HF symptoms but its association with 30-day all-cause readmission remains unknown.
Methods and Results
Of the 8032 Medicare beneficiaries hospitalized for HF in 106 Alabama hospitals (1998–2001), 182 (2%) received discharge hospice referrals. Of the 7850 patients not receiving hospice referrals, 1608 (20%) died within 6 months post-discharge (the hospice-eligible group). Propensity scores for hospice referral were estimated for each of the 1790 (182+1608) patients and were used to match 179 hospice-referral patients with 179 hospice-eligible patients who were balanced on 28 baseline characteristics (mean age, 79 years, 58% women, 18% African American). Overall, 22% (1742/8032) died in 6 months, of whom 8% (134/1742) received hospice referrals. Among the 358 matched patients, 30-day all-cause readmission occurred in 5% and 41% of hospice-referral and hospice-eligible patients, respectively (hazard ratio {HR} associated with hospice referral, 0.12; 95% confidence interval {CI}, 0.06–0.24). HRs (95% CIs) for 30-day all-cause readmission associated with hospice referral among the 126 patients who died and 232 patients who survived 30-day post-discharge were 0.03 (0.04–0.21) and 0.17 (0.08–0.36), respectively. Although 30-day mortality was higher in the hospice referral group (43% vs. 27%), it was similar at 90 days (64% vs. 67% among hospice-eligible patients).
A discharge hospice referral was associated with lower 30-day all-cause readmission among hospitalized HF patients. However, most HF patients who died within 6 months of hospital discharge did not receive a discharge hospice referral.
PMCID: PMC4964848  PMID: 26019151
Medicare beneficiaries; heart failure; discharge hospice referral; 30-day all-cause readmission
15.  Cerebral Blood Flow Velocity and Vasomotor Reactivity during Autonomic Challenges in Heart Failure 
Nursing research  2014;63(3):194-202.
Significant alterations in autonomic nervous system (ANS) function, vasomotor reactivity, and cerebral blood flow may develop from damage to brain ANS regulatory areas in heart failure (HF). This preferentially right-sided injury occurs largely in autonomic structures perfused by the middle cerebral artery. Indications of altered, asymmetrical perfusion raise the potential for further neural damage.
To determine whether the extent of middle cerebral artery blood flow velocity and vasomotor reactivity is altered on one side of the brain over the other in HF vs. control subjects, three ANS challenges were administered—each challenge recruited ANS regulatory areas potentially injured in HF.
Transcranial Doppler ultrasonography was used to measure cerebral blood flow velocity and vasomotor reactivity in 40 HF (mean age = 52.7 years, SD = 7.5; 27 males; left ventricular ejection fraction 26.8, SD = 8.3) and 42 control subjects (mean age = 48.3 years; SD = 6.0; 22 males) during 5% CO2 and hyperventilation, Valsalva, and orthostatic (upper body tilt) challenges.
Lower cerebral blood flow velocity and abnormal vasomotor reactivity (p < .01) were noted in HF middle cerebral arteries during all challenges. More right-sided flow velocity reductions appeared in HF, with laterality differences noted during CO2 and orthostatic (p < .05), but not Valsalva challenges.
Diminished cerebral blood flow velocity and altered vasomotor reactivity were associated with HF, changes being preferentially on the right-side; the asymmetry was more pronounced during CO2 and orthostatic challenges. The impaired blood flow regulation may contribute to the lateralized brain pathology in ANS areas, undermining autonomic control in HF.
PMCID: PMC4024060  PMID: 24785247
asymmetrical brain injury; carbon dioxide; heart failure; orthostatic challenge; transcranial Doppler ultrasonography; Valsalva maneuver
We sought to examine whether characteristics, implant strategy, and outcomes in patients who receive continuous-flow left ventricular assist devices (CF-LVAD) differ across geographic regions in the United States (US).
A total of 7,404 CF-LVAD patients enrolled in the INTERMACS from 134 participating institutions were analyzed from four distinct regions: Northeast (n=2605, 35%), Midwest (n=2210, 30%), West (n=973, 13%) and South (n=1616, 22%).
At baseline, patients in the Northeast and South were more likely to have INTERMACS risk profiles 1 and 2. Bridge to transplant (BTT) strategy was more common in the Northeast (Northeast=31.7%; West=18.5%; South=26.9%; Midwest=25.5%; p<0.0001). In contrast, destination therapy (DT) was more likely in the South (South=40.6%; Northeast=32.3%; Midwest=27.3%; West=27.3%, p<0.0001). While all regions showed a high one year survival rate, some regional differences in long term mortality were observed. Notably, South had a significantly lower survival beyond 1 year after LVAD implant. However, when stratified by device strategy, no significant differences in survival for BTT or DT patients were found among regions. Finally, with the exception of right ventricular failure that was more common in the South region, no other significant differences in causes of death were observed among regions.
Regional differences in clinical profile and LVAD strategy exist in the US. Despite an overall high survival rate at 1 year, differences in mortality among regions were noted. The lower survival rate in the South may be attributed to patient characteristics and higher use of LVAD as DT.
PMCID: PMC4475666  PMID: 25824553
17.  Novel Oral Anticoagulant Use Among Patients with Atrial Fibrillation Hospitalized with Ischemic Stroke or Transient Ischemic Attack 
Novel oral anticoagulants (NOACs) have been shown to be at least as good as warfarin for preventing stroke or transient ischemic attack (TIA) in patients with atrial fibrillation (AF), yet diffusion of these therapies and patterns of use among AF patients with ischemic stroke and TIA have not been well characterized.
Methods and Results
Using data from Get With The Guidelines®–Stroke, we identified a cohort of 61,655 AF patients with ischemic stroke or TIA hospitalized between 10/2010–09/2012 and discharged on warfarin or NOAC (either dabigatran or rivaroxaban). Multivariable logistic regression was used to identify factors associated with NOAC versus warfarin therapy. In our study population, warfarin was prescribed to 88.9%, dabigatran to 9.6%, and rivaroxaban to 1.5%. NOAC use increased from 0.04% to a 16–17% plateau during the study period, though anticoagulation rates among eligible patients did not change appreciably (93.7% vs. 94.1% from first quarter 2011 to second quarter 2012), suggesting a trend of switching from warfarin to NOACs rather than increased rates of anticoagulation among eligible patients. Several bleeding risk factors and CHA2DS2-VASc scores were lower among those discharged on NOAC versus warfarin therapy (47.9% vs. 40.9% with CHA2DS2-VASc ≤5, p<0.001 for difference in CHA2DS2-VASc).
NOACs have had modest but growing uptake over time among AF patients hospitalized with stroke or TIA and are prescribed to patients with lower stroke risk compared to warfarin.
PMCID: PMC4512906  PMID: 26058721
anticoagulant; anticoagulation; stroke; fibrillation
18.  Early Medication Nonadherence After Acute Myocardial Infarction: Insights into Actionable Opportunities from the TRANSLATE-ACS Study 
Nonadherence to prescribed evidence-based medications after acute myocardial infarction (MI) can contribute to worse outcomes and higher costs. We sought to better understand the modifiable factors contributing to early nonadherence of evidence-based medications after acute MI.
Methods and Results
We assessed 7,425 acute MI patients treated with percutaneous coronary intervention (PCI) at 216 United States hospitals participating in TRANSLATE-ACS between 04/2010–05/2012. Using the validated Morisky instrument to assess cardiovascular medication adherence at 6 weeks post-MI, we stratified patients into self-reported high (score 8), moderate (score 6–7), and low (score <6) adherence groups. Moderate and low adherence was reported in 25% and 4% of patients, respectively. One-third of low adherence patients described missing doses of antiplatelet therapy at least twice a week after PCI. Signs of depression and patient-reported financial hardship due to medication expenses were independently associated with a higher likelihood of medication nonadherence. Patients were more likely to be adherent at 6 weeks if they had follow-up appointments made prior to discharge and had a provider explain potential side effects of their medications. Lower medication adherence may be associated with a higher risk of 3-month death/readmission (adjusted HR 1.35, 95% CI 0.98, 1.87) although this did not reach statistical significance.
Even early after MI, a substantial proportion of patients report suboptimal adherence to prescribed medications. Tailored patient education and pre-discharge planning may represent actionable opportunities to optimize patient adherence and clinical outcomes.
Clinical Trial Registry Information
clinical trial #NCT01088503; URL:
PMCID: PMC4512913  PMID: 26038524
acute myocardial infarction; adherence; antiplatelet therapy; percutaneous coronary intervention
19.  Digoxin use and subsequent outcomes among patients in a contemporary atrial fibrillation cohort 
Although digoxin has long been used to treat atrial fibrillation (AF) and heart failure (HF), its safety remains controversial.
This study sought to describe digoxin use over time in patients with AF stratified by presence or absence of HF; characterize predictors of digoxin use and initiation; and correlate digoxin use with outcomes.
Longitudinal patterns of digoxin use and its association with a variety of outcomes were assessed in a prospective outpatient registry conducted at 174 U.S. sites with enrollment from June 2010 to August 2011.
Among 9,619 patients with AF and serial follow-up every 6 months for up to 3 years, 2,267 (23.6%) were receiving digoxin at study enrollment, 681 (7.1%) were initiated on digoxin during follow-up, and 6,671 (69.4%) were never prescribed digoxin. Adjusting for other medications, heart rate was 72.9 beats/min among digoxin users and 71.5 among nonusers (p < 0.0001). Prevalent digoxin use at registry enrollment was not associated with subsequent onset of symptoms, hospitalization, or mortality (in patients with HF, adjusted hazard ratio [HR] for death: 1.04; without HF, HR: 1.22). Incident digoxin use during follow-up was not associated with subsequent death in patients with HF (propensity-adjusted HR: 1.05) but was in those without HF (propensity-adjusted HR: 1.99).
After adjustment for detailed clinical factors, digoxin use in registry patients with AF had a neutral association with outcomes under most circumstances. Given multiple conflicting observational reports about digoxin’s safety and possible concerns in specific clinical situations, a large pragmatic trial of digoxin therapy in AF is needed.
PMCID: PMC4483195  PMID: 26112191
heart failure; mortality; patient outcome assessment; safety
20.  Clinical Effectiveness of CRT and ICD Therapy in Heart Failure Patients by Racial/Ethnic Classification 
Clinical trials have demonstrated benefit for cardiac resynchronization therapy (CRT) and implantable cardioverter-defibrillator (ICD) therapies in patients with heart failure with reduced ejection fraction (HFrEF); yet, questions have been raised with regard to the benefit of device therapy for minorities.
The purpose of this study was to determine the clinical effectiveness of CRT and ICD therapies as a function of race/ethnicity in outpatients with HFrEF (ejection fraction ≤35%).
Data from IMPROVE HF (Registry to Improve the Use of Evidence-Based Heart Failure Therapies in the Outpatient Setting) were analyzed by device status and race/ethnicity among guideline-eligible patients for mortality at 24 months. Multivariate Generalized Estimating Equations analyses were conducted, adjusting for patient and practice characteristics.
The ICD/cardiac resynchronization defibrillator (CRT-D)–eligible cohort (n = 7,748) included 3,391 (44%) non-Hispanic white, 719 (9%) non-Hispanic black, and 3,638 (47%) other racial/ethnic minorities or race-not-documented patients. The cardiac resynchronization pacemaker (CRT-P)/CRT-D–eligible cohort (n = 1,188) included 596 (50%) non-Hispanic white, 99 (8%) non-Hispanic black, and 493 (41%) other/not-documented patients. There was clinical benefit associated with ICD/CRT-D therapy (adjusted odds ratio: 0.64, 95% confidence interval: 0.52 to 0.79, p = 0.0002 for 24-month mortality), which was of similar proportion in white, black, and other minority/not-documented patients (device–race/ethnicity interaction p = 0.7861). For CRT-P/CRT-D therapy, there were also associated mortality benefits (adjusted odds ratio: 0.55, 95% confidence interval: 0.33 to 0.91, p = 0.0222), and the device–race/ethnicity interaction was not significant (p = 0.5413).
The use of guideline-directed CRT and ICD therapy was associated with reduced 24-month mortality without significant interaction by racial/ethnic group. Device therapies should be offered to eligible heart failure patients, without modification based on race/ethnicity.
PMCID: PMC4319359  PMID: 25145524
cardiac resynchronization therapy; clinical effectiveness; heart failure; mortality; race/ethnicity
21.  Lateralized Resting-State Functional Brain Network Organization Changes in Heart Failure 
PLoS ONE  2016;11(5):e0155894.
Heart failure (HF) patients show brain injury in autonomic, affective, and cognitive sites, which can change resting-state functional connectivity (FC), potentially altering overall functional brain network organization. However, the status of such connectivity or functional organization is unknown in HF. Determination of that status was the aim here, and we examined region-to-region FC and brain network topological properties across the whole-brain in 27 HF patients compared to 53 controls with resting-state functional MRI procedures. Decreased FC in HF appeared between the caudate and cerebellar regions, olfactory and cerebellar sites, vermis and medial frontal regions, and precentral gyri and cerebellar areas. However, increased FC emerged between the middle frontal gyrus and sensorimotor areas, superior parietal gyrus and orbito/medial frontal regions, inferior temporal gyrus and lingual gyrus/cerebellar lobe/pallidum, fusiform gyrus and superior orbitofrontal gyrus and cerebellar sites, and within vermis and cerebellar areas; these connections were largely in the right hemisphere (p<0.005; 10,000 permutations). The topology of functional integration and specialized characteristics in HF are significantly changed in regions showing altered FC, an outcome which would interfere with brain network organization (p<0.05; 10,000 permutations). Brain dysfunction in HF extends to resting conditions, and autonomic, cognitive, and affective deficits may stem from altered FC and brain network organization that may contribute to higher morbidity and mortality in the condition. Our findings likely result from the prominent axonal and nuclear structural changes reported earlier in HF; protecting neural tissue may improve FC integrity, and thus, increase quality of life and reduce morbidity and mortality.
PMCID: PMC4874547  PMID: 27203600
22.  Opportunities for Improving Global Cardiovascular Quality of Care and Outcomes 
PMCID: PMC4323777  PMID: 25304855
Editorials; acute myocardial infarction; aspirin; outcomes; quality of care
23.  Utility of Socioeconomic Status in Predicting 30-Day Outcomes After Heart Failure Hospitalization 
Circulation. Heart failure  2015;8(3):473-480.
An individual's socioeconomic status (SES) is associated with health outcomes and mortality, yet it is unknown whether accounting for SES can improve risk-adjustment models for 30-day outcomes among Centers for Medicare & Medicaid Services (CMS) beneficiaries hospitalized with heart failure (HF).
Methods and Results
We linked clinical data on hospitalized HF patients in the Get With The Guidelines®-HF™ database (01/2005–12/2011) with CMS claims and county-level SES data from the 2012 Area Health Resources Files. We compared the discriminatory capabilities of multivariable models that adjusted for SES, patient, and/or hospital characteristics to determine whether county-level SES data improved prediction or changed hospital rankings for 30-day all-cause mortality and rehospitalization. After adjusting for patient and hospital characteristics, median household income (per $5,000 increase) was inversely associated with odds of 30-day mortality (OR 0.97, 95% CI 0.95–1.00, p=0.032), and the percentage of persons with at least a high school diploma (per 5 unit increase) was associated with lower odds of 30-day rehospitalization (OR 0.95, 95% CI 0.91–0.99).After adjustment for county-level SES data, relative to whites, Hispanic ethnicity (OR 0.70, 95% CI 0.58, 0.83) and black race (OR 0.57, 95% CI: 0.50–0.65) remained significantly associated with lower 30-day mortality, but had similar 30-day rehospitalization. County-level SES did not improve risk adjustment or change hospital rankings for 30-day mortality or rehospitalization.
County-level SES data are modestly associated with 30-day outcomes for CMS beneficiaries hospitalized with HF, but do not improve risk adjustment models based on patient characteristics alone.
PMCID: PMC4439274  PMID: 25747700
heart failure; predictive models; risk stratification
24.  Regional Hippocampal Damage in Heart Failure 
European journal of heart failure  2015;17(5):494-500.
Heart failure (HF) patients show cognitive and mood impairments, including short-term memory loss and depression, adversely impacting quality of life and self-care management. Brain regions, including the hippocampus, a structure significantly involved in memory and mood, show injury in HF, but the integrity of specific hippocampal subregions is unclear.
Methods and results
To assess regional hippocampal volume loss, we evaluated 17 HF patients (mean age ± SD, 54.4 ± 2.0 years; 12 male, LVEF 28.3 ± 6.8%; NYHA Class II/III 94%/6%) and 34 healthy control subjects (52.3 ± 1.3 years; 24 male) using high-resolution T1-weighted magnetic resonance imaging and evaluated localized surface changes with morphometric procedures. Hippocampi were manually outlined, and volumes calculated from normalized tracings.
Volume differences between groups were assessed by two-sample t-tests, and regional differences were assessed by surface morphometry. HF patients exhibited smaller hippocampal volumes than controls (Right: 3060±146 vs. 3478±94 mm3; p = 0.02, Left: 3021±145 vs. 3352±98 mm3; p = 0.06). Volume reductions were detected principally in CA1, an area integral to an array of learning and memory functions, as well as in mid- to posterior CA3 and subiculum.
The hippocampus shows regional volume reduction in HF, which may contribute to short-term memory loss and depression associated with the condition.
PMCID: PMC4651448  PMID: 25704495
Magnetic resonance imaging; brain; hippocampus; memory; cognition
25.  Clinical Characteristics, Oral Anticoagulation Patterns, and Outcomes of Medicaid Patients With Atrial Fibrillation: Insights From the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT‐AF I) Registry 
Whereas insurance status has been previously associated with care patterns, little is currently known about the association between Medicaid insurance and the clinical characteristics, treatment, or outcomes of patients with atrial fibrillation (AF).
Methods and Results
We used data from adults with AF enrolled in the Outcomes Registry for Better Informed Treatment of AF (ORBIT‐AF), a national outpatient registry conducted at 176 community, multispecialty sites. The primary outcome of interest was the proportion of patients prescribed any oral anticoagulation (OAC; warfarin or novel oral anticoagulants [NOAC]). Secondary outcomes of interest included the proportion of patients prescribed NOACs (dabigatran or rivaroxaban); time in therapeutic range (TTR) for warfarin users, all‐cause mortality, stroke/systemic embolism, and major bleed. Of 10 133 patients, N=470 (4.6%) had Medicaid insurance. Medicaid patients were similarly likely to receive OAC at baseline (72.8% vs 76.3%; unadjusted P=0.079), but less likely to receive NOAC at baseline or follow‐up (12.1% vs 16.3%; unadjusted P=0.019). After risk adjustment, Medicaid status was associated with lower use of OAC at baseline among patients with high stroke risk (odds ratio [OR]=0.68; 95% CI=0.49, 0.94), but was not associated with OAC use overall (OR=0.82; 95% CI=0.61, 1.09). Among warfarin users, median TTR was lower among Medicaid patients (60% vs 68%; P<0.0001; adjusted TTR difference, −2.9; 95% CI=−5.7, −0.2; P=0.04). Use of an NOAC over 2 years of follow‐up was not statistically different by insurance. Compared with non‐Medicaid patients, Medicaid patients had higher unadjusted rates of mortality, stroke/systemic embolism, and major bleeding; however, these differences were attenuated following adjustment for clinical characteristics.
In a contemporary AF cohort, use of OAC overall and use of NOACs were not significantly lower among Medicaid patients relative to others. However, among warfarin users, Medicaid patients spent less time in therapeutic range compared with those with other forms of insurance.
PMCID: PMC4889165  PMID: 27146448
anticoagulation; atrial fibrillation; Medicaid; quality of care; stroke prevention; Atrial Fibrillation; Health Services; Quality and Outcomes; Primary Prevention

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