Artificial intelligence approaches for phenotyping heart failure in U.S. Veterans Health Administration electronic health record.

AIMS: Heart failure (HF) is a clinical syndrome with no definitive diagnostic tests. HF registries are often based on manual reviews of medical records of hospitalized HF patients identified using International Classification of Diseases (ICD) codes. However, most HF patients are not hospitalized, and manual review of big electronic health record (EHR) data is not practical. The US Department of Veterans Affairs (VA) has the largest integrated healthcare system in the nation, and an estimated 1.5 million patients have ICD codes for HF (HF ICD-code universe) in their VA EHR. The objective of our study was to develop artificial intelligence (AI) models to phenotype HF in these patients. METHODS AND RESULTS: The model development cohort (n = 20 000: training, 16 000; validation 2000; testing, 2000) included 10 000 patients with HF and 10 000 without HF who were matched by age, sex, race, inpatient/outpatient status, hospital, and encounter date (within 60 days). HF status was ascertained by manual chart reviews in VA's External Peer Review Program for HF (EPRP-HF) and non-HF status was ascertained by the absence of ICD codes for HF in VA EHR. Two clinicians annotated 1000 random snippets with HF-related keywords and labelled 436 as HF, which was then used to train and test a natural language processing (NLP) model to classify HF (positive predictive value or PPV, 0.81; sensitivity, 0.77). A machine learning (ML) model using linear support vector machine architecture was trained and tested to classify HF using EPRP-HF as cases (PPV, 0.86; sensitivity, 0.86). From the 'HF ICD-code universe', we randomly selected 200 patients (gold standard cohort) and two clinicians manually adjudicated HF (gold standard HF) in 145 of those patients by chart reviews. We calculated NLP, ML, and NLP + ML scores and used weighted F scores to derive their optimal threshold values for HF classification, which resulted in PPVs of 0.83, 0.77, and 0.85 and sensitivities of 0.86, 0.88, and 0.83, respectively. HF patients classified by the NLP + ML model were characteristically and prognostically similar to those with gold standard HF. All three models performed better than ICD code approaches: one principal hospital discharge diagnosis code for HF (PPV, 0.97; sensitivity, 0.21) or two primary outpatient encounter diagnosis codes for HF (PPV, 0.88; sensitivity, 0.54). CONCLUSIONS: These findings suggest that NLP and ML models are efficient AI tools to phenotype HF in big EHR data to create contemporary HF registries for clinical studies of effectiveness, quality improvement, and hypothesis generation.

Identification and outcomes of KDIGO-defined chronic kidney disease in 1.4 million U.S. Veterans with heart failure.

AIMS: According to the Kidney Disease: Improving Global Outcomes (KDIGO) guideline, the definition of chronic kidney disease (CKD) requires the presence of abnormal kidney structure or function for >3 months with implications for health. CKD in patients with heart failure (HF) has not been defined using this definition, and less is known about the true health implications of CKD in these patients. The objective of the current study was to identify patients with HF who met KDIGO criteria for CKD and examine their outcomes. METHODS AND RESULTS: Of the 1 419 729 Veterans with HF not receiving kidney replacement therapy, 828 744 had data on ≥2 ambulatory serum creatinine >90 days apart. CKD was defined as estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 (n = 185 821) or urinary albumin-to-creatinine ratio (uACR) >30 mg/g (n = 32 730) present twice >3 months apart. Normal kidney function (NKF) was defined as eGFR ≥60 ml/min/1.73 m2, present for >3 months, without any uACR >30 mg/g (n = 365 963). Patients with eGFR <60 ml/min/1.73 m2 were categorized into four stages: 45-59 (n = 72 606), 30-44 (n = 74 812), 15-29 (n = 32 077), and <15 (n = 6326) ml/min/1.73 m2. Five-year all-cause mortality occurred in 40.4%, 57.8%, 65.6%, 73.3%, 69.7%, and 47.5% of patients with NKF, four eGFR stages, and uACR >30mg/g (albuminuria), respectively. Compared with NKF, hazard ratios (HR) (95% confidence intervals [CI]) for all-cause mortality associated with the four eGFR stages and albuminuria were 1.63 (1.62-1.65), 2.00 (1.98-2.02), 2.49 (2.45-2.52), 2.28 (2.21-2.35), and 1.22 (1.20-1.24), respectively. Respective age-adjusted HRs (95% CIs) were 1.13 (1.12-1.14), 1.36 (1.34-1.37), 1.87 (1.84-1.89), 2.24 (2.18-2.31) and 1.19 (1.17-1.21), and multivariable-adjusted HRs (95% CIs) were 1.11 (1.10-1.12), 1.24 (1.22-1.25), 1.46 (1.43-1.48), 1.42 (1.38-1.47), and 1.13 (1.11-1.16). Similar patterns were observed for associations with hospitalizations. CONCLUSION: Data needed to define CKD using KDIGO criteria were available in six out of ten patients, and CKD could be defined in seven out of ten patients with data. HF patients with KDIGO-defined CKD had higher risks for poor outcomes, most of which was not explained by abnormal kidney structure or function. Future studies need to examine whether CKD defined using a single eGFR is characteristically and prognostically different from CKD defined using KDIGO criteria.

Impact of the COVID-19 Pandemic on the Provision of Dialysis Service and Mortality in Veterans Receiving Maintenance Hemodialysis in the VA: An Interrupted Time-Series Analysis.

INTRODUCTION: According to the US Renal Data System (USRDS), patients with end-stage kidney disease (ESKD) on maintenance dialysis had higher mortality during early COVID-19 pandemic. Less is known about the effect of the pandemic on the delivery of outpatient maintenance hemodialysis and its impact on death. We examined the effect of pandemic-related disruption on the delivery of dialysis treatment and mortality in patients with ESKD receiving maintenance hemodialysis in the Veterans Health Administration (VHA) facilities, the largest integrated national healthcare system in the USA. METHODS: Using national VHA electronic health records data, we identified 7,302 Veterans with ESKD who received outpatient maintenance hemodialysis in VHA healthcare facilities during the COVID-19 pandemic (February 1, 2020, to December 31, 2021). We estimated the average change in the number of hemodialysis treatments received and deaths per 1,000 patients per month during the pandemic by conducting interrupted time-series analyses. We used seasonal autoregressive moving average (SARMA) models, in which February 2020 was used as the conditional intercept and months thereafter as conditional slope. The models were adjusted for seasonal variations and trends in rates during the pre-pandemic period (January 1, 2007, to January 31, 2020). RESULTS: The number (95% CI) of hemodialysis treatments received per 1,000 patients per month during the pre-pandemic and pandemic periods were 12,670 (12,525-12,796) and 12,865 (12,729-13,002), respectively. Respective all-cause mortality rates (95% CI) were 17.1 (16.7-17.5) and 19.6 (18.5-20.7) per 1,000 patients per month. Findings from SARMA models demonstrate that there was no reduction in the dialysis treatments delivered during the pandemic (rate ratio: 0.999; 95% CI: 0.998-1.001), but there was a 2.3% (95% CI: 1.5-3.1%) increase in mortality. During the pandemic, the non-COVID hospitalization rate was 146 (95% CI: 143-149) per 1,000 patients per month, which was lower than the pre-pandemic rate of 175 (95% CI: 173-176). In contrast, there was evidence of higher use of telephone encounters during the pandemic (3,023; 95% CI: 2,957-3,089), compared with the pre-pandemic rate (1,282; 95% CI: 1,241-1,324). CONCLUSIONS: We found no evidence that there was a disruption in the delivery of outpatient maintenance hemodialysis treatment in VHA facilities during the COVID-19 pandemic and that the modest rise in deaths during the pandemic is unlikely to be due to missed dialysis.

Cardiorespiratory fitness and risk of Alzheimer's disease and related dementias among American veterans.

INTRODUCTION: Cardiorespiratory fitness (CRF) is associated with improved health and survival. Less is known about its association with Alzheimer's disease and related dementias (ADRD). METHODS: We identified 649,605 US veterans 30 to 95 years of age and free of ADRD who completed a standardized exercise tolerance test between 2000 and 2017 with no evidence of ischemia. We examined the association between five age- and sex-specific CRF categories and ADRD incidence using multivariate Cox regression models. RESULTS: During up to 20 (median 8.3) years of follow-up, incident ADRD occurred in 44,105 (6.8%) participants, with an incidence rate of 7.7/1000 person-years. Compared to the least-fit, multivariable-adjusted hazard ratios (95% confidence intervals) for incident ADRD were: 0.87 (0.85-0.90), 0.80 (0.78-0.83), 0.74 (0.72-0.76), and 0.67 (0.65-0.70), for low-fit, moderate-fit, fit, and high-fit individuals, respectively. DISSCUSSION: These findings demonstrate an independent, inverse, and graded association between CRF and incident ADRD. Future studies may determine the amount and duration of physical activity needed to optimize ADRD risk reduction.

Hydroxychloroquine and Risk of Long QT Syndrome in Rheumatoid Arthritis: A Veterans Cohort Study With Nineteen-Year Follow-up.

OBJECTIVE: Recent evidence suggests that hydroxychloroquine use is not associated with higher 1-year risk of long QT syndrome (LQTS) in patients with rheumatoid arthritis (RA). Less is known about its long-term risk, the examination of which was the objective of this study. METHODS: We conducted a propensity score-matched active-comparator safety study of hydroxychloroquine in 8,852 veterans (mean age 64 ± 12 years, 14% women, 28% Black) with newly diagnosed RA. A total of 4,426 patients started on hydroxychloroquine and 4,426 started on another nonbiologic disease-modifying antirheumatic drug (DMARD) and were balanced on 87 baseline characteristics. The primary outcome was LQTS during 19-year follow-up through December 31, 2019. RESULTS: Incident LQTS occurred in 4 (0.09%) and 5 (0.11%) patients in the hydroxychloroquine and other DMARD groups, respectively, during the first 2 years. Respective 5-year incidences were 17 (0.38%) and 6 (0.14%), representing 11 additional LQTS events in the hydroxychloroquine group (number needed to harm 403; [95% confidence interval (95% CI)], 217-1,740) and a 181% greater relative risk (95% CI 11%-613%; P = 0.030). Although overall 10-year risk remained significant (hazard ratio 2.17; 95% CI 1.13-4.18), only 5 extra LQTS occurred in hydroxychloroquine group over the next 5 years (years 6-10) and 1 over the next 9 years (years 11-19). There was no association with arrhythmia-related hospitalization or all-cause mortality. CONCLUSIONS: Hydroxychloroquine use had no association with LQTS during the first 2 years after initiation of therapy. There was a higher risk thereafter that became significant after 5 years of therapy. However, the 5-year absolute risk was very low, and the absolute risk difference was even lower. Both risks attenuated during longer follow-up. These findings provide evidence for long-term safety of hydroxychloroquine in patients with RA.

Assessment of Lung Cancer Risk Among Smokers for Whom Annual Screening Is Not Recommended.

Importance: The US Preventive Services Task Force does not recommend annual lung cancer screening with low-dose computed tomography (LDCT) for adults aged 50 to 80 years who are former smokers with 20 or more pack-years of smoking who quit 15 or more years ago or current smokers with less than 20 pack-years of smoking. Objective: To determine the risk of lung cancer in older smokers for whom LDCT screening is not recommended. Design, Settings, and Participants: This cohort study used the Cardiovascular Health Study (CHS) data sets obtained from the National Heart, Lung and Blood Institute, which also sponsored the study. The CHS enrolled 5888 community-dwelling individuals aged 65 years and older in the US from June 1989 to June 1993 and collected extensive baseline data on smoking history. The current analysis was restricted to 4279 individuals free of cancer who had baseline data on pack-year smoking history and duration of smoking cessation. The current analysis was conducted from January 7, 2022, to May 25, 2022. Exposures: Current and prior tobacco use. Main Outcomes and Measures: Incident lung cancer during a median (IQR) of 13.3 (7.9-18.8) years of follow-up (range, 0 to 22.6) through December 31, 2011. A Fine-Gray subdistribution hazard model was used to estimate incidence of lung cancer in the presence of competing risk of death. Cox cause-specific hazard regression models were used to estimate hazard ratios (HRs) and 95% CIs for incident lung cancer. Results: There were 4279 CHS participants (mean [SD] age, 72.8 [5.6] years; 2450 [57.3%] women; 663 [15.5%] African American, 3585 [83.8%] White, and 31 [0.7%] of other race or ethnicity) included in the current analysis. Among the 861 nonheavy smokers (<20 pack-years), the median (IQR) pack-year smoking history was 7.6 (3.3-13.5) pack-years for the 615 former smokers with 15 or more years of smoking cessation, 10.0 (5.3-14.9) pack-years for the 146 former smokers with less than 15 years of smoking cessation, and 11.4 (7.3-14.4) pack-years for the 100 current smokers. Among the 1445 heavy smokers (20 or more pack-years), the median (IQR) pack-year smoking history was 34.8 (26.3-48.0) pack-years for the 516 former smokers with 15 or more years of smoking cessation, 48.0 (35.0-70.0) pack-years for the 497 former smokers with less than 15 years of smoking cessation, and 48.8 (31.6-57.0) pack-years for the 432 current smokers. Incident lung cancer occurred in 10 of 1973 never smokers (0.5%), 5 of 100 current smokers with less than 20 pack-years of smoking (5.0%), and 26 of 516 former smokers with 20 or more pack-years of smoking with 15 or more years of smoking cessation (5.0%). Compared with never smokers, cause-specific HRs for incident lung cancer in the 2 groups for whom LDCT is not recommended were 10.54 (95% CI, 3.60-30.83) for the current nonheavy smokers and 11.19 (95% CI, 5.40-23.21) for the former smokers with 15 or more years of smoking cessation; age, sex, and race-adjusted HRs were 10.06 (95% CI, 3.41-29.70) for the current nonheavy smokers and 10.22 (4.86-21.50) for the former smokers with 15 or more years of smoking cessation compared with never smokers. Conclusions and Relevance: The findings of this cohort study suggest that there is a high risk of lung cancer among smokers for whom LDCT screening is not recommended, suggesting that prediction models are needed to identify high-risk subsets of these smokers for screening.

Beta-Blocker Use and Outcomes in Nursing Home Residents with Heart Failure with Reduced Ejection Fraction.

BACKGROUND: Beta-blockers improve clinical outcomes in patients with heart failure with reduced ejection fraction (HFrEF). Less is known about their role in older nursing home residents with HFrEF. METHODS: From the combined OPTIMIZE-HF and Alabama Heart Failure Project data sets, we assembled a propensity score-matched balanced cohort of 6494 hospitalized patients ≥65 years with HFrEF (ejection fraction ≤40%). In our primary approach, hazard ratios (HRs) and 95% confidence intervals (CI)s for outcomes associated with discharge prescriptions for beta- blockers were estimated, examining for heterogeneity by admission from nursing homes. In our sensitivity approach, we examined these associations in a separately assembled propensity score-matched cohort of 122 patients admitted from nursing homes. RESULTS: In the matched primary cohort of 6494 patients, HRs (95% CIs) for 12-month all-cause mortality and heart failure readmission were 0.80 (0.74-0.87) and 0.94 (0.86-1.02), respectively. Respective HRs (95% CIs) in the nursing home and non-nursing home subgroups were 0.77 (0.51-1.16) and 0.81 (0.74-0.87) for all-cause mortality (interaction P: 0.653) and 1.06 (0.53-2.12) and 0.89 (0.82-0.96) for heart failure readmission (interaction P: 0.753). In the matched sensitivity cohort of 122 patients admitted from nursing homes, HRs (95% CIs) for 12-month all-cause mortality and heart failure readmission were 0.86 (0.55-1.35) and 1.07 (0.52-2.22), respectively. Similar associations were observed for 30-day outcomes. CONCLUSIONS: Beta-blocker use was associated with a lower risk of all-cause mortality but not of heart failure readmission in older patients with HFrEF, which were similar for patients admitted and not admitted from nursing homes.

Length of stay and readmission in older adults hospitalized for heart failure.

INTRODUCTION: Hospital length of stay (LoS) and hospital readmissions are metrics of healthcare performance. We examined the association between these two metrics in older patients hospitalized with decompensated heart failure (HF). MATERIAL AND METHODS: Eight thousand and forty-nine patients hospitalized for HF in 106 U.S. hospitals had a median LoS of 5 days; among them, 3777 had a LoS > 5 days. Using propensity scores for LoS > 5 days, we assembled 2723 pairs of patients with LoS 1-5 vs. > 5 days. The matched cohort of 5446 patients was balanced on 40 baseline characteristics. We repeated the above process in 7045 patients after excluding those with LoS > 10 days, thus assembling a second matched cohort of 2399 pairs of patients with LoS 1-5 vs. 6-10 days. Hazard ratios (HR) and 95% confidence intervals (CI) for outcomes associated with longer LoS were estimated in matched cohorts. RESULTS: In the primary matched cohort (n = 5446), LoS > 5 days was associated with a higher risk of all-cause readmission at 30 days (HR = 1.16; 95% CI: 1.04-1.31; p = 0.010), but not during longer follow-up. A longer LoS was also associated with a higher risk of mortality during 8.8 years of follow-up (HR = 1.13; 95% CI: 1.06-1.21; p < 0.001). LoS had no association with HF readmission. Similar associations were observed among the matched sensitivity cohort (n = 4798) that excluded patients with LoS > 10 days. CONCLUSIONS: In propensity score-matched balanced cohorts of patients with HF, a longer LoS was independently associated with poor outcomes, which persisted when LoS > 10 days were excluded.

Cardiovascular Safety of Hydroxychloroquine in US Veterans With Rheumatoid Arthritis.

OBJECTIVE: Hydroxychloroquine (HCQ) may prolong the QT interval, a risk factor for torsade de pointes, a potentially fatal ventricular arrhythmia. This study was undertaken to examine the cardiovascular safety of HCQ in patients with rheumatoid arthritis (RA). METHODS: We conducted an active comparator safety study of HCQ in a propensity score-matched cohort of 8,852 US veterans newly diagnosed as having RA between October 1, 2001 and December 31, 2017. Patients were started on HCQ (n = 4,426) or another nonbiologic disease-modifying antirheumatic drug (DMARD; n = 4,426) after RA diagnosis, up to December 31, 2018, and followed up for 12 months after therapy initiation, up to December 31, 2019. RESULTS: Patients had a mean ± SD age of 64 ± 12 years, 14% were women, and 28% were African American. The treatment groups were balanced with regard to 87 baseline characteristics. There were 3 long QT syndrome events (0.03%), 2 of which occurred in patients receiving HCQ. Of the 56 arrhythmia-related hospitalizations (0.63%), 30 occurred in patients in the HCQ group (hazard ratio [HR] associated with HCQ 1.16 [95% confidence interval (95% CI) 0.68-1.95]). All-cause mortality occurred in 144 (3.25%) and 136 (3.07%) of the patients in the HCQ and non-HCQ groups, respectively (HR associated with HCQ 1.06 [95% CI, 0.84-1.34]). During the first 30 days of follow-up, there were no long QT syndrome events, 2 arrhythmia-related hospitalizations (none in the HCQ group), and 13 deaths (6 in the HCQ group). CONCLUSION: Our findings indicate that the incidence of long QT syndrome and arrhythmia-related hospitalization is low in patients with RA during the first year after the initiation of HCQ or another nonbiologic DMARD. We found no evidence that HCQ therapy is associated with a higher risk of adverse cardiovascular events or death.

Loop Diuretic Prescription and 30-Day Outcomes in Older Patients With Heart Failure.

BACKGROUND: Heart failure (HF) is a major source of morbidity and mortality. Fluid retention and shortness of breath are its cardinal manifestations for which loop diuretics are used. Although their usefulness is well accepted, less is known about their role in improving clinical outcomes. OBJECTIVES: The purpose of this study was to determine the relationship between loop diuretics and clinical outcomes in patients with HF. METHODS: Of the 25,345 older patients hospitalized for HF in the Medicare-linked OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure) registry, 9,866 (39%) received no pre-admission diuretics. The study excluded 1,083 patients receiving dialysis and 847 discharged on thiazide diuretics. Of the remaining 7,936 patients, 5,568 (70%) were prescribed loop diuretics at discharge. Using propensity scores for receipt of loop diuretics estimated for each of the 7,936 patients, a matched cohort of 2,191 pairs of patients was assembled balanced on 74 baseline characteristics. Hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes were estimated in the matched cohort. RESULTS: Matched patients (n = 4,382) had a mean age of 78 years, 54% were women, and 11% were African American. The 30-day all-cause mortality occurred in 4.9% (107 of 2,191) and 6.6% (144 of 2,191) of patients in the loop diuretic and no loop diuretic groups, respectively (HR when the use of loop diuretics was compared with nonuse: 0.73; 95% CI: 0.57 to 0.94; p = 0.016). Patients in the loop diuretic group had a significantly lower risk of 30-day HF readmission (HR: 0.79; 95% CI: 0.63 to 0.99; p = 0.037) but not of 30-day all-cause readmission (HR: 0.89; 95% CI: 0.79 to 1.01; p = 0.081). None of the associations was statistically significant during 60 days of follow-up. CONCLUSIONS: Hospitalized older patients not taking diuretics prior to hospitalization for HF decompensation who received a discharge prescription for loop diuretics had significantly better 30-day clinical outcomes than those not discharged on loop diuretics. These findings provide new information about short-term clinical benefits associated with loop diuretic use in HF.

Alzheimer's Disease and Alzheimer's Disease-Related Dementias in Older African American and White Veterans.

BACKGROUND: Racial disparity in the epidemiology of Alzheimer's disease and Alzheimer's disease-related dementias (AD/ADRD) has been reported. However, less is known about this disparity among Veterans. OBJECTIVE: To estimate the racial disparity in AD/ADRD among the Veterans. METHODS: Of the 5,413,418 Veterans≥65 years receiving care at the Veterans Health Administration (1999-2016), 4,045,269 were free of prevalent AD/ADRD, schizophrenia, or bipolar disorder at baseline. Of these, 432,469 were African American. Race was self-identified and incident AD/ADRD during 20 (median 6.7) years of follow-up was ascertained using International Classification of Diseases codes. RESULTS: Patients had a mean age of 70.4 (±6.6) years and 97.8% were men. Age-sex-adjusted incidence of AD/ADRD per 1,000 person-year was 19.3 and 10.8 for African American and white Veterans, respectively (age-sex-adjusted hazard ratio associated with African American race, 1.77; 95% confidence interval, 1.75-1.79; p < 0.0001). This association remained essentially unchanged after multivariable adjustment (hazard ratio, 1.67; 95% confidence interval, 1.65-1.69; p < 0.0001). Among the key baseline characteristics that were significant predictors of AD/ADRD in both races, stroke was a significantly stronger predictor among African Americans, and Hispanic ethnicity and depression among whites (p-value for all interaction,<0.0001). CONCLUSION: The findings of a higher incidence of AD/ADRD among African American Veterans is consistent with the findings in the general population reported in the literature, although the overall incidence appears to be lower than that in the general population. Future studies need to examine this disparity in incidence as well as the between-race heterogeneity in AD/ADRD risk.

Opioid Use and Outcomes in Hospitalized Older Patients With Heart Failure Receiving and Not Receiving Hospice Referrals.

BACKGROUND: The use of opioids is associated with poor outcomes. Less is known about this association in patients with heart failure (HF) and whether it varies by the receipt of hospice care. METHODS: Of the 7467 patients hospitalized for HF without previous opioid use, 124 received discharge opioids. We matched 123 of these patients with 123 not receiving opioids based on their propensity scores for opioid use, thus assembling a matched cohort of 246 patients balanced on 30 baseline characteristics (mean age, 76 years, 60% women, and 11% African American). We repeated the process in hospice (n = 155; 20 received opioids) and nonhospice (n = 7298; 104 received opioids) subgroups, thus assembling 2 matched cohorts of 22 and 208 patients, respectively. Hazard ratios (HRs) and 95% confidence intervals (CIs) associated with opioid use were estimated from matched cohorts. RESULTS: During 8.6 (median, 1.4) years of follow-up, all-cause mortality occurred in 80% and 68% of matched patients in the opioid and nonopioid groups, respectively (HR, 1.49; 95% CI, 1.11-1.99; P = 0.008). There was evidence of heterogeneity in this association between hospice and nonhospice patients (P for interaction, 0.027). Among matched hospice and nonhospice patients, HRs (95% CIs) for mortality were 6.37 (2.06-19.69; P = 0.001) and 1.42 (1.03-1.96; P = 0.035), respectively. HRs (95% CIs) for 30-day and 1-year mortality were 1.98 (1.06-3.70; P = 0.033) and 1.72 (1.18-2.49; P = 0.004), respectively. HRs (95% CIs) for all-cause, HF, and non-HF readmissions were 1.31 (0.97-1.76; P = 0.079), 1.03 (0.71-1.49; P = 0.866), and 1.75 (1.05-2.91; P = 0.031), respectively. Readmission associations were similar among matched nonhospice patients. There was no readmission among matched hospice patients receiving opioids. CONCLUSIONS: In older patients with HF, opioid use is associated with a higher risk of mortality, which is greater in the hospice subgroup, and a higher risk of non-HF readmission in the nonhospice subgroup.

Renin-Angiotensin Inhibition and Outcomes in Nursing Home Residents With Heart Failure.

BACKGROUND: Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEIs-ARBs) improve outcomes in heart failure (HF). Less is known about this association in nursing home (NH) residents. METHODS: Of the 8024 hospitalized HF patients, 542 were NH residents, of whom 250 received ACEIs-ARBs. We assembled a propensity score-matched cohort of 157 pairs of NH residents receiving and not receiving ACEIs-ARBs balanced on 29 baseline characteristics (mean age, 83 years, 74% women, 17% African American), in which we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes associated with ACEI-ARB use. We then checked for interaction in a matched cohort of 5130 patients (378 were NH residents) assembled from the 8024 patients. RESULTS: Among 314 matched NH residents, HRs (95% CIs) for 30-day all-cause readmission, HF readmission, and all-cause mortality were 0.78 (0.47-1.28), 0.68 (0.29-1.60), and 1.26 (0.70-2.27), respectively. Respective HRs (95% CIs) at 1 year were 0.76 (0.56-1.02), 0.68 (0.42-1.09), and 1.04 (0.78-1.38). Among 5130 matched patients, ACEI-ARB use was associated with a significantly lower risk of all outcomes at both times, with no significant interactions, except for 1-year mortality, which was only significant in the non-NH subgroup (P for interaction, 0.026). CONCLUSIONS: We found no evidence that the use of ACEIs or ARBs is associated with improved outcomes in patients with HF in the NH setting. However, we also found no evidence that this association is different in NH residents with HF versus non-NH patients with HF. Future larger studies are needed to demonstrate effectiveness of these drugs in the NH setting.

Spironolactone and Outcomes in Older Patients with Heart Failure and Reduced Ejection Fraction.

BACKGROUND: The efficacy of mineralocorticoid receptor antagonists or aldosterone antagonists in heart failure with reduced ejection fraction (HFrEF) is well known. Less is known about their effectiveness in real-world older patients with HFrEF. METHODS: Of the 8206 patients with heart failure and ejection fraction ≤35% without prior spironolactone use in the Medicare-linked OPTIMIZE-HF registry, 6986 were eligible for spironolactone therapy based on serum creatinine criteria (men ≤2.5 mg/dL, women ≤2.0 mg/dL) and 865 received a discharge prescription for spironolactone. Using propensity scores for spironolactone use, we assembled a matched cohort of 1724 (862 pairs) patients receiving and not receiving spironolactone, balanced on 58 baseline characteristics (Creatinine Cohort: mean age, 75 years, 42% women, 17% African American). We repeated the above process to assemble a secondary matched cohort of 1638 (819 pairs) patients with estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 (eGFR Cohort: mean age, 75 years, 42% women, 17% African American). RESULTS: In the matched Creatinine Cohort, spironolactone-associated hazard ratios (95% confidence intervals) for all-cause mortality, heart failure readmission, and combined endpoint of heart failure readmission or all-cause mortality were 0.92 (0.81-1.03), 0.87 (0.77-0.99), and 0.87 (0.79-0.97), respectively. Respective hazard ratios (95% confidence intervals) in the matched eGFR Cohort were 0.87 (0.77-0.98), 0.92 (0.80-1.05), and 0.91 (0.82-1.02). CONCLUSIONS: These findings provide evidence of consistent, albeit modest, clinical effectiveness of spironolactone in older patients with HFrEF regardless of renal eligibility criteria used. Additional strategies are needed to improve the effectiveness of aldosterone antagonists in clinical practice.

Digoxin use and lower risk of 30-day all-cause readmission in older patients with heart failure and reduced ejection fraction receiving ß-blockers.

BACKGROUND: Digoxin use has been associated with a lower risk of 30-day all-cause admission and readmission in patients with heart failure and reduced ejection fraction (HFrEF). HYPOTHESIS: Digoxin use will be associated with improved outcomes in patients with HFrEF receiving ß-blockers. METHODS: Of the 3076 hospitalized Medicare beneficiaries with HFrEF (EF <45%), 1046 received a discharge prescription for ß-blockers, of which 634 were not on digoxin. Of the 634, 204 received a new discharge prescription for digoxin. Propensity scores for digoxin use, estimated for each of the 634 patients, were used to assemble a matched cohort of 167 pairs of patients receiving and not receiving digoxin, balanced on 30 baseline characteristics. Matched patients (n = 334) had a mean age of 74 years and were 46% female and 30% African American. RESULTS: 30-day all-cause readmission occurred in 15% and 27% of those receiving and not receiving digoxin, respectively (hazard ratio [HR]: 0.51, 95% confidence interval [CI]: 0.31-0.83, P = 0.007). This beneficial association persisted during 4 years of follow-up (HR: 0.72, 95% CI: 0.57-0.92, P = 0.008). Digoxin use was also associated with a lower risk of the combined endpoint of all-cause readmission or all-cause mortality at 30 days (HR: 0.54, 95% CI: 0.34-0.86, P = 0.009) and at 4 years (HR: 0.76, 95% CI: 0.61-0.96, P = 0.020). CONCLUSIONS: In hospitalized patients with HFrEF receiving ß-blockers, digoxin use was associated with a lower risk of 30-day all-cause readmission but not mortality, which persisted during longer follow-up.

Digoxin and 30-Day All-Cause Readmission in Long-Term Care Residents Hospitalized for Heart Failure.

BACKGROUND: Digoxin use has been shown to be associated with a lower risk of 30-day all-cause hospital readmissions in older patients with heart failure (HF). In the current study, we examined this association among long-term care (LTC) residents hospitalized for HF. METHODS: Of the 8049 Medicare beneficiaries discharged alive after hospitalization for HF from 106 Alabama hospitals, 545 (7%) were LTC residents, of which 227 (42%) received discharge prescriptions for digoxin. Propensity scores for digoxin use, estimated for each of the 545 patients, were used to assemble a matched cohort of 158 pairs of patients receiving and not receiving digoxin who were balanced on 29 baseline characteristics. Hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes associated with digoxin among matched patients were estimated using Cox regression models. RESULTS: Matched patients (n = 316) had a mean age of 83 years, 74% were women, and 18% African American. Thirty-day all-cause readmission occurred in 21% and 20% of patients receiving and not receiving digoxin, respectively (HR, 1.02; 95% CI, 0.63-1.66). Digoxin had no association with all-cause mortality (HR, 0.90; 95% CI, 0.48-1.70), HF readmission (HR, 0.90; 95% CI, 0.38-2.12), or a combined endpoint of all-cause readmission or all-cause mortality (HR, 0.97; 95% CI, 0.65-1.45) at 30 days. These associations remained unchanged at 1 year postdischarge. CONCLUSIONS: The lack of an association between digoxin and 30-day all-cause readmission in older nursing home residents hospitalized for HF is intriguing and needs to be interpreted with caution given the small sample size.

Isolated diastolic hypertension and incident heart failure in community-dwelling older adults: Insights from the Cardiovascular Health Study.

BACKGROUND: Isolated systolic hypertension and isolated diastolic hypotension are common in older adults and associated with a higher risk of incident heart failure (HF). However, little is known about the prevalence and impact of isolated diastolic hypertension in this population. METHODS: In the Cardiovascular Health Study (CHS), of the 5776 community-dwelling older adults ≥65years who had data on baseline systolic and diastolic blood pressure (SBP and DBP), 28 had isolated diastolic hypertension (DBP ≥90mmHg and SBP <140mmHg). From the 5748 without isolated diastolic hypertension, we excluded those with SBP ≥120mmHg (n=4451), DBP 80-89mmHg (n=20), DBP <60mmHg (n=425), normal BP taking anti-hypertensive medications (n=311), normal BP taking no anti-hypertensive medications but with history of hypertension (n=38), and baseline HF (n=5). The final cohort of 524 participants included 27 with isolated diastolic hypertension. RESULTS: Patients (n=524) had a mean (±SD) age of 71 (±5) years, 58% were women and 9% African American. There were no significant between-group age or sex differences; 37% of those with isolated diastolic hypertension (versus 7% without) were African American. Incident HF occurred in 19% and 7% of participants with and without isolated diastolic hypertension, respectively (multivariable-adjusted hazard ratio {HR}, 4.65; 95% confidence interval {CI}, 1.09-19.90; p=0.038). There was a trend toward higher cardiovascular mortality (HR, 4.59; 95% CI, 0.92-23.88; p=0.063). CONCLUSION: Among community-dwelling older adults, isolated diastolic hypertension is rare and is associated with higher risk for incident HF and cardiovascular mortality.

Systolic-diastolic hypertension versus isolated systolic hypertension and incident heart failure in older adults: Insights from the Cardiovascular Health Study.

BACKGROUND: Isolated systolic hypertension (ISH) is common in older adults and is a risk factor for incident heart failure (HF). We examined the association of systolic-diastolic hypertension (SDH) with incident HF and other outcomes in older adults. METHODS: In the Cardiovascular Health Study (CHS), 5776 community-dwelling adults≥65years had data on baseline systolic and diastolic blood pressure (SBP and DBP). We excluded those with DBP<60mmHg (n=821), DBP≥90 and SBP<140mmHg (n=28), normal BP, taking anti-hypertensive drugs (n=1138), normal BP, not taking anti-hypertensive drugs, history of hypertension (n=193), and baseline HF (n=101). Of the remaining 3495, 1838 had ISH (SBP≥140 and DBP<90mmHg) and 240 had SDH (SBP≥140 and DBP≥90mmHg). The main outcome was centrally-adjudicated incident HF over 13years of follow-up. RESULTS: Participants had a mean (±SD) age of 73 (±6)years, 57% were women, and 16% African American. Incident HF occurred in 25%, 22% and 11% of participants with ISH, SDH and no hypertension, respectively. Compared to no hypertension, multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI) for incident HF associated with ISH and SDH were 1.86 (1.51-2.30) and 1.73 (1.23-2.42), respectively. Cardiovascular mortality occurred in 22%, 24% and 9% of those with ISH, SDH and no hypertension, respectively with respective multivariable-adjusted HRs (95% CIs) of 1.88 (1.49-2.37) and 2.30 (1.64-3.24). CONCLUSION: Among older adults with hypertension, both SDH and ISH have similar associations with incident HF and cardiovascular mortality.