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.

Considerations Regarding Management of Heart Failure in Older Adults.

Understanding noncardiovascular comorbidities and geriatric syndromes in elderly patients with heart failure (HF) is important as the average age of the population increases. Healthcare professionals need to consider these complex dynamics when managing older adults with HF, especially those older than 80. A number of small studies have described associations between HF and major geriatric domains. With information on patients' cognitive, functional decline, and ability to adhere to therapy, physicians can plan for individualized treatment goals and recommendations for these patients.

Early Ventricular Arrhythmias After Left Ventricular Assist Device Implantation.

BACKGROUND: Although sustained ventricular arrhythmias (VAs) are a common complication after durable left ventricular assist device (LVAD) implantation, the incidence, risk factors, and prognostic implications of postoperative early VAs (EVAs) in contemporary patients with LVAD are poorly understood. METHODS AND RESULTS: A single-center retrospective analysis was performed of patients who underwent LVAD implantation from October 1, 2006, to October 1, 2022. EVA was defined as an episode of sustained VA identified ≤30 days after LVAD implantation. A total of 789 patients underwent LVAD implantation (mean age 62.9 ± 0. years 5, HeartMate 3 41.4%, destination therapy 43.3%). EVAs occurred in 100 patients (12.7%). A history of end-stage renal disease (odds ratio [OR] 5.6, 95% confidence interval [CI] 1.45-21.70), preoperative electrical storm (OR 2.82, 95% CI 1.11-7.16), and appropriate implantable cardiac defibrillator therapy before implantation (OR 2.8, 95% CI 1.26-6.19) are independently associated with EVAs. EVA was associated with decreased 30-day survival (hazard ratio 3.02, 95% CI 1.1-8.3, P = .032). There was no difference in transplant-free survival time between patients with and without EVAs (hazard ratio 0.82, 95% CI 0.5-1.4, P = .454). CONCLUSIONS: EVAs are common after durable LVAD implantation and are associated with an increased risk of 30-day mortality.

Predictors and Outcomes of Sudden Cardiac Arrest in Heart Failure With Preserved Ejection Fraction: A Nationwide Inpatient Sample Analysis.

Sudden cardiac arrest (SCA) is the leading cause of cardiovascular mortality in heart failure with preserved ejection fraction (HFpEF), contributing to around 25% of deaths observed in pivotal HFpEF trials. However, predictors and outcomes of in-hospital SCA in HFpEF have not been well characterized. We queried the Nationwide Inpatient Sample (2016 to 2017) to identify adult hospitalizations with a diagnosis of HFpEF. Patients with acute or chronic conditions associated with SCA (e.g., acute myocardial infarction, acute pulmonary embolism, sarcoidosis) were excluded. We ascertained whether SCA occurred during these hospitalizations, identified predictors of SCA using multivariate logistic regression, and determined outcomes of SCA in HFpEF. Of 2,909,134 hospitalizations, SCA occurred in 1.48% (43,105). The mean age of the SCA group was 72.3 ± 12.4 years, 55.8% were women, and 66.4% were White. Presence of third-degree atrioventricular block (odds ratio [OR] 5.95, 95% confidence interval [CI] 5.31 to 6.67), left bundle branch block (OR 1.96, 95% CI 1.72 to 2.25), and liver disease (OR 1.87, 95% CI 1.73 to 2.02) were the leading predictors of SCA in HFpEF. After excluding patients with do-not-resuscitate status, the SCA group versus those without SCA had higher mortality (25.9% vs 1.6%), major bleeding complications (4.1% vs 1.7%), increased use of percutaneous coronary intervention (2.5% vs 0.7%), and mechanical circulatory assist device (1.2% vs 0.1%). These observational inpatient data suggest identifiable risk factors for SCA in HFpEF including cardiac arrhythmias. Further research is warranted to identify the best tools to risk-stratify patients with HFpEF to implement targeted SCA prevention strategies.

Stable Ventricular Fibrillation: A Paradigm Rather Than Septal Shift?

Awake patients in ventricular fibrillation is a phenomenon limited to patients who are mechanically supported. We describe a cohort of patients supported by left ventricular assist devices (LVADs) presenting to the emergency department (ED) at a high-volume LVAD center while in awake ventricular fibrillation (VF)/ventricular tachycardia (VT). Among 175 patients reviewed, a total of 19 LVAD patients presented to the ED in awake VF/VT between December 2015 and July 2021. On ED presentation, patients maintained a median mean arterial blood pressure (MAP) of 70 mm Hg with a mean LVAD flow of 3.77 L/minute. ED management included cardioversion in the majority of cases: 58% were defibrillated once, 21% were defibrillated multiple times, 68% received amiodarone, and 21% received lidocaine. Inpatient management included defibrillation, ablation, and antiarrhythmic initiation in 37%, 11%, and 84% of cases, respectively. In total, five patients (26%) died with one death attributed to recurrent VT. Our findings support the short-term tolerability of sustained ventricular arrhythmias in LVAD patients, as evidenced by the maintained MAPs and mental status. Clinical teams, however, should be aware of the potential harbinger for in-hospital mortality heralded by an awake VF/VT presentation.

Guideline-Directed Medical Therapy for the Treatment of Heart Failure with Reduced Ejection Fraction.

Guideline-directed medical therapy (GDMT) is the cornerstone of pharmacological therapy for patients with heart failure with reduced ejection fraction (HFrEF) and consists of the four main drug classes: renin-angiotensin system inhibitors, evidence-based ß-blockers, mineralocorticoid inhibitors and sodium glucose cotransporter 2 inhibitors. The recommendation for use of GDMT is based on the results of multiple major randomized controlled trials demonstrating improved clinical outcomes in patients with HFrEF who are maintained on this therapy. The effect is most beneficial when medications from the four main drug classes are used in conjunction. Despite this, there is an underutilization of GDMT, partially due to lack of awareness of how to safely and effectively initiate and titrate these medications. In this review article, we describe the different drug classes included in GDMT and offer an approach to initiation and effective titration in both the inpatient as well as outpatient setting.

Renin-Angiotensin Inhibition and Outcomes in HFrEF and Advanced Kidney Disease.

BACKGROUND: Renin-angiotensin system inhibitors improve outcomes in patients with heart failure with reduced ejection fraction (HFrEF). However, less is known about their effectiveness in patients with HFrEF and advanced kidney disease. METHODS: In the Medicare-linked Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF), 1582 patients with HFrEF (ejection fraction ≤40%) had advanced kidney disease (estimated glomerular filtration rate <30 mL/min/1.73 m2). Of these, 829 were not receiving angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) prior to admission, of whom 214 were initiated on these drugs prior to discharge. We calculated propensity scores for receipt of these drugs for each of the 829 patients and assembled a matched cohort of 388 patients, balanced on 47 baseline characteristics (mean age 78 years; 52% women; 10% African American; 73% receiving beta-blockers). Hazard ratios (HR) and 95% confidence intervals (CI) were estimated comparing 2-year outcomes in 194 patients initiated on ACE inhibitors or ARBs to 194 patients not initiated on those drugs. RESULTS: The combined endpoint of heart failure readmission or all-cause mortality occurred in 79% and 84% of patients initiated and not initiated on ACE inhibitors or ARBs, respectively (HR associated with initiation, 0.79; 95% CI, 0.63-0.98). Respective HRs (95% CI) for the individual endpoints of - Respective HRs (95% CI) for the individual endpoints of all-cause mortality and heart failure readmission were 0.81 (0.63-1.03) and 0.63 (0.47-0.85). CONCLUSIONS: The findings from our study add new information to the body of cumulative evidence that suggest that renin-angiotensin system inhibitors may improve clinical outcomes in patients with HFrEF and advanced kidney disease. These hypothesis-generating findings need to be replicated in contemporary patients.

Imaging modality for left ventricular ejection fraction estimation and effect of implantable cardioverter-defibrillator on mortality in patients with heart failure.

BACKGROUND: Implantable cardioverter-defibrillators (ICDs) improve outcomes in patients with heart failure (HF) with left ventricular ejection fraction (LVEF) ≤35%. Less is known about whether outcomes varied between the 2 noninvasive imaging modalities used to estimate LVEF-2-dimensional echocardiography (2DE) and multigated acquisition radionuclide ventriculography (MUGA)-which use different principles (geometric vs count-based, respectively). OBJECTIVE: The purpose of this study was to examine whether the effect of ICD on mortality in patients with HF and LVEF ≤35% varied on the basis of LVEF measured by 2DE or MUGA. METHODS: Of the 2521 patients with HF with LVEF ≤35% in the Sudden Cardiac Death in Heart Failure Trial, 1676 (66%) were randomized to either placebo or ICD, of whom 1386 (83%) had LVEF measured by 2DE (n = 971) or MUGA (n = 415). Hazard ratios (HRs) and 97.5% confidence intervals (CIs) for mortality associated with ICD were estimated overall, checking for interaction, and within the 2 imaging subgroups. RESULTS: Of the 1386 patients in the present analysis, all-cause mortality occurred in 23.1% (160 of 692) and 29.7% (206 of 694) of patients randomized to ICD or placebo, respectively (HR 0.77; 97.5% CI 0.61-0.97), which is consistent with that in 1676 patients in the original report. HRs (97.5% CIs) for all-cause mortality in the 2DE and MUGA subgroups were 0.79 (0.60-1.04) and 0.72 (0.46-1.11), respectively (P = .693 for interaction). Similar associations were observed for cardiac and arrhythmic mortalities. CONCLUSION: We found no evidence that in patients with HF and LVEF ≤35%, the effect of ICD on mortality varied by the noninvasive imaging method used to measure LVEF.

Review of Pathophysiology of Cardiogenic Shock and Escalation of Mechanical Circulatory Support Devices.

PURPOSE OF REVIEW: Cardiogenic shock (CS) is a complex clinical entity that continues to carry a high risk of mortality. The landscape of CS management has changed with the advent of several temporary mechanical circulatory support (MCS) devices designed to provide hemodynamic support. It remains challenging to understand the role of different temporary MCS devices in patients with CS, as many of these patients are critically ill, requiring complex care with multiple MCS device options. Each temporary MCS device can provide different types and levels of hemodynamic support. It is important to understand the risk/benefit profile of each one of them for appropriate device selection in patients with CS. RECENT FINDINGS: MCS may be beneficial in CS patients through augmentation of cardiac output with subsequent improvement of systemic perfusion. Selecting the optimal MCS device depends on several variables including the underlying etiology of CS, clinical strategy of MCS use (bridge to recovery, bridge to transplant or durable MCS, or abridge to decision), amount of hemodynamic support needed, associated respiratory failure, and institutional preference. Furthermore, it is even more challenging to determine the appropriate time to escalate from one MCS device to another or combine different MCS devices. In this review, we discuss the current available data published in the literature on the management of CS and propose a standardized approach for escalation of MCS devices in patients with CS. Shock teams can play an important role to help in hemodynamic-guided management and algorithm-based step-by-step approach in early initiation and escalation of temporary MCS devices at different stages of CS. It is important to define the etiology of CS, and stage of shock and recognize univentricular vs biventricular shock for appropriate device selection and escalation of therapy.

Risk of Stroke in Older Adults With Heart Failure.

Heart failure (HF) is a risk factor for incident stroke. However, less is known about the independent nature of this association and to what extent various baseline characteristics may mediate this risk. Of the 5,795 community-dwelling adults aged ≥65 years in the Cardiovascular Health Study, 5,448 were free of baseline stroke, of whom 229 had baseline HF. We used a multivariable-adjusted Cox regression model to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for centrally adjudicated incident stroke associated with HF. Participants had a mean age of 73 years, 58% were women, and 15% were African-American. During 23 years of follow-up, incident stroke occurred in 18.8% and 19.3% of those with and without HF, respectively, but the time to first stroke was shorter in those with HF (age-gender-race-adjusted HR 1.64, 95% CI 1.21 to 2.25). The association remained essentially unchanged after adjustments for tobacco, alcohol, and physical activity (HR 1.63, 95% CI 1.21 to 2.24), attenuated after adjustment for hypertension, atrial fibrillation, myocardial infarction, and diabetes mellitus (HR 1.26, 95% CI 0.92 to 1.72), and further attenuated after additional adjustment for 10 baseline functional and subclinical variables (HR 1.05, 95% CI 0.76 to 1.46). In conclusion, despite a similar 23-year stroke incidence, time to first stroke was shorter in older adults with HF than without. However, this extra risk appears to be mediated primarily by 4 cardiovascular diseases that are also risk factors for HF. These findings highlight the importance of the primary prevention of these HF risk factors to reduce the extra risk of stroke in HF.

Initiation of anti-hypertensive drugs and outcomes in patients with heart failure with preserved ejection fraction and persistent hypertension.

BACKGROUND: National heart failure (HF) guidelines recommend that in patients with HF with preserved ejection fraction (EF;HFpEF) and hypertension, systolic blood pressure (SBP) should be maintained below 130 mmHg. The objective of the study is to examine the association between initiation of anti-hypertensive drugs and outcomes in patients with HFpEF with persistent hypertension. METHODS: Of the 8873 hospitalized patients with HFpEF (EF ≥50%) with a history of hypertension without renal failure in Medicare-linked OPTIMIZE-HF, 3315 had a discharge SBP ≥130 mmHg, of whom 1971 were not receiving anti-hypertensive drugs, thiazides and calcium channel blockers, before hospitalization. Of these, 366 received discharge prescriptions for those drugs. We assembled a propensity score-matched cohort of 365 pairs of patients initiated and not initiated on anti-hypertensive drugs, balanced on 37 baseline characteristics. Hazard ratios (HR) and 95% confidence intervals (CI) for outcomes associated with anti-hypertensive drug initiation were estimated in the matched cohort. RESULTS: Matched patients (n = 730) had a mean age of 78 years; 67% were women and 17% African Americans. During 6 (median 2.5) years of follow-up, 66% of the patients died and 45% had HF readmission. HRs (95% CIs) for all-cause mortality at 30 days, 12 months and 6 years associated with anti-hypertensive drug initiation were 0.64 (0.30-1.36), 0.70 (0.51-0.97), and 0.95 (0.79-1.13), respectively. Respective HRs (95% CIs) for HF readmission were 1.65 (0.97-2.80), 1.18 (0.90-1.56) and 1.09 (0.88-1.35). CONCLUSIONS: Among hospitalized older patients with HFpEF with uncontrolled hypertension, the initiation of therapy with anti-hypertensive drugs was not associated with all-cause mortality or hospital readmission.

Beta-blockers and Ambulatory Inotropic Therapy.

BACKGROUND: Continuous infusion of ambulatory inotropic therapy (AIT) is increasingly used in patients with end-stage heart failure (HF). There is a paucity of data concerning the concomitant use of beta-blockers (BB) in these patients. METHODS: We retrospectively reviewed all patients discharged from our institution on AIT. The cohort was stratified into 2 groups based on BB use. The 2 groups were compared for differences in hospitalizations due to HF, ventricular arrhythmias and ICD therapies (shock or antitachycardia pacing). RESULTS: Between 2010 and 2017, 349 patients were discharged on AIT (95% on milrinone); 74% were males with a mean age of 61 ± 14 years. BB were used in 195 (56%) patients, whereas 154 (44%) did not receive these medications. Patients in the BB group had longer duration of AIT support compared to those in the non-BB group (141 [1-2114] vs 68 [1-690] days). After adjusting for differences in baseline characteristics and indication for AIT, patients in the BB group had significantly lower rates of hospitalizations due to HF (hazard ratio [HR] 0.61 (0.43-0.86); P = 0.005), ventricular arrhythmias (HR 0.34 [0.15-0.74]; P = 0.007) and ICD therapies (HR 0.24 [0.07-0.79]; P = 0.02). CONCLUSION: In patients with end-stage HF on AIT, the use of BB with inotropes was associated with fewer hospitalizations due to HF and fewer ventricular arrhythmias.

In-Hospital Weight Loss and Outcomes in Patients With Heart Failure.

BACKGROUND: Acute decompensation of heart failure (HF) is often marked by fluid retention, and weight loss is a marker of successful diuresis. We examined the relationship between in-hospital weight loss and post-discharge outcomes in patients with HF. METHODS: We conducted a propensity score-matched study of 8830 patients hospitalized for decompensated HF in the Medicare-linked Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF) registry, in which 4415 patients in the weight-loss group and 4415 patients in the no-weight-loss group were balanced on 75 baseline characteristics. We defined weight loss as an admission-to-discharge weight loss of 1-30 kilograms, and we defined no weight loss as a weight gain or loss of < 1 kilogram. Hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes associated with weight loss were estimated. RESULTS: Patients had a mean age of 78 years, 57% were women, and 11% were African American. The median weight loss in the weight-loss group was 3.6 (interquartile range, 2.0-6.0) kilograms. HRs and 95% CIs for 30-day all-cause mortality, all-cause readmission and HF readmission associated with weight loss were 0.75 (0.63-0.90), 0.90 (0.83-0.99) and 0.83 (0.72-0.96), respectively. Respective 60-day HRs (95% CIs) were 0.80 (0.70-0.92), 0.91 (0.85-0.98) and 0.88 (0.79-0.98). These associations were attenuated and lost significance during 6 months of follow-up. CONCLUSIONS: Among older patients hospitalized for decompensated HF, in-hospital weight loss was associated with a lower risk of mortality and hospital readmission. These findings suggest that in-hospital weight loss, a marker of successful diuresis and decongestion, is also a marker of improved clinical outcomes.

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.

Initiation of Anti-Hypertensive Drugs and Outcomes in Patients with Heart Failure with Reduced Ejection Fraction.

BACKGROUND: In patients with heart failure with reduced ejection fraction (HFrEF) and hypertension, systolic blood pressure is recommended to be maintained below 130 mmHg, although this has not been shown to be associated with improved outcomes. We examined the association between anti-hypertensive drug initiation and outcomes in patients with HFrEF. METHODS: In the Medicare-linked OPTIMIZE-HF, 7966 patients with HFrEF (ejection fraction ≤40%) without renal failure were not receiving anti-hypertensive drugs before hospitalization, of whom 692 received discharge prescriptions for those drugs (thiazides and calcium channel blockers). We assembled a propensity score-matched cohort of 687 pairs of patients initiated and not initiated on anti-hypertensive drugs, balanced on 38 baseline characteristics. Hazard ratios (HR) and 95% confidence intervals (CIs) for outcomes associated with anti-hypertensive drug initiation were estimated in the matched cohort. RESULTS: Matched patients (n = 1374) had a mean age of 74 years, 41% were female, 17% were African-American, 66% were discharged on renin-angiotensin system inhibitors and beta blockers, and 10% on aldosterone antagonists. During 6 (median 2.5) years of follow-up, 70% of the patients died and 53% had heart failure readmission. Anti-hypertensive drug initiation was not significantly associated with all-cause mortality (HR, 0.95; 95% CI, 0.83-1.07) or heart failure readmission (HR, 0.93; 95% CI, 0.80-1.07). Similar associations were observed during 30 days and 12 months of follow-up. CONCLUSIONS: Among hospitalized older patients with HFrEF receiving contemporary treatments for heart failure, initiation of an anti-hypertensive drug was not associated with a lower risk of all-cause mortality or hospital readmission.

Right Ventricular Ejection Fraction and Beta-Blocker Effect in Heart Failure With Reduced Ejection Fraction.

BACKGROUND: A low right ventricular ejection fraction (RVEF) is a marker of poor outcomes in patients with heart failure with reduced ejection fraction (HFrEF). Beta-blockers improve outcomes in HFrEF, but whether this effect is modified by RVEF is unknown. METHODS AND RESULTS: Of the 2798 patients in Beta-Blocker Evaluation of Survival Trial (BEST), 2008 had data on baseline RVEF (mean 35%, median 34%). Patients were categorized into an RVEF of less than 35% (n = 1012) and an RVEF of 35% or greater (n = 996). We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) within each RVEF subgroup and formally tested for interactions between bucindolol and RVEF. The effect of bucindolol on all-cause mortality in 2008 patients with baseline RVEF (HR 0.88, 95% CI 0.75-1.02) is consistent with that in 2798 patients in the main trial (HR 0.90, 95% CI 0.78-1.02). Bucindolol use was associated with a lower risk of all-cause mortality in patients with an RVEF of 35% or greater (HR 0.70, 95% CI 0.55-0.89), but not in those with an RVEF of less than 35% (HR 1.02, 95% CI 0.83-1.24, P for interaction = .022). Similar variations were observed for cardiovascular mortality (P for interaction = .009) and sudden cardiac death (P for interaction = .018), but not for pump failure death (P for interaction = .371) or HF hospitalization (P for interaction = .251). CONCLUSIONS: The effect of bucindolol on mortality in patients with HFrEF was modified by the baseline RVEF. If these hypothesis-generating findings can be replicated using approved beta-blockers in contemporary patients with HFrEF, then RVEF may help to risk stratify patients with HFrEF for optimization of beta-blocker therapy.

Income disparity and incident cardiovascular disease in older Americans.

OBJECTIVE: To examine the association between income and cardiovascular disease (CVD) in community-dwelling older adults. METHODS: Of the 5795 Medicare-eligible community-dwelling older Americans aged 65-100 years in the Cardiovascular Health Study (CHS), 4518 (78%) were free of baseline CVD, defined as heart failure, acute myocardial infarction, stroke, or peripheral arterial disease. Of them, 1846 (41%) had lower income, defined as a total annual household income <$16,000. Using propensity scores for lower income, estimated for each of the 4518 participants, we assembled a matched cohort of 1078 pairs balanced on 42 baseline characteristics. Outcomes included centrally adjudicated incident CVD and mortality. RESULTS: Matched participants (n = 2156) had a mean age of 73 years, 63% were women, and 13% African American. During an overall follow-up of 23 years, incident CVD, all-cause mortality and the combined endpoint of incident CVD or mortality occurred in 1094 (51%), 1726 (80%) and 1867 (87%) individuals, respectively. Compared with the higher income group, hazard ratio (HR) for time to the first occurrence of incident CVD in the lower income group was 1.16 with a 95% confidence interval (CI) of 1.03 to 1.31. A lower income was also associated with a significantly higher risk of all-cause mortality (HR, 1.19; 95% CI, 1.08-1.30), and consequently a higher risk of the combined endpoint of incident CVD or death (HR, 1.20; 95% CI, 1.09-1.31). CONCLUSION: Among community-dwelling older Americans free of baseline CVD, an annual household income <$16,000 is independently associated with significantly higher risks of new-onset CVD and death.