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Objectives: Heart failure risk is elevated in people with HIV (PWH). We investigated whether initial antiretroviral therapy (ART) regimens influenced heart failure risk., Design: Cohort study., Methods: PWH who initiated an ART regimen between 2000 and 2016 were identified from three integrated healthcare systems. We evaluated heart failure risk by protease inhibitor, nonnucleoside reverse transcriptase inhibitors (NNRTI), and integrase strand transfer inhibitor (INSTI)-based ART, and comparing two common nucleotide reverse transcriptase inhibitors: tenofovir disoproxil fumarate (tenofovir) and abacavir. Follow-up for each pairwise comparison varied (i.e. 7 years for protease inhibitor vs. NNRTI; 5 years for tenofovir vs. abacavir; 2 years for INSTIs vs. PIs or NNRTIs). Hazard ratios were from working logistic marginal structural models, fitted with inverse probability weighting to adjust for demographics, and traditional cardiovascular risk factors., Results: Thirteen thousand six hundred and thirty-four PWH were included (88% men, median 40 years of age; 34% non-Hispanic white, 24% non-Hispanic black, and 24% Hispanic). The hazard ratio (95% CI) were: 2.5 (1.5-4.3) for protease inhibitor vs. NNRTI-based ART (reference); 0.5 (0.2-1.8) for protease inhibitor vs. INSTI-based ART (reference); 0.1 (0.1-0.8) for NNRTI vs. INSTI-based ART (reference); and 1.7 (0.5-5.7) for tenofovir vs. abacavir (reference). In more complex models of cumulative incidence that accounted for possible nonproportional hazards over time, the only remaining finding was evidence of a higher risk of heart failure for protease inhibitor compared with NNRTI-based regimens (1.8 vs. 0.8%; P  = 0.002)., Conclusion: PWH initiating protease inhibitors may be at higher risk of heart failure compared with those initiating NNRTIs. Future studies with longer follow-up with INSTI-based and other specific ART are warranted., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The optimal approach to classifying multimorbidity burden in assessing treatment-associated outcomes using real-world data remains uncertain. We assessed whether 2 measurement approaches to characterize multimorbidity influenced observed associations of β-blocker use with outcomes in adults with heart failure (HF)., Methods: We conducted a retrospective study on adults with HF from 4 integrated health care delivery systems. Multimorbidity burden was characterized by either (1) simple counts of chronic conditions or (2) a weighted multiple chronic conditions score using data from electronic health records. We assessed the impact of these 2 approaches to characterizing multimorbidity on associations between exposure to β-blockers and subsequent all-cause death, hospitalization for HF, and hospitalization for any cause., Results: The study population characterized by a count of chronic conditions included 9988 adults with HF who had a mean (SD) age of 76.4 (12.5) years, with 48.7% women and 24.7% racial/ethnic minorities. The cohort characterized by weighted multiple chronic conditions included 10,082 adults with HF who had a mean (SD) age of 76.4 (12.4) years, 48.9% women, and 25.5% racial/ethnic minorities. The multivariable associations of risks of death or hospitalizations for HF or for any cause associated with incident β-blocker use were similar regardless of how multimorbidity burden was characterized., Conclusions: Simple counts of chronic conditions performed similarly to a weighted multimorbidity score in predicting outcomes using real-world data to examine clinical outcomes associated with β-blocker therapy in HF. Our findings challenge conventional wisdom that more complex measures of multimorbidity are always necessary to characterize patients in observational studies examining therapy-associated outcomes., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Current clinical practice guidelines recommend routine kidney function and serum potassium testing within 30 days of initiating angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) therapy. However, evidence is lacking on whether routine follow-up testing reduces therapy-related adverse events in adults with heart failure and if multimorbidity influences the association between laboratory testing and these adverse events., Methods: We conducted a retrospective cohort study among adults with heart failure from 4 US integrated health care delivery systems. Multimorbidity was defined using counts of chronic conditions. Patients with outpatient serum creatinine and potassium tests in the 30 days after starting ACEI or ARB therapy were matched 1:1 to patients without follow-up tests. We evaluated the association of follow-up testing with 30-day all-cause mortality and hospitalization with acute kidney injury or hyperkalemia using Cox regression., Results: We identified 3629 matched adults with heart failure initiating ACEI or ARB therapy between January 1, 2005, and December 31, 2012. Follow-up testing was not significantly associated with 30-day all-cause mortality (adjusted hazard ratio [aHR] 0.45, 95% confidence interval [CI] 0.14; 1.39) and hospitalization with hyperkalemia (aHR 0.73, 95% CI, 0.33; 1.61). However, follow-up testing was significantly associated with hospitalization with acute kidney injury (aHR, 1.40, 95% CI, 1.01; 1.94). Interaction between multimorbidity burden and follow-up testing was not statistically significant in any of the outcome models examined., Conclusions: Routine laboratory monitoring after ACEI or ARB therapy initiation was not associated with risk of 30-day all-cause mortality or hospitalization with hyperkalemia across the spectrum of multimorbidity burden in a cohort of patients with heart failure., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: HIV is an independent risk factor for heart failure (HF). However, the association of HIV severity with incident HF and the potential interaction with sex are incompletely understood., Setting: Integrated health care system., Methods: We conducted a cohort study of people with HIV (PWH) and matched people without HIV (PWoH), all aged ≥ 21 years and with no previous HF. Poisson regression was used to compare incident HF by HIV status, with PWH stratified by severity of HIV infection [defined by recent (<6 months) CD4 count, nadir CD4 count, or recent HIV RNA level]. Models were adjusted for sociodemographic characteristics, substance use, and HF risk factors. Analyses were conducted for men and women combined, then by sex., Results: The study included 38,868 PWH and 386,569 PWoH (mean baseline age = 41.0 ± 10.8 years; 88% men). Compared with PWoH, incident HF risk was higher among PWH with lower recent CD4 [200-499 cells/µL, adjusted rate ratio (aRR) = 1.82, 95% confidence interval (CI) = 1.50 to 2.21 and <200 cells/µL, aRR = 3.26 (2.47 to 4.30)] and a low nadir CD4 [<200 cells/µL, aRR = 1.56 (1.37 to 1.79)] but not among PWH with normal CD4 [≥500 cells/µL, aRR = 1.14 (0.90 to 1.44)]. Higher incident HF risk was observed among PWH at all HIV RNA levels, with greater HF risk at higher HIV RNA levels. The excess HF risk associated with low CD4 (recent or nadir) and high HIV RNA was stronger among women than men (P interactions=0.05, 0.08, and 0.01, respectively)., Conclusions: Given the association of HIV severity with HF, optimizing HIV treatment and management may be important for HF prevention among PWH., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Influenza infection can result in decompensation or exacerbation of heart failure (HF) symptoms, hospitalization, and death., Objective: To examine the association of influenza vaccination with mortality and hospitalization during influenza and non-influenza seasons between 2009 and 2018., Design, Setting, and Participants: In this prospective, observational cohort study, we included Kaiser Permanente Southern California members with a HF diagnosis prior to September 1 each year from 2009 to 2017., Exposure: The first influenza vaccination in each season (September 1 to May 31) was recorded. Vaccinated/unvaccinated patients were matched 1:1 on age, sex, and ejection fraction at the vaccination date (n-total = 74,870)., Main Outcomes: Patients were followed through the end of each influenza season for all-cause mortality. Secondary outcomes included cardiovascular mortality and all-cause hospitalization. In a sensitivity analysis, we examined mortality in the non-influenza season., Results: Influenza vaccinated vs unvaccinated patients had more comorbidities and higher healthcare utilization. After multivariable adjustment for utilization, sociodemographics, comorbidities, and medications, influenza vaccinated vs unvaccinated patients had a lower risk of all-cause mortality and cardiovascular mortality during the influenza season (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.63, 0.70 and HR 0.68, 95% CI 0.63, 0.74, respectively) but a higher risk of all-cause hospitalization (HR 1.27, 95% CI 1.21, 1.31). There was no association between influenza vaccination and all-cause or cardiovascular mortality during the non-influenza season (HR 0.99, 95% CI 0.89, 1.09 and HR 1.00, 95% CI 0.84, 1.21, respectively)., Conclusions: Influenza vaccination in HF patients was associated with a lower risk of mortality during the influenza season. Our findings provide support for recommendations of universal influenza vaccination in patients with HF., (© 2021. Society of General Internal Medicine.)

Background Randomized clinical trials in populations with heart failure with reduced ejection fraction may not be reflective of the general population with heart failure with reduced ejection fraction. Our study assessed the representativeness of the GALACTIC-HF (Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure) patient population in Kaiser Permanente Southern California. Methods and Results We identified 9770 patients with a diagnosis of heart failure with reduced ejection fraction from 2014 to 2018 using electronic health records. Four mutually exclusive cohorts were created, including GALACTIC-HF-ineligible cohorts: (1) not taking guideline-directed medical therapy (GDMT) and (2) taking GDMT; and GALACTIC-HF-eligible cohorts with: (3) ejection fraction (EF) ≤28% and (4) EF 29% to 35%. Patients were followed for 30-day and 1-year mortality and 30-day, 180-day, and 1-year hospitalization. Overall, 3626 (37.1%) met GALACTIC-HF inclusion criteria with EF ≤35%, and 2367 (65.3%) of those individuals had EF ≤28%. The risk of 1-year mortality was lower among all cohorts versus the GALACTIC-HF-ineligible cohort not taking GDMT (hazard ratio, 0.80 [95% CI, 0.70-0.91], 0.84 [95% CI, 0.72-0.98], and 0.62 [95% CI, 0.51-0.75] for the GALACTIC-HF-ineligible cohort taking GDMT and GALACTIC-HF-eligible cohorts with EF ≤28% and 29%-35%, respectively). Compared with the GALACTIC-HF-ineligible cohort not taking GDMT, the short-term hospitalization risk at 30 and 180 days were similar for both GALACTIC-HF-eligible cohorts and the hospitalization risk at 1 year was similar for the GALACTIC-HF-eligible cohort with EF ≤28%. Conclusions A large portion of patients with heart failure with reduced ejection fraction with low EF met inclusion criteria for the GALACTIC-HF trial and, despite being on GDMT, had hospitalization rates similar to those not taking GDMT, suggesting potential benefits from other innovative treatments.

Importance: Prior studies found a higher risk of acute cardiovascular disease (CVD) around population-wide psychosocial or environmental stressors. Less is known about acute CVD risk in relation to political events., Objective: To examine acute CVD hospitalizations following the 2020 presidential election., Design, Setting, and Participants: This retrospective cohort study examined acute CVD hospitalizations following the 2020 presidential election. Participants were adult members aged 18 years or older at Kaiser Permanente Southern California and Kaiser Permanente Northern California, 2 large, integrated health care delivery systems. Statistical analysis was performed from March to July 2021., Exposure: 2020 US presidential election., Main Outcomes and Measures: Hospitalizations for acute CVD around the 2020 presidential election were examined. CVD was defined as hospitalizations for acute myocardial infarction (AMI), heart failure (HF), or stroke. Rate ratios (RR) and 95% CIs were calculated comparing rates of CVD hospitalization in the 5 days following the 2020 election with the same 5-day period 2 weeks prior., Results: Among 6 396 830 adults (3 970 077 [62.1%] aged 18 to 54 years; 3 422 479 [53.5%] female; 1 083 128 [16.9%] Asian/Pacific Islander, 2 101 367 [32.9%] Hispanic, and 2 641 897 [41.3%] White), rates of hospitalization for CVD following the election (666 hospitalizations; rate = 760.5 per 100 000 person-years [PY]) were 1.17 times higher (95% CI, 1.05-1.31) compared with the same 5-day period 2 weeks prior (569 hospitalizations; rate = 648.0 per 100 000 PY). Rates of AMI were significantly higher following the election (RR, 1.42; 95% CI, 1.13-1.79). No significant difference was found for stroke (RR, 1.02; 95% CI, 0.86-1.21) or HF (RR, 1.18; 95% CI, 0.98-1.42)., Conclusions and Relevance: Higher rates of acute CVD hospitalization were observed following the 2020 presidential election. Awareness of the heightened risk of CVD and strategies to mitigate risk during notable political events are needed.

Objectives: To evaluate the risk of heart failure (HF) linked to human immunodeficiency virus (HIV) infection, how risk varies by demographic characteristics, and whether it is explained by atherosclerotic disease or risk factor treatment., Patients and Methods: We performed a retrospective cohort study of persons with HIV (PWHs) from January 1, 2000, through December 31, 2016, frequency-matched 1:10 to persons without HIV on year of entry, age, sex, race/ethnicity, and treating facility. We evaluated the risk of incident HF associated with HIV infection, overall and by left ventricular systolic function, and whether HF risk varied by demographic characteristics., Results: Among 38,868 PWHs and 386,586 matched persons without HIV, mean ± SD age was 41.4±10.8 years, with 12.3% female, 21.1% Black, 20.5% Hispanic, and 3.9% Asian/Pacific Islander. During median follow-up of 3.8 years (interquartile range, 1.4-9.0 years), the rate (per 100 person-years) of incident HF was 0.23 in PWHs vs 0.15 in those without HIV (P<.001). The PWHs had a higher adjusted HF rate (adjusted hazard ratio [aHR], 1.73; 95% confidence interval [CI], 1.57 to 1.91), which was only modestly attenuated after accounting for interim acute coronary syndrome events. Results were similar by systolic function category. The adjusted risk of HF in PWHs was more prominent for those 40 years and younger (aHR, 2.45; 95% CI, 1.92 to 3.03), women (aHR, 2.48; 95% CI, 1.90 to 3.26), and Asian/Pacific Islanders (aHR, 2.46; 95% CI, 1.27 to 4.74)., Conclusion: HIV infection increases the risk of HF, which varied by demographic characteristics and was not primarily mediated through atherosclerotic disease pathways or differential use of cardiopreventive medications., (Copyright © 2021 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Purpose: Our objective was to calculate the positive predictive value (PPV) of the ICD-9 diagnosis code for angioedema when physicians adjudicate the events by electronic health record review. Our secondary objective was to evaluate the inter-rater reliability of physician adjudication., Methods: Patients from the Cardiovascular Research Network previously diagnosed with heart failure who were started on angiotensin-converting enzyme inhibitors (ACEI) during the study period (July 1, 2006 through September 30, 2015) were included. A team of two physicians per participating site adjudicated possible events using electronic health records for all patients coded for angioedema for a total of five sites. The PPV was calculated as the number of physician-adjudicated cases divided by all cases with the diagnosis code of angioedema (ICD-9-CM code 995.1) meeting the inclusion criteria. The inter-rater reliability of physician teams, or kappa statistic, was also calculated., Results: There were 38 061 adults with heart failure initiating ACEI in the study (21 489 patient-years). Of 114 coded events that were adjudicated by physicians, 98 angioedema events were confirmed for a PPV of 86% (95% CI: 80%, 92%). The kappa statistic based on physician inter-rater reliability was 0.65 (95% CI: 0.47, 0.82)., Conclusions: ICD-9 diagnosis code of 995.1 (angioneurotic edema, not elsewhere classified) is highly predictive of angioedema in adults with heart failure exposed to ACEI., (© 2021 John Wiley & Sons Ltd.)

Background: In recent years, decreases in mortality rates attributable to cardiovascular diseases have slowed but mortality attributable to heart failure (HF) has increased., Methods: Between 2001-2017, trends in age-adjusted mortality with HF as an underlying cause for Kaiser Permanente Southern California (KPSC) members were derived through linkage with state death files and compared with trends among California residents and the US. Average annual percent change (AAPC) and 95% confidence intervals (CI) were calculated using Joinpoint regression. Analyses were repeated examining HF as a contributing cause of death., Results: In KPSC, the age-adjusted HF mortality rates were comparable to California but lower than the US, increasing from 23.9 per 100,000 person-years (PY) in 2001 to 44.7 per 100,000 PY in 2017, representing an AAPC of 1.3% (95% CI 0.0%, 2.6%). HF mortality also increased in California from 33.9 to 46.5 per 100,000 PY (AAPC 1.5%, 95% CI 0.3%, 2.7%), while remaining unchanged in the US at 57.9 per 100,000 PY in 2001 and 2017 (AAPC 0.0%, 95% CI - 0.5%, 0.5%). Trends among KPSC members ≥ 65 years old were similar to the overall population, while trends among members 45-64 years old were flat between 2001-2017. Small changes in mortality with HF as a contributing cause were observed in KPSC members between 2001 and 2017, which differed from California and the US., Conclusion: Lower rates of HF mortality were observed in KPSC compared to the US. Given the aging of the US population and increasing prevalence of HF, it will be important to examine individual and care-related factors driving susceptibility to HF mortality.

Background: To examine the individual and combined associations of noncardiac-related conditions and mobility limitation with morbidity and mortality in adults with heart failure (HF)., Methods: We conducted a retrospective cohort study in a large, diverse group of adults with HF from five U.S. integrated healthcare delivery systems. We characterized patients with respect to the presence of noncardiac conditions (<3 vs ≥3) and/or mobility impairment (defined by the use/nonuse of a wheelchair, cane, or walker), categorizing them into four subgroups. Outcomes included all-cause death and hospitalizations for HF or any cause., Results: Among 114,553 adults diagnosed with HF (mean age: 73 years old, 46% women), compared with <3 noncardiac conditions/no mobility limitation, adjusted hazard ratios (HR) for all-cause death among those with <3 noncardiac conditions/mobility limitation, ≥3 noncardiac conditions/no mobility limitation, ≥3 noncardiac conditions/mobility limitation (vs) were 1.40 (95% CI, 1.31-1.51), 1.72 (95% CI, 1.69-1.75), and 1.93 (95% CI, 1.85-2.01), respectively. We did not observe an increased risk of any-cause or HF-related hospitalization related to the presence of mobility limitation among those with a greater burden of noncardiac multimorbidity. Consistent findings regarding mortality were observed within groups defined according to age, gender, and HF type (preserved, reduced, mid-range ejection fraction), with the most prominent impact of mobility limitation in those <65 years of age., Conclusions: There is an additive association of mobility limitation, beyond the burden of noncardiac multimorbidity, on mortality for patients with HF, and especially prominent in younger patients., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Low transferrin saturation (TSAT) or reduced serum ferritin level are suggestive of iron deficiency but the relationship between iron parameters and outcomes has not been systematically evaluated in older adults with heart failure (HF) and anemia., Methods: We identified a multicenter cohort of adults age ≥ 65 years with HF and incident anemia (hemoglobin <13 g/dL [men] or < 12 g/dL [women]) between 2005 and 2012. Patients were included if ferritin (ng/mL) and TSAT (%) were evaluated within 90 days of incident anemia. HF hospitalizations and all-cause death were ascertained from electronic health records., Results: Among 4103 older adults with HF and incident anemia, 47% had TSAT <20% and the median (IQR) ferritin was 126 (53, 256) ng/mL. In multivariable analyses, compared with TSAT ≥20%, patients with TSAT <20% were at increased risk of HF hospitalization for serum ferritin <100 ng/mL (adjusted HR [aHR] 1.40, 95% CI:1.16-1.70) and 100-300 ng/mL (aHR 1.24, 95% CI:1.01-1.52) but not for a ferritin >300 ng/mL (aHR 0.89, 95% CI 0.65-1.23). In addition, TSAT <20% was independently associated with an increased risk of all-cause death regardless of serum ferritin level (<100 ng/mL: aHR 1.42, 95% CI:1.20-1.68; 100-300 ng/mL: aHR 1.18, 95% CI:1.00-1.38; >300 ng/mL: aHR 1.33, 95% CI:1.06-1.69)., Conclusions: Among older adults with HF and incident anemia who had iron studies tested, nearly half had a TSAT <20%, which was independently associated with higher rates of morbidity and death., Competing Interests: Declaration of competing interest Jerry H. Gurwitz reported personal fees and service on the pharmacy and therapeutics committee from UnitedHealthcare outside the submitted work., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Aims: Limited data exist on the epidemiology, evaluation, and prognosis of otherwise unexplained anaemia of the elderly in heart failure (HF). Thus, we aimed to determine the incidence of anaemia, to characterize diagnostic testing patterns for potentially reversible causes of anaemia, and to evaluate the independent association between incident anaemia and long-term morbidity and mortality., Methods and Results: Within the Cardiovascular Research Network (CVRN), we identified adults age ≥65 years with diagnosed HF between 2005 and 2012 and no anaemia at entry. Incident anaemia was defined using World Health Organization (WHO) haemoglobin thresholds (<13.0 g/dL in men; <12.0 g/dL in women). All-cause death and hospitalizations for HF and any cause were identified from electronic health records. Among 38 826 older HF patients, 22 163 (57.1%) developed incident anaemia over a median (interquartile range) follow-up of 2.9 (1.2-5.6) years. The crude rate [95% confidence interval (CI)] per 100 person-years of incident anaemia was 26.4 (95% CI 26.0-26.7) and was higher for preserved ejection fraction (EF) [29.2 (95% CI 28.6-29.8)] compared with borderline EF [26.5 (95% CI 25.4-27.7)] or reduced EF [26.6 (95% CI 25.8-27.4)]. Iron indices, vitamin B12 level, and thyroid testing were performed in 20.9%, 14.9%, and 40.2% of patients, respectively. Reduced iron stores, vitamin B12 deficiency, and/or hypothyroidism were present in 29.7%, 3.2%, and 18.6% of tested patients, respectively. In multivariable analyses, incident anaemia was associated with excess mortality [hazard ratio (HR) 2.14, 95% CI 2.07-2.22] as well as hospitalization for HF (HR 1.80, 95% CI 1.72-1.88) and any cause (HR 1.77, 95% CI 1.72-1.83)., Conclusion: Among older adults with HF, incident anaemia is common and independently associated with substantially increased risks of morbidity and mortality. Additional research is necessary to clarify the value of routine evaluation and treatment of potentially reversible causes of anaemia., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Objectives: To assess multimorbidity burden and its association with clinical outcomes in adults with heart failure (HF) according to sex, age, and HF type., Design: Retrospective cohort study., Setting: Five healthcare delivery systems across the United States., Participants: Adults with HF (N=114,553)., Measurements: We characterized participants with respect to the presence of 26 chronic conditions categorized into quartiles based on overall burden of comorbidity (<5, 5-6, 7-8, ≥9). Outcomes included all-cause death and hospitalization for HF or any cause. Multivariable Cox regression was used to evaluate the adjusted association between categorized burden of multimorbidity burden and outcomes., Results: Individuals with more morbidities were more likely to die than those with fewer then 5 morbidities (5-6 morbidities: adjusted hazard ratio (aHR)=1.27 (95% confidence interval (CI)=1.24-1.31; 7-8 morbidities: aHR=1.52, 95% CI=1.48-1.57; ≥9 morbidities: aHR=1.92, 95% CI=1.86-1.99). There was a graded, higher adjusted rate of any-cause hospitalization associated with 5 or 6 (aHR=1.28, 95% CI=1.25-1.30), 7 or 8 (aHR=1.47, 95% CI=1.44-1.50), or 9 or more (aHR=1.77, 95% CI=1.73-1.82) morbidities (vs <5). Similar findings were observed for HF-specific hospitalization in those with 5 or 6 (aHR=1.22, 95% CI=1.19-1.26), 7 or 8 (aHR=1.39, 95% CI=1.34-1.44), or 9 or more (aHR 1.68, 95% CI=1.61-1.74) morbidities (vs <5). Consistent findings were seen according to sex, age group, and HF type (preserved, reduced, borderline HF), in the association between categorical burden of multimorbidity and outcomes especially prominent in individuals younger than 65., Conclusion: After adjustment, higher levels of multimorbidity predicted worse HF outcomes and may be an important consideration in strategies to improve clinical and person-centered outcomes. J Am Geriatr Soc 66:2305-2313, 2018., (© 2018, Copyright the Authors Journal compilation © 2018, The American Geriatrics Society.)

Background: In US clinical practice, many patients who undergo placement of an implantable cardioverter-defibrillator (ICD) for primary prevention of sudden cardiac death receive dual-chamber devices. The superiority of dual-chamber over single-chamber devices in reducing the risk of inappropriate ICD shocks in clinical practice has not been established. The objective of this study was to compare risk of adverse outcomes, including inappropriate shocks, between single- and dual-chamber ICDs for primary prevention., Methods and Results: We identified patients receiving a single- or dual-chamber ICD for primary prevention who did not have an indication for pacing from 15 hospitals within 7 integrated health delivery systems in the Longitudinal Study of Implantable Cardioverter-Defibrillators from 2006 to 2009. The primary outcome was time to first inappropriate shock. ICD shocks were adjudicated for appropriateness. Other outcomes included all-cause hospitalization, heart failure hospitalization, and death. Patient, clinician, and hospital-level factors were accounted for using propensity score weighting methods. Among 1042 patients without pacing indications, 54.0% (n=563) received a single-chamber device and 46.0% (n=479) received a dual-chamber device. In a propensity-weighted analysis, device type was not significantly associated with inappropriate shock (hazard ratio, 0.91; 95% confidence interval, 0.59-1.38 [ P =0.65]), all-cause hospitalization (hazard ratio, 1.03; 95% confidence interval, 0.87-1.21 [ P =0.76]), heart failure hospitalization (hazard ratio, 0.93; 95% confidence interval, 0.72-1.21 [ P =0.59]), or death (hazard ratio, 1.19; 95% confidence interval, 0.93-1.53 [ P =0.17])., Conclusions: Among patients who received an ICD for primary prevention without indications for pacing, dual-chamber devices were not associated with lower risk of inappropriate shock or differences in hospitalization or death compared with single-chamber devices. This study does not justify the use of dual-chamber devices to minimize inappropriate shocks., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Objective: Patients with chronic kidney disease (CKD) have higher risk of sudden cardiac death; however, they may not receive implantable cardioverter defibrillators (ICDs), in part due to higher risk of complications. We evaluated whether CKD is associated with greater risk of device-delivered shocks/antitachycardia pacing (ATP) therapies among patients receiving a primary prevention ICD., Methods: We studied participants in the observational Cardiovascular Research Network Longitudinal Study of Implantable Cardioverter Defibrillators. CKD was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m 2 . Outcomes included all delivered shocks/ATPs therapies and type of shock/ATP therapies (inappropriate or appropriate, determined by physician adjudication) within the 3 years. We evaluated the associations between CKD and time to first device therapy, burden of device therapy, and inappropriate versus appropriate device therapy, adjusting for demographics, comorbidity, laboratory values and medication use., Results: Among 2161 participants, 1066 (49.3%) had CKD (eGFR 44±11 mL/min/1.73 m 2 ) at ICD implantation. During mean of 2.26±0.89 years, 9.8% and 18.5% of participants had at least one inappropriate and appropriate shock/ATP therapies, respectively. CKD was not associated with time to first shock/ATP therapies (adjusted HR 0.87, 95% CI 0.73 to 1.05), overall burden of shock/ATP therapies (adjusted relative rate 0.93, 95% CI 0.74 to 1.17) or inappropriate versus appropriate shock/ATP therapies (adjusted relative risk 0.88, 95% CI 0.68 to 1.14) compared with not having CKD., Conclusions: In adults receiving a primary prevention ICD, mild-to-moderate CKD was not associated with the timing, burden or appropriateness of subsequent device therapy. Potential concern for inappropriate ICD-delivered therapies should not preclude ICDs among eligible patients with CKD., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Because heart failure (HF) with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF) are different clinical entities with differing demographic characteristics, common HF outcomes may occur at different rates. Comparative outcome studies have been equivocal, and studies comparing resource utilization are scant. We used an observational cohort design to study 6,513 patients hospitalized for HF who had an EF measured during the hospitalization and were discharged alive within 30 days. We excluded 677 patients with borderline EF values (41% to 49%) and categorized the remaining as HFrEF (EF ≤40%, n = 2,205) and HFpEF (EF >50%, n = 3,631). Patients were followed for up to 1 year for all-cause re-hospitalization and mortality and annualized medical resource utilization. Patients with HFrEF and HFpEF experienced similar adjusted incidence rates of re-hospitalization, but those with HFrEF had a 39% increased risk of mortality at 30 days (rate ratio 1.39, 95% confidence interval 1.10 to 1.76) and 25% greater risk at 1 year (rate ratio1.25, 95% confidence interval 1.12 to 1.41). After adjustment for covariates, patients with HFpEF incurred significantly more annualized outpatient visits (21.5 vs 20.1, p = 0.002) and emergency room visits (3.24 vs 2.94, p = 0.002) than those with HFrEF, but absolute differences were small. High inpatient and pharmacy utilization did not differ. Our study suggests that whether a patient has HFrEF or HFpEF has little bearing on risk of re-hospitalization or inpatient resource utilization in the year after an HF hospitalization. Both groups experienced high mortality, but those with HFrEF had greater risk. In conclusion, from the standpoint of resource use, HF can be considered a single entity., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Heart failure (HF) hospitalization length of stay (LOS) has been associated with the risk of subsequent readmission and mortality. We identified 19,927 hospitalized patients with HF who were discharged alive from 2008 to 2011 from 3 Kaiser Permanente regions. In adjusted Cox models using LOS 3 to 4 days as the reference category, shorter LOS was not significantly associated with hospital readmissions. LOS of 5 to 10 days was associated with 17% greater risk of readmission within 30 days (hazard ratio [HR] 1.17, 95% confidence interval [CI] 1.07 to 1.28) and 9% greater risk within 1 year (HR 1.09, 95% CI 1.03 to 1.15). LOS of 11 to 29 days was associated with increased readmission risk of 52% at 30 days (HR 1.52, 95% CI 1.30 to 1.76) and 25% at 1 year (HR 1.25, 95% CI 1.16 to 1.35). Mortality risk within 30 days among those with LOS of 1 day was 47% lower (HR 0.53, 95% CI 0.43 to 0.65) and 32% lower at 1 year (HR 0.68, 95% CI 0.62 to 0.74). LOS of 2 days was associated with lower mortality risk of 17% (HR 0.83, 95% CI 0.76 to 0.90) at 1 year. At LOS 5 to 10 days, 30-day and 1-year risk of mortality was increased by 52% (HR 1.52, 95% CI 1.30 to 1.76) and 25% (HR 1.25, 95% CI 1.16 to 1.35), respectively. LOS of 11 to 29 days was associated with 171% higher mortality risk at 30 days (HR 2.71, 95% CI 2.19 to 3.35) and 73% at 1 year (HR 1.73, 95% CI 1.53 to 1.97). Longer LOS during the index HF hospitalization was associated with readmission and mortality within 30 days and 1 year independent of co-morbidities and cardiovascular risk factors. These results suggest that LOS may be a proxy for the severity of HF during the index hospitalization., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Although the benefits of physical activity for risk of coronary heart disease are well established, less is known about its effects on heart failure (HF). The risk of prolonged sedentary behavior on HF is unknown., Methods and Results: The study cohort included 82 695 men aged≥45 years from the California Men's Health Study without prevalent HF who were followed up for 10 years. Physical activity, sedentary time, and behavioral covariates were obtained from questionnaires, and clinical covariates were determined from electronic medical records. Incident HF was identified through International Classification of Diseases, Ninth Revision codes recorded in electronic records. During a mean follow-up of 7.8 years (646 989 person-years), 3473 men were diagnosed with HF. Controlling for sedentary time, sociodemographics, hypertension, diabetes mellitus, unfavorable lipid levels, body mass index, smoking, and diet, the hazard ratio (95% confidence interval [CI]) of HF in the lowest physical activity category compared with those in the highest category was 1.52 (95% CI, 1.39-1.68). Those in the medium physical activity category were also at increased risk (hazard ratio, 1.17 [95% CI, 1.06-1.29]). Controlling for the same covariates and physical activity, the hazard ratio (95% CI) of HF in the highest sedentary category compared with the lowest was 1.34 (95% CI, 1.21-1.48). Medium sedentary time also conveyed risk (hazard ratio, 1.13 [95% CI, 1.04-1.24]). Results showed similar trends across white and Hispanic subgroups, body mass index categories, baseline hypertension status, and prevalent coronary heart disease., Conclusions: Both physical activity and sedentary time may be appropriate intervention targets for preventing HF.

We sought to compare the risk of end-stage renal disease (ESRD), ischemic heart event (IHE), congestive heart failure (CHF), cerebrovascular accident (CVA), and all-cause mortality among 470,386 individuals with resistant and nonresistant hypertension (non-RH). Resistant hypertension (60,327 individuals) was subcategorized into two groups: 23,104 patients with cRH (controlled on four or more medicines) and 37,223 patients with uRH (uncontrolled on three or more medicines) in a 5-year retrospective cohort study. Cox proportional hazard modeling was used to estimate hazard ratios adjusting for age, gender, race, body mass index, chronic kidney disease (CKD), and comorbidities. Resistant hypertension (cRH and uRH), compared with non-RH, had multivariable adjusted hazard ratios (95% confidence intervals) of 1.32 (1.27-1.37), 1.24 (1.20-1.28), 1.46 (1.40-1.52), 1.14 (1.10-1.19), and 1.06 (1.03-1.08) for ESRD, IHE, CHF, CVA, and mortality, respectively. Comparison of uRH with cRH had hazard ratios of 1.25 (1.18-1.33), 1.04 (0.99-1.10), 0.94 (0.89-1.01), 1.23 (1.14-1.31), and 1.01 (0.97-1.05) for ESRD, IHE, CHF, CVA, and mortality, respectively. Men and Hispanics had a greater risk for ESRD within all three cohorts. Individuals with resistant hypertension had a greater risk for ESRD, IHE, CHF, CVA, and mortality. The risk of ESRD and CVA were 25% and 23% greater, respectively, in uRH compared with cRH, supporting the linkage between blood pressure and both outcomes.

Background: Influenza infection can result in decompensation or exacerbation of heart failure (HF) symptoms, hospitalization, and death. Objective: To examine the association of influenza vaccination with mortality and hospitalization during influenza and non-influenza seasons between 2009 and 2018. Design, Setting, and Participants: In this prospective, observational cohort study, we included Kaiser Permanente Southern California members with a HF diagnosis prior to September 1 each year from 2009 to 2017. Exposure: The first influenza vaccination in each season (September 1 to May 31) was recorded. Vaccinated/unvaccinated patients were matched 1:1 on age, sex, and ejection fraction at the vaccination date (n-total = 74,870). Main Outcomes: Patients were followed through the end of each influenza season for all-cause mortality. Secondary outcomes included cardiovascular mortality and all-cause hospitalization. In a sensitivity analysis, we examined mortality in the non-influenza season. Results: Influenza vaccinated vs unvaccinated patients had more comorbidities and higher healthcare utilization. After multivariable adjustment for utilization, sociodemographics, comorbidities, and medications, influenza vaccinated vs unvaccinated patients had a lower risk of all-cause mortality and cardiovascular mortality during the influenza season (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.63, 0.70 and HR 0.68, 95% CI 0.63, 0.74, respectively) but a higher risk of all-cause hospitalization (HR 1.27, 95% CI 1.21, 1.31). There was no association between influenza vaccination and all-cause or cardiovascular mortality during the non-influenza season (HR 0.99, 95% CI 0.89, 1.09 and HR 1.00, 95% CI 0.84, 1.21, respectively). Conclusions: Influenza vaccination in HF patients was associated with a lower risk of mortality during the influenza season. Our findings provide support for recommendations of universal influenza vaccination in patients with HF. [ABSTRACT FROM AUTHOR]

Background: Examining trends in cardiovascular events and mortality in US health systems can guide the design of targeted clinical and public health strategies to reduce cardiovascular events and mortality rates.Methods and Results: We conducted an observational cohort study from 2005 to 2011 among 1.25 million diabetic subjects and 1.25 million nondiabetic subjects from 11 health systems that participate in the Surveillance, Prevention and Management of Diabetes Mellitus (SUPREME-DM) DataLink. Annual rates (per 1000 person-years) of myocardial infarction/acute coronary syndrome (International Classification of Diseases-Ninth Revision, 410.0–410.91, 411.1–411.8), stroke (International Classification of Diseases-Ninth Revision, 430–432.9, 433–434.9), heart failure (International Classification of Diseases-Ninth Revision, 428–428.9), and all-cause mortality were monitored by diabetes mellitus (DM) status, age, sex, race/ethnicity, and a prior cardiovascular history. We observed significant declines in cardiovascular events and mortality rates in subjects with and without DM. However, there was substantial variation by age, sex, race/ethnicity, and prior cardiovascular history. Mortality declined from 44.7 to 27.1 (P<0.0001) for those with DM and cardiovascular disease (CVD), from 11.2 to 10.9 (P=0.03) for those with DM only, and from 18.9 to 13.0 (P<0.0001) for those with CVD only. Yet, in the [almost equal to]85% of subjects with neither DM nor CVD, overall mortality (7.0 to 6.8; P=0.10) and stroke rates (1.6–1.6; P=0.77) did not decline and heart failure rates increased (0.9–1.15; P=0.0005).Conclusions: To sustain improvements in myocardial infarction, stroke, heart failure, and mortality, health systems that have successfully focused on care improvement in high-risk adults with DM or CVD must broaden their improvement strategies to target lower risk adults who have not yet developed DM or CVD. [ABSTRACT FROM AUTHOR]