Association of the Charlson comorbidity index with mortality in systemic lupus erythematosus

Objective

To investigate whether comorbidity as assessed by the Charlson Comorbidity Index (CCI) is associated with mortality in a long‐term followup of systemic lupus erythematosus (SLE) patients.

Methods

Data were collected from 499 SLE patients attending the Lupus Clinic at the McGill University Health Center, Montreal, Quebec, Canada, and 170 SLE patients from the Department of Rheumatology at Lund University Hospital, Lund, Sweden. This included data on comorbidity, demographics, disease activity, the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI), and antiphospholipid antibody syndrome (APS). Variables were entered into a Cox proportional hazards survival model.

Results

Mortality risk in the Montreal cohort was associated with the CCI (hazard ratio [HR] 1.57 per unit increase in the CCI, 95% confidence interval [95% CI] 1.18–2.09) and age (HR 1.04 per year increase in age, 95% CI 1.00–1.09). The CCI and age at diagnosis were also associated with mortality in the Lund cohort (CCI: HR 1.35, 95% CI 1.13–1.60; age: HR 1.09, 95% CI 1.05–1.12). Furthermore, the SDI was associated with mortality in the Lund cohort (HR 1.40, 95% CI 1.19–1.64), while a wide CI for the estimate in the Montreal cohort prevented a definitive conclusion (HR 1.20, 95% CI 0.97–1.48). We did not find a strong association between mortality and sex, race/ethnicity, disease activity, or APS in either cohort.

Conclusion

In this study, comorbidity as measured by the CCI was associated with decreased survival independent of age, lupus disease activity, and damage. This suggests that the CCI may be useful in capturing comorbidity for clinical research in SLE.     

The association of left ventricular ejection fraction,mortality, and cause of death in stable outpatients with heart failure

OBJECTIVES: The aim of this study was to assess the prognostic importance of left ventricular ejection fraction (LVEF) in stable outpatients with heart failure (HF). BACKGROUND: Although LVEF is an accepted prognostic indicator of prognosis in HF patients, the relationship of LVEF and mortality across the full spectrum of LVEF is incompletely understood. METHODS: We examined the association of LVEF and outcomes among 7,788 stable HF patients enrolled in the Digitalis Investigation Group trial. RESULTS: During mean follow-up of 37 months, mortality was substantial in all LVEF groups (range, LVEF 55%, 23.5%). Among patients with LVEF 45% both before (LVEF 46% to 55%: 23.3%; LVEF > 55%: 23.5%; p = 0.25), and after multivariable adjustment (LVEF 46% to 55%: HR 0.92, 95% CI 0.77 to 1.10; LVEF > 55%: HR 0.88, 95% CI 0.71 to 1.09; LVEF 36% to 45%: referent). Patients with lower LVEF were at increased absolute risk of death due to arrhythmia and worsening HF, but these were leading causes of death in all LVEF groups. CONCLUSIONS: Among HF patients in sinus rhythm, higher LVEFs were associated with a linear decrease in mortality up to an LVEF of 45%. However, increases above 45% were not associated with further reductions in mortality.     

Influence of diabetes on cardiac resynchronization therapy with or without defibrillator in patients with advanced heart failure

ObjectivesWe performed a post hoc analysis to determine the influence of cardiac resynchronization therapy with a defibrillator (CRT-D) or without a defibrillator (CRT-P) on outcomes among diabetic patients with advanced heart failure (HF).BackgroundIn patients with systolic HF, diabetes is an independent predictor of morbidity and mortality. No data are available on its impact on CRT-D or CRT-P in advanced HF.MethodsThe database of the Comparison of Medical Therapy, Pacing and Defibrillation in Heart Failure trial was examined to determine the influence of CRT (CRT-D and CRT-P) on outcomes among diabetic patients. All-cause mortality or hospitalization, all-cause mortality or cardiovascular hospitalization, all-cause mortality or HF hospitalization, and all-cause mortality were analyzed among diabetic patients (n = 622). A Cox proportional hazard model, adjusting for age, gender, New York Heart Association, ischemic status, body mass index, left ventricular ejection fraction, heart rate, QRS, left or right bundle branch block, blood pressure, comorbidities (renal failure, carotid artery disease, peripheral vascular disease, hypertension, coronary artery bypass grafting, and atrial fibrillation), medications, and device (with or without defibrillator), was used to estimate hazard ratios (HRs) and significance.ResultsThe overall outcome of diabetic patients was similar to that of nondiabetic patients in the optimal pharmacologic therapy arm. With CRT, diabetic patients experienced a substantial reduction in all-cause mortality or all-cause hospitalization (HR = 0.77, 95% confidence interval [CI] 62–0.97), all-cause mortality or cardiovascular hospitalization (HR = 0.67, 95% CI 0.53–0.85), all-cause mortality or HF hospitalization (HR = 0.52, 95% CI 0.40–0.69), and all-cause mortality (HR = 0.67, 95% CI 0.45–0.99) compared with optimal pharmacologic therapy. Procedure-related complications and length of stay were identical in diabetic and nondiabetic patients.ConclusionIn diabetic patients with advanced HF, there is a substantial benefit from device therapy with significant improvement in all end points.     

The Relationship Between Valproate and Lamotrigine/Levetiracetam Use and Prognosis in Patients With Epilepsy and Heart Failure: A Danish Register-Based Study

ObjectiveTo compare the hazard for all-cause mortality and mortality due to heart failure (HF) between valproate (VPA) and levetiracetam (LEV)/lamotrigine (LTG) users in patients aged ≥ 65 with comorbidities of epilepsy and HF.MethodsThis was a cohort study using Danish registers during the period from January 1996 to July 2018. The study population included new users of LTG, LEV or VPA. A Cox regression model was used to compute crude and adjusted hazard ratios for the outcome, using an intention-to-treat approach. Average treatment effects (eg, 1-year absolute risks), risk differences and the ratio of risks were computed using the G-formula based on a Cox regression model for the outcomes at the end of the follow-up period.ResultsWe included 1345 subjects in the study population. VPA users (n = 696), when compared to LTG/LEV users (n = 649), had an increased hazard of mortality due to HF (hazard ratio [HR] 2.39; 95% CI 1.02–5.60) and to all-cause mortality (HR 1.37; 95% CI 1.01–1.85) in both crude and adjusted analyses. The 1-year absolute risks for all-cause mortality were 29% (95% CI 25%–33%) and 22% (95% CI 18%–26%) for VPA and LTG/LEV users. For mortality due to HF, 1-year absolute risks were 5% (95% CI 3%–7%) and 2% (95% CI 1%–4%) for VPA and LTG/LEV users. The average risk ratio, with LTG/LEV as the reference group, was 1.31 (95% CI 1.02–1.71) for all-cause mortality and 2.35 (95% CI 1.11–5.76) for HF mortality.ConclusionIn older people with HF and epilepsy, treatment with VPA was associated with a higher risk of all-cause and HF mortality compared to treatment with LTG and LEV.     

Biomarker Predictors of Cardiac Hospitalization in Chronic Heart Failure: A Recurrent Event Analysis

BackgroundIdentification of heart failure (HF) patients at risk for hospitalization may improve care and reduce costs. We evaluated 9 biomarkers as predictors of cardiac hospitalization in chronic HF.Methods and ResultsIn a multicenter cohort of 1,512 chronic HF outpatients, we assessed the association between 9 biomarkers and cardiac hospitalization with the use of a recurrent events approach. Over a median follow-up of 4 years, 843 participants experienced ≥1 hospitalizations (total 2,178 hospitalizations). B-type natriuretic peptide (BNP) and troponin I (TnI) exhibited the strongest associations with risk of hospitalization (hazard ratio [HR] 3.8 [95% confidence interval (CI) 2.9-4.9] and HR 3.3 [95% CI 2.8-3.9]; 3rd vs 1st tertiles). Soluble Fms-like tyrosine kinase receptor 1 (sFlt-1) exhibited the next strongest association (HR 2.8 [95% CI 2.4–3.4]), followed by soluble Toll-like receptor 2 (HR 2.3 [95% CI 2.0–2.8]) and creatinine (HR 1.9 [95% CI 1.6–2.4]). Within ischemic/nonischemic subgroups, BNP and TnI remained most strongly associated. Except for creatinine, HRs for all biomarkers studied were smaller within the ischemic subgroup, suggesting greater importance of cardiorenal interactions in decompensation of ischemic HF.ConclusionAlthough BNP and TnI exhibited the strongest associations with hospitalization, etiology-dependent associations for the remaining biomarkers suggest etiology-specific mechanisms for HF exacerbation. sFlt-1 exhibited a strong association with cardiac hospitalization, highlighting its potential role as a biomarker of HF morbidity.     

The impact of chronic obstructive pulmonary disease in patients hospitalized for worsening heart failure with reduced ejection fraction: an analysis of the EVEREST Trial

BackgroundChronic obstructive pulmonary disease (COPD) is prevalent in heart failure (HF) patients, yet these patients are poorly characterized. We aimed to describe the characteristics and outcomes of patients with systolic dysfunction and COPD in a contemporary HF randomized trial.Methods and ResultsEVEREST investigated 4,133 patients hospitalized with worsening HF and an ejection fraction (EF) ≤40%. We analyzed the characteristics and outcomes (all-cause mortality and cardiovascular mortality/HF hospitalization) of patients according to baseline COPD status. COPD was present in 10% (n = 416) of patients. Patients with COPD had a higher prevalence of comorbidities and were less likely to receive a β-blocker, angiotensin-converting enzyme inhibitor, or aldosterone antagonist. On univariate analysis, COPD was associated with increased all-cause mortality (HR 1.41, 95% CI 1.18–1.67) and cardiovascular mortality/HF hospitalization (HR 1.29, 95% CI 1.11–1.49). After adjusting for potential confounders, the risk associated with COPD remained increased, but was not statistically significant.ConclusionThe presence of COPD in HF patients is associated with an increased burden of comorbidities, lower use of HF therapies, and a trend toward worse outcomes. These findings provide a starting point for prospective investigations of the treatment of HF comorbidities to reduce the high postdischarge event rates.     

Causes and Determinants of Heart Failure Readmissions Post Transcutaneous Aortic Valve Replacement: A Systematic Review and Meta-Analysis

Transcutaneous aortic valve implantation (TAVI) has transformed the management of aortic stenosis (AS) and is increasingly being used for patients with symptomatic, severe aortic stenosis who are ineligible or at high risk for conventional cardiac surgery. PUBMED, Google Scholar, and SCOPUS databases were searched to identify studies reporting heart failure hospitalization after TAVI. Major factors evaluated for HF hospitalization were age, comorbidities such as hypertension, atrial fibrillation (AF), chronic pulmonary disease including COPD, chronic kidney disease, baseline LVEF before the procedure, NYHA symptom class, and society of thoracic surgeons (STS) score. Hazard ratio (HR) with a 95% confidence interval were computed using random-effects models. A total of eight studies were included comprising 77,745 patients who underwent TAVI for severe aortic stenosis. The presence of diabetes mellitus (HR: 1.39, 95% CI [1.17, 1.66], chronic kidney disease (CKD) (HR: 1.39, 95% CI [1.31, 1.48], atrial fibrillation (HR: 1.69, 95% CI [1.42, 2.01], chronic pulmonary disease (HR: 1.33, 95% CI [1.12, 1.58], and a high STS score (HR: 1.07, 95% CI [1.03, 1.11] were positive predictors of 1-year HF hospitalization after TAVI. Patients with diabetes mellitus, AF, CKD, chronic pulmonary disease, and a high STS score are at an increased risk of heart failure hospitalization at 1-year of TAVI, whereas increasing age, hypertension, LVEF <50%, and NYHA class III/IV symptoms did not predict HF hospitalization. Careful follow-up after TAVI in high-risk patients, with closer surveillance for HF particularly, is key to preventing HF hospitalizations and death.     

Multiparametric risk stratification in patients with mild to moderate chronic heart failure

BackgroundWhether brain natriuretic peptide (BNP) combined with cardiopulmonary exercise test (CPx) and echocardiographic findings improves prognostic stratification in mild-to-moderate systolic heart failure (HF) is unclear.Methods and ResultsA total of 244 consecutive stable outpatients, median age of 71 (62–76) years, with New York Heart Association (NYHA) Class I-III HF and left ventricular ejection fraction (LVEF) <45% underwent BNP measurement, Doppler echocardiography, and a maximal CPx. Median BNP was 166 (70–403) pg/mL, median LVEF 35% (28%–40%). A restrictive filling pattern (RFP) was present in 44 patients (18%). At CPx, peak oxygen uptake was 12 (9.7, 14.4) mL/kg/min and an enhanced ventilatory response to exercise (EVR, slope of the ventilation to CO₂ production ratio, ≥35) was found in 90 patients (37%) During 18 (9–37) follow-up months, 80 patients died or were admitted for worsening HF (33%). In addition to simple bedside clinical variables (NYHA Class III, creatinine clearance, hemoglobin), BNP levels were predictive of outcome (HR 1.35 [1.12–1.63]). However, both RFP (HR 3.36 [2.09–5.41]) and a steeper minute ventilation-carbon dioxide output slope (HR 1.50 [1.19–1.88]) outperformed BNP as prognostic markers. Patients with both RFP and EVR had a 7.30 (95% CI 4.02–13.25) HR for death or HF-admission versus subjects with neither predictor.ConclusionsThis study highlights the importance of a multiparametric approach for optimal risk stratification in the elderly with mild-to-moderate HF. Patients at high risk should undergo closer follow-up and be carefully evaluated for different therapeutic options, including nonpharmacologic treatment.     

Galectin-3 Levels and Outcomes After Myocardial Infarction: A Population-Based Study

BackgroundGalectin-3 (Gal-3) is implicated in cardiac fibrosis, but its association with adverse outcomes after myocardial infarction (MI) is unknown.ObjectivesThe purpose of this study was to examine the prognostic value of Gal-3 in a community cohort of incident MI.MethodsA population-based incidence MI cohort was prospectively assembled in Olmsted County, Minnesota, between 2002 and 2012. Gal-3 levels were measured at the time of MI. Patients were followed for heart failure (HF) and death.ResultsA total of 1,342 patients were enrolled (mean age 67.1 years; 61.3% male; 78.8% non–ST-segment elevation MI). Patients with elevated Gal-3 were older and had more comorbidities. Over a mean follow-up of 5.4 years, 484 patients (36.1%) died and 368 (27.4%) developed HF. After adjustment for age, sex, comorbidities, and troponin, patients with Gal-3 values in tertiles 2 and 3 had a 1.3-fold (95% confidence interval [CI]: 0.9-fold to 1.7-fold) and a 2.4-fold (95% CI: 1.8-fold to 3.2-fold) increased risk of death, respectively (p_trend < 0.001) compared with patients with Gal-3 values in tertile 1. Patients with Gal-3 values in tertiles 2 and 3 had a higher risk of HF with hazard ratios of 1.4 (95% CI: 1.0 to 2.0) and 2.3 (95% CI: 1.6 to 3.2), respectively (p_trend < 0.001). With further adjustment for soluble suppression of tumorigenicity-2, elevated Gal-3 remained associated with increased risk of death and HF. The increased risk of HF did not differ by HF type and was independent of the occurrence of recurrent MI.ConclusionsGal-3 is an independent predictor of mortality and HF post-MI. These findings suggest a role for measuring Gal-3 levels for risk stratification post-MI.     

Prevalence and impact of comorbidities on disease prognosis among patients with COVID-19 in Bangladesh: A nationwide study amid the second wave

BackgroundSocio-demographics and comorbidities are involved in determining the severity and fatality in patients with COVID-19 suggested by studies in various countries, but study in Bangladesh is insufficient.AimsWe designed the study to evaluate the association of sociodemographic and comorbidities with the prognosis of adverse health outcomes in patients with COVID-19 in Bangladesh.MethodsA multivariate retrospective cohort study was conducted on data from 966 RT-PCR positive patients from eight divisions during December 13, 2020, to February 13, 2021. Variables included sociodemographic, comorbidities, symptoms, Charlson comorbidity index (CCI) and access to health facilities. Major outcome was fatality. Secondary outcomes included hospitalization, duration of hospital stay, requirement of mechanical ventilation and severity.ResultsMale (65.8%, 636 of 966) was predominant and mean age was 39.8 ± 12.6 years. Fever (79%), dry cough (55%), and loss of test/smell (51%) were frequent and 74% patients had >3 symptoms. Fatality was recorded in 10.5% patients. Comorbidities were found in 44% patients. Hypertension (21.5%) diabetes (14.6%), and cardiovascular diseases (11.3%) were most prevalent. Age >60 years (OR: 4.83, 95% CI: 2.45–6.49), and CCI >3 (OR: 5.48, 95% CI: 3.95–7.24) were predictors of hospitalizations. CCI >4 (aOR: 3.41, 95% CI: 2.57–6.09) was predictor of severity. Age >60 years (aOR: 3.77, 95% CI: 1.07–6.34), >3 symptoms (aOR: 2.14, 95% CI: 0.97–4.91) and CCI >3 vs. CCI <3 (aOR: 5.23, 95% CI: 3.77–8.09) were independently associated with fatality.ConclusionsIncreased age, >3 symptoms, increasing comorbidities, higher CCI were associated with increased hospitalization, severity and fatality in patients with COVID-19.     

Comorbidity assessment for mortality risk stratification in elderly patients with acute coronary syndrome

BackgroundThe Charlson's is the most used comorbidity index. It comprises 19 comorbidities, some of which are infrequent in elderly patients with acute coronary syndrome (ACS), while some others are manifestations of cardiac disease rather than comorbidities. Our goal was to simplify comorbidity assessment in elderly non-ST-segment elevation ACS patients.MethodsThe study group consisted of 1 training (n = 920, 76 ± 7 years) and 1 testing (n = 532; 84 ± 4 years) cohorts. The end-point was all-cause mortality at 1-year follow-up. Comorbidities were assessed selecting those medical disorders other than cardiac disease that were independently associated with mortality by multivariable analysis.ResultsA total of 130 (14%) patients died in the training cohort. Six comorbidities were predictive: renal failure, anemia, diabetes, peripheral artery disease, cerebrovascular disease and chronic lung disease. The increase in the number of comorbidities yielded a gradient of risk on top of well-known clinical predictors: ≥3 comorbidities (27% mortality, HR = 1.90, 95% CI 1.20–3.03, p = .006); 2 comorbidities (16% mortality, HR = 1.29, 95% CI 0.81–2.04, p = .30); and 0–1 comorbidities (7.6% mortality, reference category). The discrimination accuracy (C-statistic = 0.80) and calibration (Hosmer-Lemeshow test, p = .20) of the predictive model using the 6 comorbidities was comparable to the predictive model using the Charlson index (C-statistic = 0.80; Hosmer-Lemeshow test, p = .70). Similar results were reproduced in the testing cohort (≥3 comorbidities: 24% mortality, HR = 2.37, 95% CI 1.25–4.49, p = .008; 2 comorbidities: 14% mortality, HR = 1.59, 95% CI 0.82–3.07, p = .20; 0–1 comorbidities: 7.5% reference category).ConclusionA simplified comorbidity assessment comprising 6 comorbidities provides useful risk stratification in elderly patients with ACS.     

Comparative Effectiveness of Dosing of Medical Therapy for Heart Failure: From the CHAMP-HF Registry

BackgroundThe comparative effectiveness of differing dosages of guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) on clinical and patient-reported outcomes in clinical practice in the United States is unknown. This study sought to characterize associations between the dosing of GDMT and outcomes for patients with HFrEF in U.S. clinical practice.MethodsThis analysis included 4832 outpatients who had chronic HFrEF across 150 practices in the U.S. in the Change the Management of Patients with Heart Failure (CHAMP-HF) registry with no contraindication and available dosing data for at least 1 GDMT at baseline. Baseline dosing of angiotensin-converting enzyme (ACEI)/angiotensin II receptor blocker (ARB)/angiotensin receptor-neprilysin inhibitor (ARNI), beta-blocker, and mineralocorticoid receptor antagonist (MRA) therapies were examined. For each medication class, multivariable models assessed associations between medication dosing and clinical outcomes over 24 months (all-cause mortality, HF hospitalization) and patient-reported outcomes at 12 months (change in the Kansas City Cardiomyopathy Questionnaire Overall Summary score [KCCQ-OS]).ResultsAfter adjustment, compared with target dosing, lower dosing was associated with higher all-cause mortality for ACEIs/ARBs/ARNIs (50% to < 100% target dosage, HR 1.16 [95% CI 0.87–1.55]; < 50% target dosage, HR 1.37 [95% CI 1.05–1.79]; none, HR 1.75 [95% CI 1.32–2.34; overall P< 0.001) and beta-blockers (50% to < 100% target dosage, HR 1.30 [95% CI 1.00–1.69]; < 50% target dosage, HR 1.41 [95% CI 1.11–1.79; none, HR 1.24 [95% CI 0.92–1.67]; overall P= 0.042). Lower dosing of ACEIs/ARBs/ARNIs was independently associated with higher risk of HF hospitalization (50% to < 100% target dosage, HR 1.08 [95% CI 0.90–1.30]; < 50% target dosage, HR 1.23 [1.04–1.47]; none, HR 1.29 [1.04–1.60]; overall P= 0.046), but beta-blocker dosing was not (overall P= 0.085). Target dosing of MRAs was not associated with risk of mortality or HF hospitalization. For each GDMT, compared with target dosing, lower dosing was not associated with change in the KCCQ-OS at 12 months, with the potential exception of worsening KCCQ-OS scores with lower dosing of ACEIs/ARBs/ARNIs.ConclusionsIn this contemporary U.S. outpatient HFrEF registry, target dosing of ACEI/ARB/ARNI and beta-blocker therapy was associated with reduced mortality and was variably associated with HF hospitalization and patient-reported outcomes. MRA dosing was not associated with outcomes. The totality of these findings support the benefits of target dosing of GDMT in routine practice, as tolerated, with unmeasured differences among patients receiving differing dosages potentially explaining the differing results seen here compared with randomized clinical trials.     

Improving the Characterization of Stage A and B Heart Failure by Adding Global Longitudinal Strain

BackgroundCurrent guidelines distinguish stage B heart failure (SBHF) (asymptomatic left ventricular [LV] dysfunction) from stage A heart failure (SAHF) (asymptomatic with heart failure [HF] risk factors) on the basis of myocardial infarction, LV remodeling (hypertrophy or reduced ejection fraction [EF]) or valvular disease. However, subclinical HF with preserved EF may not be identified with these criteria.ObjectivesThe purpose of this study was to assess the prediction of incident HF with global longitudinal strain (GLS) in patients with SAHF and SBHF.MethodsThe authors analyzed echocardiograms (including GLS) in 447 patients (age 65 ± 11 years; 77% male) enrolled in a prospective study of HF in individuals at risk of incident HF, with normal or mildly impaired EF (≥40%). Long-term follow-up was obtained via data linkage. Analysis was performed using a competing risks model.ResultsAfter a median of 9 years of follow-up, 50 (10%) of the 447 patients had new HF admissions, and 87 (18%) died. In multivariable analysis, all imaging variables were independent predictors of HF admissions, including left ventricular ejection fraction (LVEF) (HR: 0.97 [95% CI: 0.94-0.99]), LV mass index (HR: 1.01 [95% CI: 1.00-1.02]), left atrial volume index (HR: 1.02 [95% CI: 1.00-1.05]), and E/e′ (HR: 1.05 [95% CI: 1.01-1.24]), incremental to clinical variables (age and Charlson comorbidity score). However, the addition of GLS provided value incremental to both clinical and other echocardiographic parameters (P = 0.004). Impaired GLS (<18%) (HR: 4.09 [95% CI: 1.87-8.92]) was independent and incremental to all clinical and other echocardiographic variables in predicting HF, and impaired LVEF, left ventricular hypertrophy, left atrial enlargement, high E/e′, or SBHF were not predictive.ConclusionsThe inclusion of GLS as a criterion for SBHF would add independent and incremental information to standard markers of SBHF for the prediction of subsequent HF admissions.     

The Association Between Secondhand Smoke Exposure and Survival for Patients With Heart Failure

BackgroundThe effect of secondhand tobacco smoke (SHS) exposure on patients with heart failure (HF) is uncertain. We investigated the association of mortality with SHS exposure for patients with HF.MethodsNonsmokers with clinical HF were enrolled from 2003 to 2008 in a single-center longitudinal cohort study. The effect of SHS exposure determined by high-sensitivity urinary cotinine on mortality was estimated by multivariable proportional hazards modeling.ResultsMortality was assessed after median 4.3 years. Of 202 patients, enrollment urinary cotinine levels were below the limit of detection for 106 (52%) considered unexposed to SHS. The median detectable cotinine was 0.47 ng/mL (interquartile range: [0.28, 1.28]). Participants were 41% female, 65 ± 17 years old, and 57% white race. Elevated cotinine was associated with increased mortality after multivariate adjustment: hazard ratio (HR) per 1 ng/mL increase in urinary cotinine: 1.15, 95% confidence interval (CI): 1.08–1.23, P < .001. Higher age (HR per 5-year increase: 1.32, 95% CI: 1.22–1.43, P < .001), male sex (HR vs female: 1.52, 95% CI: 1.02–2.28, P = .040), and New York Heart Association class (HR for class III vs I: 2.91, 95% CI: 1.71–4.99, P < .001) were also associated with mortality.ConclusionsSHS exposure is associated with a dose-dependent increase in mortality for patients with HF.     

Effect of digoxin in patients with heart failure and mid‐range (borderline) left ventricular ejection fraction

Aims

To evaluate the effects of digoxin in patients with the newly described phenotype of heart failure (HF) and mid‐range ejection fraction (HFmrEF), attributed to mild left ventricular systolic dysfunction.

Methods and results

We carried out a retrospective analysis of the Digitalis Investigation Group (DIG) trial which had 7788 patients available for analysis with a left ventricular ejection fraction (LVEF) ranging between 3% and 85%. We compared the effect of digoxin to placebo in three mutually exclusive groups of patients defined by LVEF category: <40% (HF with reduced LVEF, HFrEF, n = 5874), 40–49% (HFmrEF, n = 1195) and ≥50% (HF with preserved LVEF, HFpEF, n = 719). The primary outcome was the composite of cardiovascular death or HF hospitalisation. Patients with HFmrEF resembled patients with HFrEF, more than those with HFpEF, with respect to age, sex and aetiology but were more like HFpEF patients with respect to blood pressure and the prevalence of hypertension. Event rates in patients with HFmrEF were similar to those in HFpEF and much lower than in HFrEF. Digoxin reduced the primary endpoint in patients with HFrEF, mainly due to reduced HF hospitalisation: the digoxin/placebo hazard ratio (HR) for HF hospitalisation was 0.71 [95% confidence interval (CI) 0.65–0.77]. The digoxin/placebo HR for HF hospitalisation in patients with HFmrEF was 0.80 (95% CI 0.63–1.03) and 0.85 (95% CI 0.62–1.17) in those with HFpEF. The digoxin/placebo HR for the composite of HF death or HF hospitalisation was 0.74 (95% CI 0.68–0.81) in HFrEF, 0.83 (95% CI 0.66–1.05) in HFmrEF and 0.88 (95% CI 0.65–1.19) in HFpEF.

Conclusions

In this study, event rates in patients with HFmrEF were closer to those in HFpEF than HFrEF. Digoxin had most effect on HF hospitalisation in patients with HFrEF, an intermediate effect in HFmrEF, and the smallest effect in HFpEF.

     

Hyponatremia and long-term outcomes in chronic heart failure--an observational study from the Duke Databank for Cardiovascular Diseases

BackgroundHyponatremia is a well known predictor of short-term outcomes in heart failure (HF); however, its impact on long-term survival in HF patients with systolic dysfunction is not well established.Methods and ResultsUsing the Duke Databank for Cardiovascular Diseases, we identified 1,045 patients with HF and systolic dysfunction undergoing cardiac catheterization from January 2000 through December 2008. The effect of hyponatremia as independent predictor of all-cause death and cardiovascular death/rehospitalization was examined using a multivariable Cox proportional regression model. Hyponatremia was present in 107/1,045 patients (10.2%). Hyponatremic patients were older, more likely to be anemic, with higher heart rate and levels of blood urea nitrogen, lower blood pressure, and more severe HF. Using an unadjusted analysis, hyponatremia was associated with higher risk of all-cause death (hazard ratio [HR] 1.89, 95% confidence interval [CI] 1.44–2.49; P < .0001) and of cardiovascular death/rehospitalization (HR 1.40, 95% CI 1.11–1.77; P = .005) at 4.5 years. When entered into a multivariable Cox model, hyponatremia remained significant for all-cause death (HR 1.42, 95% CI 1.07–1.88) and for cardiovascular death/rehospitalization (HR 1.45, 95% CI 1.14–1.86).ConclusionsHyponatremia is relatively common in HF patients with LV dysfunction and is independently associated with increased risk of all-cause mortality and cardiovascular mortality/rehospitalization.     

Effects of angiotensin-converting enzyme inhibitor and angiotensin Ⅱ receptor blocker on one-year outcomes of patients with atrial fibrillation:insights from a multicenter registry study in China

ObjectiveTo evaluate the effect of angiotensin-converting enzyme inhibitor (ACEI)/angiotensin II receptor blocker (ARB) therapy on the prognosis of patients with atrial fibrillation (AF).MethodsA total of 1, 991 AF patients from the AF registry were divided into two groups according to whether they were treated with ACEI/ARB at recruitment. Baseline characteristics were carefully collected and analyzed. Logistic regression was utilized to identify the predictors of ACEI/ARB therapy. The primary endpoint was all-cause mortality, while the secondary endpoints included cardiovascular mortality, stroke and major adverse events (MAEs) during the one-year follow-up period. Univariable and multivariable Cox regression were performed to identify the association between ACEI/ARB therapy and the one-year outcomes.ResultsIn total, 759 AF patients (38.1%) were treated with ACEI/ARB. Compared with AF patients without ACEI/ARB therapy, patients treated with ACEI/ARB tended to be older and had a higher rate of permanent AF, hypertension, diabetes mellitus, heart failure (HF), left ventricular ejection fraction (LVEF) < 40%, coronary artery disease (CAD), prior myocardial infarction (MI), left ventricular hypertrophy, tobacco use and concomitant medications (all P < 0.05). Hypertension, HF, LVEF < 40%, CAD, prior MI and tobacco use were determined to be predictors of ACEI/ARB treatment. Multivariable analysis showed that ACEI/ARB therapy was associated with a significantly lower risk of one-year all-cause mortality [hazard ratio (HR) (95% CI): 0.682 (0.527-0.882), P = 0.003], cardiovascular mortality [HR (95% CI): 0.713 (0.514-0.988), P = 0.042] and MAEs [HR (95% CI): 0.698 (0.568-0.859), P = 0.001]. The association between ACEI/ARB therapy and reduced mortality was consistent in the subgroup analysis.ConclusionsIn patients with AF, ACEI/ARB was related to significantly reduced one-year all-cause mortality, cardiovascular mortality and MAEs despite the high burden of cardiovascular comorbidities.     

Type 2 diabetes increases the risk of hospital admission for heart failure and reduces the risk of in hospital mortality in Spain (2001–2015)

BackgroundTo compare trends in incidence, clinical characteristics and outcomes of heart failure (HF) hospitalizations among patients with or without type 2 diabetes (T2DM) in Spain (2001–2015).MethodsWe used national hospital discharge data to select hospital admissions for HF as primary diagnosis. Incidence, comorbidities, diagnostic and therapeutic procedures, and in hospital mortality (IHM) were analyzed.ResultsWe identified a total of 1,501,811 admissions for HF (36.87% with T2DM). Incidences were higher among those with T2DM than those without diabetes. The adjusted incidence of HF among T2DM patients was 4.93 higher than for non-diabetic subjects (IRR 4.93;95%CI 4.91–4.95). Jointpoint analysis showed that sex-age-adjusted admissions in T2DM patients with HF increased by 7.12% per year from 2001 to 2007 and stabilized afterwards. For non-diabetic patients a constant increase overtime of around 1% was found.Patients with T2DM were significantly younger than patients without diabetes (77.22 vs. 79.36 years) and had more coexisting medical conditions according to the Charlson Comorbidity Index (mean CCI 1.99 ± 0.88 vs. 1.90 ± 0.86). For the total time period, crude IHM was lower for T2DM patients than for non-diabetic people (8.35% vs, 10.57%; p < 0.05) and the association remained significant after multivariable adjustment ((OR, 0.84; 95%CI 0.83–0.86).). Female sex, older age and multiple comorbidities were significant risk factors for IHM.ConclusionsT2DM increases the risk of admission for HF by five-fold. Our study demonstrates an increase in hospitalization for HF in diabetic patients from 2001 to 2007 and stabilization afterwards. T2DM was associated with a lower IHM after hospitalization for HF.     

Clonal Hematopoiesis and Risk of Progression of Heart Failure With Reduced Left Ventricular Ejection Fraction

BackgroundClonal hematopoiesis driven by somatic mutations in hematopoietic cells, frequently called clonal hematopoiesis of indeterminate potential (CHIP), has been associated with adverse cardiovascular outcomes in population-based studies and in patients with ischemic heart failure (HF) and reduced left ventricular ejection fraction (LVEF). Yet, the impact of CHIP on HF progression, including nonischemic etiology, is unknown.ObjectivesThe purpose of this study was to assess the clinical impact of clonal hematopoiesis on HF progression irrespective of its etiology.MethodsThe study cohort comprised 62 patients with HF and LVEF <45% (age 74 ± 7 years, 74% men, 52% nonischemic, and LVEF 30 ± 8%). Deep sequencing was used to detect CHIP mutations with a variant allelic fraction >2% in 54 genes. Patients were followed for at least 3.5 years for various adverse events including death, HF-related death, and HF hospitalization.ResultsCHIP mutations were detected in 24 (38.7%) patients, without significant differences in all-cause mortality (p = 0.151). After adjusting for risk factors, patients with mutations in either DNA methyltransferase 3 alpha (DNMT3A) or Tet methylcytosine dioxygenase 2 (TET2) exhibited accelerated HF progression in terms of death (hazard ratio [HR]: 2.79; 95% confidence interval [CI]: 1.31 to 5.92; p = 0.008), death or HF hospitalization (HR: 3.84; 95% CI: 1.84 to 8.04; p < 0.001) and HF-related death or HF hospitalization (HR: 4.41; 95% CI: 2.15 to 9.03; p < 0.001). In single gene-specific analyses, somatic mutations in DNMT3A or TET2 retained prognostic significance with regard to HF-related death or HF hospitalization (HR: 4.50; 95% CI: 2.07 to 9.74; p < 0.001, for DNMT3A mutations; HR: 3.18; 95% CI: 1.52 to 6.66; p = 0.002, for TET2 mutations). This association remained significant irrespective of ischemic/nonischemic etiology.ConclusionsSomatic mutations that drive clonal hematopoiesis are common among HF patients with reduced LVEF and are associated with accelerated HF progression regardless of etiology.     

Resting Heart Rate and Chronotropic Response to Exercise: Prognostic Implications in Heart Failure Across the Left Ventricular Ejection Fraction Spectrum

Background:

We studied the relationship between resting heart rate (HR), chronotropic response to exercise, and clinical outcomes in patients with heart failure (HF) across the spectrum of left ventricle ejection fraction (LVEF).