Impact of hyper-polypharmacy due to non-cardiovascular medications on long-term clinical outcomes following endovascular treatment for lower limb artery disease: A sub-analysis of the I-PAD Nagano registry.

BACKGROUND: Lower limb artery disease (LEAD) is accompanied by multiple comorbidities; however, the effect of hyperpolypharmacy on patients with LEAD has not been established. This study investigated the associations between hyperpolypharmacy, medication class, and adverse clinical outcomes in patients with LEAD. METHODS: This study used data from a prospective multicenter observational Japanese registry. A total of 366 patients who underwent endovascular treatment (EVT) for LEAD were enrolled in this study. The primary endpoints were major adverse cardiac events (MACE), including myocardial infarction, stroke, and all-cause death. RESULTS: Of 366 patients with LEAD, 12 with missing medication information were excluded. Of the 354 remaining patients, 166 had hyperpolypharmacy (≥10 medications, 46.9 %), 162 had polypharmacy (5-9 medications, 45.8 %), and 26 had nonpolypharmacy (<5 medications, 7.3 %). Over a 4.7-year median follow-up period, patients in the hyperpolypharmacy group showed worse outcomes than those in the other two groups (log-rank test, p < 0.001). Multivariate analysis revealed that the total number of medications was significantly associated with an increased risk of MACE (hazard ratio per medication increase 1.07, 95 % confidence interval 1.02-1.13 p = 0.012). Although an increased number of non-cardiovascular medications was associated with an elevated risk of MACE, the increase in cardiovascular medications was not statistically significant (log-rank test, p = 0.002 and 0.35, respectively). CONCLUSIONS: Hyperpolypharmacy due to non-cardiovascular medications was significantly associated with adverse outcomes in patients with LEAD who underwent EVT, suggesting the importance of medication reviews, including non-cardiovascular medications.

Prognostic Impact of Hyperpolypharmacy Due to Noncardiovascular Medications in Patients After Acute Decompensated Heart Failure　- Insights From the Clue of Risk Stratification in the Elderly Patients With Heart Failure (CURE-HF) Registry.

BACKGROUND: Hyperpolypharmacy is associated with adverse outcomes in older adults, but because literature on its association with cardiovascular (CV) outcomes after acute decompensated heart failure (ADHF) is sparse, we investigated the relationships among hyperpolypharmacy, medication class, and death in patients with HF.Methods and Results: We evaluated the total number of medications prescribed to 884 patients at discharge following ADHF. Patients were categorized into nonpolypharmacy (<5 medications), polypharmacy (5-9 medications), and hyperpolypharmacy (≥10 medications) groups. We examined the relationship of polypharmacy status with the 2-year mortality rate. The proportion of patients taking ≥5 medications was 91.3% (polypharmacy, 55.3%; hyperpolypharmacy, 36.0%). Patients in the hyperpolypharmacy group showed worse outcomes than patients in the other 2 groups (P=0.002). After multivariable adjustment, the total number of medications was significantly associated with an increased risk of death (hazard ratio [HR] per additional increase in the number of medications, 1.05; 95% confidence interval [CI], 1.01-1.10; P=0.027). Although the number of non-CV medications was significantly associated with death (HR, 1.07; 95% CI, 1.02-1.13; P=0.01), the number of CV medications was not (HR, 1.01; 95% CI, 0.92-1.10; P=0.95). CONCLUSIONS: Hyperpolypharmacy due to non-CV medications was associated with an elevated risk of death in patients after ADHF, suggesting the importance of a regular review of the prescribed drugs including non-CV medications.

Clinical Profile and Prognosis of Dementia in Patients With Acute Decompensated Heart Failure　- From the CURE-HF Registry.

BACKGROUND: Acute decompensated heart failure (ADHF) has a poor prognosis and common comorbidities may be contributory. However, evidence for the association between dementia and clinical outcomes in patients with is sparse and it requires further investigation into risk reduction.Methods and Results: We assessed the clinical profiles and outcomes of 1,026 patients (mean age 77.8 years, 43.2% female) with ADHF enrolled in the CURE-HF registry to evaluate the relationship between investigator-reported dementia status and clinical outcomes (all-cause death, cardiovascular (CV) death, non-CV death, and HF hospitalization) over a median follow-up of 2.7 years. In total, dementia was present in 118 (11.5%) patients, who experienced more drug interruptions and HF admissions due to infection than those without dementia (23.8% vs. 13.1%, P<0.01; 11.0% vs. 6.0%, P<0.01, respectively). Kaplan-Meier analysis revealed that dementia patients had higher mortality rates than those without dementia (log-rank P<0.001). After multivariable adjustment for demographics and comorbidities, dementia was significantly associated with an increased risk of death (adjusted hazard ratio, 1.43; 95% confidence interval, 1.06-1.93, P=0.02) and non-CV death (adjusted hazard ratio, 1.65; 95% confidence interval, 1.04-2.62, P=0.03), but no significant associations between dementia and CV death or HF hospitalization were observed (both, P>0.1). CONCLUSIONS: In ADHF patients dementia was associated with aggravating factors for HF admission and elevated risk of death, primarily non-CV death.

Gender difference in heart failure with preserved ejection fraction: clinical profiles, examinations, and prognosis.

Heart failure with preserved ejection fraction (HFpEF) has currently become a major concern in the aging society owing to its substantial and growing prevalence. Recent investigations regarding sacubitril/valsartan have suggested that there is a gender difference in the efficacy of the medication in HFpEF cohort. However, information of gender difference in clinical profiles, examination, and prognosis have not been well investigated. The present study aimed to evaluate the differences in baseline characteristics and outcomes between women and men in a Japanese HFpEF cohort. We analyzed the data from our prospective, observational, and multicenter cohort study. Overall, 1036 consecutive patients hospitalized for acute decompensated heart failure were enrolled. We defined patients with an ejection fraction (EF) of ≥ 50% as HFpEF. Patients with severe valvular disease were excluded; the remaining 379 patients (women: n = 201, men: n = 178) were assessed. Women were older than men [median: 85 (79-89) years vs. 83 (75-87) years, p = 0.013]. Diabetes mellitus, hyperuricemia, and coronary artery disease were more prevalent in men than in women (34.8% vs. 23.9%, p = 0.019, 23.6% vs. 11.4%, p = 0.002, and 23.0% vs. 11.9%, p = 0.005, respectively). EF was not significantly different between women and men. The cumulative incidence of cardiovascular death or hospitalization for congestive heart failure (CHF) was significantly lower in women than in men (log-rank p = 0.040). Women with HFpEF were older and less often exhibited an ischemic etiology; further, they were associated with a lower risk for cardiovascular death or hospitalization for CHF compared with men in the Japanese population.

Comparison of prognostic impact of anticoagulants in heart failure patients with atrial fibrillation and renal dysfunction: direct oral anticoagulants versus vitamin K antagonists.

Although high thromboembolic risk was assumed in elderly patients with heart failure (HF) and atrial fibrillation (AF), inadequate control of prothrombin time/international normalized ratio was often observed in patients using vitamin K antagonists (VKAs). We hypothesized that patients treated with direct oral anticoagulants (DOAC) would have a better outcome than those treated with VKAs. The aim of this study was to compare the efficacies of DOACs and VKAs in elderly patients with HF and AF. We retrospectively analyzed data from a multicenter, prospective observational cohort study. A total of 1036 patients who were hospitalized for acute decompensated HF were enrolled. We assessed 329 patients aged > 65 years who had non-valvular AF and divided them into 2 groups according to the anticoagulant therapy they received. A subgroup analysis was performed using renal dysfunction based on estimated glomerular filtration rate (eGFR; mL/min/1.73 m2). The primary outcome was all-cause mortality, and the secondary outcomes were non-cardiovascular death or stroke. The median follow-up period was 730 days (range 334-1194 days). The primary outcome was observed in 84 patients; non-cardiovascular death, in 25 patients; and stroke, in 14 patients. The Kaplan-Meier analysis revealed that all-cause mortality was significantly lower in the DOAC group than in the VKA group (log-rank p = 0.033), whereas the incidence rates of non-cardiovascular death (log-rank p = 0.171) and stroke (log-rank p = 0.703) were not significantly different in the crude population. DOAC therapy was not associated with lower mortality in the crude population (log-rank p = 0.146) and in the eGFR ≥ 45 mL/min/1.73 m2 subgroup (log-rank p = 0.580). However, DOAC therapy was independently associated with lower mortality after adjustments for age, diabetes mellitus, and albumin level (hazard ratio, 0.55; 95% confidence interval, 0.30-0.99; p = 0.045) in the eGFR < 45 mL/min/1.73 m2 subgroup. Compared with VKA therapy, DOAC therapy was associated with lower risk of all-cause mortality in the elderly HF patients with AF and renal dysfunction.

Inflammation-based assessment for the risk stratification of mortality in patients with heart failure.

The Glasgow Prognostic Score (GPS) has been established as a useful resource to evaluate inflammation and malnutrition and predict prognosis in several cancers. However, its prognostic significance in patients with heart failure (HF) is not well established. To investigate the association between the GPS and mortality in patients with HF, we assessed 870 patients who were 20 years old and more and had been admitted for acute decompensated HF. The GPS ranged from 0 to 2 points as previously reported. Over the 18-month follow-up (follow-up rate, 83.9%), 143 patients died. Increasing GPS was associated with higher HF severity assessed by New York Heart Association functional class and B-type natriuretic peptide (BNP) levels. Kaplan-Meier analysis showed significant associations for mortality and increased GPS. In multivariate analysis, compared to the GPS 0 group, the GPS 2 group was associated with high mortality (hazard ratio 2.92, 95% confidence interval 1.77-4.81, p < 0.001) after adjustment for age, sex, blood pressure, HF history, HF severity, hemoglobin, renal function, sodium, BNP, left ventricular ejection fraction, and anti-HF medications. In conclusion, high GPS was significantly associated with worse prognosis in patients with HF. Inflammation-based assessment by the GPS may enable simple evaluation of HF severity and prognosis.

Prognostic ability of mid-term worsening renal function after percutaneous coronary intervention: findings from the SHINANO registry.

Chronic kidney disease is a prognostic factor for cardiovascular disease. Worsening renal function (WRF), specifically, is an important predictor of mortality in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention (PCI). We evaluate the prognostic impact of mid-term WRF after PCI on future cardiovascular events. We examined the renal function data of 1086 patients in the first year after PCI using the SHINANO 5-year registry. Patients were divided into two groups, mid-term WRF and non-mid-term WRF, and primary outcomes were major adverse cardiovascular events (MACE) and death. Mid-term WRF was defined as an increase in creatinine (≥ 0.3 mg/dL) in the first year after PCI. Mid-term WRF was found in 101 patients (9.3%), and compared to non-mid-term WRF, it significantly increased the incidence of MACE (p < 0.001), and all-cause death (p < 0.001), myocardial infarction (p = 0.001). Furthermore, mid-term WRF patients had higher incidence of future heart failure (p < 0.001) and new-onset atrial fibrillation (p = 0.01). Patients with both mid-term WRF and chronic kidney disease had increased MACE compared to patients with either condition alone (p < 0.001). Similarly, patients with mid-term WRF and acute kidney injury had increased MACE compared to patients with either condition alone (p < 0.001). Multivariate Cox regression analysis revealed mid-term WRF as a strong predictor of MACE (hazard ratio: 2.50, 95% confidence interval 1.57-3.98, p < 0.001). Mid-term WRF after PCI negatively affects MACE, as well as future admission due to heart failure and new-onset atrial fibrillation, chronic kidney disease, and acute kidney injury.

Cardio-renal and cardio-hepatic interactions predict cardiovascular events in elderly patients with heart failure.

BACKGROUND: The composite Model for End-Stage Liver Disease Excluding International Normalized Ratio Score (MELD-XI) is a novel tool to evaluate cardio-renal and cardio-hepatic interactions in patients with advanced heart failure (HF). However, its prognostic ability remains unclear in elderly HF patients. METHODS AND RESULTS: From July 2014 to July 2018, patients hospitalized for HF were prospectively recruited at 16 centers. Clinical features, laboratory findings, and echocardiography results were assessed prior to discharge. Cardiovascular (CV) death and HF re-hospitalization were recorded. Of the 676 patients enrolled, 264 (39.1%) experienced CV events throughout a 1-year median follow-up period. Patients with high MELD-XI were predominantly male and had a higher prevalence of NYHA III/IV, history of HF admission, hyperuricemia, ventricular tachycardia, anemia, and ischemic heart disease. In Kaplan-Meyer analysis, patients with higher MELD-XI (≥11) scores showed a worse prognosis than did those with lower (<11) scores (log-rank p≤0.001). Multivariate Cox proportional hazards testing revealed MELD-XI as an independent predictor of CV events (HR: 1.033, 95% CI: 1.006-1.061, p = 0.015) after adjusting for age, gender, body mass index, NYHA III/IV, prior HF hospitalization, systolic blood pressure, ischemic etiology, ventricular tachycardia, anemia, BNP, and left ventricular ejection fraction. CONCLUSIONS: Cardio-renal and cardio-hepatic interactions predicted CV events in aged HF patients.

Impact of inpatient cardiac rehabilitation on Barthel Index score and prognosis in patients with acute decompensated heart failure.

BACKGROUND: Although cardiac rehabilitation (CR) can improve exercise capacity and quality of life in patients with chronic heart failure (HF), the long-term prognostic influence of inpatient CR on patients with acute decompensated HF (ADHF) is not well established. We examined the impact of inpatient CR on disability and prognosis in patients with ADHF. METHODS: A total of 171 patients admitted for ADHF underwent CR that included resistance training and aerobic exercise. Patient disability was evaluated using Barthel Index (BI) scores at pre- (BIpre) and post- (BIpost) rehabilitation. All-cause mortality was retrospectively recorded after discharge. RESULTS: In the study cohort (median age: 76 years), 46 patients experienced all-cause mortality during a median of 478 days of follow-up. Impaired BIpost (i.e., BI < 60) was significantly correlated with older age and lower albumin, hemoglobin, estimated glomerular filtration rate (eGFR), and B-type natriuretic peptide (BNP). In Kaplan-Meier analysis, impaired BIpre and BIpost were significantly associated with all-cause mortality. Better outcomes were observed for improved BI (ΔBI > 15) among patients with impaired baseline BI. BIpost was an independent predictor of all-cause mortality after adjusting for age, sex, eGFR, BNP, hemoglobin, albumin, and left ventricular ejection fraction. CONCLUSIONS: Inpatient CR led to improvements in disabilities among patients with ADHF. Baseline disabilities were associated with a poor prognosis. Greater improvements in BI to inpatient CR were significantly related to better outcomes in patients with impaired baseline BI. CR should be indicated for patients with ADHF.