Impact of the method of calculating 30-day readmission rate after hospitalization for heart failure. Data from the VancOuver CoastAL Acute Heart Failure (VOCAL-AHF) registry.

BACKGROUND: Thirty-day readmission rate after heart failure (HF) hospitalization is widely used to evaluate healthcare quality. Methodology may substantially influence estimated rates. We assessed the impact of different definitions on HF and all-cause readmission rates. METHODS: Readmission rates were examined in 1,835 patients discharged following HF hospitalization using 64 unique definitions derived from five methodological factors: (1) ICD-10 codes (broad vs narrow), (2) index admission selection (single admission only first-in-year vs. random sample; or multiple admissions in year with vs. without 30-day blanking period), (3) variable denominator (number alive at discharge vs. number alive at 30-days), (4) follow-up period start (discharge date vs day following discharge), and (5) annual reference-period (calendar vs fiscal). The impact of different factors was assessed using linear-regression. RESULTS: The calculated 30-day readmission rate for HF varied more than 2-fold depending solely on the methodological approach (6.5% to 15.0%). All-cause admission rates exhibited similar variation (18.8% to 29.9%). The highest rates included all consecutive index admissions (HF 11.1-15.0%, all-cause 24.0-29.9%), and lowest only one index admission per patient per year (HF 6.5-11.3%, all-cause 18.8-22.7%). When including multiple index admissions and compared to blanking the 30-days post-discharge, not blanking was associated with 2.3% higher readmission rates. Selecting a single admission per year with a first-in-year approach lowered readmission rates by 1.5%, while random-sampling admissions lowered estimates further by 5.2% (p<0.001). CONCLUSION: Calculated 30-day readmission rates varied more than 2-fold by altering methods. Transparent and consistent methods are needed to ensure reproducible and comparable reporting.

Variability in Nonvitamin K Oral Anticoagulant Dose Eligibility and Adjustment According to Renal Formulae and Clinical Outcomes in Patients With Atrial Fibrillation With and Without Chronic Kidney Disease: Insights From ORBIT-AF II.

Background Nonvitamin K oral anticoagulants require dose adjustment based on kidney function.The most common estimate of kidney function employed in clinical practice is estimated glomerular filtration rate (eGFR); however, product monographs recommend the use of the Cockcroft-Gault estimated creatinine clearance (eCrCl) for dose adjustment. Methods and Results The authors included patients enrolled in the ORBIT-AF II (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation AF II) trial. Dosing was considered inappropriate when use of eGFR resulted in a lower (undertreatment) or higher (overtreatment) dose than that recommended by the eCrCl. The primary outcome of major adverse cardiovascular and neurological events was a composite of cardiovascular death, stroke or systemic embolism, new-onset heart failure, and myocardial infarction. Among 8727 in the overall cohort, agreement between eCrCl and eGFR was observed in 93.5% to 93.8% of patients. Among 2184 patients with chronic kidney disease (CKD), the agreement between eCrCl and eGFR was 79.9% to 80.7%. Dosing misclassification was more frequent in the CKD population (41.9% of rivaroxaban users, 5.7% of dabigatran users, and 4.6% apixaban users). At 1 year, undertreated patients in the CKD group had significantly greater major adverse cardiovascular and neurological events (adjusted hazard ratio, 2.93 [95% CI, 1.08-7.92]) compared with the group with appropriate nonvitamin K oral anticoagulants dosing (P=0.03). Conclusions The prevalence of misclassification of nonvitamin K oral anticoagulants dosing was high when using eGFR, particularly among patients with CKD. Among patients with CKD, potential undertreatment due to inappropriate and off-label renal formulae may result in worse clinical outcomes. These findings highlight the importance of using eCrCl, and not eGFR, for dose adjustment in all patients with AF receiving nonvitamin K oral anticoagulants.

Aging Impairs the Cellular Interplay between Myeloid Cells and Mesenchymal Cells during Skin Healing in Mice.

Impaired wound healing is a major issue in the elderly population and is associated with substantial health and economic burden, which is exponentially increasing with the growing aging population. While the underlying pathobiology of disturbed skin healing by aging is linked to several genetic and epigenetic factors, little is known about the cell-cell interaction during the wound healing process in aged individuals, particularly the mesenchymal stem cell (MSCs)-macrophages axis. In this study, by using a thermal injury animal model in which we compared the wound healing process of adult and young mice, we found that the insufficient pool of MSCs in adult animals are deficient in migrating to the wound bed and instead are restricted to the wound edge. We identified a deficiency of a CD90-positive MSC subpopulation in the wounds of adult animals, which is positively correlated with the number of F4/80+ macrophages. In vitro, we found that CD90+ cells preferentially adhere to the myeloid cells forming doublet cells. Thus, our findings highlight that in adult mice subjected to a thermal injury, impaired wound healing is likely mediated by a disturbed cellular interplay between myeloid cells and mesenchymal cells.

Management strategies and clinical outcomes in breast cancer patients who develop left ventricular dysfunction during trastuzumab therapy.

BACKGROUND: Trastuzumab reduces risk of breast cancer recurrence but carries risk of cardiotoxicity that may be reversible upon treatment cessation and institution of left ventricular (LV) enhancement therapies (LVETx). We assessed management patterns of trastuzumab-induced cardiotoxicity (TIC) in a contemporary real-world setting. METHODS: We reviewed charts of all breast cancer patients who received adjuvant trastuzumab in British Columbia between January 2010 and December 2013, spanning the opening of a cardio-oncology clinic. LV dysfunction (LVD) was classified as minimal (LVEF nadir 45-49%), mild (40-44%) or moderate-severe (< 40%). Charts were reviewed for baseline characteristics, management strategies, and outcomes. Multivariable analysis was performed to identify patient characteristics associated with trastuzumab completion and cardiology referral. RESULTS: Of 967 patients receiving trastuzumab, 171 (17.7%) developed LVD, including 114 patients (11.8%) with LVEF declines of ≥10 to < 50%. Proportions of patients receiving cardiology referrals and LVETx increased and wait times to consultation decreased after a dedicated cardio-oncology clinic opened. LVETx was used more frequently in patients with moderate-severe LVD compared to minimal or mild LVD. Factors associated with completion of trastuzumab included mastectomy (OR 5.1, 95% CI 1.1-23.0) and proximity to quaternary care centre (OR 7.7, 95% CI 2.2-26.2). Moderate-severe LVD was associated with a lower probability of completing trastuzumab (OR 0.07 vs. minimal LVD, 95% CI 0.01-0.74). Factors associated with cardiology referral included heart failure symptoms (OR 8.0, 95% CI 1.5-42.9), proximity to quaternary care centre (OR 6.8, 95% CI 1.3-34.2), later year of cancer diagnosis (OR 2.4 per year, 95% CI 1.4-4.3), node-positive disease (OR 0.18, 95% CI 0.06-0.56), mastectomy (OR 0.05, 95% CI 0.01-0.52), and minimal LVD (OR 0.14, 95% CI 0.05-0.46). LVEF recovered to > 50% in 90.7% of patients. CONCLUSIONS: Management strategies in patients with TIC are associated with cancer characteristics and severity of cardiotoxicity. Access to dedicated cardio-oncology clinics may facilitate optimal care of this complex patient population.

Impact of Female Sex on Clinical Presentation and Ablation Outcomes in the CIRCA-DOSE Study.

OBJECTIVES: This study sought to evaluate sex-specific differences in atrial fibrillation (AF) presentation and catheter ablation outcomes in the prospective, multicenter, randomized CIRCA-DOSE (Cryoballoon vs. Irrigated Radiofrequency Catheter Ablation: Double Short vs. Standard Exposure Duration) study. BACKGROUND: Similar to other cardiovascular conditions, significant sex-specific differences have been observed in the epidemiology, pathophysiology, presentation, and natural history of AF. Unfortunately, there are major gaps in our understanding of the pathophysiological basis for the observed sex-specific differences and their implications on therapy and prognosis. METHODS: This study examined sex-specific differences in AF presentation, symptom severity and health-related quality of life, symptomatic and asymptomatic arrhythmia recurrence, AF burden, and health care utilization. RESULTS: Freedom from any atrial tachyarrhythmia and symptomatic atrial tachyarrhythmia were similar between male (hazard ratio: 1.18; 95% confidence interval: 0.85 to 1.64; p = 0.39) and female patients (hazard ratio: 1.00; 95% confidence interval: 0.62 to 1.59; p = 0.92). Post-ablation, the median AF burden (percentage time in AF) was 0.00% (interquartile range: 0.00% to 0.16%) in male patients and 0.00% (interquartile range: 0.00% to 0.17%) in female patients, with no difference observed between the sexes (p = 0.30). Periprocedural complications occurred twice as frequently in female patients (3.5% vs. 7.0%; p = 0.18). In comparison to male patients, female patients reported a significantly worse symptom score and quality of life at baseline and all follow-up intervals, but they derived similar magnitude of improvement post-ablation. There was no difference between male and female patients with respect to emergency department visits, hospitalization, cardioversion, or repeat ablation. CONCLUSIONS: When compared with male patients, female patients have significantly worse symptom scores and quality of life at baseline. Despite this, female patients with symptomatic paroxysmal AF derive similar benefit in freedom from recurrent arrhythmia and similar improvements in quality of life following AF ablation. (Cryoballoon vs. Irrigated Radiofrequency Catheter Ablation: Double Short vs. Standard Exposure Duration [CIRCA-DOSE]; NCT01913522).

Sensitivity, specificity, positive and negative predictive values of identifying atrial fibrillation using administrative data: a systematic review and meta-analysis.

INTRODUCTION: Atrial fibrillation (AF) is the commonest arrhythmia and a major cause of stroke and health care utilization. Researchers and administrators use electronic health data to assess disease burden, quality and variance in care, value of interventions and prognosis. We performed a systematic review and meta-analysis to assess the validity of AF case definitions in administrative databases. METHODS: Medline was searched from 2000 to 2018. Extracted information included sensitivity, specificity, positive and negative predictive values (PPV and NPV) for various AF case definitions. Estimates were pooled using random-effects models due to significant heterogeneity between studies. RESULTS: We identified 24 studies, including 21 from North America or Scandinavia. Hospital, ambulatory and mixed data sources were assessed in 10, 4 and 10 studies, respectively. Nine different AF case definitions were evaluated, most based on ICD-9 or 10 codes. Twenty-two studies assessed case definitions in patients diagnosed with AF and thus could generate PPV alone. Half the studies sampled unrestricted populations including a mix of those with and without AF to assess sensitivity. Only 13 studies included ECG confirmation as a gold standard. The pooled random effects estimates were: sensitivity 80% (95% CI 72-86%); specificity 98% (96-99%); PPV 88% (82-94%); NPV 97% (94-99%). Only 3 studies reported all accuracy parameters and included rhythm monitoring in the gold standard definition. CONCLUSION: Relatively few studies examined sensitivity, and fewer still included rhythm monitoring in the gold standard comparison. Administrative data may fail to identify a significant proportion of patients with AF. This, in turn, may bias estimates of quality of care and prognosis.

Clinical effectiveness of a systematic "pill-in-the-pocket" approach for the management of paroxysmal atrial fibrillation.

BACKGROUND: For patients with symptomatic, sustained atrial fibrillation (AF), a "pill-in-the-pocket" antiarrhythmic drug (PIP-AAD) strategy has been proposed to reduce emergency department (ED) use. OBJECTIVE: To assess the clinical utility of a protocolled PIP-AAD approach within contemporary practice. METHODS: Consecutive patients who hemodynamically tolerated symptomatic, sustained AF were prospectively managed with the PIP-AAD strategy. All patients were given an atrioventricular nodal blocker 30 minutes prior to a single oral dose of a class Ic antiarrhythmic drug. If the initial PIP-AAD in the ED was efficacious and tolerated, PIP-AADs were given out of hospital for subsequent sustained AF episodes. Usage and complications were systematically recorded. RESULTS: During a median follow-up period of 565 days, 43 of 80 patients presented to the ED for initial PIP-AAD. Sinus rhythm was restored without complication in 30 of 43 patients. The reasons for initial PIP-AAD failure were inefficacy (6 patients), significant hypotension (4 patients), conversion to flutter necessitating cardioversion (2 patients), and syncopal conversion pause (1 patient). For the 30 patients with successful initial PIP-AAD, 159 out-of-hospital PIP-AAD treatments occurred (mean 5.3 ± SD 1.3 per patient). Compared with ED visits in the period prior to PIP-AAD initiation, there was a significant reduction in visits (2.6 ± 3.0 vs. 0.4±0.9 ED visits per patient, P < .001) and the need for cardioversion (2.3 ± 3.1 vs. 0.0 ± 0.2 treatments per patient, P < .001). Adverse events associated with out-of-hospital PIP-AAD include presyncope (3 of 30 patients), syncope necessitating pacemaker implantation (1 patient), and conversion to flutter (1 patient). CONCLUSION: Out-of-hospital PIP-AAD can be an effective for highly selected patients; however, the rates of treatment failure and adverse events are clinically relevant, which limits the widespread application of a PIP-AAD approach.