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BACKGROUND: Increased hsCRP (high-sensitivity C-reactive protein), a marker of inflammation, is associated with incident cardiovascular events. We aim to determine whether the baseline or trajectory of hsCRP levels over time predicts incident heart failure (HF) hospitalization. METHODS: JHS (Jackson Heart Study) participants' (n=3920 Black adults) hsCRP levels were measured over 3 visits (from 2000 to 2013). We assessed the association of hsCRP at baseline (visit 1) with incident HF hospitalization using Cox proportional hazards models. Furthermore, we assessed the association of the trajectory of hsCRP over repeated measurements (visits 1-3) with incident HF using joint models. Hazard ratios are reflective of an increase in hsCRP by 1 SD on a log2 scale. We also assessed the association of change in hsCRP between visit 1 and visit 3 with Cox proportional hazards models by grouping patients by low (<2 mg/L) and high (=2 mg/L) hsCRP levels. The 4 groups were low-to-low (referent), low-to-high, high-to-low, and high-to-high. RESULTS: Mean baseline age of participants was 54±13 years, and 63.8% were women. Over a median follow-up of 12 years, 308 (7.9%) participants were hospitalized with incident HF. Baseline hsCRP was not associated with incident HF (adjusted hazard ratio, 1.08 [95% CI, 0.96-1.22]). However, increasing hsCRP levels over repeated measures were associated with a higher risk of incident HF overall (adjusted hazard ratio, 1.22 [95% CI, 1.03-1.44]) and HF with preserved ejection fraction (adjusted hazard ratio, 1.30 [95% CI, 1.02-1.65]) but not HF with reduced ejection fraction (P>0.05). Furthermore, changes in hsCRP from low-to-high and high-to-low levels were associated with incident HF (P<0.05). CONCLUSIONS: While baseline hsCRP was not associated with incident HF, an increasing trajectory of hsCRP over time was associated with increased risk for incident HF (particularly HF with preserved ejection fraction). Temporal change in hsCRP may be an important marker of risk for incident HF with preserved ejection fraction in Black adults. [ABSTRACT FROM AUTHOR]

Hospital at home (HaH) is an innovative care model that may be particularly suited for heart failure (HF). Outpatient visits and inpatient care have been the 2 traditional settings for HF care, yet may not match the social and medical needs of patients at all times. Alternative models such as HaH may represent an effective and patient-centered option for select patients with worsening HF. To date, limited research in HF and other disease states has supported HaH as being safe and lower cost than traditional inpatient admission. Supporting HaH are new payment structures, such as Medicare's Acute Hospital Care at Home waiver program. In combination with outpatient visits, outpatient intravenous diuretic clinics, inpatient care, and cardiac intensive care, HaH could be a core component of a comprehensive care model with the potential to match resource utilization with the needs of patients across the spectrum of HF severity, and improve patient outcomes. [ABSTRACT FROM AUTHOR]

Achieving optimal cardiovascular health in rural populations can be challenging for several reasons including decreased access to care with limited availability of imaging modalities, specialist physicians, and other important health care team members. Therefore, innovative solutions are needed to optimize health care and address cardiovascular health disparities in rural areas. Mobile examination units can bring imaging technology to underserved or remote communities with limited access to health care services. Mobile examination units can be equipped with a wide array of assessment tools and multiple imaging modalities such as computed tomography scanning and echocardiography. The detailed structural assessment of cardiovascular and lung pathology, as well as the detection of extracardiac pathology afforded by computed tomography imaging combined with the functional and hemodynamic assessments acquired by echocardiography, yield deep phenotyping of heart and lung disease for populations historically underrepresented in epidemiological studies. Moreover, by bringing the mobile examination unit to local communities, innovative approaches are now possible including engagement with local professionals to perform these imaging assessments, thereby augmenting local expertise and experience. However, several challenges exist before mobile examination unit–based examinations can be effectively integrated into the rural health care setting including standardizing acquisition protocols, maintaining consistent image quality, and addressing ethical and privacy considerations. Herein, we discuss the potential importance of cardiac multimodality imaging to improve cardiovascular health in rural regions, outline the emerging experience in this field, highlight important current challenges, and offer solutions based on our experience in the RURAL (Risk Underlying Rural Areas Longitudinal) cohort study. [ABSTRACT FROM AUTHOR]

BACKGROUND: The association between angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) doses on outcomes in patients with heart failure (HF) with reduced ejection fraction is uncertain. The objective of this study was to investigate the effect of dose of ACEI and ARBs on outcomes and drug discontinuation in patients with HF with reduced ejection fraction. METHODS AND RESULTS: MEDLINE, Ovid SP, and Embase were searched from the inception of these databases till August 2016. Randomized controlled trials that compared high doses of ACEI or ARB against low doses among patients with HF with reduced ejection fraction were included. Pooled analysis was done using a random-effects model, and quality of the studies was assessed by JADAD scale. The main outcomes were all-cause mortality and drug discontinuation. A total of 6 studies (4841 patients in low-dose and 4330 patients in high-dose groups) were included. Compared with low dose, high-dose ACEI or ARBs decreased all-cause mortality modestly (relative risk, 0.94; 95% confidence interval (CI), 0.89--1.00; P=0.05; I²=0%) and composite of HF hospitalizations and all-cause mortality (relative risk, 0.93; 95% CI, 0.87--1.00; P=0.04; I² =39.8%). No significant difference was found between the 2 groups in HF hospitalizations (relative risk, 0.94; 95% CI, 0.70--1.26; P=0.68; I²=52.8%) and all-cause hospitalizations (relative risk, 0.97; 95% CI, 0.85--1.11; P=0.67; I²=31.7%) risk. Discontinuation rates were also not significantly different in both groups (odds ratio, 1.13; 95% CI, 0.92--1.39; P=0.25; I²=32.6%). CONCLUSIONS: In patients with HF with reduced ejection fraction, compared with lower doses, higher doses of ACEI and ARB significantly though modestly improved the composite end point of all-cause mortality or HF hospitalization without significantly increasing the chances of discontinuation. [ABSTRACT FROM AUTHOR]

Background: The American College of Cardiology guidelines recommend 3 months of anticoagulation after replacement of the aortic valve with a bioprosthesis. However, there remains great variability in the current clinical practice and conflicting results from clinical studies. To assist clinical decision making, we pooled the existing evidence to assess whether anticoagulation in the setting of a new bioprosthesis was associated with improved outcomes or greater risk of bleeding.Methods and Results: We searched the PubMed database from the inception of these databases until April 2015 to identify original studies (observational studies or clinical trials) that assessed anticoagulation with warfarin in comparison with either aspirin or no antiplatelet or anticoagulant therapy. We included the studies if their outcomes included thromboembolism or stroke/transient ischemic attacks and bleeding events. Quality assessment was performed in accordance with the Newland Ottawa Scale, and random effects analysis was used to pool the data from the available studies. I(2) testing was done to assess the heterogeneity of the included studies. After screening through 170 articles, a total of 13 studies (cases=6431; controls=18210) were included in the final analyses. The use of warfarin was associated with a significantly increased risk of overall bleeding (odds ratio, 1.96; 95% confidence interval, 1.25-3.08; P<0.0001) or bleeding risk at 3 months (odds ratio, 1.92; 95% confidence interval, 1.10-3.34; P<0.0001) compared with aspirin or placebo. With regard to composite primary outcome variables (risk of venous thromboembolism, stroke, or transient ischemic attack) at 3 months, no significant difference was seen with warfarin (odds ratio, 1.13; 95% confidence interval, 0.82-1.56; P=0.67). Moreover, anticoagulation was also not shown to improve outcomes at time interval >3 months (odds ratio, 1.12; 95% confidence interval, 0.80-1.58; P=0.79).Conclusions: Contrary to the current guidelines, a meta-analysis of previous studies suggests that anticoagulation in the setting of an aortic bioprosthesis significantly increases bleeding risk without a favorable effect on thromboembolic events. Larger, randomized controlled studies should be performed to further guide this clinical practice. [ABSTRACT FROM AUTHOR]

Background: We examined the effects of vericiguat compared with placebo in patients with heart failure with reduced ejection fraction enrolled in VICTORIA (Vericiguat Global Study in Patients With Heart Failure With Reduced Ejection Fraction) on health status outcomes measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ) and evaluated whether clinical outcomes varied by baseline KCCQ score. Methods: KCCQ was completed at baseline and 4, 16, and 32 weeks. We assessed treatment effect on KCCQ using a mixed-effects model adjusting for baseline KCCQ and stratification variables. Cox proportional-hazards modeling was performed to evaluate the effect of vericiguat on clinical outcomes by tertiles of baseline KCCQ clinical summary score (CSS), total symptom score (TSS), and overall summary score (OSS). Results: Of 5050 patients, 4664, 4741, and 4470 had KCCQ CSS (median [25th to 75th], 65.6 [45.8–81.8]), TSS (68.8 [47.9–85.4]), and OSS (59.9 [42.0–77.1]) at baseline; 94%, 88%, and 82% had data at 4, 16, and 32 weeks. At 16 weeks, CSS improved by a median of 6.3 in both arms; no significant differences in improvement were seen for TSS and OSS between the 2 groups (P =0.69, 0.97, and 0.13 for CSS, TSS, and OSS). Trends were similar at 4 and 32 weeks. Vericiguat versus placebo reduced cardiovascular death or heart failure hospitalization risk similarly across tertiles of baseline KCCQ CSS, TSS, and OSS (interaction P =0.13, 0.21, and 0.65). Conclusions: Vericiguat did not significantly improve KCCQ scores compared with placebo. Vericiguat reduced the risk of cardiovascular death or heart failure hospitalization across the range of baseline health status. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02861534. [ABSTRACT FROM AUTHOR]

Background: Heart failure (HF) accounts for a significant proportion of morbidity, mortality, and health care costs among older adults in the United States. We evaluated trends in clinical outcomes and the economic burden of HF hospitalizations in older patients (≥80 years). Methods: This analysis included data from the National Inpatient Sample between January 2004 and December 2018. We examined the trends of clinical characteristics, inpatient mortality, and health care cost utilization in older US adults for HF hospitalizations. Results: We identified 6 034 951 weighted HF hospitalizations for older adults (3527 per 100 000 person-years). After an initial decline in HF hospitalizations per 100 000 older US older adults from 4211 in 2004 to 3089 in 2014, there was increase to 3388 in 2018 (P trend <0.001 for both). There was an overall increase in cardiometabolic and chronic comorbidities during the study period. Overall, inpatient mortality was 4.7%; the adjusted inpatient mortality decreased from 6.1% in 2004 to 3.6% in 2018 (P trend <0.001). There was a decrease in adjusted mean length of stay (from 6.0 days in 2004 to 4.7 days in 2018) and adjusted inflation-adjusted care costs (from $11 865 in 2004 to $9677 in 2018) during the study period (P trend <0.001 for both). In comparison with younger adults (<80 years), older adults had higher inpatient mortality (4.7% versus 2.2%) but lower inflation-adjusted care costs ($10 587 versus $14 088). Conclusions: This 15-year national data suggests that despite a higher comorbidity burden and the recent increase in hospitalizations for HF in older patients, there has been an encouraging trend towards lower inpatient mortality, health care cost, and hospital length of stay among older adults in the United States. [ABSTRACT FROM AUTHOR]

Preload augmentation represents a critical mechanism for the cardiovascular system to increase effective circulating blood volume to increase cardiac filling pressures and, subsequently, for the heart to increase cardiac output. The splanchnic vascular compartment is the primary source of vascular capacity and thus the primary target for preload recruitment in humans. Under normal conditions, sympathetic stimulation of these primary venous vessels promotes the shift of blood from the splanchnic to the thoracic compartment and elevates preload and cardiac output. However, in heart failure, since filling pressures may be elevated at rest due to decreased venous capacitance, incremental recruitment of preload to enhance cardiac output may exacerbate congestion and limit exercise capacity. Accordingly, recent attention has focused on therapies designed to regulate splanchnic vascular redistribution to improve cardiac filling pressures and patient-centered outcomes such as quality of life and exercise capacity in patients with heart failure. In this review, we discuss the relevance of splanchnic circulation as a venous reservoir, the contribution of stressed blood volume to heart failure pathogenesis, and the implications for pharmacological therapeutic interventions to prevent heart failure decompensation. Further, we review emerging device-based approaches for cardiac preload reduction such as partial/complete occlusion of the superior vena cava or the inferior vena cava. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text. Background: Diuretics are a mainstay therapy for the symptomatic treatment of heart failure. However, in contemporary US outpatient practice, the degree to which diuretic dosing changes over time and the associations with clinical outcomes and health care resource utilization are unknown. Methods: Among 3426 US outpatients with chronic heart failure with reduced ejection fraction in the Change the Management of Patients with Heart Failure registry with complete medication data and who were prescribed a loop diuretic, diuretic dose increase was defined as: (1) change to a total daily dose higher than their previous total daily dose, (2) addition of metolazone to the regimen, (3) change from furosemide to either bumetanide or torsemide, and the change persists for at least 7 days. Adjusted hazard ratios or rate ratios along with 95% CIs were reported for clinical outcomes among patients with an increase in oral diuretic dose versus no increase in diuretic dose. Results: Overall, 796 (23%) had a diuretic dose increase (18 episodes per 100 patient-years). The proportion of patients with dyspnea at rest (38% versus 26%), dyspnea at exertion (79% versus 67%), orthopnea (32% versus 21%), edema (60% versus 43%), and weight gain (40% versus 23%) were significantly (all P <0.001) higher in the diuretic increase group. Baseline angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (hazard ratio, 0.75 [95% CI, 0.65–0.87]) use were associated with lower likelihood of diuretic increase over time. Patients with a diuretic dose increase had a significantly higher number of heart failure hospitalizations (rate ratio, 2.53 [95% CI, 2.10–3.05]), emergency department visits (rate ratio, 1.84 [95% CI, 1.56–2.17]), and home health visits (rate ratio, 1.88 [95% CI, 1.39–2.54]), but not all-cause mortality (hazard ratio, 1.10 [95% CI, 0.89–1.36]). Similarly, greater furosemide dose equivalent increases were associated with greater resource utilization but not with mortality, compared with smaller increases. Conclusions: In this contemporary US registry, 1 in 4 patients with heart failure with reduced ejection fraction had outpatient escalation of diuretic therapy over longitudinal follow-up, and these patients were more likely to have sign/symptoms of congestion. Outpatient diuretic dose escalation of any magnitude was associated with heart failure hospitalizations and resource utilization, but not all-cause mortality. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text. Background: The impact of hospital readmission reduction program (HRRP) on heart failure (HF) outcomes has been debated. Limited data exist regarding trends of HF readmission rates beyond 30 days from all-payer sources. The aim of this study was to investigate temporal trends of 30- and 90-day HF readmissions rates from 2010 to 2017 in patients from all-payer sources. Methods: The National Readmission Database was utilized to identify HF hospitalizations between 2010 and 2017. In the primary analysis, a linear trend in 30-day and 90-day readmissions from 2010 to 2017 was assessed. While in the secondary analysis, a change in aggregated 30- and 90-day all-cause and HF-specific readmissions pre-HRRP penalty phase (2010–2012) and post-HRRP penalties (2013–2017) was compared. Subgroup analyses were performed based on (1) Medicare versus non-Medicare insurance, (2) low versus high HF volume, and (3) HF with reduced versus preserved ejection fraction (heart failure with reduced ejection fraction and heart failure with preserved ejection fraction). Multiple logistic and adjusted linear regression analyses were performed for annual trends. Results: A total of 6 669 313 index HF hospitalizations for 30-day, and 5 077 949 index HF hospitalizations for 90-day readmission, were included. Of these, 1 213 402 (18.2%) encounters had a readmission within 30 days, and 1 585 445 (31.2%) encounters had a readmission within 90 days. Between 2010 and 2017, both 30 and 90 days adjusted HF-specific and all-cause readmissions increased (8.1% to 8.7%, P trend 0.04, and 18.3% to 19.9%, P trend <0.001 for 30-day and 14.8% to 16.0% and 30.9% to 34.6% for 90-day, P trend <0.001 for both, respectively). Readmission rates were higher during the post-HRRP penalty period compared with pre-HRRP penalty phase (all-cause readmission 30 days: 18.6% versus 17.5%, P <0.001, all-cause readmission 90 days: 32.0% versus 29.9%, P <0.001) across all subgroups except among the low-volume hospitals. Conclusions: The rates of adjusted HF-specific and all-cause 30- and 90-day readmissions have increased from 2010 to 2017. Readmissions rates were higher during the HRRP phase across all subgroups except the low-volume hospitals. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text. Background: The association of obesity on outcomes in patients with cardiogenic shock requiring acute mechanical circulatory support has not been thoroughly investigated. Methods: We evaluated the National Readmission Database for adults with either acute myocardial infarction or heart failure complicated by cardiogenic shock requiring acute mechanical circulatory support between January 2016 and November 2017. Exposure was assessed using International Classification of Diseases , Tenth Revision codes for the degree of obesity with the reference being body mass index (BMI) of 20.0 to 29.9 group. Multiple logistic regression and Cox regression analysis were used to analyze in-hospital mortality and 30-day readmission, respectively. Results: The survey-weighted sample included a total of 35 555 hospitalizations with a mean age of 65.4±0.2 years and 29.8% females. Obesity was associated with higher in-hospital mortality (no obesity, 26.4% [BMI, 20.0–29.9] versus class I obesity, 25.0% [BMI, 30.0–34.9] versus class II obesity, 28.7% [BMI, 35.0–39.9] versus class III obesity, 34.9% [BMI, ≥40]; P <0.001). On stratified analysis, compared with a nonobese phenotype, younger adults (age <60) with class II and class III obesity (odds ratio, 1.9 [95% CI, 1.1–3.5], P =0.02; odds ratio, 2.1 [95% CI, 1.2–3.7], P =0.01) and older adults (age ≥60) with class III obesity (odds ratio, 1.7 [95% CI, 1.2–2.4], P =0.005) had higher mortality. There was no association between the degree of obesity and 30-day readmission. Conclusions: Among adults with acute myocardial infarction or acute heart failure resulting in cardiogenic shock requiring acute mechanical circulatory support, younger adults with class II and class III obesity and older patients with class III obesity have a higher risk of in-hospital mortality compared with nonobese patients. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text. Background: Assessment of heterogeneity in meta-analyses is critical to ensure the consistency of pooled results. Therefore, we sought to assess the evaluation and reporting of heterogeneity in heart failure (HF) meta-analyses. Methods: Study level meta-analyses pertaining to HF were selected from January 2009 to July 2019, published in 11 high impact factor journals. We tabulated the overall proportion of the meta-analyses reporting statistical heterogeneity and specific metrics and methods employed to quantify and explore heterogeneity. Results: Of 126 HF meta-analyses (612 outcomes), heterogeneity was reported for 422 outcomes (68.9 %) in 108 meta-analyses. Out of the 422 outcomes reporting statistical heterogeneity, 137 outcomes (32.5%) had no observable heterogeneity: (I 2=0%), 40 outcomes (9.5%) had low heterogeneity (I 2<25%), 76 outcomes (18%) had moderate heterogeneity (I 2 =25%–50%), and 169 outcomes (40%) had high heterogeneity (I 2>50%). Reporting of statistical heterogeneity was not significantly associated with year of publication, funding source, disclosure information, or the type of studies pooled. Sensitivity analysis (n=68) was the most common statistical technique employed to evaluate the source of heterogeneity followed by subgroup analyses (n=59) and meta-regression (n=40). Conclusions: Despite being an essential component of meta-analyses, heterogeneity was not reported for nearly 30% of outcomes and variably handled in contemporary HF meta-analyses. As meta-analyses increase across HF science, interpreting and handling of heterogeneity should be standardized. [ABSTRACT FROM AUTHOR]

Background: Efficacy of an intervention is commonly evaluated using P values, in addition to effect size measures such as absolute risk reduction, relative risk reduction, and numbers needed to treat. However, these measures are not always intuitive to clinicians. The fragility index (FI) is a more intuitive number that can facilitate interpretation but can only be used with binary outcomes. FI is the minimum number of patients who must be moved from the nonevent group to the event group to turn a significant result nonsignificant. In this retrospective analysis, we assessed the robustness of cardiovascular randomized controlled trials (RCTs), which report a positive (statistically significant) primary outcome by using the FI.Methods and Results: We searched Medline from 2007 to 2017 to identify cardiovascular RCTs published in 6 high impact journals (The Lancet, New England Journal of Medicine, Journal of the American Medical Association, Circulation, Journal of the American College of Cardiology and European Heart Journal). Only RCTs with sample sizes >500 and a 2-by-2 factorial design or dichotomous primary outcomes were selected. FI was calculated using a defined approach. Among the cohort of 123 RCTs that met inclusion criteria, median FI was 13 (interquartile range, 5-26). In 28 trials (22.8%), FI ranged between 1 and 4. In 37 trials (30.1%), number of patients lost to follow-up was higher than the FI. Pharmaceutical interventions had higher FI compared with other interventions, FI=19 (7-52; P=0.002). Median FI varied according to subspecialty (electrophysiology=2; heart failure=11; interventional cardiology=8; P=0.020) and multiregional RCTs had higher FI=22 (12-53.25; P=0.023). FI did not differ based on risk of bias indicators, funding, or publication year.Conclusions: Considerable variations in FI were observed among cardiovascular trials, suggesting the need for careful interpretation of results, particularly when number of patients lost to follow-up exceeds FI. [ABSTRACT FROM AUTHOR]

Background: Despite the publication of several randomized clinical trials comparing catheter ablation (CA) with medical therapy (MT) in patients with atrial fibrillation (AF), the superiority of one strategy over another is still questioned by many. In this meta-analysis of randomized controlled trials, we compared the efficacy and safety of CA with MT for AF.Methods: We systematically searched MEDLINE, EMBASE, and other online sources for randomized controlled trials of AF patients that compared CA with MT. The primary outcome was all-cause mortality. Secondary outcomes included cardiovascular hospitalizations and recurrence of atrial arrhythmia. Subgroup analyses stratified by the presence of heart failure with reduced ejection fraction, type of AF, age, and sex were performed. Risk ratios (RRs) with 95% CIs were calculated using a random effects model, and Mantel-Haenszel method was used to pool RR.Results: Eighteen randomized controlled trials comprising 4464 patients (CA, n=2286; MT, n=2178) were included. CA resulted in a significant reduction in all-cause mortality (RR, 0.69; 95% CI, 0.54-0.88; P=0.003) that was driven by patients with AF and heart failure with reduced ejection fraction (RR, 0.52; 95% CI, 0.35-0.76; P=0.0009). CA resulted in significantly fewer cardiovascular hospitalizations (hazard ratio, 0.56; 95% CI, 0.39-0.81; P=0.002) and fewer recurrences of atrial arrhythmias (RR, 0.42; 95% CI, 0.33-0.53; P<0.00001). Subgroup analyses suggested that younger patients (age, <65 years) and men derived more benefit from CA compared with MT.Conclusions: CA is associated with all-cause mortality benefit, that is driven by patients with AF and heart failure with reduced ejection fraction. CA reduces cardiovascular hospitalizations and recurrences of atrial arrhythmia for patients with AF. Younger patients and men appear to derive more benefit from CA. [ABSTRACT FROM AUTHOR]

Background: In the busy world of cardiovascular medicine, abstracts may be the only part of a publication that clinicians read. Therefore, it is critical for abstracts to accurately reflect article content. The extended CONSORT (Consolidated Standards of Reporting Trials) Statement for Abstracts was developed to ensure high abstract quality. However, it is unknown how often adherence to CONSORT guidelines occurs among cardiovascular journals.Methods and Results: We searched MEDLINE for randomized controlled trials published in 3 major cardiovascular journals ( Circulation, Journal of the American College of Cardiology, and European Heart Journal) from 2011 to 2017. Post hoc, interim, and cost-effective analyses of randomized controlled trials were excluded. Two independent investigators extracted the data using a prespecified data collection form and a third investigator adjudicated the data. The primary outcome was frequency of subcategory adherence to CONSORT guidelines. A total of 478 abstracts were included in the analysis. Approximately half of the abstracts (53%; 255/478; 95% CI, 49%-57%) identified the article as randomized in the title. All abstracts detailed the interventions for both study groups (100%) and 81% (95% CI, 78%-85%) reported trial registration. Methodological quality reporting was relatively low: 9% (45/478; 95% CI, 6%-12%) described participant eligibility criteria with settings for data collection, 43% (204/478; 95% CI, 39%-47%) reported details of blinding, and <1% (4/478; 95% CI, 0%-2%) reported allocation concealment. Approximately 60% (301/478; 95% CI, 59%-67%) of the included abstracts provided primary outcome results while 55% (262/478; 95% CI, 51%-60%) reported harms or adverse effects.Conclusions: There is a high prevalence of nonadherence to CONSORT guidelines among leading cardiovascular journals. Efforts by editors, authors, and reviewers should be made to increase adherence and promote transparent and unbiased presentation of study results. [ABSTRACT FROM AUTHOR]

Background Data about anticoagulation in pulmonary arterial hypertension (PAH) patients are inconsistent. The objective of this study was to examine the impact of adjunctive oral anticoagulants in patients with PAH through meta-analysis, and to further assess whether response differs by PAH subtype. Methods and Results Cochrane CENTRAL, Medline, and Scopus databases were searched for randomized or nonrandomized studies that assessed the association between anticoagulation and outcomes in patients with PAH. Hazard ratios (HRs) for mortality were pooled using the random effects model. Subgroup analyses were performed for type of PAH and study design. Twelve nonrandomized studies, at moderate risk of bias, were included. These consisted of 2512 patients (1342 receiving anticoagulation and 1170 controls). Anticoagulation significantly reduced mortality in the overall PAH cohort (HR, 0.73 [0.57, 0.93]; P=0.001; I2=64%). On subgroup analysis, a significant mortality reduction was seen in idiopathic PAH patients (HR, 0.73 [0.56, 0.95]; P=0.02; I2=46%), whereas no significant difference was observed in connective tissue disease-related PAH (HR, 1.16 [0.58, 2.32]; P=0.67; I2=71%). Sensitivity analysis specific to scleroderma-associated PAH demonstrated a significant increase in mortality with anticoagulant use (HR, 1.58 [1.08, 2.31]; P=0.02; I2=9%). Conclusions This meta-analysis shows that use of anticoagulation may improve survival in idiopathic PAH patients, while increasing mortality when used in scleroderma-associated-PAH patients. Currently, no randomized clinical trials have been published, and until randomized data are available, anticoagulant use in PAH should be tailored to PAH subtype. [ABSTRACT FROM AUTHOR]

Various pharmacotherapies exist for heart failure with preserved ejection fraction (HFpEF), but with unclear comparative efficacy. We searched EMBASE, Medline, and Cochrane Library from inception through August 2021 for all randomized clinical trials in HFpEF (EF >40%) that evaluated beta-blockers, mineralocorticoid receptor antagonist (MRA), angiotensin-converting enzyme inhibitors (ACE), angiotensin receptor blockers (ARB), angiotensin receptor-neprilysin inhibitor (ARNI), and sodium-glucose cotransporter-2 inhibitors (SGLT2i). Outcomes assessed were cardiovascular mortality, all-cause mortality, and HF hospitalization. A frequentist network meta-analysis was performed with a random-effects model. We included 22 randomized clinical trials (30,673 participants; mean age = 71.7 ± 4.2 years; females = 49.3 ± 7.7%; median follow-up = 24.4 ± 11.1 months). Compared with placebo, there was no statistically significant difference in cardiovascular mortality [beta-blockers; odds ratio (OR) 0.79 (0.46-1.34), MRA; OR 0.90 (0.70-1.14), ACE OR 0.95 (0.59-1.53), ARB; OR 1.02 (0.87-1.19), ARNI; OR 0.97 (0.74-1.26) and SGLT2i; OR 1.00 (0.84-1.18)] or all-cause mortality [beta blockers; OR 0.75 (0.54-1.04), MRA; OR 0.90 (0.75-1.08) ACE; OR 1.05 (0.71-1.54), ARB; OR 1.03 (0.91-1.15), ARNI; OR 0.99 (0.82-1.20) and SGLT2i; OR 1.00 (0.89-1.13)]. The certainty in these estimates was low or very low. There was a significantly reduction in HF hospitalization with the use of SGLT2i [OR 0.71 (0.62-0.82), moderate certainty], ARNI [OR 0.77 (0.63-0.94), low certainty], and MRA [OR 0.81 (0.66-0.98), moderate certainty]; with corresponding P scores of 0.84, 0.68, and 0.58, respectively. In HFpEF, the use of beta-blockers, MRA, ACE/ARB/ARNI, or SGLT2i was not associated with improved cardiovascular or all-cause mortality. SGLT2i, ARNI, and MRA reduced the risk of HF hospitalizations., Competing Interests: Disclosure: Dr S.J.G. has received research support from the Duke University Department of Medicine Chair’s Research Award, American Heart Association, Amgen, AstraZeneca, Bristol Myers Squibb, Cytokinetics, Merck, Novartis, and Pfizer; has served on advisory boards for Amgen, AstraZeneca, Bristol Myers Squibb, and Cytokinetics; and serves as a consultant for Amgen, Bayer, Bristol Myers Squibb, Merck, and Vifor. N.R.D. works under contract with the Centers for Medicare and Medicaid Services to develop and maintain performance measures used for public reporting and pay for performance programs. He reports research grants and consulting for Amgen, Astra Zeneca, Boehringer Ingelheim, Cytokinetics, MyoKardia, Novartis, SCPharmaceuticals, and Vifor Pharma. Dr E.D.M. reports Advisory Boards for AstraZeneca, Amarin, Bayer, Esperion, Novartis, and Novo Nordisk. Dr R.J.M. received research support and honoraria from Abbott, American Regent, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim/Eli Lilly, Boston Scientific, Cytokinetics, Fast BioMedical, Gilead, Innolife, Medtronic, Merck, Novartis, Relypsa, Respicardia, Roche, Sanofi, Vifor, Windtree Therapeutics, and Zoll. All other authors have no conflicts of interests to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The optimal approach to identify individuals with diabetes who are at a high risk for developing heart failure (HF) to inform implementation of preventive therapies is unknown, especially in those without atherosclerotic cardiovascular disease (ASCVD)., Methods: Adults with diabetes and no HF at baseline from 7 community-based cohorts were included. Participants without ASCVD who were at high risk for developing HF were identified using 1-step screening strategies: risk score (WATCH-DM [Weight, Age, Hypertension, Creatinine, HDL-C, Diabetes Control, QRS Duration, MI, and CABG] ≥12), NT-proBNP (N-terminal pro-B-type natriuretic peptide ≥125 pg/mL), hs-cTn (high-sensitivity cardiac troponin T ≥14 ng/L; hs-cTnI ≥31 ng/L), and echocardiography-based diabetic cardiomyopathy (echo-DbCM; left atrial enlargement, left ventricular hypertrophy, or diastolic dysfunction). High-risk participants were also identified using 2-step screening strategies with a second test to identify residual risk among those deemed low risk by the first test: WATCH-DM/NT-proBNP, NT-proBNP/hs-cTn, NT-proBNP/echo-DbCM. Across screening strategies, the proportion of HF events identified, 5-year number needed to treat and number needed to screen to prevent 1 HF event with an SGLT2i (sodium-glucose cotransporter 2 inhibitor) among high-risk participants, and cost of screening were estimated., Results: The initial study cohort included 6293 participants (48.2% women), of whom 77.7% without prevalent ASCVD were evaluated with different HF screening strategies. At 5-year follow-up, 6.2% of participants without ASCVD developed incident HF. The 5-year number needed to treat to prevent 1 HF event with an SGLT2i among participants without ASCVD was 43 (95% CI, 29-72). In the cohort without ASCVD, high-risk participants identified using 1-step screening strategies had a low 5-year number needed to treat (22 for NT-proBNP to 37 for echo-DbCM). However, a substantial proportion of HF events occurred among participants identified as low risk using 1-step screening approaches (29% for echo-DbCM to 47% for hs-cTn). Two-step screening strategies captured most HF events (75-89%) in the high-risk subgroup with a comparable 5-year number needed to treat as the 1-step screening approaches (30-32). The 5-year number needed to screen to prevent 1 HF event was similar across 2-step screening strategies (45-61). However, the number of tests and associated costs were lowest for WATCH-DM/NT-proBNP ($1061) compared with other 2-step screening strategies (NT-proBNP/hs-cTn: $2894; NT-proBNP/echo-DbCM: $16 358)., Conclusions: Selective NT-proBNP testing based on the WATCH-DM score efficiently identified a high-risk primary prevention population with diabetes expected to derive marked absolute benefits from SGLT2i to prevent HF., Competing Interests: Disclosures Dr Patel has served as a consultant to Novo Nordisk. Dr Segar has received honoraria from Merck. Dr Klonoff has served as a consultant for Afon, Atropos Health, Better Therapeutics, Glucotrack, Lifecare, Novo, Samsung, and Thirdwayv. Dr Khan has received personal fees from Merck. Dr Lam has received research support from AstraZeneca, Bayer, Boston Scientific, and Roche Diagnostics; has served as a consultant or on advisory boards/steering committees/executive committees for Actelion, Alleviant Medical, Allysta, Amgen, ANaCardio AB, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Cytokinetics, Darma, EchoNous, Impulse Dynamics, Ionis Pharmaceutical, Janssen Research and Development, Medscape, Merck, Novartis, Novo Nordisk, Radcliffe Group, Roche Diagnostics, Sanofi, Siemens Healthcare Diagnostics, Us2.ai, and WebMD Global; and has served as cofounder and nonexecutive director of Us2.ai. Dr Verma holds a Tier 1 Canada Research Chair in Cardiovascular Surgery; has received research grants and honoraria from Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, HLS Therapeutics, Janssen, Novartis, Novo Nordisk, PhaseBio, and Pfizer; has received honoraria from Sanofi, Sun Pharmaceuticals, and the Toronto Knowledge Translation Working Group; is a member of the scientific excellence committee of the EMPEROR-Reduced trial (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure With Reduced Ejection Fraction); has served as a national lead investigator of the DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) and EMPEROR-Reduced trials; and is the president of the Canadian Medical and Surgical Knowledge Translation Research Group, a federally incorporated not-for-profit physician organization. Dr Nasir is on the advisory board of Amgen, Novartis, and Novo Nordisk, and his research is partly supported by the Jerold B. Katz Academy of Translational Research. Dr Butler has served as a consultant for Abbott, American Regent, Amgen, Applied Therapeutic, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardiac Dimension, Cardior, CVRx, Cytokinetics, Daxor Edwards, Element Science, Innolife, Impulse Dynamics, Imbria, Inventiva, Lexicon, Lilly, LivaNova, Janssen, Medtronics, Merck, Occlutech, Owkin, Novartis, Novo Nordisk, Pfizer, Pharmacosmos, Pharmain, Prolaio, Roche, Secretome, Sequana, SQ Innovation, Tenex, and Vifor. Dr Vaduganathan is supported by the KL2/Catalyst Medical Research Investigator Training award from Harvard Catalyst (National Institutes of Health/National Center for Advancing Translational Sciences Award UL 1TR002541) and has served on advisory boards or has received research grant support from American Regent, Amgen, AstraZeneca, Baxter Healthcare, Bayer AG, Boehringer Ingelheim, Cytokinetics, and Relypsa. Dr Pandey has received research support from the National Institute on Aging GEMSSTAR Grant (1R03AG067960-01) and the National Institute on Minority Health and Disparities (R01MD017529). Dr Pandey has received grant funding (to the institution) from Applied Therapeutics, Gilead Sciences, Ultromics, Myovista, and Roche; has served as a consultant for and/or has received honoraria outside of the present study as an advisor/consultant for Tricog Health Inc, Lilly USA, Rivus, Cytokinetics, Roche Diagnostics, Sarfez Therapeutics, Edwards Lifesciences, Merck, Bayer, Novo Nordisk, Alleviant, Axon Therapies; and has received nonfinancial support from Pfizer and Merck. Dr Pandey is also a consultant for Palomarin Inc with stocks compensation. The other authors report no conflicts.

Left ventricular assist device (LVAD) implantation in patients with advanced heart failure due to hypertrophic or restrictive cardiomyopathy (HCM/RCM) presents technical and physiologic challenges. We conducted a systematic review of observational studies to evaluate the utilization and clinical outcomes associated with LVAD implantation in patients with HCM/RCM and compared these to patients with dilated or ischemic cardiomyopathy (DCM/ICM). We searched MEDLINE, EMBASE, and Scopus from inception through May 2019 and included appropriate studies describing the use of an LVAD in patients with HCM/RCM. We identified six studies with a total of 2,766 patients with HCM/RCM and advanced heart failure, among whom 338 patients (12.2%) underwent LVAD implantation. In patients listed for transplant, the rate of LVAD implantation was significantly lower in patients with HCM/RCM compared to that in patients with DCM/ICM (4.4% vs. 18.2%, p < 0.001). Adverse clinical outcomes were significantly higher in HCM/RCM than in DCM/ICM, including operative/short-term mortality (14.0% vs. 9.0%), right ventricular failure (50.0% vs. 21.0%), infection (15.5% vs. 11.2%), bleeding (40.2% vs. 12.5%), renal failure (15.0% vs. 5.1%), stroke (5.0% vs. 2.4%), and arrhythmias (18.0% vs. 7.7%) (all p values <0.001)., Competing Interests: The authors have no conflicts of interest to report., (Copyright © ASAIO 2020.)

Background: Sodium-glucose cotransporter 2 inhibitors improve outcomes in patients with heart failure with reduced ejection fraction, but additional information is needed about whether glycemic status influences the magnitude of their benefits on heart failure and renal events., Methods: Patients with Class II-IV heart failure and a left ventricular ejection fraction ≤40% were randomized to receive empagliflozin (10 mg daily) or placebo in addition to recommended therapy. We prespecified a comparison of the effect of empagliflozin in patients with and without diabetes., Results: Of the 3730 patients enrolled, 1856 (50%) had diabetes, 1268 (34%) had prediabetes (hemoglobin A1c [HbA1c] 5.7-6.4%), and 606 (16%) had normoglycemia (HbA1c <5.7%). The risks of the primary outcome (cardiovascular death or hospitalization for heart failure), total hospitalizations for heart failure, and adverse renal outcomes were higher in patients with diabetes, but were similar between patients with prediabetes and normoglycemia. Empagliflozin reduced the risk of the primary outcome in patients with and without diabetes (hazard ratio, 0.72 [95% CI, 0.60-0.87] and 0.78 [95% CI, 0.64-0.97], respectively, P -interaction=0.57). Patients with and without diabetes also did not differ with respect to the effect of empagliflozin on total hospitalizations for heart failure, on the decline in estimated glomerular filtration rate over time, and on the risk of serious adverse renal outcomes. Among these end points, the effects of the drug did not differ in patients with prediabetes or normoglycemia. When analyzed as a continuous variable, baseline HbA1c did not significantly modify the benefits of empagliflozin on the primary outcome ( P -interaction=0.40). Empagliflozin did not lower HbA1c in patients with prediabetes or normoglycemia and was not associated with increased risk of hypoglycemia., Conclusions: In EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction), empagliflozin significantly improved cardiovascular and renal outcomes in patients with heart failure and a reduced ejection fraction, independent of baseline diabetes status and across the continuum of HbA1c. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03057977.

Background: The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention with drug-eluting stents remains uncertain. We compared short-term (<6-month) DAPT followed by aspirin or P2Y12 inhibitor monotherapy; midterm (6-month) DAPT; 12-month DAPT; and extended-term (>12-month) DAPT after percutaneous coronary intervention with drug-eluting stents., Methods: Twenty-four randomized, controlled trials were selected using Medline, Embase, Cochrane library, and online databases through September 2019. The coprimary end points were myocardial infarction and major bleeding, which constituted the net clinical benefit. A frequentist network meta-analysis was conducted with a random-effects model., Results: In 79 073 patients, at a median follow-up of 18 months, extended-term DAPT was associated with a reduced risk of myocardial infarction in comparison with 12-month DAPT (absolute risk difference, -3.8 incident cases per 1000 person-years; relative risk, 0.68 [95% CI, 0.54-0.87]), midterm DAPT (absolute risk difference, -4.6 incident cases per 1000 person-years; relative risk, 0.61 [0.45-0.83]), and short-term DAPT followed by aspirin monotherapy (absolute risk difference, -6.1 incident cases per 1000 person-years; relative risk, 0.55 [0.37-0.83]), or P2Y12 inhibitor monotherapy (absolute risk difference, -3.7 incident cases per 1000 person-years; relative risk, 0.69 [0.51-0.95]). Conversely, extended-term DAPT was associated with a higher risk of major bleeding than all other DAPT groups. In comparison with 12-month DAPT, no significant differences in the risks of ischemic end points or major bleeding were observed with midterm or short-term DAPT followed by aspirin monotherapy, with the exception that short-term DAPT followed by P2Y12 inhibitor monotherapy was associated with a reduced risk of major bleeding. There were no significant differences with respect to mortality between the different DAPT strategies. In acute coronary syndrome, extended-term in comparison with 12-month DAPT was associated with a reduced risk of myocardial infarction without a significant increase in the risk of major bleeding., Conclusions: The present network meta-analysis suggests that, in comparison with 12-month DAPT, short-term DAPT followed by P2Y12 inhibitor monotherapy reduces major bleeding after percutaneous coronary intervention with drug-eluting stents, whereas extended-term DAPT reduces myocardial infarction at the expense of more bleeding events.

With worsening epidemiological trends for both the incidence and prevalence of type 2 diabetes mellitus (T2DM) and heart failure (HF) worldwide, it is critical to implement optimal prevention and treatment strategies for patients with these comorbidities, either alone or concomitantly. Several guidelines and consensus statements have recommended glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter type 2 inhibitors as add-ons to lifestyle interventions with or without metformin in those at high atherosclerotic cardiovascular disease risk. However, these recommendations are either silent about HF or fail to differentiate between the prevention of HF in those at risk versus the treatment of individuals with manifest HF. Furthermore, these documents do not differentiate among those with different HF phenotypes. This distinction, even though important, may not be critical for sodium-glucose cotransporter type 2 inhibitors in view of the consistent data for benefit for both atherosclerotic cardiovascular disease- and HF-related outcomes that have emerged from the regulatory-mandated cardiovascular outcome trials for all sodium-glucose cotransporter type 2 inhibitors and the recent DAPA-HF trial (Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction)demonstrating the benefit of dapagliflozin on HF-related outcomes in patients with HF with reduced ejection fraction with or without T2DM. However, the distinction may be crucial for glucagon-like peptide-1 receptor agonists and other antihyperglycemic agents. Indeed, in several of the new statements, glucagon-like peptide-1 receptor agonists are suggested treatment not only for patients with T2DM and atherosclerotic cardiovascular disease, but also in those with manifest HF, despite a lack of evidence for the latter recommendation. Although glucagon-like peptide-1 receptor agonists may be appropriate to use in patients at risk for HF, mechanistic insights and observations from randomized trials suggest no clear benefit on HF-related outcomes and even uncertainty regarding the safety in those with HF with reduced ejection fraction. Conversely, theoretical rationales suggest that these agents may benefit patients with HF with preserved ejection fraction. Considering that millions of patients with T2DM have HF, these concerns have public health implications that necessitate the thoughtful use of these therapies. Achieving this aim will require dedicated trials with these drugs in both patients who have HF with reduced ejection fraction and HF with preserved ejection fraction with T2DM to assess their efficacy, safety, and risk-benefit profile.

Current data suggest that obesity does not impact survival, but may predispose patients to a higher rate of adverse events during left ventricular assist device (LVAD) support. We performed a systematic review and meta-analysis to assess the effects of obesity on clinical outcomes in LVAD recipients. We searched Medline, Scopus, Cochrane library, and clinicaltrials.gov from inception to February 2019 for studies comparing outcomes in obese (body mass index [BMI]> or ≥30 kg/m) and nonobese (BMI< or ≤30 kg/m) heart failure (HF) patients after LVAD implantation. Our primary endpoint was short-term (≤1 year) and long-term (>1 year) all-cause mortalities. The estimates are presented as random-effects risk ratios (RR) with 95% confidence intervals. In this meta-analysis of 15 observational studies (n = 26,842), obese patients receiving LVAD had significantly decreased 6 months (RR = 0.79 [0.73, 0.86]; p < 0.001, I = 0%) and 1 year all-cause mortality (RR = 0.87 [0.79, 0.97]; p = 0.008, I = 69%) compared with nonobese patients. However, both groups showed no significant difference in all-cause mortality at 2 years (RR = 0.95 [0.87, 1.04]; p = 0.12, I = 55%) or 3 years (RR = 0.84 [0.61, 1.15]; p = 0.28, I = 43%). Obese patients had significantly higher risk of device-related infections (RR = 1.48 [1.25, 1.75]; p < 0.001, I = 37%), right heart failure (RR = 1.41 [1.21, 1.65]; p < 0.001, I = 28%), and pump thrombosis (RR = 1.55 [1.37, 1.76]; p < 0.001, I = 0%) compared with nonobese patients. This meta-analysis suggests that obese patients with HF have short- but not long-term survival benefit after LVAD implantation when compared to nonobese patients, although bias may have impacted these findings.

Background: Recently, several deaths secondary to cardiac arrhythmias have been reported in association with substitutive use of loperamide. Therefore, we conducted a systematic review of all reported cases to overview the epidemiologic patterns and clinical outcomes to better elucidate loperamide-induced cardiac complications., Areas of Uncertainty: Association between substitutive use of loperamide and cardiac arrhythmias., Data Sources: A comprehensive literature search was conducted across 6 databases using variety of keywords to identify all reports of cardiac side effects associated with loperamide abuse. Only original case reports of cardiac toxicity or cardiac arrhythmias after loperamide abuse or overuse were included. Data were extracted by 2 authors independently using a structured template from the selected reports. Quality assessment of the reports was performed by using a high-quality evaluation tool., Results: Thirteen reports describing 19 cases were included in our review. Except for coronary artery spasm in one case, cardiac arrhythmias were the major reported cardiac adverse event. The average age of patients was 31 years with majority being men (79%). The most common presentation was syncope (63%). All cases were reported in US except for 1 case. Three patients were concomitantly taking cimetidine, which is known to cause inhibition of CYP3A4 and CYP2C8 leading to increased levels of loperamide. Thirteen of 19 patients were successfully treated and discharged in a stable condition., Conclusions: Our results indicate that measures such as restricting over-the-counter availability of loperamide and increasing awareness regarding loperamide's toxicity are imperative to prevent deaths associated with loperamide abuse.