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Abstract Existing risk prediction models for hospitalized heart failure patients are limited. We identified patients hospitalized with a diagnosis of heart failure between 7 May 2013 and 26 April 2022 from a large academic, quaternary care medical centre (training cohort). Demographics, medical comorbidities, vitals, and labs were collected and were used to construct random forest machine learning models to predict in‐hospital mortality. Models were compared with logistic regression, and to commonly used heart failure risk scores. The models were subsequently validated in patients hospitalized with a diagnosis of heart failure from a second academic, community medical centre (validation cohort). The entire cohort comprised 21 802 patients, of which 14 539 were in the training cohort and 7263 were in the validation cohort. The median age (25th–75th percentile) was 70 (58–82) for the entire cohort, 43.2% were female, and 6.7% experienced inpatient mortality. In the overall cohort, 7621 (35.0%) patients had heart failure with reduced ejection fraction (EF ≤ 40%), 1271 (5.8%) had heart failure with mildly reduced EF (EF 41–49%), and 12 910 (59.2%) had heart failure with preserved EF (EF ≥ 50%). Random forest models in the validation cohort demonstrated a c‐statistic (95% confidence interval) of 0.96 (0.95–0.97), sensitivity (SN) of 87.3%, and specificity (SP) of 90.6% for the prediction of in‐hospital mortality. Models for those with HFrEF demonstrated a c‐statistic of 0.96 (0.94–0.98), SN 88.2%, and SP 91.0%, and those for patients with HFpEF showed a c‐statistic of 0.95 (0.93–0.97), SN 87.4%, and SP 89.5% for predicting in‐hospital mortality. The random forest model significantly outperformed logistic regression (c‐statistic 0.87, SN 75.9%, and SP 86.9%), and current existing risk scores including the Acute Decompensated Heart Failure National Registry risk score (c‐statistic of 0.70, SN 69%, and SP 62%), and the Get With the Guidelines‐Heart Failure risk score (c‐statistic 0.69, SN 67%, and SP 63%); P

Abstract Aims Heart failure (HF) is a clinical syndrome with no definitive diagnostic tests. HF registries are often based on manual reviews of medical records of hospitalized HF patients identified using International Classification of Diseases (ICD) codes. However, most HF patients are not hospitalized, and manual review of big electronic health record (EHR) data is not practical. The US Department of Veterans Affairs (VA) has the largest integrated healthcare system in the nation, and an estimated 1.5 million patients have ICD codes for HF (HF ICD‐code universe) in their VA EHR. The objective of our study was to develop artificial intelligence (AI) models to phenotype HF in these patients. Methods and results The model development cohort (n = 20 000: training, 16 000; validation 2000; testing, 2000) included 10 000 patients with HF and 10 000 without HF who were matched by age, sex, race, inpatient/outpatient status, hospital, and encounter date (within 60 days). HF status was ascertained by manual chart reviews in VA's External Peer Review Program for HF (EPRP‐HF) and non‐HF status was ascertained by the absence of ICD codes for HF in VA EHR. Two clinicians annotated 1000 random snippets with HF‐related keywords and labelled 436 as HF, which was then used to train and test a natural language processing (NLP) model to classify HF (positive predictive value or PPV, 0.81; sensitivity, 0.77). A machine learning (ML) model using linear support vector machine architecture was trained and tested to classify HF using EPRP‐HF as cases (PPV, 0.86; sensitivity, 0.86). From the ‘HF ICD‐code universe’, we randomly selected 200 patients (gold standard cohort) and two clinicians manually adjudicated HF (gold standard HF) in 145 of those patients by chart reviews. We calculated NLP, ML, and NLP + ML scores and used weighted F scores to derive their optimal threshold values for HF classification, which resulted in PPVs of 0.83, 0.77, and 0.85 and sensitivities of 0.86, 0.88, and 0.83, respectively. HF patients classified by the NLP + ML model were characteristically and prognostically similar to those with gold standard HF. All three models performed better than ICD code approaches: one principal hospital discharge diagnosis code for HF (PPV, 0.97; sensitivity, 0.21) or two primary outpatient encounter diagnosis codes for HF (PPV, 0.88; sensitivity, 0.54). Conclusions These findings suggest that NLP and ML models are efficient AI tools to phenotype HF in big EHR data to create contemporary HF registries for clinical studies of effectiveness, quality improvement, and hypothesis generation.

Abstract Objective Population-based national data on the trends in expenditures related to coexisting atherosclerotic cardiovascular diseases (ASCVD) and diabetes is scarce. We assessed the trends in direct health care expenditures for ASCVD among individuals with and without diabetes, which can help to better define the burden of the co-occurrence of diabetes and ASCVD. Methods We used 12-year data (2008–2019) from the US national Medical Expenditure Panel Survey including 28,144 U.S individuals aged ≥ 18 years. Using a two-part model (adjusting for demographics, comorbidities and time), we estimated mean and adjusted incremental medical expenditures by diabetes status among individuals with ASCVD. The costs were direct total health care expenditures (out-of-pocket payments and payments by private insurance, Medicaid, Medicare, and other sources) from various sources (office-based visits, hospital outpatient, emergency room, inpatient hospital, pharmacy, home health care, and other medical expenditures). Results The total direct expenditures for individuals with ASCVD increased continuously by 30% from $14,713 (95% confidence interval (CI): $13,808–$15,619) in 2008–2009 to $19,145 (95% CI: $17,988–$20,301) in 2008–2019. Individuals with diabetes had a 1.5-fold higher mean expenditure that those without diabetes. A key driver of the observed increase in direct costs was prescription drug costs, which increased by 37% among all individuals with ASCVD. The increase in prescription drug costs was more pronounced among individuals with ASCVD and diabetes, in whom a 45% increase in costs was observed, from $5184 (95% CI: $4721–$5646) in 2008–2009 to $7501 (95% CI: $6678–$8325) in 2018–2019. Individuals with ASCVD and diabetes had $5563 (95% CI: $4643–$6483) higher direct incremental expenditures compared with those without diabetes, after adjusting for demographics and comorbidities. Among US adults with ASCVD, the estimated adjusted total direct excess medical expenditures were $42 billion per year among those with diabetes vs. those without diabetes. Conclusions In the setting of ASCVD, diabetes is associated with significantly increased health care costs, an increase that was driven by marked increase in medication costs.

Background Patients with acute coronary syndrome without standard modifiable cardiovascular risk factors (SMuRFs; hypertension, smoking, dyslipidemia, diabetes) have not been well studied, with little known about their characteristics, quality of care, or outcomes. We sought to systematically analyze patients with ACS without SMuRFs, especially to evaluate the effectiveness of guideline‐directed medical therapy for these patients. Methods and Results In the CCC‐ACS (Improving Care for Cardiovascular Disease in China‐Acute Coronary Syndrome) project (2014–2019), we examined the presence and absence of SMuRFs and features among 89 462 patients with initial acute coronary syndrome. The main outcome was in‐hospital all‐cause mortality. Among eligible patients, 11.0% had none of the SMuRFs (SMuRF‐less). SMuRF‐less patients had higher in‐hospital mortality (unadjusted hazard ratio [HR], 1.49 [95% CI, 1.19–1.87]). After adjustment for clinical characteristics and treatments, the associations between SMuRF status and in‐hospital mortality persisted (adjusted HR, 1.35 [95% CI, 1.07–1.70]). Guideline‐directed optimal medical therapy (receiving angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers, β‐blockers, and statins) was not associated with lower mortality (adjusted HR, 0.98 [95% CI, 0.58–1.67]) in SMuRF‐less patients, unlike the association in patients with SMuRFs (adjusted HR, 0.80 [95% CI, 0.66–0.98]). Sensitivity analyses were consistent with these results. Conclusions SMuRF‐less patients were associated with an increased risk of in‐hospital mortality. Guideline‐directed medical therapy was less effective in SMuRF‐less patients than in patients with SMuRFs. Dedicated studies are needed to confirm the optimal therapy for SMuRF‐less patients. REGISTRATION URL: https://www.clinicaltrials.gov; Unique identifier: NCT02306616.

Background Immigrants experience changes in cardiovascular risk factors and racial disparities in both cardiovascular health prevention and outcomes upon immigration. We aimed to examine cardiovascular risk factors and outcomes among Chinese American immigrants enrolled in the MESA (Multi‐Ethnic Study of Atherosclerosis) cohort. Methods and Results We analyzed data from 746 Chinese American immigrants in the MESA study with a median follow‐up period of 17.8 years. The mean age of the cohort was 62.3 years, with 52.7% being women. Kaplan–Meier curves and Cox proportional hazards models were used to assess the association of immigration history, geographic location, biomarkers, and cardiac imaging parameters with cardiovascular risk factors and cardiovascular outcomes. The Cox hazards models were adjusted for known family history of heart disease, education level, sex, diabetes, hypertension, age, and body mass index. Although immigration history categorized as earlier (

Study objective: The association of prior to admission guideline-directed medical therapy (GDMT) use in patients hospitalized with Heart Failure with Reduced Ejection Fraction (HFrEF, ejection fraction ≤40 %) and Coronavirus Disease 2019 (COVID-19) with in-hospital outcomes has not been well studied. Design/setting/participants/interventions/outcome measures: Using the American Heart Association's Get With The Guidelines Heart Failure Registry, we identified HFrEF patients presenting with acute decompensated heart failure (ADHF) and compared rates of GDMT prescription between those presenting prior to and during the pandemic. In a subgroup of patients with a concomitant COVID-19 diagnosis, we evaluated the association of prior to admission GDMT use with in-hospital mortality and severe COVID-19. Results: 23,899 patients were admitted with HFrEF during the pandemic (2/16/20–3/24/21) and 26,459 patients were admitted in the year prior (2/16/19–2/15/20). In this overall cohort, prior to admission ACEI/ARB/ARNI (45.6 % vs 48.1 %, p

Abstract Background Different breast cancer pharmacotherapy agents cause different forms of cardiovascular toxicity. We aim to assess if breast cancer pharmacotherapy trials approach cardiovascular safety in a targeted or generalized manner when administering different agents. Methods We searched Embase and Medline for phase 2 and 3 breast cancer pharmacotherapy trials. We examined exclusion criterion for cardiovascular conditions and cardiovascular safety assessment through cardiovascular imaging, electrocardiogram, troponin, or natriuretic peptides. Fisher’s exact test was utilized to compare reporting. Results Fifty breast cancer clinical trials were included in this study. Trials administering microtubule inhibitors were most likely to exclude patients with any CV condition compared with trials administering other agents (93.5% vs. 68.4%; p

Abstract. Background:. Oral anti-coagulants (OAC) are the intervention for the prevention of stroke, which consistently improve clinical outcomes and survival among patients with atrial fibrillation (AF). The main purpose of this study is to identify problems in OAC utilization among hospitalized patients with AF in China. Methods:. Using data from the Improving Care for Cardiovascular Disease in China-Atrial Fibrillation (CCC-AF) registry, guideline-recommended OAC use in eligible patients was assessed. Results:. A total of 52,530 patients with non-valvular AF were enrolled from February 2015 to December 2019, of whom 38,203 were at a high risk of stroke, 9717 were at a moderate risk, and 4610 were at a low risk. On admission, only 20.0% (6075/30,420) of patients with a diagnosed AF and a high risk of stroke were taking OAC. The use of pre-hospital OAC on admission was associated with a lower risk of new-onset ischemic stroke/transient ischemic attack among the diagnosed AF population (adjusted odds ratio: 0.54, 95% confidence interval: 0.43–0.68; P 70% of AF patients were at a high risk of stroke. Although poor performance on guideline-recommended OAC use was found in this study, over time the CCC-AF project has made progress in stroke prevention in the Chinese AF population.Registration:ClinicalTrials.gov, NCT02309398.

Background: Low-dose colchicine has been shown to lower major adverse cardiovascular events (MACE) among those with cardiovascular disease (CVD). It remains unclear how long a CVD patient needs to live to potentially benefit from colchicine. Our study aimed to determine the time to benefit (TTB) of colchicine in individuals with CVD. Methods: Literature searches were performed in PubMed for the cardiovascular outcome trial of colchicine in patients with CVD until October 12, 2023. The primary outcome measured was MACE. Reconstructed individual participant data (IPD) and the stratified Cox proportional hazards model were used to calculate the hazard ratio (HR) and 95 % confidence interval (CI) to estimate the efficacy of colchicine, and Weibull survival curves were fitted to estimate TTB for specific absolute risk reduction (ARR) thresholds (0.002, 0.005, and 0.01). Results: Four trials randomizing 11,594 adults aged between 59.8 and 66.5 years were included (follow-up duration: 12–28.6 months). Compared with placebo, colchicine reduced the risk of MACE (HR 0.68, 95 % CI: 0.60 to 0.78) but had no impact on cardiovascular and all-cause mortality. A TTB of 11.0 months (95 % CI: 0.59 to 21.3) was estimated to be needed to prevent 1 MACE in 100-colchicine-treated patients. The TTB for acute coronary syndrome was similar compared to stable coronary artery disease (10.7 vs. 11.2 months for ARR = 0.010). Conclusions: By using reconstructed IPD, this pooled analysis demonstrated that colchicine was associated with reduced nonfatal MACE, and the TTB was approximately 11.0 months to prevent 1 MACE per 100 patients.

Objective: To evaluate the impact of age and COVID-19 variant time period on morbidity and mortality among those hospitalized with COVID-19. Patients and Methods: Patients from the American Heart Association’s Get With The Guidelines COVID-19 cardiovascular disease registry (January 20, 2020-February 14, 2022) were divided into groups based on whether they presented during periods of wild type/alpha, delta, or omicron predominance. They were further subdivided by age (young: 18-40 years; older: more than 40 years), and characteristics and outcomes were compared. Results: The cohort consisted of 45,421 hospitalized COVID-19 patients (wild type/alpha period: 41,426, delta period: 3349, and omicron period: 646). Among young patients (18-40 years), presentation during delta was associated with increased odds of severe COVID-19 (OR, 1.6; 95% CI, 1.3-2.1), major adverse cardiovascular events (MACE) (OR, 1.8; 95% CI, 1.3-2.5), and in-hospital mortality (OR, 2.2; 95% CI, 1.5-3.3) when compared with presentation during wild type/alpha. Among older patients (more than 40 years), presentation during delta was associated with increased odds of severe COVID-19 (OR, 1.2; 95% CI, 1.1-1.3), MACE (OR, 1.5; 95% CI, 1.4-1.7), and in-hospital mortality (OR, 1.4; 95% CI, 1.3-1.6) when compared with wild type/alpha. Among older patients (more than 40 years), presentation during omicron associated with decreased odds of severe COVID-19 (OR, 0.7; 95% CI, 0.5-0.9) and in-hospital mortality (OR, 0.6; 95% CI, 0.5-0.9) when compared with wild type/alpha. Conclusion: Among hospitalized adults with COVID-19, presentation during a time of delta predominance was associated with increased odds of severe COVID-19, MACE, and in-hospital mortality compared with presentation during wild type/alpha. Among older patients (aged more than 40 years), presentation during omicron was associated with decreased odds of severe COVID-19 and in-hospital mortality compared with wild type/alpha.

Background Secondary prevention of ischemic stroke (IS) requires adequate diagnostic evaluation to identify the likely etiologic subtype. We describe hospital‐level variability in diagnostic testing and IS subtyping in a large nationwide registry. Methods and Results We used the GWTG‐Stroke (Get With The Guidelines–Stroke) registry to identify patients hospitalized with a diagnosis of acute IS at 1906 hospitals between January 1, 2016, and September 30, 2017. We compared the documentation rates and presence of risk factors, diagnostic testing, achievement/quality measures, and outcomes between patients with and without reported IS subtype. Recording of diagnostic evaluation was optional in all IS subtypes except cryptogenic, where it was required. Of 607 563 patients with IS, etiologic IS subtype was documented in 57.4% and missing in 42.6%. Both the rate of missing stroke pathogenesis and the proportion of cryptogenic strokes were highly variable across hospitals. Patients missing stroke pathogenesis less frequently had documentation of risk factors, evidence‐based interventions, or discharge to home. The reported rates of major diagnostic testing, including echocardiography, carotid and intracranial vascular imaging, and short‐term cardiac monitoring were 40% of patients. Long‐term cardiac rhythm monitoring was rarely reported, even in cryptogenic stroke. Conclusions Reporting of IS etiologic subtype and supporting diagnostic testing was low overall, with high rates of missing optional data. Improvement in the capture of these data elements is needed to identify opportunities for quality improvement in the diagnostic evaluation and secondary prevention of stroke.

Background There is a paucity of large‐scale epidemiological studies on the link between cardiac autonomic neuropathy (CAN) and the risk of silent myocardial infarction (SMI) in type 2 diabetes. We evaluated the association between CAN and the risk of SMI in a large sample of adults with type 2 diabetes. Methods and Results Participants with type 2 diabetes from the ACCORD (Action to Control Cardiovascular Risk in Diabetes) study without atherosclerotic cardiovascular disease at baseline were included. CAN was ascertained using heart rate variability indices calculated from 10‐s resting electrocardiograms. The heart rate variability indices included standard deviation of all normal‐to‐normal R‐R intervals and root mean square of successive differences between normal‐to‐normal R‐R intervals. CAN was defined as both the standard deviation of all normal‐to‐normal R‐R intervals and root mean square of successive differences between normal‐to‐normal R‐R intervals less than the fifth percentile of the general population. We used Cox proportional hazards regression to generate hazard ratios (HRs) for incident SMI in relation to CAN measures. Among 4842 participants (mean age, 62.5 years; 46.6% women; 60.2% White), there were 73 incident SMI cases over a median follow‐up of 4.9 years (incidence rate 3.1 out of 1000 person‐years [95% CI, 2.5–3.9]). After adjusting for confounders, low heart rate variability was associated with a higher risk of SMI (HR, 1.67 [95% CI, 1.02–2.72] and HR, 1.56 [95% CI, 0.94–2.58] for low standard deviation of all normal‐to‐normal R‐R intervals and root mean square of successive differences between normal‐to‐normal R‐R intervals, respectively). Participants with CAN had a 1.9‐fold greater risk of SMI (HR, 1.91 [95% CI, 1.14–3.20]). Conclusions In a large cohort of adults with type 2 diabetes, CAN was significantly associated with an increased risk of incident SMI.

AimsWe sought to conduct a meta-analysis to evaluate the efficacy and safety of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in patients with heart failure (HF) with preserved ejection fraction (HFpEF) and HF with mildly reduced ejection fraction (HFmrEF).MethodsWe searched the Cochrane Library, MEDLINE (via PubMed), Embase, and ClinicalTrials.gov till March 2023 to retrieve all randomized controlled trials of SGLT2i in patients with HFpEF or HFmrEF. Risk ratios (RRs) and standardized mean differences (SMDs) with their 95% confidence intervals (95% CIs) were pooled using a random-effects model.ResultsWe included data from 14 RCTs. SGLT2i reduced the risk of the primary composite endpoint of first HF hospitalization or cardiovascular death (RR 0.81, 95% CI: 0.76, 0.87; I2 = 0%); these results were consistent across the cohorts of HFmrEF and HFpEF patients. There was no significant decrease in the risk of cardiovascular death (RR 0.96, 95% CI: 0.82, 1.13; I2 = 36%) and all-cause mortality (RR 0.97, 95% CI: 0.89, 1.05; I2 = 0%). There was a significant improvement in the quality of life in the SGLT2i group (SMD 0.13, 95% CI: 0.06, 0.20; I2 = 51%).ConclusionThe use of SGLT2i is associated with a lower risk of the primary composite outcome and a higher quality of life among HFpEF/HFmrEF patients. However, further research involving more extended follow-up periods is required to draw a comprehensive conclusion.Systematic Review RegistrationPROSPERO (CRD42022364223).

Summary: Background: Whether the accuracy of the phenotype ascribed to patients in electronic health records (EHRs) is associated with variation in prognosis and care provision is unknown. We investigated this for heart failure (HF, characterised as HF with preserved ejection fraction [HFpEF], HF with reduced ejection fraction [HFrEF] and unspecified HF). Methods: We included individuals aged 16 years and older with a new diagnosis of HF between January 2, 1998 and February 28, 2022 from linked primary and secondary care records in the Clinical Practice Research Datalink in England. We investigated the provision of guideline-recommended diagnostic investigations and pharmacological treatments. The primary outcome was a composite of HF hospitalisation or all-cause death, and secondary outcomes were time to HF hospitalisation, all-cause death and death from cardiovascular causes. We used Kaplan–Meier curves and log rank tests to compare survival across HF phenotypes and adjusted for potential confounders in Cox proportional hazards regression analyses. Findings: Of a cohort of 95,262 individuals, 1271 (1.3%) were recorded as having HFpEF, 10,793 (11.3%) as HFrEF and 83,198 (87.3%) as unspecified HF. Individuals recorded as unspecified HF were older with a higher prevalence of dementia. Unspecified HF, compared to patients with a recorded HF phenotype, were less likely to receive specialist assessment, echocardiography or natriuretic peptide testing in the peri-diagnostic period, or receive angiotensin-converting enzyme inhibitors, beta blockers or mineralocorticoid receptor antagonists up to 12 months after diagnosis (risk ratios compared to HFrEF, 0.64, 95% CI 0.63–0.64; 0.59, 0.58–0.60; 0.57, 0.55–0.59; respectively) and had significantly worse outcomes (adjusted hazard ratios compared to HFrEF, HF hospitalisation and death 1.66, 95% CI 1.59–1.74; all-cause mortality 2.00, 1.90–2.10; cardiovascular death 1.77, 1.65–1.90). Interpretation: Our findings suggested that absence of specification of HF phenotype in routine EHRs is inversely associated with clinical investigations, treatments and survival, representing an actionable target to mitigate prognostic and health resource burden. Funding: Japan Research Foundation for Healthy Aging and British Heart Foundation.

Abstract Aims To describe clinical characteristics and outcomes for those with STEMI and reduced left ventricular ejection fraction (LVEF) in low‐income and middle‐income countries (LMICs). Methods and results Adults presenting with STEMI to two government‐owned tertiary care centres in Delhi, India were prospectively enrolled in the North India ST‐elevation myocardial infarction (NORIN‐STEMI) registry. LVEF was evaluated at presentation and clinical characteristics were compared across LVEF categories. Overall, 3597 patients were included, of whom 468 (13%) had LVEF >50%, 1482 (41%) had mildly reduced LVEF (40–49%), 1357 (38%) had moderately reduced LVEF (30–39%), and 290 (8%) had severely reduced LVEF (24 h, prior MI, and hyperlipidaemia were associated with decreasing LVEF category. Although most patients with reduced LVEF were discharged on appropriate guideline‐directed therapies, adherence at 1 year was low (ACE inhibitor/ARB 91% to 41%, beta blocker 98% to 78%, aldosterone receptor antagonist 69% to 6%). After multivariable adjustment, a Cox regression model showed moderately reduced LVEF (HR 1.77, 95% CI 1.20, 2.60) and severely reduced LVEF (HR 3.63, 95% CI 2.41, 5.48) were associated with increased risk of all‐cause mortality compared with LVEF ≥50%. Conclusions On presentation for STEMI, almost 90% of NORIN‐STEMI participants had at least mildly reduced LVEF and almost half had LVEF

Background Many patients with heart failure (HF) have severely reduced ejection fraction but do not meet threshold for consideration of advanced therapies (ie, stage D HF). The clinical profile and health care costs associated with these patients in US practice is not well described. Methods and Results We examined patients hospitalized for worsening chronic heart failure with reduced ejection fraction ≤40% from 2014 to 2019 in the GWTG‐HF (Get With The Guidelines‐Heart Failure) registry, who did not receive advanced HF therapies or have end‐stage kidney disease. Patients with severely reduced EF defined as EF ≤30% were compared with those with EF 31% to 40% in terms of clinical profile and guideline‐directed medical therapy. Among Medicare beneficiaries, postdischarge outcomes and health care expenditure were compared. Among 113 348 patients with EF ≤40%, 69% (78 589) had an EF ≤30%. Patients with severely reduced EF ≤30% tended to be younger and were more likely to be Black. Patients with EF ≤30% also tended to have fewer comorbidities and were more likely to be prescribed guideline‐directed medical therapy (“triple therapy” 28.3% versus 18.2%, P

Abstract Aims Recent trials have evaluated sodium–glucose co‐transporter 2 inhibitors in patients with heart failure (HF). We sought to assess the robustness of findings from these trials using the fragility index (FI). Methods and results Fragility index is defined as the minimum number of patients that must be moved from the ‘non‐event’ to the ‘event’ group to turn a statistically significant result to non‐significant. In addition to FI, fragility quotient [(FQ); FI divided by the sample size] was calculated to assess the proportion of events that must be moved to change the significance. For statistically non‐significant outcomes, reverse fragility index (RFI) and reverse fragility quotient (RFQ) were calculated. Robustness of findings after pooling data from all three trials was also assessed. A robust reduction in first HF hospitalization or cardiovascular mortality was seen with dapagliflozin (FI = 62 and FQ = 0.013), empagliflozin (FI = 50 and FQ = 0.013), and sotagliflozin (FI = 60 and FQ = 0.049). Dapagliflozin nominally improved all‐cause and cardiovascular mortality, with modest FI (n = 8 and 5) and FQ (0.002 and 0.001). Empagliflozin and sotagliflozin did not demonstrate statistically significant reductions in all‐cause mortality, with modest RFI (empagliflozin: RFI = 26 and RFQ = 0.007; sotagliflozin: RFI = 6 and RFQ = 0.005). A similar trend was seen with cardiovascular mortality (empagliflozin: RFI = 24 and RFQ = 0.006; sotagliflozin: RFI = 7 and RFQ = 0.006). Upon meta‐analysis, the result for first HF hospitalization or cardiovascular mortality was robust (FI = 95 and FQ = 0.010). The reductions in all‐cause (FI = 12 and FQ = 0.001) and cardiovascular mortality (FI = 9 and FQ = 0.001), while statistically significant, were fragile. Conclusion Improvement in the composite outcome of first HF hospitalization or cardiovascular death was highly concordant and robust across sodium–glucose co‐transporter 2 inhibitor trials. In contrast, secondary endpoints of all‐cause and cardiovascular mortality were statistically fragile, underscoring the need to power trials for mortality to fully understand the benefit of therapies on fatal events.

Abstract Background Data on the relations between kidney function abnormalities and stroke in type 2 diabetes are limited. We evaluated the associations of kidney function abnormalities and chronic kidney disease (CKD) stages with incident stroke in a large sample of adults with type 2 diabetes. Methods Participants with type 2 diabetes from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study without history of stroke at baseline were included. Urine albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) were assessed at baseline. CKD categories were defined according to the KDIGO (Kidney Disease: Improving Global Outcomes) guidelines. Cox proportional hazards regression models were used to compute hazard ratios (HR) and 95% confidence intervals (CI) for stroke in relation to measures of kidney function and CKD categories. Results A total of 9170 participants (mean age 62.8 [SD: 6.6] years, 38.2% women, 62.9% white) were included. Over a median follow-up of 4.9 years (interquartile range: 4.0–5.7), 156 participants developed a stroke (incidence rate 3.6/1000 person-years [95% CI 3.0–4.2]). After adjusting for relevant confounders, higher UACR and lower eGFR were each associated with increased risk of stroke. Compared to UACR

Abstract Aims We aimed to develop a risk prediction tool that incorporated both clinical events and worsening health status for patients with heart failure (HF) with reduced ejection fraction (HFrEF). Identifying patients with HFrEF at increased risk of a poor outcome may enable proactive interventions that improve outcomes. Methods and results We used data from a longitudinal HF registry, CHAMP‐HF, to develop a risk prediction tool for poor outcomes over the next 6 months. A poor outcome was defined as death, an HF hospitalization, or a ≥20‐point decrease (or decrease below 25) in 12‐item Kansas City Cardiomyopathy Questionnaire (KCCQ‐12) overall summary score. Among 4546 patients in CHAMP‐HF, 1066 (23%) experienced a poor outcome within 6 months (1.3% death, 11% HF hospitalization, and 11% change in KCCQ‐12). The model demonstrated moderate discrimination (c‐index = 0.65) and excellent calibration with observed data. The following variables were associated with a poor outcome: age, race, education, New York Heart Association class, baseline KCCQ‐12, atrial fibrillation, coronary disease, diabetes, chronic kidney disease, smoking, prior HF hospitalization, and systolic blood pressure. We also created a simplified model with a 0–10 score using six variables (New York Heart Association class, KCCQ‐12, coronary disease, chronic kidney disease, prior HF hospitalization, and systolic blood pressure) with similar discrimination (c‐index = 0.63). Patients scoring 0–3 were considered low risk (event rate 40%). Conclusions The PROMPT‐HF risk model can identify outpatients with HFrEF at increased risk of poor outcomes, including clinical events and health status deterioration. With further validation, this model may help inform therapeutic decision making.

Abstract Background It remains unclear how the variability of adiposity indices relates to incident HF. This study evaluated the associations of the variability in several adiposity indices with incident heart failure (HF) in individuals with type 2 diabetes (T2DM). Methods We included 4073 participants from the Look AHEAD (Action for Health in Diabetes) study. We assessed variability of body mass index (BMI), waist circumference (WC), and body weight across four annual visits using three variability metrics, the variability independent of the mean (VIM), coefficient of variation (CV), and intraindividual standard deviation (SD). Multivariable Cox regression models were used to generate adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for incident HF. Results Over a median of 6.7 years, 120 participants developed incident HF. After adjusting for relevant confounders including baseline adiposity levels, the aHR for the highest (Q4) versus lowest quartile (Q1) of VIM of BMI was 3.61 (95% CI 1.91–6.80). The corresponding aHRs for CV and SD of BMI were 2.48 (95% CI 1.36–4.53) and 2.88 (1.52–5.46), respectively. Regarding WC variability, the equivalent aHRs were 1.90 (95% CI 1.11–3.26), 1.79 (95% CI 1.07–3.01), and 1.73 (1.01–2.95) for Q4 versus Q1 of VIM, CV and SD of WC, respectively. Conclusions In a large sample of adults with T2DM, a greater variability of adiposity indices was associated with higher risks of incident HF, independently of traditional risk factors and baseline adiposity levels. Registration-URL: https://clinicaltrials.gov/ct2/show/NCT00000620 .

Objective To evaluate the adoption and discontinuation of four broadly used non-pharmaceutical interventions on shifts in the covid-19 burden among US states.Design Retrospective, observational cohort study.Setting US state data on covid-19 between 19 January 2020 and 7 March 2021.Participants US population with a diagnosis of covid-19.Main outcome measures Empirically derived breakpoints in case and mortality velocities (ie, rate of change) were used to identify periods of stable, decreasing, or increasing covid-19 burden. Associations between adoption of non-pharmaceutical interventions and subsequent decreases in case or death rates were estimated by use of generalised linear models accounting for weekly variability across US states. State level case and mortality counts per day were obtained from the Covid-19 Tracking Project. State level policies on non-pharmaceutical interventions included stay-at-home orders, indoor public gathering bans (mild >10 or severe ≤10 people), indoor restaurant dining bans, and public mask mandates. National policies were not included in statistical models.Results 28 602 830 cases and 511 899 deaths were recorded during the study. Odds of a reduction in covid-19 case velocity increased for stay-at-home orders (odds ratio 2.02, 95% confidence interval 1.63 to 2.52), indoor dining bans (1.62, 1.25 to 2.10), public mask mandates (2.18, 1.47 to 3.23), and severe indoor public gathering bans (1.68, 1.31 to 2.16) in univariate analysis. In mutually adjusted models, odds remained elevated for orders to stay at home (adjusted odds ratio 1.47, 95% confidence interval 1.04 to 2.07) and public mask mandates (2.27, 1.51 to 3.41). Stay-at-home orders (odds ratio 2.00, 95% confidence interval 1.53 to 2.62; adjusted odds ratio 1.89, 95% confidence interval 1.25 to 2.87) was also associated with a greater likelihood of decrease in death velocity in unadjusted and adjusted models.Conclusions State level non-pharmaceutical interventions used in the US during the covid-19 pandemic, in particular stay-at-home orders, were associated with a decreased covid-19 burden.

Background Persistence to P2Y12 inhibitors after myocardial infarction (MI) remains low. Out‐of‐pocket cost is cited as a factor affecting medication compliance. We examined whether a copayment intervention affected 1‐year persistence to P2Y12 inhibitors and clinical outcomes. Methods and Results In an analysis of ARTEMIS (Affordability and Real‐World Antiplatelet Treatment Effectiveness After Myocardial Infarction Study), patients with MI discharged on a P2Y12 inhibitor were stratified by baseline out‐of‐pocket medication burden: low ($0–$49 per month), intermediate ($50–$149 per month), and high (≥$150 per month). The impact of the voucher intervention on 1‐year P2Y12 inhibitor persistence was examined using a logistic regression model with generalized estimating equations. We assessed the rates of major adverse cardiovascular events among the groups using a Kaplan–Meier estimator. Among 7351 MI‐treated patients at 282 hospitals, 54.2% patients were in the low copay group, 32.0% in the middle copay group, and 13.8% in the high copay group. Patients in higher copay groups were more likely to have a history of prior MI, heart failure, and diabetes compared with the low copay group (all P

BackgroundFew studies have evaluated whether acute myocardial infarction (AMI) patients with relatively low blood pressure benefit from early ACEI/ARB use in the era of percutaneous coronary intervention (PCI).ObjectivesThis study evaluated the associations of ACEI/ARB use within 24 h of admission with in-hospital outcomes among AMI patients with SBP < 100 mmHg and undergoing PCI.MethodsThis study was based on the Improving Care for Cardiovascular Disease in China-ACS project, a collaborative registry and quality improvement project of the American Heart Association and the Chinese Society of Cardiology. Between November 2014 and December 2019, a total of 94,623 patients with AMI were enrolled. Of them, 4,478 AMI patients with SBP < 100 mmHg and undergoing PCI but without clinically diagnosed cardiogenic shock at admission were included. Multivariable logistic regression and propensity score-matching analysis were used to evaluate the association between early ACEI/ARB use and in-hospital major adverse cardiac events (MACEs), a combination of all-cause death, cardiogenic shock, and cardiac arrest.ResultsOf AMI patients, 24.41% (n = 1,093) were prescribed ACEIs/ARBs within 24 h of admission. Patients with early ACEI/ARB use had a significantly lower rate of MACEs than those without ACEI/ARB use (1.67% vs. 3.66%, p = 0.001). In the logistic regression analysis, early ACEI/ARB use was associated with a 45% lower risk of MACEs (odds ratio: 0.55, 95% CI: 0.33–0.93; p = 0.027). Further propensity score-matching analysis still showed that patients with early ACEI/ARB use had a lower rate of MACEs (1.96% vs. 3.93%, p = 0.009).ConclusionThis study found that among AMI patients with an admission SBP < 100 mmHg undergoing PCI, early ACEI/ARB use was associated with better in-hospital outcomes. Additional studies of the early use of ACEIs/ARBs in AMI patients with relatively low blood pressure are warranted.

Abstract Aims Improving the health status (symptoms, function, and quality of life) of patients with heart failure with reduced ejection fraction (HFrEF) is a primary treatment goal. Angiotensin receptor neprilysin inhibitors (ARNI) improve short‐term health status in clinical practice, but the sustainability of these improvements is unknown. Methods and results In CHAMP‐HF, a multicentre observational study of outpatients with HFrEF, patients initiated on ARNI were propensity score matched 1:2 to patients not using ARNI with Cox regression modelling time to ARNI initiation, adjusted for sociodemographic and clinical variables, medical history, medications, and baseline Kansas City Cardiomyopathy Questionnaire (KCCQ) scores. Repeated measures models for the overall KCCQ score and each domain compared the health status trajectories of patients initiated on ARNI vs. not. Among 3930 participants, 746 (19.0%) began ARNI, of whom 576 were matched to 1152 non‐ARNI patients. Prior to matching, participants initiated on ARNI were younger, non‐Hispanic, had lower EFs, more commonly had a history of ventricular arrhythmia, were less likely to be taking an ACEI/ARB, and more likely to be treated with beta‐blockers and mineralocorticoid receptor antagonists. There were no differences after matching. In the matched cohort, participants initiated on ARNI experienced improved health status by 3 months that persisted through 12 months [KCCQ Overall Summary Score (OSS) = 73.4 vs. 70.8; P

Background Several cancer therapies have been associated with cardiovascular harm in early‐phase clinical trials. However, some cardiovascular harms do not manifest until later‐phase trials. To limit interdisease variability, we focused on breast cancer. Thus, we assessed the reporting of cardiovascular safety monitoring and outcomes in phase 2 and 3 contemporary breast cancer clinical trials. Methods and Results We searched Embase and Medline records for phase 2 and 3 breast cancer pharmacotherapy trials. We examined exclusion criterion as a result of cardiovascular conditions, adverse cardiovascular event reporting, and cardiovascular safety assessment through cardiovascular imaging, ECG, troponin, or natriuretic peptides. Fisher's exact test was utilized to compare reporting. Fifty clinical trials were included in our study. Patients were excluded because of cardiovascular conditions in 42 (84%) trials. Heart failure was a frequent exclusion criterion (n=31; 62% trials). Adverse cardiovascular events were reported in 43 (86%) trials. Cardiovascular safety assessments were not reported in 23 (46%) trials, whereas natriuretic peptide and troponin assessments were not reported in any trial. Cardiovascular safety assessments were more frequently reported in industry‐funded trials (69.2% versus 0.0%; P

Background There are limited data on the use of angiotensin receptor neprilysin inhibitors (ARNIs) in minority populations with heart failure (HF) with reduced ejection fraction. We used data from the CHAMP‐HF (Change the Management of Patients With Heart Failure) registry to evaluate ARNI initiation and associated changes in health status and clinical outcomes across different races and ethnicities. Methods and Results CHAMP‐HF was a prospective, observational registry of US outpatients with chronic HF with reduced ejection fraction. We compared patients starting ARNI with patients not starting ARNI using a propensity‐matched analysis. Patients were grouped as Hispanic, non‐Hispanic Black, non‐Hispanic White, or non‐Hispanic other individuals, where “non‐Hispanic other” consists of all patients who did not identify as Hispanic, Black, or White. Health status was assessed using the 12‐item Kansas City Cardiomyopathy Questionnaire. Outcomes were analyzed with multivariable models that included race and ethnicity, ARNI initiation, and an interaction term between race and ethnicity and ARNI initiation. Cox proportional hazards models were used for death/HF hospitalization, and multiple regression was used for change in Kansas City Cardiomyopathy Questionnaire score. The analysis included 1516 patients, with 758 patients in each group (ARNI and no ARNI). Changes in Kansas City Cardiomyopathy Questionnaire score after ARNI initiation were similar among all race and ethnicity groups (mean [SD], non‐Hispanic White individuals, 3.5 [19.0]; non‐Hispanic Black individuals, 2.0 [17.0]; non‐Hispanic other individuals, 5.5 [20.3]; and Hispanic individuals, 3.2 [20.1]), with no statistically significant interaction between race and ethnicity and ARNI initiation (P=0.21). There was similarly no statistically significant interaction between race and ethnicity and ARNI initiation for HF hospitalization (P=0.82) or all‐cause mortality (P=0.92). Conclusions In a large registry of outpatients with HF with reduced ejection fraction, the association between ARNI initiation and outcomes did not differ by race and ethnicity. These data support the use of ARNI therapy for chronic HF with reduced ejection fraction irrespective of race and ethnicity.

Abstract Aims The intermediate‐term effects of dietary protein on cardiometabolic risk factors in overweight and obese patients with heart failure and diabetes mellitus are unknown. We compared the effect of two calorie‐restricted diets on cardiometabolic risk factors in this population. Methods and results In this randomized controlled study, 76 overweight and obese (mean weight, 107.8 ± 20.8 kg) patients aged 57.7 ± 9.7 years, 72.4% male, were randomized to a high‐protein (30% protein, 40% carbohydrates, and 30% fat) or standard‐protein diet (15% protein, 55% carbohydrates, and 30% fat) for 3 months. Reductions in weight and cardiometabolic risks were evaluated at 3 months. Both diets were equally effective in reducing weight (3.6 vs. 2.9 kg) and waist circumference (1.9 vs. 1.3 cm), but the high‐protein diet decreased to a greater extent glycosylated haemoglobin levels (0.7% vs. 0.1%, P = 0.002), cholesterol (16.8 vs. 0.9 mg/dL, P = 0.031), and triglyceride (25.7 vs. 5.7 mg/dL, P = 0.032), when compared with the standard‐protein diet. The high‐protein diet also significantly improved both systolic and diastolic blood pressure than the standard‐protein diet (P

Abstract Background The U.S. lacks a stroke surveillance system. This study develops a method to transform an existing registry into a nationally representative database to evaluate acute ischemic stroke care quality. Methods Two statistical approaches are used to develop post-stratification weights for the Get With The Guidelines-Stroke registry by anchoring population estimates to the National Inpatient Sample. Post-stratification survey weights are estimated using a raking procedure and Bayesian interpolation methods. Weighting methods are adjusted to limit the dispersion of weights and make reasonable epidemiologic estimates of patient characteristics, quality of hospital care, and clinical outcomes. Standardized differences in national estimates are reported between the two post-stratification methods for anchored and non-anchored patient characteristics to evaluate estimation quality. Primary measures evaluated are patient and hospital characteristics, stroke severity, vital and laboratory measures, disposition, and clinical outcomes at discharge. Results A total of 1,388,296 acute ischemic strokes occurred between 2012 and 2014. Raking and Bayesian estimates of clinical data not available in administrative data are estimated within 5 to 10% of margin for expected values. Median weight for the raking method is 1.386 and the weights at the 99th percentile is 6.881 with a maximum weight of 30.775. Median Bayesian weight is 1.329 and the 99th percentile weights is 11.201 with a maximum weight of 515.689. Conclusions Leveraging existing databases with patient registries to develop post-stratification weights is a reliable approach to estimate acute ischemic stroke epidemiology and monitoring for stroke quality of care nationally. These methods may be applied to other diseases or settings to better monitor population health.

Abstract Aims Discontinuation or non‐publication of trials may hinder scientific progress and violates the commitment made to research participants. We sought to identify the prevalence of discontinuation and non‐publication of heart failure (HF) clinical trials. Methods and results We conducted a cross‐sectional search of ClinicalTrials.gov to identify all completed and discontinued HF clinical trials. We limited our search to only include trials that were completed by 31 December 2017. Trials were investigated to identify reasons for discontinuation. Informative termination was defined as trial termination due to safety or efficacy concerns. Data pertaining to the trial phase, funding, intervention, enrolment, and trial completion date were extracted for each trial. A total of 572 trials were included. Of these, 21% (n = 118) were discontinued before completion. Patient accrual was the most frequently cited reason (n = 42; 36%) for trial discontinuation, followed by informative termination (n = 16; 14%) and funding (n = 14; 12%). Overall, 24 780 patients were enrolled in trials that were terminated. Of trials that were completed and not terminated, nearly one‐third (n = 131/454; 29%) were not published. Seventy‐nine (24%) trials were published within 12 months, 192 (59%) within 24 months, and 252 (78%) trials within 36 months. Conclusions Discontinuation and non‐publication of HF trials is common. This raises ethical concerns towards participants who volunteer for research and are exposed to potential risks, inconvenience, and discomfort without furthering scientific progress.

Abstract Aims This study aimed to investigate the reporting of subgroup analyses in heart failure (HF) randomized controlled trials (RCTs) and to determine the strength and credibility of subgroup claims. Methods and results All primary HF RCTs published in nine high‐impact journals from 1 January 2008 to 31 December 2017 were included. Multivariable regression analysis was used to identify factors that may favour the reporting of results in specific subgroups. Strength of the subgroup effect claimed was classified into (i) strong, (ii) likely, or (iii) suggestive. Credibility of subgroup claim was scored using a pre‐specified 10 pointer criteria. Of the 261 HF RCTs studied, 107 (41%) reported subgroup analyses. Twenty‐five (23%) RCTs claimed a subgroup effect for the primary outcome of which six (24%) made a strong claim, eight (32%) claimed a likely effect, and 11 (44%) suggested a possible subgroup effect. Seven of the 25 RCTs did not employ interaction testing for subgroup claims of the primary outcome. Three out of 10 pre‐specified credibility criteria were satisfied by half of the trials. Fourteen trials justified the choice of subgroups, and 10 explicitly stated they were underpowered to detect differences within subgroups. Source of funding did not influence the frequency of reporting subgroup analyses (OR 0.53, 95% CI 0.78–3.62, P = 0.52). Conclusions Appropriate credibility criteria were rarely met even by HF RCTs that held strong subgroup claims. Subgroup analyses should be pre‐specified, be adequately powered, present interaction terms, and be replicated in independent data before being integrated into clinical decision making.

Abstract Aims The aim of our study was to investigate heterogeneity of health status treatment response of sacubitril/valsartan in patients with heart failure with reduced ejection fraction (HFrEF). Methods and results We leveraged data from CHAMP‐HF, an observational registry of 140 US clinics and 5026 outpatients with chronic HFrEF, where health status was serially assessed using the Kansas City Cardiomyopathy Questionnaire (KCCQ)‐12 Overall Summary Scale (range from 0 to 100; ≥20‐point improvement is a very large improvement). In 334 patients newly initiated on sacubitril/valsartan, we used hierarchical multivariable logistic regression (13 patient‐level characteristics as well as baseline KCCQ‐12 score) to calculate the odds ratio (OR) of any characteristic being associated with a very large health status improvement. A total of 104/334 (31.1%) of patients achieved the primary endpoint, where only worse baseline health status [KCCQ‐12 score of 0–60 points had an OR = 0.86/5‐point higher score (CI 0.79, 0.93)], and those with a KCCQ‐12 score of 60–80 points had an OR = 0.61/5‐point higher score (0.45–0.82), which was associated with a very large benefit. No other patient characteristic was associated with a very large health status improvement (P > 0.05). Conclusions We found that, after initiation of sacubitril/valsartan, only worse baseline health status was associated with very large health status improvement. Accordingly, a trial of therapy—particularly in those with worse symptoms, function, and quality of life—and assessing treatment response are likely to be the best prospective strategy.

Abstract Background Heart failure is a common and devastating complication of type 2 diabetes (T2D). Prompt recognition of heart failure may avert hospitalization, facilitate use of guideline-directed therapies, and impact choice of T2D medications. We sought to determine the rate and factors associated with heart failure documentation in T2D patients with evidence of volume overload requiring loop diuretics. Methods DCR is an on-going, prospective US registry of outpatient T2D patients from > 5000 cardiology, endocrinology, and primary care clinicians (current analysis used data from 2013–2019). Among T2D patients receiving loop diuretics, we examined the rate of chart documentation of heart failure. We used a 3-level hierarchical logistic regression model (patients nested within physician within practice) to examine factors associated with heart failure diagnosis. Results Among 1,322,640 adults with T2D, 225,125 (17.0%) were receiving a loop diuretic, of whom 91,969 (40.9%) had documentation of heart failure. Male sex, lower body mass index, atrial fibrillation, chronic kidney disease, and coronary artery disease were associated with greater odds of heart failure diagnosis. After accounting for patient factors, patients seen by cardiologists were the most likely to have HF documented followed by PCPs and then endocrinologists. Conclusions Among US outpatients with T2D, 17% of patients had evidence of volume overload—defined by loop diuretic prescription—of whom fewer than half had a clinical diagnosis of heart failure. While there may be non-heart failure indications for loop diuretics, our data suggest that a substantial proportion of T2D patients may have unrecognized heart failure and therefore could be missing opportunities for targeted therapies that could alter the clinical course of heart failure.

Abstract Background Due to the overlapping clinical features of coronavirus disease 2019 (COVID-19) and influenza, parallels are often drawn between the two diseases. Patients with pre-existing cardiovascular diseases (CVD) are at a higher risk for severe manifestations of both illnesses. Considering the high transmission rate of COVID-19 and with the seasonal influenza approaching in late 2020, the dual epidemics of COVID-19 and influenza pose serious cardiovascular implications. This review highlights the similarities and differences between influenza and COVID-19 and the potential risks associated with coincident pandemics. Main body COVID-19 has a higher mortality compared to influenza with case fatality rate almost 15 times more than that of influenza. Additionally, a significantly increased risk of adverse outcomes has been noted in patients with CVD, with ~ 15 to 70% of COVID-19 related deaths having an underlying CVD. The critical care need have ranged from 5 to 79% of patients hospitalized due to COVID-19, a proportion substantially higher than with influenza. Similarly, the frequency of vascular thrombosis including deep venous thrombosis and pulmonary embolism is markedly higher in COVID-19 patients compared with influenza in which vascular complications are rarely seen. Unexpectedly, while peak influenza season is associated with increased cardiovascular hospitalizations, a decrease of ~ 50% in cardiovascular hospitalizations has been observed since the first diagnosed case of COVID-19, owing in part to deferred care. Conclusion In the coming months, increasing efforts towards evaluating new interventions will be vital to curb COVID-19, especially as peak influenza season approaches. Currently, not enough data exist regarding co-infection of COVID-19 with influenza or how it would progress clinically, though it may cause a significant burden on an already struggling health care system. Until an effective COVID-19 vaccination is available, high coverage of influenza vaccination should be of utmost priority.

BackgroundThere are limited data available on the impact of early (within 24 h of admission) β-blocker therapy on in-hospital outcomes of patients with ST-elevation myocardial infarction (STEMI) and mild-moderate acute heart failure. This study aimed to explore the association between early oral β-blocker therapy and in-hospital outcomes.MethodsInpatients with STEMI and Killip class II or III heart failure from the Improving Care for Cardiovascular Disease in China project (n = 10,239) were enrolled. The primary outcome was a combined endpoint composed of in-hospital all-cause mortality, successful cardiopulmonary resuscitation after cardiac arrest, and cardiogenic shock. Inverse-probability-of-treatment weighting, multivariate Cox regression, and propensity score matching were performed.ResultsEarly oral β-blocker therapy was administered to 56.5% of patients. The incidence of the combined endpoint events was significantly lower in patients with early therapy than in those without (2.7 vs. 5.1%, P < 0.001). Inverse-probability-of-treatment weighting analysis demonstrated that early β-blocker therapy was associated with a low risk of combined endpoint events (HR = 0.641, 95% CI: 0.486–0.844, P = 0.002). Similar results were shown in multivariate Cox regression (HR = 0.665, 95% CI: 0.496–0.894, P = 0.007) and propensity score matching (HR = 0.633, 95% CI: 0.453–0.884, P = 0.007) analyses. A dose-response trend between the first-day β-blocker dosages and adverse outcomes was observed in a subset of participants with available data. No factor could modify the association of early treatment and the primary outcomes among the subgroups analyses.ConclusionBased on nationwide Chinese data, early oral β-blocker therapy is independently associated with a lower risk of poor in-hospital outcome in patients with STEMI and Killip class II or III heart failure.

Background: Guideline-directed device therapies (GDDT) improve outcomes for eligible patients with heart failure (HF) with reduced ejection fraction (HFrEF). Utilization rates of device therapies in HFrEF after the 2012 ACCF/AHA/HRS Focused Update for Device-based Therapies of Cardiac Rhythm Abnormalities have not been well studied. Objective: Characterize the use of GDDT in newly indicated HFrEF patients from 2012 to 2019 using aggregated electronic health record (EHR) data. Methods: Computable phenotyping algorithms for implantable cardioverter defibrillator/cardiac resynchronization therapy-defibrillator (ICD/CRT-D) indications from the GuideLine Indications Detected in EHR for Heart Failure program (GLIDE-HF) used diagnoses, procedures, measures, prescriptions, and the output of natural language processed provider notes from de-identified Optum® EHR data. Patients had a diagnosis of HF, dilated cardiomyopathy, or prior infarct, and were included if they had HFrEF with >1 year of records prior to a new Class 1 or Class 2a indication for an ICD or cardiac resynchronization therapy with defibrillator (CRT-D) from 2012 to 2019. Results: Records showed 137,476 HFrEF patients were newly indicated for an ICD or CRT-D. GDDT was used in 14,892 of 36,358 (41.0%) CRT-D indicated patients and in 14,904 of 101,118 (14.7%) ICD-indicated patients. While GDDT use was low, 95.7% had echocardiography and 92.1% had prescriptions for beta-blockers or angiotensin-converting enzyme/angiotensin-receptor blockers medications. Conclusions: In this modern cohort of HF patients, a large proportion of eligible patients did not receive ICDs or CRT-Ds, while frequently receiving other indicated cardiovascular interventions and treatments.

ObjectiveCardiogenic shock (CS) is the leading cause of death in patients with acute myocardial infarction (AMI) despite advances in care. This study aims to derive and validate a risk score for in-hospital development of CS in patients with AMI.MethodsIn this study, we used the Improving Care for Cardiovascular Disease in China–Acute Coronary Syndrome (CCC–ACS) registry of 76,807 patients for model development and internal validation. These patients came from 158 tertiary hospitals and 82 secondary hospitals between 2014 and 2019, presenting AMI without CS upon admission. The eligible patients with AMI were randomly assigned to derivation (n = 53,790) and internal validation (n = 23,017) cohorts. Another cohort of 2,205 patients with AMI between 2014 and 2016 was used for external validation. Based on the identified predictors for in-hospital CS, a new point-based CS risk scheme, referred to as the CCC–ACS CS score, was developed and validated.ResultsA total of 866 (1.1%) and 39 (1.8%) patients subsequently developed in-hospital CS in the CCC–ACS project and external validation cohort, respectively. The CCC–ACS CS score consists of seven variables, including age, acute heart failure upon admission, systolic blood pressure upon admission, heart rate, initial serum creatine kinase-MB level, estimated glomerular filtration rate, and mechanical complications. The area under the curve for in-hospital development of CS was 0.73, 0.71, and 0.85 in the derivation, internal validation and external validation cohorts, respectively.ConclusionThis newly developed CCC–ACS CS score can quantify the risk of in-hospital CS for patients with AMI, which may help in clinical decision making.Clinical Trial Registrationwww.ClinicalTrials.gov, identifier: NCT02306616.

Introduction Endovascular therapy (EVT) use increased following clinical trials publication in 2015, but limited data suggest there may be persistent race and ethnicity differences. Methods and Results We included all patients with acute ischemic stroke arriving within 6 hours of last known well and with National Institute of Health Stroke Scale (NIHSS) score ≥6 between April 2012 and June 2019 in the Get With The Guidelines‐Stroke database and evaluated the association between race and ethnicity and EVT use and outcomes, comparing the era before versus after 2015. Of 302 965 potentially eligible patients; 42 422 (14%) underwent EVT. Although EVT use increased over time in all racial and ethnic groups, Black patients had reduced odds of EVT use compared with non‐Hispanic White (NHW) patients (adjusted odds ratio [aOR] before 2015, 0.68 [0.58‒0.78]; aOR after 2015, 0.83 [0.76‒0.90]). In‐hospital mortality/discharge to hospice was less frequent in Black, Hispanic, and Asian patients compared with NHW. Conversely discharge home was more frequent in Hispanic (29.7%; aOR, 1.28 [1.16‒1.42]), Asian (28.2%; aOR, 1.23 [1.05‒1.44]), and Black (29.1%; aOR, 1.08 [1.00‒1.18]) patients compared with NHW (24%). However, at 3 months, functional independence (modified Rankin Scale, 0–2) occurred less frequently in Black (37.5%; aOR, 0.84 [0.75‒0.95]) and Asian (33%; aOR, 0.79 [0.65‒0.98]) patients compared with NHW patients (38.1%). Conclusions In a large cohort of patients treated with EVT, Black versus NHW patient disparities in EVT use have narrowed over time but still exist. Discharge related outcomes were slightly more favorable in racial and ethnic underrepresented groups; 3‐month functional outcomes were worse but improved across all groups with time.

Resumo Fundamento Existem grandes oportunidades de melhoria da qualidade do cuidado cardiovascular em países em desenvolvimento por meio da implementação de um programa de qualidade. Objetivo Avaliar o efeito de um programa de Boas Práticas em Cardiologia (BPC) nos indicadores de desempenho e desfechos clínicos dos pacientes relacionados à insuficiência cardíaca, fibrilação atrial e síndromes coronarianas agudas em um subconjunto de hospitais públicos brasileiros. Métodos O programa Boas Práticas em Cardiologia (BPC) foi adaptado do programa Get With The Guidelines (GWTG) da American Heart Association (AHA) para ser utilizado no Brasil. O programa está sendo iniciado em três domínios de cuidado simultaneamente (síndrome coronariana aguda, fibrilação atrial e insuficiência cardíaca), o que consiste em uma abordagem nunca testada no GWTG. Existem seis eixos de intervenções utilizadas pela literatura sobre tradução do conhecimento que abordará barreiras locais identificadas por meio de entrevistas estruturadas e reuniões regulares para auditoria e feedback. Planeja-se incluir no mínimo 10 hospitais e 1500 pacientes por doença cardíaca. O desfecho primário inclui as taxas de adesão às medidas de cuidado recomendadas pelas diretrizes. Desfechos secundários incluem o efeito do programa sobre o tempo de internação, mortalidade global e específica, taxas de readmissão, qualidade de vida, percepção do paciente sobre saúde e adesão dos pacientes às intervenções prescritas. Resultados Espera-se, nos hospitais participantes, uma melhoria e a manutenção das taxas de adesão as recomendações baseadas em evidência e dos desfechos dos pacientes. Este é o primeiro programa em melhoria da qualidade a ser realizado na América do Sul, que fornecerá informações importantes de como programas de sucesso originados em países desenvolvidos como os Estados Unidos podem ser adaptados às necessidades de países com economias em desenvolvimento como o Brasil. Um programa bem sucedido dará informações valiosas para o desenvolvimento de programas de melhoria da qualidade em outros países em desenvolvimento. Conclusões Este estudo de mundo real proverá informações para a avaliação e aumento da adesão às diretrizes de cardiologia no Brasil, bem como a melhora dos processos assistenciais. (Arq Bras Cardiol. 2020; 115(1):92-99)

Abstract Aims Hypokalaemia is a risk factor for ventricular arrhythmias and sudden death in ambulatory patients with chronic heart failure (HF). The objective of this study was to examine the association between hypokalaemia and outcomes in hospitalized patients with decompensated HF in whom sudden death is less common. Methods and results Of the 5881 hospitalized patients with HF, 1052 had consistent hypokalaemia (both admission and discharge serum potassium

Abstract Aims Sodium–glucose co‐transporter (SGLT)‐2 inhibitors have been shown to reduce the risk of cardiovascular death and heart failure (HF) hospitalization in patients with type 2 diabetes mellitus (DM) and high cardiovascular risk in two large clinical outcome trials: empagliflozin in EMPA‐REG OUTCOME and canagliflozin in CANVAS. The scope of eligibility for SGLT‐2 inhibitors (empagliflozin and canagliflozin) among patients with type 2 DM and HF, based on clinical trial criteria and current US Food and Drug Administration (FDA) labelling criteria, remains unknown. Methods and results Using data from the US Get With The Guidelines (GWTG)—Heart Failure registry, we evaluated the proportion of patients with DM and HF eligible for SGLT‐2 inhibitor therapy based on the clinical trial criteria and the US FDA labelling criteria. The GWTG‐HF registry is a quality improvement registry of patients admitted in hospital with HF in the USA. We included GWTG‐HF registry participants meeting eligibility criteria hospitalized between August 2014 and 30 June 2017 from sites fully participating in the registry. The initial inclusion time point reflects when both drugs had FDA approval. Among the 139 317 patients (out of 407 317) with DM hospitalized with HF (in 460 hospitals; 2014 to 2017), the median age was 71 years, 47% (n = 65 685) were female, and 43% (n = 59 973) had HF with reduced ejection fraction. Overall, 43% (n = 59 943) were eligible for the EMPA‐REG OUTCOME trial, 45% (n = 62 818) were eligible for the CANVAS trial, and 34% (n = 47 747) of patients were eligible for either SGLT‐2 inhibitors based on the FDA labelling criteria. Among the FDA‐eligible patients, 91.5% (n = 43 708) were eligible for either the EMPA‐REG OUTCOME trial or the CANVAS trial. Patients who were FDA eligible, compared with those who were not, were younger (70.0 vs. 72.0 years of age), more likely to be male (57.7 vs. 50.3%), and had less burden of co‐morbidities. Conclusions The majority of patients with DM who are hospitalized with HF are not eligible for SGLT‐2 inhibitor therapies. Ongoing studies evaluating the safety and efficacy of SGLT‐2 inhibitors among patients with HF may potentially broaden the population that may benefit from these therapies.

Background Currently, little is known regarding seasonal variation for atrial fibrillation (AF) in the United States and whether quality of care for AF varies between seasons. Methods and Results The GWTG‐AFib (Get With The Guidelines–AFib) registry was initiated by the American Heart Association to enhance national guideline adherence for treatment and management of AF. Our analyses included 61 291 patients who were admitted at 141 participating hospitals from 2014 to 2018 across the United States. Outcomes included numbers of AF admissions and quality‐of‐care measures (defect‐free care, defined as a patient’s receiving all eligible measures). For quality‐of‐care measures, generalized estimating equations accounting for within‐site correlations were used to estimate odds ratios (ORs) with 95% CIs, adjusting patient and hospital characteristics. The proportion of AF admissions for each season was similar, with the highest percentage of AF admissions being observed in the fall (spring 25%, summer 25%, fall 27%, and winter 24%). Overall, AF admissions across seasons were similar, with no seasonal variation observed. No seasonal variation was observed for incident AF. There were no seasonal differences in care quality (multivariable adjusted ORs and 95% CIs were 0.93 (0.87–1.00) for winter, 1.09 (1.01–1.18) for summer, and 1.08 (0.97–1.20) for fall, compared with spring). Conclusions In a nationwide quality improvement registry, no seasonal variation was observed in hospital admissions for AF or quality of care for AF.

Background Early administration of intravenous tissue plasminogen activator (IV alteplase) improves functional outcomes in patients with acute ischemic stroke, yet many patients are not treated with IV alteplase. There is a need to understand the reasons for nontreatment and the short‐ and long‐term outcomes in this patient population. Methods We analyzed patients ≥65 years old with a primary diagnosis of acute ischemic stroke presenting within 24 hours of time last known well (LKW) but not treated with IV alteplase from 1630 Get With The Guidelines‐Stroke hospitals in the United States between January 2016 and December 2016. We report clinical characteristics, reasons for withholding treatment, in‐hospital mortality, and 90‐day and 1‐year outcomes including costs, stratified by time from LKW to presentation (≤4.5, >4.5–6, and >6–24 hours). Results Of 39 760 patients (median age 80 [25th–75th quartiles: 73–87], 56.7% female), 19 391 (48.8%) presented within 4.5 hours of LKW. In those with documented reasons for withholding IV alteplase, the most common reasons were rapid improvement of symptoms (3985/14 782, 27.0%) and mild symptoms (3791/14 782, 25.6%). In 1100 out of 1174 (93.7%) patients presenting in the >3.0‐ to 4.5‐hour time window, the most common reason for not treating was a delay in patient arrival. The most common discharge location for those presenting ≤4.5 hours since LKW was home (8660/19 391, 44.7%). The 90‐day mortality and readmission rates were 18.9% and 23.0% in those presenting ≤4.5 hours since LKW, 19.0% and 22.2% in those presenting between 4.5 and 6 hours, and 19.1% and 23.2% in those presenting between 6 and 24 hours. Median 90‐day total in‐hospital costs remained relatively high at $9471 (Q25–Q75: $5622–$21 356) in patients presenting ≤4.5 hours since LKW. Conclusions Patients within the Get With The Guidelines‐Stroke registry not treated with IV alteplase have a high risk of readmission and mortality and have high total in‐hospital and postdischarge costs. This study may inform future efforts to address the unmet need to improve the scope of IV alteplase delivery along with other aspects of acute ischemic stroke care and, consequently, outcomes in this patient population.

Objective: Major bleeding is a common complication following treatment for an acute coronary syndrome (ACS) and is associated with increased mortality. We aimed to explore the temporal trend of bleeding events in relation to changes of therapeutic strategies among patients hospitalized for ACS in China.Methods: The CCC-ACS project (Improving Care for Cardiovascular Disease in China–Acute Coronary Syndrome) is a collaborative initiative of the American Heart Association and the Chinese Society of Cardiology. We analyzed 113,567 ACS patients from 241 hospitals in China from 2015 to 2019. Major bleeding was defined as intracranial bleeding, retroperitoneal bleeding, a decline in hemoglobin levels ≥3 g/dL, transfusion with overt bleeding, bleeding requiring surgical intervention, and fatal bleeding. Kruskal–Wallis test was used to examine the trend of major bleeding over time.Results: The rate of in-hospital major bleeding decreased from 6.3% in 2015 to 4.7% in 2019 (unadjusted OR = 0.74, 95% CI: 0.68–0.80, and P < 0.001). The relative changes were consistent across almost all subgroups including patients with NSTE-ACS and STEMI, although the trend was more pronounced in NSTE-ACS patients. The decrease in bleeding was accompanied by a decrease in use of GP IIb/IIIa inhibitors and parenteral anticoagulation therapy during hospitalization. The annual reduced risk of bleeding (OR = 0.91, 95% CI: 0.89–0.93) was attenuated after stepwise adjusting for baseline characteristics and antithrombotic treatments (OR = 0.95, 95% CI: 0.93–0.97), but did not change after adjusting for invasive treatment (OR = 0.95, 95% CI: 0.93–0.97).Conclusions: There was a temporal reduction in in-hospital bleeding among Chinese ACS patients during the last 5 years, which was associated with more evidence-based use of antithrombotic therapies.Clinical Trial Registration:https://www.clinicaltrials.gov, identifier: NCT02306616.

There are gaps in the use of therapies that save lives and improve quality of life for patients with heart failure with reduced ejection fraction, both in the US and abroad. The evidence is clear that initiation and titration of guideline-directed medical therapy (GDMT) and comprehensive disease-modifying medical therapy (CDMMT) to maximally tolerated doses improves patient-focused outcomes, yet observational data suggest this does not happen. The purpose of this review is to describe the gap in the use of optimal treatment worldwide and discuss the benefits of newer heart failure therapies including angiotensin receptor-neprilysin inhibitors and sodium-glucose cotransporter 2 inhibitors. It will also cover the efficacy and safety of such treatments and provide potential pathways for the initiation and rapid titration of GDMT/CDMMT.

Background Evidence suggests intracerebral hemorrhage survivors have earlier recovery compared with ischemic stroke survivors. The Centers for Medicare and Medicaid Services prospective payment system instituted documentation rules for inpatient rehabilitation facilities (IRFs) in 2010, with the goal of optimizing patient selection. We investigated whether these requirements limited IRF and increased skilled nursing facility (SNF) use compared with home discharge. Methods and Results Intracerebral hemorrhage discharges to IRF, SNF, or home were estimated using GWTG (Get With The Guidelines) Stroke registry data between January 1, 2008, and December 31, 2015 (n=265 444). Binary hierarchical models determined associations between the 2010 Rule and discharge setting; subgroup analyses evaluated age, geographic region, and hospital type. From January 1, 2008, to December 31, 2009, 45.5% of patients with intracerebral hemorrhage had home discharge, 22.2% went to SNF, and 32.3% went to IRF. After January 1, 2010, there was a 1.06% absolute increase in home discharge, a 0.46% increase in SNF, and a 1.52% decline in IRF. The adjusted odds of IRF versus home discharge decreased 3% after 2010 (adjusted odds ratio [aOR], 0.97; 95% CI, 0.95–1.00). Lower odds of IRF versus home discharge were observed in people aged

Background Sacubitril/Valsartan has been highly efficacious in randomized trials of heart failure with reduced ejection fraction (HFrEF). However, the effectiveness of sacubitril/valsartan in older patients hospitalized for HFrEF in real‐world US practice is unclear. Methods and Results This study included Medicare beneficiaries age ≥65 years who were hospitalized for HFrEF ≤40% in the Get With The Guidelines–Heart Failure registry between October 2015 and December 2018, and eligible for sacubitril/valsartan. Associations between discharge prescription of sacubitril/valsartan and clinical outcomes were assessed after inverse probability of treatment weighting and adjustment for other HFrEF medications. Overall, 1551 (10.9%) patients were discharged on sacubitril/valsartan. Of those not prescribed sacubitril/valsartan, 7857 (62.0%) were prescribed an angiotensin‐converting enzyme inhibitor/angiotensin II receptor blocker. Over 12‐month follow‐up, compared with a discharge prescription of angiotensin‐converting enzyme inhibitor/angiotensin II receptor blocker, sacubitril/valsartan was independently associated with lower all‐cause mortality (adjusted hazard ratio [HR], 0.82; 95% CI, 0.72–0.94; P=0.004) but not all‐cause hospitalization (adjusted HR, 0.97; 95% CI, 0.89–1.07; P=0.55) or heart failure hospitalization (adjusted HR, 1.04; 95% CI, 0.91–1.18; P=0.59). Patients prescribed sacubitril/valsartan versus those without a prescription had lower risk of all‐cause mortality (adjusted HR, 0.69; 95% CI, 0.60–0.79; P

Background Previous studies of patients with nontraumatic subarachnoid hemorrhage (SAH) suggest better outcomes at hospitals with higher case and procedural volumes, but the shape of the volume‐outcome curve has not been defined. We sought to establish minimum volume criteria for SAH and aneurysm obliteration procedures that could be used for comprehensive stroke center certification. Methods and Results Data from 8512 discharges in the National Inpatient Sample (NIS) from 2010 to 2011 were analyzed using logistic regression models to evaluate the association between clinical outcomes (in‐hospital mortality and the NIS‐SAH Outcome Measure [NIS‐SOM]) and measures of hospital annual case volume (nontraumatic SAH discharges, coiling, and clipping procedures). Sensitivity and specificity analyses for the association of desirable outcomes with different volume thresholds were performed. During 8512 SAH hospitalizations, 28.7% of cases underwent clipping and 20.1% underwent coiling with rates of 21.2% for in‐hospital mortality and 38.6% for poor outcome on the NIS‐SOM. The mean (range) of SAH, coiling, and clipping annual case volumes were 30.9 (1–195), 8.7 (0–94), and 6.1 (0–69), respectively. Logistic regression demonstrated improved outcomes with increasing annual case volumes of SAH discharges and procedures for aneurysm obliteration, with attenuation of the benefit beyond 35 SAH cases/year. Analysis of sensitivity and specificity using different volume thresholds confirmed these results. Analysis of previously proposed volume thresholds, including those utilized as minimum standards for comprehensive stroke center certification, showed that hospitals with more than 35 SAH cases annually had consistently superior outcomes compared with hospitals with fewer cases, although some hospitals below this threshold had similar outcomes. The adjusted odds ratio demonstrating lower risk of poor outcomes with SAH annual case volume ≥35 compared with 20 to 34 was 0.82 for the NIS‐SOM (95% CI, 0.71–094; P=0.0054) and 0.80 (95% CI, 0.68–0.93; P=0.0055) for in‐hospital mortality. Conclusions Outcomes for patients with SAH improve with increasing hospital case volumes and procedure volumes, with consistently better outcomes for hospitals with more than 35 SAH cases per year.