Implementing a Clinical Decision Support Tool to Improve Physical Activity.

BACKGROUND: Currently, only about half of U.S. adults achieve current physical activity guidelines. Routine physical activity is not regularly assessed, nor are patients routinely counseled by their healthcare provider on achieving recommended levels. The three-question physical activity vital sign (PAVS) was developed to assess physical activity duration and intensity and identify adults not meeting physical activity guidelines. Clinical decision support provided via a best practice advisory in an electronic health record (EHR) system can be triggered as a prompt, reminding healthcare providers to implement the best practice intervention when appropriate. Remote patient monitoring of physical activity can provide objective data in the EHR. OBJECTIVES: This study aimed to evaluate the feasibility and clinical utility of embedding the PAVS and a triggered best practice advisor into the EHR in an ambulatory preventive cardiology practice setting to alert providers to patients reporting low physical activity and prompt healthcare providers to counsel these patients as needed. METHODS: Three components based in the EHR were integrated for the purpose of this study: Patients completed the PAVS through their electronic patient portal prior to an office visit, a best practice advisory was created to prompt providers to counsel patients who reported low levels of physical activity, and remote patient monitoring via Fitbit synced to the EHR provided objective physical activity data. The intervention was pilot-tested in the Epic EHR for 1 year (July 1, 2021 to June 30, 2022). Qualitative feedback on the intervention from both providers and patients was obtained at the completion of the study. RESULTS: Monthly assessments of the use of the PAVS and best practice advisory and remote patient monitoring were completed. Patients' completion of the PAVS varied from 35% to 48% per month. The best practice advisory was signed by providers between 2% and 65% and was acknowledged by 2%-22% per month. The majority (58%) of patients were able to sync a Fitbit device to their EHR for remote monitoring. DISCUSSION: Although uptake of each component needs improvement, this pilot demonstrated the feasibility of incorporating a physical activity promotion intervention into the EHR. Qualitative feedback provided guidance for future implementation.

Renin-Angiotensin-Aldosterone System Inhibitors and Risk of Covid-19.

BACKGROUND: There is concern about the potential of an increased risk related to medications that act on the renin-angiotensin-aldosterone system in patients exposed to coronavirus disease 2019 (Covid-19), because the viral receptor is angiotensin-converting enzyme 2 (ACE2). METHODS: We assessed the relation between previous treatment with ACE inhibitors, angiotensin-receptor blockers, beta-blockers, calcium-channel blockers, or thiazide diuretics and the likelihood of a positive or negative result on Covid-19 testing as well as the likelihood of severe illness (defined as intensive care, mechanical ventilation, or death) among patients who tested positive. Using Bayesian methods, we compared outcomes in patients who had been treated with these medications and in untreated patients, overall and in those with hypertension, after propensity-score matching for receipt of each medication class. A difference of at least 10 percentage points was prespecified as a substantial difference. RESULTS: Among 12,594 patients who were tested for Covid-19, a total of 5894 (46.8%) were positive; 1002 of these patients (17.0%) had severe illness. A history of hypertension was present in 4357 patients (34.6%), among whom 2573 (59.1%) had a positive test; 634 of these patients (24.6%) had severe illness. There was no association between any single medication class and an increased likelihood of a positive test. None of the medications examined was associated with a substantial increase in the risk of severe illness among patients who tested positive. CONCLUSIONS: We found no substantial increase in the likelihood of a positive test for Covid-19 or in the risk of severe Covid-19 among patients who tested positive in association with five common classes of antihypertensive medications.

Design and pilot implementation for the BETTER CARE-HF trial: A pragmatic cluster-randomized controlled trial comparing two targeted approaches to ambulatory clinical decision support for cardiologists.

BACKGROUND: Beart failure with reduced ejection fraction (HFrEF) is a leading cause of morbidity and mortality. However, shortfalls in prescribing of proven therapies, particularly mineralocorticoid receptor antagonist (MRA) therapy, account for several thousand preventable deaths per year nationwide. Electronic clinical decision support (CDS) is a potential low-cost and scalable solution to improve prescribing of therapies. However, the optimal timing and format of CDS tools is unknown. METHODS AND RESULTS: We developed two targeted CDS tools to inform cardiologists of gaps in MRA therapy for patients with HFrEF and without contraindication to MRA therapy: (1) an alert that notifies cardiologists at the time of patient visit, and (2) an automated electronic message that allows for review between visits. We designed these tools using an established CDS framework and findings from semistructured interviews with cardiologists. We then pilot tested both CDS tools (n = 596 patients) and further enhanced them based on additional semistructured interviews (n = 11 cardiologists). The message was modified to reduce the number of patients listed, include future visits, and list date of next visit. The alert was modified to improve noticeability, reduce extraneous information on guidelines, and include key information on contraindications. CONCLUSIONS: The BETTER CARE-HF (Building Electronic Tools to Enhance and Reinforce CArdiovascular REcommendations for Heart Failure) trial aims to compare the effectiveness of the alert vs. the automated message vs. usual care on the primary outcome of MRA prescribing. To our knowledge, no study has directly compared the efficacy of these two different types of electronic CDS interventions. If effective, our findings can be rapidly disseminated to improve morbidity and mortality for patients with HFrEF, and can also inform the development of future CDS interventions for other disease states. (Trial registration: Clinicaltrials.gov NCT05275920).

An Evaluation of Alternative Technology-Supported Counseling Approaches to Promote Multiple Lifestyle Behavior Changes in Patients With Type 2 Diabetes and Chronic Kidney Disease.

OBJECTIVES: Although technology-supported interventions are effective for reducing chronic disease risk, little is known about the relative and combined efficacy of mobile health strategies aimed at multiple lifestyle factors. The purpose of this clinical trial is to evaluate the efficacy of technology-supported behavioral intervention strategies for managing multiple lifestyle-related health outcomes in overweight adults with type 2 diabetes (T2D) and chronic kidney disease (CKD). DESIGN AND METHODS: Using a 2 × 2 factorial design, adults with excess body weight (body mass index ≥27 kg/m2, age ≥40 years), T2D, and CKD stages 2-4 were randomized to an advice control group, or remotely delivered programs consisting of synchronous group-based education (all groups), plus (1) Social Cognitive Theory-based behavioral counseling and/or (2) mobile self-monitoring of diet and physical activity. All programs targeted weight loss, greater physical activity, and lower intakes of sodium and phosphorus-containing food additives. RESULTS: Of 256 randomized participants, 186 (73%) completed 6-month assessments. Compared to the ADVICE group, mHealth interventions did not result in significant changes in weight loss, or urinary sodium and phosphorus excretion. In aggregate analyses, groups receiving mobile self-monitoring had greater weight loss at 3 months (P = .02), but between 3 and 6 months, weight losses plateaued, and by 6 months, the differences were no longer statistically significant. CONCLUSIONS: When engaging patients with T2D and CKD in multiple behavior changes, self-monitoring diet and physical activity demonstrated significantly larger short-term weight losses. Theory-based behavioral counseling alone was no better than baseline advice and demonstrated no interaction effect with self-monitoring.

The Impact of an Electronic Best Practice Advisory on Patients' Physical Activity and Cardiovascular Risk Profile.

BACKGROUND: Regular physical activity (PA) is a component of cardiovascular health and is associated with a lower risk of cardiovascular disease (CVD). However, only about half of US adults achieved the current PA recommendations. OBJECTIVE: The study purpose was to implement PA counseling using a clinical decision support tool in a preventive cardiology clinic and to assess changes in CVD risk factors in a sample of patients enrolled over 12 weeks of PA monitoring. METHODS: This intervention, piloted for 1 year, had 3 components embedded in the electronic health record: assessment of patients' PA, an electronic prompt for providers to counsel patients reporting low PA, and patient monitoring using a Fitbit. Cardiovascular disease risk factors included PA (self-report and Fitbit), body mass index, blood pressure, lipids, and cardiorespiratory fitness assessed with the 6-minute walk test. Depression and quality of life were also assessed. Paired t tests assessed changes in CVD risk. RESULTS: The sample who enrolled in the remote patient monitoring (n = 59) were primarily female (51%), White adults (76%) with a mean age of 61.13 ± 11.6 years. Self-reported PA significantly improved over 12 weeks (P = .005), but not Fitbit steps (P = .07). There was a significant improvement in cardiorespiratory fitness (469 ± 108 vs 494 ± 132 m, P = .0034), and 23 participants (42%) improved at least 25 m, signifying a clinically meaningful improvement. Only 4 participants were lost to follow-up over 12 weeks of monitoring. CONCLUSIONS: Patients may need more frequent reminders to be active after an initial counseling session, perhaps getting automated messages based on their step counts syncing to their electronic health record.

Missed opportunities in medical therapy for patients with heart failure in an electronically-identified cohort.

BACKGROUND: National registries reveal significant gaps in medical therapy for patients with heart failure and reduced ejection fraction (HFrEF), but may not accurately (or fully) characterize the population eligible for therapy. OBJECTIVE: We developed an automated, electronic health record-based algorithm to identify HFrEF patients eligible for evidence-based therapy, and extracted treatment data to assess gaps in therapy in a large, diverse health system. METHODS: In this cross-sectional study of all NYU Langone Health outpatients with EF ≤ 40% on echocardiogram and an outpatient visit from 3/1/2019 to 2/29/2020, we assessed prescription of the following therapies: beta-blocker (BB), angiotensin converting enzyme inhibitor (ACE-I)/angiotensin receptor blocker (ARB)/angiotensin receptor neprilysin inhibitor (ARNI), and mineralocorticoid receptor antagonist (MRA). Our algorithm accounted for contraindications such as medication allergy, bradycardia, hypotension, renal dysfunction, and hyperkalemia. RESULTS: We electronically identified 2732 patients meeting inclusion criteria. Among those eligible for each medication class, 84.8% and 79.7% were appropriately prescribed BB and ACE-I/ARB/ARNI, respectively, while only 23.9% and 22.7% were appropriately prescribed MRA and ARNI, respectively. In adjusted models, younger age, cardiology visit and lower EF were associated with increased prescribing of medications. Private insurance and Medicaid were associated with increased prescribing of ARNI (OR = 1.40, 95% CI = 1.02-2.00; and OR = 1.70, 95% CI = 1.07-2.67). CONCLUSIONS: We observed substantial shortfalls in prescribing of MRA and ARNI therapy to ambulatory HFrEF patients. Subspecialty care setting, and Medicaid insurance were associated with higher rates of ARNI prescribing. Further studies are warranted to prospectively evaluate provider- and policy-level interventions to improve prescribing of these evidence-based therapies.

Vascular endothelium as a target for perfluroalkyl substances (PFAs).

INTRODUCTION: Perfluoroalkyl substances (PFAs) are ubiquitous, anthropogenic organic compounds that have been linked with cardiovascular disease and cardiovascular risk factors. Older, long-chain PFAs have been phased out due to adverse cardiometabolic health effect and replaced by newer short-chain PFAs. However, emerging research suggests that short-chain PFAs may also have adverse cardiovascular effects. Non-invasive measures of vascular function can detect preclinical cardiovascular disease and serve as a useful surrogate for early CVD risk. We hypothesized that serum concentrations of PFAs would be associated with noninvasive measures of vascular function, carotid-femoral pulse wave velocity (PWV) and brachial artery reactivity testing (BART), in adults with non-occupational exposure to PFAs. METHODS: We measured serum concentrations of 14 PFAs with hybrid solid-phase extraction and ultrahigh-performance liquid chromatography-tandem mass spectrometry in 94 adult outpatients with no known cardiovascular disease. We collected clinical and demographic data; and measured vascular function, PWV and BART, using standard protocols. We assessed associations of individual PFAs with log-transformed BART and PWV using linear regression. We used weighted quantile sum regression to assess effects of correlated PFA mixtures on BART and PWV. RESULTS: Ten PFAs were measured above the limit of detection in >50% of participants. Each standard deviation increase in concentration of perfluoroheptanoic acid (PFHpA) was associated with 15% decrease in BART (95% CI: -28.5, -0.17). The weighted index of a mixture of PFAs with correlated concentrations was inversely associated with BART: each tertile increase in the weighted PFA mixture was associated with 25% lower BART, with 73% of the effect driven by PFHpA. In contrast, no PFAs or mixtures were associated with PWV. CONCLUSIONS: Serum concentration of PFHpA, a new, short-chain PFA, was associated with impaired vascular function among outpatients without CVD. Our findings support a potential adverse cardiovascular effect of newer, short-chain PFAs.

Factors Associated With Cognitive Impairment in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Cognitive impairment is prevalent in heart failure and is associated with higher mortality rates. The mechanism behind cognitive impairment in heart failure with preserved ejection fraction (HFpEF) has not been established. OBJECTIVE: The aim of this study was to evaluate associations between abnormal cardiac hemodynamics and cognitive impairment in individuals with HFpEF. METHODS: A secondary analysis of Atherosclerosis Risk in Communities (Atherosclerosis Risk in Communities) study data was performed. Participants free of stroke or dementia who completed in-person assessments at visit 5 were included. Neurocognitive test scores among participants with HFpEF, heart failure with reduced ejection fraction (HFrEF), and no heart failure were compared. Sociodemographics, comorbid illnesses, medications, and echocardiographic measures of cardiac function that demonstrated significant (P < .10) bivariate associations with neurocognitive test scores were included in multivariate models to identify predictors of neurocognitive test scores among those with HFpEF. Multiple imputation by chained equations was used to account for missing values. RESULTS: Scores on tests of attention, language, executive function, and global cognitive function were worse among individuals with HFpEF than those with no heart failure. Neurocognitive test scores were not significantly different among participants with HFpEF and HFrEF. Worse diastolic function was weakly associated with worse performance in memory, attention, and language. Higher cardiac index was associated with worse performance on 1 test of attention. CONCLUSIONS: Cognitive impairment is prevalent in HFpEF and affects several cognitive domains. The current study supports the importance of cognitive screening in patients with heart failure. An association between abnormal cardiac hemodynamics and cognitive impairment was observed, but other factors are likely involved.

Missed Opportunities in Identifying Cardiomyopathy Aetiology Prior to Advanced Heart Failure Therapy.

BACKGROUND: Specific aetiologies of cardiomyopathy can significantly impact treatment options as well as appropriateness and prioritisation for advanced heart failure therapies such as ventricular assist device (VAD) or orthotopic heart transplantation (OHT). We reviewed the tissue diagnoses of patients who underwent advanced therapies for heart failure (HF) to identify diagnostic discrepancies. METHODS: This study presents a retrospective cohort of the aetiology of cardiomyopathy in 118 patients receiving either durable VAD or OHT. Discrepancies between the preoperative aetiological diagnosis of cardiomyopathy with the pathological diagnosis were recorded. Echocardiographic and haemodynamic data were reviewed to examine differences in patients with differing aetiological diagnoses. RESULTS: Twelve (12) of 118 (12/118) (10.2%) had a pathological diagnosis that was discordant with pre-surgical diagnosis. The most common missed diagnoses were infiltrative cardiomyopathy (5) and hypertrophic cardiomyopathy (3). Patients with misidentified aetiology of cardiomyopathy had smaller left ventricular (LV) dimensions on echocardiography than patients with dilated cardiomyopathy (5.8±0.9 vs 6.7±1.1 respectively p=0.01). CONCLUSIONS: Most HF patients undergoing VAD and OHT had a correct diagnosis for their heart failure prior to treatment, but a missed diagnosis at time of intervention (VAD or OHT) was not uncommon. Smaller LV dimension on echocardiogram in a patient with a non-ischaemic cardiomyopathy warrants further workup for a more specific aetiology.

COVID-19 and the Heart and Vasculature: Novel Approaches to Reduce Virus-Induced Inflammation in Patients With Cardiovascular Disease.

The coronavirus disease 2019 (COVID-19) pandemic presents an unprecedented challenge and opportunity for translational investigators to rapidly develop safe and effective therapeutic interventions. Greater risk of severe disease in COVID-19 patients with comorbid diabetes mellitus, obesity, and heart disease may be attributable to synergistic activation of vascular inflammation pathways associated with both COVID-19 and cardiometabolic disease. This mechanistic link provides a scientific framework for translational studies of drugs developed for treatment of cardiometabolic disease as novel therapeutic interventions to mitigate inflammation and improve outcomes in patients with COVID-19.

Dapagliflozin Effects on Biomarkers, Symptoms, and Functional Status in Patients With Heart Failure With Reduced Ejection Fraction: The DEFINE-HF Trial.

BACKGROUND: Outcome trials in patients with type 2 diabetes mellitus have demonstrated reduced hospitalizations for heart failure (HF) with sodium-glucose co-transporter-2 inhibitors. However, few of these patients had HF, and those that did were not well-characterized. Thus, the effects of sodium-glucose co-transporter-2 inhibitors in patients with established HF with reduced ejection fraction, including those with and without type 2 diabetes mellitus, remain unknown. METHODS: DEFINE-HF (Dapagliflozin Effects on Biomarkers, Symptoms and Functional Status in Patients with HF with Reduced Ejection Fraction) was an investigator-initiated, multi-center, randomized controlled trial of HF patients with left ventricular ejection fraction ≤40%, New York Heart Association (NYHA) class II-III, estimated glomerular filtration rate ≥30 mL/min/1.73m2, and elevated natriuretic peptides. In total, 263 patients were randomized to dapagliflozin 10 mg daily or placebo for 12 weeks. Dual primary outcomes were (1) mean NT-proBNP (N-terminal pro b-type natriuretic peptide) and (2) proportion of patients with ≥5-point increase in HF disease-specific health status on the Kansas City Cardiomyopathy Questionnaire overall summary score, or a ≥20% decrease in NT-proBNP. RESULTS: Patient characteristics reflected stable, chronic HF with reduced ejection fraction with high use of optimal medical therapy. There was no significant difference in average 6- and 12-week adjusted NT-proBNP with dapagliflozin versus placebo (1133 pg/dL (95% CI 1036-1238) vs 1191 pg/dL (95% CI 1089-1304), P=0.43). For the second dual-primary outcome of a meaningful improvement in Kansas City Cardiomyopathy Questionnaire overall summary score or NT-proBNP, 61.5% of dapagliflozin-treated patients met this end point versus 50.4% with placebo (adjusted OR 1.8, 95% CI 1.03-3.06, nominal P=0.039). This was attributable to both higher proportions of patients with ≥5-point improvement in Kansas City Cardiomyopathy Questionnaire overall summary score (42.9 vs 32.5%, adjusted OR 1.73, 95% CI 0.98-3.05), and ≥20% reduction in NT-proBNP (44.0 vs 29.4%, adjusted OR 1.9, 95% CI 1.1-3.3) by 12 weeks. Results were consistent among patients with or without type 2 diabetes mellitus, and other prespecified subgroups (all P values for interaction=NS). CONCLUSIONS: In patients with heart failure and reduced ejection fraction, use of dapagliflozin over 12 weeks did not affect mean NT-proBNP but increased the proportion of patients experiencing clinically meaningful improvements in HF-related health status or natriuretic peptides. Benefits of dapagliflozin on clinically meaningful HF measures appear to extend to patients without type 2 diabetes mellitus. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02653482.

Coronary artery bypass grafting versus percutaneous coronary intervention for myocardial infarction complicated by cardiogenic shock.

BACKGROUND: Myocardial infarction (MI) complicated by cardiogenic shock (CS) is associated with high mortality. Early coronary revascularization improves survival, but the optimal mode of revascularization remains uncertain. We sought to characterize practice patterns and outcomes of coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) in patients with MI complicated by CS. METHODS: Patients hospitalized for MI with CS between 2002 and 2014 were identified from the United States National Inpatient Sample. Trends in management were evaluated over time. Propensity score matching was performed to identify cohorts with similar baseline characteristics and MI presentations who underwent PCI and CABG. The primary outcome was in-hospital all-cause mortality. RESULTS: A total of 386,811 hospitalizations for MI with CS were identified; 67% were STEMI. Overall, 62.4% of patients underwent revascularization, with PCI in 44.9%, CABG in 14.1%, and a hybrid approach in 3.4%. Coronary revascularization for MI and CS increased over time, from 51.5% in 2002 to 67.4% in 2014 (P for trend < .001). Patients who underwent CABG were more likely to have diabetes mellitus (35.5% vs. 29.2%, P < .001) and less likely to present with STEMI (48.7% vs. 80.9%, P < .001) than those who underwent PCI. CABG (without PCI) was associated with lower mortality than PCI (without CABG) overall (18.9% vs. 29.0%, P < .001) and in a propensity-matched subgroup of 19,882 patients (19.0% vs. 27.0%, P < .001). CONCLUSIONS: CABG was associated with lower in-hospital mortality than PCI among patients with MI complicated by CS. Due to the likelihood of residual confounding, a randomized trial of PCI versus CABG in patients with MI, CS, and multi-vessel coronary disease is warranted.

Coronary revascularization and circulatory support strategies in patients with myocardial infarction, multi-vessel coronary artery disease, and cardiogenic shock: Insights from an international survey.

Cardiogenic shock (CS) complicating acute myocardial infarction (MI) is associated with high mortality. In the absence of data to support coronary revascularization beyond the infarct artery and selection of circulatory support devices or medications, clinical practice may vary substantially. METHODS: We distributed a survey to interventional cardiologists and cardiothoracic surgeons through relevant professional societies to determine contemporary coronary revascularization and circulatory support strategies for MI with CS and multi-vessel coronary artery disease (CAD). RESULTS: A total of 143 participants completed the survey between 1/2019 and 8/2019. Overall, 55.2% of participants reported that the standard approach to coronary revascularization was single vessel PCI of the infarct related artery (IRA) with staged PCI of non-culprit lesions. Single vessel PCI of the IRA only (28.0%), emergency multi-vessel PCI (11.9%), and coronary artery bypass grafting (CABG) (4.9%) were standard approaches at some centers. A plurality of survey respondents (46.9%) believed initial PCI with staged CABG for multi-vessel CAD would be associated with the most favorable outcomes. A minority of respondents believed PCI-only strategies (23.1%) and CABG alone (6.3%) provided optimal care, and 23.1% were unsure of the best strategy. After PCI for CS, Impella (76.9%), intra-aortic balloon pump (IABP) (12.8%), and extra-corporeal membrane oxygenation (ECMO) (7.7%) were preferred. After CABG, IABP (34.3%), Impella (32.2%), and ECMO (28%) were preferred. CONCLUSIONS: This survey indicates substantial heterogeneity in clinical care in CS. There is evidence of provider uncertainty and clinical equipoise regarding the optimal management of patients with MI, multi-vessel CAD, and CS. SHORT ABSTRACT: We sought to determine contemporary practice patterns of coronary revascularization and circulatory support in patients with MI, multi-vessel coronary artery disease (CAD), and cardiogenic shock. A survey was distributed to interventional cardiologists and cardiothoracic surgeons through relevant professional societies. Survey respondents identified substantial heterogeneity in clinical care and evidence of provider uncertainty and clinical equipoise regarding the optimal management of patients with MI, multi-vessel CAD, and CS.

Identification of Patients with Heart Failure in Large Datasets.

Large registries, administrative data, and the electronic health record (EHR) offer opportunities to identify patients with heart failure, which can be used for research purposes, process improvement, and optimal care delivery. Identification of cases is challenging because of the heterogeneous nature of the disease, which encompasses various phenotypes that may respond differently to treatment. The increasing availability of both structured and unstructured data in the EHR has expanded opportunities for cohort construction. This article reviews the current literature on approaches to identification of heart failure, and looks toward the future of machine learning, big data, and phenomapping.

Mineralocorticoid receptor antagonist use after hospitalization of patients with heart failure and post-discharge outcomes: a single-center retrospective cohort study.

BACKGROUND: Mineralocorticoid receptor antagonists (MRA) are an underutilized therapy for heart failure with a reduced ejection fraction (HFrEF), but the current impact of hospitalization on MRA use is not well characterized. The objective of this study was to describe contemporary MRA prescription for heart failure patients before and after the full scope of hospitalizations and the association between MRA discharge prescription and post-hospitalization outcomes. METHODS: We conducted a retrospective cohort study at an academic hospital system in 2013-2016. Among 1500 included hospitalizations of 1009 unique patients with HFrEF and without MRA contraindication, the mean age was 71.9 ± 13.6 years and 443 (29.5%) were female. We compared MRA prescription before and after hospitalizations with McNemar's test and between patients with principal and secondary diagnoses of HFrEF with the chi-square test, and association of MRA discharge prescription with 30-day and 180-day mortality and readmissions using generalized estimating equations. RESULTS: MRA prescriptions increased from 303 (20.2%) to 375 (25.0%) at discharge (+4.8%, p < 0.0001). More patients with principal diagnosis of HFrEF compared to those hospitalized for other reasons received MRA (34.9% versus 21.3%, p < 0.0001) and had them initiated (21.8% versus 9.7%, p < 0.0001). MRA prescription at discharge was not associated with mortality or readmission at 30 and 180 days, and there was no interaction with principal/secondary diagnosis. CONCLUSIONS: Among hospitalized HFrEF patients, 75% did not receive MRA before or after hospitalization, and nearly 90% of eligible patients did not have MRA initiated. As we found no signal for short-term harm after discharge, hospitalization may represent an opportunity to initiate guideline-directed heart failure therapy.

Diagnosis and treatment of heart failure in hereditary transthyretin amyloidosis.

Amyloidosis describes a family of related disease states associated with the extracellular tissue deposition of fibrils composed of low-molecular-weight subunits of a variety of proteins circulating as constituents of plasma. Depending on the disease subtype, fibrillar deposits in a several organs including the heart, kidney, liver, and peripheral nerves cause organ dysfunction and associated morbidity and mortality. The most common amyloid fibril deposits associated with cardiac manifestations are of monoclonal light-chain or transthyretin (ATTR) types. This review will focus on the ATTR types of cardiac amyloidosis. ATTR amyloidosis may be associated with abnormal metabolism of wild-type transthyretin (previously called senile systemic amyloidosis) or with hereditary variants in the transthyretin gene. Cardiac amyloidosis is often under-recognized in its early stages, and when a diagnosis of cardiac amyloidosis is made, patients are often at the advanced stages of the disease. Treatments now available appear to exert their benefit predominantly in individuals with the early stages of disease. Increased awareness and early diagnosis of cardiac amyloidosis and continued discovery of effective therapies will increase opportunities to improve clinical outcomes in this patient population.

Early Identification of Patients With Acute Decompensated Heart Failure.

BACKGROUND: Interventions to reduce readmissions after acute heart failure hospitalization require early identification of patients. The purpose of this study was to develop and test accuracies of various approaches to identify patients with acute decompensated heart failure (ADHF) with the use of data derived from the electronic health record. METHODS AND RESULTS: We included 37,229 hospitalizations of adult patients at a single hospital during 2013-2015. We developed 4 algorithms to identify hospitalization with a principal discharge diagnosis of ADHF: 1) presence of 1 of 3 clinical characteristics, 2) logistic regression of 31 structured data elements, 3) machine learning with unstructured data, and 4) machine learning with the use of both structured and unstructured data. In data validation, algorithm 1 had a sensitivity of 0.98 and positive predictive value (PPV) of 0.14 for ADHF. Algorithm 2 had an area under the receiver operating characteristic curve (AUC) of 0.96, and both machine learning algorithms had AUCs of 0.99. Based on a brief survey of 3 providers who perform chart review for ADHF, we estimated that providers spent 8.6 minutes per chart review; using this this parameter, we estimated that providers would spend 61.4, 57.3, 28.7, and 25.3 minutes on secondary chart review for each case of ADHF if initial screening were done with algorithms 1, 2, 3, and 4, respectively. CONCLUSIONS: Machine learning algorithms with unstructured notes had the best performance for identification of ADHF and can improve provider efficiency for delivery of quality improvement interventions.

Right Ventricular Dysfunction in Acute Myocardial Infarction Complicated by Cardiogenic Shock: A Hemodynamic Analysis of the Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock (SHOCK) Trial and Registry.

BACKGROUND: The prevalence and significance of right ventricular dysfunction (RVD) in patients with cardiogenic shock due to acute myocardial infarction (AMI-CS) have not been well characterized. We hypothesized that RVD is common in AMI-CS and associated with worse clinical outcomes. METHODS AND RESULTS: We retrospectively analyzed patients with available hemodynamics enrolled in the Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock (SHOCK) trial (n = 139) and registry (n = 258) to identify RVD in AMI-CS. RVD was defined by an elevated central venous pressure (CVP), elevated CVP-pulmonary capillary wedge pressure (PCWP) ratio, decreased pulmonary artery pulsatility index, and decreased right ventricular stroke work index. A P value of <.01 was used to infer significance. In the SHOCK trial and registry, respectively, 38% and 37% of patients had RVD, but RVD was not associated with 30-day or 6-month survival (hazard ratio [HR] 1.51, (99% CI 0.92-2.49; P = .10). RV failure with the use of inclusion criteria from the Recover Right Trial for RV Failure (RR-RVF) requiring percutaneous mechanical circulatory support included elevated CVP and CVP/PCWP and a low cardiac index despite ≥1 inotrope or vasopressor. In the SHOCK trial and registry, respectively, 45% (n = 63/139) and 38% (n = 98/258) of patients met RR-RVF criteria. The RR-RVF criteria were not significantly associated with 30-day mortality in the registry cohort (HR 1.44, 99% CI 1.01-2.04; P = .04), or in the trial cohort (HR 1.51, 99% CI 0.92-2.49; P = .10). CONCLUSIONS: Hemodynamically defined RVD is common in AMI-CS. Routine assessment with pulmonary artery catherization allows detection of RVD; however, further work is needed to identify interventions that will result in improved outcomes for these patients.

Norepinephrine deficiency with normal blood pressure control in congenital insensitivity to pain with anhidrosis.

OBJECTIVE: Congenital insensitivity to pain with anhidrosis (CIPA) is caused by mutations in the NKTR1 gene. This affects the development of nerve growth factor (NGF)-dependent neurons including sympathetic cholinergic neurons in the skin, causing anhidrosis. Cardiovascular and blood pressure regulation appears normal, but the integrity of sympathetic adrenergic neurons has not been tested. METHODS: We examined the effect of posture on blood pressure, heart rate, plasma concentration of catecholamines, vasopressin, endothelin, and renin activity in 14 patients with CIPA, 10 patients with chronically deficient sympathetic activity (pure autonomic failure), and 15 normal age-matched controls. RESULTS: In all 14 patients with CIPA, plasma norepinephrine levels were very low or undetectable and failed to increase when the patient was upright, yet upright blood pressure was well maintained. Plasma epinephrine levels were normal and increased when the patient was upright. Plasma renin activity also increased appropriately when the patient was upright and after furosemide-induced volume depletion. Nitric oxide-mediated endothelial function was intact. Patients with pure autonomic failure also had very low levels of plasma norepinephrine both supine and upright, but in contrast to patients with CIPA failed to maintain blood pressure upright. INTERPRETATION: The results indicate that postganglionic sympathetic neurons are severely depleted in CIPA, but chromaffin cells of the adrenal medulla are spared. This confirms the differential effect of NGF signaling for sympathetic neural and chromaffin cell development. The finding that patients with CIPA maintain blood pressure well on standing challenges current concepts of the role of norepinephrine in the regulation of arterial pressure.