Association of cardiovascular diseases with cognitive performance in older adults.

BACKGROUND: Cognitive function and cardiovascular disease (CVD) have a bidirectional relationship, but studies on the impact of CVD subtypes and aging spectrum have been scarce. METHODS: We assessed older adults aged ≥60 years from the 2011 to 2012 and 2013 to 2014 cycles of the National Health and Nutrition Examination Survey who had coronary heart disease, angina, prior myocardial infarction, congestive heart failure, or prior stroke. We compared CERAD-IR, CERAD-DR, Animal Fluency test, and DSST scores to assess cognitive performance in older adults with and without CVD. RESULTS: We included 3,131 older adults, representing 55,479,673 older adults at the national level. Older adults with CVD had lower CERAD-IR (mean difference 1.8, 95% CI 1.4-2.1, P < .001), CERAD-DR (mean difference 0.8, 95% CI 0.6-1.0, P < .001), Animal Fluency test (mean difference 2.1, 95% CI 1.6-2.6, P < .001), and DSST (mean difference 9.5, 95% CI 8.0-10.9, P < .001) scores compared with those without CVD. After adjustment, no difference in CERAD-IR, CERAD-DR, and Animal Fluency test scores was observed, but DSST scores were lower in older adults with CVD (adjusted mean difference 2.9, 95% CI 1.1-4.7, P = .001). Across CVD subtypes, individuals with congestive heart failure had lower performance on the DSST score. The oldest-old cohort of patients ≥80 years old with CVD had lower performance than those without CVD on both the DSST and Animal Fluency test. CONCLUSION: Older adults with CVD had lower cognitive performance as measured than those free of CVD, driven by pronounced differences among those with CHF and those ≥80 years old with CVD.

Comparative analysis of treatment options for chronic heart failure and depression: a systematic review and Bayesian network meta-analysis.

Different interventions have been evaluated for the treatment of depression in heart failure (HF) patients. However, clear and established recommendations are lacking. PubMed, Scopus, and Web of Science databases were systematically searched for randomized controlled trials (RCT) evaluating the effect of various treatment options on depression scores in heart failure patients. The primary outcome was a change in depression scores presented as standardized mean difference (SMD). A Bayesian network for meta-analysis was constructed. Twenty-five RCTs were included, randomizing 6014 patients with confirmed heart failure and depression between 2003 and 2022. Compared to treatment as usual (TAU), only cognitive behavioral therapy (CBT) (SMD - 0.60, CI95% [- 1.0, - 0.17]) leads to a significant reduction in depression scores. Other interventions did not improve depression scores significantly. Our results show that for patients with HF and depression, CBT can significantly improve measures of depression, being the most efficacious treatment.

The management of heart failure cardiogenic shock: an international RAND appropriateness panel.

BACKGROUND: Observational data suggest that the subset of patients with heart failure related CS (HF-CS) now predominate critical care admissions for CS. There are no dedicated HF-CS randomised control trials completed to date which reliably inform clinical practice or clinical guidelines. We sought to identify aspects of HF-CS care where both consensus and uncertainty may exist to guide clinical practice and future clinical trial design, with a specific focus on HF-CS due to acute decompensated chronic HF. METHODS: A 16-person multi-disciplinary panel comprising of international experts was assembled. A modified RAND/University of California, Los Angeles, appropriateness methodology was used. A survey comprising of 34 statements was completed. Participants anonymously rated the appropriateness of each statement on a scale of 1 to 9 (1-3 as inappropriate, 4-6 as uncertain and as 7-9 appropriate). RESULTS: Of the 34 statements, 20 were rated as appropriate and 14 were rated as inappropriate. Uncertainty existed across all three domains: the initial assessment and management of HF-CS; escalation to temporary Mechanical Circulatory Support (tMCS); and weaning from tMCS in HF-CS. Significant disagreement between experts (deemed present when the disagreement index exceeded 1) was only identified when deliberating the utility of thoracic ultrasound in the immediate management of HF-CS. CONCLUSION: This study has highlighted several areas of practice where large-scale prospective registries and clinical trials in the HF-CS population are urgently needed to reliably inform clinical practice and the synthesis of future societal HF-CS guidelines.

Electronic Health Record Embedded Strategies for Improving Care of Patients With Heart Failure.

PURPOSE: A majority of clinical decisions use the electronic health record (EHR) and there is an unmet need to use its capability to help providers to make evidence-based decisions that improve care for heart failure patients. These electronic nudges are rooted in the human psychology of decision-making and often target specific cognitive biases. This review outlines the development of novel EHR nudges and specific lessons learned from each experience to inform the development of future interventions. RECENT FINDINGS: There have been several randomized clinical trials examining the impact of EHR alerts on quality of care for heart failure patients. These interventions have targeted both clinicians and patients. There are features of each trial that inform best practices and future directions for EHR nudges. Recent clinical trials have demonstrated that some EHR alerts can improve care for heart failure patients. These trials utilized default options, involved clinicians in the alert design process, provided actionable recommendations, and aimed to minimize disruptions to typical workflow. Alerts aimed at improving care should be examined in a randomized fashion in order to evaluate their impact on clinician satisfaction and patient care.

Venous thromboembolism among patients hospitalized with COVID-19 at Veterans Health Administration Hospitals.

Patients with coronavirus disease 2019 (COVID-19) are at heightened risk of venous thromboembolic events (VTE), though there is no data examining when these events occur following a COVID-19 diagnosis. We therefore sought to characterize the incidence, timecourse of events, and outcomes of VTE during the COVID-19 pandemic in a national healthcare system using data from Veterans Affairs Administration.

Contemporary Use of Venoarterial Extracorporeal Membrane Oxygenation: Insights from the Multicenter RESCUE Registry.

BACKGROUND: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used as a life-saving therapy for patients with cardiovascular collapse, but identifying patients unlikely to benefit remains a challenge. METHODS AND RESULTS: We created the RESCUE registry, a retrospective, observational registry of adult patients treated with VA-ECMO between January 2007 and June 2017 at 3 high-volume centers (Columbia University, Duke University, and Washington University) to describe short-term patient outcomes. In 723 patients treated with VA-ECMO, the most common indications for deployment were postcardiotomy shock (31%), cardiomyopathy (including acute heart failure) (26%), and myocardial infarction (17%). Patients frequently suffered in-hospital complications, including acute renal dysfunction (45%), major bleeding (41%), and infection (33%). Only 40% of patients (n = 290) survived to discharge, with a minority receiving durable cardiac support (left ventricular assist device [n = 48] or heart transplantation [n = 7]). Multivariable regression analysis identified risk factors for mortality on ECMO as older age (odds ratio [OR], 1.26; 95% confidence interval [CI], 1.12-1.42) and female sex (OR, 1.44; 95% CI, 1.02-2.02) and risk factors for mortality after decannulation as higher body mass index (OR 1.17; 95% CI, 1.01-1.35) and major bleeding while on ECMO support (OR, 1.92; 95% CI, 1.23-2.99). CONCLUSIONS: Despite contemporary care at high-volume centers, patients treated with VA-ECMO continue to have significant in-hospital morbidity and mortality. The optimization of outcomes will require refinements in patient selection and improvement of care delivery.

Cardiogenic Shock After Acute Myocardial Infarction: A Review.

IMPORTANCE: Cardiogenic shock affects between 40 000 and 50 000 people in the US per year and is the leading cause of in-hospital mortality following acute myocardial infarction. OBSERVATIONS: Thirty-day mortality for patients with cardiogenic shock due to myocardial infarction is approximately 40%, and 1-year mortality approaches 50%. Immediate revascularization of the infarct-related coronary artery remains the only treatment for cardiogenic shock associated with acute myocardial infarction supported by randomized clinical trials. The Percutaneous Coronary Intervention Strategies with Acute Myocardial Infarction and Cardiogenic Shock (CULPRIT-SHOCK) clinical trial demonstrated a reduction in the primary outcome of 30-day death or kidney replacement therapy; 158 of 344 patients (45.9%) in the culprit lesion revascularization-only group compared with 189 of 341 patients (55.4%) in the multivessel percutaneous coronary intervention group (relative risk, 0.83 [95% CI, 0.71-0.96]; P = .01). Despite a lack of randomized trials demonstrating benefit, percutaneous mechanical circulatory support devices are frequently used to manage cardiogenic shock following acute myocardial infarction. CONCLUSIONS AND RELEVANCE: Cardiogenic shock occurs in up to 10% of patients immediately following acute myocardial infarction and is associated with mortality rates of nearly 40% at 30 days and 50% at 1 year. Current evidence and clinical practice guidelines support immediate revascularization of the infarct-related coronary artery as the primary therapy for cardiogenic shock following acute myocardial infarction.

Assessment of cardiac allograft systolic function by global longitudinal strain: From donor to recipient.

BACKGROUND: Cardiac allografts are routinely evaluated by left ventricular ejection fraction (LVEF) before and after transplantation. However, myocardial deformation analyses with LV global longitudinal strain (GLS) are more sensitive for detecting impaired LV myocardial systolic performance compared with LVEF. METHODS: We analyzed echocardiograms in 34 heart donor-recipient pairs transplanted at Duke University from 2000 to 2013. Assessments of allograft LV systolic function by LVEF and/or LV GLS were performed on echocardiograms obtained pre-explanation in donors and serially in corresponding recipients. RESULTS: Donors had a median LVEF of 55% (25th, 75th percentile, 54% to 60%). Median donor LV GLS was -14.6% (-13.7 to -17.3%); LV GLS was abnormal (ie, >-16%) in 68% of donors. Post-transplantation, LV GLS was further impaired at 6 weeks (median -11.8%; -11.0 to -13.4%) and 3 months (median -11.4%; -10.3 to -13.9%) before recovering to pretransplant levels in follow-up. Median LVEF remained ≥50% throughout follow-up. We found no association between donor LV GLS and post-transplant outcomes, including all-cause hospitalization and mortality. CONCLUSIONS: GLS demonstrates allograft LV systolic dysfunction in donors and recipients not detected by LVEF. The clinical implications of subclinical allograft dysfunction detected by LV GLS require further study.

Safety of sodium-glucose cotransporter 2 inhibitors drugs among heart failure patients: a systematic review and meta-analysis.

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) reduce morbidity and mortality for heart failure (HF) patients and are recommended as cornerstones for their medical therapy. Utilization in clinical practice remains low for multiple reasons, one of which may be adverse events. We investigated the incidence of these events to see if they are associated with SGLT2i use. A systematic search was performed in databases, including PubMed, Embase, Cochrane Library, Clinicaltrials.gov, and WHO's International Clinical Trials Registry Platform. Relevant randomized controlled trial studies assessing the safety outcomes of SGLT2i in HF patients were included in this study. We conducted the common-effect meta-analysis to estimate the relative risk (RR) and 95% confidence interval (CI) of safety outcomes in SGLT2i compared with placebo. Eighteen studies were included in the meta-analysis composed of 12 925 HF patients taking an SGLT2i and 12 747 taking a placebo. The meta-analysis indicated that the all-cause mortality and serious adverse events (SAEs) were lower in the SGLT2i group (RR, 0.91; 95% CI, 0.85-0.97; P = 0.005, I2 = 0%; and RR, 0.92; 95% CI, 0.90-0.95; P < 0.001, I2 = 43%, respectively). Volume depletion and genitourinary infections were more prevalent in the SGLT2i group (RR, 1.17; 95% CI, 1.06-1.28; P = 0.001, I2 = 0%; and RR, 1.27; 95% CI, 1.13-1.43; P < 0.001, I2 = 17%, respectively). Our meta-analysis demonstrated that using SGLT2is in HF patients was correlated with reduced mortality and SAEs, with a more prominent effect in HF with reduced ejection fraction patients and those taking dapagliflozin.

Association Between Frailty and Management and Outcomes of Acute Myocardial Infarction Complicated by Cardiogenic Shock.

Background: Cardiogenic shock (CS) in the setting of acute myocardial infarction (AMI) is associated with high morbidity and mortality. Frailty is a common comorbidity in patients with cardiovascular disease and is also associated with adverse outcomes. The impact of preexisting frailty at the time of CS diagnosis following AMI has not been studied. Objectives: The purpose of this study was to examine the prevalence of frailty in patients admitted with AMI complicated by CS (AMI-CS) hospitalizations and its associations with in-hospital outcomes. Methods: We retrospectively analyzed the National Inpatient Sample from 2016 to 2020 and identified all hospitalizations for AMI-CS. We classified them into frail and nonfrail groups according to the hospital frailty risk score cut-off of 5 and compared in-hospital outcomes. Results: A total of 283,700 hospitalizations for AMI-CS were identified. Most (70.8%) occurred in the frail. Those with frailty had higher odds of in-hospital mortality (adjusted OR [aOR]: 2.17, 95% CI: 2.07 to 2.26, P < 0.001), do-not-resuscitate status, and discharge to a skilled nursing facility compared with those without frailty. They also had higher odds of in-hospital adverse events, including intracranial hemorrhage, gastrointestinal hemorrhage, acute kidney injury, and delirium. Importantly, AMI-CS hospitalizations in the frail had lower odds of coronary revascularization (aOR: 0.55, 95% CI: 0.53-0.58, P < 0.001) or mechanical circulatory support (aOR: 0.89, 95% CI: 0.85-0.93, P < 0.001). Lastly, hospitalizations for AMI-CS showed an overall increase from 53,210 in 2016 to 57,065 in 2020 (P trend <0.001), with this trend driven by a rise in the frail. Conclusions: A high proportion of hospitalizations for AMI-CS had concomitant frailty. Hospitalizations with AMI-CS and frailty had higher rates of in-hospital morbidity and mortality compared to those without frailty.

Prognostic Impact of Repeated NT-proBNP Measurements in Patients With Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Although clinical studies have demonstrated the association between a single N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurement and clinical outcomes in chronic heart failure, the biomarker is frequently measured serially in clinical practice. OBJECTIVES: The aim of this study was to determine the added prognostic value of repeated NT-proBNP measurements compared with single measurements alone for chronic heart failure patients. METHODS: In the GUIDE-IT (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure) study, 894 study participants with chronic heart failure with reduced ejection fraction were enrolled at 45 outpatient sites in the United States and Canada. Repeated NT-proBNP levels were measured over a 2-year study period. Associations between repeated NT-proBNP measurements and trial endpoints were assessed using a joint longitudinal and survival model. RESULTS: After adjustment for baseline covariates, each doubling of the baseline NT-proBNP level was associated with a HR of 1.17 (95% CI: 1.08-1.28; P = 0.0003) for the primary trial endpoint of cardiovascular death or heart failure hospitalization. Serial measurements increased the adjusted HR for the primary trial endpoint to 1.66 (95% CI: 1.50-1.84; P < 0.0001), and a similar increased risk was observed across secondary trial endpoints. In joint modeling, an increase in NT-proBNP occurred weeks before the onset of adjudicated events. CONCLUSIONS: Repeated NT-proBNP measurements are a strong predictor of outcomes in heart failure with reduced ejection fraction with an increase in concentration occurring well before event onset. These results may support routine NT-proBNP monitoring to assist in clinical decision making. (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure [GUIDE-IT]; NCT01685840).

Frailty and In-Hospital Outcomes for Management of Cardiogenic Shock without Acute Myocardial Infarction.

(1) Background: Cardiogenic shock (CS) is associated with high morbidity and mortality. Frailty and cardiovascular diseases are intertwined, commonly sharing risk factors and exhibiting bidirectional relationships. The relationship of frailty and non-acute myocardial infarction with cardiogenic shock (non-AMI-CS) is poorly described. (2) Methods: We retrospectively analyzed the National Inpatient Sample from 2016 to 2020 and identified all hospitalizations for non-AMI-CS. We classified them into frail and non-frail groups according to the hospital frailty risk score cut-off of 5 and compared in-hospital outcomes. (3) Results: A total of 503,780 hospitalizations for non-AMI-CS were identified. Most hospitalizations involved frail adults (80.0%). Those with frailty had higher odds of in-hospital mortality (adjusted odds ratio [aOR] 2.11, 95% confidence interval [CI] 2.03-2.20, p < 0.001), do-not-resuscitate status, and discharge to a skilled nursing facility compared with those without frailty. They also had higher odds of in-hospital adverse events, such as acute kidney injury, delirium, and longer length of stay. Importantly, non-AMI-CS hospitalizations in the frail group had lower use of mechanical circulatory support but not rates of cardiac transplantation. (4) Conclusions: Frailty is highly prevalent among non-AMI-CS hospitalizations. Those accompanied by frailty are often associated with increased rates of morbidity and mortality compared to those without frailty.

Patient Perspectives on Digital Interventions to Manage Heart Failure Medications: The VITAL-HF Pilot.

Use of guideline-directed medical therapy (GDMT) for treatment of heart failure with reduced ejection fraction (HFrEF) remains unacceptably low. The purpose of this study was to determine whether a digital health tool can augment GDMT for patients with HFrEF. Participants ≥ 18 years old with symptomatic HFrEF (left ventricular ejection fraction ≤ 40%) and with access to a mobile phone with internet were included. Participants were given a blood pressure cuff, instructed in its use, and given regular symptom surveys via cell-phone web-link. Data were transmitted to the Story Health web-based platform, and automated alerts were triggered based on pre-specified vital sign and laboratory data. Health coaches assisted patients with medication education, pharmacy access, and lab access through text messages and phone calls. GDMT titration plans were individually created in the digital platform by local clinicians based on entry vitals and labs. Twelve participants enrolled and completed the study. The median age and LVEF were 52.5 years (IQR, 46.5-63.5) and 25% (IQR, 22.5-35.5), respectively. There were 10 GDMT initiations, 52 up-titrations, and 13 down-titrations. Five participants engaged in focus-group interviews following study completion to understand first-hand perspectives regarding the use of digital tools to manage GDMT. Participants expressed comfort knowing that there were clinicians regularly reviewing their data. This alleviated concerns of uncertainty in daily living, led to an increased feeling of security, and empowered patients to understand decision-making regarding GDMT. Frequent medication changes, and the associated financial impact, were common concerns. Remote titration of GDMT for HFrEF is feasible and appears to be a patient-centered approach to care.

Network Meta-Analysis Comparing Angiotensin Receptor-Neprilysin Inhibitors, Angiotensin Receptor Blockers, and Angiotensin-Converting Enzyme Inhibitors in Heart Failure With Reduced Ejection Fraction.

The superiority of angiotensin receptor-neprilysin inhibitor (ARNI) over angiotensin-converting enzyme inhibitor (ACE-I) and angiotensin receptor blocker (ARB) has not been reassessed after the publication of recent trials that did not find clinical benefits. Therefore, we performed an updated network meta-analysis comparing the efficacy and safety of ARNI, ACE-I, ARB, and placebo in heart failure with reduced ejection fraction. We included randomized clinical trials that compared ARNI, ARB, ACE-I, and placebo in heart failure with reduced ejection fraction. We extracted prespecified efficacy end points and produced network estimates, p scores, and surface under the cumulative ranking curve scores using frequentist and Bayesian network meta-analysis approaches. A total of 28 randomized controlled trials including 47,407 patients were included. ARNI was associated with lower risk of all-cause mortality (relative risk [RR] 0.81, 95% confidence interval [CI] 0.68 to 0.96), cardiac death (RR 0.79, 95% CI 0.64 to 0.99), and major adverse cardiac events (MACEs; RR 0.83, 95% CI 0.72 to 0.97) but higher risk of hypotension (RR 1.46, 95% CI 1.02 to 2.10) than ARB. ARNI was associated with lower risk of MACE (RR 0.85, 95% CI 0.74 to 0.97), but higher risk of hypotension (RR 1.69, 95% CI 1.27 to 2.24) compared with ACE-I. P scores and surface under the cumulative ranking curve scores demonstrated superiority of ARNI over ARB and ACE-I in all-cause mortality, cardiac death, MACE, and hospitalization for heart failure. In conclusion, ARNI was associated with improved clinical outcomes, except for higher risk of hypotension, compared with ARB and ACE-I.

Use of Structured Electronic Health Records Data Elements for the Development of Computable Phenotypes to Identify Potential Adverse Events Associated with Intravenous Immunoglobulin Infusion.

INTRODUCTION: Detection of adverse reactions to drugs and biologic agents is an important component of regulatory approval and post-market safety evaluation. Real-world data, including insurance claims and electronic health records data, are increasingly used for the evaluation of potential safety outcomes; however, there are different types of data elements available within these data resources, impacting the development and performance of computable phenotypes for the identification of adverse events (AEs) associated with a given therapy. OBJECTIVE: To evaluate the utility of different types of data elements to the performance of computable phenotypes for AEs. METHODS: We used intravenous immunoglobulin (IVIG) as a model therapeutic agent and conducted a single-center, retrospective study of 3897 individuals who had at least one IVIG administration between 1 January 2014 and 31 December 2019. We identified the potential occurrence of four different AEs, including two proximal AEs (anaphylaxis and heart rate alterations) and two distal AEs (thrombosis and hemolysis). We considered three different computable phenotypes: (1) an International Classification of Disease (ICD)-based phenotype; (2) a phenotype-based on EHR-derived contextual information based on structured data elements, including laboratory values, medication administrations, or vital signs; and (3) a compound phenotype that required both an ICD code for the AE in combination with additional EHR-derived structured data elements. We evaluated the performance of each of these computable phenotypes compared with chart review-based identification of AEs, assessing the positive predictive value (PPV), specificity, and estimated sensitivity of each computable phenotype method. RESULTS: Compound computable phenotypes had a high positive predictive value for acute AEs such as anaphylaxis and bradycardia or tachycardia; however, few patients had both ICD codes and the relevant contextual data, which decreased the sensitivity of these computable phenotypes. In contrast, computable phenotypes for distal AEs (i.e., thrombotic events or hemolysis) frequently had ICD codes for these conditions in the absence of an AE due to a prior history of such events, suggesting that patient medical history of AEs negatively impacted the PPV of computable phenotypes based on ICD codes. CONCLUSIONS: These data provide evidence for the utility of different structured data elements in computable phenotypes for AEs. Such computable phenotypes can be used across different data sources for the detection of infusion-related adverse events.