Frailty in the Cardiac Intensive Care Unit: Assessment and Impact.

Frailty, a clinical syndrome of increased vulnerability, due to diminished cognitive, physical, and physiological reserves is a growing concern in the cardiac intensive care unit (CICU). It contributes to morbidity, mortality, and complications and often exerts a bidirectional association with cardiovascular disease. Althought it predominately affects older adults, frailty can also be observed in younger patients less than 65 years of age, with approximately 30% of those admitted CICU are frail. Acute cardiovascular illness can also impair physical and cognitive functioning among survivors and these survivors often suffer from frailty and functional declines post-CICU discharge. Patients with frailty in the CICU often have higher comorbidity burden and they are less likely to receive optimal therapy for their acute cardiovascular conditions. Given the significance of this geriatric syndrome, this review will focus on assessment, clinical outcomes, and interventions, in an attempt to establish appropriate assessment, management, and resource utilization in frail patients during and after CICU admission.

Role of Cognitive Frailty in Older Adults With Cardiovascular Disease.

As the older adult population expands, an increasing number of patients affected by geriatric syndromes are seen by cardiovascular clinicians. One such syndrome that has been associated with poor outcomes is cognitive frailty: the simultaneous presence of cognitive impairment, without evidence of dementia, and physical frailty, which results in decreased cognitive reserve. Driven by common pathophysiologic underpinnings (eg, inflammation and neurohormonal dysregulation), cardiovascular disease, cognitive impairment, and frailty also share the following risk factors: hypertension, diabetes, obesity, sedentary behavior, and tobacco use. Cardiovascular disease has been associated with the onset and progression of cognitive frailty, which may be reversible in early stages, making it essential for clinicians to diagnose the condition in a timely manner and prescribe appropriate interventions. Additional research is required to elucidate the mechanisms underlying the development of cognitive frailty, establish preventive and therapeutic strategies to address the needs of older patients with cardiovascular disease at risk for cognitive frailty, and ultimately facilitate targeted intervention studies.

Machine Learning Multicenter Risk Model to Predict Right Ventricular Failure After Mechanical Circulatory Support: The STOP-RVF Score.

Importance: The existing models predicting right ventricular failure (RVF) after durable left ventricular assist device (LVAD) support might be limited, partly due to lack of external validation, marginal predictive power, and absence of intraoperative characteristics. Objective: To derive and validate a risk model to predict RVF after LVAD implantation. Design, Setting, and Participants: This was a hybrid prospective-retrospective multicenter cohort study conducted from April 2008 to July 2019 of patients with advanced heart failure (HF) requiring continuous-flow LVAD. The derivation cohort included patients enrolled at 5 institutions. The external validation cohort included patients enrolled at a sixth institution within the same period. Study data were analyzed October 2022 to August 2023. Exposures: Study participants underwent chronic continuous-flow LVAD support. Main Outcome and Measures: The primary outcome was RVF incidence, defined as the need for RV assist device or intravenous inotropes for greater than 14 days. Bootstrap imputation and adaptive least absolute shrinkage and selection operator variable selection techniques were used to derive a predictive model. An RVF risk calculator (STOP-RVF) was then developed and subsequently externally validated, which can provide personalized quantification of the risk for LVAD candidates. Its predictive accuracy was compared with previously published RVF scores. Results: The derivation cohort included 798 patients (mean [SE] age, 56.1 [13.2] years; 668 male [83.7%]). The external validation cohort included 327 patients. RVF developed in 193 of 798 patients (24.2%) in the derivation cohort and 107 of 327 patients (32.7%) in the validation cohort. Preimplant variables associated with postoperative RVF included nonischemic cardiomyopathy, intra-aortic balloon pump, microaxial percutaneous left ventricular assist device/venoarterial extracorporeal membrane oxygenation, LVAD configuration, Interagency Registry for Mechanically Assisted Circulatory Support profiles 1 to 2, right atrial/pulmonary capillary wedge pressure ratio, use of angiotensin-converting enzyme inhibitors, platelet count, and serum sodium, albumin, and creatinine levels. Inclusion of intraoperative characteristics did not improve model performance. The calculator achieved a C statistic of 0.75 (95% CI, 0.71-0.79) in the derivation cohort and 0.73 (95% CI, 0.67-0.80) in the validation cohort. Cumulative survival was higher in patients composing the low-risk group (estimated <20% RVF risk) compared with those in the higher-risk groups. The STOP-RVF risk calculator exhibited a significantly better performance than commonly used risk scores proposed by Kormos et al (C statistic, 0.58; 95% CI, 0.53-0.63) and Drakos et al (C statistic, 0.62; 95% CI, 0.57-0.67). Conclusions and Relevance: Implementing routine clinical data, this multicenter cohort study derived and validated the STOP-RVF calculator as a personalized risk assessment tool for the prediction of RVF and RVF-associated all-cause mortality.

Hierarchical Development of Physical Frailty and Cognitive Impairment and Their Association With Incident Cardiovascular Disease.

BACKGROUND: Frailty and cognitive impairment (CI) are geriatric conditions that lead to poor health outcomes among older adults with cardiovascular disease. The association between their temporal patterns of development and cardiovascular risk is unknown. OBJECTIVES: This study aims to examine the 5-year cardiovascular outcomes by the pattern of development of frailty and CI in older adults without a history of coronary artery disease. METHODS: We used the National Health and Aging Trends Study, linked to Medicare data. Frailty was measured using the physical frailty phenotype. CI was measured using the AD8 Dementia Screening Interview, measured cognitive performance, or self-report by patient or caregiver for a diagnosis given by a physician. The primary outcome was incident major adverse cardiovascular event at 5 years. RESULTS: Of a total 2,189 study participants aged 65 and older, 38.5% were male. In this study population, 154 (7%) participants developed frailty first, 829 (38%) developed CI first, and 195 (9%) participants developed both simultaneously (frail-CI group). Those who developed frailty and CI simultaneously were older, more likely to be female, and had multiple chronic conditions. The frail-CI group had the highest risk of major adverse cardiovascular event (hazard ratio [HR]: 1.81; 95% CI: 1.47-2.23) followed by frail first (HR: 1.46; 95% CI: 1.17-1.81) and CI first (HR: 1.31; 95% CI: 1.15-1.50). Frailty first was associated with the greater risk of stroke (HR: 1.49; 95% CI: 1.06-2.09) compared to the intact group. CONCLUSIONS: The simultaneous development of frailty and CI is associated with an increased risk of adverse cardiovascular outcomes including death compared with the development of each syndrome alone. Diagnostics to detect frailty and CI are critical in assessment of cardiovascular risk in the older population.

Nonalcoholic Fatty Liver Disease Is Independently Associated With Higher All-Cause and Cause-Specific Mortality.

BACKGROUND & AIMS: The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing globally. We assessed independent associations of NAFLD with all-cause and cause-specific mortality in older community-dwelling adults in the United States. METHODS: Data from the Rancho Bernardo Study cohort, who participated in the research from 1992 to 1996 with mortality data (followed up to July 2019), were analyzed. NAFLD was determined by the improved Fatty Liver Index for the multiethnic US population in the absence of secondary causes of liver disease. Hazard ratios (HRs), 95% CIs, and population-attributable fractions of risk factors on mortality were calculated. Competing-risk analyses of cause-specific mortality were performed. RESULTS: Of the 1523 eligible participants (mean age, 71.8 y; 39.9% male; 99.3% non-Hispanic White; and 10.7% obese), 404 (26.4%) had NAFLD. During 23,311 person-years of follow-up evaluation (mean, 15.22 y; SD, 8.41 y), among NAFLD and non-NAFLD, there were 296 and 717 deaths from all causes, 113 and 263 cardiac deaths, 62 and 112 cancer deaths, and 6 and 2 liver deaths, respectively. NAFLD had a 26% higher all-cause mortality (HR, 1.26; 95% CI, 1.08-1.47) and a 33% (HR, 1.33; 95% CI, 1.04-1.70) and 55% (HR, 1.55; 95% CI, 1.11-2.15) higher cardiac and cancer mortality, respectively, than non-NAFLD. Population-attributable fractions showed 13.9% of deaths, 6.2% of cardiac deaths, and 12.1% of cancer deaths were attributable to NAFLD after adjustments of risk factors (sedentary lifestyle, obesity, hypertension, hyperlipidemia, diabetes). CONCLUSIONS: NAFLD is associated independently with all-cause, cardiac, and cancer mortality. Efforts must continue to raise awareness about NAFLD and develop care pathways and public health efforts to reduce NAFLD burden and associated mortality.

Interventions for Frailty Among Older Adults With Cardiovascular Disease: JACC State-of-the-Art Review.

With the aging of the world's population, a large proportion of patients seen in cardiovascular practice are older adults, but many patients also exhibit signs of physical frailty. Cardiovascular disease and frailty are interdependent and have the same physiological underpinning that predisposes to the progression of both disease processes. Frailty can be defined as a phenomenon of increased vulnerability to stressors due to decreased physiological reserves in older patients and thus leads to poor clinical outcomes after cardiovascular insults. There are various pathophysiologic mechanisms for the development of frailty: cognitive decline, physical inactivity, poor nutrition, and lack of social supports; these risk factors provide opportunity for various types of interventions that aim to prevent, improve, or reverse the development of frailty syndrome in the context of cardiovascular disease. There is no compelling study demonstrating a successful intervention to improve a global measure of frailty. Emerging data from patients admitted with heart failure indicate that interventions associated with positive outcomes on frailty and physical function are multidimensional and include tailored cardiac rehabilitation. Contemporary cardiovascular practice should actively identify patients with physical frailty who could benefit from frailty interventions and aim to deliver these therapies in a patient-centered model to optimize quality of life, particularly after cardiovascular interventions.

Framework to Classify Reverse Cardiac Remodeling With Mechanical Circulatory Support: The Utah-Inova Stages.

BACKGROUND: Variable definitions and an incomplete understanding of the gradient of reverse cardiac remodeling following continuous flow left ventricular assist device (LVAD) implantation has limited the field of myocardial plasticity. We evaluated the continuum of LV remodeling by serial echocardiographic imaging to define 3 stages of reverse cardiac remodeling following LVAD. METHODS: The study enrolled consecutive LVAD patients across 4 study sites. A blinded echocardiographer evaluated the degree of structural (LV internal dimension at end-diastole [LVIDd]) and functional (LV ejection fraction [LVEF]) change after LVAD. Patients experiencing an improvement in LVEF ≥40% and LVIDd ≤6.0 cm were termed responders, absolute change in LVEF of ≥5% and LVEF <40% were termed partial responders, and the remaining patients with no significant improvement in LVEF were termed nonresponders. RESULTS: Among 358 LVAD patients, 34 (10%) were responders, 112 (31%) partial responders, and the remaining 212 (59%) were nonresponders. The use of guideline-directed medical therapy for heart failure was higher in partial responders and responders. Structural changes (LVIDd) followed a different pattern with significant improvements even in patients who had minimal LVEF improvement. With mechanical unloading, the median reduction in LVIDd was -0.6 cm (interquartile range [IQR], -1.1 to -0.1 cm; nonresponders), -1.1 cm (IQR, -1.8 to -0.4 cm; partial responders), and -1.9 cm (IQR, -2.9 to -1.1 cm; responders). Similarly, the median change in LVEF was -2% (IQR, -6% to 1%), 9% (IQR, 6%-14%), and 27% (IQR, 23%-33%), respectively. CONCLUSIONS: Reverse cardiac remodeling associated with durable LVAD support is not an all-or-none phenomenon and manifests in a continuous spectrum. Defining 3 stages across this continuum can inform clinical management, facilitate the field of myocardial plasticity, and improve the design of future investigations.

Second trimester amniotic fluid bisphenol A concentration is associated with decreased birth weight in term infants.

Bisphenol A (BPA) is an endocrine disrupting chemical with ubiquitous environmental exposure. Animal studies have demonstrated that in utero BPA exposure leads to increased adult body weight. Our aim was to characterize human fetal BPA exposure by measuring BPA concentration in second trimester amniotic fluid (AF) samples and to study its relationship with birth weight (BW) in full term infants. To achieve these goals, we developed a total BPA assay utilizing derivatization with pentafluorobenzyl followed by analysis with LC-ECAPCI-MS/MS with a limit of detection of 0.08ng/mL and limit of quantification (LOQ) of 0.25ng/mL. The mean BW of infants with AF BPA 0.40-2.0ng/mL was 241.8g less than infants with AF BPA less than the LOQ after controlling for covariates (p=0.049). No effect was seen outside this range indicating a non-monotonic effect. Our data suggest that low level BPA exposure in utero decreases BW and needs further study.