Neurocognitive disorders-including mild cognitive impairment, dementia, and delirium-are common yet often underrecognized in heart failure, impairing self-care and outcomes. These heart failure-related neurocognitive disorders pose a significant public health challenge due to high morbidity and mortality. Despite recent advances, timely detection, prevention, and intervention remain difficult. Most research focuses on pharmacological treatments, with limited attention to nonpharmacological approaches and mental health integration in heart failure care teams. Progress requires collaboration among internal medicine, surgery, nursing, and psychology. This review highlights interconnected pathways-cerebral hypoperfusion, microvascular and endothelial dysfunction, thromboembolic injury, and neuroendocrine-inflammatory activation-and discusses targeted interventions like simplified treatment plans, caregiver involvement, and multidisciplinary referrals.
BACKGROUND:Pulmonary hypertension (PH) due to left-sided heart disease (Group 2 PH) is the most common type of PH and comprises 2 subtypes with distinct clinical profiles and outcomes: isolated postcapillary PH and combined pre- and postcapillary PH (Cpc-PH). Bioactive lipid derivatives may underlie these divergent subphenotypes. This study aimed to investigate the molecular heterogeneity underlying Group 2 PH subtypes and identify shared pathways between Cpc-PH and pulmonary arterial hypertension (PAH). METHODS:In a cross-sectional study, we profiled plasma bioactive lipids using liquid chromatography-mass spectrometry in 128 patients with isolated postcapillary PH (n=21), Cpc-PH (n=69), or PAH (n=38), as well as in plasma samples from animal models of severe PH. RESULTS:Of the 844 profiled metabolites, 158 differed between Cpc-PH and isolated postcapillary PH at a false discovery rate of q<0.05. Of those, 28 were higher in Cpc-PH, particularly those in the polyunsaturated fatty acid and fatty acyl esters of hydroxy fatty acid pathways. Notably, 24 of these 28 did not differ from PAH, indicating a PAH-like bioactive lipid signature. Several metabolites, including adrenic acid, linoleic acid, docosatrienoic acid, palmitoleic acid, and fatty acyl esters of hydroxy fatty acids, were associated with increased mortality. These findings were corroborated in the Su/Hx rat model of PAH, where a subset of Cpc-PH-elevated metabolites was similarly increased. CONCLUSIONS:Cpc-PH exhibits a distinct, PAH-like metabolomic signature characterized by higher polyunsaturated fatty acids and fatty acyl esters of hydroxy fatty acids and lower pro-resolvin/vasodilatory oxylipins compared with isolated postcapillary PH. These findings have implications for PH classification, may inform diagnostic strategies, and nominate lipid pathways for therapeutic targeting.
BACKGROUND:Cardiac sarcoidosis (CS) may lead to serious outcomes, but large-scale data are lacking because of its rarity, diagnostic uncertainty, and heterogeneous clinical presentations. Actual management and outcomes, including recurrence, are not well understood. This study aimed to clarify the actual management and outcomes of CS from a nationwide large-scale registry. METHODS:This multicenter retrospective registry enrolled 2366 consecutive patients with CS. Of these, 1852 patients newly diagnosed between 2012 and 2021 were analyzed. Patients were stratified into 4 groups: definite CS, probable CS, presumed systemic sarcoidosis, and presumed isolated CS based on diagnostic criteria. The primary end point was a composite of all-cause death, heart failure hospitalization, or fatal ventricular arrhythmic event. The secondary end point was recurrence of CS. RESULTS:Cardiac imaging performance rates were high (cardiac magnetic resonance: 64%, 18F-fluorodeoxyglucose positron emission tomography: 82%), and 974 (53%) patients were diagnosed clinically without histological evidence. During a median 5.1-year follow-up, the primary outcome occurred in 519 (28%, 6.4/100 patient-years) patients, and the 4 groups exhibited different clinical presentations and prognoses; definite CS and presumed isolated CS groups showed a high incidence of the primary end point, fatal ventricular arrhythmic event, hospitalization for heart failure, and cardiovascular death. Most patients (89%) received immunosuppressive therapy, but 291 (18%, 4.1/100 patient-years) patients developed recurrence during steroid tapering, with a 5-year recurrence rate of 17.0%. Recurrence was associated with subsequent primary end point (hazard ratio, 1.38 [95% CI, 1.00-1.89]; P=0.048). CONCLUSIONS:This large-scale multicenter registry showed that clinical presentation and prognosis differ depending on the presence or absence of extracardiac lesions and histological evidence; therefore, it is necessary to recognize the characteristics of each phenotype in managing CS.
