Jonathan W. Cunningham

Background: The PREVENT-HF equations estimate 10-year risk of overall heart failure (HF), inclusive of both HF with preserved and reduced ejection fraction (HFpEF; HFrEF). Given differential risk factor profiles, pathophysiology, and therapeutic strategies for each HF subtype, we sought to examine the performance of PREVENT-HF for subtype-specific risk assessment. Methods: We included data from five pooled longitudinal cohort studies (baseline exam 1989 to 2013) and two longitudinal primary-care electronic health record-based samples (Beth Israel Deaconess Medical Center [BIDMC], baseline 2004 to 2014; Mass General Brigham [MGB], baseline 2001 to 2018). We assessed the performance of the PREVENT-HF equations in predicting 10-year incident HFrEF and HFpEF, including model discrimination (area under the receiver operating characteristic curve [AUROC]; average precision [AP]/event rate) and calibration (integrated calibration index [ICI]), in adults aged 30-79 years without prevalent cardiovascular disease or HF. Results: The pooled cohort studies included 23,652 (55% women, age 60 ± 13 years), of whom 1,232 developed HF (432 [35%] HFpEF, 522 [42%] HFrEF). The BIDMC sample included 29,815 (55% women, 50 ± 13 years), of whom 259 (1%) developed HF (133 [51%] HFpEF, 101 [39%] HFrEF). MGB included 138,999 (62% women, 52 ± 13 years), of whom 1050 developed HF (586 [56%] HFpEF, 381 [36%] HFrEF). PREVENT-HF demonstrated better discrimination for HFpEF than HFrEF across all samples: in the pooled cohorts, the AUROC for HFpEF was 0.824 (95% CI 0.807, 0.839) versus 0.789 (95% CI 0.770, 0.807) for HFrEF; in BIDMC, the AUROC for HFpEF was 0.897 (95% CI 0.874, 0.918) versus 0.833 (95% CI 0.791, 0.869) for HFrEF; in MGB, the AUROC for HFpEF was 0.864 (95% CI 0.848, 0.880) versus 0.797 (95% CI 0.771, 0.820) for HFrEF. Similar results were reflected in the AP/event rate ratios: 2.92 (95% CI 2.47, 3.54) for HFpEF compared to 2.66 (95% CI 2.33, 3.14) for HFrEF in the pooled cohorts; 8.08 (95% CI 6.12, 12.30) for HFpEF compared to 5.12 (95% CI 3.84, 8.17) for HFrEF in BIDMC; and 6.84 (95% CI 5.66, 8.28) for HFpEF compared to 4.12 (95% CI 3.37, 5.16) for HFrEF in MGB. Calibration was similar for HFpEF and HFrEF across samples. For example, in the pooled cohorts, the ICI for HFpEF was 0.041 (95% CI 0.039, 0.043) and for HFrEF was 0.038 (95% CI 0.036, 0.040). Conclusions: PREVENT-HF demonstrated excellent discrimination for both HF subtypes across community-based cohorts and real-world samples, with consistently better discrimination for HFpEF as compared to HFrEF. Given PREVENT-HF was developed to estimate overall HF risk rather than subtype-specific risk, future studies are needed to establish subtype-specific risk thresholds.

Aims: Early detection of congestion among adults with heart failure and preserved ejection fraction (HFpEF) is critical to optimize therapy prior to overt decompensation, yet traditional tools are insensitive. We sought to examine the association between B-lines on lung ultrasound (LUS) in ambulatory adults with HFpEF and relate these to one-year outcomes. Methods: In a prospective, multi-site observational study, using a pocket ultrasound device, 8-zone LUS was performed in outpatients with HFpEF, left ventricular ejection fraction ≥45% and NYHA class II-IV. Ultrasound videos were analyzed centrally, blinded to clinical findings and adjudicated outcomes. Results: Among 415 participants (mean age 74 years, 52% women, 51% with obesity, median N-terminal pro-B-type natriuretic peptide (NT-proBNP) 744 pg/ml) B-lines ranged from 0 to 36 (median 3 [interquartile range 1, 6]). A total of 108 events occurred during follow-up (89 HF events, 19 deaths). Participants in the highest B-line tertile (>5 B-lines) had a higher risk of total HF events and all-cause death (rate ratio 2.37 [95% CI 1.33, 4.25; P=0.004]) and a first HF event or death (HR 2.68 [95% CI 1.54, 4.64; P<0.001]) during one-year follow-up. These associations persisted after adjusting for age, sex, body mass index, diabetes, atrial fibrillation/flutter and NT-proBNP (first events only). Conclusions: Among ambulatory adults with HFpEF, a higher number of B-lines at baseline identified those at increased risk of both total HF events and all-cause death, and first HF event or death independent of known risk markers. LUS is a scalable, non-invasive strategy to assess congestion and prognosis in adults with HFpEF.

Patients with CKD have a disproportionate burden of cardiovascular (CV) disease, and the majority die from CV causes before ever reaching kidney failure. Atherosclerotic cardiovascular disease (ASCVD), which includes coronary artery disease, cerebrovascular disease, and peripheral arterial disease, develops in CKD through the convergence of traditional risk factors and a distinct group of CKD-related, nontraditional mechanisms, including mineral and bone disorder with vascular calcification, chronic inflammation and oxidative stress, uremic toxicity, and an atherogenic dyslipidemia. CV and kidney disease interact in a bidirectional manner in which each accelerates the other. Reflecting this unique pathophysiology, the burden of ASCVD rises steeply as kidney function declines, reaching a several-fold higher risk of myocardial infarction, stroke, and peripheral arterial disease at the lowest eGFR and highest albuminuria. Nonetheless, ASCVD in CKD remains under-recognized and undertreated, owing partly to atypical clinical presentations, conventional risk-prediction tools that underestimate risk, and to the exclusion of patients with advanced CKD from most landmark CV trials. In this review, which focuses primarily on coronary artery disease in non–dialysis-dependent CKD, we examine the epidemiology and key pathogenic mechanisms of ASCVD in this setting and appraise diagnostic and risk-prediction approaches together with their limitations, including contemporary CKD-adapted risk equations, cardiac biomarkers, and noninvasive imaging. We also summarize the current evidence for management, spanning lipid-lowering, antiplatelet, and BP therapies, newer cardiometabolic agents (including sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, and nonsteroidal mineralocorticoid receptor antagonists), coronary revascularization, and lifestyle modification. Throughout, we highlight where high-quality, CKD-specific evidence is lacking, and we outline priority research gaps and emerging therapies directed at CKD-relevant pathways, such as inflammation. Recognizing and aggressively modifying CV risk in CKD, across both traditional and CKD-specific pathways, represents a substantial, and currently underrealized, opportunity to reduce morbidity and mortality in this high-risk population.