Citations

BACKGROUND: Left atrial (LA) stiffening augments the LA V wave, pressurizing the pulmonary artery (PA) out of proportion to left ventricular end-diastolic pressure. We characterized the pathophysiologic, diagnostic, and clinical implications of LA stiffening, as defined by prominent V waves, in heart failure with preserved ejection fraction. METHODS: In this retrospective cohort study, patients with heart failure with preserved ejection fraction and less than moderate mitral regurgitation at rest underwent invasive hemodynamic exercise testing. Patients with heightened operant LA stiffening were defined by the PA wedge pressure (PAWP) V wave exceeding mean PAWP by ≥10 mm Hg. A previously used formula for V wave–corrected PAWP was validated against the PAWP waveform pressure-time-area to explore impact of the V wave on transpulmonary pressure gradients. Clinical, echocardiographic, hemodynamic, and outcome data were compared for patients with and without prominent V waves. RESULTS: Compared with patients without prominent V waves (n=844, 79%), those with prominent V waves (n=225, 21%) were older and more likely to be women, with more severe LA myopathy, evidenced by greater LA volume index (42.2±15.0 versus 32.5±13.0 mL/m 2 , P <0.001), lower LA reservoir strain (16.4±7.5% versus 23.2±8.3%, P <0.001), more atrial fibrillation (61.3% versus 22.9%, P <0.001), and increased operant LA reservoir stiffness (0.59±0.25 versus 0.23±0.24 mm Hg/mL, P <0.001). Patients with prominent V waves had markedly higher PA systolic pressure than those without (54±16 versus 38±12 mm Hg, P <0.001) despite no difference in end-diastolic PAWP-PA pressure gradient (3±5 versus 3±4 mm Hg, P =0.950). Incorporating the V wave into PAWP improved correlation between directly measured PAWP pressure-time integral compared with mid–A wave PAWP (R 2 =0.96 versus R 2 =0.86, P <0.001 for comparison). In patients with prominent V waves, the prevalence of combined pre- and postcapillary pulmonary hypertension decreased from 60.2% to 29.3% after V wave correction for the transpulmonary pressure gradients. Despite similar corrected pulmonary vascular resistances in patients with and without prominent V waves, apparent PA compliance was much lower in patients with prominent V waves (3.03±1.56 versus 4.90±2.27 mL/mm Hg, P <0.001), augmenting right ventricular afterload, and these changes were coupled with more severe right ventricular dysfunction, tricuspid regurgitation, blunted cardiopulmonary exercise reserve, and increased risk of hospitalization for heart failure or death in patients with versus without prominent V waves (adjusted hazard ratio, 2.09 [95% CI, 1.53–2.86]; P <0.001). CONCLUSIONS: More than 1 in 5 patients with heart failure with preserved ejection fraction display prominent V waves in excess of end-diastolic PAWP. This augments right ventricular afterload due to backward transmission of the V wave, contributing to right heart failure that is independent of the pulmonary vasculature. Failure to account for the V wave during hemodynamic assessment overestimates the severity of pulmonary vascular disease present.

Abstract Living clinical guidelines revise recommendations as evidence emerges, so an AI answer can be faithful to a real guideline and still be out of date. Here we examine this failure using ASCOBench, 288 unique questions in 96 three-turn conversations grounded in versioned American Society of Clinical Oncology (ASCO) breast and prostate cancer guidelines, with oncologist-reviewed reference answers. Oncologists corrected one in four version-sensitive answers drafted by a frontier model, against fewer than one in ten factual ones. Across the guideline corpus, 19 recommendations changed between versions, seven of them reversals, yet only 1 of 14 superseded documents states that it has been replaced. With a strong model, retrieval over several guideline versions made stale answers four times more frequent than answering without retrieval. SentryLine, a verification-first system, lowered incorrect answers to 4.2-5.2% from 9.7-22.9% for baselines across three models. Recognizing change before a guideline declares it remains an open problem.

ABSTRACT Background Left atrial appendage occlusion (LAAO) has emerged as a non‐pharmacological alternative to oral anticoagulation (OAC) for stroke prevention in patients with atrial fibrillation (AF). Following the publication of recent CHAMPION‐AF and CLOSURE‐AF trials, an updated synthesis of evidence is warranted to clarify the long‐term comparative efficacy and safety of LAAO versus OAC in patients with AF. Methods We conducted a systematic review and meta‐analysis of randomized controlled trials (RCTs) comparing LAAO with OAC in adults with AF. A comprehensive search of major databases was performed from inception to April 2026. The primary efficacy outcomes were major adverse cardiovascular events (MACE) and stroke. The primary safety outcome was non–procedure‐related bleeding. Random‐effects models were used to calculate pooled risk ratios (RRs) with 95% confidence intervals (CIs). Results Six RCTs including 7,004 patients (3,681 LAAO; 3,323 OAC) were analyzed. No statistically significant difference was observed for MACE (7.5% vs 6.9%; RR 1.03, 95% CI 0.79‐1.34) or stroke (3.7% vs 3.2%; RR 1.07, 95% CI 0.80‐1.43). LAAO was associated with a significantly lower risk of non‐procedure‐related bleeding (9.8% vs 16.7%; RR 0.63, 95% CI 0.52‐0.77), corresponding to an absolute risk reduction of 6.9% and an approximate number needed to treat of 15 based on crude pooled event rates over the observed trial follow‐up. Trial sequential analysis indicated that the accumulated evidence for MACE and stroke remained inconclusive. Comparator‐type subgroup analyses showed no significant interaction for MACE ( p = 0.67) or stroke ( p = 0.81) between contemporary predominantly‐DOAC and VKA comparator trials. Conclusions LAAO was associated with lower non‐procedure‐related bleeding, while no statistically significant differences were observed for MACE or stroke. The available efficacy evidence remains inconclusive regarding equivalence or non‐inferiority, and larger trials are needed. These findings support individualized consideration of LAAO when the long‐term bleeding burden of anticoagulation is clinically important.

Clostridioides difficile infection (CDI) remains a major cause of healthcare-associated diarrhea and is being increasingly recognized in community settings. The management of CDI is complicated by diagnostic uncertainty, recurrent disease, and uneven access to newer therapies. Clinicians must distinguish infection from colonization, individualize therapy selection, and anticipate barriers to recurrence prevention. This narrative review examines diagnostic and therapeutic barriers in adult CDI care, with particular emphasis on the U.S. healthcare, regulatory, and reimbursement setting. Several guidelines prefer fidaxomicin for an initial nonfulminant CDI episode when available. Oral vancomycin is an effective alternative, and metronidazole is reserved for initial nonsevere CDI when preferred agents are unavailable. Antibiotic options for recurrent CDI include standard or extended-pulsed fidaxomicin and standard-course or tapered-and-pulsed vancomycin regimens. After antibacterial treatment, conventional fecal microbiota transplantation (FMT) and two FDA-approved microbiota products, fecal microbiota spores, live-brpk (VOS) and fecal microbiota, live-jslm (RBL), may be used in appropriately selected patients to prevent another recurrence. In ECOSPOR III, recurrence through 8 weeks was 12.4% of VOS recipients and 39.8% of placebo recipients. In PUNCH CD3, Bayesian model–estimated treatment success through 8 weeks was 70.6% with RBL and 57.5% with placebo. Because the trials used different populations, endpoints, definitions, and analytical frameworks, these figures should not be interpreted as a head-to-head comparison. The discontinuation of bezlotoxumab in the United States and reduced availability of stool bank-derived FMT have further constrained recurrence prevention options. Practical considerations include diagnostic stewardship, assessment of recurrence risk, and timely access to indicated recurrence prevention therapy.

Background Obstructive sleep apnea (OSA)–chronic obstructive pulmonary disease overlap syndrome has been linked to worse cardiovascular outcomes. Preserved ratio impaired spirometry (PRISm) is recognized as an early stage of chronic obstructive pulmonary diseas. However, whether the coexistence of OSA and PRISm confers increased cardiovascular risk remains unknown. Methods Using data from the Sleep Heart Health Study, participants were categorized into 4 groups according to OSA and PRISm status. The primary outcome was major adverse cardiovascular and cerebrovascular events. The secondary outcome was cardiovascular disease mortality. Multivariable Cox regression models were used to evaluate the association of these groups with the risk of cardiovascular outcomes. Results During a median follow‐up of 11.45 years, the incidence of major adverse cardiovascular and cerebrovascular events was 17.00% in non‐OSA with normal lung function, 27.52% in non‐OSA with PRISm, 25.28% in OSA with normal lung function, and 49.40% in OSA with PRISm. After multivariable adjustment, compared with non‐OSA with normal lung function, the adjusted hazard ratios (HRs) for major adverse cardiovascular and cerebrovascular events were 1.20 (95% CI, 0.82–1.75) in non‐OSA with PRISm, 1.04 (95% CI, 0.89–1.21) in OSA with normal lung function, and 1.52 (95% CI, 1.08–2.12) in OSA with PRISm. Corresponding HRs for CVD mortality were 2.02 (95% CI, 1.26–3.24), 1.05 (95% CI, 0.81–1.35), and 2.17 (95% CI, 1.41–3.34), respectively. A significant sex interaction was observed ( P for interaction=0.009), with the association present only in women. Conclusions The coexistence of OSA and PRISm is independently associated with increased risk of adverse cardiovascular outcomes. This association is observed predominantly in women.

ABSTRACT The contemporary intensive care unit generates an overwhelming magnitude of high‐frequency, granular physiological data. However, conventional decision‐making for patients requiring temporary mechanical circulatory support (tMCS) remains tethered to reactive, threshold‐driven manual adjustments, underutilizing continuous data streams and failing to optimize the complex patient–machine interaction. This review examines the integration of deep neural networks (DNNs) as a candidate strategy for advanced clinical decision support. By identifying a continuous “digital phenotype,” hierarchical deep learning architectures signal a shift toward real‐time trajectory recognition in tMCS. We establish a four‐tier functional taxonomy—prognosticative, descriptive, predictive, and prescriptive—to categorize translational milestones from automated pump‐speed optimization to closed‐loop homeostatic regulation. Operational challenges are analyzed through the TEIP (Transparency, Explainability, Interpretability, and Performance) Core‐Lens Framework, navigating the dynamic equilibrium between computational density and clinical explainability. We further evaluate the evolving global regulatory landscape, advocating for a foundation on verified empirical safety and rigorous clinical trial validation over absolute mathematical transparency in high‐density architectures. Implementing a strategic roadmap including context‐specific validation, multimodal integration, and human‐centered design is quintessential to safely transform passive hardware into intelligent systems. As the field evolves, DNN technology offers a consequential opportunity to advance early cardiopulmonary failure recognition into a clinical reality.

Date presented: April 24, 2026 Primary Author and Speaker: Tamra Trenary, trenary.tamra@mayo.edu

Date presented: April 25, 2026 Primary Author and Speaker: Randi Bukovac Nagyvathy, rb@bukie.net