Richard Sutton

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Aim: Artificial intelligence may support syncope evaluation, but reliability of language models in structured syncope care remains uncertain. We evaluated diagnostic performance, safety, and within-case consistency of Generative Pre-trained Transformer-5 (GPT-5) in patients with transient loss of consciousness (T-LOC). Methods: This prospective cohort study included 55 patients evaluated in syncope units. GPT-5 and a syncope-expert assessed identical case information after core evaluation (CE: history-taking, physical examination, active standing test, and 12-lead electrocardiogram) and extended evaluation (EE: CE plus additional testing when indicated). An expert panel adjudicated the final diagnosis after 18 months. Outcomes were diagnostic yield, final-diagnosis inclusion rate, diagnostic precision score (DPS), cardiac diagnostic safety, and within-case consistency across five repeated GPT-5 runs. Results: Of 55 patients, 54 had complete follow-up for performance analyses. Diagnostic yield was 94% for the syncope-expert at CE and EE, and 100% and 96% for GPT-5 at CE and EE, respectively. GPT-5 included the final diagnosis in 52% (CE) and 57% (EE) of cases, versus 67% for the syncope-expert. DPS remained negative for GPT-5 at CE (mean −0.03, SD 0.54) and EE (mean −0.01, SD 0.49). Among four final cardiac syncope cases, GPT-5 selected the final diagnosis in one case and the syncope-expert in three. First-diagnosis consistency across five GPT-5 runs was 69% after CE and 74% after EE. Conclusions: GPT-5 generated diagnostic outputs frequently but showed limited precision, cardiac safety concerns, and within-case variability. Its role in syncope evaluation should remain supportive within clinician-led pathways rather than autonomous.

Aims: Unlike ventricular electrical disease, the impact of similar atrial disease on cardiac function has received insufficient importance. We aimed to examine data on atrial anatomy, electrical disease, and pacing to ameliorate abnormalities, offering pointers towards future practice. Methods and results: We used PubMed to explore atrial anatomy, activation, and pacing aiming to improve function. From inception of pacing, causes of deterioration in ventricular systolic function went unrecognized. Their eventual recognition led to fresh pacing strategies, termed conduction system pacing, which have yielded improved and preserved long-term ventricular function: now standard practice. Study of atrial anatomy/conduction implies that similar approaches may improve atrial function and also reduce incidence of atrial fibrillation. Impact of atrial electrical disease on diastolic and subsequent ventricular systolic function has been ignored, despite data showing how pacing alternative atrial sites can abbreviate atrial activation and improve ventricular filling: methods that have not been widely adopted. Comprehension of atrial anatomy/conduction underpins abandonment of right atrial appendage pacing paralleling the move away from right ventricular apical pacing on similar principles. Conclusion: When treating heart failure, atrial resynchronization should be considered along with ventricular resynchronization. Crucially, convenient pacing sites have been outmoded by active-fixation leads that can be placed at stimulation sites approximating normal conduction, including the atria; achievement hinges on understanding atrial anatomy and activation. Atrial resynchronization may significantly improve cardiac function where dyssynchrony relates to atrial disease/conduction delay, but more evidence of benefits must be collected. As resynchronization therapy moves forward, there should be parallel focus on evaluating coordination of atrial activation and timing with respect to the ventricles.

Aims: Reflex syncope occurs infrequently but may benefit from pacing intervention. However, reflex syncope poses special problems for successful cardiac pacing. Between episodes, monitoring by the implanted device is required to provide warning of an impending syncope and initiate pacing therapy if appropriate. This article aims to review available devices and their function in different forms of reflex syncope. Methods and results: The first device dedicated to address detection of VVS was the Rate Drop Response (RDR) (Medtronic Inc., MN, USA). It used a modified rate hysteresis approach to detect falls in heart rate that are faster than physiological but slower than those in cardiac conduction tissue disease. Since the introduction of RDR more has been learnt about the development of vasodepression and cardiac inhibition in vasovagal syncope (VVS). Detection of vasodepression, which occurs substantially earlier than cardioinhibition, assumes great importance. Currently, such detection is only offered by the Closed Loop System (CLS) (Biotronik GmbH, Berlin, Germany). Carotid sinus syndrome (CSS) shows different haemodynamic features from VVS with early vasodepression absent which demands rethinking of device selection and programming. RDR yielded improved management of both VVS and CSS. CLS has demonstrated clear benefits in two important recent randomized controlled VVS pacing trials. So far, no comparative trial between RDR and CLS has been undertaken. Conclusion: Pacing the bradycardia of reflex syncope requires a full appreciation of its haemodynamic events, including timing of vasodepression and cardioinhibition requiring sophisticated detection and therapy delivery.

Aims: Wolff–Parkinson–White (WPW) syndrome is a rare cardiac disorder that predisposes to supraventricular arrhythmias. Prognosis is usually benign, yet there is an increased lifetime risk of sudden death. While typically sporadic, familial clustering has been reported. This study aimed to assess the risk of WPW, arrhythmias, and mortality among siblings of individuals with WPW. Methods and results: This population-based sibling cohort included 5 338 434 individuals born in Sweden (1932–2018), with 3172 WPW cases identified from the Swedish National Patient Registers. Familial risks among siblings were assessed using incidence rate ratios (IRRs) and adjusted subdistributional hazard ratios (SHRs). Sensitivity analyses excluded syndromic WPW and cases without electrophysiologic procedural confirmation. Although familial occurrence of WPW was exceedingly rare with only 14 of 3172 cases (0.4%; ≈0.0003% of the total population), siblings of affected individuals showed a significantly higher rate of WPW diagnosis (0.121 vs. 0.032 per 1000 person-years; IRR 3.83; 95% CI 2.27–6.46; P < 0.001) translating to an almost four-fold higher adjusted risk (SHR 3.79; 95% CI 1.81–7.97; P < 0.001). Risks of atrial fibrillation (SHR 1.19; 95% CI 1.05–1.35; P < 0.01) and ventricular arrhythmias (SHR 1.84; 95% CI 1.45–2.35; P < 0.001) were also higher, whereas all-cause mortality was comparable irrespective of sibling history (HR 1.01; 95% CI 0.92–1.11; P = 0.88). Conclusion: WPW features familial aggregation and increased arrhythmic risk among siblings of affected individuals despite its extremely low absolute frequency in the general population. The evidence of a measurable hereditary component within an otherwise sporadic, non-syndromic condition points to a genetic contribution driven by complex inheritance patterns.

Summary Elevated HDL-C levels are generally regarded as prognostically favorable in cardiovascular disease. Our study shows that higher HDL cholesterol levels are prospectively associated with 18% increased risk of new-onset fractures in men but not in women. Higher HDL cholesterol may be a novel risk factor for developing fractures in men. Purpose Increased high-density lipoprotein cholesterol (HDL-C) is associated with reduced risk of cardiovascular disease but inversely associated with bone mineral density. Methods We assessed the relationship between HDL-C and incident fractures using a prospective population-based cohort. In total 18,240 subjects had available data on HDL-C levels (mean age 69 years, 37% women, mean follow-up 13 years). Fracture endpoints were identified through national registers. Follow-up was from 2002 until the first episode of incident fracture or end of follow-up December 31, 2020. The primary and secondary outcomes were total incident fractures and incident fractures of the hip and lower limb, respectively. Results Incident fractures occurred in 26% (n = 4,710) of all subjects (mean follow-up of 13 years). Subjects with incident fractures had higher HDL-C levels (mmol/L ± standard deviation) compared with subjects without fractures (1.5 ± 0.4 vs. 1.4 ± 0.4 mmol/L). In multivariate regression analysis, higher HDL-C levels were associated with increased risk of total incident fractures in the general population (HR 1.12, 95%CI 1.03–1.22, p = 0.006), and in men (HR 1.18, 95%CI 1.04–1.35, p = 0.02). No statistically significant relationship was found in women or between incident fractures of hip and lower limb fractures (p > 0.05). Conclusions Higher HDL cholesterol levels are prospectively associated with 18% increased risk of new-onset fractures in men from the general population but not in women. Higher HDL cholesterol may be a novel risk factor for developing fractures in men.

BACKGROUND Orthostatic hypotension (OH), defined as a sustained drop in systolic or diastolic blood pressure upon standing, is known to negatively affect survival in the general population. However, its impact on outcomes in patients with advanced coronary artery disease remains unclear. The aim of this study was to assess the prevalence and prognostic value of OH in patients undergoing isolated coronary artery bypass grafting (CABG). MATERIAL AND METHODS This prospective observational study enrolled 392 patients (74.7% male, median age 66 [61-74] years) scheduled for elective CABG between 2013 and 2016. Structured clinical interviews and orthostatic tests (OT) were performed preoperatively. OH was diagnosed using standard criteria. Survival status was obtained from the Polish Ministry of Digitization on August 31, 2024. Cox regression and logistic regression were used to identify predictors of long-term mortality. RESULTS The median follow-up was 9.7 (9.0-10.5) years. OH was diagnosed in 80 patients (20.4%). During follow-up, 148 patients (37.8%) died. OH-positive patients had higher baseline systolic and diastolic blood pressure (P 0.001), but did not differ significantly from OH-negative patients in other clinical variables. Independent predictors of mortality included advanced age, male sex, heart failure, and renal failure. OH was not associated with long-term mortality (odds ratio: 0.694; 95% CI: 0.386-1.246; P=0.22). CONCLUSIONS Orthostatic hypotension is present in approximately 20% of patients undergoing elective CABG. A positive orthostatic test prior to surgery does not independently affect long-term survival in this population.