Heart Rhythm

Background: Anatomic isthmus 3 (AI 3) is defined as the myocardium between the pulmonary valve annulus and the ventricular septal defect patch that persists after tetralogy of Fallot (ToF) repair. Ventricular tachycardia (VT) propagated through slow conducting AI 3 (SCAI 3) represents a significant cause of morbidity in ToF. There is an unmet need for non-invasive identification of SCAI 3 in patients with ToF. Objectives: To assess whether the anatomic features of AI 3 as derived from cardiac computed tomography (CT) can predict slow conduction velocity during EP study. Methods: This retrospective single-center study included patients with ToF who underwent an electrophysiologic study and had AI 3 width measured from the pre-procedure cardiac CT. All patients underwent programmed ventricular stimulation, and electroanatomic. Logistic regression was performed to assess the relationship between AI 3 width and the presence of SCAI 3. Results: Of 27 consecutive patients with ToF, twelve patients were found to have SCAI 3, and ten patients were found to have SCAI 3 mediated VT. The AI 3 was significantly narrower in patients with SCAI 3 compared to those with normal AI 3 conduction (18.4 +/- 6.6 mm vs. 29.2 +/- 9.0 mm; p = 0.001). An AI 3 width above 21.5 mm carried a negative predictive value of 80.0%. Conclusion: In adults with repaired ToF referred for electrophysiology study, a narrower CT-derived AI 3 width was associated with SCAI 3 identification. AI 3 width measured on a CT obtained before PV replacement could help guide invasive risk stratification.

Background: Atrial fibrillation (AF) has been observed in adults with anomalous pulmonary venous return (APVR), but data on catheter ablation outcomes in this population remain limited to case reports and small series. Methods: We retrospectively reviewed 14 adult patients with confirmed APVR who underwent catheter ablation for AF at three tertiary academic centers in the United States between July 2003 and May 2025. Baseline, procedural, electroanatomic mapping, and outcome data were collected. Freedom from atrial arrhythmia recurrence was estimated by Kaplan-Meier analysis. Results: Mean age was 56 +/- 13 years and 79% were male. Heart failure was present in 64%, and hypertension and coronary artery disease in 43% each. Most had partial APVR (86%), and 57% had prior surgical correction. Radiofrequency ablation was used in all patients, combined with pulsed-field ablation in one. Acute success was achieved in all patients, although areas with residual pulmonary vein or SVC electrical activity were left untreated in 3 (21%). Non-pulmonary-vein electrical activity was more common in patients with prior surgical correction than in those without (43% vs 17%). Median follow-up was 3.4 years (IQR, 2.0-9.6). Freedom from arrhythmia recurrence was 78.6% at 1 year and 53.9% at 5 years. Two patients (14%) required reablation; complications occurred in 3 (21%) without long-term sequelae. Conclusions: Catheter ablation was acutely successful in all patients in this largest reported APVR cohort, despite substantial comorbidity burden and anatomic complexity. The arrhythmogenic substrate often extended beyond the anomalous vein, particularly in surgically corrected patients, supporting individualized, substrate-guided ablation in this population.

Background Pulsed-field ablation (PFA) has recently been approved in the USA as a new method for treating atrial fibrillation (AF). PFA provides a promising new approach in the treatment of atrial fibrillation (AF), which historically has a high recurrence rate post-ablation. Of significance, PFA has shown promising data in terms of safety and procedural efficiency to radiofrequency ablation (RFA). Objective The purpose of this study was to compare the procedural and health outcomes in patients with recurrent AF undergoing ablation using PFA or RFA. Methods Consecutive patients with a history of previous radiofrequency ablation and recurrent AF undergoing redo ablation with PFA or RFA were included. Patients were seen for follow-up in the clinic ranging from 4 months to a year and we reported ablation strategy and arrhythmia type. The primary outcome was recurrence of any atrial arrhythmia after a 90-day blanking period. Results A total of 242 patients with recurrent AF underwent redo ablation using PFA (n = 54, 22.5%) or RFA (n = 188, 77.5%). The PFA cohort was younger on average (66 vs. 70 years) with a lower mean CHA2DS2-VASc score (2.2 vs. 3.06, p=0.001) compared to the RFA cohort. PFA procedures were shorter (162{+/-}53 vs 206{+/-}60 minutes, p<0.001) but required more fluoroscopy (13.9{+/-}8.9 vs 8.7{+/-}6.3 minutes, p<0.001). Among patients seen on follow-up, recurrence occurred in 28% of PFA versus 55% of RFA patients, with longer arrhythmia-free survival after PFA (log-rank p=0.03). PFA remained associated with lower recurrence after multivariable adjustment (HR 0.4, 95% CI 0.2?0.9, p=0.04). Adverse events, predominantly vascular access?related, were similar. Conclusion Among patients with recurrent atrial arrhythmias after prior RFA, repeat PFA was associated with shorter procedures, greater fluoroscopy use, and lower arrhythmia recurrence, with comparable safety.

Instability of the cardiac electrical system is a major cause of life-threatening arrhythmias. Current safety guidelines have traditionally emphasized QT interval prolongation on the electrocardiogram (ECG) as a primary biomarker of proarrhythmic risk. However, this approach does not capture all forms of electrical instability. In this study, we demonstrate that beat-to-beat variability in action potential duration (APD), a cellular surrogate of the QT interval, better stratifies proarrhythmic risk than mean APD prolongation alone. Using a validated computational model of a human ventricular myocyte, we simulated the effects of the {beta}-adrenergic agonist isoproterenol (ISO). Increasing the ISO concentration shortened mean APD but paradoxically increased beat-to-beat APD variability, measured as the standard deviation of APDs. In our simulations, the emergence of early afterdepolarizations (EADs), abnormal oscillations of the membrane potential during the plateau phase of the action potential, at higher ISO concentrations was consistently preceded by a marked rise in APD variability, even while mean APD was reduced. Mechanistic analysis revealed that ISO-induced enhancement of L-type Ca2+ current (ICaL) and slow delayed rectifier K+ current (IKs) steepens the APD restitution slope, which reflects action potential instability, even when the net effect is a reduction in APD. These results support APD variability as a more sensitive and mechanistically plausible marker of proarrhythmic risk than APD prolongation alone. Our findings suggest that QT interval variability may improve risk stratification and provide a more robust mechanistic foundation for drug safety evaluation.

Background: Pacing-induced cardiomyopathy (PICM) is a major complication of chronic right ventricular pacing and develops in up to 25% of patients. Reliable prediction of PICM may facilitate individualized pacing strategy selection; however, currently available approaches demonstrate limited discriminative performance. This study aimed to develop and validate machine learning (ML) models for predicting PICM in patients with atrioventricular block (AVB) underlying heart failure with mildly reduced or preserved ejection fraction. Methods: In this multicenter prospective study derived from the RISK-PICM registry (January 2002 to January 2026), 125 patients with AVB who underwent pacemaker implantation were analyzed. PICM was defined as a ?10% reduction in left ventricular ejection fraction (LVEF) resulting in an LVEF <50%. Four ML algorithms, including logistic regression, support vector machine, random forest, and XGBoost, were trained using stratified 4-fold cross-validation with hyperparameter optimization and model discrimination was evaluated. Results: PICM developed in 41 patients (32.8%) during a median follow-up of 4.8 years. Male sex, pre-implant minimum QTc interval, and post-implant maximum QRS duration were significantly associated with PICM in univariable Cox regression. XGBoost achieved the highest discriminative performance (AUROC 0.831; sensitivity 0.805; specificity 0.845). Feature importance analysis identified baseline LVEF and post-implant maximum QRS duration as the most influential features. Model-derived risk stratification significantly differentiated high-risk and low-risk groups on Kaplan-Meier analysis (P < 0.001). Conclusions: ML-based models, particularly XGBoost, demonstrated clinically meaningful performance for PICM and may support individualized pacing strategy selection in patients with AVB and underlying heart failure with mildly reduced or preserved ejection fraction.

Background: Loss- and gain-of-function variants in SCN5A, encoding the cardiac sodium channel Nav1.5, are major causes of inherited cardiac channelopathies. Their pathophysiology has almost exclusively been attributed to altered cardiomyocyte excitability and cardiac conduction. However, growing evidence indicates that autonomic dysfunction contributes to these disorders, raising the possibility that Nav1.5 dysfunction may also affect the intrinsic cardiac nervous system. Objectives: We investigated whether Nav1.5 is functionally expressed in murine intrinsic cardiac neurons and evaluated its contribution to neuronal excitability. Methods: Scn5a expression was investigated by digital PCR and immunocytochemistry in isolated murine intracardiac neurons. Whole-cell patch-clamp recordings were used to characterize sodium currents and action potential properties in wild-type and Scn5a+/- mice. Results: Scn5a transcripts and Nav1.5 protein were detected in intrinsic cardiac neurons. Voltage-clamp recordings identified a tetrodotoxin-resistant sodium current accounting for approximately 8% of the total sodium current and displaying pharmacological and biophysical properties consistent with Nav1.5. Activation and inactivation analyses indicated that Nav1.5 is the predominant sodium conductance available at most polarized membrane potentials. Accordingly, Scn5a haploinsufficiency selectively altered action potential threshold, maximal upstroke velocity, overshoot and duration in neurons resting below -60 mV, whereas more depolarized neurons were essentially unaffected. No structural or neurochemical remodeling of intrinsic cardiac ganglia was detected. Conclusion: Nav1.5 is a functional determinant of intrinsic cardiac neuronal excitability. These findings identify the intrinsic cardiac nervous system as a new cellular target of SCN5A dysfunction and suggest that inherited cardiac sodium channelopathies could involve alterations in both myocardial and intrinsic neuronal electrophysiology.

BACKGROUND: Radiofrequency catheter ablation (RFCA) uses rigid metallic electrodes whose fixed geometry limits tissue contact, lesion continuity, and safe energy delivery near vulnerable structures. We evaluated a moldable, tissue-conforming conductive hydrogel as an RFCA electrode ex vivo. METHODS: Poly(ether urethane diacrylamide) hydrogels with saline-tuned conductivity were molded into plugs, disks, and bars and affixed to an irrigated 8-Fr catheter. Ablations were performed on excised porcine tissue in circulated saline at 37 C under fixed contact force and irrigation. Lesion geometry, intramural temperatures, and steam pops were compared with bare-metal (BM) electrodes and size-matched metallic analogs; an atrioesophageal stack model assessed collateral injury. Lesions were delineated using triphenyltetrazolium chloride staining. RESULTS: Hydrogel bars produced wide, ellipsoidal lesions (width 10.51 {+/-} 1.40 versus 8.71 {+/-} 1.65 mm for BM; P=0.031; aspect ratio 1.72); size-matched metal bars produced none. Hydrogel disks produced lesions statistically indistinguishable from BM in depth (4.54 {+/-} 0.90 versus 4.84 {+/-} 0.55 mm) and width (9.47 {+/-} 0.89 versus 11.41 {+/-} 2.39 mm), whereas metal disks produced significantly shallower lesions (2.30 {+/-} 1.70 mm; P=0.015 versus BM). In the atrioesophageal model, hydrogel plugs achieved transmural atrial lesions with a reduced esophageal lumen temperature (56.33 {+/-} 3.80 versus 61.30 {+/-} 5.14 C; P=0.046), total lesion depth (4.03 {+/-} 1.25 versus 7.58 {+/-} 0.78 mm; P<0.001), and esophageal lesion width (3.05 {+/-} 2.35 versus 8.70 {+/-} 2.69 mm; P<0.001) compared with BM. Hydrogel electrodes reduced steam-pop risk (relative risk 0.34; 95% CI 0.13-0.88). Plug characterization confirmed saline-dependent conductivity and attenuated energy delivery, with lower subsurface peak temperatures and shallower lesions than BM. CONCLUSIONS: Moldable, conductivity-tunable hydrogels shape RF lesions and may improve ablation safety, supporting evaluation for contiguous or linear lesion sets and ablation near sensitive structures.

Brugada syndrome (BrS) is an inherited arrhythmia disorder with limited drug therapy, quinidine being the principal agent. Loss-of-function variants in SCN5A reduce the cardiac sodium current (INa), but the arrhythmogenic imbalance also depends on the transient outward potassium current (Ito). Here we generated human induced pluripotent stem cell-derived cardioids with right-ventricular identity from a patient carrying an SCN5A frameshift variant (p.A665Gfs*16) and characterised them by patch-clamp and optical mapping. BrS cardioids showed 60% lower peak INa, more than doubled Ito, 38% slower conduction and 76% longer spontaneous cycle length. We then tested AR-788, a benzylaminothiazole-benzimidazole carboxamide of the ARumenamide class. In wild-type (WT) cardiomyocytes AR-788 inhibited Ito concentration-dependently (12%, 30% and 42% at 5, 10 and 20 uM; extrapolated IC50 25.4 uM), and at 10 uM it returned BrS Ito to the level of untreated WT cells (21.71 vs 21.48 pA/pF, p = 0.9716) without reducing INa. It also reduced the rapid delayed-rectifier current (IKr) tail current by 40%, a liability requiring formal proarrhythmia profiling. These data identify AR-788 as an Ito-suppressing member of the ARumenamide class and provide proof of concept that a small molecule can correct the potassium-current excess in a human BrS model.

Background Implantable loop recorders (ILRs) provide continuous rhythm monitoring. Professional society guidelines and expert consensus statements recommend ILR use for patients with recurrent syncope and cryptogenic stroke, but recommendations are weaker for other indications. We assessed ILR use over time and concordance between indication and clinical guidance. Methods We conducted a retrospective cohort study using Epic Cosmos data from 1/1/2020-12/31/2025. Among active patients with at least one of 13 diagnoses potentially eligible for ILR placement, we identified ILR placements and classified them by concordance with professional society guidance: concordant, possibly, or non-addressed. Annual incidence was estimated overall and by indication. We also described the proportion of patients who received longer-term (>7 days) rhythm monitoring in the year prior to placement. Results Of 47,046,706 patients with diagnoses potentially eligible for ILR placement, 201,103 (0.4%) had an ILR placed. ILR placements increased from 3.08 ILRs per 100,000 patient-days in 2020 to 4.13 in 2025 (5.9% annual growth). The most common indications were cryptogenic stroke (28.6%) and atrial fibrillation without prior ablation (21.4%). Overall, 43.9% were guidance concordant, 28.5% possibly concordant, and 24.8% non-addressed. Relative annual growth in ILR placements per 100,000 patient-days was significant across all guidance categories: concordant (1.3%, 95% CI, 0.9%-1.7%), possibly concordant (5.5%, 95% CI, 5.0%-6.0%) and non-addressed (7.4%, 95% CI, 6.8%-8.0%). Among 125,631 outpatient placements, 50,181 (39.9%) had any prior long-term rhythm monitoring. Conclusion ILR placements are uncommon but increasing, with faster annual growth for indications that may not be guidance concordant. More than half of patients lacked long-term rhythm monitoring prior to outpatient ILR placement.

Background: Pulsed field ablation (PFA) has been rapidly adopted for atrial fibrillation (AF) on the premise of greater safety than thermal ablation. Real-world signals of hemolysis, coronary spasm, and neurologic events have since emerged, and prior Manufacturer and User Facility Device Experience (MAUDE) analyses relied on term matching without prospective signal detection. Methods: We queried MAUDE for AF ablation catheter reports received January 2016 through June 2026 and assigned each to PFA, radiofrequency ablation (RFA), or cryoballoon ablation. We adjudicated injury and death narratives into predefined complication families and severity tiers with a large language model, checked against a larger model and by physician review. We calculated reporting odds ratios (ROR) and Bayesian shrinkage estimators compared against an empirical null, applied interrupted time series and prospective sequential detection, and repeated estimates on a 2026 hold-out. Results: Among 44,623 reports, 30.1% were PFA, 50.9% RFA, and 19.0% cryoballoon, with 91.8% model agreement on event occurrence (? = 0.83). PFA carried an ROR of 527 (95% CI, 33, 8,509) for hemolysis, 2.83 (2.55, 3.16) for arrhythmia, 2.83 (2.30, 3.48) for coronary, and 2.39 (2.10, 2.73) for cerebrovascular events, against 0.024 (0.008, 0.075) for esophageal and 0.34 (0.32, 0.37) for pericardial events. The cerebrovascular excess was largest for VARIPULSE, but without it the class proportional reporting ratio was 1.36 (1.13, 1.65), concordant with the 1.56 measured in EMBOL-AF. In the hold-out, the cerebrovascular, arrhythmia and hemolysis signals replicated, and coronary events kept their direction without meeting the signal rule. Prospective detection flagged cerebrovascular events 13 months before AVANT GUARD published its neurologic events. Conclusions: PFA showed disproportionate reporting of hemolysis, cerebrovascular, coronary, and arrhythmic events across sequential testing. Machine learning methods allowed for flagging these signals months before confirmatory trials, demonstrating a scalable tool for early detection of procedural risk.

Background: Human induced pluripotent stem cell-derived cardiomyocytes are valuable for cardiac disease modelling and drug testing but remain limited by immature structural and electrophysiological properties in conventional two-dimensional cultures. Three-dimensional cardiac models, including cardioids, provide a more physiological environment through multicellular organization and enable tissue-level functional analysis. Their electrophysiological properties and maturation, however, remain incompletely characterized. Methods: We performed an integrated electrophysiological characterization of human cardioids over the first three weeks of maturation using sharp microelectrode recordings, calcium transient measurements, whole-cell patch clamp recordings, immunofluorescence, transcriptomic analysis, and pharmacological interventions. Results: During maturation, cardioids exhibited progressive electrophysiological maturation, characterized by more physiological resting membrane potentials (-54.0{+/-}3.1mV to -68.1{+/-}1.2mV), increased action potential amplitude (73.5{+/-}4.8mV to 101.7{+/-}2.1mV) and upstroke velocity (44.3{+/-}5mV/ms to 86.6{+/-}8.4mV/ms), and shorter action potential duration (178.9{+/-}8.7ms to 144.0{+/-}4.8ms at 1Hz stimulation). These changes were associated with progressively increased INa density and enhanced SCN5A mRNA and Nav1.5 protein expression, consistent with progressive maturation of cardiac excitability. IKr current and KCNH2/hERG expression were already present at early maturation stages and remained stable, as evidenced by preserved sensitivity to dofetilide-blockade. Pharmacological inhibition of barium- and HMR-sensitive currents altered resting membrane and/or action potential characteristics in intact cardioids, whereas in isolated cardiomyocytes classical IK1 remained undetectable and IKs was small, highlighting a certain degree of persisting immaturity of the model. Conclusions: These findings demonstrate that human cardioids undergo progressive electrophysiological maturation and provide complementary tissue- and cellular-level insights into cardiac function, establishing their suitability for investigating INa and IKr-related cardiac pathologies.

Rationale: Atrial fibrillation (AF) is sustained by electrical triggers and atrial substrate, but whether AF itself generates circulating factors that acutely reinforce arrhythmogenesis is unknown. Objective: To determine whether rhythm-dependent serum bioactivity directly destabilizes atrial electrophysiology and to identify associated cellular mechanisms and circulating mediators. Methods and Results: Cardiac samples were obtained from patients with persistent atrial fibrillation (AF) during AF and after restoration of sinus rhythm (SR) using electrical cardioversion. In isolated Langendorff-perfused mouse hearts, AF serum increased the duration, frequency, and cumulative burden of spontaneous atrial depolarizations compared with paired control perfusate. In human induced pluripotent stem cell derived atrial cardiomyocytes, AF patient serum decreased Ca2-transient amplitudes without significant effect on kinetics or Ca2 spark activity. Moreover, AF serum reduced peak sodium current without materially altering voltage-dependent gating or paced action-potential properties. Data-independent acquisition proteomics identified rhythm-associated changes in extracellular-matrix, proteolytic, inflammatory, and signaling proteins, including MMP9, Ccathepsin G, and 14-3-3 family members. Targeted pathway perturbation differentially modified serum-induced Ca2 phenotypes, indicating context-dependent, multifactorial bioactivity. Serum-induced Ca2 responses were not associated with indices of atrial disease severity, including low-voltage substrate burden and left atrial pressure. Conclusions: Persistent AF is accompanied by rhythm-dependent circulating bioactivity that acutely promotes atrial electrical instability and Ca2-dependent trigger formation. These findings extend the concept that AF begets AF beyond tissue-intrinsic remodeling and identify a potentially reversible serum-mediated feed-forward mechanism linking rhythm status and circulating proteomic signals in an atrial substrate severity independent fashion. Keywords: atrial fibrillation; serum; atrial cardiomyopathy; calcium signaling; circulating factors; proteomics

Background. Real-world 12-lead electrocardiograms (ECGs) often have missing or corrupted leads. A deep-learning classifier can be prepared for this by random lead masking during training, or by injecting clinical knowledge, for example by pulling its attention towards the leads that guidelines use for each diagnosis. Whether this knowledge adds robustness beyond masking is unknown. Methods. Pre-registered comparison of three arms sharing one network (per-lead 1D-ResNet encoder and per-diagnosis attention over the 12 leads): standard training (M0); random whole-lead masking (M1); masking plus a Kullback-Leibler penalty pulling attention towards a fixed guideline-derived key-lead map (M2, guideline-based attention guidance). Six diagnoses; five seeds per arm. Development on PTB-XL (21,799 ECGs); single sealed evaluation on PTB-XL fold 10 (2,198 ECGs) and on CODE-15% (233,204 exams, external validation). Primary endpoint: AUROC difference M2 - M1, averaged over first-degree AV block, right and left bundle branch block and atrial fibrillation and over 1 to 6 lost (zeroed) leads, with a patient-level paired BCa bootstrap 95% confidence interval. Results. The guidance did not change robustness: {Delta}AUROC -0.0010 (95% CI -0.0033 to +0.0006), an interval entirely within the pre-specified +-0.02 margin; the result was unchanged with another bootstrap seed, other interval methods and leave-one-diagnosis-out analyses. Masking improved AUROC: M1 - M0 = +0.0134 (95% CI +0.0102 to +0.0172) when one key lead was lost, and the number of lost leads tolerated before AUROC fell by more than 0.02 rose from 7 (M0) to 10 (M1). M2 attention matched the map and M2 was non-inferior on intact ECGs, but its calibration slope was lower for all six diagnoses in both datasets. M2 lost slightly more when all key leads were lost together (-0.0067) and gained only when one to three leads remained (exploratory; AUROC 0.9408 vs 0.9210 with 11 leads lost). CODE-15% reproduced every pattern (primary -0.0007, 95% CI -0.0011 to -0.0003). Conclusions. Random lead masking suffices to make an ECG classifier robust to missing leads; adding guideline knowledge aligns attention with clinical criteria but adds no robustness and worsens calibration. Guideline-aligned attention should not be taken as evidence of robustness.

Background: Sleep-disordered breathing (SDB) is an established adverse prognostic factor in heart failure (HF). Sleep apnea-specific hypoxic burden (SASHB), which reflects the duration and depth of respiratory event-related oxygen desaturation, has shown stronger prognostic value than the apnea-hypopnea index (AHI) in general populations and patients with coronary artery disease. However, its clinical utility in patients hospitalized due to acute HF remains unclear. Objectives: This study evaluated the prognostic value of SASHB in patients hospitalized for acute HF and compared its performance with AHI for risk stratification and identification of patients who may benefit from positive airway pressure (PAP) therapy. Methods: This post hoc analysis included 230 patients from a prospective single-center observational cohort of adults hospitalized for acute HF. The primary analysis included 178 patients who did not receive PAP treatment. Associations of SASHB and AHI with the composite endpoint of cardiovascular death or rehospitalization for worsening HF were evaluated using Cox proportional hazards models. Model improvement after adding SASHB or AHI to a model including established clinical risk factors was assessed using changes in the C index and Brier score, reflecting changes in model discrimination and prediction error, respectively. In the full cohort, the interaction between PAP treatment and SDB metrics was evaluated using the g-formula. Results: During a median follow-up of 3.7 years, 58 of 178 patients (32.6%) reached the composite endpoint. Both SASHB and AHI were independently associated with the composite outcome after multivariable adjustment. However, only SASHB consistently predicted outcomes across analyses and improved model performance beyond established prognostic factors (bootstrap {Delta} C index, 0.020 [95% CI: 0.008 - 0.031]; bootstrap {Delta} Brier score, - 0.007 [95% CI: - 0.014 to - 0.001]), whereas AHI did not. In the analysis including PAP-treated patients, both SASHB and AHI showed interaction with PAP treatment. Conclusions: In patients hospitalized for acute HF, SASHB showed a consistent independent association with adverse clinical outcomes and provided additional prognostic information beyond AHI. SASHB may improve risk stratification and may help identify patients who are more likely to benefit from PAP therapy.

Background Real-world data regarding mavacamten use in underserved and racially diverse populations remain limited, particularly for long-term therapy implementation. Structural barriers such as financial instability, fragmented healthcare access, and challenges adhering to REMS-related monitoring requirements may affect longitudinal therapy implementation. Methods We performed a retrospective observational study of consecutive patients with symptomatic obstructive hypertrophic cardiomyopathy (oHCM) evaluated for mavacamten therapy at a tertiary HCM center in Bronx, NY, between 6/2022-10/2025. Patients were followed for up to 48 weeks after treatment initiation. Clinical characteristics, treatment interruptions, adverse events, echocardiographic and functional outcomes, and implementation barriers were assessed descriptively. Results Seventy-two patients with symptomatic oHCM were evaluated for mavacamten; sixty-seven initiated treatment. Mean age was 66.9{+/-}15.3 years, 72% were female, and 61% identified as Black or Hispanic. Median resting left ventricular outflow tract (LVOT) gradient decreased from 51mmHg (IQR30-88) at baseline to 7mmHg (IQR5-10) at 48 weeks. Median Valsalva LVOT gradient decreased from 74mmHg (IQR50-104) to 20mmHg (IQR10-29). At final follow-up, 80% of patients improved by [&ge;]1 NYHA functional class. LVEF declined below 50% in five patients and recovered in all cases. Approximately one-quarter experienced treatment interruption or discontinuation, nearly half related to insurance instability, non-adherence, and REMS-related monitoring barriers. Conclusions Mavacamten demonstrated efficacy and safety outcomes comparable to those reported in clinical trials and prior registries in this predominantly underserved minority urban cohort. However, structural and healthcare-access barriers substantially affected long-term treatment implementation. These findings highlight the need to address healthcare-system barriers to ensure equitable implementation of contemporary HCM therapies.

Background Cardiac amyloidosis is an increasingly recognized cause of heart failure in older adults, yet Colombian data, and data from the southwest of the country in particular, remain scarce. We describe the clinical, diagnostic, imaging and outcome profile of patients with cardiac amyloidosis at two high-complexity institutions in Cali. Methods Observational, descriptive, retrospective, two-center study. Patients were identified in the institutional registries of both centers using ICD-10 codes for amyloidosis, and clinical data were abstracted manually from medical records. Continuous variables are reported as median (interquartile range) and categorical variables as counts and percentages over the number of patients with available data. Results Thirty-two patients were analyzed (median age 77 years; 68.8% men). Heart failure (90.6%), atrial fibrillation (46.9%) and carpal tunnel syndrome (31.2%) were frequent. The etiological classification depended on the test considered: bone scintigraphy was positive (Perugini 2-3) in 23 of 26 patients studied (88.5%), but a monoclonal protein was screened for in only 22, and the full non-invasive criteria for ATTR were met in 16 of 32 (50.0%). Genetic testing was positive in 9 of 18 tested, and the variant was Val142Ile in all 8 patients in whom it was characterized. The working diagnosis was ATTR in 26 patients (81.2%) and AL in 6 (18.8%). Tafamidis was used in 37.5%. Eleven of the 31 patients with known vital status died (35.5%), and NT-proBNP was markedly higher among those who died (6640 vs 1186 pg/mL; p=0.003). Conclusions In this southwestern Colombian cohort, cardiac amyloidosis presented as the classic transthyretin phenotype, with the Val142Ile variant in all 8 patients in whom it was characterized. Bone scintigraphy was frequently positive, but screening for a monoclonal protein was often omitted, so only half the cohort met the full non-invasive criteria for ATTR. Mortality was high and closely associated with NT-proBNP.

Abstract Background: Mean arterial pressure (MAP) is pharmacologically augmented in selected perioperative and critical care settings, including acute neurological conditions and after cardiac arrest, with the aim of improving cerebral perfusion, although it remains uncertain whether higher arterial pressure translates into increased cerebral blood flow (CBF). We investigated the CBF response to MAP augmentation with norepinephrine (NE), a commonly used vasopressor in perioperative and critical care settings, during propofol-based general anesthesia. Methods: In this prospective within-subject interventional study, 16 neurologically intact patients with ASA physical status I-II undergoing elective surgery were studied using phase-contrast magnetic resonance imaging. CBF was quantified in the awake state and during propofol-based general anesthesia before and after NE-induced MAP augmentation. During general anesthesia, NE was titrated to increase MAP by approximately 25% from baseline. Concurrent systemic hemodynamics were assessed. Results: General anesthesia was associated with a 50.1% (interquartile range, 42.1?55.7%) reduction in CBF and a 24.2% (20.3-29.2%) reduction in MAP compared with the awake state (both P<0.001). During general anesthesia, NE-induced MAP augmentation increased MAP by 25.7% (21.9-32.0%; P<0.001), whereas CBF remained unchanged (P=1.000). Cardiac output remained unchanged (P=0.163), whereas systemic vascular resistance index and cerebrovascular resistance increased by 40.0% (28.7-45.2%) and 36.2% (17.7-42.8%), respectively (both P<0.001). Changes in CBF during MAP augmentation were not associated with concurrent changes in MAP, cardiac output, or systemic vascular resistance index. Conclusions: In neurologically intact patients undergoing propofol-based general anesthesia, clinically relevant NE-induced MAP augmentation did not increase CBF despite an approximately 50% lower CBF than in the awake state. These findings challenge the assumption that pharmacological elevation of an otherwise adequate MAP improves cerebral perfusion in this setting. While maintaining adequate arterial pressure remains essential, further MAP augmentation should not be assumed to increase CBF. Clinical Trial Registration: https://clinicaltrials.gov/study/NCT06855407; NCT06855407.

Condensed Abstract: Using the 2016?2022 National Inpatient Sample, this study evaluated temporal trends and demographic adoption patterns of percutaneous left atrial appendage occlusion (LAAO). Among 190,020 weighted procedures, annual volume increased from 4,875 to 60,445. In-hospital mortality was exceptionally low (0.1%). Age-adjusted procedural rates rose from 34.19 to 379.87 per 100,000 population. However, significant disparities persisted, characterized by heavy centralization in urban teaching hospitals (87.0%) and disproportionately lower absolute age-adjusted utilization among female, Black, Hispanic, and Asian/Pacific Islander patients compared to male and White cohorts. Targeted initiatives are needed to ensure equitable access to structural heart interventions.

Rural patients with heart failure (HF) have poor access to care, worse outcomes, and may benefit from at-home monitoring. We evaluated whether foot temperature measured using a thermographic floor mat was associated with invasively measured cardiac output and whether longitudinal temperature changes preceded HF events. We conducted a two-part prospective, observational single-center study using the SmartMat (Podimetrics, Somerville, MA), which acquires plantar thermograms and ambient temperature. In the acute study, patients undergoing clinically indicated right heart catheterization completed 4 scans on the same day. In the chronic study, patients with a HF hospitalization in the past year and New York Heart Association Class II-III symptoms were instructed to use the device and a scale daily for 6 months. A HF event was defined as receiving at least one dose of intravenous or subcutaneous diuretic. Thirty patients were enrolled in the acute study. Mean right hallux temperature positively correlated with thermodilution cardiac output (r=0.63, p<0.001). 42 patients were enrolled in the chronic study. Among patients experiencing an HF event, ambient-adjusted hallux temperature declined in the 15 days immediately preceding the event compared with days 15-30 before the event. Plantar thermograms are associated with invasively measured cardiac output and may detect subclinical worsening before HF events. Foot temperature may provide complementary information regarding HF decompensation, supporting further evaluation of plantar thermography for remote HF monitoring.

Introduction: In hypertrophic cardiomyopathy (HCM), wall stress and subclinical myocardial injury related in part to pathological hypercontractility, which in turn are associated with worse outcomes. Cell-free DNA (cfDNA) is released from cardiomyocytes (cfDNA-CM) through irreversible cellular injury and death. We investigated the feasibility of quantifying cfDNA-CM and its relationship to HCM patient characteristics. Methods: We analyzed 57 plasma samples from stable patients with HCM and 10 plasma samples from patients with acute myocardial infarction (AMI). Plasma cfDNA was isolated from both groups. Whole genome bisulfite sequencing (WGBS) libraries were generated and sequenced with short-read sequencing. Methylation patterns were used for tissue deconvolution analysis and cell-specific cfDNA quantification. Results: Yields of cfDNA (p = 0.003) and cfDNA-CM (p = 0.002) fractions were higher in AMI controls than HCM, supporting the validity of the assay. Within the HCM cohort, the median cfDNA yield was 12.22 ng [IQR: 7.77, 18.94]. The cfDNA-CM fraction in this cohort ranged from 0% to 6.4% of total cfDNA. Higher cfDNA-CM tertiles were associated with higher body mass index (BMI, p=0.001), a greater prevalence of BMI 30 kg/m2 (p<0.001), and a higher prevalence of obstructive sleep apnea (p=0.038). No significant differences were observed in other demographic, genetic, and laboratory characteristics. Higher cfDNA-CM tertile was numerically associated with higher New York Heart Association (NYHA) functional class and left ventricular outflow tract (LVOT) obstruction, while circulating biomarkers of wall stress (NT-proBNP) and myocardial injury (troponin) did not differ across tertiles (p=0.83 and p=0.29, respectively). Conclusion: Isolation and quantification of cfDNA as well as detection of cfDNA-CM in chronic stable patients with HCM are feasible. Higher cfDNA-CM fraction was associated with increasing BMI and cardiometabolic comorbidity burden. The absence of association with traditional circulating biomarkers suggests that cfDNA-CM may reflect a distinct domain of myocardial health, injury, and adverse remodeling.