Postural Orthostatic Tachycardia Syndrome (POTS) is a chronic autonomic disorder characterized by chronic (> 3 months) orthostatic intolerance and an increase in heart rate (HR) of ≥ 30 beats per minute (bpm) without orthostatic hypotension. Traditional diagnostic approaches, such as the active standing or tilt-table test, are typically conducted under controlled clinical conditions, limiting their ability to capture the natural variability of symptoms and the intricate physiological responses occurring in daily life. These tests may cause patient discomfort, dizziness, nausea, or syncope. Furthermore, they are timeconsuming and cannot be used as a screening tool for POTS. To address these limitations, this study explored wearable devices that continuously collect physiological data-specifically, electrocardiogram (ECG) and accelerometer (ACC)-derived metrics-from POTS patients and healthy controls during routine daily activities. Physiological features around posturechange events identified in the data were processed and used to train and test a baseline deep learning model. The model demonstrated promising performance in accurately differentiating POTS patients from healthy controls in a relatively small cohort (66 from POTS patients and 20 from controls), indicating its potential as a feasibility study for clinical decision support. Future studies involving larger and more diverse samples under varying clinical conditions would be necessary to enhance the robustness and viability of our diagnostic model.

BACKGROUND:Heart failure (HF) is a global health challenge with a significant impact on patients and health care systems. Identifying those at risk of cardiac death (CD) remains difficult but essential. Elevated sympathetic nerve activity (SNA) is linked to ventricular arrhythmias, highlighting its value in diagnosis and risk stratification. OBJECTIVE:This study aimed to investigate the use of skin sympathetic nerve activity (SKNA) as a marker for stratifying patients at risk of CD beyond established clinical predictors and heart rate variability (HRV). METHODS:We analyzed 20-minute, 1-kHz orthogonal electrocardiogram recordings from 588 patients with HF in the MUerte Subita en Insuficiencia Cardiaca dataset after excluding device carriers. SKNA was extracted using high-pass filtering (>300 Hz). We quantified traditional amplitude-based SKNA metrics derived from moving average and root mean square signals and raw SKNA (rSKNA) signal distribution and nonlinear complexity features, including the largest Lyapunov exponent (LE) and multiscale entropy (MSE). Associations with outcomes were assessed using univariate analyses and multivariable Cox models adjusted for age, body mass index, left ventricular ejection fraction, New York Heart Association class, diabetes, and previous myocardial infarction. HRV indices (standard deviation of normal-to-normal interval, low-frequency power to high-frequency power ratio) were evaluated for comparison. RESULTS:Moving average-/root mean square-based SKNA metrics did not show consistent between-group differences. In contrast, rSKNA complexity measures (LE and MSE) were lower in patients who experienced CD (sudden and nonsudden). In adjusted Cox models, LE and MSE remained independently associated with CD (hazard ratio ≈0.75-0.80; P < .05), whereas the standard deviation of normal-to-normal interval and the low-frequency power to high-frequency power ratio were not independently associated. CONCLUSION:rSKNA complexity measures, particularly MSE, provide complementary, noninvasive prognostic information for sudden and nonsudden CD in HF beyond established clinical predictors and HRV.

J-wave syndromes (JWS)-comprising Brugada syndrome (BrS) and early repolarization syndrome (ERS)-are important causes of malignant ventricular arrhythmias and sudden cardiac death in patients whose hearts appear structurally normal. Since the 2016 consensus, advances in genetics, pathophysiology, and therapy have redefined both understanding and management. BrS, once viewed as a purely electrical disorder, is now recognized along a microstructural-electrical continuum, with sodium-channel dysfunction and subtle epicardial fibrosis of the right ventricular outflow tract as key contributors. Likewise, ERS-historically considered benign-carries significant risk when inferolateral J-waves coexist with arrhythmic events. Genetically, SCN5A remains the sole gene with definitive disease association, while polygenic susceptibility materially modulates risk, underscoring complex inheritance. Risk stratification remains challenging: patients with prior cardiac arrest or arrhythmic syncope are highest risk, whereas asymptomatic individuals warrant multiparametric assessment integrating clinical features, ECG markers, electrophysiologic studies, and genetics. For decades, treatment centered on implantable cardioverter-defibrillators and quinidine, both limited by availability, tolerance, and device complications. More recently, epicardial substrate ablation has emerged as a transformative therapy, with large registries and randomized trials demonstrating durable suppression of ventricular fibrillation and acceptable safety. This APHRS-organized international consensus updates and extends the 2016 Expert Consensus and the 2022 ESC Guidelines, providing contemporary diagnostic frameworks, pragmatic risk-stratification tools, and treatment algorithms for BrS and ERS. It emphasizes JWS as a microstructural-electrical disease spectrum and elevates substrate ablation as a major therapeutic advance, while outlining priorities for genetics, risk-stratification and treatment algorithms.

OBJECTIVES:To evaluate angiography-based index of microcirculatory resistance (angio-IMR) in assessing microvascular obstruction (MVO) and infarct size (IS) in ST-segment elevation myocardial infarction (STEMI). BACKGROUND:The effect of thrombolysis on post-percutaneous coronary intervention (PCI) angio-IMR, and its associations with MVO and IS remains unclear. METHODS:One hundred twenty-three STEMI patients randomized to receive 5 mg intravenous bolus of recombinant staphylokinase (r-SAK) or normal saline (NS) before PCI were recruited. Angio-IMR was computed in infarct-related arteries. MVO and IS were detected by cardiac magnetic resonance imaging. RESULTS:Compared with NS group, r-SAK group exhibited numerically lower post-PCI angio-IMR (39.12 U vs. 42.57 U; p = 0.567), MVO (54.0% vs. 70.9%; p = 0.059), MVO extent (0.70% vs. 1.90%; p = 0.101) and IS (21.30% vs. 24.50%; p = 0.079). Post-PCI angio-IMR was positively correlated with MVO extent (ρ = 0.347; p < 0.001) and IS (ρ = 0.324; p < 0.001). Receiver operating characteristic analyses showed moderate diagnostic performance of angio-IMR for MVO (area under the curve [AUC] = 0.750; p < 0.001), MVO > 2.6% (AUC = 0.735; p < 0.001) and IS > 25% (AUC = 0.712; p < 0.001). The exploratory optimal cut-off values for these endpoints were approximately 40 U. CONCLUSIONS:In STEMI patients, a single bolus of r-SAK before PCI was associated with numeric reductions in post-PCI angio-IMR, MVO, MVO extent and IS. Additionally, angio-IMR exhibited a significantly positive correlation with both MVO extent and IS, demonstrating the diagnostic value of this wire-free method for assessing microvascular injury.

We previously found that isoproterenol activates apamin-sensitive small-conductance Ca2+-activated K+ currents (IKAS) more in female than male rabbit ventricles. Isoproterenol activates all β-adrenoceptors (ARs). It remains unknown which AR is responsible for IKAS activation. We studied Langendorff-perfused rabbit hearts with dual optical mapping to determine the action potential duration and intracellular Ca2 + (Cai) during atrial pacing. Study I (six females and six males): baseline - 1 µm denopamine (specific β1-AR agonist) - 100 nm apamin. Study II (seven females and six males): baseline - pirbuterol 1 or 10 µm (specific β2-AR agonist) - 100 nm apamin. Study III (three females): baseline - 1 µm mirabegron (specific β3-AR agonist) - 100 nm apamin. During denopamine infusion, at a pacing cycle length (PCL) of 200 ms, apamin significantly prolonged action potential duration (APD) at the level of 25% repolarization (APD25) and 80% repolarization (APD80) in female ventricles, but not male ventricles. The Cai time-to-peak duration was significantly shortened by denopamine only in females, but not in males. At aPCL of 250 ms, Cai time-to-peak duration was significantly shortened following denopamine administration in both females and males. Subsequent administration of apamin significantly prolonged APD25 and APD80 in both females and males in the presence of denopamine. Neither pirbuterol nor mirabegron shortened Cai time-to-peak duration. Subsequent administration of apamin did not prolong APD80. We conclude that β1-AR, but not β2 or β3-AR, activates IKAS in rabbit ventricles. This rate-dependent effect exhibits a sex difference and is associated with a significant shortening of Cai time-to-peak duration. KEY POINTS: β1-adrenoceptor (AR) agonist denopamine activates the apamin-sensitive small-conductance Ca2+-activated K+ current (IKAS) in female rabbit ventricles at a pacing cycle length (PCL) of both 200 ms and 250 ms and in male ventricles only at a PCL of 250 ms. A significantly shortened time-to-peak of intracellular Ca2+ (Cai) transient is associated with IKAS activation. β2-AR agonist pirbuterol and β3-AR agonist mirabegron do not activate IKAS or shorten the Cai time-to-peak duration.

BACKGROUND:Women had a higher risk of heart failure with preserved ejection fraction (HFpEF) and diastolic dysfunction than men. OBJECTIVES:We hypothesize that (1) the high cholesterol (HC) diet causes HFpEF in female but not male hearts, and (2) adding salt to the HC diet worsens HFpEF. METHODS:We fed rabbits an HC diet (4 males and 4 females) or a high salt (HS)-HC diet (4 males and 4 females) for 14 weeks. The hearts were Langendorff-perfused for optical mapping. RESULTS:The HC diet and female sex were associated with increased E/e' ratios at sacrifice (P < .001 for both). The E/e' ratios were higher in the HC than in the HS-HC group (P < .001). Females had a larger left atrial diameter (P = .002) and more atrial fibrosis than males (P < .001). There was more ventricular fibrosis in HC than in HS-HC (P < .001). Apamin, a specific blocker of apamin-sensitive small conductance calcium-activated potassium current (IKAS), lengthened action potential duration more in females than males (by 8 ± 2 ms, P = .002) in the absence of isoproterenol. Apamin reduced intracellular calcium amplitudes (P < .001) and conduction velocity (P = .008), the phase singularities during ventricular fibrillation (VF) (P = .002), and dominant frequency during VF (P = .016) more in females. HC females (but not HC males or any HS-HC rabbits) showed significant increases in N-terminal pro-B-type natriuretic peptide levels at sacrifice (P < .001). CONCLUSION:The HC rabbit is a female-specific model of HFpEF. Adding salt to the HC diet improved rather than worsened the HFpEF. Apamin modulates this HFpEF model's electrophysiological parameters and VF patterns.