Background:Olanzapine is an antipsychotic agent with alpha-1-adrenergic receptor blockade properties. While olanzapine therapy has been associated with orthostatic hypotension. symptomatic hypotension unrelated to increased postural stress has not been previously reported. Case summary:A 24-year-old male, newly initiated on the antipsychotic olanzapine, presented with new-onset multiple apparent near-syncope and syncope episodes often occurring while he was seated. Physical and neurologic exams were normal. complete bood count, basic metabolic panel, and urine drug testing were unremarkable. Baseline electroencephalogram (EEG) and head CT were normal. Echocardiogram revealed preserved biventricular function with left ventricular ejection fraction 60%-65%. Comprehensive autonomic testing, including multi-channel ECG recording, beat-to-beat blood pressure monitoring, and simultaneous EEG, documented multiple symptomatic paroxysmal hypotensive episodes occurring while the patient remained seated, without associated bradyarrhythmia or tachyarrhythmia. EEG slowing (delta waves) consistent with cerebral hypoperfusion accompanied the hypotensive episodes. In the absence of an alternative explanation, olanzapine was discontinued, and the symptoms resolved over the following weeks, supporting an olanzapine-induced aetiology. Discussion:The antipsychotic olanzapine may trigger hypotension without orthostatic stress or evident arrhythmia, suggesting an accentuated vasodepressor effect consistent with olanzapine's known alpha-adrenergic blocker properties. Thus, olanzapine is a potential cause of intermittent, non-orthostatic hypotension; dose reduction or discontinuation should be considered in such cases.

BACKGROUND:The available risk prediction models are inadequate to identify a true low-risk patient for developing new-onset atrial fibrillation (AF) after typical atrial flutter (AFL) ablation. We aimed to determine whether adding markers of atrial myopathy to HATCH score (hypertension, age ≥75 years, transient ischemic attack/stroke, chronic obstructive pulmonary disease, and heart failure) can improve prediction of new-onset AF after ablation of typical AFL. METHODS:The study included 208 consecutive patients who underwent successful ablation of typical AFL at Minneapolis VA Medical Center and University of Minnesota Medical Center. Patients with history of AF prior to ablation were excluded. RESULTS:Among the 208 patients, 76 (36.5%) developed new-onset AF post AFL ablation. Mean follow-up duration was 62 ± 31.8 months. HATCH score was not associated with new-onset AF. When adding atrial myopathy (presence of at least one of the following: PTFV1 > 5000 µV*ms, interatrial block determined by biphasic inferior p wave with duration >120 ms, left atrium (LA) diameter ≥44 mm, or LA index ≥3 cm/m2) to HATCH score (HATCH-A2), the combination was independently associated with new-onset AF. The AF incidence between HATCH-A2 score of 0-1 and ≥2 were 6.7% and 40.5%, respectively (Odds ratio 9.04, 95% confidence interval: 2.05-39.81, p = 0.004). Particularly, when HATCH-A2 score was 0, none of the patients developed AF. CONCLUSIONS:Adding atrial myopathy to HATCH score improved predictability and could be used to delineate a true low-risk patient of new-onset AF after typical AFL ablation.

A drop of systemic blood pressure (BP) occurring shortly after individuals move from supine or seated position to upright posture with subsequent prompt spontaneous resolution is a common physiological occurrence in humans. If the induced hypotension is severe, lightheadedness or postural instability leading to falls and injury may occur. By consensus, a transient systolic BP drop >40 mmHg within 15 s of standing is deemed abnormal and has become termed 'initial orthostatic hypotension' (initial OH, iOH). However, the term 'initial OH' implies that another hypotensive event will follow shortly. In essence, if an OH event is deemed to be 'initial', then one might reasonably assume that a subsequent OH event is imminent. However, in the setting of abrupt movement to upright posture, the BP drop is usually solitary and brief (resolution within 15-30 s); thereafter the individual is usually OH symptom-free until they undertake another similar postural change. Currently, there is no single descriptor for a posture change driven, short-lived, spontaneously resolving OH event, without the implication that further hypotension is imminent as is implied by the term 'initial OH'. In order to foster more accurate nomenclature, we recommend that 'initial OH' be retired, and 'immediate OH' or transient 'immediate OH' be substituted. While 'immediate' OH may be imperfect, it conveys an early onset event without implying additional imminent OH. Thus immediate OH or transient immediate are more accurate descriptors of this common transient hypotensive event. The abbreviation, 'iOH', remains unchanged.

Sudden cardiac arrest, and in particular sudden out-of-hospital cardiac arrest (OHCA) remains a major public health concern in which survival statistics, and in particular neurologically intact survival statistics, have remained largely unimproved over many decades. Overall survival remains approximately 10%, being somewhat better in victims receiving bystander cardiopulmonary resuscitation (CPR), and those who are found to have a shockable rhythm (i.e., VT or VF). CPR and defibrillation (especially public-access defibrillation) remain the essential immediate management tools. However, recent research has introduced several novel adjunctive interventions (e.g., mechanical compression-decompression devices, 'head-up' CPR methodology, portable extra-corporeal circulatory assistance [ECPR]) that will hopefully impact survival positively. In any case, it is apparent that no single resuscitative tool will be sufficient to markedly improve OHCA survival; the combined application of a multi-faceted strategy is needed. This might comprise bystander CPR, combined use of 'head-up' CPR along with impedance threshold valve [ITD] and active compression-decompression mechanical chest compression devices. Application of mobile ECPR devices as early as possible during resuscitation appears to improve outcomes albeit expensive and complex to deploy broadly. Employed together, these novel steps, offer the possibility of moving the survival needle in a positive direction.

Background/Introduction: Immediate/Initial orthostatic hypotension (iOH) presents as an abnormal transient blood pressure (BP) decrease immediately upon assuming upright posture, with prompt recovery. The pathophysiology underlying this BP drop and subsequent recovery is incompletely understood. Hypothesis: We hypothesized that the initial BP nadir is determined primarily by gravitational forces and therefore should be similar in healthy subjects (Controls) and individuals exhibiting pure autonomic failure (PAF), whereas recovery time is more likely determined by reflex sympathetic activation, and thus would be expected to be delayed in PAF. Methods: Autonomic testing was undertaken in 116 healthy individuals (age 36±14.3 years) and 35 PAF patients in whom iOH was measurable (age 67±13 years). Continuous non-invasive beat-to-beat BP and ECG recordings were obtained with subjects seated and then during movement to Active Standing (AS). We measured initial systolic BP drop (ΔSBP), time to BP nadir, recovery time (seconds from nadir to 90% of baseline), heart rate increment (ΔHR), and the ΔHR/ΔSBP ratio. Data underwent Shapiro-Wilk normality testing followed by parametric or non-parametric analyses as appropriate. Results: Initial systolic BP decrements with AS were comparable in Controls and PAF patients (-33±14 mmHg vs -36.4±21, p=0.38) despite significantly different baseline SBP values (126±18mmHg vs 142±22, p<0.01). Conversely, compared to Controls, Recovery time was significantly prolonged in PAF (38.6±14.2 vs 18.7±6.3 seconds, p<0.001). Further, compensatory HR response initiated by BP drop was markedly attenuated in PAF (+8±9 vs +19±11 bpm, p<0.01), yielding significantly reduced ΔHR/ΔSBP ratios (0.22±0.25 vs 0.76±0.58 bpm/mmHg, p<0.01). Conclusion: These findings provide physiological evidence that in iOH, BP decrease is driven principally by gravitational hydrostatic effect whereas BP recovery kinetics are importantly determined by autonomic tone, most likely baroreflex-mediated sympathetic activation, and thus are delayed in PAF.

Background: Outcomes after pulmonary vein isolation (PVI) for persistent atrial fibrillation (AF) remain limited, motivating patient-specific strategies to identify non-PV sources. Ripple Frequency is an automated mapping algorithm designed to localize AF sources for targeted ablation by highlighting regions with high frequency directional changes in electrogram dV/dT. Objective: To evaluate 12-month freedom from AF and any atrial arrhythmia following non-PV Ripple Frequency-guided ablation for persistent AF. Methods: We analyzed 72 patients undergoing first-time ablation for persistent AF. After PVI, ablation was directed at non-PV atrial regions in the top quartile of each patient's Ripple Frequency maps. The primary endpoint was first AF recurrence >30 s after a 90-day blanking period on or off antiarrhythmic drugs (AADs); secondary endpoints included atrial tachycardia/flutter (AT/AFL), any atrial arrhythmia, and safety. Freedom from AF at 12 months was compared with that observed in the PVI arm of the STAR-AF II trial for additional context. Results: Ripple Frequency targets were ablated in 66/72 patients (92%), yielding acute AF termination in 64/72 patients (88.9%). Single procedure 12-month freedom from AF was 95.8% (95% CI 87.6-98.6) on/off AAD, and freedom from any atrial arrhythmia was 72.2% (95% CI 60.3-81.1). After 1.2 procedures, these rose to 97.2% and 90.3%. Compared with the STAR-AF II PVI arm (60%), 12-month AF freedom was 35.8% (95% CI 22.3-40.0%) higher. Conclusion: In this single-center cohort, non-PV ablation guided by Ripple Frequency was associated with a high 12-month AF and any arrhythmia freedom with no major complications. ### Competing Interest Statement Dr Melby contributed to developing the Ripple Frequency algorithm but holds no equity, royalties, or licensing income related to the technology. Dr Melby has received educational honoraria and consulting fees from J&J MedTech (payments to the author). Dr Itah is an employee of J&J MedTech. J&J MedTech had no role in study design, data collection, analysis, interpretation, manuscript preparation, or the decision to submit. All other authors report no conflict of interest. ### Funding Statement No external funding was received. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Ripple Frequency software obtained FDA 510(k) approval (K221112). The Allina Health Institutional Review Board, Minneapolis, Minnesota, approved this study (IRB # 2083021). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes De-identified participant data and statistical code will be made available upon reasonable request to the corresponding author, following publication.

The pulmonary root has emerged as a critical target for catheter ablation of ventricular arrhythmias, accounting for approximately 11

Voluntary stretching of upper back and shoulder muscles is often associated with a sense of well-being of unknown cause. The goal of this study was to examine the impact of shoulder/upper back stretching on heart rate (HR) and blood pressure (BP) responses in healthy individuals. Twenty-four healthy individuals underwent continuous beat-to-beat HR and BP monitoring during active standing (AS) and during shoulder/upper back extension stretching. Measurements were compared using appropriate statistical tests. With AS, HR increased (median 24 bpm) and systolic BP decreased (median - 28 mmHg). Shoulder/upper back stretching elicited a similar BP drop but a lesser HR increment (p < 0.001). The HR increase per mmHg BP fall (∆HR/∆BP) was significantly lower during stretch than during AS (0.34 vs. 1.1 beats/min/mmHg; p < 0.001). Thus, the HR response with stretch-induced BP fall averaged only 30.9% of that seen with AS. Shoulder/upper back muscle stretching induces transient BP reduction with only limited compensatory tachycardia compared to hypotension during AS. These findings suggest a neural reflex mechanism possibly initiated by muscle mechanoreceptors, with predominant vasodepression that may contribute to relaxation and a sense of well-being.

Aims:Syncope remains a diagnostic challenge despite advancements in testing and treatment. Cardiac syncope is an independent predictor of mortality and can be difficult to distinguish from other causes of transient loss of consciousness (TLOC). This paper explores whether artificial intelligence (AI) can improve the evaluation and management of patients with syncope. Methods and results:We conducted a literature review and incorporated the opinions of experts in the fields of syncope and AI. The cause of TLOC is often unclear, hospitalization criteria are ambiguous, diagnostic tests are frequently non-informative, and assessments are costly. Patients are left with unanswered questions and limited guidance. Artificial intelligence (AI) has the potential to optimize syncope evaluation by processing large data sets, detecting imperceptible patterns, and assisting clinicians. However, AI has limitations, including errors, lack of human empathy, and uncertain clinical utility. Liability issues further complicate its integration. We present three viewpoints: (i) AI is crucial for advancing syncope management; (ii) AI can enhance the patient experience; and (iii) AI in syncope care is inevitable. Conclusion:Artificial intelligence may improve syncope diagnosis and management, particularly through machine learning-based test interpretation and wearable device data. However, it has yet to surpass human clinical judgment in complex decision-making. Current challenges include gaps in understanding syncope mechanisms, AI interpretability, generalizability, and clinical integration. Standardized diagnostic approaches, real-world validation, and curated data sets are essential for progress. Artificial intelligence may enhance efficiency and communication but raises concerns regarding confidentiality, bias, inequities, and legal implications.

BACKGROUND:The path from paroxysmal to persistent atrial fibrillation (AF) is still poorly understood, leading to suboptimal treatment outcomes. OBJECTIVES:In this study, the authors sought to investigate the level of fibrosis in different stages of AF with the use of 18F-labeled aluminum fluoride (AlF) targeting fibroblast activation protein inhibitor (FAPI) positron emission tomography (PET)-magnetic resonance imaging (MRI). METHODS:A total of 78 patients with AF and 49 health volunteers were enrolled in this study. All participants received FAPI-PET-MRI. Measurement of positive ratios and the proportion was performed in various regions of the left atrium posterior wall (LAPW), the atrial septum, anterior wall, appendage, and roof. Patients were categorized into paroxysmal (PAF), persistent (PsAF), and permanent (PmAF) AF groups based on 7-day ambulatory monitoring and history. Another cohort of 36 patients undergoing cardiac surgery, with 124 fragments of image-guided tissue, consented to biopsy during cardiac surgery for histology examinations. RESULTS:The positive ratio for fibrosis was significantly higher in the PsAF and PmAF groups compared with the PAF and healthy volunteer groups across all atrial regions (P < 0.05). The LAPW showed the highest level of fibrosis. The AUC for the positive ratio was 0.991 to differentiate PAF from PsAF in the LA (cutoff: 0.072), and 0.983 in the LAPW (cutoff: 0.025). Between PsAF and PmAF, the AUC was 0.756 in the LA (cutoff: 0.382). Histologic analysis demonstrated an increased area of fibrotic deposition in regions with increased 18F-FAPI uptake. CONCLUSIONS:LAPW fibrosis may be an important factor in the progression from PAF to PsAF. (A Single-Center, Prospective, Cohort Study on the Clinical Application of 18F-FAPI PET Imaging in Atrial Fibrillation; ChiCTR2300075806).

Background: Postural Orthostatic Tachycardia Syndrome (POTS) is characterized by exaggerated heart rate increase upon standing, often accompanied by disabling symptoms such as palpitations, lightheadedness, fatigue and ‘brain fog’. As awareness of POTS has grown, its diagnosis has become more frequent; however, symptom overlap with other conditions such as orthostatic hypotension, vasovagal syncope, long-COVID, and anxiety raises the possibility of overdiagnosis and misclassification. Objective: To assess the frequency with which comprehensive autonomic testing confirms the diagnosis in patients referred with a presumptive clinical diagnosis of POTS Methods: The study population comprised 36 patients with presumed clinical diagnoses of POTS who were referred for autonomic testing between 2023 and 2025. All patients underwent standardized autonomic evaluation including active stand (AS), tilt table testing, Valsalva maneuver, and respiratory sinus arrhythmia. Laboratory confirmation of POTS was established by a baseline heart rate (HR) >60 bpm, a HR increase ≥30 bpm (or ≥40 bpm in those <20 years) on orthostatic challenge without hypotension and ultimate HR >100 bpm within 10 minutes. Results: The cohort was predominantly female (94%) with a median age of 31 years [21–48]. Common presenting symptoms included lightheadedness (55%), palpitations (50%), syncope or near-syncope (30%), and fatigue (5%). Notably, 75% had documented anxiety or depression, 22% had Ehlers-Danlos Hypermobility syndrome, and 36% had prior COVID-19 infection. Autonomic testing confirmed a diagnosis of POTS in 11% (4/36) of patients. Normal autonomic testing was observed in 61% (22/36), and 27% (10/36) were reclassified with alternative diagnoses such as orthostatic hypotension or vasovagal syncope. The mean HR increase for POTS patients with AS was 34.33±25 bpm, the maximum HR achieved was 124±17 bpm, and the average orthostatic systolic blood pressure drop was 23±17 mmHg. Conclusion: In this cohort of patients referred for suspected POTS, only 11% met diagnostic criteria during autonomic testing, while the majority either had normal results or were reclassified with alternative autonomic conditions. These findings suggest that overdiagnosis of POTS is common in the referral population and highlight the role of formal autonomic testing to improve diagnostic accuracy. Testing may help prevent misdiagnosis, reduce unnecessary treatment, and support more precise assessment of prognosis.

The Head-Up Tilt Test (HUTT) has been widely used for the past four decades as part of the overall assessment of the potential causes of collapse in patients with recurring transient loss of consciousness (TLOC) of unknown cause. The ability of a positive HUTT often to reproduce patient symptoms and illustrate to the patient that the physician is confident of the diagnosis have been major advances in clinical TLOC management. Tilt testing has been particularly important in understanding and diagnosing vasovagal syncope (VVS) and orthostatic hypotension. Despite HUTT having great clinical utility, different HUTT protocols and drug provocations result in different test yields. Limited HUTT reproducibility has led some researchers to criticize HUTT utility. As in most medical tests, limitations are part of the test. Herein, we provide a contemporary review of HUTT's utility in diagnosing and managing various TLOC disorders with intent to clarify its role in clinical practice.

Background/Introduction: Ventricular fibrillation (VF) storm represents a life-threatening emergency with high mortality. When VF becomes incessant and refractory to antiarrhythmic therapy, catheter ablation is not usually considered. We present a case of successful VF ablation in a patient with incessant, refractory VF requiring mechanical circulatory support. Objective: To report a successful catheter ablation of incessant VF in a patient with ischemic cardiomyopathy on mechanical circulatory support. Methods: N/A Results: A 77-year-old male with ischemic cardiomyopathy (LVEF 35%), multivessel CAD status post PCI, severe aortic stenosis status post TAVR, and prior out-of-hospital cardiac arrest with ICD implantation, presented with VF storm despite amiodarone and lidocaine infusions. Despite deep sedation, intubation, stellate ganglion block, and maximal antiarrhythmic therapy, he developed incessant VF with hemodynamic collapse, requiring emergent VA ECMO. Post-ECMO, VF became incessant over three consecutive days, and unresponsive to defibrillation. VF catheter ablation was performed while on VA ECMO support. Since the patient could not be defibrillated successfully, we decided to map the left ventricle during ongoing VF. We targeted the posterior and mid fascicular area based on high frequency fascicular signals on the border of a basal septal scar using 40-watt lesions for 30 seconds (Images 1 and 2). Following septal “defasciculation”, a single defibrillation at 360 joules successfully converted the patient to atrial-paced, ventricular-sensed rhythm. The QRS duration increased from 108 ms to 156 ms, which recovered the next day. For the first time in three days, the patient remained VF-free. Post-ablation, there was immediate hemodynamic improvement with reduced vasopressor requirements. The patient was decannulated after 48 hours and the antiarrhythmic therapy was rapidly de-escalated. He was discharged home on low dose amiodarone and in normal sinus rhythm. Conclusion: This case demonstrates that targeted catheter ablation can successfully terminate incessant VF refractory to medical and adrenergic suppressive therapies by defasciculation of the septal scar and targeting very high frequency fascicular signals. VA ECMO provided essential circulatory support enabling precise ablation during VF. This potentially expands the role of catheter ablation as a life-saving intervention for incessant refractory VF.

BACKGROUND:Stretch-induced syncope (SIS) is a poorly understood condition that we hypothesized may be due to a neural reflex hypotensive response triggered by stretching of shoulder/upper back muscles. OBJECTIVE:This study compared the impact of shoulder/upper back stretching on heart rate (HR) and blood pressure (BP) responses in patients with SIS, with the findings in controls evaluated for symptoms unrelated to stretching. METHODS:The study population comprised 33 individuals: 9 otherwise healthy patients with SIS and 24 healthy controls. Beat-to-beat HR and systolic BP (SBP) and mean arterial pressure (MAP) responses were recorded during active standing (AS), Valsalva maneuver, and respiratory sinus arrhythmia. Patients with SIS also underwent carotid sinus massage while seated. In addition, all subjects undertook an active shoulder/upper back extension maneuver for approximately 10-15 seconds while keeping forearms still and breathing normally. RESULTS:Stretch elicited a drop in BP to nadir values of SBP and MAP (95.9 ± 24.2 and 76.2 ± 17.3 mm Hg in patients with SIS and controls, respectively). However, stretch-induced SBP and MAP decrease was greater in patients with SIS (P=.003 and P=.013). Further, the ratio of the ΔHR increase to ΔBP drop was lower (P=.001) during stretch-induced hypotension than during comparable hypotension induced immediately after AS. CONCLUSION:Shoulder/upper back stretching induces a transient hypotensive response in humans, with BP fall greater in patients with SIS than in controls. Further, compensatory HR increment associated with stretch-induced hypotension was less in both patients with SIS and controls than comparable transient BP fall with AS, suggesting chronotropic restraint. Thus, SIS results from exaggerated stretch-induced vasodepression with limited compensatory tachycardia favoring a neural reflex mechanism.