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OBJECTIVES: Immune checkpoint inhibitor (ICI)-associated myocarditis, particularly severe ICI-associated myocarditis, has a high mortality rate. However, the predictive value of electrocardiogram (ECG) remains unclear. The present study aimed to evaluate the predictive value of clinical and electrocardiographic parameters for severe myocarditis. METHODS: Clinical and electrocardiographic data of 73 cancer patients with ICI-associated myocarditis were retrospectively collected. The severity of ICI-associated myocarditis was graded using the NCCN guidelines for managing immunotherapy-related toxicities. Myocarditis grades 1-2 and grades 3-4 were classified as mild and severe myocarditis, respectively. Logistic regression analysis was performed to analyze the predictive value of each parameter in predicting severe myocarditis. RESULTS: Among the 73 patients with myocarditis, 20 (27.4%) patients had severe myocarditis. Compared with mild myocarditis group, sinus tachycardia (p = 0.001), QRS duration ≥110 ms (p = 0.001), prolonged QTc interval (p < 0.001), and bundle branch block (p = 0.007) at the time of myocarditis were more common in the severe myocarditis group. Logistic regression analysis revealed that sinus tachycardia (p = 0.028) and QTc interval prolongation (p = 0.007) were predictors of severe myocarditis. Whereas the predictive value of other electrocardiographic parameters was weak. Concurrent targeted therapy didn't increase the risk of severe myocarditis. A high NT-proBNP level was associated with severe myocarditis. CONCLUSIONS: ECG at the onset of myocarditis manifested as sinus tachycardia and prolonged QTc interval predicted a high risk of severe myocarditis. Early detection of ECG abnormalities may faciliate early detection of severe ICI-associated myocarditis.

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Persistent sinus tachycardia (pST) has been associated with adverse cardiovascular events in critically ill patients. Pharmacological control of heart rate with negative inotropic agents has proven to be safe but could be potentially dangerous in patients with concomitant right ventricular (RV) dysfunction. Ivabradine, a medication devoid of negative inotropy, could be a potentially safe solution for this patient population when adequate heart rate control is desired. A 17-year-old male with a history of vaping developed acute respiratory distress syndrome (ARDS) and RV dysfunction, requiring extra corporal life support (ECLS). He suffered from pST. Given his RV dysfunction, a beta-blocker was avoided, and ivabradine was used safely with improvement of his pST. This case demonstrates the efficacy of ivabradine to reduce heart rate and avoid the use of beta-blockers for patients with RV dysfunction, which could be detrimental. Ivabradine was shown to lower the heart rate without altering hemodynamic parameters.

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INTRODUCTION: Inappropriate sinus tachycardia (IST) is a common condition with frequently not tolerated beta-blockers or ivabradine and a high rate of complication in ablation strategy; we describe an alternative anatomical approach of sinus node (SN) modulation. METHODS: This retrospective study describes a case series of 6 patients from two centers diagnosed with symptomatic IST undergoing SN ablation. RESULTS: The mean age was 40.6 ± 13.9 years; five of the six patients were female, 100% of patients reported heart palpitations, and 66% reported dizziness, the average heart rate (HR) on a 24-h Holter was 93.2 ± 7.9 bpm. HR during the first stage of a stress test using a standard Bruce protocol was 150 ± 70 bpm, The average HR on 24-h Holter postablation was 75 ± 5.6 bpm, the sinus rate HR during stage 1 of a Bruce protocol exercise stress test was 120 ± 10 bpm. CONCLUSION: This is the first case series reporting the acute and long-term results of a novel anatomical approach for SN modulation to treat IST targeting the arcuate ridge (AR) under intracardiac echography (ICE) guidance. The novel anatomic ICE-guided catheter ablation approach aimed to identify the earliest activation at the AR with an extension of RF lesions toward its septal region seems effective and safe to modulate the SN in symptomatic patients with IST refractory to medical treatment.

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Background Within the cardiovascular system, sinus tachycardia has been a noted finding in patients with post-COVID-19 syndrome (symptoms persisting beyond 12 weeks post-infection). To better understand post-COVID-19 tachycardia, we examined the prevalence of sinus tachycardia 12-16 weeks after diagnosis of SARS-COV-2 infection and its correlation with intensive care utilization, ventilator use, and mortality in vaccinated and unvaccinated patients. Methods We identified adult patients in the TriNetX COVID-19 Research Network with confirmed SARS-COV-2 diagnosis from January 20th, 2020, to February 14th, 2022, and sinus tachycardia 12-16 weeks after diagnosis. Two cohorts were created: patients who developed tachycardia 12 weeks after initial diagnosis and patients without tachycardia. The tachycardia cohort was divided further based on vaccination status. Results Of 1,363,907 patients included, 30,705 (2.2%) developed tachycardia. The patients with tachycardia had more comorbidities. Using propensity score matching (PSM), two cohorts of 30,702 were created. The SARS-COV-2 tachycardic cohort had higher mortality (5.1% vs 2.1%, p<0.001), critical care utilization (5.8% vs 2.2%, p<0.001), and ventilator use (1.8% vs 0.5%, p<0.001). Out of 22,878 patients with persistent tachycardia and recorded vaccination status, 14,840 (65%) were not vaccinated. Mortality (5.9% vs 2.3%, p<0.001), critical care utilization (8.3% vs 3.6%, p<0.001), and ventilator use (3.8% vs 0.6%, p<0.001) were higher in the non-vaccinated patients compared with the vaccinated patients after PSM.  Conclusion The prevalence of persistent tachycardia after SARS-COV-2 infection is notable at 2.2%. Patients with persistent tachycardia have higher mortality rates and demonstrate greater healthcare utilization at one year compared to patients without persistent tachycardia, particularly if unvaccinated.

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The pathogenesis of inappropriate sinus tachycardia is not well understood, and the symptoms of inappropriate sinus tachycardia can be difficult to manage. Here, we present a case of inappropriate sinus tachycardia refractory to medical therapy and discuss our approach to sinus node modification by catheter ablation.

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Inappropriate sinus tachycardia (IST) is one of the manifestations of the post-COVID-19 syndrome (PCS), which pathogenesis remains largely unknown. This study aimed to identify potential risk factors for IST in individuals with PCS. The 1349 patients with PCS were included into the study. Clinical examination, 24H Holter ECG, 24H ambulatory blood pressure monitoring and biochemical tests were performed 12-16 weeks after the COVID-19 in all participants. IST was found in 69 (3.5%) individuals. In the clinical assessment IST patients were characterized by a higher age (p < 0.001) and lower prevalence of the diagnosed hypertension (p = 0.012), compared to remaining patients. Biochemical testing showed higher serum triglycerides (1.66 vs. 1.31 pmol/L, p = 0.007) and higher prevalence of a low high-density lipoprotein (HDL) cholesterol (24.6% vs. 15.2%, p = 0.035) in the IST group. Subsequently, the triglicerydes (TG)/HDL ratio, an indicator of insulin resistance, was significantly higher in the IST individuals (3.2 vs. 2.4, p = 0.005). 24H monitoring revealed a significantly higher minimum diastolic, maximum systolic and mean arterial blood pressure values in the IST group (p < 0.001 for all), suggesting a high prevalence of undiagnosed hypertension. A multivariate analysis confirmed the predictive value TG/HDL ratio >3 (OR 2.67, p < 0.001) as predictors of IST development. A receiver operating characteristic curve analysis of the relationship between the TG/HDL ratio and the IST risk showed that the predictive cut-off point for this parameter was 2.46 (area under the ROC curve = 0.600, p = 0.004). Based on these findings, one can conclude that insulin resistance seems to be a risk factor of IST, a common component of PCS.

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Background: Pericarditis is the most common complication following hybrid sinus node-sparing ablation for inappropriate sinus tachycardia (IST)/postural orthostatic tachycardia syndrome (POTS). Objective: The study sought to evaluate the association of prophylaxis therapy on the risk of symptomatic pericarditis following hybrid IST/POTS ablation. Methods: All consecutive patients undergoing to hybrid ablation of symptomatic IST/POTS refractory or intolerant to drugs were retrospectively analyzed. Pharmacological prophylaxis therapy was based on acetylsalicylic acid and colchicine started on the day of the ablation and continued for at least 3 months. The primary endpoint was occurrence of symptomatic pericarditis. The secondary endpoint was occurrence of pericarditis-related complications, including the following: duration of pericarditis >3 months, hospitalization for pericarditis, postpericardiectomy pleuro-pericarditis, and pericardiectomy. Results: A total of 220 patients undergone to hybrid IST/POTS ablation were included and 44 (20%) underwent prophylaxis therapy. Pericarditis occurred in 101 (45.9%) patients, with 97 (96%) in the first 5 days. At survival analysis, prophylaxis was associated with higher rate of freedom from pericarditis (81.9% vs 47.2%, log-rank P < .001). Pericarditis-related complications were low, occurring in 7 (3.2%) patients. There was no difference in pericarditis-related complications between the patients who underwent prophylaxis therapy and patients who did not. At Cox multivariate analysis, predictors of pericarditis were IST (vs POTS) (hazard ratio 0.61, 95% confidence interval0.39-0.99, P = .04) and prophylaxis therapy (hazard ratio 0.27, 95% confidence interval 0.13-0.55, P < .001). Conclusion: In a large cohort of patients undergoing hybrid ablation for IST/POTS, a prophylaxis therapy with acetylsalicylic acid and colchicine was associated with a lower rate of symptomatic pericarditis.

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AIMS: A novel sinus node (SN) sparing hybrid ablation for inappropriate sinus node tachycardia (IST)/postural orthostatic tachycardia syndrome (POTS) has been demonstrated to be an effective and safe therapeutic option in patients with symptomatic drug-resistant IST/POTS. The aim of this study was to evaluate the long-term rate of redo procedures after hybrid IST ablation and procedural strategy, outcomes and safety of redo procedures. METHODS AND RESULTS: All consecutive patients from 2015 to 2023 were prospectively enrolled in the UZ Brussel monocentric IST/POTS registry. They were analysed if the following inclusion criteria were fulfilled: 1) diagnosis of IST or POTS, 2) symptomatic IST/POTS refractory or intolerant to drugs, and 3) hybrid SN sparing ablation performed. The primary endpoint was redo procedure. The primary safety endpoint was pacemaker (PM) implantation. A total of 220 patients undergone to hybrid IST ablation were included, 185 patients (84.1%) were treated for IST and 61 patients (27.7%) for POTS.After a follow-up of 73.3 ± 16.2 months, 34 patients (15.4%) underwent a redo. A total of 23 patients (67.6%) had a redo for IST recurrence and 11 patients (32.4%) for other arrhythmias. Pacemaker implantation was performed in 21 patients (9.5%). Nine patients (4.1%) had no redo procedure and experienced sick sinus syndrome requiring a PM. Twelve patients (5.4%) received a PM as a shared therapeutic choice combined with SN ablation procedure. CONCLUSION: In a large cohort of patients the long-term free survival from redo procedure after hybrid IST ablation was 84.6% with a low PM implantation rate.

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In a family with inappropriate sinus tachycardia (IST), we identified a mutation (p.V240M) of the hyperpolarization-activated cyclic nucleotide-gated type 4 (HCN4) channel, which contributes to the pacemaker current (If) in human sinoatrial node cells. Here, we clinically study fifteen family members and functionally analyze the p.V240M variant. Macroscopic (IHCN4) and single-channel currents were recorded using patch-clamp in cells expressing human native (WT) and/or p.V240M HCN4 channels. All p.V240M mutation carriers exhibited IST that was accompanied by cardiomyopathy in adults. IHCN4 generated by p.V240M channels either alone or in combination with WT was significantly greater than that generated by WT channels alone. The variant, which lies in the N-terminal HCN domain, increased the single-channel conductance and opening frequency and probability of HCN4 channels. Conversely, it did not modify the channel sensitivity for cAMP and ivabradine or the level of expression at the membrane. Treatment with ivabradine based on functional data reversed the IST and the cardiomyopathy of the carriers. In computer simulations, the p.V240M gain-of-function variant increases If and beating rate and thus explains the IST of the carriers. The results demonstrate the importance of the unique HCN domain in HCN4, which stabilizes the channels in the closed state.

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BACKGROUND: Supraventricular tachycardias (SVTs), despite having various anatomical substrates and pathophysiological mechanisms, frequently show similar electrocardiographic presentations. OBJECTIVES: To locate and characterize atrial deflections (ADs) on 12-lead electrocardiograms in dogs with sustained rapid SVT and assess the utility of different electrocardiographic variables in differentiating types of tachycardia. ANIMALS: Ninety-two dogs with orthodromic atrioventricular reciprocating tachycardia, 17 with atrial flutter, 33 with focal atrial tachycardia recorded and confirmed by electrophysiological study, and 40 dogs with sinus tachycardia. METHODS: Atrial deflection position on the 12-lead surface electrocardiogram was assessed according to the sequence of intracardiac activation. Its features were evaluated together with the relationship between AD and QRS complex interval (AD-R) and QRS complex and AD interval (R-AD). RESULTS: Orthodromic atrioventricular reciprocating tachycardia was characterized by an AD-AD interval of 213 ± 30 ms, mean electrical axis (MEA) of AD of -90 (-90/-78)°, R-AD interval of 75 (65-80) ms, and R-AD/AD-R of 0.54 (0.45-0.64). Atrial flutter was characterized by an AD-AD interval of 199 ± 57 ms, MEA of 76° (72/81), R-AD of 120 (72-144) ms, and R-AD/AD-R of 0.81 (0.63-1.13). Focal atrial tachycardia was characterized by an AD-AD interval of 270 ± 38 ms, MEA of 49 (-72/76)°, R-AD of 160 (120-200) ms, and R-AD/AD-R of 1.45 (0.92-1.67). Sinus tachycardia was characterized by an AD-AD interval of 292 ± 31 ms, MEA of 66° (52/73), R-AD of 215 (192-222) ms, and R-AD/AD-R of 2.68 (2.25-3.08). CONCLUSIONS AND CLINICAL IMPORTANCE: Analyzing AD on 12-lead electrocardiogram is helpful in differentiating the most common SVTs in dogs.

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Background: Inappropriate sinus tachycardia (IST) is characterized by a continuum of symptoms, and the aetiology of IST is imprecise. IST-induced autonomic dysfunction is well known, but IST-induced atrio-ventricular block is not reported to our knowledge. Case summary: A 67-year-old female presented with a 4-day history of random intermittent difficulty in breathing, chest tightness, palpitations, and dizziness, with a recorded heart rate of 30 beats per minute (BPM) on home monitoring equipment. The initial electrocardiogram (ECG) demonstrated sinus rhythm with intermittent Mobitz type I second degree atrio-ventricular (AV) block, with continuous cardiac monitoring demonstrating frequent episodes of Wenckebach phenomenon throughout the day, with a sinus rate of 100-120 BPM. Echocardiogram showed no significant structural abnormalities. The patient was on bisoprolol, and hence, it was suspected Wenckebach may be due to that and so stopped. However, there was no tangible effect on rhythm 48 hours after stopping bisoprolol, leading to a suspicion of IST-induced Mobitz type I second degree AV block; and so decided to introduce ivabradine 2.5 mg twice daily. After 24 hours of Ivabradine, the patient remained in sinus rhythm with no documented episodes of Wenckebach phenomenon on cardiac monitor, a finding subsequently confirmed by 24-hour Holter monitoring. During a recent follow-up visit in clinic, the patient remained symptom-free, with an ECG demonstrating sinus rhythm at a physiological rate. Discussion: Mobitz type I second degree AV block is usually due to reversible conduction block at the level of the AV node whereby malfunctioning AV nodal cells tend to progressively fatigue until they fail to conduct an impulse. Under conditions of increased vagal tone and autonomic dysfunction, Wenckebach occurrence will be increased. Thus, selective impulse conduction within the sinoatrial (SA) node by ivabradine to reduce beat conduction to the AV node in patients with IST/dysautonomia-induced Mobitz type I AV will reduce the occurrence of Wenckebach.

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Postural orthostatic tachycardia is a syndrome characterized by an elevated heart rate in response to standing. This syndrome typically presents in late adolescence and early adulthood, with a higher percentage occurring in females. This syndrome is often seen following a viral infection, pregnancy, surgery, or intense psychological stress. This condition presents a wide range of symptoms that vary depending on its unclear etiology. We present the case of a 21-year-old woman with convulsions associated with postural orthostatic tachycardia syndrome after being misdiagnosed with a psychiatric condition for many years.

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Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder caused by dystrophin gene mutation resulting in muscle weakness, motor delays, difficulty in standing, and inability to walk by 12 years. As disease progresses, it leads to cardiac and respiratory failure. Evaluation of cardiac autonomic status and echocardiography in DMD patients at a young age can be a potential biomarker to assess disease progression. This study aimed to investigate the younger DMD population of 5-11years of age with mild to moderate cardiac involvement for early detection using non-invasive and cost-effective tools. Genetically confirmed male DMD patients, aged 5-11 years (n = 47), screened from the outpatient department of a tertiary neuroscience institution were subjected to heart rate variability and echocardiographic analysis, and values were correlated with their clinical variables. DMD patients showed a significantly higher difference in HR, interventricular septum, E m/s, and E-wave to A-wave (E/A) ratio than normal values (p < 0.001). Significantly higher HR indicates initial sinus tachycardia and decreased IVD (d), and increased E m/s and E/A ratio mark the onset of cardiac symptoms in DMD patients even though its chamber dimension remains normal and are associated with cardiac muscle fibrosis.

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Neuroleptic malignant syndrome (NMS) is a rare, life-threatening emergency caused more commonly by typical antipsychotics. However, unusual presentations of NMS are intermittently reported with the use of atypical antipsychotics. We present the case of a 42-year-old gentleman with schizoaffective and bipolar disorder who was admitted for change in mentation and lithium toxicity. His mentation did not improve despite being dialyzed and the resolution of lithium level to baseline. He developed persistent tachycardia and hyperthermia, initially attributed to Streptococcal infection. But despite appropriate antibiotic therapy, his clinical symptoms did not improve. An extensive workup for his neurological symptoms, including lumbar puncture, 5-hydroxy indole acetic acid urine test, and brain magnetic resonance imaging, was inconclusive of any underlying etiology. Given the suspicion of atypical NMS, bromocriptine 2.5 mg three times daily was initiated. This led to the gradual resolution of his symptoms and a return to his baseline mental status. Diagnosing atypical NMS can be challenging and must be differentiated from similar disorders. Lithium toxicity can predispose patients to develop NMS.

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BACKGROUND: Dysautonomia seems to be important for the pathophysiology of psychosomatic diseases and, more recently, for long COVID. This concept may explain the clinical symptoms and could help open new therapeutic approaches. METHODS: We compared our data from an analysis of heart rate variability (HRV) in an active standing test in 28 adolescents who had developed an inappropriate sinus tachycardia (IST, n = 13) or postural orthostatic tachycardia syndrome (POTS, n = 15) after contracting COVID-19 disease and/or vaccination with 64 adolescents from our database who developed dysautonomia due to psychosomatic diseases prior to the COVID-19 pandemic. We prove the effects of our treatment: omega-3 fatty acid supplementation (O3-FA, n = 18) in addition to propranolol (low dose, up to 20-20-0 mg, n = 32) or ivabradine 5-5-0 mg (n = 17) on heart rate regulation and heart rate variability (HRV). RESULTS: The HRV data were not different between the adolescents with SARS-CoV-2-related disorders and the adolescents with dysautonomia prior to the pandemic. The heart rate increases in children with POTS while standing were significantly lower after low-dose propranolol (27.2 ± 17.4 bpm***), ivabradine (23.6 ± 8.12 bpm*), and O-3-FA (25.6 ± 8.4 bpm*). The heart rate in children with IST while lying/standing was significantly lower after propranolol (81.6 ± 10.1 bpm**/101.8 ± 18.8***), ivabradine (84.2 ± 8.4 bpm***/105.4 ± 14.6**), and O-3-FA (88.6 ± 7.9 bpm*/112.1/14.9*). CONCLUSIONS: The HRV data of adolescents with dysautonomia after COVID-19 disease/vaccination are not significantly different from a historical control of adolescents with dysautonomia due to psychosomatic diseases prior to the pandemic. Low-dose propranolol > ivabradine > omega-3 fatty acids significantly decrease elevated heart rates in patients with IST and the heart rate increases in patients with POTS and may be beneficial in these children with dysautonomia.

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Pre-workout supplement use has increased in recent years. Multiple side effects and off-labeled substances have been reported. We report a case of a 35-year-old patient who recently started a pre-workout and was found to have sinus tachycardia, elevated troponin, and subclinical hyperthyroidism. The echocardiogram showed normal ejection fraction and no wall motion abnormality. Beta-blockade therapy with propranolol was offered, but she refused, and her symptoms and troponin levels improved after proper hydration within 36 hours. A cautious and accurate assessment of young, fitness-enthusiastic patients experiencing unusual chest pain is essential to identify a reversible cardiac injury and possible off-label substances in over-the-counter supplements.

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Two electrocardiographic (ECG) aberrations encountered daily in ECG interpretation/overreading, which appear to be either unknown or ignored, by all caring for patients, are described herein: the 1st is the transient increase in the amplitude of QRS complexes in the right precordial ECG leads, leading to the erroneous diagnosis of left ventricular hypertrophy, often encountered in patients with episodes of supraventricular tachycardia, rapid sinus tachycardia, and atrial fibrillation; the 2nd is the spurious ST-segment elevations in lateral and/or inferior ECG leads in patients with right bundle branch block, interpreted by the automated ECG diagnostic algorithms as due to "acute myocardial infarction," "ischemic injury," "pericarditis," and "early repolarization," in the absence of such pathologies or electrophysiological explanations.

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