A gain-of-function HCN4 mutant in the HCN domain is responsible for inappropriate sinus tachycardia in a Spanish family.

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.

Triglicerydes/high-density lipoprotein ratio as a risk factor of post-Covid-19 sinus tachycardia: A retrospective study.

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.

Intracardiac echocardiography guided anatomical ablation of the arcuate ridge for drug refractory inappropriate sinus tachycardia.

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.

Electrocardiographic Changes at the Early Stage of Status Epilepticus: First Insights From the ICTAL Registry.

OBJECTIVES: To describe early electrocardiogram (ECG) abnormalities after status epilepticus (SE) and evaluate their association with 90-day neurological outcomes. DESIGN: Retrospective analysis of a multicenter, national prospective registry between February 2018 and June 2020. SETTING: Sixteen ICUs in France, IctalGroup Research Network. PATIENTS: Adults with available ECG performed less than or equal to 24 hours after the onset of SE and less than or equal to 12 hours after its resolution. INTERVENTION: Double-blinded review of all ECGs was performed by two independent cardiologists. ECGs were categorized as normal/abnormal and then with minor/major early ECG abnormalities according to the Novacode ECG Classification system. MEASUREMENTS AND MAIN RESULTS: Among 155 critically ill patients with SE, early ECG abnormalities were encountered in 145 (93.5%), categorized as major in 91 of 145 (62.8%). In addition to sinus tachycardia, the main abnormalities were in the ST segment (elevation [16.6%] or depression [17.9%]) or negative T waves (42.1%). Major early ECG abnormalities were significantly associated with respiratory distress and sinus tachycardia at the scene and hyperlactatemia at ICU admission. By multivariable analysis, three variables were significantly associated with 90-day poor outcome: age, preexisting ultimately fatal comorbidity, and cerebral insult as the cause of SE. Early major ECG abnormalities were not independently associated with 90-day functional outcome. CONCLUSIONS: In our study, early ECG abnormalities in the acute phase of SE were frequent, often unrecognized and were associated with clinical and biological stigma of hypoxemia. Although they were not independently associated with 90-day functional outcome, ECG changes at the early stage of SE should be systematically evaluated. TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT03457831 .

Redo procedures after sinus node sparing hybrid ablation for inappropriate sinus tachycardia/postural orthostatic sinus tachycardia.

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.

Ivabradine in the treatment of non-paroxysmal junctional tachycardia with interference atrioventricular dissociation: A case report.

Ivabradine reduces the heart rate by selectively inhibiting the If current of the sinoatrial node, mainly for the treatment of chronic heart failure with decreased left ventricular systolic function and inappropriate sinus tachycardia, but the inhibitory effect on the atrioventricular node is rarely reported. The patient was admitted to hospital mainly because of intermittent chest pain for 7 years, which worsened for 10 days. Admission electrocardiogram (ECG) considered sinus tachycardia, with QS wave and T wave inversion in II, III, aVF, V3 R-V5 R, V4 -V9 leads, and non-paroxysmal junctional tachycardia (NPJT) with interference atrioventricular dissociation. After treatment with ivabradine the ECG returned to normal conduction sequence. NPJT with interference atrioventricular dissociation is a fairly rare electrocardiographic phenomenon. This case reports for the first time that ivabradine is used in the treatment of NPJT with interference atrioventricular dissociation. It is speculated that ivabradine has a potential inhibitory effect on the atrioventricular node.

Successful use of ivabradine in a 10-year-old patient with graft failure after heart transplantation.

We encountered a paediatric case of graft failure due to antibody-mediated rejection after heart transplantation in which ivabradine was effective. Inappropriate sinus tachycardia in denervated transplanted hearts is a good indication for ivabradine administration as beta-blockers have a limited efficacy. To our knowledge, this is the first report on the effectiveness of ivabradine in a paediatric heart transplant rejection case.

Comparison of the effects of conventional method and primary sutureless techniques on early postoperative rhythm problems in patients with total abnormal pulmonary venous return anomaly.

BACKGROUND: Total abnormal pulmonary venous return anomaly is a CHD characterised by abnormal pulmonary venous flow directed to the right atrium. In this study, we aimed to compare the effects of these techniques on early rhythm problems in total abnormal pulmonary venous return anomaly cases operated with conventional or primary sutureless techniques. METHOD: Seventy consecutive cases (median age 1 month, median weight 4 kg) who underwent total abnormal pulmonary venous return anomaly repair with conventional or primary sutureless technique between May 1 2020 and May 1 2022 were evaluated. The rate, diagnosis, and possible risk factors of postoperative arrhythmias were investigated. The results were evaluated statistically. RESULTS: When the total abnormal pulmonary venous return anomaly subgroup of 70 cases was evaluated, 40 cases were supracardiac, 18 cases were infracardiac, 7 cases were cardiac, and 5 cases were mixed type. Twenty-eight (40%) cases had a pulmonary venous obstruction. Primary sutureless technique (57%, supracardiac n = 24, mixed = 3, infracardiac = 13) was used in 40 patients. Median cardiopulmonary bypass time (110 versus 95 minutes) and median aortic clamp time (70 versus 60 minutes), median peak lactate (4.7 versus 4.8 mmol/l) in the first 72 hours, and median peak vasoactive inotropic score in the first 72 hours of the primary sutureless and conventional technique used cases value (8 versus 10) were similar. The total incidence of arrhythmias in the conventional group was significantly higher than in the primary sutureless group (46.7% versus 22.5%, p = 0.04). Supraventricular early beat was observed in 3 (7.5%), sinus tachycardia was seen in 6 (15%), junctional ectopic tachycardia was seen in 1 (2.5%), intra-atrial reentry tachycardia was seen in 1 (2.5%), usual supraventricular tachyarrhythmia was seen in 2 cases (5%) in the primary sutureless group. In the conventional group, supraventricular early beat was observed in six of the cases (20%), sinus tachycardia in five (16.7%), junctional ectopic tachycardia in four (13.3%), intra-atrial reentry tachycardia (10%) in three, and supraventricular tachyarrhythmia in seven cases (23.3%). In the first 30 days, there was a similar mortality rate (10% versus 10%), with four patients in the primary sutureless group and three in the conventional group. The median follow-up period of the cases was 8 months (interquartile range (IQR) 6-10 months). In the follow-up, arrhythmias were detected in two cases (one supraventricular tachyarrhythmia and one intra-atrial reentry tachycardia) in the primary sutureless group and three cases (two supraventricular tachyarrhythmia, one intra-atrial reentry tachycardia) in the conventional technique. All cases were converted to normal sinus rhythm with cardioversion and combined antiarrhythmic therapy. CONCLUSION: Different arrhythmias can be observed in the early period in patients with operated total abnormal pulmonary venous return anomaly. Although a higher rate of rhythm problems was observed in the early period in the conventional method compared to the primary sutureless technique, no significant effect was found on mortality and morbidity between the groups.

Inappropriate sinus tachycardia: an examination of existing definitions.

AIMS: Inappropriate sinus tachycardia (IST) is a syndrome characterized by an elevated sinus rate unassociated with known physiological, pathological, or pharmacological causes. Despite published consensus documents, IST definitions appear to vary in the literature. In this study, we reviewed IST publications to evaluate IST definition variability and ascertain the degree to which consensus definitions are being adopted. METHODS AND RESULTS: English-language articles in PubMed, Ovid MEDLINE, Ovid Embase, and Google Scholar published from 1 January 1970 to 1 June 2021 with the title terms 'inappropriate sinus tachycardia,' 'non-paroxysmal sinus tachycardia,' or 'permanent sinus tachycardia' were searched. In each, the IST definition used, qualifying characteristics, and publications cited to support each definition were recorded. We identified 138 publications meeting the search criteria. Inappropriate sinus tachycardia definitions were provided in 114 of 138 articles (83%). A majority of definitions (92/114, 81%) used distinct heart rate (HR) thresholds. Among these, the most common threshold was ≥100 beats per minute (BPM) (75/92, 82%), mainly measured at rest (54/92, 59%). Most definitions (47/92, 51%) included a second criterion to qualify for IST; these were most often an HR threshold of 90 BPM measured over 24 h by ambulatory electrocardiogram (37/47, 79%). Diagnosis of exclusion was a common criterion (75/92, 82%) but symptom status was not (41/92, 45%). The 2015 Heart Rhythm Society IST consensus was commonly cited but adopted in only 37% of definitions published after 2015. CONCLUSIONS: Inappropriate sinus tachycardia definitions in current literature are inconsistent, and professional society consensus IST definitions have, to date, had limited impact.

Clinical significance of unexplained persistent sinus tachycardia in women with structurally normal heart during the peripartum period.

BACKGROUND: Persistent sinus tachycardia (ST) is frequently encountered during pregnancy and peripartum period and its etiology often remains elusive. We sought to examine the possible association between unexplained persistent ST and obstetric outcomes. METHODS: A case control study was conducted using chart review of women admitted in labor to one of 7 hospitals of Northwell Health between January 2015 to June 2021. After excluding women with structurally abnormal hearts, we identified patients with persistent ST during the peripartum period, defined as a heart rate of more than 100 bpm for more than 48 h. A control group was created by randomly subsampling those who did not meet the inclusion criteria for sinus tachycardia. Obstetric outcomes were measured as mother's length of stay (LOS), pre-term labor (PTL), admission to the neonatal ICU (NICU), and whether she received cesarean-section (CS). RESULTS: Seventy-eight patients with persistent ST were identified, out of 141,769 women admitted for labor throughout the Northwell Health system. 23 patients with ST attributable to infection or hypovolemia from anemia requiring transfusion and 55 with unclear etiology were identified. After adjusting for age and parity, pregnant mothers with ST were 2.35 times more likely to have a CS than those without (95% CI: 1.46-3.81, p = 0.0005) and had 1.38 times the LOS (1.21- 1.56, p < 0.0001). Among mothers with ST, those with unexplained ST were 2.14 times more likely to have a CS (1.22-3.75, p = 0.008). CONCLUSION: Among pregnant patients, patients with ST have higher rates of CS.This association is unclear, however potential mechanisms include catecholamine surge, indolent infection, hormonal fluctuations, and medications. More studies are needed to explore the mechanism of ST in pregnant woman to determine the clinical significance and appropriate management.

Electrocardiographic findings in pregnant women in Angola.

BACKGROUND: Studies on the electrocardiogram findings in African pregnant women are limited. There is no information available in the literature on the electrocardiographic parameters of pregnant Angolan women. OBJECTIVES: The aim of this study was to describe electrocardiographic findings in women with normal pregnancies in Bengo Province, Angola. METHODS: This is a community-based study with a cross-sectional design conducted between September 2013 and March 2014 in Bengo. The study involved 114 black pregnant women, compared with a paired control group comprising of 120 black non-pregnant women, aged 15 to 42 years. A 12-lead electrocardiogram and a rhythm strip were recorded for all participants. RESULTS: In this study, the mean age was 26.2 ± 7.3 years. Comparing pregnant women vs. non-pregnant, we found the following mean values: Heart rate (83 bpm vs. 74 bpm, p < .001), PR interval (146 ms vs. 151 ms, p = .034), QT interval (360 ms vs. 378 ms, p < .001), QTIc Fridericia (398 ms vs. 403, p = .017), QTIc Framingham (399 ms vs. 404 ms, p = .013) and T-wave axis (340 vs. 410 , p = .001).The main electrocardiographic changes found were: Sinus tachycardia (4.4% vs. 2.5%), T-wave inversion (14.9% vs. 1.7%), Minor ST segment depression (4.5% vs. 0%) and left ventricular hypertrophy (11.4% vs. 11.7%, p = .726). CONCLUSIONS: Pregnant Angolan women compared with controls, had several significantly higher values for heart rate, and significantly lower values of systolic blood pressure and diastolic blood pressure, PR interval, QT interval, QTc interval by Fridericia and Framingham and T-wave axis. Sinus tachycardia, T-wave inversion, and left ventricular hypertrophy, were the main electrocardiographic changes found.

Prognostic value of initial electrocardiography in predicting long-term all-cause mortality in COVID-19.

BACKGROUND: The electrocardiography (ECG) has short-term prognostic value in coronavirus disease 2019 (COVID-19), yet its ability to predict long-term mortality is unknown. This study aimed to elucidate the predictive role of initial ECG on long-term all-cause mortality in patients diagnosed with COVID-19. METHODS: In this prospective cohort study, adults with COVID-19 who underwent ECG testing within a 17-hospital health system in Northeast Ohio and Florida between 03/2020-06/2020 were identified. An expert ECG reader analyzed all studies blinded to patient status. The associations of ECG characteristics with long-term all-cause mortality and intensive care unit (ICU) admission were assessed using Cox proportional hazards regression model and multivariable logistic regression models, respectively. Status of long-term mortality was adjudicated on 01/07/2022. RESULTS: Of 837 patients (median age 65 years, 51% female, 44% Black), 683 (81.6%) were hospitalized, 281 (33.6%) required ICU admission, 67 (8.0%) died in-hospital, and 206 (24.6%) died at final follow-up after a median (IQR) of 21 (9-103) days after ECG. Overall, 179 (20.7%) patients presented with sinus tachycardia, 12 (1.4%) with atrial flutter, and 45 (5.4%) with atrial fibrillation (AF). After multivariable adjustment, sinus tachycardia (E-value for HR=3.09, lower CI=2.2) and AF (E-value for HR=3.13, lower CI=2.03) each independently predicted all-cause mortality. At final follow-up, patients with AF had 64.5% probability of death compared with 20.5% for those with normal sinus rhythm (P<.0001). CONCLUSIONS: Sinus tachycardia and AF on initial ECG strongly predict long-term all-cause mortality in COVID-19. The ECG can serve as a powerful long-term prognostic tool in COVID-19.

Efficacy of medical and ablation therapy for inappropriate sinus tachycardia: A single-center experience.

BACKGROUND: Effective therapy for inappropriate sinus tachycardia (IST) remains challenging with high rates of treatment failure and symptom recurrence. It is uncertain how effective pharmacotherapy and procedural therapy are long-term, with poor response to medical therapy in general. METHODS: We retrospectively reviewed all patients with the diagnosis of IST at a tertiary academic medical center from 1998 to 2018. We extracted data related to prescribing patterns and symptom response to medical therapy and sinus node modification (SNM), assessing efficacy and periprocedural complication rates. RESULTS: A total of 305 patients with a formal diagnosis of IST were identified, with 259 (84.9%) receiving at least one prescription medication related to the condition. Beta-blockers were the most commonly used medication (n = 245), with a majority of patients reporting no change or worsening of symptoms, and poor response was seen to other medication classes. Improvement was seen significantly more often with ivabradine than beta blockers, though the sample size was limited (p = .003). Fifty-five patients (18.0% of all IST patients), mean age 32.0 ± 9.1 years, underwent a SNM procedure, with an average of 1.8 ± 0.9 procedures per patient. Acute symptomatic improvement (<6 months) was seen in 58.2% of patients. Long-term complete resolution of symptoms was seen in 5.5% of patients, modest improvement in 29.1%, and no long-term benefit was seen in 65.5% of patients. CONCLUSIONS: Among all medical therapies, there were high rates of treatment failure or symptom worsening in over three-quarters of patients in our study. Ivabradine was most beneficial, though the sample size was small. While most patients receiving SNM ablation for IST perceive an acute symptomatic improvement, almost two-thirds of patients have no long-term improvement, and resolution of symptoms is quite rare. AV node ablation with pacemaker implantation following lack of response to SNM offered increased success, though the sample size was limited.

Inappropriate sinus tachycardia: a review.

Inappropriate sinus tachycardia (IST) has been defined as a resting heart rate of >100 beats per minute and an average 24-hour heart rate >90 bpm with distressing symptoms resulting from the persistent tachycardia. IST is prevalent in 1% of the middle-aged population, mostly females. Rarely can elderly patients also present with IST. Possible mechanisms of IST include intrinsic sinus node abnormality, beta-adrenergic receptor stimulating autoantibody, beta-adrenergic receptor supersensitivity, muscarinic receptor autoantibody, or hyposensitivity, impaired baroreflex control, depressed efferent parasympathetic/vagal function, nociceptive stimulation, central autonomic overactivity, aberrant neurohumoral modulation, etc. Symptoms associated with IST are palpitations, chest pain, fatigue, shortness of breath, presyncope, and syncope. Despite these distressing symptoms, IST has not been associated with tachycardia-associated cardiomyopathy or increased major cardiovascular events. Various treatment options for patients with IST are ivabradine, beta-adrenergic blockers, calcium channel blockers, psychiatric evaluation, and exercise training. Although, endocardial radiofrequency ablation targeting the sinus node has been used as a treatment modality for otherwise treatment-refractory IST, the results have been dismal. The other modalities used for refractory IST treatment are endocardial modification of the sinus node using radiofrequency energy, combined endo and epicardial ablation of the sinus node, thoracoscopic epicardial ablation of the sinus node, sinus node sparing thoracoscopic and endocardial hybrid ablation. The goal of this review is to provide the readership with the pathophysiological basis of IST and its management options.

M2 muscarinic autoantibodies and thyroid hormone promote susceptibility to atrial fibrillation and sinus tachycardia in an autoimmune rabbit model.

NEW FINDINGS: What is the central question of this study? Do autoantibodies to the M2 muscarinic receptor (M2R-AAbs) have the potential to facilitate specific sustained tachyarrhythmias in the presence of thyroxine (T4 ) in rabbits? What is the main finding and its importance? The M2R-AAb and T4 jointly destabilized the electrophysiological properties, thus promoting the occurrence of atrial and sinus tachyarrhythmias in rabbits. These findings provide a practical basis for understanding the pathophysiological role of M2R-AAb alone and with T4 in arrhythmia induction and might provide an innovative option for treatment of Graves' disease with rhythm disturbance. ABSTRACT: Activating autoantibodies toward the ß1/2 -adrenergic receptors (ß1/2AR-AAbs) and M2 muscarinic receptor (M2R-AAbs) are present in a high proportion of patients with Graves' disease. We previously demonstrated that ß1/2AR-AAbs with or without the presence of M2R-AAbs in combination with excessive thyroxine (T4 ) increased the induction of sustained tachyarrhythmias in an autoimmune rabbit model. However, the separate role of M2R-AAbs and their interaction with T4 are not clear. The aim of this study was to investigate the impact of M2R-AAbs and T4 on the induction of cardiac arrhythmias in a similar rabbit model. Ten New Zealand White rabbits were randomly divided into two groups. In group A (n = 6), the rabbits were immunized with the second extracellular loop peptide of M2R and subjected to 2 weeks of T4 treatment. In group B (n = 4), the rabbits were treated only with T4 for 2 weeks. After induction of general anaesthesia, rabbits were subjected to an electrophysiological study at 0 (pre-immune), 6 (post-immune) and 8 weeks (post-immune+T4 treatment) in group A and at 0 (baseline) and 8 weeks (T4 treatment) in group B. Each rabbit served as its own control. In group A, high levels and activity of M2R-AAbs were detected in all immunized animals. Thyroxine in combination with immunization significantly increased induction of sustained sinus tachycardia and atrial fibrillation in comparison to the pre-immune state. In group B, T4 predominantly induced sustained sinus tachycardia. This study demonstrated that M2R-AAbs and T4 jointly increased the susceptibility to both sinus and atrial tachyarrhythmias. The data supported the pathophysiological role of M2R-AAbs in hyperthyroidism-associated supraventricular tachyarrhythmias.

Ivabradine in Cardiovascular Disease Management Revisited: a Review.

Ivabradine is a unique agent that is distinct from beta-blockers and calcium channel blockers as it reduces heart rate without affecting myocardial contractility or vascular tone. Ivabradine is a use-dependent inhibitor targeting the sinoatrial node. It is approved for use in the United States as an adjunct therapy for heart rate reduction in patients with heart failure with reduced ejection fraction. In this scenario, ivabradine has demonstrated improved clinical outcomes due to reduction in heart failure readmissions. However, there has been conflicting evidence from prospective studies and randomized controlled trials for its use in stable ischemic heart disease regarding efficacy in symptom reduction and mortality benefit. Ivabradine may also play a role in the treatment of patients with inappropriate sinus tachycardia, who often cannot tolerate beta-blockers and/or calcium channel blockers. In this review, we highlight the evidence for the nuances of using ivabradine in heart failure, stable ischemic heart disease, and inappropriate sinus tachycardia to raise awareness for its vital role in the treatment of select populations.

Prognosis and role of clinical and imaging features in patients with malignant pericardial effusion: a single-center study in China.

BACKGROUND: The diagnosis of malignant pericardial effusion (MPE) is often associated with a poor prognosis, but due to the complexity and unspecific nature of MPE patients' clinical manifestations, imaging often performs an essential role in diagnosis and prognosis. METHODS: Patients diagnosed with MPE between 2013 and 2018 at one tumor hospital were included and followed up. The data covered the basic clinical features, imaging findings, treatments and prognosis of patients with MPE, and the factors that may have affected the prognosis were explored. RESULTS: A total of 216 patients with MPE were included with the median age of 60 years. The most common primary cancer type was lung cancer (73.6%), the most common symptom was dyspnea (62.9%) and the most common abnormal electrocardiogram finding was sinus tachycardia (42.1%). The median survival time of the 216 patients with MPE was 13.7 months. The factors affecting prognosis were echocardiographic fluid signs (HR = 2.37, P = 0.010), electrocardiographic evidence of sinus tachycardia (HR = 1.76, P = 0.006) and echocardiographic evidence of cardiac tamponade (HR = 3.33, P < 0.001). CONCLUSIONS: MPE has complex clinical manifestations and an unsatisfactory prognosis. Echocardiographic fluid signs, electrocardiographic evidence of sinus tachycardia, and echocardiographic evidence of cardiac tamponade are independent risk factors affecting prognosis.

Natural history and clinical outcomes of inappropriate sinus tachycardia.

BACKGROUND: Limited data are available regarding the demographics, disease associations, and long-term prognosis of patients with inappropriate sinus tachycardia (IST). OBJECTIVE: To establish epidemiologic data for patients with IST, including symptom onset, comorbid disease, and long-term outcomes. METHODS: We retrospectively reviewed all patients with an IST diagnosis at the Mayo Clinic (Rochester, MN) during a 20-year period (1998-2018). We extracted demographic data and clinical outcomes compared to an age and gender-matched control group with atrioventricular nodal reentry tachycardia (AVNRT). RESULTS: Within the study period, a total of 305 patients with IST were identified (mean follow-up 3.5 years) with 92.1% female and mean age 33.2 ± 11.2 years. The most frequently identified circumstances triggering the condition included pregnancy (7.9%) and infectious illness (5.9%) while the most common comorbid conditions were depression (25.6%) and anxiety (24.6%). At diagnosis, the mean left ventricular ejection fraction (LVEF) was 62.3 ± 6.2%, with 77 patients having follow-up echocardiographic data. No significant difference in LVEF was seen after a mean 4.9 ± 4.3-year follow-up (baseline LVEF 59.8 ± 10.7% vs subsequent 61.4 ± 8.1%; P = .2971). Two deaths occurred within the study period, with one related to myocardial infarction and the other noncardiac; compared to an age and gender-matched AVNRT control group there was no excess mortality during the follow-up period. CONCLUSIONS: In our study cohort, IST predominately affects young females with structurally normal hearts and modest coexistent psychiatric disease. In most cases of IST, a major event occurring just before or at the time of diagnosis could not be identified, although nearly 8% of patients first noted symptoms during or shortly after pregnancy. In our cohort, there was no evidence of cardiomyopathy or mortality related to IST.

Atropine-induced sinus tachycardia protects against exercise-induced ventricular arrhythmias in patients with catecholaminergic polymorphic ventricular tachycardia.

AIMS: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome characterized by exercise-induced ventricular arrhythmias, sudden death, and sinus bradycardia. Elevating supraventricular rates with pacing or atropine protects against catecholaminergic ventricular arrhythmias in a CPVT mouse model. We tested the hypothesis that increasing sinus heart rate (HR) with atropine prevents exercise-induced ventricular arrhythmias in CPVT patients. METHODS AND RESULTS: We performed a prospective open-label trial of atropine prior to exercise in CPVT patients (clinicaltrials.gov NCT02927223). Subjects performed a baseline standard Bruce treadmill test on their usual medical regimen. After a 2-h recovery period, subjects performed a second exercise test after parasympathetic block with atropine (0.04 mg/kg intravenous). The primary outcome measure was the total number of ventricular ectopic beats during exercise. All six subjects (5 men, 22-57 years old) completed the study with no adverse events. Atropine increased resting sinus rate from median 52 b.p.m. (range 52-64) to 98 b.p.m. (84-119), P = 0.02. Peak HRs (149 b.p.m., range 136-181 vs. 149 b.p.m., range 127-182, P = 0.46) and exercise duration (612 s, range 544-733 vs. 584 s, range 543-742, P = 0.22) were not statistically different. All subjects had ventricular ectopy during the baseline exercise test. Atropine pre-treatment significantly decreased the median number of ventricular ectopic beats from 46 (6-192) to 0 (0-29), P = 0.026; ventricular ectopy was completely eliminated in 4/6 subjects. CONCLUSION: Elevating sinus rates with atropine reduces or eliminates exercise-induced ventricular ectopy in patients with CPVT. Increasing supraventricular rates may represent a novel therapeutic strategy in CPVT.

Electrocardiographic findings of methanol toxicity: a cross-sectional study of 356 cases in Iran.

BACKGROUND: Methanol is widely used in industry; however, methanol poisoning is not common. In this regard, a number of outbreaks have been recently reported due to inappropriate processing of alcoholic beverages. Shiraz, a city located in the southern part of Iran, faced one of such outbreaks in 2020 during COVID-19 pandemic. There is no sufficient literature on the electrocardiographic findings in methanol toxicity. This study aimed to address this gap in the literature. METHOD: A total of 356 cases with methanol toxicity referred to Shiraz University of Medical Science Tertiary Hospitals (Faghihi and Namazi) in March and April, 2020. The clinical findings of blindness and impaired level of consciousness, lab data such as arterial blood gas, electrolytes, and creatinine, and the most common findings from ECGs were collected. RESULTS: The most common ECG findings were J point elevation (68.8%), presence of U wave (59.2%), QTc prolongation (53.2% in males and 28.6% in females), and fragmented QRS (33.7%). An outstanding finding in this study was the presence of myocardial infarction in 5.3% of the cases. This finding, to the best of our knowledge, has only been reported in a few case reports. Brugada pattern (8.1%) and Osborn wave (3.7%) were the other interesting findings. In multivariate analysis, when confounding factors were adjusted, myocardial infarction, atrioventricular conduction disturbances, sinus tachycardia, and the prolonged QTC > 500 msecond were four independent factors correlated with methanol toxicity severity measured with arterial blood PH on arterial blood gas measurements, with odds ratios of 12.82, 4.46, 2.32 and 3.15 (P < 0.05 for all), respectively. CONCLUSION: Electrocardiographic variations during methanol intoxication are remarkable and well-correlated with poisoning severity. Myocardial infarction was an egregious and yet a common concerning finding in this sample, which need to be ruled out in methanol toxicity.