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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., Competing Interests: Conflict of interest: C.d.A receives research grants on behalf of the centre from Biotronik, Medtronic, Abbott, LivaNova, Boston Scientific, AtriCure, Philips, and Acutus; C.d.A. received compensation for teaching purposes and proctoring from Medtronic, Abbott, Biotronik, Livanova, Boston Scientific, AtriCure, and Acutus Medical Daiichi Sankyo. A.S. received research grants from Daiichi Sankyo and Bayer; he has received speaker fees from Menarini and Bayer. PB received compensation for teaching purposes from Biotronik. G.C. received compensation for teaching purposes and proctoring from Medtronic, Abbott, Biotronik, Boston Scientific, and Acutus Medical. MLM is consultant for AtriCure. The remaining authors have nothing to disclose., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

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.

Aims: Sinus tachycardia potentially leads to a deterioration of cardiac function in critically ill infants. The ultrashort-acting beta-blocker landiolol hydrochloride is a new pharmacological option for a selective heart rate (HR) control in patients with sinus tachycardia and heart failure., Methods and Results: This study was a monocentric retrospective medical chart review study at the University Children's Hospital Bonn (Germany) from 01 January 2018 until 30 June 2020. This study included a cohort of 62 term and preterm infants with a diagnosis of ventricular dysfunction and/or pulmonary hypertension (PH), in combination with preexisting tachycardia and treatment with landiolol hydrochloride. Infants were allocated to subgroups according to weeks of gestational age (GA): born at <35 weeks of GA (Group A) and born at >35 weeks of GA (Group B). Tachycardia was defined depending on GA (<35 weeks of GA: >170 b.p.m.; ≥ 35 weeks of GA: >150 b.p.m.). The primary endpoint was defined as percentage of patients achieving HR normalization during the first 24 h of landiolol treatment. Twenty-nine infants were allocated to Group A and 33 infants to Group B. The overall median GA of the infants was 35.3 (23.3/41.3), with 53% female infants. The primary endpoint was achieved in 57 patients (91.9%). The median time to reach target HR was 1.8 (0.3-24) h. The median starting dose of landiolol was 8.8 (3.9-25.3) μk/kg/min, with a median dosing during the first 24 h of landiolol treatment of 9.9 (2.8-35.4) μk/kg/min. The median landiolol dose while achieving the target HR was 10 (2.4-44.4) μk/kg/min. The right ventricular dysfunction improved significantly in both groups 24 h after onset of landiolol infusion (P = 0.001 in Group A and P = 0.045 in Group B). The left ventricular and biventricular dysfunction improved significantly 24 h after onset of landiolol infusion in infants of Group B (P = 0.004 and P = 0.006, respectively). The severity of PH improved significantly after 24 h in infants of Group A (P < 0.001). During landiolol treatment, no severe drug-related adverse event was noted., Conclusions: The use of landiolol hydrochloride for HR control of non-arrhythmic tachycardia in critically ill infants is well tolerated. Reduction of HR can be guided quickly and landiolol treatment is associated with an improvement of ventricular dysfunction and PH., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Cardiac graft denervation causes inadequate sinus tachycardia in patients after heart transplantation (HTX) which is associated with reduced survival. This study investigated the 5-year results of heart rate control with ivabradine or metoprolol succinate in patients after HTX., Methods: This registry study analyzed 104 patients receiving either ivabradine (n = 50) or metoprolol succinate (n = 54) within 5 years after HTX. Analysis included patient characteristics, medication, echocardiographic features, cardiac catheterization data, cardiac biomarkers, heart rates, and post-transplant survival including causes of death., Results: Demographics and post-transplant medication revealed no significant differences except for ivabradine and metoprolol succinate use. At 5-year follow-up, patients with ivabradine had a significantly lower heart rate (73.3 bpm) compared to baseline (88.6 bpm; P < 0.01) and to metoprolol succinate (80.4 bpm; P < 0.01), a reduced left ventricular mass (154.8 g) compared to baseline (179.5 g; P < 0.01) and to metoprolol succinate (177.3 g; P < 0.01), a lower left ventricular end-diastolic pressure (LVEDP; 12.0 mmHg) compared to baseline (15.5 mmHg; P < 0.01) and to metoprolol succinate (17.1 mmHg; P < 0.01), and a reduced NT-proBNP level (525.4 pg/ml) compared to baseline (3826.3 pg/ml; P < 0.01) and to metoprolol succinate (1038.9 pg/ml; P < 0.01). Five-year post-transplant survival was significantly better in patients with ivabradine (90.0%) versus metoprolol succinate (68.5%; P < 0.01)., Conclusion: Patients receiving ivabradine showed a superior heart rate reduction and a better left ventricular diastolic function along with an improved 5-year survival after HTX., (© 2020. The Author(s).)

Aim: The aim of our study was to compare ivabradine versus bisoprolol in the short-term and long-term treatment of inappropriate sinus tachycardia., Methods: From this prospective, parallel-group, open-label study, consecutive patients affected by inappropriate sinus tachycardia received ivabradine or bisoprolol and were evaluated with Holter ECG, ECG stress test, European Heart Rhythm Association score and Minnesota Living With Heart Failure Questionnaire at baseline, after 3 and 24 months., Results: Overall, 40 patients were enrolled. Baseline parameters were comparable in the ivabradine and bisoprolol subgroups. Two patients had transient phosphenes with ivabradine and two others interrupted the drug after 3 months as they planned to become pregnant. Eight individuals treated with bisoprolol experienced hypotension and weakness, which caused drug discontinuation in five of them. Ivabradine was superior to bisoprolol in reducing Holter ECG mean heart rate (HR) and mean HR during daytime at short- and long-term follow-up. Moreover, ivabradine but not bisoprolol significantly reduced Holter ECG mean HR during night-time as well as maximal and minimal HR and significantly increased the time duration and maximal load reached at ECG stress test. The quality of life questionnaires significantly improved in both subgroups., Conclusion: This study suggests that ivabradine is better tolerated than bisoprolol and seems to be superior in controlling the heart rate and improving exercise capacity in a small population of individuals affected by inappropriate sinus tachycardia during a short-term and long-term follow-up., (Copyright © 2021 Italian Federation of Cardiology - I.F.C. All rights reserved.)

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., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The purpose of the study was to evaluate the long-term outcomes of sinus node modification (SNM) in treating patients with severely symptomatic drug-refractory inappropriate sinus tachycardia (IST)., Methods: The study included 39 patients with symptomatic drug-refractory IST who have undergone SNM at Saint Louis University Hospital. Data was reviewed retrospectively. Recurrence of symptoms was assessed at 3-6-month follow-up intervals., Results: The mean age of our cohort was 31.5 ± 11. The mean HR at diagnosis was 135 ± 25.4 beats per minute (BPM). Thirty-seven of 39 (94.8%) patients had complete resolution of symptoms. Of these 37 patients, 16 required 1 SNM, 17 patients required 2 SNM, and 4 patients required 3 SNM in order to achieve complete symptom resolution. Mean HR post-procedure was 78.6 ± 12.3 BPM. Thirteen of 39 patients required rate control medication post-procedure, all of whom were prescribed beta-blockers. Patients were followed every 3 to 6 months with a mean follow-up duration of 62.3 ± 42.9 months from the patient's last SNM procedure. Thirteen of those 37 patients (35.1%) developed intermittent symptomatic bradycardia requiring permanent pacemaker implantation. Two of the 39 patients had phrenic nerve injury, and 6 patients had post-procedure pericarditis., Conclusions: This study provides additional information to the limited dataset available in the literature and shows that SNM might provide patients with long-term symptomatic relief bearing in mind the potential increased risk for the need for permanent pacing., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Inappropriate sinus tachycardia (IST) is an arrhythmic complication observed after coronary artery bypass graft (CABG) surgery which left untreated, commonly increases chances of postoperative stroke. The primary study objective was comparing effectiveness of beta blocker-metoprolol; a specific I f blocker-ivabradine and its combination in patients who develop IST as a complication following CABG., Materials and Methods: An open-labeled, investigator initiated, clinical study was conducted on 150 patients who developed IST (heart rate [HR] >100 beats/min) following elective CABG surgery. The patients were randomized into three treatment groups. Group I - received ivabradine (5 mg), Group II - metoprolol (25 mg), and Group III - ivabradine (5 mg) and metoprolol (25 mg). Treatment was given orally, twice a day for 7 days in all the three groups postoperatively. Primary endpoints were comparative effectiveness in HR and blood pressure reduction following treatment., Results: IST was diagnosed by an electrocardiogram (12-lead) considering morphological features of P-wave and with 32% increase from baseline HR in all the three groups. Compared to IST arrthymic rate, HR was reduced in all groups following respective treatment (P = 0.05). Reduction in HR was significant (P < 0.05) in combination group followed by ivabradine which was significantly greater than metoprolol treated group. None of the treatments clinically changed the systolic, diastolic and mean blood pressure till discharge. No surgery/treatment-related complications were observed in any groups., Conclusion: Ivabradine stands as a pharmacological option for controlling HR and rhythm without associated side effects in postoperative CABG patients with IST., Competing Interests: None

A 22-year-old woman was referred with exertional dyspnoea and chest tightness 3 weeks following a diagnosis of COVID-19. Evaluation revealed a resting sinus tachycardia and criteria for postural orthostatic tachycardia syndrome were met. After non-pharmacological interventions failed to yield symptomatic improvement, ivabradine was commenced. This intervention was followed by a substantial improvement in the patient's exercise tolerance and energy levels and an objective reduction in supine and standing heart rate., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© 2021 Wiley Periodicals LLC.)

Management of ventricular arrhythmia in structural heart disease is complicated by the toxicity of the limited antiarrhythmic options available. In others, proarrhythmia and deleterious hemodynamic and noncardiac effects prevent practical use. This necessitates new thinking in therapeutic agents for ventricular arrhythmia in structural heart disease. Ivabradine, a funny current (I f ) inhibitor, has proven safety in heart failure, angina, and inappropriate sinus tachycardia. Although it is commonly known that funny channels are primarily expressed in the sinoatrial node, atrioventricular node, and conducting system of the ventricle, ivabradine is known to exert effects on metabolism, ion homeostasis, and membrane electrophysiology of remodeled ventricular myocardium. This review considers novel concepts and evidence from clinical and experimental studies regarding this paradigm, with a potential role of ivabradine in ventricular arrhythmia., (Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Összefoglaló. Bevezetés: Az inadekvát, aránytalan sinuscsomó-tachycardia a szív nomotop ingerképzési zavarával járó, nem ritka klinikai szindróma. A szívritmuszavar-entitást a nem paroxysmalis, magas nyugalmi sinusfrekvencia, a fizikai/pszichés stresszre adott aránytalan sinustachycardia, valamint főként palpitációs panaszok jellemzik. Célkitűzés: Az aránytalan sinuscsomó-tachycardiás betegeink gyógyszeres kezelésével szerzett tapasztalataink ismertetése. Módszerek: 2008 és 2018 között 104 beteget (92 nő, 12 férfi; átlagéletkor 31 ± 10 év) kezeltünk ezzel a szívritmuszavarral. A betegek kivizsgálásuk után 12 elvezetéses EKG-, terheléses EKG-, valamint 24 órás Holter-monitoros EKG-megfigyeléseken vettek részt a gyógyszeres kezelés előtt és után (bizoprolol: 2 × 5 mg/nap; ivabradin: 2 × 5 mg/nap). Az életminőség változását a European Heart Rhythm Association (EHRA) tüneti skálája szerint állapítottuk meg. Eredmények: Mindkét gyógyszer jelentősen csökkentette a nyugalmi sinusfrekvenciát (kontroll: 102 ± 10/min; bizoprolol: 78 ± 6/min; ivabradin: 74 ± 8/min, mindkettő: p<0,0001). A gyógyszeres kezelés nélküli, 24 órás Holter-monitoros EKG-felvételek során mért szívfrekvenciák (minimum-maximum [átlag] sinusfrekvencia/min) a kontrollértékekről (58 ± 8-159 ± 14 [94 ± 6]/min) mindkét gyógyszerre egyaránt szignifikánsan csökkentek (bizoprolol: 53 ± 7-132 ± 13 [77 ± 9]/min [mindhárom: p<0,0001]; ivabradin 51 ± 6-134 ± 18 [77 ± 8]/min [mindhárom: p<0,0001]). A terheléses EKG-vizsgálatok előtt (kontroll: 99 ± 13/min; bizoprolol 81 ± 11/min [p<0,0001]; ivabradin: 84 ± 10/min [p<0,0001]) és a terhelés csúcspontján mért sinusfrekvenciák (kontroll: 164 ± 15/min; bizoprolol: 140 ± 16/min [p<0,0001]; ivabradin: 142 ± 14/min [p<0,0001]) is jelentősen mérséklődtek. Az azonos dózisban adott két gyógyszer szívfrekvencia-csökkentő hatásai között számottevő különbséget nem tapasztaltunk. Az életminőséget tükröző EHRA tüneti skálán (kontroll: 2,3 ± 0,7) mind a bizoprolol (1,4 ± 1,4; p<0,0001), mind az ivabradin (1,1 ± 0,2; p<0,0001) egyformán csökkentette a betegek tüneteit, panaszait. Számottevő cardiovascularis mellékhatás egyik betegcsoportban sem jelentkezett. Következtetések: Vizsgálati eredményeink alapján megállapítható, hogy az aránytalan sinuscsomó-tachycardiás betegek gyógyszeres kezelésére: (1) a kardiospecifikus adrenerg béta-blokkoló bizoprolol és az If-csatorna-gátló ivabradin egyaránt hatékonynak és biztonságosnak bizonyult; (2) az azonos adagban adott két gyógyszer hatékonysága között számottevő különbség nem volt; (3) a gyógyszeres kezelés nemcsak a sinusfrekvenciát csökkentette, hanem a betegek panaszait, tüneteit is mérsékelte. Orv Hetil. 2020; 161(46): 1953-1958., Introduction: The inadequate, inappropriate sinus-node tachycardia is not a rare clinical syndrome, defined as a disturbance of the nomotopic impulse formation of the heart. This cardiac arrhythmic entity is characterized by a non-paroxismal, increased sinus rate at rest, and/or inadequate response to physical and/or emotional stress and palpitations., Objective: The aim of this study was to describe our experiences with pharmacological therapy of patients with inappropriate sinus tachycardia syndrome., Methods: Between 2008 and 2018, 104 patients (92 women, 12 men, mean age: 31 ± 10 years) were treated with this cardiac arrhythmia entity. All patients underwent 12-lead ECG, 24-hour Holter-ECG monitoring and standard bicycle dynamic exercise tests before and after drug treatment (bisoprolol: 5 mg bid; ivabradine: 5 mg bid). Changes in the quality of life were estimated by using the European Heart Rhythm Association (EHRA) score., Results: Both drugs decreased significantly the resting heart rate (control: 102 ± 10/min; bisoprolol 78 ± 6/min (p<0.0001), ivabradine: 74 ± 8/min (p<0.0001). The results of the parameters of the 24-hour Holter ECG recordings (expressed as minimal-maximal [average] heart rate/min) with drug therapy showed a significant decrease from control values in all three parameters: control 58 ± 8-159 ± 14 (94 ± 6)/min; bisoprolol 53 ± 7-132 ±13 (77 ± 9)/min (all three: p<0.0001); ivabradine: 51 ± 6-134 ± 18 (77 ± 8)/min (all three: p<0.0001). The sinus rate reduced significantly both before the bicycle dynamic exercise tests (control: 99 ± 13/min; bisoprolol: 81 ± 11/min [p<0.0001]; ivabradine: 84 ± 10/min [p<0.0001]) and at the peaks of the exercise test (control: 164 ± 15/min; bisoprolol: 140 ± 16/min [p<0.0001]; ivabradine 142 ± 14/min [p<0.0001]). The heart rate reducing effects of the two drugs did not differ significantly. The EHRA quality of life score was equally improved by the two drugs (control: 2.3 ± 0.7; bisoprolol: 1.4 ± 1.4 [p<0.0001]; ivabradine: 1.1 ± 0.2 [p<0.0001]). No cardiovascular side effects were observed while taking bisoprolol or ivabradine., Conclusions: Based on our clinical results, it can be pointed out that in the drug therapy of patients with inappropriate sinus node tachycardia: (1) bisoprolol (5 mg bid) and ivabradine (5 mg bid) proved to be equally effective and safe; (2) the heart rate reducing effect of the two drugs - given in the same dosage - did not differ considerably; (3) the pharmacological therapy significantly decreased not only the sinus frequency, but also reduced the symptoms of the patients. Orv Hetil. 2020; 161(46): 1953-1958.

Background: Treatment with ivabradine became a new therapeutic alternative for patients with inappropriate sinus tachycardia (IST). The aim was to determine a relation between intrinsic heart rate (IHR) and response to ivabradine treatment., Methods: Twenty-seven patients (mean age 37 ± 11; 23 women) with symptomatic IST despite medical treatment were recruited into the study. Resting ECG, 24-hr ECG monitoring (24hECG), exercise treadmill test, and symptoms evaluation were performed initially and after 60 days on ivabradine. IHR was acquired at baseline after pharmacological autonomic blockade., Results: Nineteen patients (70%) were classified as abnormal IHR group (AIHR) while eight showed normal IHR (NIHR). No significant differences in ECG parameters were found between NIHR and AIHR subgroups, while baseline exercise capacity was higher in AIHR patients (10.9 vs. 9.5 METs, p < .05). Ivabradine treatment resulted in significant reduction in resting heart rate, average 24hECG heart rate, improvement in exercise capacity and reduction of symptoms in both subgroups. Nevertheless, favorable influence of ivabradine was significantly more exaggerated in AIHR subgroup (HR 116 vs. 90 bpm, av. HR 98 vs. 79 bpm, 10.9 vs. 13.6 METS, EHRA score 3.1 vs. 1.1, p < .001 for all) than in NIHR patients (HR 112 vs. 98 bpm, av. HR 97 vs. 88 bpm, 9.5 vs. 11.1 METs, EHRA score 3.1 vs. 1.9; p < .05 for all)., Conclusions: Intrinsic heart rate may be useful in predicting response to ivabradine in patients with IST. More intense response to ivabradine in patients with AIHR may be attributed to different pathophysiological mechanisms underlying IST in AIHR and NIHR groups., (© 2019 The Authors. Annals of Noninvasive Electrocardiology published by Wiley Periodicals, LLC.)

Muscular dystrophies are a heterogeneous group of disorders that commonly involve cardiac and skeletal muscle. Comprehensive guidelines for the management of cardiac failure and arrhythmias are available. However, the studies from which their recommendations are derived did not include any patients with muscular dystrophy. Some medications (eg, betablockers) may have significant side effects in this cohort. In some situations the use of agents with unique mechanisms of action such as ivabradine (a 'funny' channel inhibitor) may be more appropriate. Use of ivabradine has not previously been reported in limb girdle muscular dystrophy (LGMD). We describe the course of a patient with LGMD type 2I, cardiomyopathy and inappropriate sinus tachycardia treated with ivabradine. As advances in respiratory support have improved the outcomes of patients with muscular dystrophy; the prognostic significance of cardiac disease has increased. Ivabradine is tolerated and may reduce symptoms, morbidity and mortality in this cohort., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Sinus tachycardia coupled with high-dose catecholamine is common after cardiopulmonary bypass (CPB). The present study assessed the hemodynamic efficacy and safety of combination therapy using low-dose β 1 -selective adrenergic blocker (landiolol) and inotropes., Methods: This was a retrospective, single center, self-comparison study at post-anesthesia care unit within a tertiary care center. The study included adults who underwent cardiac surgery with CPB and received landiolol between April 2007 and November 2011. We assessed hemodynamic data prior to and 1 h after initiation of landiolol therapy., Results: We evaluated 11 patients who were administered 2.6 ± 1.3 μg/kg/min (mean ± SD) landiolol with sinus tachycardia and received catecholamine therapy after on-pump cardiovascular surgery. Landiolol administration led to a significant reduction in heart rate (HR; 112.4 ± 5.8 vs 126.0 ± 7.6 beats/min, p < 0.001), and a significant increase in stroke volume index (SVI) assessed by pulmonary artery catheterization (22.4 ± 5.4 vs. 18.9 ± 4.2 mL/m 2 , p = 0.04). Only one patient showed no HR reduction, whereas seven patients showed decreased HR and increased SVI (64, 95% confidence interval: 30-98%). Moreover, all five patients who received high-dose catecholamine support showed improved hemodynamics. In terms of safety, no patients required cessation of landiolol therapy., Conclusions: Low-dose landiolol therapy may safely decrease HR and improve hemodynamics among patients with sinus tachycardia receiving catecholamine treatment after cardiovascular surgery., Trial Registration: This study is retrospective. Registration number: 11. Duration of registration: April 2007~November 2011.

Background: Patients after heart transplantation (HTX) present with sinus tachycardia due to graft denervation. As elevated heart rates negatively affect survival, the aim of this study was to analyze the effects of ivabradine vs metoprolol succinate on heart rate, left ventricular (LV) mass and survival following HTX., Methods: This observational retrospective single-center study assessed 84 patients continuously receiving either ivabradine (n = 40) or metoprolol succinate (n = 44) within 2 years after HTX. Patients with dual therapy (ivabradine and metoprolol succinate), other beta blockers, amiodarone, or digitalis were excluded. Patient characteristics, post-transplant medication, heart rates, LV mass, and survival were investigated., Results: Analysis of patient characteristics, immunosuppressive drug regimen, and post-transplant medication showed no significant differences between groups except for ivabradine and metoprolol succinate. Baseline heart rates differed not significantly between patients treated with ivabradine [87.0 beats per minute (bpm)] and metoprolol succinate (86.2 bpm; P = 0.6395). At 2-year follow-up, patients with ivabradine (76.7 bpm) had a significantly lower heart rate compared to baseline (P < 0.0001) and to metoprolol succinate (82.0 bpm; P = 0.0283). LV mass in patients receiving ivabradine was lower at 2-year follow-up compared to baseline (P = 0.0067) and patients receiving metoprolol succinate (P = 0.0179). Patients with ivabradine had a superior 2-year survival after HTX (P = 0.0049)., Conclusion: Treatment with ivabradine in patients within 2 years after HTX significantly reduced post-transplant heart rate and LV mass and was associated with a superior survival in comparison with patients receiving metoprolol succinate.

Objective Sinus tachycardia is frequently reported in systemic lupus erythematosus (SLE), while there are limited data on post-exercise ability to slow heart rate (i.e. heart rate recovery, HRR) in this group of patients. Methods We studied consecutive 70 patients with SLE and 30 healthy controls. All examined individuals underwent detailed clinical examination, echocardiography, Holter monitoring with heart rate variability and treadmill stress test using Bruce's protocol. HRR values were calculated as the difference between maximum HR during exercise and HR at the first (HRR1) and third (HRR3) minute of rest. Individuals with coronary artery disease, diabetes mellitus and suspected pulmonary hypertension were excluded from further analysis ( n = 15). Results Fifty-five SLE patients were eligible for this study: aged 41.5 ± 12.4 years, 87.3% women, SLICC/ACR-DI score 3.58 ± 1.85. In the SLE group 36.4% patients received beta-blockers, usually for previously detected sinus tachycardia and/or arterial hypertension. Mean HRR1 (36.9 ± 12.6 vs 49.5 ± 18.6, p = 0.0004) and HRR3 (55.5 ± 14.3 vs 69.2 ± 16.4, p = 0.0001) were significantly lower in SLE than in healthy individuals. Significantly negative correlations between SLICC/ACR-DI score and HRR1 ( r = -0.299, p = 0.01), HRR3 ( r = -0.361, p = 0.001) and exercise capacity ( r = -0.422, p < 0.0001) were revealed. Additionally, beta-blocker treatment was also revealed to alter significantly HRR1, HRR3 and exercise capacity in SLE. Conclusion Patients with SLE are characterized by attenuated HRR after exercise. In our study impaired HRR was associated with disease severity and beta-blocker treatment and probably with disease duration. The use of HRR assessment in SLE can be used as an additional marker of cardiac autonomic nervous system dysfunction.

Background: Inappropriate sinus tachycardia (IST) is debilitating despite available treatment. Off-label use of ivabradine for IST prompted this systematic analysis of existing data quality and sample size estimates for adequately powered studies., Objective: To determine clinical efficacy of ivabradine in IST from pooled prospective studies., Methods: Analysis included ivabradine studies for IST participants without structural heart disease and with follow-up of ≥2 weeks. Heart rate and symptom reduction with ivabradine were estimated based on results of subjective change in symptoms assessed by various data instruments used in each study. Studies were assessed for quality using validated checklists. Sample sizes were calculated based on the magnitude of symptom reduction encountered after treatment with ivabradine., Results: Nine studies met criteria, culminating in 145 patients pooled. Most patients were women (≥70%). Studies were small and not adequately powered, and all reported a decrease in maximum or mean resting heart rate or both, with complete or considerable amelioration of symptoms with ivabradine. Most studies had moderate quality with excellent consistency of study quality and narrow limits of agreement between the quality checklists. Sample size estimates for adequately powered studies with various placebo effects and comparisons with β-blockade are reported., Conclusions: Ivabradine effectively reduces heart rate and symptoms in IST, but no study was adequately powered to account for the expected placebo effect on symptoms. A multicenter, randomized, placebo-controlled, active, comparative study with a β-blocker is needed for confirmation. This is especially relevant given the ivabradine's potential teratogenic effect, as many IST patients are females of childbearing potential., (Published by Elsevier Inc.)

Background: Sinus tachycardia (ST) is common after heart transplantation (HTx). The aim of the study was to evaluate the effect of diltiazem treatment during the first year after HTx on heart rate (HR), cardiac allograft function, and exercise capacity., Methods: From the total cohort, 25 HTx recipients started diltiazem treatment 4±2 weeks after HTx and continued it for at least 1 year (diltiazem group). Each study case was matched to a control. All patients underwent hemodynamic assessment and cardiopulmonary exercise test (CPET) at 1 year after HTx., Results: HR decreased in the diltiazem group from 99±11 bpm to 94±7 bpm (P=.03) and did not change in the controls (98±11 bpm vs 100±13 bpm, P=.14). The difference between the groups at 1 year after HTx was significant (P=.04). In the diltiazem group left ventricular (LV), stroke volume and ejection fraction increased (48±16 vs 55±17 mL, P=.02, and 60%±10% vs 62%±12% P=.03, respectively) but did not differ from controls. E/E' decreased (10.7±2.7 vs 7.3±1.9, P=.003) while cardiac index was higher (3.5±0.8 vs 3.1±0.5; P=.05) in the diltiazem group at 1-year follow-up. The absolute peak VO 2 (21±4 vs 18±6 mL/kg/min; P=.05) and normalized peak VO 2 (73%±17% vs 58%±14%; P=.004) were significantly higher in the diltiazem group., Conclusions: This study showed that diltiazem treatment reduces ST, may improve cardiac allograft function and exercise tolerance during the first year after HTx., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

A 26-year-old man presented to our syncope service with debilitating daily palpitations, shortness of breath, presyncope and syncope following a severe viral respiratory illness 4 years previously. Mobitz type II block had previously been identified, leading to a permanent pacemaker and no further episodes of frank syncope. Transthoracic echocardiography, electophysiological study and repeated urine metanepherines were normal. His palpitations and presyncope were reproducible on deep inspiration, coughing, isometric hand exercise and passive leg raises. We demonstrated rapid increases in heart rate with no change in morphology on his 12 lead ECG. His symptoms were resistant to fludrocortisone, flecainide, β blockers and ivabradine. Initiation of clonidine in combination with ivabradine led to rapid resolution of his symptoms. We suggest that an excessive respiratory sinus arrhythmia was responsible for his symptoms and achieved an excellent response with the centrally acting sympatholytic clonidine, where previous peripherally acting treatments had failed., Competing Interests: Competing interests: None declared., (2017 BMJ Publishing Group Ltd.)

Objectives: The goal of this study was to describe short- and long-term outcomes in all patients referred for inappropriate sinus tachycardia ablation, along with the potential complications of the intervention., Background: Sinus node (SN) ablation/modification has been proposed for patients refractory to pharmacological therapy. However, available data derive from limited series., Methods: The electronic databases MEDLINE, Embase, CINAHL, Cochrane, and Scopus were systematically searched (January 1, 1995-December 31, 2015). Studies were screened according to predefined inclusion and exclusion criteria., Results: A total of 153 patients were included. Their mean age was 35.18 ± 10.02 years, and 139 (90.8%) were female. All patients had failed to respond to maximum tolerated doses of pharmacological therapy (3.5 ± 2.4 drugs). Mean baseline heart rates averaged 101.3 ± 16.4 beats/min according to electrocardiography and 104.5 ± 13.5 beats/min according to 24-h Holter monitoring. Two electrophysiological strategies were used, SN ablation and SN modification, with the latter being used more. Procedural acute success (using variably defined pre-determined endpoints) was 88.9%. Consistently, all groups reported high-output pacing from the ablation catheter to confirm absence of phrenic nerve stimulation before radiofrequency delivery. Need of pericardial access varied between 0% and 76.9%. Thirteen patients (8.5%) experienced severe procedural complications, and 15 patients (9.8%) required implantation of a pacemaker. At a mean follow-up interval of 28.1 ± 12.6 months, 86.4% of patients demonstrated successful outcomes. The symptomatic recurrence rate was 19.6%, and 29.8% of patients continued to receive antiarrhythmic drug therapy after procedural intervention., Conclusions: Inappropriate sinus tachycardia ablation/modification achieves acute success in the vast majority of patients. Complications are fairly common and diverse. However, symptomatic relief decreases substantially over longer follow-up periods, with a corresponding high recurrence rate., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Inappropriate sinus tachycardia (IST) is an incompletely understood condition, characterised by an elevation in heart rate (HR) accompanied by wide ranging symptoms in the absence of an underlying physiological stimulus. The condition often takes a chronic course with significant adverse effects on quality of life. Currently, there is no effective treatment for IST. Beta-blockers, generally considered the cornerstone of treatment, are often ineffective and poorly tolerated. Ivabradine is a novel sinus node If 'funny current' inhibitor, which reduces the HR. It has been approved for the treatment of beta-blocker refractory chronic systolic heart failure and chronic stable angina but more recently has shown promise in the treatment of IST. This review provides an overview of IST prevalence and mechanisms followed by an examination of the evidence for the role and efficacy of ivabradine in the treatment of IST., (© 2016 Royal Australasian College of Physicians.)

Background: Clozapine is an efficacious treatment for treatment-resistant schizophrenia; however its use can be limited by side effect intolerability. Sinus tachycardia is a common adverse event associated with clozapine treatment. Various pharmacological treatments are used to control heart rate increase due to clozapine use and can include a decreased rate of clozapine titration, a switch to a different antipsychotic, or treatment with negative chronotropic drugs., Objectives: To assess the clinical effects and efficacy of pharmacological interventions for clozapine-induced sinus tachycardia.To systematically review the adverse events associated with pharmacological interventions for clozapine-induced sinus tachycardia., Search Methods: On 23 March 2015, we searched the Cochrane Schizophrenia Group's Study-Based Register of Trials, which is based on regular searches of CINAHL, BIOSIS, AMED, EMBASE, PubMed, MEDLINE, PsycINFO and registries of clinical trials. There are no language, date, document type or publication status limitations for inclusion of records in the register., Selection Criteria: Randomised controlled trials comparing pharmacological interventions, at any dose and by any route of administration, for clozapine-induced tachycardia., Data Collection and Analysis: We independently screened and assessed studies for inclusion using pre-specified inclusion criteria., Main Results: The electronic searches located three references. However, we did not identify any studies that met our inclusion criteria., Authors' Conclusions: With no studies meeting the inclusion criteria, it is not possible to arrive at definitive conclusions. There are currently insufficient data to confidently inform clinical practice. We cannot, therefore, conclude whether specific interventions, such as beta-blockers, are less effective or more effective than standard courses of alternative treatments for tachycardia. This lack of evidence for the treatment of clozapine-induced tachycardia has implications for research and practice. Well-planned, conducted and reported randomised trials are indicated. One trial is currently underway. Current practice outside of well-designed randomised trials should be clearly justified.

Inappropriate sinus tachycardia is a challenging problem to manage. There are limited data on the best method to evaluate and treat the problem. Here, we consider a conventional approach to inappropriate sinus tachycardia.

Background: Inappropriate sinus tachycardia (IST) often causes palpitations, dyspnea, and exercise intolerance, that are generally treated with beta blockers and non-dihydropyridine calcium-channel antagonists. Ivabradine, a selective inhibitor of cardiac pacemaker If current, has recently emerged as an effective and safe alternative to conventional drugs for IST., Methods: We performed a systematic overview of clinical studies on the therapeutic yield of ivabradine in patients with inappropriate sinus tachycardia, published in MEDLINE database from January 2000 to March 2015., Results: Overall, five case reports were found, all showing efficacy of ivabradine in subjects affected by IST. Eight non-randomized clinical studies demonstrated short- and medium-term safety and efficacy of ivabradine administration in IST, also in adjunction to or in comparison with metoprolol. One double-blind randomized crossover study also showed that ivabradine is superior to placebo for heart rate (HR) reduction and symptoms control in patients affected by IST., Conclusions: Ivabradine is effective and safe in short- and medium-term treatment of IST. However, long-term follow-up studies and randomized studies comparing ivabradine with beta blockers are still lacking.

Cardiac arrhythmias are an important aspect of fetal and neonatal medicine. Premature complexes of atrial or ventricular origin are the main cause of an irregular heart rhythm. The finding is typically unrelated to an identifiable cause and no treatment is required. Tachyarrhythmia most commonly relates to supraventricular reentrant tachycardia, atrial flutter, and sinus tachycardia. Several antiarrhythmic agents are available for the perinatal treatment of tachyarrhythmias. Enduring bradycardia may result from sinus node dysfunction, complete heart block and nonconducted atrial bigeminy as the main arrhythmia mechanisms. The management and outcome of bradycardia depend on the underlying mechanism., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Tacrolimus is a potent immunosuppressive agent widely used after organ transplantation. In this present study we present eight patients who complained of palpitation after kidney transplantation. Eight out of 31 patients who received tacrolimus after kidney transplantation suffered from tachycardia. Resting electrocardiography, 24 hours Holter monitorization, echocardiography were performed, and serum levels of cardiac troponin T, creatine kinase, CKMB, brain natriuretic peptide and tacrolimus were measured. The median time to palpitation after kidney transplantation was 30 days in seven patients, and one patient complained of palpitation five years after transplantation. Cardiovascular assessment revealed sinus tachycardia in all patients. Beta-blocker was instituted in five patients. After two months all patients were asymptomatic and their pulse rates were within normal limits. Transient sinus tachycardia is a frequent adverse event during tacrolimus therapy in children and young adults, at therapeutic levels. Patients may benefit from beta-blockers.

Left ventricular (LV) systolic dysfunction and chronic systolic heart failure (HF) predispose to intraventricular thrombus formation and embolization resulting in stroke. Current guideline recommends the use of oral anticoagulants in patients with atrial fibrillation and history of previous thromboembolism. However, anticoagulant treatment in patients with LV systolic dysfunction with sinus rhythm and without history of previous thromboembolism is still on debate. Recent epidemiologic date has reported increased stroke rate in patients with systolic HF shortly after diagnosis. This review focuses on the possible causes of increased stroke rate shortly after the diagnosis of HF and subsequently suggests a rationale for the use of oral anticoagulant in these patient groups., (© The Author(s) 2013.)

Tachycardia induced cardiomyopathy is a potentially lethal cause of heart failure generally because of atrial tachycardia and less frequently ventricular tachycardia. We present two cases of Marines with severe traumatic blast injuries secondary to improvised explosive device attacks whose hospital courses included amputation, massive blood transfusions, and multiple surgeries. Both patients had prolonged sinus tachycardia averaging >110 beats per minute and developed depressed left ventricular function, which recovered when treated with β blockers. Sinus tachycardia is often considered a physiological response to stress, and the purpose of this manuscript is to describe the cardiac injury apparently related to a prolonged stress response. In addition, the literature does not clearly recommend controlling heart rates in trauma patients with persistent sinus tachycardia, but it is a therapeutic option that should be considered by providers., (Reprint & Copyright © 2014 Association of Military Surgeons of the U.S.)

Inappropriate sinus tachycardia (IST) is a syndrome characterized by unexplained tachycardia (heart rate > 100 beats /min) and related symptoms at rest. We describe a case of a 35 year old male with end stage renal disease who developed IST after renal transplant in the surgical intensive care unit. Management of IST is usually nonspecific and includes bradycardic agents, radiofrequency ablation or surgical ablation of the sinus node. This patient was well managed with ivabradine (If pacemaker current inhibitor) after failure and intolerance of β-adrenergic blockers.

We report the case of a 38-year patient who presented in our outpatient clinic for cardiac evaluation and assessment as volunteer firefighter. The patient had an asymptomatic sinustachycardia, which was diagnosed at the age of 15. After we excluded secondary etiologies, as well as a postural orthostatic tachycardia syndrome (POTS) diagnosis of inappropriate sinus tachycardia (IST) was confirmed. A metoprolol therapy was established, however to resistant tachycardia, we suggested a combined therapy of Bisoprolol and Ivabradin, which resulted successfully in normocard sinus rhythm.

Background: Inappropriate sinus tachycardia (IST) and postural tachycardia syndrome (POTS) are 2 disorders characterized by sinus tachycardia. It is debated whether the pathophysiology of IST and POTS results from abnormal autonomic regulation or abnormal sinus node function. We hypothesized that intrinsic heart rate (IHR) after autonomic blockade would be increased in patients with IST but not POTS., Methods and Results: We enrolled 48 POTS patients, 8 IST patients, and 17 healthy control (HC) subjects. Intravenous propranolol and atropine were given to block the sympathetic and parasympathetic limbs of the autonomic nervous system in order to determine the IHR. Patients with IST have a higher sympathetic contribution to heart rate when compared with POTS patients (31±13 bpm versus 12±7 bpm, P<0.001) and HC (8±4 bpm; P<0.001) and a trend to less parasympathetic contribution than POTS and HC (IST: 31±11 bpm versus POTS: 46±11 bpm versus HC: 48±11 bpm, ANOVA P=0.108). IHR was not significantly different between IST and either POTS or HC (IST: 111±11 bpm versus POTS: 108±11 bpm versus HC: 106±12 bpm, ANOVA P=0.237)., Conclusions: IST patients have more sympathetic tone when compared with either POTS or HC, but IST patients do not have abnormal sinus node automaticity. These data suggest that the treatment of IST and POTS should focus on sympatholysis, reserving sinus node modification for patients with continued debilitating symptoms after beta-blockade and possibly ivabradine., Clinical Trial Registration Url: http://clinicaltrials.gov/. Unique identifier: NCT00262470.

Aim of the Study: The analysis of supraventricular rhythm disorders encountered in hypertensive patients and the establishment of correlations with other associated risk factors, duration of hypertension, the evolution and prognosis., Material and Methods: The study included a group of 110 patients, 80 men and 30 women, aged between 40 and 85, admitted in the 1st Cardiology Clinic during 2010-2013, diagnosed with essential arterial hypertension second and third degree. For the detection of arrhythmic events surface 12-lead ECG and 24-hour Holter monitoring were used., Results and Discussion: Supraventricular arrhythmias encountered in the patients of the group were: ESA (mostly isolated, but also doublets, atrial bigeminy), atrial fibrillation, atrial flutter, sinus tachycardia, sinus bradycardia. Some arrhythmias may be an expression of the excessive activation of the sympathetic nervous system or on the contrary, vagal predominance, (ex. sinus bradycardia). Part of the arrhythmias occurring in hypertensive patients are hypertensive heart disease expressions, others are due to associated risk factors (smoking, alcohol) and even medication administered. In some cases, rhythm disturbances disappear with the normalization of the blood pressure; however, most of the times, the specific combination of anti-arrhythmic medication with antihypertensive medication is required., Conclusions: Supraventricular arrhythmias are frequently found in hypertensive patients, especially in those with long-term, uncontrolled hypertension, with impact on the evolution, prognosis and therapeutic management.

Aims: Ivabradine, an I(f) current blocker, has shown promising results in treatment of postural orthostatic tachycardia syndrome (POTS). There is a subgroup of vasovagal syncope (VVS) patients, who demonstrate sinus tachycardia before collapse on tilt testing mimicking some features of POTS. These patients may also respond to ivabradine therapy. University Hospital Syncope Clinic where ivabradine was prescribed in a prospective fashion on humanitarian grounds between October 2008 and December 2011., Methods and Results: Twenty-five patients of mean age 33±years presenting syncope in all and palpitation in 23, duration 9±years underwent tilt testing with reproduction of usual symptoms including tachycardia preceding collapse. Ivabradine was prescribed in doses of 5-20 mg/day, mean 10.7 mg, as once or twice daily medication. The response to treatment was classified as deterioration in none, no change in 5, improvement in 10, and symptoms abolished in 8 patients. Side effects were minimal; one patient required discontinuation., Conclusion: In this pilot study of ivabradine, in patients with VVS, of patients who demonstrated sinus tachycardia before collapse on tilt, 72% reported a marked benefit or complete resolution of symptoms. The drug was well tolerated. A randomized controlled trial against placebo is justified.