Jerzy Krzysztof Wranicz

Metoprolol succinate vs. ivabradine in the treatment of inappropriate sinus tachycardia in patients unresponsive to previous pharmacological therapy

AIMS Inappropriate sinus tachycardia (IST) is a clinical syndrome characterized by excessive resting heart rate (HR) or disproportional increasing HR during exercise. The treatment of IST symptoms using beta-blockers or calcium channel-blockers is often non-effective or not well tolerated. Ivabradine is a new agent inhibiting sinus node I(f) current, resulting in a decrease of HR without haemodynamic compromise. METHODS AND RESULTS We enrolled 20 patients (36 ± 10 years; 14 women) affected by IST and resistant to previous administered therapy by using beta-blockers or verapamil. After 4 weeks of treatment with metoprolol succinate (up to 190 mg once a day) the therapy was switched to ivabradine up to 7.5 mg twice daily. Holter monitoring and treadmill stress test were performed after 1 and 2 months following start of the study. We observed a significant reduction of resting HR both for metoprolol and for ivabradine compared with baseline (92.8 vs. 90.2 vs. 114.3 b.p.m.; P< 0.001). During daily activity there was an even larger decrease of HR on ivabradine (mean daytime HR 94.6 vs. 87.1 vs. 107.3 b.p.m.; P< 0.001). Ivabradine was very well tolerated whereas in 10 patients on metoprolol we observed hypotension or bradycardia requiring dose reduction. Significantly lower incidence of IST-related symptoms were registered on ivabradine therapy than on metoprolol. Fourteen patients (70%) treated with I(f) blocker were free of IST-related complaints. CONCLUSIONS Metoprolol and ivabradine exert a similar effect on resting HR in patients with IST. Ivabradine seems to be more effective to relieve symptoms during exercise or daily activity.

Relationship between heart rate turbulence and heart rate, heart rate variability, and number of ventricular premature beats in coronary patients.

Introduction: Heart rate variability (HRV) illustrates regulation of the heart by the autonomic nervous system whereas heart rate turbulence (HRT) is believed to reflect baroreflex sensitivity. The aim of this study was to determine the association between HRT and HRV parameters and the relationship between HRT parameters and heart rate and number of ventricular premature beats (VPBs) used to calculate HRT parameters.

Sex steroids and heart rate variability in patients after myocardial infarction

Background: Although the relationship between sex steroid levels and coronary artery disease (CAD) has been the subject of many studies there are still controversies concerning the role of sex steroids in CAD. In patients with CAD, especially after a myocardial infarction, there is evidence for autonomic nervous system dysfunction. However, there is no data detailing the relationship between sex steroids and cicardian autonomic activity in patients with CAD. The aim of the study was to evaluate the association between sex steroids and heart rate variability (HRV) parameters in postinfarction patients.

Clinical covariates of abnormal heart rate turbulence in coronary patients.

Background: The aim of this study is to evaluate the association between heart rate turbulence (HRT) parameters and clinical characteristics of coronary artery disease (CAD) patients.

Ivabradine in Combination With Metoprolol Succinate in the Treatment of Inappropriate Sinus Tachycardia

Background: Inappropriate sinus tachycardia (IST) is a clinical syndrome characterized by excessive resting heart rate (HR) or a disproportional increase in HR during exercise. β-blocker or calcium channel-blocker therapy is often noneffective or not well tolerated. The HR reduction on ivabradine is similar to β-blockers but in some patients its efficacy to resolve all IST-related symptoms is limited. The aim of the study was to assess the efficacy and safety of combining ivabradine with metoprolol succinate in patients with refractory highly symptomatic IST. Methods: Twenty patients (36 ± 10 years; 16 women) with IST were enrolled. All patients received metoprolol succinate 95 mg single dose during the first month of the study. After 4 weeks of treatment with metoprolol, ivabradine was administered as adjuvant therapy up to 7.5 mg twice daily. Holter monitoring and treadmill stress test were performed at baseline, after 4, and 8 weeks of the study, respectively. Results: We observed significant and similar reduction in resting HR both for metoprolol and for combined therapy compared to the baseline. The mean HR during daily activity was significantly lower on ivabradine and metoprolol compared to monotherapy with β-blocker. The combined treatment yielded a significant increase in exercise capacity as assessed by treadmill stress test. After 4 weeks of combined therapy a significant reduction in IST-related symptoms, measured by means of the European Heart Rhythm Association score, was observed. Conclusion: Combining ivabradine with metoprolol is an effective and well-tolerated treatment option for IST in patients with refractory to monotherapy.

Chronic kidney disease and arrhythmias: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference

Patients with chronic kidney disease (CKD) are predisposed to heart rhythm disorders, including atrial fibrillation (AF)/atrial flutter, supraventricular tachycardias, ventricular arrhythmias, and sudden cardiac death (SCD). While treatment options, including drug, device, and procedural therapies, are available, their use in the setting of CKD is complex and limited. Patients with CKD and end-stage kidney disease (ESKD) have historically been under-represented or excluded from randomized trials of arrhythmia treatment strategies,1 although this situation is changing.2 Cardiovascular society consensus documents have recently identified evidence gaps for treating patients with CKD and heart rhythm disorders.3–7 To identify key issues relevant to the optimal prevention, management, and treatment of arrhythmias and their complications in patients with kidney disease, Kidney Disease: Improving Global Outcomes (KDIGO) convened an international, multidisciplinary Controversies Conference in Berlin, Germany, titled CKD and Arrhythmias in October 2016. The conference agenda and discussion questions are available on the KDIGO website (http://kdigo.org/conferences/ckd-arrhythmias/; 13 February 2018).

WORK-RELATED RISK FACTORS OF MYOCARDIAL INFARCTION

OBJECTIVES The aim of the study was to find out which occupational factors account for the risk of the myocardial infarction. MATERIAL AND METHODS A questionnaire survey was performed during the period of one calendar year in all patients (1053 subjects, 692 men and 361 women) hospitalized at the Medical University of Łódź because of the first myocardial infarction. The questionnaire was prepared especially for the purpose of this study and consisted of two parts. The first part comprised: demographic data, health status at admittance, traditional risk factors for the ischaemic heart disease and was filled-in by physicians. Part II was done by occupational hygiene specialists and referred to education, job title and characteristics, employment data, self assessment of work-related and general stress, fatigue, socio-economic status, physical activity, alcohol intake, tobacco smoking, dietary habits. RESULTS Mean age in the study group was 59.9 ± 10.4 years (26-85 years), 58.7 ± 10.0 (26-84 years) for men and 62.3 ± 10.7 (32-85 years) for women, employment duration was 32.9±8.8 (4-65 years), for men 34.0 ± 8.6 (5-65 years), for women 30.7 ± 8.8 (4-60 years. Most of myocardial infarction cases both in the group of men and women were noted in the age interval 56-60 years, 22.3% vs. 17.4%, respectively. The majority of examined men were farmers, low and middle management and self-employed workers. Among women prevailed clerks, seamstresses and farmers. The most frequent occupational risk factors were: work-related stress, experienced by 54.2% of the examined subjects, occupational noise (45,5%), dust (41,7%) and various chemical factors (33%). A majority of the study group (76.5% women and 54.4% men) linked the cardiac infarction with stress, while 39.1% men vs. 16.5% women correlated it with physical effort. CONCLUSION Our studies indicate that, among a wide spectrum of occupational factors, stress, noise and fine particulate dust are major contributors to the increased risk of myocardial infarction.

Rationale and design of the BUDAPEST-CRT Upgrade Study: A prospective, randomized, multicentre clinical trial

Abstract Aims There is lack of conclusive evidence from randomized clinical trials on the efficacy and safety of upgrade to cardiac resynchronization therapy (CRT) in patients with implanted pacemakers (PM) or defibrillators (ICD) with reduced left ventricular ejection fraction (LVEF) and chronic heart failure (HF). The BUDAPEST-CRT Upgrade Study was designed to compare the efficacy and safety of CRT upgrade from conventional PM or ICD therapy in patients with intermittent or permanent right ventricular (RV) septal/apical pacing, reduced LVEF, and symptomatic HF. Methods and results The BUDAPEST-CRT study is a prospective, randomized, multicentre, investigator-sponsored clinical trial. A total of 360 subjects will be enrolled with LVEF ≤ 35%, NYHA functional classes II–IVa, paced QRS ≥ 150 ms, and a RV pacing ≥ 20%. Patients will be followed for 12 months. Randomization is performed in a 3:2 ratio (CRT-D vs. ICD). The primary composite endpoint is all-cause mortality, a first HF event, or less than 15% reduction in left ventricular (LV) end-systolic volume at 12 months. Secondary endpoints are all-cause mortality, all-cause mortality or HF event, and LV volume reduction at 12 months. Tertiary endpoints include changes in quality of life, NYHA functional class, 6 min walk test, natriuretic peptides, and safety outcomes. Conclusion The results of our prospective, randomized, multicentre clinical trial will provide important information on the role of cardiac resynchronization therapy with defibrillator (CRT-D) upgrade in patients with symptomatic HF, reduced LVEF, and wide-paced QRS with intermittent or permanent RV pacing. Clinical trials.gov identifier NCT02270840.

Pacing and sensing disturbances in patients with DDD pacemakers in the early period after implantation.

Objectives — We sought to determine the usefulness of ambulatory 24-hour Holter monitoring in detecting asymptomatic pacemaker (PM) malfunction episodes in patients with dual-chamber pacemakers whose pacing and sensing parameters were proper, as seen in routine post-implantation follow-ups.This aspect has not been widely discussed so far. Methods and results — Ambulatory 24-hour Holter recordings [HM] were performed in 100 patients with DDD pacemakers one day after the implantation. Only asymptomatic patients with proper pacing and sensing parameters (assessed on PM telemetry on the first day post-implantation) were enrolled in the study.The following parameters were assessed: failure to pace, failure to sense (both oversensing and undersensing episodes) as well as the percentage of all PM disturbances. Despite proper sensing and pacing parameters, HM revealed PM disturbances in 23% of the patients. Atrial undersensing episodes were found in 12 patients and failure to capture in 1 patient. T wave oversensing was the most common ventricular channel disorder (9 patients). Malfunction episodes occurred sporadically, leading to pauses of up to 1.6 s or temporary bradycardia, which were, nevertheless, not accompanied by clinical symptoms. No ventricular pacing disturbances were found. Conclusion — Asymptomatic pacemaker dysfunction may be observed in nearly 25% of patients with proper DDD parameters after implantation.Thus, ambulatory HM during the early post-implantation period may be a useful tool to detect the need to reprogramme PM parameters.

Inflammation and arrhythmias: potential mechanisms and clinical implications

Inflammation is a pathological condition known since ancient times. Recent discoveries of inflammatory markers have given new insights into the role of inflammation in the pathogenesis of arrhythmias. This article reviews global data on possible correlations between inflammation – acute or chronic – and cardiac arrhythmias. The authors discuss the role of inflammation in patients with supraventricular and ventricular arrhythmias. Collected data support the hypothesis that the inflammatory process may be an important factor in cardiac rhythm disturbances.