[Telemedicine for patients with cardiac implants : Insights into everyday practice of remote monitoring in Germany in 2022]. / Telemedizinische Versorgung von Patienten mit kardialen Implantaten : Einblick in die telekardiologische Versorgungsrealität in Deutschland im Jahr 2022.

BACKGROUND: As telemedical structures continues to be developed in the German healthcare system, remote monitoring is becoming increasingly important to ensure comprehensive, outpatient, and tailored care. The national quality assurance measure "DOQUVIDE-Documentation of quality in the assessment of vital parameters by implanted devices" is used to provide insight into everyday care for patients with telemedicine-enabled devices in Germany. METHODS: DOQUVIDE is a measuring instrument for recording outpatient remote monitoring for patients with implanted pacemaker, implantable cardioverter defibrillator (ICD), cardiac resynchronization therapy with a pacemaker (CRT-P), CRT defibrillator (CRT-D) devices and event recorder. DOQUVIDE records telemedically measured vital signs as well as cardiac events and the associated procedures initiated by cardiologists using standardized forms. RESULTS: In 74 practices/clinics in 14 federal states, 6687 patients received telemedical care in 2022; 937 were newly enrolled. These (60% male) were on average 77.8 years old, mainly with New York Heart Association (NYHA) class II (62.6%). A total of 5801 electronic records were generated as a result of telecardiology events, of which 3590 were due to pathological atrial fibrillation and 1812 due to ventricular high-frequency episodes. 295 events were triggered by event recorders and 95 by device therapies. The main measures taken were telephone contacts or outpatient visits. CONCLUSION: Remote monitoring has become a reality in German healthcare. Standardized processes and the establishment of quality assurance measures enable the definition of common quality standards and the identification of the potential for further development and simplify implementation in day-to-day care for practices.

A Randomized Controlled Trial Comparing Apixaban With the Vitamin K Antagonist Phenprocoumon in Patients on Chronic Hemodialysis: The AXADIA-AFNET 8 Study.

BACKGROUND: Non-vitamin K oral anticoagulants have become the standard therapy for preventing stroke and ischemic thromboembolism in most patients with atrial fibrillation (AF). The effectiveness and safety of non-vitamin K oral anticoagulants in patients on hemodialysis is not well known. METHODS: From June 2017 through May 2022, AXADIA-AFNET 8 (Compare Apixaban and Vitamin K Antagonists in Patients With Atrial Fibrillation and End-Stage Kidney Disease), an investigator-initiated PROBE (prospective randomized open blinded end point) outcome assessment trial, randomized patients with AF on chronic hemodialysis to either apixaban (2.5 mg BID) or the vitamin K antagonist (VKA) phenprocoumon (international normalized ratio, 2.0 to 3.0). The composite primary safety outcome was defined by a first event of major bleeding, clinically relevant nonmajor bleeding, or all-cause death. The primary efficacy outcome was a composite of ischemic stroke, all-cause death, myocardial infarction, and deep vein thrombosis or pulmonary embolism. Our hypothesis was that apixaban is noninferior to VKA. RESULTS: Thirty-nine sites randomized 97 patients (30% women; mean age 75 years; mean CHA2DS2-VASc [congestive heart failure, hypertension, age ≥75 years, diabetes, stroke or transient ischemic attack, vascular disease, age 65 to 74 years, female sex] score, 4.5; baseline characteristics balanced between groups): 48 to apixaban and 49 to VKA. The median follow-up time was 429 days (range, 37 to 1370) versus 506 days (range, 101 to 1379), respectively. Adherence to apixaban was >80% in 44 of 48 patients; the median time in therapeutic range on VKA was 50.7%. Composite primary safety outcome events occurred in 22 patients (45.8%) on apixaban and in 25 patients (51.0%) on VKA (hazard ratio, 0.93 [95% CI, 0.53-1.65]; Pnoninferiority=0.157). Composite primary efficacy outcome events occurred in 10 patients (20.8%) on apixaban and in 15 patients (30.6%) on VKA (P=0.51; log rank). There were no significant differences regarding individual outcomes (all-cause mortality, 18.8% versus 24.5%; major bleeding, 10.4% versus 12.2%; and myocardial infarction, 4.2% versus 6.1%, respectively). CONCLUSIONS: In this randomized trial comparing apixaban and VKA in patients with AF on hemodialysis with long follow-up, no differences were observed in safety or efficacy outcomes. Even on oral anticoagulation, patients with AF on hemodialysis remain at high risk of cardiovascular events. Larger randomized trials are needed to determine the optimal anticoagulation regimen for patients with AF on hemodialysis. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02933697.

[Tachycardia and syncope in a 15-year-old teenager]. / Herzrasen und Synkope bei einer 15-jährigen Jugendlichen.

Patients with highly symptomatic tachycardia may suffer significantly; in addition to a standardized rule-out of structural heart disease, secondary causes need to be excluded. Disorders such as inappropriate sinus tachycardia and postural tachycardia syndrome are caused by cardiac autonomic dysregulation which may be part of a rare underlying noncardiac disease.

Cardiology meets neurology: clinical presentation and management of patients with primary neurogenic disorders and orthostatic intolerance.

Patients with primary neurogenic disorders such as pure autonomic failure or multiple system atrophy may initially present with cardiocirculatory symptoms such as orthostatic intolerance or fluctuations in heart rate with symptomatic tachycardia. It is therefore clinically important to identify such patients since circulatory manifestations are only one of a series of symptoms resulting from autonomic dysfunction in various organ systems. These patients require a multimodal diagnostic and therapeutic approach and should undergo extensive evaluation in a specialized autonomic nervous system (ANS) outpatient unit. Based on a clinical case presentation, the current review summarizes the diagnostic and therapeutic approach to key cardiovascular symptoms of primary autonomic disorders and their neurological work-up in a specialized autonomic function laboratory.

Baseline intrinsic heart rate and response to ivabradine treatment in patients with inappropriate sinus tachycardia.

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.

Transtelephonic ECG Monitoring to Guide Outpatient Antiarrhythmic Drug Therapy in Patients With Non-Permanent Atrial Fibrillation: Efficacy and Safety From a Single-Center Experience.

Initiation of antiarrhythmic drug therapy (AADx) for atrial fibrillation (AF) on an outpatient basis requires intensive ECG monitoring in order to assess antiarrhythmic efficacy as well as ECG signals of potential proarrhythmia. Dronedarone (DRO) reduces cardiovascular endpoints in AF patients fulfilling criteria of the ATHENA trial [1]. In the present study transtelephonic ECG monitoring was used to guide initiation of AADx in AF patients fulfilling the ATHENA criteria. In 19 consecutive patients (37% female; age 65+10 years; LVEF 62+7%; mean CHA2DS2-VASc score 2.9 + 1.6 (median=2), with symptomatic non-permanent AF and additional cardiovascular risk factors, DRO was prescribed as AADx of first choice. Initiation of therapy and follow-up were monitored by transtelephonic ECG recordings (VITAPHONE™100 IR; Vitaphone GmbH; Germany). In patients with persistent AF, electrical cardioversion was performed on an outpatient basis when DRO was started. Patients were followed for changes in QT intervals as well as AF recurrency. ECGs were transmitted according to a scheduled FU form as well as any time in case of pts symptoms. Patients in whom DRO did not prevent AF recurrence were switched to alternative AADx, or to pulmonary vein isolation (PVI), respectively. At the end of long-term follow-up, DRO alone was successful in preventing AF recurrence in 5 of 19 patients (26%). When pts who responded to AADx of second or third choice or who underwent PVI were included, SR could be maintained in 17/19 pts (89%). No patient required discontinuation of AADx due to ventricular depolarization abnormalities, symptomatic bradycardia or pathologic QT prolongation. In conclusion, transtelephonic ECG transmission is useful for close rhythm monitoring during initiation and follow-up of AADx, also during change from DRO to other AADx. DRO was effective to prevent AF recurrence in 26% of patients during a mean long-term follow-up of more than 30 months - which is well in line with data from the literature.

The clinical value of T-wave alternans derived from Holter monitoring.

Microvolt-level T-wave alternans (TWA) assessed by spectral method during an exercise stress test has been widely studied for risk stratification. Several studies have documented the association of a positive TWA with total mortality and arrhythmic events. Nevertheless, the need to achieve an elevated and stabilized heart rate resulting in a considerable proportion of indeterminate test results constitutes one of the main limitations of this method. It is well recognized that arrhythmic events may be triggered not only by physical but also by mental stress and are not necessarily associated with exercise. Detection of TWA in ambulatory electrocardiogram recordings during daily activities might be a valuable option in risk stratification. This review describes the modified moving average (MMA) technique for detection of TWA and summarizes the results of clinical studies on the prognostic value of MMA-TWA. So far, MMA-TWA has been studied in over 5000 patients including those evaluated during exercise as well as during daily activities with ambulatory ECG recordings. The results of these studies indicate that increased MMA-TWA is associated with higher risk of cardiac mortality and arrhythmic events.

Fludrocortisone for the Prevention of Vasovagal Syncope: A Randomized, Placebo-Controlled Trial.

BACKGROUND: There is limited evidence whether being on fludrocortisone prevents vasovagal syncope. OBJECTIVES: The authors sought to determine whether treatment with fludrocortisone reduces the proportion of patients with recurrent vasovagal syncope by at least 40%, representing a pre-specified minimal clinically important relative risk reduction. METHODS: The multicenter POST 2 (Prevention of Syncope Trial 2) was a randomized, placebo-controlled, double-blind trial that assessed the effects of fludrocortisone in vasovagal syncope over a 1-year treatment period. All patients had >2 syncopal spells and a Calgary Syncope Symptom Score >-3. Patients received either fludrocortisone or matching placebo at highest tolerated doses from 0.05 mg to 0.2 mg daily. The main outcome measure was the first recurrence of syncope. RESULTS: The authors randomized 210 patients (71% female, median age 30 years) with a median 15 syncopal spells over a median of 9 years equally to fludrocortisone or placebo. Of these, 96 patients had ≥1 syncope recurrences, and only 14 patients were lost to follow-up before syncope recurrence. There was a marginally nonsignificant reduction in syncope in the fludrocortisone group (hazard ratio [HR]: 0.69: 95% confidence interval [CI]: 0.46 to 1.03; p = 0.069). In a multivariable model, fludrocortisone significantly reduced the likelihood of syncope (HR: 0.63; 95% CI: 0.42 to 0.94; p = 0.024). When the analysis was restricted to outcomes after 2 weeks of dose stabilization, there was a significant benefit due to fludrocortisone (HR: 0.51; 95% CI: 0.28 to 0.89; p = 0.019). CONCLUSIONS: The study did not meet its primary objective of demonstrating that fludrocortisone reduced the likelihood of vasovagal syncope by the specified risk reduction of 40%. The study demonstrated a significant effect after dose stabilization, and there were significant findings in post hoc multivariable and on-treatment analyses. (A randomised clinical trial of fludrocortisone for the prevention of vasovagal syncope; ISRCTN51802652; Prevention of Syncope Trial 2 [POST 2]; NCT00118482).

Estradiol regulates human QT-interval: acceleration of cardiac repolarization by enhanced KCNH2 membrane trafficking.

BACKGROUND: Modulation of cardiac repolarization by sexual hormones is controversial and hormonal effects on ion channels remain largely unknown. In the present translational study, we therefore assessed the relationship between QTc duration and gonadal hormones and studied underlying mechanisms. METHODS AND RESULTS: We measured hormone levels and QTc intervals in women during clomiphene stimulation for infertility and women before, during, and after pregnancy. Three heterozygous LQT-2 patients (KCNH2-p.Arg752Pro missense mutation) and two unaffected family members additionally were studied during their menstrual cycles. A comprehensive cellular and molecular analysis was done to identify the mechanisms of hormonal QT-interval regulation. High estradiol levels, but neither progesterone nor estradiol/progesterone ratio, inversely correlated with QTc. Consistent with clinical data, in vitro estradiol stimulation (60 pmol/L, 48 h) enhanced IKCNH2. This increase was mediated by estradiol receptor-α-dependent promotion of KCNH2-channel trafficking to the cell membrane. To study the underlying mechanism, we focused on heat-shock proteins. The heat-shock protein-90 (Hsp90) inhibitor geldanamycin abolished estradiol-induced increase in IKCNH2. Geldanamycin had no effect on KCNH2 transcription or translation; nor did it affect expression of estradiol receptors and chaperones. Estradiol enhanced the physical interaction of KCNH2-channel subunits with heat-shock proteins and augmented ion-channel trafficking to the membrane. CONCLUSION: Elevated estradiol levels were associated with shorter QTc intervals in healthy women and female LQT-2 patients. Estradiol acts on KCNH2 channels via enhanced estradiol-receptor-α-mediated Hsp90 interaction, augments membrane trafficking and thereby increases repolarizing current. These results provide mechanistic insights into hormonal control of human ventricular repolarization and open novel therapeutic avenues.

[Microvolt T-wave alternans. Ischemic vs. nonischemic dilated cardiomyopathy]. / Mikrovolt T-Wellen-Alternans. Ischämische vs. nichtischämische dilatative Kardiomyopathie.

The use of implantable cardioverter defibrillators (ICD) for primary preventive therapy of sudden arrhythmogenic death has become a mainstay in selected patients with systolic congestive heart failure, particularly in the setting of ischemic and nonischemic cardiomyopathy (Moss et al., N Engl J Med 346:877­883, 2002; Bardy et al., N Engl J Med 352:225­237, 2005). However, more accurate identification of high-risk patients is desirable in order to avoid unnecessary ICD implants. Since currently available risk stratification methods have limited predictive accuracy, development of new techniques is important in order to noninvasively assess arrhythmogenic risk in patients prone to sudden death.Microvolt level T-wave alternans (mTWA) has recently been proposed to assess abnormalities in ventricular repolarization favoring the occurrence of reentrant arrhythmias (Adam et al., J Electrocardiol 17:209­218, 1984; Pastore et al., Circulation 99:1385­1394, 1999). In 1994, a preliminary clinical study by Rosenbaum et al. convincingly demonstrated that mTWA is closely related to arrhythmia induction in the electrophysiology laboratory as well as to the occurrence of spontaneous ventricular tachyarrhythmias during follow-up (Rosenbaum et al., N Engl J Med 330:235­241,1994). More recently, a number of clinical studies have examined its clinical applicability in ischemic and nonischemic cardiomyopathy.

Noninvasive assessment of autonomic cardiovascular activity in patients with inappropriate sinus tachycardia.

Inappropriate sinus tachycardia (IST) is a clinical syndrome characterized by excessive resting heart rate (HR) or disproportional HR increase during exercise. The etiology of IST has not been fully elucidated and remains controversial. The aim of the present study was to assess autonomic function by means of noninvasive tests and commonly available electrocardiographic methods in a series of consecutive patients with symptomatic IST. Twenty-four patients (37 ± 12 years; 20 women) with IST were enrolled. Six cardiovascular reflex tests were performed: (1) HR variation during slow deep breathing, (2) 30-to-15 ratio during active standing, (3) blood pressure response to standing, (4) cold face test, (5) Valsalva maneuver, and (6) blood pressure response to sustained handgrip. Intrinsic HR was calculated and compared with HR after pharmacologic denervation. Additionally, spontaneous baroreflex sensitivity and 24-hour HR variability indices were analyzed. In IST patients, intrinsic HR was significantly higher compared with control subjects. Most cardiovascular autonomic tests revealed abnormal or borderline results, particularly those reflecting mainly parasympathetic function. The spontaneous baroreflex gain was significantly reduced in IST patients. After controlled orthostatic stress and during Valsalva maneuver, impaired baroreflex function was observed. The sympathovagal balance from HR variability was preserved, but altered activity in both bands of frequency domain analysis was recorded. In conclusion, IST is a heterogenic syndrome with enhanced sinus node automaticity modulated by complex alterations of autonomic tone.

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. ß-blocker or calcium channel-blocker therapy is often noneffective or not well tolerated. The HR reduction on ivabradine is similar to ß-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 ß-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.

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.

Ivabradine in the treatment of inappropriate sinus tachycardia in patients after successful radiofrequency catheter ablation of atrioventricular node slow pathway.

BACKGROUND: Inappropriate sinus tachycardia (IST) occurs relatively common after catheter ablation of slow pathway in patients with atrioventricular nodal reentrant tachycardia. The treatment of IST symptoms using ß-blockers or calcium channel-blockers are often noneffective or not well tolerated. Ivabradine is a new heart rate (HR)-decreasing agent inhibiting sinus node If current. The purpose of the study was to evaluate the efficacy and safety of ivabradine in patients with persistent and ß-blocker-resistant IST after successful radiofrequency (RF) ablation of atrioventricular node slow pathway. METHODS: We enrolled 14 patients (42 ± 11 years; 10 women) affected by IST after RF ablation. Holter monitoring, treadmill stress test, and IST symptoms assessment were performed at baseline and after first, and second month of the study. RESULTS: We observed significant reduction of mean resting HR after 30 and 60 days of ivabradine treatment compared to baseline (P < 0.001). 24-hour Holter monitoring showed a significant reduction of mean HR and mean HR during daily activity (P < 0.001). The study revealed significant improvement in exercise capacity during treadmill exercise test on ivabradine therapy (P < 0.001). Significantly lower incidence of IST-related symptoms were registered after administration of If current inhibitor. After 2 months of treatment no patients reported severe complaints assessed by means of European Heart Rhythm Association score. We did not observe severe side effects during therapy. CONCLUSION: Ivabradine is an effective treatment option to reduce HR and symptoms in patients with IST after RF ablation of atrioventricular node slow pathway. The therapy with ivabradine is well tolerated even with maximum daily dose.