Patient report outcomes in cryoballoon ablation of atrial fibrillation during the COVID Era: Insights from the 1STOP project.

BACKGROUND: Pulmonary vein isolation by cryoablation (PVI-C) is a standard therapy for the treatment of patients with symptomatic atrial fibrillation (AF). AF symptoms are highly subjective; however, they are important outcomes for the patient. The aim is to describe the use and impact of a web-based App to collect AF-related symptoms in a population of patients who underwent PVI-C in seven Italian centers. METHODS: A patient App to collect AF-related symptoms and general health status was proposed to all patients who underwent an index PVI-C. Patients were divided into two groups according to the utilization of the App or the non-usage. RESULTS: Out of 865 patients, 353 (41%) subjects composed the App group, and 512 (59%) composed the No-App group. Baseline characteristics were comparable between the two cohorts except for age, sex, type of AF, and body mass index. During a mean follow-up of 7.9±13.8 months, AF recurrence was found in 57/865 (7%) subjects with an annual rate of 7.36% (95% CI:5.67-9.55%) in the No-App versus 10.99% (95% CI:9.67-12.48%) in the App group, p=0.007. In total, 14,458 diaries were sent by the 353 subjects in the App group and 77.1% reported a good health status and no symptoms. In only 518 diaries (3.6%), the patients reported a bad health status, and bad health status was an independent parameter of AF recurrence during follow-up. CONCLUSIONS: The use of a web App to record AF-related symptoms was feasible and effective. Additionally, a bad health status reporting in the App was associated with AF recurrence during follow-up.

Autonomic control of heart rate and QT interval variability influences arrhythmic risk in long QT syndrome type 1.

BACKGROUND: A puzzling feature of the long QT syndrome (LQTS) is that family members carrying the same mutation often have divergent symptoms and clinical outcomes. OBJECTIVES: This study tested the hypothesis that vagal and sympathetic control, as assessed by spectral analysis of spontaneous beat-to-beat variability of RR and QT intervals from standard 24-h electrocardiogram Holter recordings, could modulate the severity of LQTS type 1 (LQT1) in 46 members of a South-African LQT1 founder population carrying the clinically severe KCNQ1 A341V mutation. METHODS: Nonmutation carriers (NMCs) (n = 14) were compared with mutation carriers (MCs) (n = 32), 22 with and 10 without major symptoms. We assessed the effect of circadian rhythm and beta-blocker therapy over traditional time and frequency domain RR and QT variability indexes. RESULTS: The asymptomatic MCs differed significantly from the symptomatic MCs and from NMCs in less vagal control of heart rate and more reactive sympathetic modulation of the QT interval, particularly during daytime when arrhythmia risk for patients with LQT1 is greatest. CONCLUSIONS: The present data identified an additional factor contributing to the differential arrhythmic risk among patients with LQT1 carrying the same mutation. A healthy autonomic control confers a high risk, whereas patients with higher sympathetic control of the QT interval and reduced vagal control of heart rate are at lower risk. This differential "autonomic make-up," likely under genetic control, will allow refinement of risk stratification within families with LQTS, leading to more targeted management.

Time, frequency and information domain analysis of heart period and QT variability in asymptomatic long QT syndrome type 2 patients.

This study was designed to characterize in time, frequency and information domains heart period (HP) and QT interval variabilities in asymptomatic (ASYMP) long QT syndrome type 2 (LQT2) subjects. HP, approximated as the temporal distance between two consecutive R-wave peaks, and QT, approximated as the temporal distance between the R-wave peak and the T-wave offset, were automatically derived from 24h Holter recordings in 10 ASYMP LQT2 patients and 13 healthy non mutation carriers (NMC) subjects. All analyses were carried out during DAY (from 2 to 6 PM) and NIGHT (from 12 to 4 AM). Mean, variance, spectral power and complexity indices at short, medium and long time scales were assessed over HP and QT beat-to-beat series. Circadian rhythmicity was evident in both NMC and ASYMP LQT2 but ASYMP LQT2 subjects were characterized by higher HP, QT interval and HP variability during both DAY and NIGHT. In addition, multiscale complexity analysis was able to differentiate the groups by showing a higher HP complexity and a lower QT complexity at long time scales in ASYMP LQT2 during DAY. ASYMP LQT2 exhibited a different autonomic control compared to NMC and such a differentiation could be protective and assure them a lower risk profile.

Multiscale complexity analysis of the cardiac control identifies asymptomatic and symptomatic patients in long QT syndrome type 1.

The study assesses complexity of the cardiac control directed to the sinus node and to ventricles in long QT syndrome type 1 (LQT1) patients with KCNQ1-A341V mutation. Complexity was assessed via refined multiscale entropy (RMSE) computed over the beat-to-beat variability series of heart period (HP) and QT interval. HP and QT interval were approximated respectively as the temporal distance between two consecutive R-wave peaks and between the R-wave apex and T-wave end. Both measures were automatically taken from 24-hour electrocardiographic Holter traces recorded during daily activities in non mutation carriers (NMCs, n = 14) and mutation carriers (MCs, n = 34) belonging to a South African LQT1 founder population. The MC group was divided into asymptomatic (ASYMP, n = 11) and symptomatic (SYMP, n = 23) patients according to the symptom severity. Analyses were carried out during daytime (DAY, from 2PM to 6PM) and nighttime (NIGHT, from 12PM to 4AM) off and on beta-adrenergic blockade (BBoff and BBon). We found that the complexity of the HP variability at short time scale was under vagal control, being significantly increased during NIGHT and BBon both in ASYMP and SYMP groups, while the complexity of both HP and QT variability at long time scales was under sympathetic control, being smaller during NIGHT and BBon in SYMP subjects. Complexity indexes at long time scales in ASYMP individuals were smaller than those in SYMP ones regardless of therapy (i.e. BBoff or BBon), thus suggesting that a reduced complexity of the sympathetic regulation is protective in ASYMP individuals. RMSE analysis of HP and QT interval variability derived from routine 24-hour electrocardiographic Holter recordings might provide additional insights into the physiology of the cardiac control and might be fruitfully exploited to improve risk stratification in LQT1 population.

Filtering approach based on empirical mode decomposition improves the assessment of short scale complexity in long QT syndrome type 1 population.

This study assesses the complexity of heart period (HP) and QT variability series through sample entropy (SampEn) in long QT syndrome type 1 individuals. In order to improve signal-to-noise ratio SampEn was evaluated over the original series (SampEn0) and over the residual computed by subtracting the first oscillatory mode identified by empirical mode decomposition (SampEn(EMD1R)). HP and QT interval were continuously extracted during daytime (2:00-6:00 PM) from 24 hour Holter recordings in 14 non mutation carriers (NMCs) and 34 mutation carriers (MCs) subdivided in 11 asymptomatic (ASYMP) and 23 symptomatic (SYMP). Both NMCs and MCs belonged to the same family line. While SampEn0 did not show differences among the three groups, Samp(EnEMD1R) assessed over the QT series significantly decreased in ASYMP subjects. SampEn(EMD1R) identified a possible factor (i.e. the lower short scale QT complexity) that might contribute to the different risk profile of the ASYMP group.

Refined multiscale entropy analysis of heart period and QT interval variabilities in long QT syndrome type-1 patients.

This study assesses complexity of cardiovascular control in patients affected by type-1 variant of long QT (LQT1) syndrome. Complexity was assessed by refined multiscale entropy of heart period (HP) and QT interval variabilities. HP was taken as the time distance between two consecutive R peaks (RR) and QT interval was approximated as the time distance between the R-peak and T-wave apex (RTa) and between R-peak and T-wave end (RTe). RR, RTa and RTe intervals were automatically extracted from 24h Holter recordings and the daytime period was analyzed (from 02:00 to 06:00 PM). Non mutation carrier (NMC) individuals (n=11), utilized as a control group, were taken from the same family line of the mutation carrier (MC) subjects (n=26). We found that, while NMC and MC groups were indistinguishable based on time domain and complexity analyses of RR dynamics, complexity analysis of RTa and RTe variabilities clearly separates the two populations and suggests an impairment in the cardiac control mechanisms acting on the ventricles.

Not all beta-blockers are equal in the management of long QT syndrome types 1 and 2: higher recurrence of events under metoprolol.

OBJECTIVES: The purpose of this study was to compare the efficacy of beta-blockers in congenital long QT syndrome (LQTS). BACKGROUND: Beta-blockers are the mainstay in managing LQTS. Studies comparing the efficacy of commonly used beta-blockers are lacking, and clinicians generally assume they are equally effective. METHODS: Electrocardiographic and clinical parameters of 382 LQT1/LQT2 patients initiated on propranolol (n = 134), metoprolol (n = 147), and nadolol (n = 101) were analyzed, excluding patients <1 year of age at beta-blocker initiation. Symptoms before therapy and the first breakthrough cardiac events (BCEs) were documented. RESULTS: Patients (56% female, 27% symptomatic, heart rate 76 ± 16 beats/min, QTc 472 ± 46 ms) were started on beta-blocker therapy at a median age of 14 years (interquartile range: 8 to 32 years). The QTc shortening with propranolol was significantly greater than with other beta-blockers in the total cohort and in the subset with QTc >480 ms. None of the asymptomatic patients had BCEs. Among symptomatic patients (n = 101), 15 had BCEs (all syncopes). The QTc shortening was significantly less pronounced among patients with BCEs. There was a greater risk of BCEs for symptomatic patients initiated on metoprolol compared to users of the other 2 beta-blockers combined, after adjustment for genotype (odds ratio: 3.95, 95% confidence interval: 1.2 to 13.1, p = 0.025). Kaplan-Meier analysis showed a significantly lower event-free survival for symptomatic patients receiving metoprolol compared to propranolol/nadolol. CONCLUSIONS: Propranolol has a significantly better QTc shortening effect compared to metoprolol and nadolol, especially in patients with prolonged QTc. Propranolol and nadolol are equally effective, whereas symptomatic patients started on metoprolol are at a significantly higher risk for BCEs. Metoprolol should not be used for symptomatic LQT1 and LQT2 patients.

Congenital short QT syndrome.

The Short QT Syndrome is a recently described new genetic disorder, characterized by abnormally short QT interval, paroxysmal atrial fibrillation and life threatening ventricular arrhythmias. This autosomal dominant syndrome can afflict infants, children, or young adults; often a remarkable family background of cardiac sudden death is elucidated. At electrophysiological study, short atrial and ventricular refractory periods are found, with atrial fibrillation and polymorphic ventricular tachycardia easily induced by programmed electrical stimulation. Gain of function mutations in three genes encoding K(+) channels have been identified, explaining the abbreviated repolarization seen in this condition: KCNH2 for I(kr) (SQT1), KCNQ1 for I(ks) (SQT2) and KCNJ2 for I(k1) (SQT3). The currently suggested therapeutic strategy is an ICD implantation, although many concerns exist for asymptomatic patients, especially in pediatric age. Pharmacological treatment is still under evaluation; quinidine has shown to prolong QT and reduce the inducibility of ventricular arrhythmias, but awaits additional confirmatory clinical data.