Holter Electrocardiographic Recordings Research Articles

Atrioventricular Synchrony Delivered by a Dual-Chamber Leadless Pacemaker System.

A dual-chamber leadless pacemaker system has been designed for atrioventricular synchronous pacing using wireless, beat-to-beat, implant-to-implant (i2i) communication between distinct atrial and ventricular leadless pacemakers. The atrioventricular synchrony achieved across various ambulatory scenarios has yet to be systematically evaluated. A prospective, single-arm, unblinded, multicenter, international clinical trial of the leadless pacemaker system was conducted in patients with a conventional dual-chamber pacing indication enrolled from February 2022 to March 2023. Leadless pacemaker systems were implanted, and 12-lead Holter electrocardiographic recordings were collected 3 months after implantation over various postures/activities: sitting, supine, left lateral recumbent, right lateral recumbent, standing, normal walk, and fast walk. An independent Holter core laboratory performed a manual adjudication of the percent of atrioventricular synchronous beats using the standard 300-millisecond PR interval limit. Atrium-to-ventricle and ventricle-to-atrium i2i communication success rates were also assessed. Post hoc summary statistics describing the relationships between atrioventricular synchrony and i2i success, posture/activity, implantation indication, atrioventricular event, and heart rate were calculated. In the evaluable population (n=384 of 464 enrolled [83%]; 61% male; age, 70 years; weight, 82 kg; 60% ejection fraction; 95% of beats evaluable), the mean atrioventricular synchrony of 98% of beats observed across all postures using the standard 300-millisecond limit was greater than both atrial-to-ventricular i2i (94%) and ventricular-to-atrial i2i (94%; P<0.001), exceeding both i2i values in 95% of patients. Atrioventricular synchrony was achieved in >95% of evaluable beats across all postures/activities, implantation indications, atrioventricular paced/sensed event combinations, and heart rate ranges (including >100 bpm). This dual-chamber leadless pacemaker system demonstrated atrioventricular synchrony in 98% of evaluable beats at 3 months after implantation. Atrioventricular synchrony was maintained across postures/activities and remained robust for heart rates >100 bpm.

Risk assessment of post-myocardial infarction patients with preserved ejection fraction using 45-min short resting Holter electrocardiographic recordings.

Risk stratification for sudden cardiac death in post-myocardial infarction (post-MI) patients remains a challenging task. Several electrocardiographic noninvasive risk factors (NIRFs) have been associated with adverse outcomes and were used to refine risk assessment. This study aimed to evaluate the performance of NIRFs extracted from 45-min short resting Holter ECG recordings (SHR), in predicting ventricular tachycardia inducibility with programmed ventricular stimulation (PVS) in post-MI patients with preserved left ventricular ejection fraction (LVEF). We studied 99 post-MI ischemia-free patients (mean age: 60.5 ± 9.5 years, 86.9% men) with LVEF ≥40%, at least 40 days after revascularization. All the patients underwent PVS and a high-resolution SHR. The following parameters were evaluated: mean heart rate, ventricular arrhythmias (premature ventricular complexes, couplets, tachycardias), QTc duration, heart rate variability (HRV), deceleration capacity, heart rate turbulence, late potentials, and T-wave alternans. PVS was positive in 24 patients (24.2%). HRV, assessed by the standard deviation of normal-to-normal R-R intervals (SDNN), was significantly decreased in the positive PVS group (42 ms vs. 51 ms, p = .039). SDNN values <50 ms were also associated with PVS inducibility (OR 3.081, p = .032 in univariate analysis, and 4.588, p = .013 in multivariate analysis). No significant differences were identified for the other NIRFs. The presence of diabetes, history of ST-elevation MI (STEMI) and LVEF <50% were also important predictors of positive PVS. HRV assessed from SHR, combined with other noninvasive clinical and echocardiographic variables (diabetes, STEMI history, LVEF), can provide an initial, practical, and rapid screening tool for arrhythmic risk assessment in post-MI patients with preserved LVEF.

Leadless atrioventricular synchronous pacing in an outpatient setting: Early lessons learned on factors affecting atrioventricular synchrony

Leadless pacemakers (PMs) capable of atrioventricular (AV) synchronous pacing have recently been introduced. Initial feasibility studies were promising but limited to just a few minutes of AV synchronous pacing. Real-world, long-term data on AV synchrony and programming adjustments affecting AV synchrony in outpatients are lacking. The purpose of this study was to investigate AV synchrony and influences of PM programming adjustments in outpatients with leadless VDD PMs. All patients who received a leadless VDD PM (Micra™ AV, Medtronic) between July 2020 and May 2021 at our center were included in this observational study. AV synchrony was assessed repeatedly postoperatively and during follow-up using Holter electrocardiographic (ECG) recordings. AV synchrony was defined as a QRS complex preceded by a p wave within 300 ms. The impact of programming changes during follow-up on AV synchrony was studied. A total of 816 hours of Holter ECG from 20 outpatients were analyzed. During predominantly paced episodes (≥80% ventricular pacing), median AV synchrony was 91% [interquartile range (IQR) 34%-100%] when patients had sinus rates 50-80/min. Median AV synchrony was lower when patients had sinus rates >80/min [33% (29%-46%); P <.001]. During a stepwise optimization protocol, AV synchrony could be improved (P <.038). Multivariate analysis showed that a shorter maximum A3 window end (P <.001), lower A3 threshold (P = .046), and minimum A4 threshold (P<.001) improved AV synchrony. Successful VDD pacing in the outpatient setting during higher sinus rates is more difficult to achieve than can be presumed based on initial feasibility studies. The devices often require multiple reprogramming to maximize AV sequential pacing.

24-Hour Electrocardiographic (ECG) Holter Recording during Hypertensive Cardiopathy in Health Facilities in Lome

Objective: To evaluate the 24-hour Holter ECG recording in hypertensive heart disease. Methods: This was a descriptive and analytical cross-sectional study on files of patients with hypertensive heart disease, carried out from October 2016 to October 2019, in two health facilities in Lome (TOGO). Electrical left ventricular hypertrophy (LVH) was defined by the Sokolow-Lyon and Cornell indices. On echocardiography, the HVG according to the criteria of the American Society of Echocardiography, was the characteristic retained for a CH. Holter-ECG recordings were carried out over 24 hours by two Holter devices. Results: 107 patients were included, with a sex ratio of 1.89 (M / F). The mean age was 62.2 ± 12 years. The mean duration of the evolution of hypertension was 10.8 ± 9.1 years. On standard ECG, arrhythmias were more frequent (32.6%) with ACFA in 5.6% of cases. The prevalence of echocardiographic HVG was 74.8%, predominantly concentric, and was significantly found in hypertensive patients over 10 years of age. During the 24-hour Holter ECG recording, ACFA was the common arrhythmia (30%), episodic in 90.6% of cases and permanent 9.4% and was statistically associated with OG size, sex and age. The Holter ECG detected sustained ventricular tachycardia in 7 patients (6.5%). The Recording was normal 12.1% of the time. Conclusion: Hypertensive heart disease is the first of the cardiac complications of hypertension. The Holter ECG is a tool for the detection of fatal severe paroxysmal events that go unnoticed on the surface ECG such as AC/AF, sustained ventricular tachycardias.

Evaluation of Cardiac Arrhythmias before, during, and after Treadmill Exercise Testing in Poorly Performing Standardbred Racehorses.

Simple SummaryIn sport horses, cardiovascular problems, such as arrhythmias, can cause poor performance. However, only the role of atrial fibrillation and severe bradyarrhythmias on athletic performance has been well established. On the other hand, the significance of other arrhythmias, such as supraventricular and ventricular premature complexes, is still not well defined. The present study reports on the prevalence of cardiac arrhythmias during maximal treadmill exercise in poorly performing Standardbreds, and investigates the possible relationship of demographic, cardiac, and performance indices on premature complexes. The results showed weak evidence of the dependence of premature complexes on minimum heart rate, and a tendency for the occurrence of premature complexes to increase with aging and increasing maximum lactate concentration. Our results suggest that premature complexes are frequent in poorly performing Standardbred racehorses, but further studies are necessary to clarify their role and clinical significance.The incidence of significant arrhythmias in sport horses and knowledge about their exact influence on athletic performance need to be clarified. The aims of the present study are to report the prevalence of cardiac arrhythmias during maximal treadmill exercise in poorly performing Standardbreds, and to investigate the possible relationship of demographic, cardiac and performance indices on premature complexes (PCs). Electrocardiographic Holter recordings before, during and after treadmill exercise testing of 158 poorly performing Standardbreds were analyzed retrospectively. Fifty horses did not have any type of arrhythmia. One hundred and eight horses had at least one type of arrhythmia, such as sinus arrhythmia (8.2%), sinoatrial block (3.2%), second-degree atrioventricular block (33.5%), supraventricular PCs (7.6%), and ventricular PCs (48.1%). A multiple regression analysis showed weak evidence that the occurrence of premature complexes decreases as the minimum heart rate increases, and a tendency for these arrhythmias to increase with increasing age and maximum lactate concentration. Our results suggest that PCs are frequent in poorly performing Standardbred racehorses, but further studies are necessary to clarify their role and clinical significance.

Are ECG changes in heart-healthy individuals of various ages related to cardiac disease 20 years later?

BackgroundThis research study aimed at assessing the electrocardiographic (ECG) changes caused by ageing in a cohort of healthy subjects with normal echocardiographic examinations.MethodsA total of 219 healthy individuals (119 males and 100 females) were evaluated for possible arrhythmias with a standard 12-lead resting ECG and 24-h Holter ECG. As the recordings were performed between 1998 and 2000, a 20-year follow-up study was carried out by assessing the local medical records to investigate whether the subjects had experienced any cardiovascular health complications or disease since the baseline assessment.ResultsEighty-three subjects (45 males and 38 females) presented with pathological ECG findings at baseline. The most common finding on analysis of Holter ECG recordings was premature atrial contractions, and the most severe pathological finding was episodes of ventricular tachycardia (eight subjects). Regarding the analysis of the standard 12-lead ECG, the most common finding was left ventricular hypertrophy, and the most severe pathological findings were ST-T changes and prolongation of the QT interval. Despite other cardiac examinations performed on these patients showing normal results, in combination with a strict inclusion criterion, this study showed that 28% of all subjects had pathological resting 12-lead ECGs at rest and 35% had pathological heart rhythms when assessed by 24-h Holter ECG. At follow-up, 21% of females and 43% of males had presented with ECG abnormalities, and 30% of females and 36% of males had cardiovascular disease. There was hypertension in 45% of females and in 58% of males. However, no association was found between the follow-up findings and ECG changes seen at baseline.ConclusionAlthough most ECG changes found at baseline could be considered as a normal variation, they may progress to more severe heart complications as the subject ages. The results of this study also validate ECG findings of previous studies and underline that diagnostic criteria should be based on gender and age.

Particulate matter air pollution and reduced heart rate variability: How the associations vary by particle size in Shanghai, China

BackgroundIt remains unclear which size of particles has the strongest effects on heart rate variability (HRV). ObjectiveTo explore the association between HRV parameters and daily variations of size-fractionated particle number concentrations (PNCs). MethodsWe conducted a longitudinal repeated-measure study among 78 participants with a 24-h continuous ambulatory Holter electrocardiographic recorder in Shanghai, China, from January 2015 to June 2019. Linear mixed-effects models were employed to evaluate the changes of HRV parameters associated with PNCs of 7 size ranges from 0.01 to 10 μm after controlling for environmental and individual confounders. ResultsOn the concurrent day, decreased HRV parameters were associated with increased PNCs of 0.01–0.3 μm, and smaller particles showed greater effects. For an interquartile range increase in ultrafine particles (UFP, those < 0.1 μm, 2453 particles/cm3), the declines in very-low-frequency power, low-frequency power, high-frequency power, standard deviation of normal R-R intervals, root mean square of the successive differences between R-R intervals and percentage of adjacent normal R-R intervals with a difference ≥ 50 ms were 5.06% [95% confidence interval (CI): 2.09%, 7.94%], 7.65% (95%CI: 2.73%, 12.32%), 9.49% (95%CI: 4.64%, 14.09%), 5.10% (95%CI: 2.21%, 7.91%), 8.09% (95%CI: 4.39%, 11.65%) and 24.98% (95%CI: 14.70%, 34.02%), respectively. These results were robust to the adjustment of criteria air pollutants, temperature at different lags, and the status of heart medication. ConclusionsParticles less than 0.3 μm (especially UFP) may dominate the acute effects of particulate air pollution on cardiac autonomic dysfunction.

Evaluation of cardiac autonomic nervous system in patients with ankylosing spondylitis using 12-lead electrocardiography and Holter monitoring.

Ankylosing spondylitis (AS) is associated with increased risk of cardiovascular problems, including complications such as conduction defects and arrhythmias, which might lead to increased morbidity and/or mortality. The objective of the present study is to evaluate the electrocardiographic (ECG) parameters, including T-peak to T-end intervals (Tpe), Tpe/corrected QT (QTc) ratio, heart rate variability (HRV), and heart rate turbulence (HRT) in AS patients. Seventy-six AS patients and 55 control subjects were included in the study. 12-lead ECG and 24-h Holter monitoring recordings were obtained. Tpe and Tpe/QTc were measured using the 12-lead ECG and HRV and HRT parameters were assessed using 24-h Holter ECG recordings. Subjects were assigned into three groups based on their HRT parameters (Tonset (TO) and Tslope (TS)) (HRT-0, normal TO or TS; HRT-1, abnormal TO or TS; HRT-2, abnormal TO and TS). Tpe was prolonged and Tpe/QTc ratio was higher in AS patients (p < 0.001 for both). Moreover, Tpe and Tpe/QTc ratio significantly correlated with disease duration. All HRV parameters (VLF, LF, HF, SDNN, SDANN, ASDNN, rMSSD, pNN50) were decreased in AS patients in comparison with those in control subjects (p < 0.05 for all parameters). Controls were significantly more likely to have normal TO and TS (82% vs 53%, p < 0.001). There was negative correlation between Holter parameters and disease duration, as well as Tpe and Tpe/QTc ratio (p < 0.05 for all parameters). This study demonstrated that AS patients have disrupted ventricular repolarization (increased Tpe, Tpe/QTc ratio). Results suggest a decreased cardiac impact of the parasympathetic system in AS patients. Key Points • This study demonstrated that AS patients have disrupted ventricular repolarization. • The study also finds that heart rate turbulence and heart rate variability are impaired in AS patients. • Impaired Holter and ECG parameters may be one of the high cardiovascular risk factors in AS patients.

Second look Holter ECG in neurorehabilitation

BackgroundMany stroke survivors suffer recurrent stroke because paroxysmal atrial fibrillation (AF) was missed and no preventive anticoagulation initiated. This prospective cohort study determined the added diagnostic yield of second-look 24-h electrocardiographic recording (ECG) in a population at high risk for AF: patients who suffered a stroke of such severity that they require inpatient neurorehabilitation.MethodsWe enrolled 508 patients with ischemic stroke admitted to post-acute inpatient neurorehabilitation and determined whether AF was detected during acute care at the referring hospital. Second-look baseline and 24-h Holter ECG were then conducted during neurorehabilitation. Primary outcome was number of newly detected AF with duration of > 30 s; secondary outcomes were number of newly detected absolute arrhythmia of 10–30 s and < 10 s duration. For comparison, we further enrolled 100 patients with hemorrhagic stroke without history of AF (age = 72 + 11 years, 51% female).ResultsIn 206 of the 508 ischemic stroke patients, AF had been detected during acute phase work-up (age = 78 + 10 years, 55% female). For the remaining 302 ischemic stroke patients, no AF was detected during acute phase work-up (age = 74 + 9 years; 47% female). Second-look 24-h ECG showed previously missed AF of > 30 s in 20 of these patients, i.e. 6.6% of the sample, and shorter absolute arrhythmia in 50 patients (i.e. 16.5%).ConclusionsSecond-look 24-Hour ECG performed during post-acute inpatient neurorehabilitation has a high diagnostic yield and should become a standard component of recurrent stroke prevention.

P2860The effects of single nucleotide polymorphisms in Korean patients with early-onset lone atrial fibrillation after catheter ablation

Abstract Background The status of SNPs among patients with extremely early-onset lone AF and the association with outcome of catheter ablation has not been evaluated before. This study evaluated the status of single nucleotide polymorphisms (SNPs) in Korean patients with early-onset (&lt;40 years old) lone AF and effects on the outcome after catheter ablation. Methods A total of 89 consecutive patients (mean age 35.7±3.7 years, 81 males) with drug-refractory AF (paroxysmal 64.0%) who underwent catheter ablation were included. Sixteen SNPs including rs13376333, rs10465885, rs10033464, rs2200733, rs17042171, rs6843082, rs7193343, rs2106261, rs17570669, rs853445, rs11708996, rs6800541, rs251253, rs3807989, rs11047543 and rs3825214 were genotyped. Serial 48-day Holter electrocardiographic recordings were acquired to detect AF recurrences during long-term follow up. Results Wild type of rs7193343 [CC; 0/7 (0%) vs. CT; 22/40 (55.0%) vs. TT; 18/41 (43.9%), p=0.025] and rs11047543 [GG; 26/69 (37.7%) vs. GA; 13/18 (72.2%) vs. AA; 0/0, p=0.009] and homozygous variant of rs3825214 [AA; 16/31 (51.6%) vs. AG; 22/43 (51.2%) vs. GG; 2/13 (15.4%), p=0.05] were significantly associated with lower rate of late recurrence. When the patients were assigned to four groups according to the number of risk alleles (n=0–3), Kaplan-Meier survival analysis showed incremental prognostic value according to the number of variant alleles (p=0.002) (Figure 1). Figure 1 Conclusions Polymorphisms on rs7193343, rs3825214 and rs11047543 modulate the risk for AF recurrence after catheter ablation during long term follow up in Korean patients with early-onset lone AF. Acknowledgement/Funding Korean Society of Cardiology

P5639Risk stratification for mortality using electrocardiographic markers based on 24-hour holter recordings: the JANIES-SHD study

Abstract Background Recent guidelines have stated that reduced left ventricular ejection fraction (LVEF) is the gold standard marker for identifying patients at risk for cardiac mortality. Although reduced LVEF identifies patients at an increased risk of cardiac arrest, sudden cardiac deaths (SCDs) occur considerably more often in patients with relatively preserved LVEF. Current guidelines on SCD risk stratification do not adequately cover this general population pool. Several noninvasive electrocardiographic (ECG) risk stratifiers that reflect depolarization abnormality, repolarization abnormality, and autonomic imbalance have been evaluated so far. With current therapeutic advances using new medicines or devices, an LVEF is often preserved in patients with structural heart disease (SHD). However, the usefulness of noninvasive ECG markers for risk stratification in such a patient population has not yet been elucidated. Purpose This study aimed to assess clinical indices and ECG markers based on 24-hour Holter ECG recordings for predicting cardiac mortality in patients with SHD who have left ventricular dysfunction (LVD) but relatively preserved LVEF. Methods In total, 1,829 patients were enrolled into the Japanese Multicenter Observational Prospective Study (JANIES study). In this study, we analyzed data of 719 patients (569 men, age 64±13 years) with SHD including mainly ischemic heart disease (65.8%). As ECG markers based on 24-hour Holter recordings, nonsustained ventricular tachycardia (NSVT), ventricular late potentials, and heart rate turbulence (HRT) were assessed. The primary endpoint was all-cause mortality, and the secondary endpoint was fatal arrhythmic events. Results During a mean follow-up of 21±11 months, all-cause mortality was eventually observed in 39 patients (5.4%). Among those patients, 32 patients (82%) suffered from cardiac causes such as heart failure and arrhythmia. Multivariate Cox regression analysis showed that after adjustment for age and LVEF, documented NSVT (hazard ratio=2.82, 95% confidence interval [CI]: 1.38–5.76, P=0.005) and abnormal HRT (hazard ratio=2.31, 95% CI: 1.15–4.65, P=0.02) were significantly associated with the primary endpoint. These two ECG markers also had significant predictive values with the secondary endpoint. The combined assessment documented NSVT and abnormal HRT improved predictive accuracy. Conclusion This study demonstrated that combined assessment of documented NSVT and abnormal HRT based on 24-hour Holter ECG recordings are recommended for predicting future serious events in SHD patients who have relatively preserved LVEF. Acknowledgement/Funding Grants-in-Aid (21590909, 24591074, and 15K09103 to T.I.) for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technol

Risk stratification for cardiac mortality using electrocardiographic markers based on 24-hour Holter recordings: the JANIES-SHD study

BackgroundRecent guidelines have stated that left ventricular ejection fraction (LVEF) is the gold standard marker for identifying patients at risk for cardiac mortality. However, little information is present regarding electrocardiographic (ECG) markers. This study aimed to assess ECG markers for predicting mortality or serious arrhythmia in patients with structural heart disease (SHD). MethodsIn total, 1829 patients were enrolled into the Japanese Multicenter Observational Prospective Study (JANIES study). In this study, we analyzed data of 719 patients (569 men, age 64 ± 13 years) with SHD including mainly ischemic heart disease (65.8%). As ECG markers based on 24-hour Holter recordings, nonsustained ventricular tachycardia (NSVT), ventricular late potentials, and heart rate turbulence (HRT) were assessed. The primary endpoint was all-cause mortality, and the secondary endpoint was fatal arrhythmic events. ResultsDuring a mean follow-up of 21 ± 11 months, all-cause mortality was eventually observed in 39 patients (5.4%). Among those patients, 32 patients (82%) suffered from cardiac causes such as heart failure and arrhythmia. Multivariate Cox regression analysis showed that after adjustment for age and LVEF, documented NSVT [hazard ratio = 2.46, 95% confidence interval (CI): 1.16–5.18, p = 0.02] and abnormal HRT (hazard ratio = 2.40, 95% CI: 1.16–4.93, p = 0.02) were significantly associated with the primary endpoint. These two ECG markers also had significant predictive values with the secondary endpoint. The combined assessment of two ECG markers improved predictive accuracy. ConclusionThis study demonstrated that combined assessment of documented NSVT and abnormal HRT based on 24-hour Holter ECG recordings are recommended for predicting future serious events in this population.

Rhythm disturbances and treatment strategies in children with congenitally corrected transposition of the great arteries.

We aimed to evaluate rhythm abnormalities in cases of congenitally corrected transposition of the great arteries (ccTGA) and associated treatment strategies. This retrospective cohort study included 65 pediatric patients with ccTGA who were admitted to the clinic between 2009 and 2017. The patients were divided into two groups, and surgical data, Holter electrocardiographic (ECG) recordings, ECG recordings, electrophysiological data, and device implantation data on the two groups were compared. Group I (n = 53, 82%) consisted of patients with significant associated lesions, and Group II (n = 12, 18%) consisted of those with minor or no associated lesions (isolated ccTGA). Rhythm abnormalities were diagnosed in 22 (34%) of the patients based on initial ECG findings and Holter ECG recordings. Eleven (17%) of these patients had atrioventricular (AV) block of different degrees, and the other 11 (17%) had supraventricular arrhythmia (SVA). The median follow-up was 49 months (range, 9-89 months), and the rhythm remained normal in 26 (42%) of the patients. Three patients died on follow-up. Of 40 patients with normal initial findings, nine required pacemaker implantation due to complete heart block, and SVA developed in seven patients on follow-up. No ventricular tachycardia was seen initially or on follow-up. Ablation was performed in four patients. During the follow-up period, pacemakers were implanted in 12 (23%) of patients in Group I and 4 (33%) of patients in Group II due to complete heart block. Cardiac resynchronization therapy (CRT) was performed in four patients due to systemic ventricular dysfunction. Notably, all four of these patients had a pacemaker implanted postoperatively.

Age‐Related Variations in Ventricular Response Rate in Individuals with Persistent or Permanent Atrial Fibrillation

To the Editor: Atrial fibrillation (AF) is the most frequent sustained arrhythmia.1 Its prevalence increases with age, affecting almost 20% of individuals aged 85 and older2 and resulting in substantial health care use and morbidity.3 Rapid heart rate (HR) is the most obvious cause of symptoms, which in turn are associated with lower quality of life and higher risk of hospitalization.4 The influence of age on ventricular rate has been previously investigated in individuals with paroxysmal AF5 but has not been well characterized in those with persistent or permanent AF. Thus, the goal was to evaluate the effect of age on ventricular response rate in these individuals. Thirty-two thousand seven hundred seventeen 24-hour electrocardiographic Holter recordings were performed in the Complexo Hospitalario Universitario A Coruña, Instituto de Investigación Biomédica de A Coruña, A Coruña, Spain, between March 1, 2000, and November 14, 2015. Those in which AF was verified were initially considered for inclusion in this study. When several Holter monitoring studies were available for the same individual, the first was selected, resulting in 3,109 available recordings with AF. Individuals in whom AF was not the sole cardiac rhythm identified throughout the recordings or in whom a pacemaker had been previously implanted were also excluded (n = 701), leaving a final study population of 2,408 individuals. Maximal, minimal, and mean HR over the 24-hour period were collected for each Holter recording. HR range was estimated as the difference between maximal and minimal HR. Correlations between age and HR were assessed using Spearman rank correlation coefficients. Age was categorized into four groups (<50, 50–64, 65–79, ≥80), and trends in HR were assessed according to age group. The relationship between age and the need for pacemaker implantation within 1 year was also evaluated in the subset of 2,178 participants with AF who underwent Holter monitoring between March 1, 2000, and November 14, 2014. The statistical significance of trends across age intervals was assessed using the Cochran-Armitage test for categorical variables and the Cuzick nonparametric test for continuous variables. The ethics committee of A Coruña-Ferrol approved this study. Mean age was 75 ± 10, and 1,381 subjects (57.4%) were male. Maximal HR was 134 ± 32 beats per minute (bpm), minimal HR was 41 ± 11 bpm, and mean HR was 74 ± 17 bpm. There were significant inverse correlations between age and maximal HR (ρ = −0.306, P < .001), minimal HR (ρ = −0.149, P < .001), mean HR (ρ = −0.230, P < .001), and HR range (ρ = −0.303, P < .001). Table 1 shows the trends in maximal, minimal, and mean HR and HR range according to age group; all these parameters decreased gradually and significantly with age. The likelihood of pacemaker implantation within 1 year after Holter recordings also increased progressively with age, (<50, 4.7%; 50–64, 5.4%; 65–79, 8.7%; ≥80, 10.2%; P for trend <.001). An inverse association was found between age and ventricular rate in individuals with persistent or permanent AF. The need for pacemaker implantation in these individuals also increased progressively with age. Although age has been shown to influence HR during episodes of paroxysmal AF,5 this study complements and expands this observation to individuals with persistent or permanent AF. The slower ventricular rate with increasing age in these subjects may mainly be due to progressive atrioventricular conduction delay6 and atrial structural changes. Impaired atrioventricular conduction or age-related decreases in sinus node function may also explain the gradual increase in the probability of pacemaker implantation during follow-up in individuals with AF.7 A lower level of physical activity in older adults might further account for the greater reduction in maximal and mean HR with age than in minimal HR. The decrease in minimal HR with increasing age occurred despite well-known higher vagal tone at rest in younger individuals. One might infer that the dosage of negative chronotropic drugs required for adequate HR control in elderly adults might be lower and that these medications may be associated with greater probability of symptomatic bradycardia than in their younger counterparts. Nonetheless, no attempt was made to account for the effect of such medications, and the study was not designed to test these assertions. Furthermore, the indications for pacemaker implantation were not evaluated. In conclusion, HR tended to decrease with age in individuals with persistent or permanent AF, and there was an apparently congruent, gradual increase in the need for pacemaker implantation with aging in these individuals. Conflict of Interest: The authors declare no competing interests. Author Contributions: Bouzas-Mosquera: study concept and design, acquisition of subjects and data, analysis and interpretation of data, preparation of manuscript. Broullón, Martínez, Yáñez, Álvarez-García, Peteiro, Vázquez-Rodríguez: acquisition of subjects and data, review of manuscript. Sponsor's Role: The study had no external funding.

Electrocardiographic abnormalities and arrhythmic risk markers in adult patients with beta thalassemia major

BackgroundThere seems to be a significant arrhythmia burden in β-thalassemia major (TM) patients without overt cardiomyopathy. Apart from conventional electrocardiographic (ECG) and arrhythmic risk markers we studied novel markers of ventricular repolarization and autonomic imbalance both at rest and after exercise testing. MethodsWe studied 47 adult TM patients without systolic heart failure and 47 age and sex-matched healthy control subjects. The median age of the studied population was 36 [32–43] years, 57% men. Baseline demographic and clinical characteristics were recorded while 12-lead electrocardiograms, 24-hour ECG Holter recordings, and treadmill exercise stress tests were analyzed. ResultsTM patients exhibited increased QTc intervals in both 12-lead ECG recordings and in 24-hour Holter recordings. In addition, they had increased indexes of ventricular repolarization heterogeneity such as QT dispersion, and T peak-to-end/QT ratios. Furthermore, TM patients had decreased indexes of heart rate variability while the heart rate recovery after exercise was significantly attenuated compared to controls. Also, they had increased P wave and QRS duration while the QRS fragmentation was very prevalent. Finally, premature atrial extrasystoles and paroxysmal atrial fibrillation episodes were more frequent in TM patients. ConclusionsTM patients with preserved left ventricular systolic function have several ECG abnormalities including alterations in ventricular depolarization and repolarization. Also, cardiac autonomic dysfunction is evident in 24-hour ECG monitoring as well as in the recovery phase after exercise testing. The prognostic value of specific arrhythmic risk indexes in this setting remains to be elucidated.

A Refined Multiscale Self-Entropy Approach for the Assessment of Cardiac Control Complexity: Application to Long QT Syndrome Type 1 Patients

The study proposes the contemporaneous assessment of conditional entropy (CE) and self-entropy (sE), being the two terms of the Shannon entropy (ShE) decomposition, as a function of the time scale via refined multiscale CE (RMSCE) and sE (RMSsE) with the aim at gaining insight into cardiac control in long QT syndrome type 1 (LQT1) patients featuring the KCNQ1-A341V mutation. CE was estimated via the corrected CE (CCE) and sE as the difference between the ShE and CCE. RMSCE and RMSsE were computed over the beat-to-beat series of heart period (HP) and QT interval derived from 24-hour Holter electrocardiographic recordings during daytime (DAY) and nighttime (NIGHT). LQT1 patients were subdivided into asymptomatic and symptomatic mutation carriers (AMCs and SMCs) according to the severity of symptoms and contrasted with non-mutation carriers (NMCs). We found that RMSCE and RMSsE carry non-redundant information, separate experimental conditions (i.e., DAY and NIGHT) within a given group and distinguish groups (i.e., NMC, AMC and SMC) assigned the experimental condition. Findings stress the importance of the joint evaluation of RMSCE and RMSsE over HP and QT variabilities to typify the state of the autonomic function and contribute to clarify differences between AMCs and SMCs.

Reduced Irregularity of Ventricular Response During Atrial Fibrillation and Long-term Outcome in Patients With Heart Failure

Reduced heart rate variability (HRV) is associated with poor outcome in patients with heart failure (HF). However, the data on predictive value of RR variability during atrial fibrillation (AF) are limited. Therefore, the aim of this study was to evaluate the association between ventricular response characteristics and long-term clinical outcome in the population of ambulatory patients with mild-to-moderate HF and AF at baseline. The study included 155 patients (mean age 69 ± 10years) with AF at 20-minute Holter electrocardiographic (ECG) recordings at enrollment. HRV analysis included SDNN, rMSSD, and pNN50, whereas irregularity indexes included 2 nonlinear parameters: approximate entropy (ApEn) and Shannon entropy. After median 41months of follow-up, 54 patients died, including 21 HF related and 16 sudden deaths. Patients with ApEn ≤1.68 (lower tertile) had 40% mortality versus 12% in others (p <0.001) at 2years of follow-up. Only nonlinear HRV parameters (irregularity but not variability indexes) identified patients at higher risk during follow-up. Decreased ApEn ≤1.68 was an independent predictor of total mortality (hazard ratio [HR] 2.81, 95% confidence interval [CI] 1.61 to 4.89, p <0.001), sudden cardiac death (HR 3.83, 95% CI 1.31 to 11.25, p= 0.014), and HF death (HR 3.45, 95% CI 1.42 to 8.38, p= 0.006) in a multivariate Cox analysis. In conclusion, in a post hoc analysis of Muerte Subita en Insufficiencia Cardiaca study AF cohort, reduced irregularity of RR intervals during AF, likely caused by autonomic dysfunction, was an independent predictor of all-cause mortality and sudden death and HF progression in patients with mild-to-moderate HF, whereas traditional HRV indexes did not predict outcome.

Novel Findings in Breath-Holding Spells: A Cross-Sectional Study.

The mechanism of breath-holding spells (BHS) is not fully understood and most probably multifactorial; so, this study was designed to clarify the pathophysiology of BHS through assessing some laboratory parameters and electrocardiographic (ECG) changes which might be contributing to the occurrence of the attacks. Another aim of the study was to evaluate the differences in the pathophysiology between pallid and cyanotic types of BHS.This was a prospective study performed in Zagazig University Hospitals. Seventy-six children diagnosed with BHS were included as follows: 32 children with cyanotic BHS, 14 children with pallid BHS, and 30 healthy children as a control group. All children were subjected to the following: full history taking, clinical examination, and laboratory work up in the form of CBC, serum iron, ferritin, and zinc levels. Twenty-four hours ambulatory ECG (Holter) recording was also performed.No significant statistical difference was found between cyanotic and pallid groups regarding family history of BHS, severity, and precipitating factors of the attacks. Frequent runs of respiratory sinus arrhythmia (RSA) during 24 hours ECG were significantly higher in children with BHS; the frequency of RSA was significantly correlated with the frequency (severity) of the attacks. Low serum ferritin was significantly associated with BHS groups but not correlated with the severity of the attacks.Autonomic dysregulation evidenced by frequent RSA is considered to be an important cause of BHS in children and is correlated with the frequency of the attacks. Low serum ferritin is additional factor in the pathophysiology. Both pallid and cyanotic BHS are suggested to be types of the same disease sharing the same pathophysiology.

A modified van der Pol equation with delay in a description of the heart action

Abstract In this paper, a modified van der Pol equation is considered as a description of the heart action. This model has a number of interesting properties allowing reconstruction of phenomena observed in physiological experiments as well as in Holter electrocardiographic recordings. Our aim is to study periodic solutions of the modified van der Pol equation and take into consideration the influence of feedback and delay which occur in the normal heart action mode as well as in pathological modes. Usage of certain values for feedback and delay parameters allows simulating the heart action when an accessory conducting pathway is present (Wolff-Parkinson-White syndrome).

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.