24-h Ambulatory Electrocardiography Research Articles

Heart rate variability and cardiac autonomic functions in post-COVID period.

BackgroundThe heart rate variability (HRV) is a non-invasive, objective and validated method for the assessment of autonomic nervous system. Although acute manifestations of COVID-19 were widely researched, long-term sequela of COVID-19 are still unknown. This study aimed to analyze autonomic function using HRV indices in the post-COVID period that may have a potential to enlighten symptoms of COVID long-haulers.MethodsThe 24-h ambulatory electrocardiography (ECG) recordings obtained >12 weeks after the diagnosis of COVID-19 were compared with age–gender-matched healthy controls. Patients who used drugs or had comorbidities that affect HRV and who were hospitalized with severe COVID-19 were excluded from the study.ResultsTime domain indices of HRV analysis (standard deviation of normal RR intervals in 24 h (SDNN 24 h) and root mean square of successive RR interval differences (RMSSD)) were significantly higher in post-COVID patients (p < 0.05 for all). Among frequency domain indices, high frequency and low frequency/high frequency ratio was significantly higher in post-COVID patients (p = 0.037 and p = 0.010, respectively). SDNN >60 ms [36 (60.0%) vs. 12 (36.4%), p = 0.028)] and RMSSD >40 ms [31 (51.7%) vs. 7 (21.2%), p = 0.003)] were more prevalent in post-COVID patients. Logistic regression models were created to evaluate parasympathetic overtone in terms of SDNN >60 ms and RMSSD >40 ms. After covariate adjustment, post-COVID patients were more likely to have SDNN >60 msn (OR: 2.4, 95% CI:1.2–12.8) and RMSSD >40 ms (OR: 2.5, 95% CI: 1.4–9.2).ConclusionThis study revealed parasympathetic overtone and increased HRV in patients with history of COVID-19. This may explain the unresolved orthostatic symptoms occurring in post-COVID period which may be associated with autonomic imbalance.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10840-022-01138-8.

Inflammatory Response after Different Ablation Strategies for Paroxysmal Atrial Fibrillation.

Catheter ablation for atrial fibrillation (AF) has been gaining popularity; however, the trend of inflammatory response markers in patients treated with different catheter ablation strategies over time and their predictability of AF recurrence remain unknown. A total of 210 patients with AF were enrolled and grouped according to surgical mode as follows: freeze group, RF group, and freeze3D group. The subjects were tested for related indexes before and after surgery. To determine AF recurrence during follow up, 24-h ambulatory electrocardiography was performed at two, three, six, and 12 months after surgery. The inflammation indexes of the three groups peaked between one and three days after surgery but fell at different time points (P < .05). The recurrence rate of paroxysmal atrial fibrillation (PAF) was positively correlated with the increase in the percentage of white blood cells and neutrophils after surgery (P < .05). The postoperative inflammation indices peaked and fell at different time points after different catheter ablation methods. In addition, the recurrence rate of AF in patients treated with freeze3D is lower.

Short term optimization of glycaemic control using insulin improves sympatho-vagal tone activities in patients with type 2 diabetes

IntroductionDiabetic cardiac autonomic neuropathy (CAN) is potentially life threatening and its severity might further be aggravated by poor glycaemic control. A decrease in Heart rate variability (HRV) is the earliest finding of CAN even at the sub clinical stage. While intensive glycaemic control prevents the development of CAN in patients with type 1 diabetes, it is not known whether the intensification of glycaemic control using insulin would improve cardiovascular autonomic functions in type 2 diabetes patients. This study aimed to determine the short term effects of optimizing glycaemic control using insulin on the HRV in type 2 diabetes patients. MethodsWe conducted a single arm open label clinical trial. Participants were poorly controlled non-insulin treated type 2 diabetes mellitus patients (HbA1c ≥ 7%). The intervention lasted 60 days and consisted in the intensification of glycaemic control through the initiation of a basal plus insulin regimen with titration of insulin to protocol defined glycaemic targets which were; fasting glycaemia: 0.70–1.30 g/L and post prandial glycaemia <1.80 g/L. Long term HRV measurement was done using a 24-h ambulatory electrocardiographic (ECG) recording on day 0 and day 60. Wilcoxon signed rank test was used to compare differences in HRV parameters before and after the intervention. ResultsA total of 29 (14 males and 15 females) consenting type 2 diabetes mellitus patients without clinical signs of CAN were enrolled and allocated to intervention (14 males and 15 females). The median age was 52 [43–59] years, and duration of diabetes 3.0 [0.6–6.7] years. The intervention induced a reduction in HbA1c from 10.1 [9.1–11.9]% to 6.7 [5.9–6.9]% (p < 0.001) without severe hypoglycaemic events. Concerning HRV parameters, there was a significant improvement in markers of the parasympathetic tone (PNN50: 5.7 [3.6–10.3]% to 8.1 [3.1–16.9]%, p = 0.008) and sympathetic tone (SDNN: 102.01 [90.45–111.05] ms to 122.40 [91.70–135.95] ms, p = 0.01). ConclusionThe optimization of glycaemic control using a basal plus insulin regimen while inducing a significant reduction in glycated hemoglobin, significantly improves 24-h ambulatory ECG derived sympathetic and parasympathetic activities. This suggests that tight glycaemic control using insulin may revert cardiac autonomic neuropathy in type 2 diabetes mellitus patients.

Audit of 24 h ambulatory electrocardiography (Holter) of 281 Nigerian patients in Benin city metropolis

Background: Recent advances in cardiovascular management have been the result of the implementation of technological advances in the form of facilities in patient care. Continuous ambulatory electrocardiography (ECG) is used for the diagnosis of symptomatic and asymptomatic arrhythmias of the cardiac patient which are not immediately apparent to the clinician, but otherwise amenable to treatment. Objective: The aim of this study is to examine the relevance of 24-h ambulatory ECG in the management of arrhythmias in the Nigerian patient. The study was carried out from Winsephs' family clinic, a private cardiology clinic in Benin City. Methods: A retrospective study of 281 adult patients referred for 24 h ambulatory ECG (Holter) between January 2006 and June 2015. Results: The indications for Holter-ECG were as follows: unexplained recurrent palpitations (174) (61.9%); effort intolerance (67) (23.8%); probable ischemic heart disease (53) (18.9%); chest pain (53) (18.9%); and an assessment of arrhythmia in congestive cardiac failure (48) (17.1%). Others were syncopal attacks (23) (8.9%) and extreme weakness (15) (5.3%). The most common rhythm abnormalities and the number of individuals affected were as follows: premature atrial contractions (PAC) (188) (66.1%), sinus tachycardia (ST) (165) (58.7%), ventricular extrasystoles (148) (52.7%), paroxysmal supraventricular tachycardia (127) (45.2%), ventricular tachycardia (55) (19.6%), bradycardia (57) (20.3%), and pause (51) (18.2%). Other significant rhythm abnormalities were atrial fibrillation (17) (6.1%) and atrial flutter (10) (3.6%). Myocardial ischemia indicated by ST depressive episodes was observed in (32) (11.4%) patients, and the majority of those affected were >55 years of age. There were five normal reports. Conclusion: Holter-ECG is becoming an indispensable tool in diagnosis, management, and follow up of the cardiac patient.

Advanced and traditional electrocardiographic risk factors in pulmonary arterial hypertension: the significance of ventricular late potentials.

Whether non-invasive electrocardiographic parameters may be of similar relevance in pulmonary arterial hy-pertension (PAH) as in left ventricular heart failure (LVHF) remains unclear. To examine a profile of electrocardiographic parameters in PAH and to determine their prognostic significance. Com-parison of profile in patients with pulmonary hypertension secondary to left ventricular dysfunction was planned in order to put PAH group results into context. We included 41 patients with type 1.1/1.4.4 (according to the European Society of Cardiology) PAH and 31 patients with LVHF and type 2.1 pulmonary hypertension. All patients underwent 24-h ambulatory electrocardiography monitoring. Among heart rate variability parameters, only RMSSD was different (mean, 75 ms [PAH] vs. 112 ms [LVHF], p = 0.016). In PAH, fewer patients had ventricular tachycardia (15% vs. 48%, p = 0.004), abnormal deceleration capacity (54% vs. 84%, p = 0.011), positive heart rate turbulence (11% vs. 48%, p = 0.003), severe autonomic failure (10% vs. 39%, p = 0.005), and ventricular late potentials (LP) (19% vs. 62%, p = 0.001). In PAH, four deaths occurred in 42 months. In univariate analysis, the risk factors for death were: LP (hazard ratio 13.55, 95% confidence interval 1.41-130.72; p = 0.024), age, N-terminal prohormone of B-type natriuretic peptide, while the protective factors were minimal and mean heart rate, as well as the six-minute walk test (6MWT) distance. In multivariate analysis, the influence of LP and the 6MWT distance remained significant. Ventricular LP were present in 19% of PAH patients and were the most powerful risk factor of mortality .

Twenty-four-hour ambulatory electrocardiography characterization of heart rhythm in Vipera berus-envenomed dogs

BackgroundVipera berus has a worldwide distribution and causes high morbidity in dogs annually. A complication to envenomation may be cardiac arrhythmias. The purpose of this study was to investigate the prevalence, types, and timing of arrhythmias, using 24-h ambulatory electrocardiography (24-AECG), in dogs bitten by V. berus in the first 24–32 h after envenomation. In addition, this study aimed to investigate if there were differences in selected clinical and hematological- and biochemical variables (including cardiac troponin I) at admission between V. berus-envenomed dogs with and without detected pathologic arrhythmias. Seventeen prospectively recruited client-owned dogs acutely envenomed by V. berus, were therefore examined clinically and echocardiographically, sampled for blood, hospitalized, and monitored by 24-AECG.ResultsClinically significant pathologic arrhythmias in this study were of ventricular origin, such as frequent single ventricular premature contractions (VPCs) and couplets of VPCs, episodes of ventricular tachycardia and idioventricular rhythm, and “R-on-T phenomenon”. Variations of these arrhythmias were detected by 24-AECG in eight (47%) of included dogs. No arrhythmias were detected by cardiac auscultation. Twenty-four hours following envenomation, four out of eight dogs experienced decreases (all P < 0.039), and three out of eight dogs experienced increases (all P < 0.034), in arrhythmic episodes. All four dogs bitten on a limb developed pathologic arrhythmias. Otherwise, no significant differences in clinical, hematological or biochemical variables were seen between dogs with pathologic arrhythmias and those without.ConclusionForty-seven percent of dogs bitten by V. berus included in this study experienced pathologic arrhythmias of abnormal ventricular depolarization. During the first 24–32 h from the snakebite, some dogs experienced a decrease in arrhythmic episodes and others an increase in arrhythmic episodes. These findings indicate a potential value of repeated or prolonged electrocardiography monitoring of envenomed dogs for identification of which dogs that might benefit the most from prolonged hospitalization for optimal monitoring and treatment of cardiac abnormalities. In the present study, dogs that developed arrhythmias could not be differentiated from dogs that did not based on clinical findings or hematological or biochemical variables obtained at admission.

Ventricular Ectopy as a Predictor of Heart Failure and Death

BackgroundStudies of patients presenting for catheter ablation suggest that premature ventricular contractions (PVCs) are a modifiable risk factor for congestive heart failure (CHF). The relationship among PVC frequency, incident CHF, and mortality in the general population remains unknown. ObjectivesThe goal of this study was to determine whether PVC frequency ascertained using a 24-h Holter monitor is a predictor of a decrease in the left ventricular ejection fraction (LVEF), incident CHF, and death in a population-based cohort. MethodsWe studied 1,139 Cardiovascular Health Study (CHS) participants who were randomly assigned to 24-h ambulatory electrocardiography (Holter) monitoring and who had a normal LVEF and no history of CHF. PVC frequency was quantified using Holter studies, and LVEF was measured from baseline and 5-year echocardiograms. Participants were followed for incident CHF and death. ResultsThose in the upper quartile versus the lowest quartile of PVC frequency had a multivariable-adjusted, 3-fold greater odds of a 5-year decrease in LVEF (odds ratio [OR]: 3.10; 95% confidence interval [CI]: 1.42 to 6.77; p = 0.005), a 48% increased risk of incident CHF (HR: 1.48; 95% CI: 1.08 to 2.04; p = 0.02), and a 31% increased risk of death (HR: 1.31; 95% CI: 1.06 to 1.63; p = 0.01) during a median follow-up of >13 years. Similar statistically significant results were observed for PVCs analyzed as a continuous variable. The specificity for the 15-year risk of CHF exceeded 90% when PVCs included at least 0.7% of ventricular beats. The population-level risk for incident CHF attributed to PVCs was 8.1% (95% CI: 1.2% to 14.9%). ConclusionsIn a population-based sample, a higher frequency of PVCs was associated with a decrease in LVEF, an increase in incident CHF, and increased mortality. Because of the capacity to prevent PVCs through medical or ablation therapy, PVCs may represent a modifiable risk factor for CHF and death.

Combination therapy with bisoprolol and amlodipine in patients with chronic obstructive pulmonary disease and hypertension

The purpose of this study was to assess efficacy of a fixed combination of bisoprolol and amlodipine (Concor AM, Takeda) in patients with chronic obstructive pulmonary disease (COPD) and hypertension (H). Methods . Thirty eight stable patients with stage 2 COPD and stage I–II H were treated with a fixed combination of bisoprolol and amlodipine. 24h ambulatory blood pressure monitoring (ABPM), electrocardiography, echocardiography, and lung function were performed at the baseline and in 12 weeks of therapy. Results . Thirty four (89.5%) patients continued the treatment after 12 weeks. The therapy with the fixed combination of bisoprolol and amlodipine in average dose of 7.5 / 10 mg/day provided a target blood pressure (BP) level in 32 (84.2%) patients. ABPM analysis demonstrated stable significant improvement in BP parameters including the heart rate variability. A trend toward normalization of the left heart diastolic function was noted during treatment. Lung function did not differ significantly before and after 12 weeks of the treatment indicating that the fixed combination of bisoprolol and amlodipine did not impact negatively on bronchial obstruction. Conclusion. The results confirm the rationale of therapy with the fixed combination of bisoprolol and amlodipine in patients COPD and H.

Increased variability of the coupling interval of premature ventricular contractions as a predictor of cardiac mortality in patients with left ventricular dysfunction.

The characteristics and prognostic value of the variability of premature ventricular contraction (PVC) coupling intervals (CIs) for cardiac mortality are not yet decisive. In 133 consecutive patients (58±14 years old, 53 women) who had left ventricular dysfunction (LVD: ejection fraction <50%) and frequent PVCs (≥10/h) who underwent 24-h ambulatory electrocardiography (AECG) recording and (123)I-metaiodobenzylguanidine myocardial single-photon emission computed tomography simultaneously, the heart rate turbulence onset, slope, and T-wave alternans were analyzed from the 24-h AECG. The CI of the PVCs (MEANNV), standard deviation of the CI of the PVCs (SDNV) as an index of the variability of the PVC CI, and their ratio to the preceding N-N intervals (SDNV/SDNN) were calculated from constructed Poincaré plots using the annotated 24-h AECG QRS data. The primary endpoint was cardiac mortality. The mean follow-up period was 63 months. Among 133 patients, 114 survived (group 1) and 19 (14%, group 2) died during the follow-up. The MEANNVand SDNVwere higher in group 2 (539±104 vs. 599±114 ms, P=0.021; 64±34 vs. 83±37 ms, P=0.022, respectively). The SDNV, PVC count, and delayed heart/mediastinum ratio remained as significant predictors of cardiac mortality in the binary logistic regression analysis. These results suggest that the SDNVcould be another adjunctive parameter for predicting cardiac mortality in LVD.

Local dynamics of heart rate: detection and prognostic implications

The original observation that reduced heart rate variability (HRV) confers poor prognosis after myocardial infarction has been followed by many studies of heart rate dynamics. We tested the hypothesis that an entropy-based local dynamics measure gave prognostic information in ambulatory patients undergoing 24-h electrocardiography. In this context, entropy is the probability that short templates will find matches in the time series. We studied RR interval time series from 24-h Holter monitors of 1564 consecutive patients over age 39. We generated histograms of the count of templates as a function of the number of templates matches in short RR interval time series, and found characteristic appearance of histograms for atrial fibrillation, sinus rhythm with normal HRV, and sinus rhythm with reduced HRV and premature ventricular contractions (PVCs). We developed statistical models to detect the abnormal dynamic phenotype of reduced HRV with PVCs and fashioned a local dynamics score (LDs) that, after controlling for age, added more prognostic information than other standard risk factors and common HRV metrics, including, to our surprise, the PVC count and the HRV of normal-to-normal intervals. Addition of the LDs to a predictive model using standard risk factors significantly increased the ROC area and the net reclassification improvement was 27%. We conclude that abnormal local dynamics of heart rate confer adverse prognosis in patients undergoing 24-h ambulatory electrocardiography.

A HOTSPOT MUTATION RYR2-R169Q FOR CHINESE PATIENTS WITH CATECHOLAMINERGIC POLYMORPHIC VENTRICULAR TACHYCARDIA

ObjectivesBackground: Catecholaminergic polymorphic ventricular tachycardia (CPVT), a malignant inherited arrhythmias, is characterised by stress-induced bidirectional or polymorphic ventricular tachycardia in absence of structural cardiac abnormalities. Unexplained syncope or sudden death...

PHENOTYPE DIFFERENCE BETWEEN GENOTYPE OF PLAKOPHILIN-2 MUTATION AND DESMOGLEIN-2 MUTATION IN SYMPTOMATIC CHINESE PATIENTS WITH ARRHYTHMOGENIC RIGHT VENTRICULAR DYSPLASIA/CARDIOMYOPATHY-A REPORT FROM CHINESE ARVD REGISTRY

ObjectivesArrhythmogenic Right Ventricular Dysplasia/cardiomyopathy (ARVD/C) is an inherited heart muscle disease associated mainly with the mutations of desmosome. Plakophilin-2 (PKP2) and desmoglein-2 (DSG-2) are reported as the most two common...

Abdominal Superficial Subcutaneous Fat

OBJECTIVEUnlike visceral adipose tissue (VAT), the association between subcutaneous adipose tissue (SAT) and obesity-related morbidity is controversial. In patients with type 2 diabetes, we assessed whether this variability can be explained by a putative favorable, distinct association between abdominal superficial SAT (SSAT) (absolute amount or its proportion) and cardiometabolic parameters.RESEARCH DESIGN AND METHODSWe performed abdominal magnetic resonance imaging (MRI) in 73 patients with diabetes (mean age 58 years, 83% were men) and cross-sectionally analyzed fat distribution at S1-L5, L5-L4, and L3-L2 levels. Patients completed food frequency questionnaires, and subgroups had 24-h ambulatory blood pressure monitoring and 24-h ambulatory electrocardiography.RESULTSWomen had higher %SSAT (37 vs. 23% in men; P < 0.001) despite a similar mean waist circumference. Fasting plasma glucose (P = 0.046) and HbA1c (P = 0.006) were both lower with increased tertile of absolute SSAT. In regression models adjusted for age, waist circumference, and classes of medical treatments used in this patient population, increased %SSAT was significantly associated with decreased HbA1c (β = −0.317; P = 0.013), decreased daytime ambulatory blood pressure (β = −0.426; P = 0.008), and increased HDL cholesterol (β = 0.257; P = 0.042). In contrast, increased percent of deep SAT (DSAT) was associated with increased HbA1c (β = 0.266; P = 0.040) and poorer heart rate variability parameters (P = 0.030). Although total fat and energy intake were not correlated with fat tissue distribution, increased intake of trans fat tended to be associated with total SAT (r = 0.228; P = 0.05) and DSAT (r = 0.20; P = 0.093), but not with SSAT.CONCLUSIONSAbdominal SAT is composed of two subdepots that associate differently with cardiometabolic parameters. Higher absolute and relative distribution of fat in abdominal SSAT may signify beneficial cardiometabolic effects in patients with type 2 diabetes.

Identifying Arrhythmias in Adults With Congenital Heart Disease by 24-h Ambulatory Electrocardiography

Adults with congenital heart disease (CHD) are at risk for the development of arrhythmias. This study aimed to assess the incidence of unsuspected arrhythmias among adults with CHD identified on electrocardiograms (ECGs) and 24-h ambulatory electrocardiographic monitoring (Holter monitoring). A review of the cardiology database at the authors' institution from July 2004 through December 2007 identified all clinic patients 18years old or older who had a recent ECG and Holter monitoring. Data collection included diagnosis, ECG and Holter monitoring results, arrhythmias, and the presence or absence of symptoms. The review identified 140 patients. Analysis of the ECGs showed that 15% of the patients had an arrhythmia. These arrhythmias consisted of ectopy (6%), supraventricular tachycardia (SVT) (3%), pacemaker issues (2%), and previously unrecognized atrioventricular block (AVB) (1%). The majority of the patients with arrhythmias were asymptomatic (76%). Analysis of the Holter monitoring results showed that 31% of the patients had arrhythmias consisting of ectopy (17%), SVT (12%), ventricular tachycardia (7%), high-grade AVB (5%), and pacemaker issues (3%). Of the patients with arrhythmias, 80% were asymptomatic. Among the patients without arrhythmias on ECG, 26% had arrhythmias noted on Holter monitoring. Of the patients with multiple Holter monitorings performed, 34% had a new arrhythmia noted on repeat monitoring. In conclusion, arrhythmias were present in a significant number of adults with CHD, but the majority were asymptomatic. Among adults with CHD, even those with normal ECGs, arrhythmias were frequently detected on Holter monitoring. In addition, repeat Holter monitoring may identify significant arrhythmias over time.

Poincaré plots and tachograms reveal beat patterning in sick sinus syndrome with supraventricular tachycardia and varying AV nodal block

Using 24-h ambulatory electrocardiography, the RR intervals of all beats were determined in a West Highland white terrier with sick sinus syndrome characterized by long sinus pauses, bradycardia, supraventricular tachycardia (SVT) and varying degrees of atrioventricular (AV) heart block. Distinctive patterns of bradycardia and 1:1, 2:1, 3:1, 4:1 and 5:1 AV block associated with SVT were evident in the tachogram (RR interval distribution over time) and Poincaré plots (short-term heart rate variability plots of RRn versus RRn + 1). These patterns differed from those of abrupt alteration in cycle length during long sinus pauses or bursts of supraventricular tachycardia. Recognition of such patterns may direct attention to time points for which close attention to the cardiac rhythm should be evaluated in the full-disclosure of the 24-h ECG recording.

Identification of Obstructive Sleep Apnea Syndrome by Ambulatory Electrocardiography: Clinical Evaluation of Time-domain and Frequency-domain Analyses of Heart Rate Variability in Chinese Patients

The application of ambulatory electrocardiography to identify obstructive sleep apnea syndrome (OSAS) patients was evaluated using time-domain and frequency-domain analyses of heart rate variability (HRV). For this, overnight sleep pattern was investigated in 95 individuals (48 OSAS(+) patients and 47 OSAS(-) controls) by polysomnography and 24-h ambulatory electrocardiography. Apnea scores were calculated using two different HRV analyses. Average age and body mass index, and percentages of men and of patients with history of hypertension and/or diabetes were higher in study group as compared with control group. PNN50(night), SDNNI(day-night) and SDNNI(day-night) in time-domain analysis were more sensitive than other indices. In frequency-domain analysis, mean night-time total power, night-time VLF power, night-time LF power, and the difference between these measures in day and night were significantly higher in study group. LF/HF ratio was also significantly higher in study group in day-time or night-time with a significant difference (P<0.05) between day and night. At sleep apnea risk score >4, sensitivity, specificity, and positive predictive value were, respectively, 81.25, 46.81, and 64.21%. At sleep apnea risk scores >5, 6, or 7, the specificity increased, while the sensitivity and positive predictive value decreased. In conclusion, time-domain and frequency-domain HRV analyses are useful methods for OSAS screening, and the frequency-domain analysis is more sensitive.

Acute cardiac effects of marathon running

We sought to clarify the significance of cardiac dysfunction and to assess its relationship with elevated biomarkers by using cardiovascular magnetic resonance imaging in healthy, middle-aged subjects immediately after they ran 26.2 miles. Cardiac dysfunction and elevated blood markers of myocardial injury have been reported after prolonged strenuous exercise. From 425 volunteers, 13 women and 12 men were randomly selected, provided medical and training history, and underwent baseline cardiopulmonary exercise testing to exhaustion. Blood biomarkers, cardiovascular magnetic resonance imaging, and 24-h ambulatory electrocardiography were performed 4 wk before and immediately after the race. Participants were 38.7+/-9.0 yr old, had baseline peak oxygen consumption of 52.9+/-5.6 ml.kg(-1).min(-1), and completed the marathon in 256.2+/-43.5 min. Cardiac troponin I and B-type natriuretic peptide increased following the race (P=0.001 and P<0.0001, respectively). Cardiovascular magnetic resonance-determined pre- and postmarathon left ventricular ejection fractions were comparable, 57.7+/-4.1% and 58.7+/-4.3%, respectively (P=0.32). Right atrial volume index increased from 46.7+/-14.4 to 57.0+/-14.5 ml/m2 (P<0.0001). Similarly, right ventricular end-systolic volume index increased from 47.4+/-11.2 to 57.0+/-14.6 ml/m2 (P<0.0001) whereas the right ventricular ejection fraction dropped from 53.6+/-7.1 to 45.5+/-8.5% (P<0.0001). There were no morphological changes observed in the left atrium or ventricle or evidence of ischemic injury to any chamber by late gadolinium enhancement. There were no significant arrhythmias. Marathon running causes dilation of the right atrium and right ventricle, reduction of right ventricular ejection fraction, and release of cardiac troponin I and B-type natriuretic peptide but does not appear to result in ischemic injury to any chamber.

Heart Rate Variability in Children with Exercise-Induced Idiopathic Ventricular Arrhythmias

Ventricular arrhythmias (VAs) are common pediatric rhythm disorders requiring comprehensive laboratory evaluation. Although usually idiopathic, implying a benign character and favorable prognosis, the initial clinical approach is still not established in all cases. Considering their prognostic significance, exercise-induced (precipitated or aggravated) VAs usually require additional diagnostics, treatment, and follow-up. A number of reports have presented experimental and clinical evidence that increased sympathetic activity can initiate, or at least facilitate, VAs. Recent data highlight the relationship between exercise-induced idiopathic VAs (IVAs) and the long-term risk of cardiovascular death. The aim of this study was to assess the utility of heart rate variability (HRV) analysis as a noninvasive method for estimating autonomic nervous activity in children with exercise induced IVAs. The study included 42 children with IVAs, who were divided into two groups: children with exercise induced (precipitated or aggravated) IVAs and children with exercised-suppressed IVAs. Time-domain HRV parameters were analyzed from 24-h ambulatory electrocardiography recordings, and the majority of children underwent an exercise stress test using the McMaster protocol. The results of this study showed no significant changes in parasympathetic index, i.e., the square root of the mean of the sum of the squares of the differences between adjacent NN intervals (the length between two successive heartbeats) between the groups examined. On the other hand, we observed diminished time-domain values for the standard deviation of all adjacent NN intervals, as well as diminished time-domain values for standard deviation of the averages of NN intervals in all 5-min segments in the group of children with exercise-induced IVAs, implicating increased sympathetic activity in such individuals. HRV analysis could be a helpful diagnostic method, giving useful information regarding cardiac autonomic control in some children with exercise-induced IVAs.

Myoblast Transfer in Ischemic Heart Failure: Effects on Rhythm Stability

Skeletal myoblast (SM) implantation promotes recovery of myocardial function after ischemic injury. Clinical observations suggest an association of SM implantation and ventricular arrhythmias. Support for this link has been sought in animal studies, but none employing models of congestive heart failure. In a canine model of postinfarction congestive heart failure (CHF) we compared the frequency of rhythm disturbances using ambulatory electrocardiography monitoring following skeletal myoblast or saline (SAL) implantation. In 19 mongrel dogs ischemic injury and CHF were induced by intracoronary microsphere infusions. Direct intramyocardial injection of autologous skeletal myoblasts (ASM) (2.7-8.3 x 10(8) cells) or SAL controls was administered to 11 and 8 dogs, respectively. Serial echocardiography and 24-h ambulatory electrocardiography were recorded at baseline (after CHF induction) and at 4 weeks and at 8-10 weeks after injection. Comparisons between groups of left ventricular ejection fraction (LVEF) and the frequency of ventricular arrhythmias, supraventricular arrhythmias, and measures of heart rate variability (HRV) were made at each of the three time points. LVEF increased from 41 +/- 6% to 47 +/- 2% (p < 0.03) in the ASM group, and did not change (42 +/- 6% to 40 +/- 2%, p = ns) in SAL. After injection, no differences were seen in the number of dogs demonstrating ventricular tachycardia (n = 3 vs. n = 2, p = ns) or frequent PVCs (n = 3 vs. n = 3, p = ns) in the ASM versus SAL groups, respectively. Significant changes were observed in a time-domain measure of HRV, standard deviation of normal-to-normal RR interval (in ms: 4 weeks 174 +/- 95 vs. 242 +/- 19; 8 weeks 174 +/- 78 vs. 276 +/- 78, ASM vs. SAL), but not in other time domain parameters. In this canine model of ischemic CHF, ASM implantation did not result in a significant increase in ventricular arrhythmias compared to controls animals. The potential for ASM implantation to affect time-domain parameters of HRV merits further study.

The hemodynamic and pharmacokinetic interactions between chronic use of oral levosimendan and digoxin in patients with NYHA Classes II

Levosimendan is a calcium-sensitizing drug for the treatment of heart failure. The aim of this exploratory study was to assess the hemodynamic and pharmacokinetic interactions between digoxin and oral levosimendan as well as the proarrhythmic potential of this combination in patients with chronic heart failure. Male or female patients (n = 24) with chronic heart failure of NYHA Classes II-III. A randomized, placebo-controlled, double-blind, parallel-group trial. After a 1-week digoxin-free washout period, the patients were randomized to receive either digoxin and levosimendan (digoxin + levosimendan), or digoxin and placebo (digoxin) orally for 14 +/- 2 days. The levosimendan dose was 1 mg 3 times daily, and the digoxin dose was 0.125-0.25 mg once daily. Systolic time intervals, electrocardiography (ECG), magneto-cardiography (MCG) and 24-h ambulatory ECG were performed at baseline and at the end of each treatment period. Pharmacokinetic variables of levosimendan and digoxin were calculated in both treatment periods. Steady-state concentrations of the active metabolites OR-1855 and OR-1896 were determined at baseline at Visit 2. There tended to be a greater shortening of QS2i (suggesting trend to positive inotropy) in the digoxin + levosimendan group (-14ms) compared with the digoxin group (-5ms), although the difference was not statistically significant (p=0.359). However, the change from baseline in QS2i after digoxin + levosimendan was of statistically borderline significance (p=0.05). The change from baseline in the digoxin group was not statistically significant. ECG and MCG repolarization measures and occurrence of nonsustained ventricular tachycardia showed no substantial differences. After 2 weeks of digoxin + levosimendan treatment, mean area under the curve (AUC) of levosimendan increased approximately by 49% (p<0.01). The maximum plasma concentration (Cmax) of levosimendan increased from 17 to 23 ng/ml. The mean concentrations of the metabolites OR-1855 and OR-1896 in plasma were 4.3 and 8.3 ng/ml, respectively. The addition of oral levosimendan to digoxin therapy produced only a modest statistically nonsignificant additive inotropic effect. In contrast to the earlier data with intravenous levosimendan, the results indicate a pharmacokinetic interaction between levosimendan and digoxin. Data obtained from repolarization analyses and ambulatory ECG did not indicate any possible proarrhythmic effects of the combination.