24-h Ambulatory ECG Research Articles

Semia: semi-automatic interactive graphic editing tool to annotate ambulatory ECG records.

We designed and developed a special purpose interactive graphic editing tool semi-automatic (Semia) to annotate transient ischaemic ST segment episodes and other non-ischaemic ST segment events in 24h ambulatory electrocardiogram (ECG) records. The tool allows representation and viewing of the data, interaction with the data globally and locally at different resolutions, examining data at any point, manual adjustment of heart-beat fiducial points, and manual and automatic editing of annotations. Efficient and fast display of ambulatory ECG signal waveforms, display of diagnostic and morphology feature-vector time-series, dynamic interface controls, and automated procedures to help annotate, made the tool efficient, user friendly and usable. Human expert annotators used the Semia tool to successfully annotate the Long-Term ST database (LTST DB), a result of a multinational effort. The tool supported paperless editing of annotations at dislocated geographical sites. We present design, characteristic "look and feel", functionality, and development of Semia annotating tool.

Differential index, a novel graphical method for measurements of heart rate variability

Background: Commonly used methods to evaluate heart rate variability require extensive filtering of the registrations in order to exclude artefacts and ectopic beats. We developed and validated a novel graphical method for time-domain measurements of heart rate variability, the differential index, which does not require filtering and is simple to use. Methods: The 24-h ambulatory long-term electrocardiogram recordings from 120 patients with angina pectoris and 49 control subjects were computerised without any filtering process. Sample density histograms of differences in the RR interval for successive beats were constructed and the widths of the histograms were used to obtain the differential index. For comparison, the same registrations were analysed by conventional methods. Results: The differential index was most closely related ( P<0.001) to conventional short-term time domain (e.g. percent of differences between adjacent normal RR intervals >50 ms, pNN50, r=0.81) and frequency-domain (e.g. high frequency power, r=0.84) components, but also to long-term time domain (e.g. standard deviation of all normal-to-normal RR intervals for all 5-min segments of the entire registration, SDNNIDX, r=0.72) and frequency-domain (e.g. low frequency power, r=0.64) components. Conclusion: The differential index method shows good agreement with established indices of heart rate variability. The insensitivity to recording artefacts and short-lasting disturbances of sinus rhythm make the differential index method particularly suited when data quality is imperfect. The simplicity of the method is valuable when large numbers of registrations are to be evaluated.

Abnormal ventricular repolarization in hypertensive patients: role of sympatho-vagal imbalance and left ventricular hypertrophy

Background: An increased risk for life-threatening arrhythmias and sudden death has been observed in hypertensive patients, associated with either left ventricular hypertrophy (LVH) or prolonged QT interval. To investigate the influence of autonomic imbalance and LVH on QT interval in hypertensive patients, we compared two different models of LVH: hypertension and endurance physical training. Methods: Forty-seven untreated subjects affected by essential hypertension and 35 endurance runners, with a similar degree of LVH, were enrolled into the study. All subjects underwent 24-h ambulatory ECG recording and morning blood sampling for catecholamines. Heart rate variability was evaluated by spectral analysis and a computerized algorithm was used to measure the QT interval; QTc was then computed by the Bazett's formula. Left ventricular mass index (LVMI) was assessed by echocardiogram. Results: No difference in LVMI was found between hypertensive patients and athletes. Athletes showed lower heart rate (64±1 vs. 75±1 bpm, p<0.001, mean±S.E.M.) and shorter QTc (401±3 vs. 434±4 ms, p<0.001) than hypertensive patients throughout the 24-h period. Athletes showed a higher vagal drive compared to hypertensive patients as suggested by bradycardia and higher values of vagal indices, which negatively correlated with QTc. Plasma norepinephrine was significantly lower in athletes than in hypertensive patients ( p<0.05) and positively correlated with QTc. Conclusion: Despite similar degrees of LVH, hypertensive patients show QTc lengthening, as compared to athletes. Heart rate variability and plasma norepinephrine levels suggest sympathetic predominance in hypertensive patients, which could contribute to abnormal ventricular repolarization, thus identifying patients with an increased arrhythmic risk.

Increased heart rate and reduced heart-rate variability are associated with subclinical inflammation in middle-aged and elderly subjects with no apparent heart disease.

Elevation of inflammation markers, high heart rate, and reduced heart-rate variability are all strong markers of mortality in a broad spectrum of patients. The association between these markers has not been clarified thoroughly. We investigated the associations between markers of inflammation, heart rate, and heart-rate variability. Six hundred and forty-three healthy men and women between 55 and 75 years of age and with no prior history of cardiovascular disease or stroke were included in the study. The baseline study included a physical examination, fasting laboratory tests, and 24-h ambulatory ECG monitoring. We selected the time-domain components of heart-rate variability for further analyses. C-reactive protein concentration and white blood cell count were selected as markers of inflammation. After identifying parameters related to measures of heart-rate variability, we used regression analyses to evaluate independent associations. Heart-rate variability, as measured by the standard deviation of the time between normal-to-normal complexes or the standard deviation of the average of normal-to-normal intervals for each 5-min period, was negatively associated with smoking, C-reactive protein, white blood cell count, blood sugar and triglyceride concentration, female gender, and diabetes. In contrast, physical activity was strongly associated with higher heart-rate variability. In multivariate regression analyses, increased heart-rate and reduced heart-rate variability were significantly and independently related to white blood cell count or C-reactive protein concentration. Increased heart rate and reduced heart-rate variability are associated with subclinical inflammation in healthy middle-aged and elderly subjects. The increased mortality that has been reported in these settings may thus have a common aetiology. An autonomic imbalance in favour of the sympathetic system may interact with inflammatory processes to play a more important role in the process of atherosclerosis than previously thought.

Sodium intake and cardiac sympatho-vagal balance in young men with high blood pressure.

We have previously reported that a high sodium intake increases sleep-time blood pressure (BP) in young men. However, there are cases in which this relation does not apply. To account for them, we investigated the relation between sodium intake and cardiac sympatho-vagal balance (SVB) in young men with high BP. Sodium intake was estimated from the amount of urinary sodium excretion over 1 week. Twenty-four-hour (24-h) urinary sodium excretion (Salt24), 24-h ambulatory BP and ECG were obtained on the last day of the observation period. As an index of sodium intake, the expression In(Salt24/Cr24) (Cr24, 24-h urinary creatinine excretion) was used. From power-spectral analysis of ECG-RR intervals during sleep, we obtained the LF/HF ratio between the low-frequency component (LF) and the high frequency component (HF) and used it as an index of SVB. The subjects were male medical students divided into a normal BP group (N-group; n=103) and a high BP group (H-group; n=26, 24-h BP>125/75 mmHg). Mean In(Salt24/Cr24) and LF/HF in the H-group were significantly higher than those in the N-group (LF/HF: 1.86+/-0.44 [SD] vs. 1.37+/-0.30, p<0.001). The calculated discriminant function (D) for the H-group and N-group was D=1.6x + 5y - 11, where x is In(Salt24/Cr24) and y is LF/HF. This formula (D) resulted in high discriminant predictive accuracy (82%) between the groups. If D=0 (the value of the cut-off line determining separation of the groups), the relation y=-0.32x + 2.2 (negative relation between y and x) was obtained. These results suggest that excessive sodium intake in combination with accentuated SVB (LF/HF) increases BP in young men.

Factors influencing return to work at one year after coronary bypass graft surgery: results of the PERISCOP study.

The aim of this study was to evaluate the predictive factors of return to work after coronary bypass graft surgery, for the subgroup of professionally active patients aged less than 60 years included in the PERISCOP study. In the principal, prospective, multicentre study, 2065 patients were evaluated 20+/-10 days after surgery by exercise testing, echocardiogram and 24-h ambulatory ECG monitoring. A questionnaire was completed one year after surgery. We studied a subgroup of this population, consisting of 530 patients previously defined (94.5% men; mean age: 50.5+/-5.8 years). One year after surgery, five of these patients had died and 21 were lost to follow-up. Among the remaining patients, 340 patients (67.5%) had returned to work. Forty patients (7.9%) had retired, 45 (8.9%) were on sick leave, 22 (4.4%) were unemployed, 49 (9.7%) returned to work after the deadline of 12 months, eight (1.6%) had given insufficient information on return to work. In multivariate analysis, the independent predictors of a failure to return to work were age >51 years [OR: 0.39 (95% CI: 0.25-0.59)], being a manual worker [OR: 0.49 (95% CI: 0.31-0.79)], being from South East France [(OR: 0.42 (95% CI: 0.23-0.74)], presence of angina [OR: 0.40 (95% CI: 0.20-0.82)], dyspnoea [(OR: 0.46 (95% CI: 0.28-0.77)] and a duration of exercise <420 s [(OR: 0.50 (95% CI: 0.33-0.76)]. Return to work after coronary bypass graft surgery is observed in 67.5% of cases and depends essentially on socio-professional factors and residual symptoms. A regional effect was also observed, which requires further study.

Circadian variation of cardiac autonomic nervous activity is well preserved in patients with mild to moderate chronic heart failure: effect of patient position

Background: It remains unclear whether circadian variation (CV) of cardiac autonomic nervous activity (CANA) is preserved in patients with chronic heart failure (CHF) as in healthy subjects. We have demonstrated that CANA in CHF patients is largely affected by patient recumbent position. Methods: We studied eight mild to moderate CHF patients and eight age, sex-matched healthy subjects. Each subject underwent 24-h ambulatory ECG monitoring. One channel was used to record the CM5 lead, and another to record the signal of patient position from a newly developed, small-sized detector. By using spectral analysis of heart rate variability, frequency-domain measures were calculated. Normalized high-frequency (HF: 0.15–0.40 Hz) power was used as an index of vagal activity and the low frequency (LF: 0.04–0.15 Hz)/HF power ratio was used as an index of sympathovagal balance. These indexes in the same recumbent position were compared between night (2:00–4:00 a.m.) and morning (6:00–8:00 a.m.). Results: In healthy subjects, a definite CV of CANA was observed in each recumbent position. In patients with CHF, in each position, normalized HF power was lower in the morning than at night, whereas LF/HF was higher in the morning than at night. Thus, CANA in CHF patients is influenced not only by patient position but also by the time of day. Conclusion: CV of CANA in mild to moderate CHF patients is well preserved when taking patient position into consideration.

Fatal potential of supraventricular tachycardia in hypertrophic cardiomyopathy

The potential of supraventricular tachycardia to cause investigated a 15-year-old male with previous out-ofsudden death among patients with hypertrophic cardiomyopathy has been acknowledged for years; however, direct evidence is scarce [1–3]. Recently, an 18-year-old female suffering from an extreme form of hypertrophic cardiomyopathy without obstruction underwent an electrophysiologic study because of recurrent palpitations and episodes of non-sustained broad QRS tachycardia found during 24-h ambulatory ECG monitoring. Baseline 12-lead ECG showed sinus rhythm with a rate of 88 beats/min. The electrophysiologic study found normal V-A and A-V conduction. Ventricular stimulation failed to induce a ventricular arrhythmia. At that stage, a drive of eight beats with cycle length 500 ms with three subsequent extrastimuli at coupling intervals 260 ms was accidentally delivered to the right atrial appendage and caused a supraventricular tachycardia with cycle length 330 ms (182 beats/min) and an immediate blood pressure drop. The ventricles started to fibrillate 22 s after the onset of the tachycardia while the atria continued with fast regular activity (Fig. 1). Surface ECG documented progressive and significant depression of ST segments in the majority of leads before the onset of ventricular fibrillation (Fig. 2). The ventricular fibrillation and atrial tachycardia were terminated by a single direct current shock of 360 J. This case documents the fatal potential of supraventricular tachycardia in hypertrophic cardiomyopathy. Stafford et al. reported a similar case in 1986 [1]. They

Correlation between dispersion of repolarization (QT dispersion) and ventricular ectopic beat frequency in patients with acute myocardial infarction: a marker for risk of arrhythmogenesis?

Background: QT dispersion (QTd) has evoked a lot of interest in recent years as regards the basic concept of dispersion of repolarization, which it is supposed to reflect on a surface ECG, as being a marker or substrate for arrhythmogenesis. QTd has been shown to be high in patients with ventricular fibrillation and tachycardia. But there is still some debate about its possible role as a marker or substrate for arrhythmogenesis. We studied whether it has any correlation with simple benign ventricular ectopic beats (VEB) after acute myocardial infarction. Study: We studied four different dispersion parameters (QTd, QTcd, JTcd, AQTd) on 2 different days after AMI and also obtained a 24-h ambulatory ECG on the 2nd day after admission in 64 out of a total of 90 patients. Patients were divided into five groups based on VEB frequency/h on a 24-h ambulatory ECG. Results: We found a gradual increase in dispersion parameters across the five groups with increasing frequency of VEB. A significant difference was noticed between group 1 (VEB 0.0–0.9/h) and group V (>30/h) on the day of admission: QTd 88.8±28.5 versus 123.3±23.4, P<0.02; QTcd 100.5±27.6 versus 160.3±30.7, P<0.01; JTcd 95.5±31.0 versus 160.4±30.9, P<0.01; AQTd 29.6±8.2 versus 48.6±13.7, P<0.01. We also noticed a significant positive correlation between VEB frequency and dispersion parameters on both days. Conclusion: We hypothesize that with increasing dispersion of repolarization the chances or the frequency of ventricular arrhythmias increase. Our findings also point to a definite role of QTd as an arrhythmogenic marker or substrate.

C-reactive protein, clinical presentation, and ischemic activity in patients with chest pain and normal coronary angiograms

ObjectivesWe sought to investigate the relationship among C-reactive protein (hs-CRP), clinical characteristics, exercise stress test responses, and ST-segment changes during daily life in patients with typical chest pain and normal coronary angiograms (CPNCA). BackgroundPatients with CPNCA have coronary microvascular endothelial dysfunction and myocardial ischemia. Elevated hs-CRP levels have been related to atherogenesis and endothelial dysfunction. The relationship between hs-CRP and disease activity has not been previously investigated in CPNCA patients. MethodsWe studied 137 consecutive CPNCA patients (mean age, 57 ± 9; 33 men). All completed standardized angina questionnaires, underwent exercise stress testing, 24-h ambulatory electrocardiogram (ECG) monitoring (Holter), and hs-CRP measurements at study entry. ResultsC-reactive protein levels (mg/l) were higher in patients with frequent (2.9 ± 3.3) and prolonged (3.9 ± 4.1) chest pain episodes, and in those with ST-segment depression on exercise testing (2.6 ± 2.8) and Holter monitoring (3.4 ± 3.1) compared with patients with occasional (1.3 ± 1.2; p = 0.002) or shorter chest pain (1.5 ± 1.3; p < 0.001) episodes, negative exercise stress testing (1.1 ± 1.1; p < 0.001), and no ST-segment shifts on Holter monitoring (0.9 ± 0.7; p < 0.001). Moreover, we found a correlation between hs-CRP concentration and number of ischemic episodes during Holter monitoring (r = 0.65; p < 0.001) and with the magnitude of ST-segment depression on exercise testing (r = −0.43; p < 0.001). The hs-CRP was the only independent variable (multivariate logistic regression) capable of predicting positive findings on Holter monitoring (odds ratio [OR], 3.8; confidence interval [CI], 2.3 to 6.2) and exercise testing (OR, 1.7; CI, 1.2 to 2.2). ConclusionsThe hs-CRP correlates with symptoms and ECG markers of myocardial ischemia in CPNCA patients. Whether hs-CRP is related to the pathogenesis of angina in these patients deserves further investigation.

Use of non-invasive cardiac investigations to predict clinical endpoints after coronary bypass graft surgery in coronary artery disease patients: results from the prognosis and evaluation of risk in the coronary operated patient (PERISCOP) study.

Little is known about which patients who have undergone coronary bypass surgery are at risk of future clinical cardiovascular events and may benefit from further medical treatment. We sought to determine if routine non-invasive cardiac investigations performed early after surgery were able to stratify the risk of cardiovascular events in this population. Two thousand and sixty-five consecutive patients were enrolled in a prospective multicenter study (PERISCOP). Exercise testing, echocardiography, and 24-h ambulatory ECG monitoring were performed at day 20+/-10 after coronary bypass surgery. Follow-up was performed 1 year after coronary bypass surgery. Causes of all hospitalisation and death occurring within 1 year were documented and classified by an End-point Committee. The principal endpoint was the combination of all-cause deaths and cardiovascular events requiring hospitalisation (myocardial infarction, unstable or severe angina, stroke, congestive heart failure). The 1-year frequency of first events was 155 (8%). In multivariate analysis, exercise duration <420s (RR=1.68; 95% CI: 1.13-2.49), exercise induced ST segment depression >1mm (RR=1.90; 95% CI: 1.18-3.05), and left ventricular (LV) dysfunction (wall motion index <1.15) (RR=1.97; 95% CI: 1.10-3.51) were independent predictors of cardiovascular events and deaths. Ambulatory ECG monitoring had no predictive value. Exercise testing and echocardiography performed early after coronary bypass surgery are able to identify high-risk patients who may benefit from intensive secondary prevention.

Circulating Levels of Tumor Necrosis Factor Correlate With Indexes of Depressed Heart Rate Variability : A Study in Patients With Mild-to-Moderate Heart Failure

Patients with heart failure have increased circulating levels of tumor necrosis factor (TNF) and TNF receptors. It is not known whether TNF, which is known to blunt beta-adrenergic responsiveness in experimental models, contributes to the loss of heart rate variability in patients with heart failure. Therefore, we examined heart rate variability in relation to circulating levels of TNF, TNF receptors, and norepinephrine in patients with heart failure and in control subjects. Heart rate variability was obtained from 24-h ambulatory ECG recordings in age-matched control subjects (n = 10) and patients with mild (n = 15) to moderate (n = 14) heart failure. Plasma levels of TNF and soluble type 1 and 2 TNF receptors were measured by enzyme-linked immunoassay; plasma norepinephrine levels were measured by high-performance liquid chromatography. There was a significant inverse linear correlation between increased circulating levels of TNF, TNF receptors, and norepinephrine for time-domain and frequency-domain indexes of heart rate variability among patients with heart failure and control subjects. Multiple stepwise linear regression analysis showed that TNF was a stronger independent predictor of frequency-domain indexes of heart rate variability than norepinephrine. TNF is an independent predictor of depressed heart rate variability in patients with heart failure. Insofar as TNF blunts beta-adrenergic signaling, this study suggests the possibility that overexpression of TNF and subsequent loss of beta-adrenergic responsiveness contributes to the decrease in heart rate variability observed in heart failure.

Simultaneous recording of blood pressure and ST-segment with combined, triggered ambulatory 24-h devices.

Silent myocardial ischemia is defined as an ischemic episode without chest pain but with transient ST abnormalities during stress testing or Holter monitoring. With Holter monitoring the prevalence of silent myocardial ischemia in hypertensive patients without coronary artery disease is between 25% and 73%. Simultaneous recording of ambulatory 24-h ECG and 24-h ambulatory blood pressure measurements (ABPM) with the option of additional ST-triggered blood pressure measurement is useful to detect silent ischemia and triggers of silent ischaemia. It is surprising that only a few combined 24-h Holter/ABPM devices are on the market, and in turn only three devices allow additional triggered blood pressure measurements. The paper provides an overview of studies investigating hypertensive patients with Holter monitoring for the detection of ST segment depression indicating myocardial ischaemia. Furthermore, requirements for combined devices allowing simultaneous ambulatory 24-h ECG and ABPM are defined.

Relationship between heart rate variability and left ventricular remodeling after reperfused first anterior wall acute myocardial infarction.

The aim of the present study was to test the hypothesis that inadequate improvement in heart rate variability (HRV) in the healing stage of acute myocardial infarction (AMI) is associated with left ventricular (LV) remodeling. The study group comprised 20 patients (14 men, 6 women; mean age, 61+/-12 years) with a reperfused first anterior AMI (</=24 h). The standard deviation of normal RR intervals (SDNN) was calculated from the 24-h ambulatory electrocardiogram recorded on day 3 of admission and at predischarge from the hospital. Left ventriculography was performed immediately after primary angioplasty and at predischarge. The change in SDNN (deltaSDNN) was compared with the change in the LV end-systolic volume index (deltaLVESVI), a parameter of LV remodeling. SDNN increased from 73+/-19 ms on day 3 to 109+/-35 ms at predischarge (p=0.0003). SDNN at predicharge and deltaSDNN correlated negatively with deltaLVESVI (r=-0.52, p=0.02, and r=-0.61, p=0.004, respectively), whereas SDNN on day 3 did not correlate with deltaLVESVI. Multiple regression analysis selected deltaLVESVI (p=0.02) as an independent factor of deltaSDNN. This study indicates that deltaSDNN and SDNN at predicharge are associated with deltaLVESVI in patients with a reperfused first anterior wall AMI, indicating that persistently reduced HRV is associated with postinfarction LV remodeling.

Long-term clinical significance of frequent and complex ventricular tachyarrhythmias in trained athletes

ObjectivesThe aim of this study was to clarify the clinical relevance of ventricular tachyarrhythmias assessed by 24-h ambulatory electrocardiograms (ECG) in a large, unique, and prospectively evaluated athletic population. BackgroundFor athletes with ventricular tachyarrhythmias, the risk of sudden cardiac death associated with participation in competitive sports is unresolved. MethodsWe assessed 355 competitive athletes with ventricular arrhythmias (VAs) on a 24-h ambulatory (Holter) ECG that was obtained because of either palpitations, the presence of ≥3 premature ventricular depolarizations (PVDs) on resting 12-lead ECG, or both. ResultsAthletes were segregated into three groups: Group A with ≥2,000 PVDs/24 h (n = 71); Group B with ≥100 <2,000 PVDs/24 h (n = 153); and Group C with only <100 PVDs/24 h (n = 131). Cardiac abnormalities were detected in 26 of the 355 study subjects (7%) and were significantly more common in Group A (21/71, 30%) than in Group B (5/153, 3%) or Group C athletes (0/131, 0% p < 0.001). Only the 71 athletes in Group A were excluded from competition. During follow-up (mean, 8 years), 70 of 71 athletes in Group A and each of the 284 athletes in Groups B and C have survived without cardiovascular events. The remaining Group A athlete died suddenly of arrhythmogenic right ventricular cardiomyopathy while participating in a field hockey game against medical advice. ConclusionsFrequent and complex ventricular tachyarrhythmias are common in trained athletes and are usually unassociated with underlying cardiovascular abnormalities. Such VAs (when unassociated with cardiovascular abnormalities) do not convey adverse clinical significance, appear to be an expression of “athlete’s heart syndrome,” and probably do not per se justify a disqualification from competitive sports.

Effects of athletic training on heart rate variability triangular index.

The purpose of this study was to assess the heart rate variability triangular index (HRVI) in elite track and field athletes. Sixty healthy males (mean aged 22.1 +/- 3.5 years) -15 long distance runners (group A), 15 speed runners (Group B), 15 throwers (Group C) and 15 non-trained subjects (Group D) were submitted to spiroergometric test, m-mode echocardiography and 24-h ambulatory ECG monitoring. The HRVI, mean heart rate, mean interval between two consecutive R waves of the QRS complexes (R-R interval) and standard deviation of the R-R (SDRR) were assessed through time domain method on computed 24-h Holter recordings. The HRVI and the SDRR were 62.2 +/- 9.6 and 220 +/- 40 ms correspondingly in group A, 52.7 +/- 6.0 and 210 +/- 40 ms in B, 44.5 +/- 5.3 and 180 +/- 40 ms in C, 39.3 +/- 6.4 and 180 +/- 30 ms in D. The HRVI and the mean R-R were found to differ statistically between groups A, B and C versus D (P < 0.05). However, the higher value in HRVI was found in group A. Maximal oxygen consumption (VO2max) was 62.0 +/- 4.4 ml kg-1 min-1 in group A, 52.7 +/- 6.0 in group B, 44.6 +/- 5.3 in C and 41.6 +/- 6.0 in D. The higher value in VO2max was also found in group A. The left ventricular mass index (LVMI) and end-diastolic volume index (EDVI) were 136 g m-2 and 83 ml m-2 correspondingly in group A, 136 and 79 in B, 124 and 56 in C and 88 and 55 in group D. The HRVI was found to have a significant relationship with VO2max and EDVI only in group A. On the other hand, no significant relationships were found between HRVI and LVMI in all groups. It is concluded, that the enhanced HRVI in athletes is affected by exercise training pattern. Moreover, HRVI depends on the level of VO2max in endurance-trained, but is independent from the extent of myocardial hypertrophy in all types of training.

Genotype-phenotype assessment in autosomal recessive arrhythmogenic right ventricular cardiomyopathy (Naxos disease) caused by a deletion in plakoglobin

OBJECTIVESThe purpose of this study was to examine the genotype-phenotype relation with respect to penetrance, age and severity of expression, disease progression and prognosis in a recessively inherited arrhythmogenic right ventricular cardiomyopathy (ARVC).BACKGROUNDNaxos disease is a recessively inherited ARVC caused by a mutation in the gene encoding plakoglobin (cell adhesion protein) in which the cardiac phenotype is associated with palmoplantar keratoderma and woolly hair.METHODSTwelve families with Naxos disease underwent cardiac and molecular genetic investigation. Serial cardiac assessment with annual resting 12-lead and 24-h ambulatory electrocardiogram (ECG) and two-dimensional echocardiography was performed during 1 to 16 years, median 7 ± 6 years in all 78 surviving members.RESULTSTwenty-eight surviving members were homozygous and 40 were heterozygous for the mutation. All adults who were homozygous (n = 26) fulfilled the diagnostic criteria for ARVC, the youngest by the age of 13 years. In eight who were heterozygous, minor ECG or echocardiographic abnormalities were observed. Of the 26 subjects who were affected homozygotes, 92% showed ECG abnormalities, 92% ventricular arrhythmias, 100% right ventricular structural alterations and 27% left ventricular involvement. During follow-up (10 ± 6 years), 16 (62%) developed structural progression, 12 (46%) arrhythmic events and 7 (27%) heart failure. The annual disease-related and sudden death mortality was 3% and 2.3%, respectively.CONCLUSIONSAutosomal recessive ARVC caused by a mutation in plakoglobin was 100% penetrant by adolescence. Affected subjects who were homozygous experienced progressive disease with adverse prognosis. A minority of subjects who were heterozygous showed minor ECG/echocardiographic changes, but clinically significant disease did not develop.

Heart rate variability in hypertrophic obstructive cardiomyopathy: association with functional classification and left ventricular outflow gradients

Background: The aim of this study was to investigate cardiac autonomic control in patients with hypertrophic obstructive cardiomyopathy (HOCM) and to assess the indexes of heart rate variability (HRV) in relation to the clinical and echocardiographic features. Methods and results: Twenty-three patients (17 male, six female: mean age 43±11) with HOCM and 18 healthy volunteers were included. M-mode and two-dimensional echocardiography, pulsed and continuous-wave Doppler studies were obtained. All patients and volunteers underwent continuous 24-h ambulatory ECG monitoring. Time domain variables considered in this study were standard deviation of mean R–R intervals (SDNN), root mean-squared successive difference (RMSSD) and percentage of cycles differing from the preceding one by more than 50 ms (PNN 50%). Patients were compared to detect associations between indices of heart rate variability, left ventricular outflow tract obstruction and clinical status. Heart rate variability parameters were also correlated with the echocardiographic and clinical characteristics of the patients. Both New York Heart Association (NYHA) functional class I–II patients (group I) and NYHA III–IV patients (group II) had lower values of SDNN, RMSSD and PNN 50% when compared with the control group ( P<0.001, P<0.05 and P<0.01, respectively, for group I and P<0.001, P<0.001 and P<0.001, respectively, for group II). Time domain heart rate variability parameters were found to be significantly correlated with the subaortic dynamic obstruction. Conclusion: Heart rate variability is reduced in HOCM and well correlated with the degree of subaortic obstruction. Heart rate variability indices are also sensitive markers of the functional status.

Seasonal variation in 1/f fluctuations of heart rate in asthmatic children

We have reported previously that asthmatic children have a seasonal variation in the power spectrum in the low frequency, LF (0.04-0.15 Hz) and high frequency, HF (0.15-0.6 Hz) bands of heart rate variability (HRV). In recent years, the I/f fluctuations of heart rate (HR) have been used as a novel index of autonomic function from a chronobiological viewpoint. As asthma is a disease with symptoms affected by seasonal chronobiological changes, we examined whether the I/f fluctuations of HR in asthmatic children changed by season. The subjects examined were 87 asthmatic and 104 healthy children. Using a Holter recorder, a 24-h ambulatory electrocardiogram (AECG) was obtained from each subject. The I/f fluctuations of HR during the time awake, the time asleep, and the 24-h period for each of the four seasons were analyzed by the MemCalc system (Suwa Trust). No seasonal variations of HR I/f fluctuations were detected in either the asthmatic or the control group for any of the three periods analyzed. There was a significant seasonal variation in the mean of the normal-to-normal R-R intervals during the 24-h period in the asthmatic children, but not in the healthy children. In the children with asthma, although their HR varied by season, the I/f fluctuations of HR did not.

Entacapone and selegiline with L-dopa in patients with Parkinson's disease: an interaction study.

Both the catechol-O-methyltransferase (COMT) inhibitor entacapone and the monoamine oxidase B (MAO-B) inhibitor selegiline are L-dopa extenders. Both are used, often simultaneously, as adjuncts to L-dopa/dopa decarboxylase (DDC) inhibitor treatment of Parkinson's disease (PD). Their possible interactions have not been previously studied in a double-blind manner.We studied clinical response, tolerability, haemodynamics and cardiac rhythm in 16 PD patients with end-of-dose-type motor fluctuations. The patients' individual L-dopa/DDC inhibitor treatment was stabilized before the experimental treatments. This was followed by three consecutive, randomized, double-blind 2-week treatment periods with entacapone (200mg with each L-dopa dose), selegiline (10mg o.d.) or both entacapone and selegiline with the L-dopa/DDC inhibitor medication. Clinical efficacy (L-dopa test with repeated motor and dyskinesia scoring) and safety (orthostatic test, 24-h ambulatory ECG, haematological and clinical chemistry variables and adverse events) evaluations were performed before each treatment (control) and at the end of each treatment period.All three treatments, entacapone, selegiline, and entacapone+selegiline as adjunct to L-dopa/DDC inhibitor improved (p<0.05) clinical disability compared to L-dopa only but they did not differ significantly from each other. Dyskinesias increased with all the treatments, statistically significantly (p<0.01) with entacapone+selegiline. No significant differences in haemodynamics were observed between control and any of the experimental treatments, or between the experimental treatments in the orthostatic test. One patient already had symptomatic orthostatism before experimental treatments (control). In two other patients orthostatism emerged after the introduction of selegiline, and in one after every experimental treatment. Twenty-four-hour ECG did not show any differences in supraventricular or ventricular extrasystoles or heart rate between treatments. No statistically significant differences were observed in adverse events or in haematology and clinical chemistry variables. One patient treated with entacapone+selegiline discontinued the study due to dizziness and insomnia. Our results suggest that co-administration of entacapone with L-dopa/DDC inhibitor, with or without selegiline, improves clinical disability, is safe, but may also enhance dopamine-related adverse events to some extent in PD patients with end-of-dose type motor fluctuations.