Emmanuel M. Kanoupakis

Left Ventricular Function and Cardiopulmonary Performance Following Surgical Treatment of Morbid Obesity

Background: It is well established that morbid obesity affects the respiratory system and the diastolic function of the heart. During exercise, cardiopulmonary reserve is exhausted because of augmented requirements, leading to a significant intolerance. A study was undertaken to investigate the influence of body weight loss on the characteristics of the left ventricle (LV) and on exercise capacity in obese patients before and 6 months following vertical banded gastroplasty (VBG). Methods: 16 morbidly obese individuals (BMI >40 kg/m2) scheduled for VBG were studied. A symptomlimited cardiopulmonary exercise test and a complete transthoracic echocardiogram were performed 1 day before operation and 6 months postoperatively (after the patients achieved a body weight loss of ≥ 20% of their pre-operative values). Results: Exercise duration increased significantly 6 months following surgery.The mean O2 consumption at peak exercise (peak VO2) and at the anaerobic threshold (VO2AT) was significantly higher after weight loss. 6 months after VBG the LV thickness decreased significantly. Regarding the diastolic indices, isovolumic relaxation time (IVRT) and early/late (E/A) velocity ratio, there was a significant improvement after weight loss. Simple linear regression analysis revealed that peak VO2 and VO2AT were significantly correlated with IVRT and E/A velocity ratio. Conclusions: Weight loss after VBG improves the cardiac diastolic function and this is associated with an improvement in cardiopulmonary exercise performance. Left ventricular filling variables could be considered among the most important determinants of exercise intolerance in obese individuals.

Changes in atrial electrical properties following cardioversion of chronic atrial fibrillation: relation with recurrence

OBJECTIVE To study the reversibility of atrial electrical remodeling and its relation with recurrence in post-conversion chronic atrial fibrillation (CAF) patients. METHODS In 28 drug-free CAF patients (mean AF duration 41+/-39 months) electrically converted to sinus rhythm effective refractory period (ERP) at 500 ms, monophasic action potential at 90% of repolarization (MAPd90) at five cycle lengths (CL, 350, 400, 450, 500, 600 ms), and P wave duration were measured three times: within the interval 5-20 min post-conversion, 24 h and 1 month later. Fifteen subjects with no history of AF and normal atrial structure served as a control group. Patients were followed up for recurrence for 1 month; 12 relapsed. RESULTS ERP changed from 205+/-20 to 243+/-31 to 241+/-24 ms (P<0. 001), attaining a level comparable to that of the controls (238+/-21 ms) within 24 h. MAPd90 significantly (P<0.001) increased (from 175+/-11 to 190+/-19 to 191+/-10 ms at CL 350 ms and 201+/-12 to 234+/-20 and 233+/-23 ms at CL 600 ms) also reaching control levels within 24 h. MAPd90 exhibited an abnormal adaptation to rate only in the first evaluation. P wave duration was prolonged (137+/-33 ms) and exhibited a slower course of shortening (130+/-32 to 123+/-27 ms, P<0.001), reaching control levels within 1 month. Patients with higher values of MAPd90 at CL 350 in the immediate post-conversion period were more likely to relapse (P<0.005). CONCLUSIONS ERP and repolarization shortening as a result of CAF are reversed within 24 h after conversion, while P wave duration reduces more slowly. Post-conversion MAPd90 values contain prognostic information for recurrence.

Low-Dose Amiodarone Versus Sotalol for Suppression of Recurrent Symptomatic Atrial Fibrillation

To compare the safety and efficacy of amiodarone and sotalol in the treatment of patients with recurrent symptomatic atrial fibrillation (AF), 70 patients were entered into a randomized, double-blind study. Of these, 35 received amiodarone and 35 sotalol. There were no significant differences in baseline clinical characteristics between groups. Patients with ejection fraction < 40% or clinically significant heart disease were excluded. Patients randomized to amiodarone began with 800 to 1,600 mg/day for 7 to 14 days orally. After the initial loading phase, the drug dose was tapered to maintenance levels over 7 to 12 days; thereafter, therapy was generally maintained at a dosage of 200 mg/day. The sotalol dosage was 80 to 360 mg twice daily, as tolerated. Follow-up clinical evaluations were conducted at 1, 2, 4, 6, 9, and 12 months. The proportion of patients remaining in sinus rhythm on each agent was calculated for the 2 groups using the Kaplan-Meier method. Ten of the 35 patients who were taking amiodarone developed AF during the 12-month observation period, compared with 21 of the 35 who were taking sotalol (p = 0.008). No significant effect of sex, age, left atrial size, or type of AF could be detected that increased the risk of development of AF. We conclude that both amiodarone and sotalol can be used for the maintenance of normal sinus rhythm in patients with recurrent symptomatic AF but that amiodarone is the more effective of the 2 drugs for this purpose.

Extracellular Matrix Alterations in Patients With Paroxysmal and Persistent Atrial Fibrillation Biochemical Assessment of Collagen Type-I Turnover

OBJECTIVES We investigated whether the serum markers of collagen turnover differed in various forms of atrial fibrillation (AF) and in sinus rhythm (SR) in humans. BACKGROUND Structural alterations and fibrosis have been implicated in the generation and perpetuation of AF. METHODS Serum C-terminal propeptide of collagen type-I (CICP), C-terminal telopeptide of collagen type-I (CITP), matrix metalloproteinase-1, and tissue inhibitor of matrix metalloproteinases-1 were measured as markers of collagen synthesis and degradation in 70 patients with AF and 20 healthy control subjects in SR. RESULTS C-terminal propeptide of collagen type-I and CITP were significantly higher in AF patients than in control subjects (91 +/- 27 ng/ml vs. 67 +/- 11 ng/ml, p < 0.001 and 0.38 +/- 0.20 ng/ml vs. 0.25 +/- 0.08 ng/ml, p < 0.001, respectively). Persistent AF patients had higher levels of CICP (105 +/- 28 ng/ml vs. 80 +/- 21 ng/ml, p < 0.001), but not CITP, compared with those with paroxysmal AF. Patients with persistent AF had lower levels of matrix metalloproteinase-1 but increased levels of tissue inhibitor of matrix metalloproteinases-1 compared with patients with paroxysmal AF (11.90 +/- 4.79 ng/ml vs. 14.98 +/- 6.28 ng/ml, p = 0.03 and 155 +/- 45 ng/ml vs. 130 +/- 38 ng/ml, p < 0.001, respectively). Tissue inhibitor of matrix metalloproteinases-1 levels were significantly lower in control subjects compared with those in both paroxysmal and persistent AF patients (102 +/- 15 ng/ml vs. 130 +/- 38 ng/ml vs. 155 +/- 45 ng/ml, respectively, p < 0.001). CONCLUSIONS Serum markers of collagen type-I turnover differed significantly between patients with AF and SR. Furthermore, these markers also differed significantly between paroxysmal and persistent AF patients, suggesting that the intensity of the extracellular synthesis and degradation of collagen type-I may be related to the burden or type of AF.

Effects of Amiodarone and Diltiazem on Persistent Atrial Fibrillation Conversion and Recurrence Rates: A Randomized Controlled Study

AbstractPurpose: To assess the effects of amiodarone and diltiazem on atrial fibrillation (AF) induced atrial electrical remodeling and their clinical implications. Methods: Persistent AF patients were randomly assigned to three treatment groups over a period from 6 weeks before to 6 weeks after internal cardioversion: group A (35 patients, oral diltiazem), group B (34 patients, oral amiodarone) and group C (37 patients, no antiarrhythmic drugs). Several electrophysiological parameters were assessed 5 min and 24 h after cardioversion. Results: Compared with controls, group B patients had significantly higher conversion rates (83% vs. 100%, p = 0.041) and a higher probability to maintain sinus rhythm (p = 0.037). Patients of group B had longer fibrillatory cycle length intervals than patients of group A and C (180 ± 18 ms vs. 161 ± 17 ms vs. 164 ± 19 ms, p = 0.001) and longer atrial effective refractory periods (211 ± 22 ms vs. 198 ± 16 ms vs. 194 ± 17 ms, p = 0.003) as assessed 5 min after conversion. Post-conversion density of supraventricular ectopics was significantly lower in group B compared to groups A and C (p = 0.001). Conclusions: Oral amiodarone increases conversion rates, prolongs fibrillatory cycle length and atrial effective refractory period and preserves sinus rhythm after cardioversion in persistent AF patients by suppressing the atrial ectopics that trigger AF.

Serum Markers of Collagen Turnover Predict Future Shocks in Implantable Cardioverter-Defibrillator Recipients With Dilated Cardiomyopathy on Optimal Treatment

OBJECTIVES We investigated prospectively whether serum markers of collagen turnover could be used as predictors for the occurrence of malignant ventricular arrhythmias in patients with nonischemic dilated cardiomyopathy (NIDC) who had received an implantable cardioverter-defibrillator (ICD) for primary prevention. BACKGROUND Extracellular matrix alterations in NIDC might provide electrical heterogeneity, thus potentially contributing to the occurrence of ventricular arrhythmia and subsequent sudden cardiac death (SCD). METHODS Serum C-terminal propeptide of collagen type-I, C-terminal telopeptide of collagen type-I, matrix metalloproteinase (MMP)-1, and tissue inhibitor of MMP-1 were measured as markers of collagen synthesis and degradation in 70 patients with mild to moderate symptomatic heart failure due to NIDC with left ventricular ejection fraction <35%, who received an ICD for primary prevention of SCD. Patients were evaluated for any appropriate ICD delivered therapy, whether shock or antitachycardia pacing, during a 1-year follow-up period. RESULTS Appropriate device therapies were delivered in 14 of the 70 patients during the follow-up period, with antitachycardia pacing in 2, antitachycardia pacing with shocks in 4, and shocks in 8. Pre-implantation serum concentrations of C-terminal telopeptide of collagen type-I levels were significantly higher in patients who had appropriate ICD-delivered therapy than in those who did not have any therapy (0.46 +/- 0.19 ng/ml vs. 0.19 +/- 0.07 ng/ml, p < 0.001, respectively). The same was true for baseline MMP-1 and tissue inhibitor of MMP-1 (27.7 +/- 1.6 ng/ml vs. 24.1 +/- 2.5 ng/ml, p < 0.001, and 89 +/- 14 ng/ml vs. 58 +/- 18 ng/ml, p = 0.008, respectively). CONCLUSIONS If the maximum benefit is to be achieved from ICD therapy in NIDC patients for the primary prevention of SCD, a more precise risk stratification is required. As extracellular matrix alterations affect the arrhythmogenic substrate in NIDC, we observed that serum markers of collagen turnover could predict arrhythmic events in ICD recipients.

Effects of Weight Loss on QT Interval in Morbidly Obese Patients

Background: Obesity causes structural changes to the heart that may influence its function. Furthermore, morbid obesity is associated with an acquired prolongation of the QTc interval that may lead to potentially hazardous arrhythmias. The present study investigated the effect of body weight loss following vertical banded gastroplasty (VBG) on the QTc interval. Methods: 17 morbidly obese patients, scheduled for elective VBG, were studied before the operation and 8-10 months postoperatively, when each patient had achieved a weight loss of ≥ 25% of the preoperative body weight. Results: 15 patients achieved significant body weight loss of ≥ 25% within the first 8-10 postoperative months (P <0.001).This weight loss, corresponding to an excess weight loss of 48.7% and a mean body mass index (BMI) reduction from 49.7 kg/m2 to 36.6 kg/m2, was followed by significant shortening of the QTc interval from 428 msec to 393 msec (P <0.001). Conclusions: The significant postoperative weight loss following VBG was accompanied by shortening of the QTc interval. This effect is expected to reduce the incidence of fatal conditions associated with the long QT syndrome, such as malignant ventricular arrhythmias and sudden death, and therefore improve morbidity and mortality.

Reproducibility of tilt table testing in patients with vasovagal syncope and its relation to variations in autonomic nervous system activity.

To assess the variability of head‐ up tilt table testing, 35 patients with vasovagal syncope, shown by a positive tilt table test, underwent a second test 1 week later. Also, on the day before each test, spectral and time‐domain indexes of heart rate variability were derived from Holter recordings to examine the stability of autonomous nervous system activity in these patients. Fifteen healthy volunteers served as a control group and also underwent two tilt table tests with prior Holter monitoring. Twenty‐one (60%) of the 35 patients had a second positive test. None of the patients in the control group experienced syncope during either of the tests. The heart rate variability measures in the control group varied slightly from 1 day to the other, in contrast to the syncopal patients, where only low frequency spectral power and the mean of all 5‐minute standard deviations of RR internals showed comparable behavior. The indexes which reflect parasympathetic activity exhibited significant fluctuations in the syncopal patients. These fluctuations were due entirely to the patients who did not reproduce the outcome of the tilt table test, where high parasympa‐thetic tone was associated with the positive test and normal parasympathetic tone with the negative test. In contrast, the patients with two positive tests had high parasympathetic tone during both test periods, with low individual variability. In conclusion, patients with vasovagal syncope show variations in vagal autonomic tone and appear to be more prone to syncope when their parasympathetic tone is elevated.

Relation of autonomic modulation to recurrence of atrial fibrillation following cardioversion

The aim of this study was to investigate the time course of changes in autonomic nervous system activity in patients with long-standing atrial fibrillation (AF) following internal electrical conversion to sinus rhythm and to look for differences between patients who do and do not relapse. Time-domain indexes of heart rate variability were calculated from 24-hour Holter recordings on the day of conversion and 1 day and 1 month afterward for 22 patients with chronic (> 3 months) AF. Ten healthy subjects served as a control group. During the day of cardioversion the mean RR interval and its circadian variation differed significantly between controls and patients. The mean values of successive RR intervals that deviated by > 50% from the prior RR interval and the root-mean-square of successive RR interval differences--indexes of vagal modulation--were initially significantly higher in patients than in controls but showed a decrease (p < 0.05) by the second day (from 12.4 +/- 7% to 8.1 +/- 5% to 7.3 +/- 5% and from 49 +/- 9 to 39 +/- 12 to 41 +/- 11 ms, respectively) to levels similar to those of the controls (7.6 +/- 5% and 40 +/- 17 ms, respectively). Only these 2 indexes contained significant prognostic information about relapse: patients who later relapsed had higher initial values than those who did not, and these values remained high during the 2 days after conversion. In conclusion, this study provides data confirming that spontaneous chronic AF in humans results in a significant increase in vagal tone that is reversed with time after restoration of sinus rhythm. Persistently higher values of vagal tone are observed in patients who relapse, and are probably a predictor for recurrence.

Spectral analysis of heart rate variability during tilt-table testing in patients with vasovagal syncope.

Spectral analysis of heart rate variability was used to assess changes in autonomic function in 44 patients with vasovagal syndrome and 20 normal controls before and during postural tilt and to attempt to relate such changes to specific types of haemodynamic response to tilt. Frequency domain measurements of the high (HF) and low (LF) frequency bands and the ratio LF/HF were derived from Holter recordings, computed by Fast Fourier Analysis for 4 min intervals immediately before tilt testing, immediately after tilting and just before the end of the test. In the syncopal patients the mean values of LF and HF decreased significantly in response to tilting, while the LF/HF ratio remained constant. All parameters showed a statistically significant increase just before the onset of syncope. In the control group there was an increase in the LF and LF/HF ratio and a decrease in the HF immediately after tilting. The three subgroups of patients had similar patterns of changes in autonomic activity. The results of this study show that syncopal patients have a different pattern of response to the tilting test. The pathological mechanism leading to vasovagal syncope appears to be independent of the specific type of haemodynamic response to tilt testing.