Impact of ablation index settings on pulmonary vein reconnection.

PURPOSE: Ablation index (AI) is a radiofrequency lesion quality marker. The AI value that allows effective and safe pulmonary vein isolation (PVI) is still debated. We evaluated the incidence of acute and late PV reconnection (PVR) with different AI settings and its predictors. METHODS: The Ablation Index Registry is a multicenter study that included patients with paroxysmal/persistent atrial fibrillation (AF) who underwent first-time ablation. Each operator performed the ablation using his preferred ablation catheter (ThermoCool® SmartTouch or Surround Flow) and AI setting (380 posterior-500 anterior and 330 posterior-450 anterior). We divided the study population into two groups according to the AI setting used: group 1 (330-450) and group 2 (380-500). Incidence of acute PVR was validated within 30 min after PVI, whereas the incidence of late PVR was evaluated at repeat procedure. RESULTS: Overall, 490 patients were divided into groups 1 (258) and 2 (232). There was no significant difference in the procedural time, fluoroscopy time, and rate of the first-pass PVI between the two study groups. Acute PVR was observed in 5.6% PVs. The rate of acute PVR was slightly higher in group 2 (64/943, 6.8%, PVs) than in group 1 (48/1045, 4.6% PVs, p = 0.04). Thirty patients (6%) underwent a repeat procedure and late PVR was observed in 57/116 (49%) PVs (number of reconnected PV per patient of 1.9 ± 1.6). A similar rate of late PVR was found in the two study groups. No predictors of acute and late PVR were found. CONCLUSION: Ablation with a lower range of AI is highly effective and is not associated with a higher rate of acute and late PVR. No predictors of PV reconnection were found.

Changes in brain natriuretic peptide level as a predictor of AF recurrence after electrical cardioversion.

AIM: Early recurrence of atrial fibrillation (AF) is common after electrical cardioversion (ECV). Accurate prediction of AF recurrence might allow more selective use of ECV and the targeted use of antiarrhtyhmic therapy in those at highest risk of recurrence. METHODS: We have screened consecutive patients attending for cardioversion of AF and recruited those without valvular heart disease, heart failure or permanent pacemakers. All patients underwent echocardiography and measurement of serum BNP levels within 24 hours before ECV. Measurement of BNP was repeated at 1, 7, 30 and 90 days after ECV and an ECG recorded on each occasion. RESULTS: We have screened 24 consecutive patients. Five were excluded. All 19 study subjects were succesfully cardioverted to sinus rhythm. AF recurred in nine cases. Recurrence of AF was associated with AF duration, left atrial size, the presence of hypertension and the BNP level before cardioversion. BNP fell significantly after cardioversion. The BNP level after cardioversion was not associated with AF recurrence. CONCLUSION: Even in persons without valvular heart disease or heart failure, an elevated level of BNP predicts recurrence of AF after ECV. The level to which BNP falls after cardioversion is not predictive of AF recurrence.

Initial energy setting, outcome and efficiency in direct current cardioversion of atrial fibrillation and flutter.

OBJECTIVES: The purpose of this study was to design a more efficient protocol for the electrical cardioversion of atrial arrhythmias. BACKGROUND: Guidelines for electrical cardioversion of atrial arrhythmias recommend starting with low energy shocks, which are often ineffective. METHODS: We recorded the sequence of shocks in 1,838 attempts at cardioversion for atrial fibrillation (AF) and 678 attempts at cardioversion for atrial flutter. These data were used to calculate the probability of success for each shock of a standard series and the probability of success with a single shock at each intensity. In 150 cases, a rhythm strip with the time of each shock allowed us to calculate the time expended on unsuccessful shocks. RESULTS: We analyzed the effects of 5,152 shocks delivered to patients for AF and 1,238 shocks delivered to patients for atrial flutter. The probability of success on the first shock in AF of > 30 days duration was 5.5% at < 200 J, 35% at 200 J and 56% at 360 J. In atrial flutter, an initial 100 J shock worked in 68%. In AF of >30 days duration, shocks of < 200 J had a 6.1% probability of success; this fell to 2.2% with a duration >180 days. In those with AF for >180 days, the initial use of a 360 J shock was associated with the eventual use of less electrical energy than with an initial shock of < or =100 J (581 +/- 316 J vs. 758 +/- 433 J, p < 0.01, Mann-Whitney U test). CONCLUSIONS: An initial energy setting of > or =360 J can achieve cardioversion of AF more efficiently in patients than traditional protocols, particularly with AF of longer duration.

CD44V6 in gastric carcinoma: a marker of tumor progression.

CD44 is a group of cell surface molecules involved in cell-cell and cell-matrix interactions. CD44 spliced variants (CD44V) have been found to enhance the metastatic potential of rat tumors. Tumors from the breast, colon, and thyroid express many alternatively spliced products; nonneoplastic tissues do not. Some authors suggest that CD44V5 and V6 may play a role in gastric carcinoma. The aim of the current study was to investigate the role of CD44V6 as a prognostic marker and predictor of metastatic potential in gastric carcinomas. One hundred fifty-five cases of gastric adenocarcinomas were studied: 36 cases of early (EGC), 19 cases of intermediate (MGC), and 100 cases of advanced gastric adenocarcinomas (AGC). A monoclonal antibody against CD44V6 (R&D) was used. CD44V6 expression was positively correlated with advanced stage (P = 0.05). Strong positivity was only detected in those cases of AGC with metastases. Patients with CD44V6 positive tumors revealed a lower 3- and 5-year survival rate (P = 0.0002). Immunohistochemical detection of CD44V6 could now be used as an indicator of tumor progression in biopsies of patients with gastric carcinoma.

Failure of magnesium to protect isolated cardiomyocytes from effects of hypoxia or metabolic poisoning.

BACKGROUND: MgSO4 appears to reduce infarct size in animal models of myocardial infarction-reperfusion, but only if given before reperfusion. The mechanisms underlying this effect have not been established, nor has the discrepancy between these results and the lack of efficacy in the Fourth International Study of Infarct Survival (ISIS-4) been explained. HYPOTHESIS: The study was undertaken to examine the hypothesis that Mg2+ protects myocardium threatened by ischemia. METHODS: We studied the effects of extracellular magnesium [Mg2+](e) at 0.6 and 1.8 mmol/l on isolated myocytes exposed to 2.5 mmol/l NaCN + 5 mmol/l 2-deoxyglucose or to profound hypoxia. RESULTS: Nonpaced cells shortened at a mean of 8.8 min after onset of metabolic inhibition in [Mg2+](e) = 1.8 mmol/l, 9.6 min in [Mg2+](e) = 0.6 mmol/l (not significant). Paced cells shortened after 9.5 min in [Mg2+](e) = 1.8 mmol/l, 10.2 min at [Mg2+](e) = 0.6 mmol/l. On washout of inhibitors, 93% of cells underwent hypercontracture at [Mg2+](e) = 1.8 mmol/l, 94.8% at [Mg2+](e) = 0.6 mmol/l. During hypoxia, nonpaced cells in [Mg2+](e) = 1.8 mmol/l shortened after 67 +/- 11 min compared with 62.5 +/- 28 min at [Mg2+](e) = 0.6 mmol/l. Paced cells shortened after 25.8 +/- 12.9 min at [Mg2+](e) = 1.8 mmol/l and after 28.7 +/- 13.6 min at [Mg2+]e = 0.6 mmol/l. Although there was a trend toward longer survival at higher [Mg2+](e), the difference was small and not significant (p > 0.05, Student's paired t-test). CONCLUSION: We find no evidence to support the hypothesis that [Mg2+] protects myocardium threatened by ischemia. This is consistent with clinical data but contradicts data from animal experiments.

Consistency of multicenter measurements of heart rate variability in survivors of acute myocardial infarction.

Heart rate variability (HRV) analysis from 24-hour ambulatory ECG has been widely used in risk stratification of patients after myocardial infarction (MI). The accuracy of HRV assessment is known to potentially vary when different commercial systems are used. However, the consistency of HRV measurements has never been fully investigated. Twenty-six post-MI patients (mean age 59 +/- 8 years, 22 men) were studied, of whom 13 succumbed to sudden cardiac death (SCD) within 1 year and 13 remained alive for at least 3 years (MI survivors). Each patient had a 24-hour Holter ECG recorded before hospital discharge. HRV analysis was performed four times from the same recordings using three different Holter tape analysis systems (Marquette, Reynolds, and CardioData) by four independent operators (CardioData system was used twice, once in the United Kingdom and once in the United States). Mean normal-to-normal RR intervals (mNN) and 3 HRV parameters (SDNN, RMSSD, and HRV triangular index [HRVi]) were derived from each recording. The consistency of mNN and HRV measurements was evaluated by coefficient of variance (CV) and by the Bland-Altman method. The results demonstrated that (1) all indices measured by different systems were statistically similar (P = NS) except the measurement of RMSSD (P = 0.01), (2) the measurements of mNN were highly reproducible with a maximum mean difference of 1.8 +/- 13.8 ms and maximum limits of agreement from -14.6 to +15.6 ms. The maximum mean differences were--1.8 +/- 1.4 unit and 4.4 +/- 9.6 ms for HRVi and SDNN, respectively, and RMSSD was less reproducible with a maximum mean difference of--11.1 +/- 11.5 ms, and limits of agreement from -16.2 to +9.6 ms; and (3) the consistency of mNN (CV 0.9% +/- 0.9%) was significantly higher than that of HRVi, SDNN, and RMSSD (P < 0.0001). The consistency of HRVi was similar to that of SDNN (4.8% +/- 2.1% vs 5.7% +/- 4.8%, P = 0.4), and the consistency of RMSSD (26.6% +/- 13.3%) was significantly lower than that of the other measurements (P < 0.00001). In conclusion, the measurements of mNN by different analytical systems are the most consistent among the parameters studied. The global 24-hour measurements of HRV (SDNN and HRVi) are highly reproducible, whereas the measurement of short-term HRV components (RMSSD) is significantly less reproducible.

Effect of moderate physical exercise on noninvasive cardiac autonomic tests in healthy volunteers.

BACKGROUND: In addition to the assessment of extreme cardiovascular reserve, new methodology is needed which is sensitive enough to detect subtle improvement in cardiovascular fitness in cardiac patients. AIM: This study modelled subtle clinical improvement by a moderate physical activity programme in healthy volunteers and investigated whether the improved fitness is detectable by non-invasive tests of cardiac autonomic status. METHODS: Twenty healthy volunteers (ten women, mean age 39.6+/-7.8 years) were divided into two groups of five women and five men in each. One group (the active group) was subjected to a moderate physical training programme for 6 months. The other group (the passive group) served as controls and continued with a predominantly sedentary lifestyle. Twice before commencing the exercise programme and regularly afterwards, subjects were investigated by a series of non-invasive autonomic tests including controlled respiration, active postural change, isometric handgrip, and Valsalva manoeuvre. A continuous three lead semi-orthogonal electrocardiogram and continuous blood pressure monitoring was obtained. Statistical descriptors of heart rate and blood pressure, spectral descriptors of their modulation, and baroreflex index giving the proportion between simultaneous heart rate and blood pressure changes were obtained from each test. RESULTS: Although the exercise programme was not extensive enough to be detected in changes of the baseline heart rate, the minimum RR interval during the Valsalva manoeuvre prolonged significantly with exercise in the active group. The mean arterial diastolic pressure decreased significantly. High frequency components of RR interval modulations decreased in supine controlled respiration and increased in standing controlled respiration and a trend towards an increase of both high frequency and low frequency components of diastolic arterial pressure modulations was noted with exercise. Baroreflex index assessed from Valsalva manoeuvre increased significantly. CONCLUSION: The study suggests that a selected set of non-invasive autonomic tests is sensitive enough to depict moderate improvement in cardiovascular fitness and that a multivariate assessment of cardiovascular fitness based on these tests might be applicable to monitoring chronic cardiac patients subjected to different clinical management modes.

Comparison of formulae for heart rate correction of QT interval in exercise electrocardiograms.

The study investigated the differences in five different formulae for heart rate correction of the QT interval in serial electrocardiograms recorded in healthy subjects subjected to graded exercise. Twenty-one healthy subjects (aged 37+/-10 years, 15 male) were subjected to graded physical exercise on a braked bicycle ergometer until the heart rate reached 120 beats/min. Digital electrocardiograms (ECG) were recorded on baseline and every 30 seconds during the exercise. In each ECG, heart rate and QT interval were measured automatically (QT Guard package, Marquette Medical Systems, Milwaukee, WI, USA). Bazett, Fridericia, Hodges, Framingham, and nomogram formulae were used to obtain QTc interval values for each ECG. For each formula, the slope of the regression line between RR and QTc values was obtained in each subject. The mean values of the slopes were tested by a one-sample t-test and the comparison of the baseline and peak exercise QTc values was performed using paired t-test. Bazett, Hodges, and nomogram formulae led to significant prolongation of QTc intervals with exercise, while the Framingham formula led to significant shortening of QTc intervals with exercise. The differences obtained with the Fridericia formula were not statistically significant. The study shows that the practical meaning of QT, interval measurements depends on the correction formula used. In studies investigating repolarization changes (e.g., due to a new drug), the use of an ad-hoc selected heart rate correction formula is highly inappropriate because it may bias the results in either direction.

Optimum lead positioning for recording bipolar atrial electrocardiograms during sinus rhythm and atrial fibrillation.

BACKGROUND: To date, Holter monitoring has been predominantly utilized in the investigation and monitoring of ventricular arrhythmias and myocardial ischemia. Whether currently employed lead configurations are optimal for recording atrial electrocardiograms (ECGs) is unknown. HYPOTHESIS: This study was undertaken to determine which conventional and novel lead configurations are optimal for recording atrial electrical activity during sinus rhythm and atrial fibrillation. METHODS: Recordings were performed on eight healthy volunteers in sinus rhythm and four patients in atrial fibrillation. Each subject had 10 ECGs of three bipolar and three augmented unipolar leads recorded during supine rest, while rising to upright, and during standing rest, yielding a total of 60 leads (30 bipolar leads). Each tracing was inspected by two observers, and parameters such as P-wave amplitude and duration, whether the P-wave onset was clearly seen, atrial fibrillatory-wave amplitude, and amplitude of noise during standing were scored. RESULTS: Leads recording inferiorly and leftward orientated bipoles provided the best registration of sinus P waves. The P-wave amplitude in the standard bipolar C5 lead (0.12 +/- 0.02 mV) was, however, inferior to others such as recordings between C1 and C6 positions (P-wave amplitude 0.16 +/- 0.02 mV) or from below the right clavicle to the left upper quadrant of the abdomen (0.16 +/- 0.01 mV). Optimal recording of fibrillatory waves was from different leads, such as a bipole from below the left clavicle to a low C1 position (fibrillatory wave amplitude 0.27 +/- 0.03 mV). CONCLUSION: When Holter recordings are performed for the investigation of atrial arrhythmias, nonstandard lead configurations provide superior recording of atrial electrical activity. We advocate the use of electrodes positioned from C1 to C6, from below the left clavicle to a low C1 position, and a vertically orientated lead from the manubium to the twelfth vertebra or the xiphisternum.

Classification of atrial fibrillation.

Atrial fibrillation (AF) is the subject of several overlapping schemes of classification in which the subgroups are often poorly defined. New methods of classification have been applied to accommodate new information and new concepts. These are often appropriate only in limited circumstances and may lead to confusion if applied out of context. We will describe the principal schemes used to classify AF and discuss the limitations of each.

Evolution of changes in the ventricular rhythm during paroxysmal atrial fibrillation.

Changes in the RR interval within episodes of paroxysmal atrial fibrillation (PAF) have not been fully characterized. A database of 177 24-hour Holter recordings were created from patients with PAF in the CRAFT studies. PAF episodes of > or = 1 minute duration containing < or = 20% noise and preceded by > or = 1 minute of sinus rhythm with < or = 20% noise were selected. Sections of each AF episode containing 10 and 25 RR intervals were identified at the onset, middle, and termination of each episode. Descriptive characteristics (mean, SD, and RMSSD of RR intervals) were calculated within each section, and compared using a nonparametric, paired Wilcoxon test. In 25 patients (17 men, 60.6 +/- 12.2 years old), 231 episodes from 44 recordings met the selection criteria. The mean RR interval increased slightly between the onset and mid-portion of AF episodes (565.9 +/- 128.3 vs 580.3 +/- 144.7 ms, P < 0.001). The RR interval at the termination of AF was significantly greater than that at the start (627.1 +/- 156.1 vs 565.9 ms, P < 10-11) or mid-portion (627.1 +/- 156.1 vs 580.3 +/- 144.7 ms, P < 10-13). SD of the RR interval increased significantly between onset and mid-portion (111.1 +/- 60.2 vs 118.2 +/- 66.7 ms, P < 0.001) and more substantially between mid-portion and termination (118.2 +/- 66.7 vs 201.8 +/- 93.7 ms, P < 10-21). During paroxysms of AF, the mean RR interval and the variability of RR intervals increases. Termination of a paroxysm is preceded by a marked increase in RR interval variability.

Rapid recurrence of pulmonary hypertension following cessation of nifedipine.

In a young woman with primary pulmonary hypertension, treatment with low-dose nifedipine resulted in resolution of symptoms and of tricuspid regurgitation. On withdrawal of nifedipine, symptomatic pulmonary hypertension recurred within 48 hours and was controlled by reintroduction of low-dose nifedipine.

Circadian variation of the QT interval in patients with sudden cardiac death after myocardial infarction.

To evaluate the potential prognostic value of the circadian variation of QT intervals in predicting sudden cardiac death (SCD) in patients after myocardial infarction (MI), 15 pairs of post-MI patients (15 died suddenly within 1 year after MI [SCD victims] and 15 remained event-free [MI survivors]) were studied (mean age 60 +/- 8 years; 24 men and 6 women). The pairs were matched for age, gender, infarct site, presence of Q wave, left ventricular ejection fraction, thrombolytic and beta-blocker therapy. Fourteen normal subjects served as controls (mean age 55 +/- 9 years; 12 men). A 24-hour Holter electrocardiographic (ECG) recording was obtained from each subject. All recordings were analyzed using a Holter ECG analyser. QT, RR, and heart rate-corrected QT intervals (QTc) were automatically calculated by the analyzer, and hourly and 24-hour mean values of each measurement were derived from each recording. There was a pronounced circadian variation in the QT interval in parallel with the trend in the RR interval in normal subjects and in MI survivors. Circadian variation in both indexes was blunted in SCD victims. The QT interval was significantly longer at night than during the day in normal subjects (388 +/- 28 vs 355 +/- 21 ms, p = 0.001) and in MI survivors (358 +/- 25 vs 346 +/- 15 ms, p = 0.008), but not in SCD victims (357 +/- 32 vs 350 +/- 31 ms, p = 0.6). The 24-hour mean value of the QT interval in SCD victims did not differ significantly from that in normal subjects or MI survivors. The QT interval at night was significantly shorter in SCD victims than in normal subjects (357 +/- 32 vs 388 +/- 28 ms, p = 0.02), but daytime values were similar. The QT interval in SCD victims did not differ significantly from that of MI survivors at any time. The QTc interval exhibited a small circadian variation in normal subjects. This variation was abolished in SCD victims and MI survivors. The 24-hour mean value of QTc was significantly longer in SCD victims than in normal subjects (424 +/- 25 vs 402 +/- 21 ms, p = 0.02), and in MI survivors (424 +/- 25 vs 404 +/- 32 ms, p < 0.05). The QTc interval of SCD victims differed from that of normal subjects during both the day (421 +/- 25 vs 400 +/- 17 ms, p = 0.02) and night (424 +/- 26 vs 403 +/- 23 ms, p = 0.03). Thus, blunted circadian variation in QT intervals, abolished circadian variation in QTc intervals, and prolonged QTc intervals may suggest an increased risk of SCD in patients after MI.

Tachycardia-induced atrial myopathy: an important mechanism in the pathophysiology of atrial fibrillation?

The atrial myocardium of patients with chronic atrial fibrillation (AF) is often abnormal in its histologic features and in its electrophysiologic properties. These abnormalities have been interpreted in some cases as the cause of AF and in others as a consequence of AF. We believe that both are the case. We will review the features of this atrial myopathy and discuss the likely mechanisms and consequences of the process.

Long-term management of atrial fibrillation.

In the past decade, catheter ablation techniques and implantable devices have revolutionized the treatment of ventricular arrhythmias, junctional arrhythmias, and atrial flutter. For most patients presenting with atrial fibrillation (AF), the treatment available today is similar to that used a century ago, although nonpharmacologic strategies of therapy have begun to emerge for selected cases. There have been important recent advances in our understanding of the pathophysiology of AF and its complications, and it may be possible to improve patient management by refinement of the way in which current drugs are used.