Massimo Mantica

Delayed afterdepolarizations elicited in vivo by left stellate ganglion stimulation.

Activation of cardiac sympathetic nerves is recognized as a triggering factor for cardiac arrhythmias. However, the mechanisms involved have only been speculated. Because evidence from studies in vitro has established a relation between catecholamines, delayed afterdepolarizations (DAD), and triggered rhythms, it seemed possible that in vivo adrenergic activation also might lead to the development of DAD. Because very little evidence was available for DAD in vivo, we have evaluated whether monophasic action potential (MAP) recording with a contact electrode could be a suitable technique for the detection of DAD from the endocardium of anesthetized cats. In six animals, atrial pacing and graded aortic constriction were performed during MAP recording to assess MAP stability during hemodynamic changes, and in no cases were modifications of the baseline observed. In 11 cats, calcium gluconate (0.5 g) and G-strophanthin (100 micrograms) were administered. Action potential duration at 50% (APD50) and 90% (APD90) repolarization were reduced (from 138 +/- 16 to 122 +/- 18 msec, p less than 0.02, and from 163 +/- 23 to 149 +/- 20 msec, p less than 0.025, respectively). In eight of 11 (73%) animals, DAD were elicited with a mean amplitude of 1.2 +/- 0.4 mV. In 14 cats, the left stellate ganglion was stimulated for 45 seconds. APD50 and APD90 decreased (from 153 +/- 15 to 145 +/- 16 msec, p less than 0.005, and from 176 +/- 18 to 165 +/- 13 msec, p less than 0.001, respectively). DAD were induced in 10 of 14 animals (71%) with a mean amplitude of 1.2 +/- 0.3 mV. These results show that DAD can be induced in vivo by administration of calcium and digitalis and by activation of the cardiac sympathetic nerves. This latter finding further strengthens the existing link between adrenergic activation and ventricular arrhythmogenesis and suggests triggered activity as a likely mechanism.

Pulmonary Vein Vestibule Ablation for the Control of Atrial Fibrillation in Patients with Impaired Left Ventricular Function

Introduction: Congestive heart failure (CHF) and atrial fibrillation (AF) are frequently linked, and when associated produce additive deleterious effects. In this prospective study, the effects of catheter ablation for AF in patients with impaired left ventricular (LV) function are presented.

Baroreflex sensitivity, but not heart rate variability, is reduced in patients with life-threatening ventricular arrhythmias long after myocardial infarction

Low values of heart rate variability (HRV, a marker of vagal tone) and baroreflex sensitivity (BRS, a marker of vagal reflexes) identify patients at higher risk soon after myocardial infarction (MI). However, it is still unknown whether HRV and BRS correlate with malignant arrhythmias after the recovery from the transient post-MI autonomic disturbance. This study assessed whether HRV and BRS would differ in patients with malignant ventricular arrhythmias occurring long after MI compared with those in a control population. Twenty-eight patients entered the study: 14 patients with episodes of sustained ventricular tachycardia or ventricular fibrillation occurring more than 1 year after MI, age (mean +/- SEM) 64 +/- 2 years, and left ventricular ejection fraction 34% +/- 3% (VT/VF group) were compared with 14 similar patients with no ventricular tachycardia (control group). Mean RR interval was not different in the two groups (844 +/- 37 msec in VT/VF and 892 +/- 24 msec in control group). Also, no difference was found in any time- or frequency-domain measure of heart rate variability. However, patients in the VT/VF group had a significantly lower baroreflex sensitivity compared with patients in the control group (4.2 +/- 0.5 vs 8.0 +/- 1.1 msec/mm Hg, p = 0.008). Thus BRS but not HRV was reduced in patients with life-threatening ventricular arrhythmias occurring long after MI. A persistent depression of vagal reflexes may play a role in the occurrence of malignant arrhythmias, and analysis of BRS may potentially be helpful in the identification of patients at high risk long after myocardial infarction.

Scopolamine increases vagal tone and vagal reflexes in patients after myocardial infarction

OBJECTIVES The goal of this study was to assess the hypothesis that transdermal scopolamine would increase vagal activity in patients after myocardial infarction. BACKGROUND In postmyocardial infarction patients, low heart rate variability and reduced baroreceptor reflex sensitivity are associated with increased mortality. Accordingly, there is an increasing interest in a mechanism for shifting the sympathovagal balance toward vagal dominance. METHODS The effects of transdermal administration of scopolamine on heart rate variability and baroreceptor reflex sensitivity were assessed in 20 patients (mean age 59 +/- 11 years) by pharmacologic washout 14 +/- 3 days after myocardial infarction. Heart rate variability and baroreceptor reflex sensitivity were measured 24 h after application of the scopolamine patch and compared with the values measured before scopolamine and after application of a placebo patch. The following variables were derived from a 15-min electrocardiographic recording: the mean RR interval and its standard deviation, the mean square successive difference, the percent of intervals differing > 50 ms from the preceding RR interval and the low and high frequency areas resulting from power spectral analysis. RESULTS The placebo patch had no effect on the variables measured. Scopolamine increased both heart rate variability and baroreceptor reflex sensitivity significantly. Specifically, the mean RR interval and its standard deviation increased by 7.1% (p = 0.01) and 25% (p = 0.004), respectively. The mean square successive difference increased by 38% (p = 0.0003) and the percent of intervals differing > 50 ms from the preceding interval by 100% (p = 0.001). The ratio of low to high frequency areas of the power spectrum decreased by 24% (p = 0.02), and baroreceptor reflex sensitivity increased by 42% (p = 0.0006). These effects were also evident in patients with very low initial values. Side effects were minimal. CONCLUSIONS Transdermal scopolamine increased measures of heart rate variability and baroreceptor reflex sensitivity in patients with a recent myocardial infarction toward values associated with a better prognosis. Pharmacologic modulation of the autonomic balance by scopolamine or related drugs deserves evaluation as a new and promising approach to reduce risk after myocardial infarction.

Is the Outcome of Cardiac Resynchronization Therapy Related to the Underlying Etiology

GASPARINI, M., et al.: Is the Outcome of Cardiac Resynchronization Therapy Related to the Underlying Etiology? This study was designed to examine the importance of the underlying cardiac pathology on outcome of cardiac resynchronization therapy (CRT), hypothesizing that myocardial infarction scar and other noncontractile segments represent limitations to the ability to resynchronize cardiac contraction in patients with congestive heart failure associated with dilated cardiomyopathy. From October 1999 to April 2002, 158 patients (mean age 65 years, 121 men) were included in a single center, longitudinal, comparative study. All patients had dilated cardiomyopathy and indications for CRT with a mean QRS duration of 174 ms. The patient population was divided into a coronary artery disease (CAD) group that included patients with significant CAD, and no indication, or a contraindication for revascularization, and a non‐CAD group that included patients with nonischemic dilated cardiomypopathy. Follow‐up data were collected at 3, 6, and 12 months, and yearly thereafter. The median follow‐up was 11.2 months. In the CAD group, the LVEF increased from 0.29 to 0.34 (P < 0.0001) , the 6‐minute walk test distance increased from 310 to 463 m (P < 0.0001) , and the percentage of patients in NYHA functional Class III–IV decreased from 83% to 23% (P = 0.04) . In the non‐CAD group, LVEF increased from 29% to 42% (P < 0.0001), the 6‐minute walk test distance increased from 332 to 471 m (P < 0.0001) , and the percentage of patients in NYHA functional Class III–IV decreased from 79% to 5%, (P < 0.0001) . Comparison of the two groups showed that patients in the non‐CAD group had a significantly greater increase in LVEF (P = 0.007) and decrease in NYHA class (P < 0.05) . Patients with CAD or non‐CAD significantly improved clinically during CRT. Non‐CAD patients had a greater increase in LVEF and decrease in NYHA functional class than patients with CAD. (PACE 2003; 26[Pt. II]:175–180)

Is the left ventricular lateral wall the best lead implantation site for cardiac resynchronization therapy

GASPARINI, M., et al.: Is the Left Ventricular Lateral Wall the Best Lead Implantation Site for Cardiac Resynchronization Therapy? Short‐term hemodynamic studies consistently report greater effects of cardiac resynchronization therapy (CRT) in patients stimulated from a LV lateral coronary sinus tributary (CST) compared to a septal site. The aim of the study was to compare the long‐term efficacy of CRT when performed from different LV stimulation sites. From October 1999 to April 2002, 158 patients (mean age 65 years, mean LVEF 0.29, mean QRS width 174 ms) underwent successful CRT, from the anterior (A) CST in 21 patients, the anterolateral (AL) CST in 37 patients, the lateral (L) CST in 57 patients, the posterolateral (PL) CST in 40 patients, and the middle cardiac vein (MCV) CST in 3 patients. NYHA functional class, 6‐minute walk test, and echocardiographic measurements were examined at baseline, and at 3, 6, and 12 months. Comparisons were made among all pacing sites or between lateral and septal sites by grouping AL + L + PL CST as lateral site (134 patients, 85%) and A + MC CST as septal site (24 patients, 15%). In patients stimulated from lateral sites, LVEF increased from 0.30 to 0.39 (P < 0.0001) , 6‐minute walk test from 323 to 458 m (P < 0.0001) , and the proportion of NYHA Class III–IV patients decreased from 82% to 10% (P < 0.0001) . In patients stimulated from septal sites, LVEF increased from 0.28 to 0.41 (P < 0.0001) , 6‐minute walk test from 314 to 494 m (P < 0.0001) , and the proportion of NYHA Class III–IV patients decreased from 75% to 23% (P < 0.0001) . A significant improvement in cardiac function and increase in exercise capacity were observed over time regardless of the LV stimulation sites, either considered singly or grouped as lateral versus septal sites. (PACE 2003; 26[Pt. II]:162–168)

Beneficial Effects of Biventricular Pacing in Patients with a “Narrow” QRS

GASPARINI, M., et al.: Beneficial Effects of Biventricular Pacing in Patients with a “Narrow” QRS. Congestive heart failure (CHF) patients with LBBB and QRS duration >150 ms are considered the best candidates to biventricular pacing (Biv‐P). However, patients with a narrow (120–150 ms) QRS may also benefit from Biv‐P since true ventricular dyssynchrony may be underestimated by considering only QRS enlargement. From October 1999 to April 2002, 158 CHF patients (121 men, mean age 65 years, mean LVEF 0.29, mean QRS width 174 ms) underwent successful Biv‐P implantation and were then followed for a mean time of 11.2 months. According to basal QRS duration, patients were divided in two groups, with wide QRS (≥150 ms, 128 patients, 81%) and with narrow QRS (<150 ms, 30 patients, 19%). In the wide QRS group, LVEF improved from 29% to 39% (P < 0.0001), 6‐minute walk test from 311 to 463 m (P < 0.0001), while NYHA Class III–IV patients decreased from 86% to 8% (P < 0.0001). In the narrow QRS group LVEF improved from 30% to 38% (P < 0.0001), 6‐minute walk test from 370 to 506 m (P < 0.0001), and NYHA Class III–IV patients decreased from 60% to 0% (P < 0.0001). The data showed that in wide and narrow QRS patients, Biv‐P significantly improved clinical parameters (NYHA class, 6‐minute walk test, quality‐of‐life, and hospitalization rate) and main echocardiographic indicators. Furthermore, narrow QRS patients had a better survival rate, rapidly regained left ventricular function, and only a few patients remained in a higher NYHA class during follow‐up. These patients should not be excluded “a priori” from cardiac resynchronization therapy. (PACE 2003; 26[Pt. II]:169–174)

Flecainide Test in Brugada Syndrome: A Reproducible but Risky Tool

GASPARINI, M., et al.: Flecainide Test in Brugada Syndrome: A Reproducible but Risky Tool. The flecainide test is widely used in Brugada syndrome. However, its reproducibility and safety remain ill‐defined. This study included 22 patients (18 men, mean age 34 years). Mutations in the SCN5A gene were found in eight patients. Two patients had aborted sudden cardiac death, 8 had syncope/presyncope, and 12 were asymptomatic. The ECG was diagnostic in 19 patients and suggestive in 3. At baseline, 21 of 22 patients underwent a flecainide test (2 mg/kg IV bolus over 10 minutes). In 21 of 21 patients the test was diagnostic or amplified the typical ECG pattern. At the end of drug infusion, sustained VT lasting 7–10 minutes developed in two patients. A second flecainide test was performed within 2 months in 20 patients. The test was not repeated in the two patients with prior development of VT. The flecainide test was diagnostic in 20 of 20 patients. Sustained VT occurred in one patient and recurrent VF in another. The reproducibility of the flecainide test was 100%. In 4 (18%) of 22 patients major VAs were documented after the end of flecainide infusion. VA occurred in 3 (43%) of 7 patients with, versus 1 (7%) 15 without SCN5A gene mutation (P < 0.05). No diagnostic ECG changes or arrhythmias developed in 25 control patients without structural heart disease who underwent the same study protocol. This study shows a high flecainide reproducibility, supporting its diagnostic value in Brugada syndrome. However, the occurrence of major VA, significantly higher in patients with documented SCN5A gene mutation, including in asymptomatic patients, mandates the performance under appropriate medical supervision. Whether a slower rate of drug infusion can lower the risk of VA induction, while maintaining the sensitivity of the test should be explored. (PACE 2003; 26[Pt. II]:338–341)

Impaired Baroreflex Sensitivity Is Correlated With Hemodynamic Deterioration of Sustained Ventricular Tachycardia

OBJECTIVES The goal of this study was to evaluate clinical and autonomic variables (heart rate variability and baroreflex sensitivity) related to hemodynamic tolerability of VT in patients with sustained monomorphic VT and a healed myocardial infarction. BACKGROUND Sustained ventricular tachycardia (VT) with hemodynamic deterioration is associated with a worse prognosis than that of well tolerated VT. The causes of hemodynamic deterioration of VT are incompletely understood. METHODS Twenty-four consecutive patients with sustained monomorphic VT and a healed myocardial infarction (mean age +/- SD 66 +/- 8 years, left ventricular [LV] ejection fraction 37 +/- 11%) were assigned to group 1 if the VT was well tolerated (n = 11) or to group 2 if faintness or syncope occurred or if systolic blood pressure was < 90 mm Hg with clinical signs of shock (n = 13). RESULTS No difference was found between the two groups in age, LV function, rate and duration of the VT or heart rate variability. However, patients in group 2 had a significantly lower baroreflex sensitivity (3.4 +/- 1.1 vs. 7.1 +/- 3.7 ms/mm Hg, p = 0.003). Multiple logistic regression analysis showed that only the value of baroreflex sensitivity (p = 0.0003)-but not age, LV ejection fraction, VT cycle length or SD of the RR interval (all p > 0.25)-correlated with the tolerability of the VT. Finally, LV ejection fraction (p = 0.0001) and baroreflex sensitivity (p = 0.0003)-but not age, cycle length of the tachycardia or SD of the RR interval-predicted cardiac death or unstable VT during follow-up. CONCLUSIONS These data suggest that an impaired cardiovascular reflex response may play a key role in the hemodynamic deterioration of sustained VT and that the evaluation of baroreflex sensitivity in patients at high risk for sustained VT may become useful both in risk stratification and in the individualization of treatment.

Safety of Single Transseptal Puncture for Ablation of Atrial Fibrillation: Retrospective Study from a Large Cohort of Patients

Introduction: Transseptal puncture (TSP) is the conventional approach to assess the left atrial chamber. This technique has been widely used in interventional cardiology and, in the last years, this approach is mostly applied to electrophysiologic procedures. For atrial fibrillation (AF) ablation, two or more transseptal sheaths are often positioned in the left atrium in the majority of centers, therefore requiring two or more transseptal punctures. Theoretically, double puncture could bear additional risks or could increase the risk of persistence of septal defects. We reported the results of a retrospective analysis of a single transseptal puncture as a simplified approach for positioning multiple catheters in the left atrium during AF ablation.