Cardiac electrophysiology in diabetes.

Patients with diabetes mellitus are at higher risk of cardiac arrhythmias and sudden death. Although there are several animal and human studies on this topic, the pathophysiology of the increased electrical vulnerability in diabetes is complex and remain undefined. It is conceivable that an interplay of several concomitant factors may facilitate the occurrence of arrhythmias. Atherosclerosis as well as microvascular disease, which are increased in diabetic patients, may facilitate myocardial ischemia that predisposes to cardiac arrhythmias and sudden death. In addition, autonomic neuropathy and/or cardiac repolarization abnormalities such as prolonged QT interval and altered T-waves of the diabetic heart also increases electrical instability. Therefore, all these factors may simultaneously contribute to create an electrical instability leading to cardiac arrhythmias and sudden cardiac death. Recently, we have demonstrated that diabetes is the strongest predictor of atrial fibrillation (AF) progression and that diabetic patients frequently have asymptomatic episodes of AF with silent arrhythmia progression. Another recent study has reported that patients with type 2 diabetes and AF are at substantially higher risk of death of any cause compared with those without AF. These seminal studies emphasize that AF in diabetic patients should be regarded as a prognostic marker of adverse outcome and then a prompt aggressive management of all risk factors is required. In conclusion, diabetes mellitus significantly alters the cardiac electrophysiology throughout several complex mechanisms greatly contributing to create an electrical instability of the heart, which may lead to potentially life-threatening arrhythmias and sudden cardiac death.

Circumferential radiofrequency ablation of pulmonary vein ostia: A new anatomic approach for curing atrial fibrillation.

BACKGROUND: The pulmonary veins (PVs) and surrounding ostial areas frequently house focal triggers or reentrant circuits critical to the genesis of atrial fibrillation (AF). We developed an anatomic approach aimed at isolating each PV from the left atrium (LA) by circumferential radiofrequency (RF) lesions around their ostia. METHODS AND RESULTS: We selected 26 patients with resistant AF, either paroxysmal (n=14) or permanent (n=12). A nonfluoroscopic mapping system was used to generate 3D electroanatomic LA maps and deliver RF energy. Two maps were acquired during coronary sinus and right atrial pacing to validate the lateral and septal PV lesions, respectively. Patients were followed up closely for >/=6 months. Procedures lasted 290+/-58 minutes, including 80+/-22 minutes for acquisition of all maps, and 118+/-16 RF pulses were deployed. Among 14 patients in AF at the beginning of the procedure, 64% had sinus rhythm restoration during ablation. PV isolation was demonstrated in 76% of 104 PVs treated by low peak-to-peak electrogram amplitude (0. 08+/-0.02 mV) inside the circular line and by disparity in activation times (58+/-11 ms) across the lesion. After 9+/-3 months, 22 patients (85%) were AF-free, including 62% not taking and 23% taking antiarrhythmic drugs, with no difference (P:=NS) between paroxysmal and permanent AF. No thromboembolic events or PV stenoses were observed by transesophageal echocardiography. CONCLUSIONS: Radiofrequency PV isolation with electroanatomic guidance is safe and effective in either paroxysmal or permanent AF.

Atrial electroanatomic remodeling after circumferential radiofrequency pulmonary vein ablation: efficacy of an anatomic approach in a large cohort of patients with atrial fibrillation.

BACKGROUND: Circumferential radiofrequency ablation around pulmonary vein (PV) ostia has recently been described as a new anatomic approach for atrial fibrillation (AF). METHODS AND RESULTS: We treated 251 consecutive patients with paroxysmal (n=179) or permanent (n=72) AF. Circular PV lesions were deployed transseptally during sinus rhythm (n=124) or AF (n=127) using 3D electroanatomic guidance. Procedures lasted 148+/-26 minutes. Among 980 lesions surrounding individual PVs (n=956) or 2 ipsilateral veins with close openings or common ostium (n=24), 75% were defined as complete by a bipolar electrogram amplitude <0.1 mV inside the lesion and a delay >30 ms across the line. The amount of low-voltage encircled area was 3594+/-449 mm(2), which accounted for 23+/-9% of the total left atrial (LA) map surface. Major complications (cardiac tamponade) occurred in 2 patients (0.8%). No PV stenoses were detected by transesophageal echocardiography. After 10.4+/-4.5 months, 152 patients with paroxysmal AF (85%) and 49 with permanent AF (68%) were AF-free. Patients with and without AF recurrence did not differ in age, AF duration, prevalence of heart disease, or ejection fraction, but the LA diameter was significantly higher (P<0.001) in permanent AF patients with recurrence. The proportion of PVs with complete lesions was similar between patients with and without recurrence, but the latter had larger low-voltage encircled areas after radiofrequency (expressed as percent of LA surface area; P<0.001). CONCLUSIONS: Circumferential PV ablation is a safe and effective treatment for AF. Its success is likely due to both PV trigger isolation and electroanatomic remodeling of the area encompassing the PV ostia.

Further observations on the electrophysiologic effects of oral amiodarone therapy.

A case is presented of a reversible intra-Hisian block occurring under amiodarone treatment for atrial tachycardia in a patient without clear intraventricular conduction abnormalities. His bundle recordings showed an atrial tachycardia with intermittent exit block and greatly prolonged BH and HV intervals (40 and 100 msec, respectively). Thirty days after amiodarone discontinuation, His bundle electrograms showed atrial flutter without intra-Hisian or infra-Hisian delay. Amiodarone should be used with caution during long-term oral therapy in patients with or without clear intraventricular conduction defects.

Effects of flecainide and propafenone on systolic performance in subjects with normal cardiac function.

Flecainide and propafenone are effective in suppressing both ventricular and supraventricular tachyarrhythmias, but their efficacy is often limited by dose-related side effects. This study was performed to evaluate noninvasively the effects of intravenous flecainide and propafenone on left ventricular systolic function indices in a selected population of 40 subjects (28 men and 12 women; mean age, 25 years) with normal cardiac structure and performance. Echocardiographic indexes of global systolic pump function (ejection fraction [EF] and percentage of fractional shortening [percent FS]) as well as monodimensional parameters of the intraventricular septum (IVS) and left ventricular posterior wall (PW) contractility (percent systolic thickening [percent th] and systolic excursion [ex]) were assessed in all subjects at baseline, immediately after, and in the early recovery (15 min) after randomized injection of either flecainide or propafenone. Heart rate and blood pressure did not significantly change after both drugs. A significant increase (p < 0.001) in left ventricular systolic internal diameter was observed after both flecainide and propafenone; simultaneously a significant decrease of percent FS (p < 0.001), EF (p < 0.001), PW percent thickening (th) (p < 0.001), and PWex (p < 0.001 after flecainide and p < 0.01 after propafenone) was recorded. These changes were comparable and promptly reversible. In analyzing individual data, a marked systolic dysfunction was observed in two patients after intravenous flecainide (percent FS from 37 percent to 17 percent and from 42 percent to 13 percent; EF from 55 percent to 40 percent and from 65 percent to 35 percent, respectively) and in one patient after intravenous propafenone (percent FS from 30 percent to 15 percent; EF from 58 percent to 35 percent). We conclude that both intravenous flecainide and propafenone exhibit mild negative inotropic effects leading to a moderate and reversible reduction of left ventricular systolic performance; however, in some cases, a dramatic impairment of systolic pump function may occur, suggesting careful use of both drugs as first-line agents also in normal subjects; finally, the true incidence of this deleterious effect is still unknown.

Sick sinus syndrome: the role of hypervagotonia.

A 58-year-old man with persistent symptomatic sinus bradycardia (52 beats/min) showed a markedly prolonged postpacing pause (3240 msec) after atrial pacing at a cycle of 840 msec. In addition, Wenckebach block occurred following atrial pacing at a cycle length of 700 msec. After atropine (2 mg) postpacing pauses returned to normal value and type 1 second-degree AV block completely reversed to 1:1 AV conduction until paced rates greater than 140/min. It may be that in some patients marked and persistent vagal overactivity may predispose to "intrinsic" sinus node dysfunction; in later stages, sinus node function may paradoxically result unaffected by changes in autonomic tone.

Sustained polymorphous ventricular tachycardia and the atropine test.

Atropine was used to diagnostic purposes in a 58-year-old man who presented with sinus bradycardia. The patient suffered immediate polymorphous ventricular tachycardia which persisted for 3 mins. External synchronized cardioversion established sinus rhythm and the subsequent hospital course was uneventful.

Ventricular parasystole and ventricular couplets: a re-entry within the parasystolic focus?

We report a 62-year-old man with a persistent ventricular rhythm originating in a parasystolic focus associated with frequent ventricular couplets with fixed coupling. Both intravenous (IV) procainamide (1 g) and propafenone (70 mg IV) promptly suppressed only the second component of ventricular couplets, suggesting that re-entry rather than enhanced automaticity was the mechanism of ventricular couplets. On the contrary, the nonresponse of ventricular rhythm and ventricular couplets to verapamil (10 mg IV) suggested that triggered activity should not play a role in the genesis of this ventricular rhythm. The mechanisms of the ventricular couplets (rapidly discharging parasystolic focus vs. re-entry) are discussed.

Paroxysmal supraventricular tachycardia: experience with propafenone.

The authors studied the efficacy of intravenous (IV) (1.5-2 mg/kg) and oral propafenone (450 to 900 mg/day) in 16 patients with paroxysmal, sustained, recurrent supraventricular tachycardia (SVT). In 5 patients IV propafenone was not given, because of intolerant SVT. Nine patients had Wolff-Parkinson-White syndrome. IV propafenone immediately stopped and prevented reinduction of SVT in 9/11 patients. Oral propafenone prevented SVT induction in 3 of 5 patients. In the 9 patients responsive to IV propafenone, oral propafenone was effective: in particular, in 6 patients SVT tachycardia was not induced by serial transesophageal pacings, and in the remaining 3 patients the arrhythmia was still induced but was slower and of brief duration (3-5 seconds). In 11/12 patients responsive to oral propafenone the minimum effective dosage in preventing the induction of the arrhythmia was 600 mg/day. In only 1 patient was the dose of 450 mg/day equally effective. Propafenone administration was not associated with major side effects. In conclusion, propafenone is very effective in the control of paroxysmal supraventricular tachycardia; intravenous propafenone can predict the efficacy of oral therapy.

Phase image analysis in Wolff-Parkinson-White syndrome. Role of transesophageal pacing.

Phase image analysis (first Fourier harmonic transformation) has been performed in 5 men with WPW syndrome to define the abnormal patterns of ventricular emptying during sinus rhythm and transesophageal pacing at different rates. All patients but one showed basal ventricular preexcitation. Of the 4 patients with basal ventricular preexcitation the earliest ventricular emptying occurred in the left ventricular free-wall in 1 patient and in the right ventricular free-wall in 3 patients. In the patient without ventricular preexcitation at rest transesophageal pacing at a rate of 100 bpm induced first ventricular activation in the left lateral ventricular free-wall while at a rate of 120 bpm it returned to normal. In the patients with ventricular preexcitation at rest, the basal image abnormalities become more evident as preexcitation was augmented. Of interest, in 1 patient with basal type B ventricular preexcitation the sequential phase image analysis, at a rate of 100 bpm confirmed the earliest ventricular activation in the right ventricular free-wall while at a rate of 120 bpm showed the earliest emptying in left ventricular free-wall suggesting the presence of 2 accessory connections. We conclude that phase mapping combined with transesophageal pacing may be a useful and reliable method to localize single as well as multiple accessory pathways in patients with ventricular preexcitation.

[The short PR syndrome: sino-atrial block with preservation of sino-nodal conduction]. / Syndrome du PR court. Bloc sino-auriculaire avec intégrité de la conduction sino-nodale.

From among the theories which have been advanced to explain the finding on ECG of a shorter than normal PR interval, in addition to the short circuit theory we should mention the explanation given by Condorelli before the first publication on the "short PR-normal QRS" syndrome appeared. While studying the mechanism of conduction of a stimulus in the atrial myocardium, he showed that a short PR may result from a conduction defect in the sino-atrial pathways, while sino-nodal conduction remains normal. In this report there is an example which supports the validity of Condorelli's hypothesis. It involves a female patient with mitral valve disease beginning to affect the tricuspid. Her rheumatic disease had just relapsed, and after this there was a long period of attacks of tachycardia with arrhythmia during the course of which the surface electrocardiogram showed a short PR and normal QRS. Electrophysiological investigations allowed us to interpret these findings in the light of Condorelli's hypothesis (sino-atrial block with normal sino-nodal conduction). This study suggests that it is useful to separate off those cases with a short PR and normal QRS to a clinical entity of their own, as this syndrome may have a different pathogenesis. Therefore, if there is no electrocardiographic evidence of an accessory pathway, far from indicating accelerated conduction, the short PR may be due to an isolated defect of conduction in the atrial myocardium, as Condorelli suggested. It is also correct that this author should be given credit for describing the first cases. To him also should go credit for first describing the short PR.

Heart failure. The pacing therapy.

Several medical therapies, including digoxin, angiotensin-converting enzyme inhibitors, and beta-blockers, have reduced the number of re-hospitalizations and slowed the progression of congestive heart failure (CHF) improving survival. Despite these benefits, medical therapy frequently fails to improve quality of life. Since 1990, there has been a growing interest in using cardiac pacing as additional treatment in severe CHF. Biventricular pacing is used in CHF patients with left bundle branch block (LBBB) to improve ventricular activation sequence which may lead to a more coordinated and efficient ventricular contraction. Since its introduction in CHF in 1994, biventricular pacing has been widely applied with many clinical trials and the development of new specific technology. With the development of new technology, the left ventricular catheterization via a coronary sinus vein, increased from 56% to over 95% during the last 2 years with an acceptable number of complications. Despite encouraging acute and short-term results, pacing strategies for CHF are still limited and currently regarded as investigational. It is clear that while some patients respond remarkably, this is high variable. Clinical trials are currently underway to assess the impact of cardiac resynchronization therapy on morbi-mortality and to assess the association with ventricular defibrillation. The whole validation process of cardiac resynchronization therapy should be completed on 2004-2005. Another novel mode of pacing therapy, which may be clinically appropriate for a broader range of CHF patients irrespective of the presence of LBBB, is contractility modulation, which involves sub-threshold pacing to increase intracellular calcium and enhance inotropy.

Cardiac pacing in heart failure patients with left bundle branch block: impact of pacing site for optimizing left ventricular resynchronization.

BACKGROUND: Acute left ventricular pacing has been associated with hemodynamic improvement in patients with congestive heart failure and wide QRS complex. We hypothesized that pacing two left ventricular sites simultaneously would produce faster activation and better systolic function than single-site pacing. METHODS: We selected 14 heart failure patients (NYHA functional class III or IV) in normal sinus rhythm with left bundle branch block and QRS > 150 ms. An 8F dual micromanometer catheter was placed in the aorta for measuring +dP/dt (mmHg/s), aortic pulse pressure (mmHg), and end-diastolic pressure (mmHg). Pacing leads were positioned via coronary veins at the posterior base and lateral wall. Patients were acutely paced VDD at the posterior base, lateral wall, and both sites (dual-site) with 5 atrioventricular delays (from 8 ms to PR -30 ms). Pacing sequences were executed in randomized order using a custom external computer (FlexStim, Guidant CRM). RESULTS: Dual-site pacing increased peak +dP/dt significantly more than posterior base and lateral wall pacing. Dual-site and posterior base pacing raised aortic pulse pressure significantly more than lateral wall pacing. Dual-site pacing shortened QRS duration by 22 %, whereas posterior base and lateral wall pacing increased it by 2 and 12%, respectively (p = 0.006). CONCLUSIONS: In heart failure patients with left bundle branch block, dual-site pacing improves systolic function more than single-site stimulation. Improved ventricular activation synchrony, expressed by paced QRS narrowing, may account for the additional benefit of dual- vs single-site pacing in enhancing contractility. This novel approach deserves consideration for future heart failure pacing studies.

Pulmonary vein isolation by circumferential radiofrequency lesions in atrial fibrillation. From substrate to clinical outcome.

Circumferential ablation around pulmonary vein ostia by CARTO system was performed in 98 patients with paroxysmal and 29 with permanent atrial fibrillation (AF). Preablation and postablation activation, propagation and voltage maps were obtained. A total of 135 +/- 18 radiofrequency pulses were delivered. After a follow-up of 14.7 +/- 3.3 months, 84 patients with paroxysmal and 22 with chronic AF are in sinus rhythm and 75 of them without antiarrhythmics. Only the area extent of low voltage potentials within and just around the lesions distinguished patients with and without successful ablation. Pulmonary vein isolation is an effective procedure to cure resistant AF; the extent of lesion area around pulmonary vein ostia may be crucial in predicting the outcome.

[Prospects of the treatment of atrial fibrillation. Circumferential radiofrequency ablation of pulmonary vein ostia]. / Prospettive nel trattamento della fibrillazione atriale. L'ablazione circonferenziale in radiofrequenza degli osti delle vene polmonari.

The dominance of the left atrium (LA) in the pulmonary vein (PV) regions for triggering and maintaining atrial fibrillation (AF) is now widely recognized. Radiofrequency (RF) PV isolation with electroanatomical guidance has recently emerged as a promising approach for AF treatment. We report the clinical outcome of the procedure in 251 consecutive patients with paroxysmal (n = 179) or permanent (n = 72) AF. Circular RF lesions were deployed transseptally during sinus rhythm or AF at 5 mm from PV ostia. Procedural and mapping times were 112 +/- 32 min and 75 +/- 27 min, respectively, with 29 +/- 11 min of fluoroscopy. Complete lesions (peak-to-peak bipolar electrogram amplitude < 0.1 mV inside the line and no double potentials) were achieved in 85% of the veins treated. Sinus rhythm was restored during RF delivery in 52% and by DC shock in the remaining. Major complications (cardiac tamponade) occurred in 3%. Extent of ablated area was 4.9 +/- 0.5 cm2, accounting for 28 +/- 9% of the total LA map surface. After 11 +/- 5 months, procedure success rates (freedom from AF without antiarrhythmic drugs) were 85% for paroxysmal and 68% for permanent AF. No PV stenoses were detected. By univariate analysis, an increased risk of recurrence was predicted by LA dilation (diameter > 50 mm), AF duration, and a low ablated area (< 15% of total LA surface). After adjustment, only the latter variable continued to be significant (odds ratio 3.5, 95% confidence interval, 1.6-5.8). In conclusion, RF PV isolation is safe and effective in either paroxysmal or permanent AF. Patients with enlarged left atrium may require wider lesions to achieve AF suppression.