Preferred QT Correction Formula for the Assessment of Drug‐Induced QT Interval Prolongation

Drug‐Induced QTc Interval Assessment. Introduction: There is debate on the optimal QT correction method to determine the degree of the drug‐induced QT interval prolongation in relation to heart rate (ΔQTc). Methods: Forty‐one patients (71 ± 10 years) without significant heart disease who had baseline normal QT interval with narrow QRS complexes and had been implanted with dual‐chamber pacemakers were subsequently started on antiarrhythmic drug therapy. The QTc formulas of Bazett, Fridericia, Framingham, Hodges, and Nomogram were applied to assess the effect of heart rate (baseline, atrial pacing at 60 beats/min, 80 beats/min, and 100 beats/min) on the derived ΔQTc (QTc before and during antiarrhythmic therapy). Results: Drug treatment reduced the heart rate (P < 0.001) and increased the QT interval (P < 0.001). The heart rate increase shortened the QT interval (P < 0.001) and prolonged the QTc interval (P < 0.001) by the use of all correction formulas before and during antiarrhythmic therapy. All formulas gave at 60 beats/min similar ΔQTc of 43 ± 28 ms. At heart rates slower than 60 beats/min, the Bazett and Framingham methods provided the most underestimated ΔQTc values (14 ± 32 ms and 18 ± 34 ms, respectively). At heart rates faster than 60 beats/min, the Bazett and Fridericia methods yielded the most overestimated ΔQTc values, whereas the other 3 formulas gave similar ΔQTc increases of 32 ± 28 ms. Conclusions: Bazett's formula should be avoided to assess ΔQTc at heart rates distant from 60 beats/min. The Hodges formula followed by the Nomogram method seem most appropriate in assessing ΔQTc. (J Cardiovasc Electrophysiol, Vol. 21, pp. 905‐913, August 2010)     

Atrial Fibrillatory Electrogram Measurement Allows Atrial Lead Placement in Patients Who Develop Atrial Fibrillation During Permanent Dual Chamber Pacemaker Implantation

The benefit of DDD(R) pacing is proven even in patients with intermittent atrial fibrillation. Atrial fibrillation developing during dual chamber pacemaker implantation creates a difficult problem. Maneuvers to reestablish a stable atrial rhythm often are required if atrial fibrillation sets in. This study was performed to determine if atrial lead placement can be performed with acceptable long-term results in the presence of atrial fibrillation. Twenty-one patients in whom atrial fibrillation developed during permanent pacemaker implantation were included in this study. In 12 patients, episodes of intermittent atrial fibrillation had been documented before the procedure. Screw-in leads were used in 15 patients and J-shaped passive fixation leads in 6 patients. AH leads were bipolar. The intraoperative atrial fibrillation electrogram amplitudes ranged from 0.9 to 3.2 mV (mean 1.8 ± 0.6 mV). One patient required lead revision due to a high atrial pacing threshold after conversion to SR. One patient remained in atrial fibrillation at 3-month follow-up. The other 20 patients converted to SR, 11 of whom had intermittent atrial fibrillation with successful mode switch activation. P wave amplitudes were 2.8 ± 6 mV (range 1.4 to 4.0 mV) after conversion to SR. The mean atrial pacing threshold was 1.1 ± 0.5 V (range 0.5 to 3.5 V). Placement of atrial leads in patients who develop atrial fibrillation during pacemaker implantation is feasible; fibrillatory electrogram amplitudes showed a good correlation with the atrial signal after conversion to an organized atrial rhythm (r = 0.698). Acceptable atrial pacing thresholds can be expected as well.     

Ranolazine as a Promising Treatment Option for Atrial Fibrillation: Electrophysiologic Mechanisms,Experimental Evidence,and Clinical Implications

Currently available agents for pharmacologic management of atrial fibrillation (AF) are limited by their suboptimal efficacy and nonnegligible proarrhythmic risk. Ranolazine (RN) is a novel antianginal agent with increasingly appreciated antiarrhythmic properties that can suppress ventricular and supraventricular arrhythmias including AF. In this review, we describe the electrophysiological properties of RN, focusing on atrial‐selective inhibition of a number of ion channels implicated in the development of AF, particularly the sodium current. We further summarize evidence from experimental studies that demonstrate a potent AF‐suppressing effect of RN, alone or in combination with other antiarrhythmic drugs. Of clinical relevance, we present growing evidence from preliminary clinical investigations indicating the safety and efficacy of RN for prevention and treatment of AF in various clinical settings including prevention of AF in patients with acute coronary syndromes, prevention and conversion of postoperative AF after surgical coronary revascularization, sinus rhythm maintenance in drug‐resistant recurrent AF, and facilitating of electrical or pharmacological cardioversion in cardioversion‐resistant patients. While current experimental and clinical evidence points to RN as a potentially promising agent for suppression of AF, well‐designed, large‐scale trials will be required before RN can be considered for pharmacological treatment of AF in clinical practice.     

Complications of Atrial Fibrillation Ablation in a High‐Volume Center in 1,000 Procedures: Still Cause for Concern?

Introduction: Catheter ablation is potentially curative treatment for atrial fibrillation (AF). However, complications are more frequent and more severe compared with other ablation procedures. We investigated the complication rate in 1,000 AF ablation procedures in a high-volume center and examined possible risk factors.
Methods and Results: One thousand consecutive circumferential pulmonary vein radiofrequency ablations were performed for symptomatic, drug-refractory AF. Major complications were defined as the ones that were life threatening, caused permanent harm, and required intervention or prolonged hospitalization. Thirty-nine (3.9%) major periprocedural complications were observed. There was no death immediately associated with the procedure. However, there were 2 deaths (0.2%) of unclear cause, 14 days and 4 weeks after ablation. The most common complications were tamponade (1.3%), treated mainly by percutaneous drainage, and vascular complications (1.1%). There were also 4 thromboembolic events (0.4%): 3 nonfatal strokes and one transient ischemic attack. Importantly, 2 cases (0.2%) of atrial-esophageal fistula and 2 cases (0.2%) of endocarditis were observed. Factors associated with an increased complication risk were age ≥75 years (hazard ratio 3.977, P = 0.022) and congestive heart failure (hazard ratio 5.174, P = 0.001).
Conclusion: AF ablation still has a considerable number of major complications that may be life threatening or may lead to severe residues. Atrial-esophageal fistula is still observed despite continuous systematic methods to prevent it. Stroke, tamponade, and vascular complications are the most frequent major complications. However, in most patients treatment can be conservative and results in complete recovery. Advanced age and congestive heart failure seem to be associated with an increased risk of complications.     

Study of Late Potentials and Ventricular Arrhythmias in Hypertensive Patients with Normal Electrocardiograms

Introduction: Although an increase in the occurrence of ventricular arrhythmias has been observed in hypertensive patients, some basic questions remain unresolved regarding the prevalence and the pathophysiology of these arrhythmias. The basic aims of this study were as follows: (1) to examine the incidence and severity of ventricular arrhythmias in a substantial number of hypertensive patients without electrocardiographic indications of hypertrophy; and (2) to examine the correlation between late potentials, hypertrophy, and ventricular arrhythmias in these patients. Materials and Methods: We studied 78 consecutive patients (31 men, 47 women), aged 60.5 ± 7.8 years, with a history of hypertension but a normal electrocardiogram. All patients had an echocardiographic study, 24-hour ambulatory monitoring, exercise test, and signal-averaged electrocardiogram. The latter was analyzed using a 40-to 250-Hz filter and with a noise level ± 0.3 μV. Results: Of the 78 patients studied, 21 (26.9%) had severe ventricular arrhythmias, while 57 (73.1 %) had either no ventricular ectopics or sporadic isolated ventricular extrasystoles. Left ventricular hypertrophy, defined by echocardiography, was found in 58 patients (74.3%), of which 16 (27.58%) had severe ventricular arrhythmias. Five (25%) of the 20 patients without hypertrophy also had severe ventricular arrhythmias (P = NS). Ventricular late potentials were recorded in 19 (24.5%) of the 78 patients. Of these, 11 (57.89%) had severe arrhythmias, while of the 59 patients without late potentials 10 (16.94%) had severe ventricular ectopic activity. Conclusions: In hypertensive patients without electrocardiographic signs of hypertrophy, the higher prevalence of ventricular arrhythmias does not appear to be related to left ventricular hypertrophy but is correlated with the existence of ventricular late potentials.     

Placement of Intracoronary Stents Mounted on "Over the Wire" Balloon Catheters Without Using Long Guidewires

The aim of this study is to investigate the feasibility, effectiveness, and safety of placement of intracoronary stents mounted on "over the wire" balloon catheters without using long guidewires. Fifteen consecutive patients underwent GR II stent placement. Over the wire balloon catheters and short guidewires were used. The new method was successful in 14 of 15 cases. No complications were observed. This novel technique using a short (instead of long) guidewire to place intracoronary stents mounted on over the wire balloon catheters was successful, and more convenient. (J Interven Cardiol 2000; 13:27–30)     

Bcl‐2 protein and DNA ploidy in renal cell carcinoma: Do they affect patient prognosis?

AIM: The aim of the present study was to correlate bcl-2 protein expression and DNA-ploidy status with established prognostic parameters in renal cell carcinoma (RCC) and to examine their impact on disease progression and patient survival. METHODS: Both parameters were prospectively measured in 50 consecutive radical nephrectomy specimens using flow cytometry. They were correlated with the tumor grade, stage and histological type. Kaplan-Meier survival analysis for all parameters was performed. RESULTS: Bcl-2 protein expression was higher in RCC compared to normal renal tissue (P < 0.0001). Aneuploid tumors had higher bcl-2 expression compared to diploid tumors (P = 0.015). Bcl-2 expression and DNA content were not correlated with tumor histological types (P = 0.277/P = 0.419), grades (P = 0.690/P = 0.449), T categories (P = 0.637/P = 0.585) or stages (P = 0.726/P = 0.800). Median follow-up time was 46 months (range, 5-84) with a mean overall survival of 61.8 months (95% confidence interval, 53.7-69.9). Tumor stage was the only statistically important prognostic factor (P = 0.0045). CONCLUSION: Although Bcl-2 expression was correlated with tumor DNA content, the prognostic value of these two parameters following radical nephrectomy was not established.     

Pacing within the Ischemic Area Significantly Decreases the Left Ventricular Ejection Fraction during Experimental Acute Myocardial Infarction

Background: The aim of this study was to examine the effects on left ventricular (LV) function of LV apical or/and lateral wall pacing during an experimental acute myocardial infarction. Methods: In 12 anesthetized pigs, epicardial LV pacing at the apex or lateral wall, or at both sites simultaneously, was performed before and after left anterior descending (LAD) ligation. Data concerning LV function were obtained by two‐dimensional echo during spontaneous sinus rhythm (SR) and during pacing before and 15, 45, 60, and 90 minutes after LAD ligation. Results: Before ligation of the LAD, pacing at the lateral wall (48.04 ± 6.25%) or both sites (45.71 ± 6.31%) reduced the LV ejection fraction (EF) significantly (P < 0.01) in comparison to SR (55.44 ± 4.10%). However, during pacing at the apex (50.19 ± 6.50%), the reduction was not significant. After LAD ligation, the EF during lateral pacing (43.02 ± 7.71%) was significantly higher than during apical pacing (38.78 ± 8.26%, P < 0.04) but was not significantly different from that during dual‐site pacing (41.65 ± 8.69%). Conclusions: Pacing within the ischemic LV apical zone after LAD ligation impairs left ventricular ejection fraction, as compared with pacing the nonischemic LV lateral wall, and should therefore be avoided in clinical settings where the LV pacing site may be chosen. (PACE 2011; 63–71)     

Monitoring Persistent Platelet Reactivity in Patients with Unprotected Left Main Stenting

Objective

This study sought to determine the rate and potential clinical impact of persistent platelet reactivity (PPR) in unprotected left main (ULMD) stenting.

Background

PPR under aspirin or thienopyridines is associated with acute events after angioplasty.

Methods

We prospectively included 125 patients referred for ULMD stenting. For the first 64 patients (ALMA‐1), angioplasty was performed under aspirin and clopidogrel without platelet reactivity assessment. For the last 61 patients (ALMA‐2), platelet reactivity was assessed before angioplasty: in patients with aspirin‐related PPR, aspirin twice daily was given and in those with clopidogrel‐related PPR, clopidogrel double dose or prasugrel was used.

Results

Overall, patients' mean age was 69 ± 13 years, 37% were diabetic, and 37% had non‐ST segment elevation myocardial infarction (NSTEMI). Patients' characteristics were similar in both studies with isolated left main in 14% and associated with 1‐, 2‐, or 3‐vessel disease in 23%, 36%, and 27%, respectively. Mean SYNTAX score was 23 ± 9. Procedural characteristics were similar using provisional T stenting in 69%, T stenting in 27%, and other techniques in 4%. In ALMA‐2, 28% patients had PPR for aspirin, 29% for clopidogrel, and 8% for both. Aspirin twice daily was given in 28% of patients, clopidogrel double dose in 26%, and prasugrel in 31%. The rate of 1‐year major adverse cardiovascular and cerebrovascular events (MACCE) was lower in ALMA‐2 versus ALMA‐1 (8.2% vs. 20.8%; P = 0.04) as a composite end‐point of cardiovascular death or stent thrombosis (0.0% vs. 8.3%; P = 0.02).

Conclusion

PPR under aspirin and thienopyridines is frequent in ULMD stenting and could be related to subsequent major events.

     

Atrial Septal Pacing to Synchronize Atrial Depolarization in Patients with Delayed Interatrial Conduction

The current method of pacing the right atrium from the appendage or free wall is often the source of delayed intraatrial conduction and discoordinate left and right atrial mechanical function. Simultaneous activation of both atria with pacing techniques involving multisite and multilead systems is associated with suppression of supraventricular tachyarrhythmias and improved hemodynamics. In the present study we tested the hypothesis that pacing from a single site of the atrial septum can synchronize atrial depolarization. Five males and two females (mean age 58 ± 6 years) with drug refractory paroxysmal atrial fibrillation (AF) were studied who were candidates for AV junctional ablation. All patients had broad P waves (118 ± 10 ms) on the surface ECG. Multipolar catheters were inserted and the electrograms from the high right atrium (HRA) and proximal, middle, and distal coronary sinus (CS) were recorded. The atrial septum was paced from multiple sites. The site of atrial septum where the timing between HRA and distal CS (d-CS) was ≤ 10 ms was considered the most suitable for simultaneous atrial activation. An active fixation atrial lead was positioned at this site and a standard lead was placed in the ventricle. The interatrial conduction time during sinus rhythm and AAT pacing and the conduction time from the pacing site to the HRA and d-CS during septal pacing were measured. Atrial septal pacing was successful in all patients at sites superior to the CS os near the fossa ovalis. During septal pacing the P waves were inverted in the inferior leads with shortened duration from 118 ± 10 ms to 93 ± 7 ms (P < 0.001), and the conduction time from the pacing site to the HRA and d-CS was 54.3 ± 6.8 ms and 52.8 ± 2.5 ms, respectively. The interatrial conduction time during AAT pacing was shortened in comparison to sinus rhythm (115 ± 18.9 ms vs 97.8 ± 10.3 ms, P < 0.05). In conclusion, simultaneous activation of both atria in patients with prolonged interatrial conduction time can be accomplished by pacing a single site in the atrial septum using a standard active fixation lead placed under electrophysiological study guidance. Such a pacing system allows proper left AV timing and may prove efficacious in preventing various supraventricular tachyarrhythmias.