Effects of Oral Propafenone Therapy on Chronic Myocardial Pacing Threshold

The effects of oral propafenone therapy on pacing threshold were studied in 36 patients chronically paced for sick sinus syndrome or AV block. The pacemakers, all unipolar models and with noninvasive threshold measurement facilities, were: 9 VVI, 15 AAI, and 12 DDD. Each patient received an initial propafenone dose of 450 mg/day, that in 18 cases was increased to 900 mg/day. Threshold was tested at baseline and at each dosage after 7 days of therapy. With the lower propafenone dosage the threshold, measured at 2.5 V, rose from 0.14 +/- 0.10 to 0.21 +/- 0.16 msec (+55%) in the atrium (P less than 0.0001) and from 0.10 +/- 0.08 to 0.15 +/- 0.09 msec (+63%) in the ventricle (P less than 0.0001). In the 18 patients who received both dosages, the mean atrial and ventricular threshold increased from 0.12 +/- 0.10 to 0.17 +/- 0.14 msec with the lower dose and to 0.27 +/- 0.22 msec (+125%) with the higher dose (P less than 0.0001 for both increments). With the 900 mg/day dose, a threshold increment greater than or equal to 300% was observed in 15% of the stimulated chambers. A good linear correlation (r = 0.76) was found between the ventricular threshold increment and the drug induced QRS widening. In conclusion, treatment with oral propafenone increases atrial and ventricular stimulation threshold in pacemaker patients. Threshold increment is dose dependent and proportional to the drug induced QRS widening. In the majority of the cases the threshold increment is not clinically significant, but caution must be used in prescribing high doses of the drug to patients with high baseline threshold.     

Use and Misuse of Multivariable Approaches in Interventional Cardiology Studies on Drug‐Eluting Stents: A Systematic Review

Aims: Randomized clinical trials (RCTs) are the most reliable evidence, even if they require important resource and logistic efforts. Large, cost‐free and real‐world datasets may be easily accessed yielding to observational studies, but such analyses often lead to problematic results in the absence of careful methods, especially from a statistic point of view. We aimed to appraise the performance of current multivariable approaches in the estimation of causal treatment and effects in studies focusing on drug‐eluting stents (DES). Methods and Results: Pertinent studies published in the literature were searched, selected, abstracted, and appraised for quality and validity features. Six studies with a logistic regression were included, all of them reporting more than 10 events for covariates and different length of follow‐up, with an overall low risk of bias. Most of the 15 studies with a Cox proportional hazard analysis had a different follow‐up, with less than 10 events for covariates, yielding an overall low or moderate risk of bias. Sixteen studies with propensity score were included: the most frequent method for variable selection was logistic regression, with underlying differences in follow‐up and less than 10 events for covariate in most of them. Most frequently, calibration appraisal was not reported in the studies, on the contrary of discrimination appraisal, which was more frequently performed. In seventeen studies with propensity and matching, the latter was most commonly performed with a nearest neighbor‐matching algorithm yet without appraisal in most of the studies of calibration or discrimination. Balance was evaluated in 46% of the studies, being obtained for all variables in 48% of them. Conclusions: Better exploitation and methodological appraisal of multivariable analysis is needed to improve the clinical and research impact and reliability of nonrandomized studies. (J Interven Cardiol 2012;25:611–621)     

Long‐Term Results of Transcatheter Atrial Fibrillation Ablation in Patients with Impaired Left Ventricular Systolic Function

AF Ablation and Impaired Left Ventricular Function. Introduction: Long‐term outcome of AF ablation in patients with impaired LVEF is unknown. The aim of this study is to evaluate sinus rhythm (SR) maintenance, clinical status, and echocardiographic parameters over a long‐term period following atrial fibrillation (AF) transcatheter ablation in patients with left ventricular ejection fraction (LVEF) <50%. Methods and Results: A total of 196 patients (87.2% males, age 60.5 ± 10.2 years) with LVEF <50% underwent radiofrequency transcatheter ablation for paroxysmal (22.4%) or persistent (77.6%) AF. Patients were followed up for 46.2 (16.4–63.5) months regarding AF recurrences, functional class, and echocardiographic parameters. All patients underwent pulmonary vein isolation, while 167 (85.2%) required additional atrial lesions. Eleven (5.6%) patients suffered procedural complications. During follow‐up, 58 (29.6%) patients required repeated ablations. At the follow‐up end, 15 (7.7%) patients died, while 74 (37.8%) documented at least one episode of AF, atrial flutter, or atrial ectopic tachycardia. Eighty‐three (47.2%) patients maintained antiarrhythmic drugs. During follow‐up, NYHA class improved by at least one class more frequently among patients maintaining SR compared to those experiencing relapses (70.6% vs 47.9%, P = 0.003). LVEF showed a broader relative increase in patients maintaining SR (32.7% vs 21.4%; P = 0.047) and mitral regurgitation grading significantly decreased (P <0.001) only within these patients. At multivariable analysis SR maintenance emerged as an independent predictor (odds ratio 4.26, 95% CI 1.69–10.74, P = 0.002) of long‐term clinical improvement (reduction in NYHA class ≥1 and relative increase in LVEF ≥10%). Conclusions: Although not substantially worse than in patients with preserved LVEF, AF ablation in patients with impaired LVEF is affected by high long‐term recurrence rate. Among these patients SR maintenance is associated with greater clinical improvement. (J Cardiovasc Electrophysiol, Vol. 24, pp. 24‐32, January 2013)     

Prospective Study of Cardiac Sarcoid Mimicking Arrhythmogenic Right Ventricular Dysplasia

Introduction: Case studies indicate that cardiac sarcoid may mimic the clinical presentation of arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C); however, the incidence and clinical predictors to diagnose cardiac sarcoid in patients who meet International Task Force criteria for ARVD/C are unknown.
Methods and Results: Patients referred for evaluation of left bundle branch block (LBBB)-type ventricular arrhythmia and suspected ARVD/C were prospectively evaluated by a standardized protocol including right ventricle (RV) cineangiography-guided myocardial biopsy. Sixteen patients had definite ARVD/C and four had probable ARVD/C. Three patients were found to have noncaseating granulomas on biopsy consistent with sarcoid. Age, systemic symptoms, findings on chest X-ray or magnetic resonance imaging (MRI), type of ventricular arrhythmia, RV function, ECG abnormalities, and the presence or duration of late potentials did not discriminate between sarcoid and ARVD/C. Left ventricular dysfunction (ejection fraction <50%) was present in 3/3 patients with cardiac sarcoid, but only 2/17 remaining patients with definite or probable ARVD/C (P = 0.01).
Conclusions: In this prospective study of consecutive patients with suspected ARVD/C evaluated by a standard protocol including biopsy, the incidence of cardiac sarcoid was surprisingly high (15%). Clinical features, with the exception of left ventricular dysfunction and histological findings, did not discriminate between the two entities.     

Automatic Management of Left Ventricular Stimulation: Hints for Technologic Improvement

Background: We used a cardiac resynchronization therapy defibrillator device with an algorithm for automatic verification of left ventricular (LV) stimulation to understand LV threshold variability, such as to provide hints to program the algorithm features. We also evaluated the algorithm performance over long term, and tested a stimulation setting to achieve 99% effective stimulation while maximizing device longevity. Methods: The LV output was programmed as threshold + 0.5 V; the upper limit of LV output adjustment was 6 V at programmed pulse width. The algorithm is insensitive to the strength of the pacing pulse, thus pulse width was conveniently programmed to minimize the use of voltage multipliers in all the patients. Follow‐ups occurred at 1 month, then every 3 months, for clinical assessment and manual threshold verification. The efficacy of this programming at long term was also evaluated by Holter validation of LV stimulation. Results: Twenty patients were followed for 14 ± 5 months (6–21). LV threshold showed no changes in 97% of consecutive days, whereas a 0.5‐V and 1‐V increase occurred, respectively, in 2.3% and 0.6%. Maximum variability of LV threshold was ≤0.5 V during 90% of the follow‐up period. Our programming of LV output provided 99–100% effective stimulation in 18 of 20 patients, and 90% efficacy in two patients because of missed threshold measurements. A 25% increase of device longevity can be expected by this programming. Conclusions: LV threshold variability is truly modest. Daily update of LV threshold should be improved to ensure 100% LV stimulation by a threshold + 0.5 V safety margin. Device longevity is maximized when LV stimulation occurs below battery voltage.     

All-trans retinoic acid shows multiple effects on the survival, proliferation and differentiation of human fetal CD34+ haemopoietic progenitor cells

Summary. To evaluate the effect of all-trans retinoic acid (RA) on fetal haemopoiesis, we performed serum-free liquid and semisolid cultures using CD34⁺ cells purified from mid-trimester human fetal blood samples. RA, at both physiological (10^-n and 10^-12M) and pharmacological (10^-6 and l(r⁷M) concentrations, significantly (P<0.01) promoted the survival of fetal CD34⁺ cells in liquid cultures from day 3 onwards, by suppressing apoptosis induced by serum and growth factor deprivation. On the other hand, RA alone had no significant effect on the proliferation and differentiation of fetal haemopoietic progenitors. In the presence of optimal concentrations of recombinant interleukin-3 (IL-3), stem cell factor (SCF), granulocyte/ macrophage-colony stimulating factor (GM-CSF), and erythropoietin (Epo), low and high doses of RA induced striking differential effects on CD34⁺ cell proliferation in liquid cultures and colony formation in semisolid assays. In fact, 1CT^U M and 1CT¹²M RA were able to: (i) significantly (P<0.05) increase ³H-thymidine uptake by fetal CD34⁺ cells in liquid cultures, and (ii) variably promote the growth of pluripotent (CFU-GEMM, P<0.05), early (BFU-meg) and late (CFU-meg, P<0.01) megakaryocyte, granulocyte/macrophage (CFU-GM. P<001) and erythroid (BFU-E) progenitors in semisolid cultures. On the contrary, 10^-6 and 10^-7 M RA induced: (i) an overall inhibition (P<0.01) of CD34⁺ cell growth in liquid cultures; (ii) a marked suppression of BFU-E colony formation (P<0.01) at all Epo concentrations examined (0-002-4IU/ml); and (iii) a significant (P<0.()1) stimulation of CFU-GM with a shift from mixed granulocyte/ macrophage to pure granulocyte colonies, whereas it had little effect on the growth of CFU-GEMM, BFU-meg and CFU-meg. Our data, as a whole, demonstrate that RA has direct complex effects on the survival, growth and clonal expansion of fetal haemopoietic progenitor cells, mainly depending on the presence of recombinant cytokines, the type of progenitor and the concentrations of RA.     

Transcutaneous Cardiac Pacing for Termination of Tachyarrhythmias

ALTAMURA, G., ET AL.: Transcutaneous Cardiac Pacing for Termination of Tachyarrhythmias. Transcutaneous cardiac pacing (TCP) was used for interruption of tachyarrhythmias in 31 patients: 20 with ventricular tachycardia (VT); eight with atrioventricular reentrant tachycardia (AVRT) and three had atrioventricular nodal tachycardia (AVNT). The stimulators used (Pace Aid 50/52) allow pacing at programmable rates (50–160 ppm) and output (10–200 mA at 20-msec pulse duration), when possible overdrive pacing was used. Short bursts of stimuli were delivered with increasing current intensity until interruption of the arrhythmia or to the maximum energy tolerated by the patient. VTs were interrupted in eight of the 20 patients: four of the six (67%) treated by overdrive pacing and four of the 14 (29%) were treated by underdrive pacing. Supraventricular tachycardias (SVT) were terminated in eight of the 11 patients: seven out of eight (88%) AVT, and one out of three AVNT (33%). We observed two cases of arrhythmia worsening: a VT acceleration and induction of ventricular fibrillation in a patient with AVNT. TCP was well tolerated by the majority of the patients. We conclude that TCP is an effective method for interruption of ventricular and supraventricular reentrant tachycardias, but the risk of arrhythmia worsening must be considered.