Ajmal Gardiwal

Efficacy of pulmonary vein isolation by cryoballoon ablation in patients with paroxysmal atrial fibrillation.

BACKGROUND Radiofrequency ablation of pulmonary veins (PVs) has emerged as an effective treatment for patients with paroxysmal atrial fibrillation (AF). However, serious complications raise concern about an even wider application. In terms of safety, cryoenergy has advantages compared with radiofrequency. A new cryoenergy balloon catheter has been recently developed to make AF ablation shorter and safer. OBJECTIVE The purpose of this study was to test the 6-month efficacy of this new device for ablation of paroxysmal AF. METHODS Twenty-one patients with highly symptomatic paroxysmal AF, normal left atrial size, and frequent episodes of AF were included. All PVs were targeted during cryoballoon ablation. Patients received 24-hour Holter electrocardiograms (ECGs) and event recorder during follow-up after 1, 3, and 6 months. RESULTS A total of 81 (95%) of 85 PVs could be completely isolated with a single-balloon technique. Procedure time was 165 +/- 35 minutes, and fluoroscopy time was 39 +/- 9 minutes. After 6 months, 86% of the patients were free of symptomatic AF. In two of three patients with recurrence of AF, complete PV isolation has not been achieved initially. After a second procedure (1.04 procedures per patient), 90% of the patients were free of symptomatic AF. Three phrenic nerve palsies occurred during ablation of the right superior PV; two completely resolved after 6 and 9 months, and one is still persisting after 2 months. CONCLUSION This is the first study that reports the results of the new cryoballoon AF ablation approach showing 86% freedom from AF recurrence after 6 months. Cryoballoon PV ablation promises to be effective for patients with paroxysmal AF and normally sized left atria.

The impact of cardiac resynchronization therapy on the incidence of ventricular arrhythmias in mild heart failure.

BACKGROUND Cardiac resynchronization therapy (CRT) decreases mortality, improves functional status, and induces reverse left ventricular (LV) remodeling in selected populations. However, the effect of CRT on ventricular arrhythmias is controversial. This is particularly important among patients with mild heart failure (HF), in whom sudden death is a leading cause of mortality. OBJECTIVE This study sought to assess the impact of CRT on ventricular arrhythmias in mild HF. METHODS The REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction (REVERSE) study is a multicenter randomized, double-blind trial of CRT among patients with mild systolic HF. The time to first appropriate, treated ventricular tachycardia/ventricular fibrillation (VT/VF) episode or spontaneous sustained VT in cardiac resynchronization therapy plus defibrillation device (CRT-D) patients was compared between groups, as were predictors of VT/VF. RESULTS The study randomized 508 patients who received CRT-D devices. There were no significant demographic differences between groups. There were no differences in VT/VF episodes or VT storm between groups. Specifically, in the CRT ON group, the estimated event rate was 18.7% at 2 years, compared with 21.9% in the CRT OFF group (hazard ratio 1.05, P = .84). However, among CRT ON patients, those with reverse remodeling had a reduced incidence of VT/VF compared with those without remodeling (5.6% vs. 16.3%, hazard ratio 0.31, P = .001). CONCLUSION CRT for up to 2 years does not impact VT/VF in mild HF despite marked clinical and remodeling effects of pacing. This neutral effect may be attributable to competing antiarrhythmic effects of reverse remodeling and proarrhythmic effect of pacing. CLINICAL TRIAL REGISTRATION http://www.clinicaltrials.gov/ct2/show/NCT00271154.

Implantable defibrillator therapy for ventricular tachyarrhythmia in left ventricular assist device patients

Ventricular arrhythmias (VA) occur frequently after permanent left ventricular assist device (LVAD) implantation in end stage heart failure. Left ventricular assist device patients require rhythm control in contrast to patients with biventricular support. However, the rationale for implantable cardioverter‐defibrillator (ICD) utilization in LVAD patients remains unclear. This study investigated the safety and efficacy of primary prevention ICD therapy and the rate of appropriate ICD interventions in LVAD patients.

Female Mice Lacking Estrogen Receptor β Display Prolonged Ventricular Repolarization and Reduced Ventricular Automaticity After Myocardial Infarction

Background—Major gender-based differences in the incidence of ventricular tachyarrhythmia after myocardial infarction have been shown in humans. Although the underlying mechanisms are unclear, earlier studies suggest that estrogen receptor–mediated effects play a major role in this process. Methods and Results—We examined the effect of estrogen receptor α (ERα) and estrogen receptor β (ERβ) on the electrophysiological phenotype in female mice with and without chronic anterior myocardial infarction. There was no significant difference in overall mortality, infarct size, and parameters of left ventricular remodeling when we compared infarcted ERα-deficient and ERβ-deficient mice with infarcted wild-type animals. In the 12-hour telemetric ECG recording 6 weeks after myocardial infarction, surface ECG parameters did not show significant differences in comparisons of ERα-deficient mice versus wild-type controls, infarcted versus noninfarcted ERα-deficient mice, and infarcted ERα-deficient versus infarcted wild-type mice. However, infarcted ERβ-deficient versus noninfarcted ERβ-deficient mice showed a significant prolongation of the QT (61±6 versus 48±8 ms; P<0.05) and QTc intervals (61±7 versus 51±9 ms; P<0.05) and the JT (42±6 versus 31±4 ms; P<0.05) and JTc intervals (42±7 versus 33±4 ms; P<0.05). Furthermore, infarcted ERβ-deficient versus infarcted wild-type mice showed a significant prolongation of the QT (61±6 versus 53±8 ms; P<0.05) and QTc intervals (61±7 versus 53±7 ms; P<0.05) and the JT (42±6 versus 31±5 ms; P<0.05) and JTc intervals (42±7 versus 31±5 ms; P<0.05), accompanied by a significant decrease of ventricular premature beats (7±21/h versus 71±110/h; P<0.05). Finally, real-time polymerase chain reaction–based quantitative analysis of mRNA levels showed a significantly lower expression of Kv4.3 (coding for Ito) in ERβ-deficient mice (P<0.05). Conclusions—Estrogen receptor β deficiency results in prolonged ventricular repolarization and decreased ventricular automaticity in female mice with chronic myocardial infarction.

Implantable defibrillator with left ventricular assist device compatibility

Implanted defibrillator (ICD) and HeartMate-II (Thoratec, Pleasanton, CA, USA) left ventricular assist device (LVAD) incompatibilities have been reported. In order to show which ICD would function regularly in Heart Mate II recipients, we conducted a systematic review of 39 consecutive patients with implanted ICD and HeartMate-II from our institutions LVAD registry. Forty-six ICDs were identified without device interactions in most ICD devices. However, loss of ICD to programmer telemetry was observed in four patients with V-193, V-196 and V-350 (St Jude Medical, Sunnyvale, CA, USA) and one patient with an Ovatio DR (Sorin, Milan, Italy) requiring ICD replacement. The majority of all investigated ICDs operated without LVAD to ICD interaction. However, surgeons implanting the Heart Mate II in ICD patients should be aware of possible interactions and incompatible devices should not be recommended in HeartMate-II recipients.

Right ventricular pacing is an independent predictor for ventricular tachycardia/ventricular fibrillation occurrence and heart failure events in patients with an implantable cardioverter-defibrillator.

AIMS There is increasing evidence that right ventricular (RV) pacing may have detrimental effects by increasing morbidity and mortality for heart failure in implantable cardioverter-defibrillator (ICD) patients. In this study we prospectively tested the hypothesis that cumulative RV pacing increases ventricular tachycardia/ventricular fibrillation (VT/VF) occurrence (primary endpoint) and hospitalization and mortality for heart failure (secondary endpoint) in a predominantly secondary prophylactic ICD patient population. METHODS AND RESULTS Two hundred and fifty patients were divided into two groups according to the median of cumulative RV pacing (< or =2 vs. >2%) and prospectively followed-up for occurrence of primary and secondary endpoints for 18 +/- 4 months. Established predictors for VT/VF occurrence and heart failure events such as age, left ventricular ejection fraction (EF), QRS duration, history of atrial fibrillation, and NT-proBNP were collected at enrollment. Multivariate Cox regression analysis revealed that cumulative RV pacing > 2% and EF < 40% were independent predictors for VT/VF occurrence and heart failure events. Kaplan-Meier analysis showed that patients with >2% cumulative RV pacing more frequently suffered from VT/VF occurrence and heart failure hospitalization. CONCLUSION Cumulative RV pacing > 2% and EF < 40% are independent predictors for VT/VF occurrence and mortality and hospitalization for heart failure in predominantly secondary prophylactic ICD patients. Our data show that algorithms capable of reducing cumulative RV pacing should be used more frequently in clinical practice.

Difference in humoral biomarkers for myocardial injury and inflammation in radiofrequency ablation versus cryoablation.

Background: Markers of myocardial injury and inflammation have been shown to be elevated following radiofrequency (RF) ablation. This study aimed to compare RF ablation and cryoablation for their impact on markers for myocardial injury and inflammation.

Effect of Restoring Sinus Rhythm on Sleep Apnea in Patients With Atrial Fibrillation or Flutter

Sleep apnea (SA) is more prevalent in patients with atrial fibrillation (AF), but the impact of cardioversion on disordered breathing is unknown. Thus, we investigated the influence of restoring sinus rhythm in patients with AF and atrial flutter (AFlut) on SA. The 16 patients (mean age 63.1 +/- 11.2) with AF (n = 6) or AFlut (n = 10) and SA (apnea-hypopnea index >10) received cardioversion or ablation of cavotricuspid isthmus. We compared the severity of SA by sleep polygraphy under AF/Aflut with the first night after restoring sinus rhythm and after 4 weeks. Apnea-hypopnea index before and immediately after restoring sinus rhythm was similar (31.7 +/- 13.2 vs 30.1 +/- 15.7, p = NS) despite a significantly reduced heart rate (86.7 +/- 26.5 vs 67.8 +/- 11.9 beats/min, p <0.02). After 4 weeks, apnea-hypopnea index remained unchanged (38.1 +/- 18.1, p = NS) although heart rate was further reduced (61.8 +/- 8.8 beats/min, p <0.003). In our study, SA could not be improved by cardioversion of AF/AFlut. Therefore, although it is well known that SA leads to AF, eliminating AF does not cure or improve SA. In conclusion, our study shows that AF should be regarded more as an innocent bystander than a causative or aggravating condition in SA.

Clinical relevance of slow ventricular tachycardia in heart failure patients with primary prophylactic implantable cardioverter defibrillator indication

AIMS Implantable cardioverter defibrillators (ICDs) have shown to reduce all-cause mortality in heart failure patients. In SCD-HeFT study, ICDs were programmed with a detection zone of ≥ 187 b.p.m. Thus, the incidence and clinical significance of slower ventricular tachycardias (VTs) in these patients remains largely unknown, though clinically important for device selection, programming, and follow-up. METHODS AND RESULTS We prospectively studied symptomatic heart failure patients with an indication for a primary prophylactic ICD with or without concomitant resynchronization therapy according to SCD-HeFT inclusion criteria. Devices were programmed to an additional monitor zone for slow VTs at heart rates 130-186 b.p.m. Two hundred consecutive patients (86% male) were followed for a mean of 509 ± 308 days. One hundred and thirty-seven patients (68.5%) were New York Heart Association class III, 75 patients (37.5%) were on cardiac resynchronization therapy, and 124 (62%) had ischaemic cardiomyopathy. We observed 473 VT episodes in 36 patients (18%) and 131 ventricular fibrillation episodes in 30 patients (15%). Ventricular tachycardia overall occurred in 40 patients (20%). The incidence of slow VTs was low in only 12 patients (6%). No patient with slow VT suffered from syncope, palpitation, or decompensation leading to hospitalization. We did not find any reliable predictor for increased long-term risk of slow VTs. CONCLUSION Incidence of slow VTs in a typical heart failure population with primary prophylactic ICD-implantation ± resynchronization therapy is very low. Slow VTs detected in the ICD monitor zone remained clinically asymptomatic. Thus, single chamber and atriobiventricular ICDs with a VT/ventricular fibrillation zone of ≥ 187 b.p.m. and one burst before shock delivery might be sufficient and pragmatic for the vast majority of these patients.

Stable Cystatin C Serum Levels Confirm Normal Renal Function in Patients With Dronedarone-Associated Increase in Serum Creatinine

Dronedarone is a new antiarrhythmic drug for patients with nonpermanent atrial fibrillation (AF). A relatively consistent finding in all trials studying dronedarone was a moderate but significant elevation of serum creatinine. Since dronedarone competes for the same organic cation transporter in the distal renal tubule with creatinine, serum creatinine and its derived estimated glomerular filtration rate might not reflect true renal function in patients on dronedarone. We therefore investigated alternative markers for renal function in these patients. We prospectively included 20 patients with nonpermanent AF in whom dronedarone 400 mg twice daily was started. Patients had normal renal function and serum creatinine; serum cystatin C and creatinine clearance were measured before treatment and 10 and 90 days after treatment started. Mean serum creatinine level for all 20 patients at baseline (day 0) was 84.55 ± 12.14 and 87.8 ± 17.59 µmol/L on day 10. This slight increase in all patients was not significant. Patients were now divided into the predefined groups of “increased creatinine” (increase in serum creatinine level > 1 standard deviation) and “not increased creatinine.” Patients with increased creatinine levels (n = 5) showed a significant elevation of serum creatinine levels from day 0 to day 10 (82.4 ± 9.18 to 104.4 ± 12.74 µmol/L; P = .003), whereas change in serum creatinine levels in the not increased creatinine group (n = 15) was not significant. Serum cystatin C levels remained stable in both of these groups (increased creatinine group: 0.76 ± 0.08 to 0.78 ± 0.08 mg/L; P = .65; not increased creatinine group: 0.77 ± 0.108 to 0.77 ± 0.107 mg/L; P = .906). In conclusion, cystatin C represents an easily available and reliable biomarker for estimation of true renal function in patients on dronedarone treatment.