Genome-wide association of implantable cardioverter-defibrillator activation with life-threatening arrhythmias.

OBJECTIVES: To identify genetic factors that would be predictive of individuals who require an implantable cardioverter-defibrillator (ICD), we conducted a genome-wide association study among individuals with an ICD who experienced a life-threatening arrhythmia (LTA; cases) vs. those who did not over at least a 3-year period (controls). BACKGROUND: Most individuals that receive implantable cardioverter-defibrillators never experience a life-threatening arrhythmia. Genetic factors may help identify who is most at risk. METHODS: Patients with an ICD and extended follow-up were recruited from 34 clinical sites with the goal of oversampling those who had experienced LTA, with a cumulative 607 cases and 297 controls included in the analysis. A total of 1,006 Caucasian patients were enrolled during a time period of 13 months. Arrhythmia status of 904 patients could be confirmed and their genomic data were included in the analysis. In this cohort, there were 704 males, 200 females, and the average age was 73.3 years. We genotyped DNA samples using the Illumina Human660 W Genotyping BeadChip and tested for association between genotype at common variants and the phenotype of having an LTA. RESULTS AND CONCLUSIONS: We did not find any associations reaching genome-wide significance, with the strongest association at chromosome 13, rs11856574 at P = 5×10⁻6. Loci previously implicated in phenotypes such as QT interval (measure of the time between the start of the Q wave and the end of the T wave as measured by electrocardiogram) were not found to be significantly associated with having an LTA. Although powered to detect such associations, we did not find common genetic variants of large effect associated with having a LTA in those of European descent. This indicates that common gene variants cannot be used at this time to guide ICD risk-stratification. TRIAL REGISTRATION: ClinicalTrials.gov NCT00664807.

Temporal stability of defibrillation thresholds with cardiac resynchronization therapy.

BACKGROUND: Defibrillation thresholds (DFTs) are typically stable over time among patients with implantable cardioverter-defibrillators (ICDs). However, the impact of cardiac resynchronization therapy (CRT) on DFTs has not been studied systematically. OBJECTIVE: This study prospectively evaluated the effect of CRT and left ventricular (LV) chamber reverse remodeling on DFTs. METHODS: This prospective, multicenter study evaluated 54 cardiac resynchronization therapy defibrillator (CRT-D) patients. Echocardiography and DFTs were performed both at implantation and at 6 months after implantation. All patients received dual-coil leads and a CRT-D pulse generator. DFTs were measured using a binary search method and tuned biphasic waveforms, where the shock pulse widths were determined by the measured shock impedance. Echocardiograms were analyzed by an independent core laboratory with a responder defined as a decrease of left ventricular end systolic volume >15%. RESULTS: The study cohort was 74% male, with a mean age of 68.7 ± 10.9 years. The baseline ejection fraction was 0.245 ± 0.076, and the mean New York Heart Association class was 2.9 ± 0.4. In CRT responders (n = 32) the mean DFT was 415.6 ± 108.1 V at implantation vs. 415.6 ± 124.7 V at 6 months (P = .9), and in nonresponders (n = 19) the mean DFT was 452.6 ± 102 V at implantation vs. 447.4 ± 112.4 V at 6 months (P = .8). There was no significant change in DFT peak voltage, delivered energy, or shock impedance over time. CONCLUSION: DFTs were unchanged at 6 months in CRT patients with or without LV chamber reverse remodeling.

Gender disparity in the use of cardiac resynchronization therapy in the United States.

BACKGROUND: Although several studies have shown the effectiveness of cardiac resynchronization therapy (CRT) for advanced congestive heart failure (CHF), gender differences in utilization of CRT are not known. METHODS: We used the Healthcare Cost and Utilization Project (HCUP) to study national rates for admissions due to CHF along with procedures for initial CRT implantation, including both CRT-defibrillator (CRT-D) and CRT-pacemakers (CRT-P) during the years of 2002-2004. Chi-square tests were used for comparison between number of women and men. A P < 0.05 was considered significant. RESULT: Women had consistently higher rates of admission for CHF during each year (574,037 (54%) vs 482,005 (46%), 2002; 601,181 (54%) vs 517,202 (46%), 2003; and 580,913 (53%) vs 521,280 (47%), 2004). The number of initial CRT device implantations (both CRT-D and CRT-P) was significantly lower during each year for women compared to men (659 (25%) vs 1,931 (75%), 2002; 6,928 (26%) vs 19,646 (74%), 2003; and 11,286 (27%) vs 42,196 (73%), 2004; P < 0.01 for all). Both CRT-P and CRT-D were used less frequently in women compared to men; however, this difference was consistently less prominent during each year with CRT-P compared to CRT-D (301 (41%) CRT-P vs 358 (19%) CRT-D, 2002; 659 (39%) CRT-P vs 2,530 (28%) CRT-D, 2003; and 2,891 (39%) CRT-P vs 8,395 (24%) CRT-D, 2004; P < 0.05). CONCLUSION: Our data clearly demonstrate a significant gender disparity in utilization of CRT devices. Further studies are needed to find possible reasons behind this disparity.

Site localization and characterization of pain during radiofrequency ablation of the pulmonary veins.

BACKGROUND: Characteristics of radiofrequency (RF) lesions producing pain with an 8-mm catheter during pulmonary vein (PV) ablation have not been prospectively studied. METHODS: We studied 46 (30 men, age 56 +/- 10 years) patients with AF who underwent RF ablation of PVs. PV isolation was achieved by using an 8F, 8-mm Biosense ablation catheter (Biosense Webster, Diamond Bar, CA, USA) guided by intracardiac echocardiography (ICE). An electroanatomic map was used to document the location of all RF lesions and the time; PV location and maximum temperature of every lesion were recorded. Location of the esophagus was determined by magnetic resonance imaging prior to the procedure and by both ICE and barium swallows during procedure. RESULT: A total of 1,448 (33 +/- 12) RF lesions were delivered to 180 veins. Thirty-nine patients (85%) had at least one lesion associated with pain (mean: 8 +/- 5 lesions) during ablation. The RF generator setting during lesions resulting in pain sensation was 48.6 +/- 7.0 Watts and 51.5 +/- 2.9 degrees C. Maximum temperature attained at the time of pain sensation was 45.7 +/- 4.2 degrees C. By logistic regression analysis the left superior PV (OR 1.54, CI 1.06-2.24, LS vs RI, P < 0.05) and left inferior PV (OR 2.74, CI 1.79-4.19, LI vs RI, P < 0.001) location were both positively correlated with the production of pain. The location of lesions associated with pain was not near the esophagus during any of the pain-producing lesions. CONCLUSION: Pain sensation is relatively common during RF ablation of PVs. There was no correlation between pain and the location of esophagus. Pain was more common during RF ablation of left inferior and left superior PVs.

Slow atrioventricular nodal reentrant arrhythmias: clinical recognition, electrophysiological characteristics, and response to radiofrequency ablation.

BACKGROUND: Atrioventricular nodal reentrant tachycardia (AVNRT) is a common form of supraventricular tachycardia (SVT). Rarely, patients may present with an unusual form of atrioventricular nodal reentrant arrhythmia (AVNRA) with a cycle length greater than 600 ms. We describe the clinical presentation, electrophysiology characteristics, and response to radiofrequency ablation in a group of patients with AVNRA. METHODS AND RESULTS: Six patients with slow documented sustained supraventricular arrhythmias at rates <100 bpm underwent electrophysiology study. Baseline clinical and electrophysiologic characteristics were: mean age 77 +/- 5 years; left ventricular ejection fraction 51 +/- 10%; hypertension 66%; diabetes mellitus 33%; coronary artery disease 33%; sinus cycle length 874 +/- 110 ms; PR 261 +/- 54 ms; atrial to His (AH) 181 +/- 49 ms. AVNRA was diagnosed based on previously described criteria for AVNRT. Mean tachycardia cycle length (TCL) during AVNRA was 668 +/- 74 ms. The AH and His to atrial (HA) intervals during the AVNRA was 434 +/- 50 and 234 +/- 81 ms, respectively. Two patients had slow-fast AVNRA while the others had slow-slow AVNRA. Most common symptoms reported during AVNRA were shortness of breath, fullness in the throat, chest tightness, dizziness, near-syncope, and syncope. Radiofrequency catheter ablation (RFCA) of the slow pathway was performed successfully in five of six patients. Post-ablation AV nodal Wenckebach occurred at 666 +/- 49 ms compared with 521 +/- 91 ms at baseline. CONCLUSION: AVNRA may occur at rates less than 100 bpm in the elderly and may be misdiagnosed as junctional rhythm. Slow AVNRA can cause significant symptoms. Slow pathway ablation can be successfully performed in AVNRA.

Cryoablation inside the pulmonary vein after failure of radiofrequency antral isolation.

BACKGROUND: Antral pulmonary vein (PV) ablation with radiofrequency (RF) energy has become widely used as a curative approach for the treatment of atrial fibrillation. In some patients, despite antral ablation, PV entry and exit conduction block (BDB) cannot be achieved with RF energy. Cryoablation inside the PV may be an effective method to achieve BDB. OBJECTIVE: This study sought to describe a strategy of cryoablation within the PV to produce BDB in patients in whom antral RF ablation has failed. METHODS: In 15 of 148 consecutive patients (57 +/- 8.9 years old, 80% male) with atrial fibrillation (14 paroxysmal, 1 chronic) undergoing PV isolation cryoablation (CryoCath Technologies, Inc., Montreal, Canada) was performed 12 +/- 2 mm inside the PV after RF antral isolation failed. Nine patients were undergoing a repeat PV isolation procedure. Procedural and follow-up data were recorded and collected. RESULTS: In these 15 patients, BDB could not be achieved in 23 veins (12 left superior PV) with antral or ostial ablation alone. After cryoablation inside the vein, all patients had documented PV BDB and were in normal sinus rhythm at the end of the procedure. The average PV diameter before and after the procedure was unchanged (1.77 +/- 0.18 vs 1.74 +/- 0.19, P = .641). The average fluoroscopic and procedure times were 57 +/- 16 min and 5.3 + 1.2 hours, respectively. At 1-year follow-up, 75% of patients remained in sinus rhythm off antiarrhythmic medication; 7 of 9 patients undergoing a repeat procedure were in sinus rhythm at 1 year off antiarrhythmics. None of the patients had clinical evidence of PV stenosis after cryoablation. CONCLUSION: Cryoablation inside the PV after failed antral isolation with RF is a safe and effective method to achieve acute BDB.

Incidence, time course, and characteristics of microbubble formation during radiofrequency ablation of pulmonary veins with an 8-mm ablation catheter.

BACKGROUND: Microbubble formation during pulmonary vein (PV) radiofrequency (RF) ablation of atrial fibrillation (AF) occurs relatively frequently. Prior studies have shown that microbubble formation may be associated with an increased risk of complications. However, the incidence, time course, and temperature characteristics of microbubble formation during AF ablation with an 8-mm catheter have not been prospectively described in humans. METHODS: We studied 46 (30 men, age 56+/-10 years) patients with AF who underwent RF ablation of PVs between January 2005 and December 2005 using an 8F, 8-mm Biosensetrade mark ablation catheter (Biosense-Webster, Diamond Bar, CA, USA). All patients underwent continuous intracardiac echocardiography (ICE). Microbubble patterns were classified as either type 1 (intermittent, scattered microbubble formation) or type 2 (explosive shower of dense microbubbles). Formation of any microbubbles was detected by ICE and the time, PV location, and electrode temperature were recorded. RESULT: A total of 1,479 (32+/-13, range 12-73) RF lesions were delivered to 167 veins. Twenty (2%) lesions were classified as type 2. Since the number of lesions resulting in type 2 bubbles was very small, only type 1 lesions were included in the final analysis. Thirty-nine (85%) patients had at least one lesion associated with bubble formation during ablation (mean: 7+/-7 lesions, range 1-28 lesions). Twenty-three percent (327) of the RF lesions resulted in bubble formation. RF generator power setting during lesions resulting in bubble formation was lower than lesions which did not result in bubble formation (47.9+/-7.4 W vs 49.7+/-7.1 W, P<0.001). Logistic regression analysis revealed a significant negative correlation (P<0.001) between RF generator power settings and a positive correlation between the generator temperature settings and formation of bubbles (both P<0.02). However, the maximum temperature attained was not different between lesions resulting in bubble formation (n=327) and those which did not result in bubble formation (n=1,139). Fifty-three (16%) of the lesions associated with bubble formation occurred within 2-10 seconds after RF was begun. Bubble formation was significantly more frequent in left superior PVs compared to the other PVs (left superior PV 27.3% left inferior PV 18.6%, right superior PV 20.5%, and right inferior PV 18.8%, P=0.005, left superior PV vs other PVs, P<0.001) even after adjustment for the other factors including generator power settings and the temperature setting. CONCLUSION: Bubble formation is common during RF ablation of PV with 8-mm tip catheter and can occur as early as 2 seconds after starting RF. RF generator power is negatively correlated with bubble formation while generator temperature settings are positively correlated with formation of bubbles. Microbubble formation is also more frequent with ablation of the left superior PV probably due to better catheter contact in that area.

Frequency of atrial tachyarrhythmias following transcatheter closure of patent foramen ovale.

BACKGROUND: Transcatheter closure of patent foramen ovale (PFO) in patients with a history of cryptogenic stroke is performed with increasing frequency. However, the long-term effects of these closure devices on atrial tachyarrhythmias (ATs) are not known. METHODS AND RESULTS: The study population included 71 patients [31 (44%) men, aged 54 +/- 14 years] with PFO, diagnosed by transesophageal echocardiography (TEE), and greater than or equal to 1 cryptogenic stroke (n = 70) or orthodoxia (n = 1). Patients underwent transcatheter closure of PFO using a 28 mm (n = 53) or a 33 mm (n = 18) CardioSEAL closure device (n = 67) or an Amplatzer occluder (n = 4). Five (7%) patients presented with newly diagnosed (n = 4) or recurrent (n = 1) episodes of AT (3 atrial fibrillation and 2 typical atrial flutter) within 1 to 480 days following the procedure, with an average time to onset of 175 +/- 221 days. ATs were more frequent in those who received a 33 mm device than those who received a 28 mm device [4/18 (22%) vs. 1/53 (2%); p < 0.05]. Patients with ATs showed a trend toward a larger left atrium only on apical view (6.5 +/- 1.4 cm vs. 5.1 +/- 0.9 cm; p = 0.05). However, the difference in left atrial size on parasternal view and right atrial size between the 2 groups was not statistically significant (4.5 +/- 1.1 cm vs. 3.7 +/- 0.8 cm and 5.9 +/- 2.4 cm vs. 4.6 +/- 0.7 cm). Conclusion. Compared to the age-matched population, sustained ATs appear to be relatively common following transcatheter closure of PFO. In our series, they seemed to occur more frequently in patients who received larger devices.

Repeated dual external direct cardioversions using two simultaneous 360-J shocks for refractory atrial fibrillation are safe and effective.

Failure of cardioversion of atrial fibrillation (AF) to sinus rhythm (SR) by standard external direct current cardioversion (DCC) may be due to failure of delivery of enough defibrillating energy rather than to the true refractoriness of AF. Ninety-nine patients with persistent AF (76 male; age 63.7 +/- 0.4 years; weight 113.1 +/- 25.1 kg) who failed standard DCC were included in this report. Under anesthesia, QRS synchronous shocks were delivered across anteroposterior electrodes in the following sequence: (1) a single 360-J shock; (2) another single 360-J shock within 2 minutes; (3) 30 minutes of rest, reinduction of anesthesia and delivery of two simultaneous monophasic 360-J shocks. All patients underwent all three DCC steps. Sixty-six (67%) patients converted to SR following the first dual simultaneous shock. Fourteen patients (14%) required more than one dual shock to achieve SR. This increased the overall success rate of resuming SR to 81%. Except for minor skin burns in three patients there were no procedure related complications. On follow-up at 1 month, 55 (56%) patients were still in SR, whereas 50 (51%) patients maintained SR at 12 months. This was similar to our general DCC population (55% of the 1698 patients were in SR 6 months post-DCC, P = ns). In conclusion, dual external monophasic 360-J DCC is an effective rescue technique for restoration of SR in patients with AF refractory to standard DCC. AF in these patients seems to be as amenable to chronic suppression as AF in the general population of DCC patients.

Efficacy and safety of sildenafil in the evaluation of pulmonary hypertension in severe heart failure.

This study sought to evaluate the utility of sildenafil in assessing pulmonary artery reactivity in left-sided cardiac failure and secondary pulmonary hypertension (PH). Fourteen consecutive patients with heart failure were studied, with oral doses of either sildenafil 25 mg (n = 8) or 50 mg (n = 6) every 8 hours for 20% decreases in pulmonary artery pressures. There was also a 20% reduction of the pulmonary vascular resistance/systemic vascular resistance ratio, indicating relative pulmonary artery selectivity. Compared with sildenafil 25 mg, sildenafil 50 mg demonstrated greater reductions of pulmonary pressures. Oral sildenafil is safe and effective for the evaluation of PH reactivity in heart failure.

Difficult cases in heart failure. Percutaneous transluminal septal myocardial ablation in the management of hypertrophic obstructive cardiomyopathy.

Hypertrophic cardiomyopathy is a complex genetic condition with a heterogeneous clinical course. Some patients remain asymptomatic throughout life while others develop one or more of the adverse clinical consequences including symptoms of congestive heart failure with exertional dyspnea and functional disability (usually with preserved left ventricular systolic function), atrial fibrillation, or sudden cardiac death. Because of this heterogenicity in the clinical presentations, management of patients with hypertrophic cardiomyopathy includes a wide range of pharmacologic therapies as well as invasive approaches. In recent years, nonsurgical catheter-based treatment of hypertrophic cardiomyopathy has been increasingly used in the management of a subset of these patients. The authors present a case of percutaneous transluminal septal myocardial ablation in a patient with hypertrophic cardiomyopathy who was symptomatic despite maximal medical treatment.

Sildenafil and assessment of pulmonary arterial reactivity in heart failure.

Pulmonary hypertension is a daunting accompaniment of advanced heart failure. Efforts to safely and consistently lower pulmonary vascular resistance are necessary but fraught with challenges. In this report the authors explore the novel use of sildenafil, an inhibitor of phosphodiesterase-5, in tackling pulmonary hypertension in heart failure. The salutary effects of this agent deserve further study.

Use of pharmaceuticals in noninvasive cardiovascular diagnosis.

A number of pharmaceuticals are employed as diagnostic agents for cardiovascular diseases. Four groups of agents are reviewed here: 1) vasoactive substances employed as adjuncts to physical maneuvers in diagnosis of structural heart disease; 2) vasodilators used to produce heterogeneity of coronary flow; 3) sympathomimetic agents simulating the effects of exercise on the heart for the purpose of detection of coronary artery stenosis; and 4) ultrasonic contrast agents used to enhance myocardial imaging for the assessment of segmental wall motion. In the first group are amyl nitrate, a vasodilator, and methoxamine and phenylephrine, both vasopressors. The vasodilators of the second group are dipyridamole and adenosine. When combined with scintigraphic perfusion imaging or with echocardiographic assessment of segmental wall motion, these agents can detect single- or multiple-vessel coronary artery disease with sensitivity and specificity comparable to submaximal exercise. They are especially useful for preoperative risk assessment before noncardiac surgery. The sympathomimetic agents of the third group, dobutamine and arbutamine, increase myocardial contractility and heart rate, and dilate the peripheral vasculature. As with the vasodilators, when combined with nuclear or echocardiographic techniques they are equivalent to exercise in detection of coronary disease. They are especially useful in patients with bronchospastic disease and for assessment of myocardial viability. Agents from groups 2 and 3 have acceptable side-effect and safety profiles. The last group reviewed includes echocardiographic contrast agents that, in this investigative setting, are employed to enhance detection of segmental wall motion when used with agents from groups 2 and 3.