Episodes Of Ventricular Arrhythmias Research Articles

Abstract 18059: Utility of Infarct Edge Homogenization in Controlling Ventricular Tachycardia in Patients With Underlying Ischemic Heart Disease

Introduction: Point source ablation may be effective in eliminating stable ventricular tachycardia (VT), where actual mapping and ablation are possible. Ablating patients with unstable VT is more complicated and may require aggressive intervention. While small linear lesions have been utilized, the actual utility of longer linear homogenization for eliminating ventricular arrhythmias has not been examined. Methods: Therefore, the results of 86 patients undergoing VT ablation at Mayo Clinic were examined. 42 had underlying ischemic heart disease with an EF of 33.5 ± 16.8 had VT with a cycle length of 326 ± 165 ms, and had 2.5± 1.6 episodes of VT in the preceding three months. 32 required shocks for that tachycardia. Results: Of these, 21 patients (16 male, 5 female Age 67±18) underwent detailed linear ablation at the scar margin in an effort to homogenize that region. This was drawn into the infarct scar by decreasing the upper voltage boundary to 2.0. In these patients, 18 showed elimination of clinical VT. In addition, 12 showed a decrease in VT from 10 ± 8.7 episodes down to 2.5 ± 1.2 episodes of actual ventricular arrhythmias. The shock requirement decreased from 8.6 ±4.7 to 1.5 ±2.7. These patients had 7 ± 3.5 different VTs at the time of ablation. These data suggest not only a decrease the occurrence of VT, but an improved control of the arrhythmia as manifested by decreased frequency of episodes and a decrease in shock. This suggests a straightforward alternative to point source ablation or to the requirement of detailed LAVA intervention. Conclusion: Linear infarct edge homogenization is a straightforward means of ablating ventricular tachycardia’s, even when unstable. This approach may be simpler than seen with LAVA interventions.

Role of electrical storm as a mortality and morbidity risk factor and its clinical predictors: a meta-analysis

Electrical storm (ES) is a devastating and life-threatening event in clinical practice, but its real weight as a risk factor and its clinical predictors remain unclear. Our objective was to evaluate ES as a mortality and morbidity risk factor and to define the clinical variables associated with ES. The meta-analysis was performed according to the PRISMA guidelines. At the end of the selection process, 13 studies were collected and included in the quantitative analysis. Mortality and morbidity due to ES were assessed. The most acknowledged ES predictors were taken into account in separate sub-analyses. The whole cohort included 5912 patients (857 with ES). Risk of death was increased in the ES group [risk ratio (RR) 3.15; 95% confidence interval (CI) 2.22-4.48]. Electrical storm was also associated with increased composite risk of all-cause death, cardiac transplantation, and hospitalization for acute heart failure (RR 3.39; 95% CI 2.31-4.97). These results were confirmed by comparing the ES group with patients with or without previous unclustered episodes of ventricular arrhythmias. Moreover, implantable cardioverter-defibrillator (ICD) for secondary prevention, lower ejection fraction, monomorphic ventricular tachycardia as triggering arrhythmia, and class I anti-arrhythmic drugs therapy were all associated with ES. Electrical storm is a strong mortality risk factor and it is associated with an increased combined risk of death, heart transplantation, and hospitalization for heart failure. Implantable cardioverter-defibrillator for secondary prevention, monomorphic ventricular tachycardia as triggering arrhythmia, lower ejection fraction, and class I anti-arrhythmic drugs therapy are all associated with ES and could be used to define specific populations with higher risk to develop ES.

Indikationen zur Katheterablation bei ventrikulärer Tachykardie

Ventricular tachyarrhythmias (VT) can cause sudden cardiac death. This can be prevented by an implantable cardioverter-defibrillator (ICD) but approximately 25% of patients with an ICD develop electrical storm (≥ 3 VTs within 24 hours) during the course of 4-5 years. This is a life-threatening event even in the presence of an ICD, particularly if incessant VT is present, and may significantly deteriorate the patient's psychological state if multiple shocks are discharged. Catheter ablation of VT has developed into a standard procedure in many specialized electrophysiology centers. Patients with hemodynamically stable and unstable VT are amendable to substrate-based ablation strategies. Catheter ablation can be performed as emergency procedure in patients with electrical storm as well as electively in patients with monomorphic VT stored in ICD memory. In patients with ischemic or non-ischemic cardiomyopathy, VT ablation is complementary to ICD implantation and can reduce the number of ventricular arrhythmia episodes and shocks and should be performed early. In patients with electrical storm, catheter ablation can acutely achieve rhythm stabilization and may improve prognosis in the long term. Further indications for catheter ablation exist in patients with idiopathic VT where catheter ablation represents a curative therapy, and in patients with symptomatic or asymptomatic frequent premature ventricular beats which may improve prognosis in patients with heart failure and cardiac resynchronization therapy.

Safety of Sports for Athletes With Implantable Cardioverter-Defibrillators

Background— The risks of sports participation for implantable cardioverter-defibrillator (ICD) patients are unknown. Methods and Results— Athletes with ICDs (age, 10–60 years) participating in organized (n=328) or high-risk (n=44) sports were recruited. Sports-related and clinical data were obtained by phone interview and medical records. Follow-up occurred every 6 months. ICD shock data and clinical outcomes were adjudicated by 2 electrophysiologists. Median age was 33 years (89 subjects <20 years of age); 33% were female. Sixty were competitive athletes (varsity/junior varsity/traveling team). A pre-ICD history of ventricular arrhythmia was present in 42%. Running, basketball, and soccer were the most common sports. Over a median 31-month (interquartile range, 21–46 months) follow-up, there were no occurrences of either primary end point—death or resuscitated arrest or arrhythmia- or shock-related injury—during sports. There were 49 shocks in 37 participants (10% of study population) during competition/practice, 39 shocks in 29 participants (8%) during other physical activity, and 33 shocks in 24 participants (6%) at rest. In 8 ventricular arrhythmia episodes (device defined), multiple shocks were received: 1 at rest, 4 during competition/practice, and 3 during other physical activity. Ultimately, the ICD terminated all episodes. Freedom from lead malfunction was 97% at 5 years (from implantation) and 90% at 10 years. Conclusions— Many athletes with ICDs can engage in vigorous and competitive sports without physical injury or failure to terminate the arrhythmia despite the occurrence of both inappropriate and appropriate shocks. These data provide a basis for more informed physician and patient decision making in terms of sports participation for athletes with ICDs.

Effect of Long-Detection Interval vs Standard-Detection Interval for Implantable Cardioverter-Defibrillators on Antitachycardia Pacing and Shock Delivery

Using more intervals to detect ventricular tachyarrhythmias has been associated with reducing unnecessary implantable cardioverter-defibrillator (ICD) therapies. To determine whether using 30 of 40 intervals to detect ventricular arrhythmias (VT) (long detection) during spontaneous fast VT episodes reduces antitachycardia pacing (ATP) and shock delivery more than 18 of 24 intervals (standard detection). Randomized, single-blind, parallel-group trial that enrolled 1902 primary and secondary prevention patients (mean [SD] age, 65 [11] years; 84% men; 75% primary prevention ICD) with ischemic and nonischemic etiology undergoing first ICD implant at 1 of 94 international centers (March 2008-December 2010). Patients were randomized 1:1 to programming with long- (n = 948) or standard-detection (n = 954) intervals. Total number of ATPs and shocks delivered for all episodes (primary outcomes) and inappropriate shocks, mortality, and syncopal rate (secondary outcomes). During a median follow-up of 12 months (interquartile range, 11-13), long-detection group had 346 delivered therapies (42 therapies per 100 person-years, 95% CI, 38-47) vs 557 in the standard-detection group (67 therapies per 100 person-years [95% CI, 62-73]; incident rate ratio [IRR], 0.63 [95% CI, 0.51-0.78]; P < .001). The long- vs the standard-detection group experienced 23 ATPs per 100 person-years (95% CI, 20-27) vs 37 ATPs per 100 person-years (95% CI, 33-41; IRR, 0.58 [95% CI, 0.47-0.72]; P < .001); 19 shocks per 100 person-years (95% CI, 16-22) vs 30 shocks per 100 person-years (95% CI, 26-34; IRR, 0.77 [95% CI, 0.59-1.01]; P = .06), with a significant difference in the probability of therapy occurrence (P < .001); and a reduction in first occurrence of inappropriate shock (5.1 per 100 patient-years [95% CI, 3.7-6.9] vs 11.6 [95% CI, 9.4-14.1]; IRR, 0.55 [95% CI, 0.36-0.85]; P = .008). Mortality (5.5 [95% CI, 4.0-7.2] vs 6.3 [95% CI, 4.8-8.2] per 100 patient-years; HR, 0.87; P = .50) and arrhythmic syncope rates (3.1 [95% CI, 2.6-4.6] vs 1.9 [95% CI, 1.1-3.1] per 100 patient-years; IRR, 1.60 [95% CI, 0.76-3.41]; P = .22) did not differ significantly between groups. Among patients receiving an ICD, the use of a long- vs standard-detection interval resulted in a lower rate of ATP and shocks, and inappropriate shocks. This programming strategy may be an appropriate alternative. clinicaltrials.gov Identifier: NCT00617175.

Double jeopardy

Torsades de pointes ("twisting of points") (TdP) is a broad complex tachyarrhythmia which was first described in 1966 by Francois Dessertenne and usually results from prolongation of the QT interval.(1) A wide variety of drugs have been shown to prolong the QT interval in susceptible individuals.(2) We present the case of a former intravenous heroin user presenting with several episodes of TdP which were caused by QT prolongation due to methadone treatment and exacerbated by hepatitis B/C infection. Despite aggressive medical treatment and withdrawal of methadone, he had recurrent episodes of TdP which required continuous temporary cardiac pacing for six days. He was found to have moderate LV dysfunction on his echocardiogram and unobstructed coronary arteries on coronary angiography. He underwent implantation of a defibrillator due to concerns about further episodes of ventricular arrhythmias which could recur even in the absence of further methadone use.

Successful Surgical Removal of a Giant Interventricular Fibroma: Surgical Approach Without Ventriculotomy

A 14-month-old boy was transported to our hospital by ambulance because of cardiopulmonary arrest after the sudden onset of convulsions. He was resuscitated and transthoracic echocardiography showed a giant interventricular tumor. The cause of this episode was thought to be ventricular arrhythmias induced by the tumor. At operation, an incision line was confirmed by direct ultrasonography. The heart was incised directly on the interventricular septum. The tumor was carefully dissected and completely removed without entering the ventricular cavity. Histologic analysis revealed a fibroma. The patient's postoperative course was uneventful, and he remains well without episodes of heart failure or ventricular arrhythmia.

Vasovagal cardiac arrest during spinal anesthesia for Cesarean section -A case report-

The vasovagal response is characterized by an inappropriate combination of bradycardia and paradoxical vasodilation. During a general or neuraxial anesthesia-induced sympathectomy, a sudden vagal activation and/or an acute reduction in sympathetic tone can cause serious vasovagal responses. Neuraxial anesthesia for Cesarean section may trigger vasovagal response, due to multiple risk factors; high neuraxial block, sudden hemorrhage, aortocarval compression, peritoneal manipulation, and emotional stress. A 39-year-old pregnant woman, at 38 weeks of gestation with episodes of non-sustained ventricular arrhythmia and newly developed vasovagal syncope during pregnancy, was scheduled to undergo a spinal anesthesia for an elective Cesarean section. Immediately after the placental expulsion, a sudden severe bradycardia, followed by a cardiac arrest occurred. The patient fully recovered after prompt cardiopulmonary resuscitation with chest compression, manual ventilation with oxygen, rapid injection of epinephrine and hydration. This case illustrates a serious potential risk of vasovagal response superimposed on neuraxial anesthesia, during a Cesarean section, especially during placental expulsion.

Ablation of ventricular tachycardia: Inside-out or outside-in?

Sustained ventricular tachycardia (VT) causes significant morbidity and sudden death in patients with structural heart disease. Currently, right or wrong, VT ablation is often reserved as a treatment of last resort after the patient has received an implantable cardioverter-defibrillator (ICD), has failed an antiarrhythmic drug, and ultimately presents with VT storm. It is estimated that 35% of the patients with a primary prevention ICD will experience their first episode of ventricular arrhythmia within 3 years, with a 450% chance of subsequent ICD therapies. 1‐3 The incidence is even higher for patients with an ICD for secondary prevention indications. As patients live longer and more primary prevention ICDs are implanted, the number of VT ablations performed has also increased. The referral patterns for VT ablation over the past several years has expanded from ischemic heart disease to include more patients with nonischemic etiology such as arrhythmogenic right ventricular cardiomyopathy and dilated cardiomyopathy, where there is minimal endocardial low-voltage regions. Since the myocardial substrate is 3-dimensional, potential VT circuits can involve not only the subendocardial layer but also the intramural and the epicardial myocardium. While the prevalence of epicardial substrate in the population with nonischemic cardiomyopathy (NICM) remains ill-defined, many patients with NICM have more extensive bipolar low-voltage regions on the epicardium than the endocardium. 4 VT ablation was initially described in the postinfarction setting and involved surgical resection of the left ventricular aneurysm and subendocardial resection guided by intraoperative mapping to remove regions of abnormal and fractionated electrograms. 5,6 As technology has evolved over the past decades, the ability to “mimic” the surgical approach of “removing” the infarct zone by using a catheterbased approach became feasible, making the catheter-based ablation the preferred strategy in treating medically refractory VT. While endocardial ablation alone is able to control infarct-related VT with reasonable success, the same cannot be said of VT occurring in the setting of a nonischemic etiology primarily owing to the epicardial nature of the nonischemic substrate. 7‐11 Furthermore, despite an apparent initial successful ablation, depending on the underlying substrate, upward of 40% of the patients have recurrent VT. 12‐14 Some of the potential causes of ablation failure are related to broad complex circuits with multiple exits; inability to adequately identify appropriate ablation targets; progression of disease; thickness and density of the scar; and inability of the radiofrequency lesion to penetrate deep enough into the muscle to disrupt the circuit. In addition, in patients with VT whose substrate is nonischemic in nature, epicardial mapping can be limited by proximity to coronary vessels or insulated by epicardial fat. Sosa et al 15 first described the subxyphoid technique of epicardial mapping and ablation in the setting of VT related to Chagas disease. As more patients with nonischemic etiology of VT are referred for ablation, the number of patients requiring an epicardial approach has also increased. With improvements in the safety and in refinement techniques of epicardial mapping and ablation, the threshold to go epicardial has been lowered. In this issue of HeartRhythm, Tung et al 16 report their experience of epicardial VT ablation and the outcomes at a single tertiary referral center. The study design was a retrospective, nonrandomized study of 144 patients referred for VT ablation from 2004 to 2011, during which a total of 109 epicardial procedures were performed in 95 patients. Patients were divided into 3 groups: ischemic, nonischemic, and idiopathic. A comparison was made between patients who underwent both endo- and epicardial mapping and ablation to those who underwent endocardial ablation alone. A successful access to the pericardial space by using the method described by Sosa was achieved in 94%, with a major complication rate of 8.8% and bleeding in 6.7%. There was no procedure-related mortality and no tamponade or surgical intervention in any of the patients. The authors found that patients with ischemic VT who underwent combined endo- and epicardial ablation had a better outcome at 6 and 12 months compared to endocardial ablation alone. In contrast, for the nonischemic group, no difference was found between those who underwent combined endo- and epicardial ablation and those who underwent endocardial ablation alone. In our experience, patients with ICM have a

Left Thoracoscopic Sympathectomy Used as Primary Therapy for a Young Child With Intractable Long QT Syndrome

A 3-year-old boy with familial long QT syndrome type 2 presented with recurrent syncope despite adequate beta-blocker therapy. Two family members had experienced sudden cardiac arrest, and one other relative had experienced sudden cardiac death. Given the high risk for ventricular arrhythmia/syncope, the decision was made to perform primary cardiac denervation therapy through a minimally invasive approach without concomitant automatic cardioverter-defibrillator implantation. Using video-assisted thoracoscopic surgery, the left-sided sympathetic ganglia from T2-T5 were identified, and dissection along the sympathetic chain with transection of the corresponding rami along T2-T5 in addition to the lower half of the stellate ganglion was performed. The chest tube was removed on day 1 after surgery, and the patient was discharged on postoperative day 4. During 14 months of follow-up evaluation, no intervening episodes of ventricular arrhythmia or syncope and no symptoms of Horner's syndrome were noted.

626 Pericardial Adhesions: Another Hurdle to Epicardial Ablation of Ventricular Tachycardia?

/ 9 yrs). The ejection fraction was 25.2% 8.3 and MVO2 was 1.55 0.48 l/min. 36 patients had ischemic and 39 nonischemic cardiomyopathy. After mean follow-up of 609 244 days, 35 therapies were delivered in 12 patients (16%), with 2 non-target therapies for atrial fibrillation. Among appropriate therapies for ventricular arrhythmias, 9 (26%) occurred while the patient was active. Patients with arrhythmias had similar follow-up time to those without (686 186 vs 596 251 days, p 0.26). Patients with arrhythmia had no difference in MVO2 than those without (1.61 0.44 vs 1.54 0.49, p 0.68) and no difference in age (58.6 7.9 vs 61.3 9.0, p 0.35). Ejection fraction was higher in patients with arrhythmia (30 10 vs 24 8, p 0.04) and remained independently associated in a multivariate logistic model that included age, BMI, MVO2, etiology, beta blockade and ACE inhibition. CONCLUSION: The majority of episodes of ventricular arrhythmia requiring ICD therapy occur while patients are at rest. If the activity-arrhythmia relationship is modified by fitness, the effect is too small for the current sample to detect. Further enrolment and study will assess this possibility. HSF of Ontario

Enhancement of intracardiac navigation by new GPS-guided location system (MediGuide Technologies)

Ventricular tachycardia in patients with structural heart disease is a clinical relevant arrhythmogenic disorder. Many of these patients require a combination of implantable cardioverter-defibrillator (ICD) for prevention of sudden cardiac death with antiarrhythmic medications to decrease the frequency of ventricular tachycardia (VT) episodes. However, ICD cannot prevent arrhythmia episodes and medication has only limited efficacy and in relevant number of patients it has to be discontinued due to multiple side effects. Severalreportsinthelastdecadehaveshownthatinpatientswith frequently recurrent ventricular arrhythmia episodes catheter ablation can be a highly effective therapy as an adjunct to ICD and/or medical treatment. In addition, the SMASH-VT and VTACH trials demonstrates, that prophylactic VT ablation results in a prolonged time to recurrence of VT in patients with stable VT, previous myocardial infarction, and reduced left ventricular ejection fraction. 1,2 According to this data it is hardlysurprising that, besides atrialfibrillation ablation, treatment of ventricular tachycardia is the next big frontier in the field of interventional therapy of cardiac arrhythmias. However, management of ventricular tachycardia is still challenging driven by a complex three-dimensional substrate. Successful treatment requires a comprehensive understanding and visualization of cardiac anatomy and electrical activation. Beside conventional fluoroscopy, 3-D electromagnetic mapping systems have been introduced to facilitate catheter navigation. Currently used techniques have some weaknesses. For instance, fluoroscopy provides only two-dimensional information, where it is difficult to repeatedly guide the catheter to the same area of interest. Thus, with prolonged procedures there is an increased X-ray exposure, adding risk for both the patient and the physician. One limitation of available 3-D-mapping system is failing to sufficiently compensate for respiratory, cardiac cycle, and patient movement and the limited integration on fluoroscopy. Recently, a new intracardiac navigation system (MediGuide TM System) was introduced to overcome this limitation and to merge the key benefits of fluoroscopy and 3-D-mapping system in a unique manner. In the following we are going to introduce this technology and present potential implications on interventional treatment of ventricular arrhythmias.

Investigation of a novel algorithm for synchronized left-ventricular pacing and ambulatory optimization of cardiac resynchronization therapy: Results of the adaptive CRT trial

In patients with sinus rhythm and normal atrioventricular conduction, pacing only the left ventricle with appropriate atrioventricular delays can result in superior left ventricular and right ventricular function compared with standard biventricular (BiV) pacing. To evaluate a novel adaptive cardiac resynchronization therapy ((aCRT) algorithm for CRT pacing that provides automatic ambulatory selection between synchronized left ventricular or BiV pacing with dynamic optimization of atrioventricular and interventricular delays. Patients (n = 522) indicated for a CRT-defibrillator were randomized to aCRT vs echo-optimized BiV pacing (Echo) in a 2:1 ratio and followed at 1-, 3-, and 6-month postrandomization. The study met all 3 noninferiority primary objectives: (1) the percentage of aCRT patients who improved in their clinical composite score at 6 months was at least as high in the aCRT arm as in the Echo arm (73.6% vs 72.5%, with a noninferiority margin of 12%; P = .0007); (2) aCRT and echo-optimized settings resulted in similar cardiac performance, as demonstrated by a high concordance correlation coefficient between aortic velocity time integrals at aCRT and Echo settings at randomization (concordance correlation coefficient = 0.93; 95% confidence interval 0.91-0.94) and at 6-month postrandomization (concordance correlation coefficient = 0.90; 95% confidence interval 0.87-0.92); and (3) aCRT did not result in inappropriate device settings. There were no significant differences between the arms with respect to heart failure events or ventricular arrhythmia episodes. Secondary end points showed similar benefit, and right-ventricular pacing was reduced by 44% in the aCRT arm. The aCRT algorithm is safe and at least as effective as BiV pacing with comprehensive echocardiographic optimization.

Is medroxyprogesterone safe in women with long QT syndrome?

G Twenty-two percent of women in the United States use depot medroxyprogesterone acetate (MPA) at some stage in their life for contraception. It is highly effective, can be elf-administered, and has high adherence rates. The World ealth Organization lists it as a first-line option for young omen, particularly those wishing to avoid the adverse ffects of estrogens, such as breast-feeding mothers, smokrs, those who are overweight, and those with atrial fibrilation, pulmonary hypertension, valvular heart disease, and ypertension in pregnancy. Thus, when a case report apears suggesting a possible link between MPA and QT rolongation with cardiac arrest, the evidence needs to be eviewed carefully; the impact of withdrawal or even cauion with MPA could be massive. Giudicessi et al report a woman with a frame shift mutation in KCNH2 (long QT type 2) who in her midtwenties had 2 episodes of ventricular arrhythmia with a prolonged QT interval while taking MPA over a period of 16 months overall. Once MPA was discontinued, no further events occurred over the next 6 years, including 2 further uneventful pregnancies and postpartum periods. Women are more prone than men to the QT-prolonging effects of drugs. Most such drugs exert their effect on the otassium channel IKr, the channel that is defective in long T syndrome type 2. Nevertheless, the case comes as a urprise since it seems beyond doubt both from clinical and n vitro studies that while estrogen prolongs the QT interval, rogesterone (and testosterone) shortens it. The QT-proonging effects of some drugs, for example, ibutilide, are itigated by progesterone. During pregnancy in long QT type 2, the risk of cardiac events is reduced. This is believed to be due to the protective (QT-shortening) effect of endogenous progesterone. During the postpartum period, the protective effect of endogenous progesterone disappears and there is an immediate high risk of cardiac events. In a transgenic rabbit model of long QT type 2, progesterone reduces the incidence of arrhythmia.

Defibrillator implantation associated with ventricular arrhythmia ablation: an emerging hybrid approach

Ventricular arrhythmias are an important cause of morbidity and mortality and are the leading cause of sudden cardiac death. Although implantable cardioverter-defibrillators (ICD) proved to be effective in reducing both sudden cardiac death and all-cause mortality, the ideal therapy remains to be defined because ICD implantation allows to interrupt life-threatening ventricular arrhythmias but does not prevent them. ICD interventions, in terms of shock delivery and antitachycardia pacing, are often associated with invalidating symptoms, such as chest pain, sensation of rapid heartbeat and syncope, and may cause depression in many patients. Both appropriate and inappropriate shocks have been shown to be associated with a worse prognosis. Transcatheter ablation proved to be safe and effective in reducing arrhythmia relapse in patients who experience multiple ICD interventions or electrical storm. In the latter patient subset, ablation often represents the only possibility of interrupting such dramatic events. Ablation has also been evaluated in patients implanted with an ICD in secondary prevention, before device intervention. To date, transcatheter ablation represents an optimal opportunity, complementary to ICD, in the treatment of patients at high risk for sudden death and episodes of ventricular arrhythmias.

Feminizing Adrenal Carcinoma Presenting with Heart Failure and Ventricular Tachycardia

We present a case of feminizing adrenal carcinoma with severe elevation in serum estradiol and otherwise unexplained congestive heart failure with ventricular arrhythmia and review the literature on feminizing adrenal tumors and the potential relationship between estrogen and cardiac problems. A 54-year-old man presented with congestive heart failure and ventricular arrhythmia. Imaging revealed a large adrenal mass. Hormonal evaluation revealed a very high serum level of estradiol, elevated DHEA-sulfate and androstenedione, and lack of cortisol suppression on a low-dose overnight dexamethasone suppression test. The patient underwent a left adrenalectomy with subsequent normalization of serum estradiol. Surgical pathology examination established adrenocortical carcinoma MacFarlane stage II. Upon 15-month followup, the patient continued to have a normal serum estradiol level, his cardiac function was significantly improved, and he had no further episodes of ventricular arrhythmia. To the best of our knowledge, the serum estradiol level that was detected in our case is the highest that has been reported. Further, we hypothesize that the very high serum concentration of estradiol in our case may have played a role in his cardiac presentation with congestive heart failure and arrhythmia, particularly as these problems resolved with normalization of his serum estradiol level.

Computational Predictions of Tissue-Specific Consequences of Long QT Mutations: Role of the Purkinje Fiber

The long QT syndrome (LQTS) is a heritable cardiac disorder that leads to prolongation of ventricular repolarization, episodes of ventricular arrhythmia, and sudden cardiac death. Mounting evidence has implicated the Purkinje fiber (PF) conduction system in the genesis of ventricular arrhythmias. This study assesses for tissue-specific consequences of the biophysical alterations induced by LQTS-related mutations, using computational models of ventricular and PF cells. Mutations causing LQT1 and LQT2 (in KCNQ1 and HERG, respectively) are first simulated by reducing density of the respective components of the delayed rectifier current. These mutations prolong action potential duration (APD) in ventricular myocytes more than in their PF counterparts, due to differences in the conductance and activation of plateau potassium currents between the two cell types. Next, the canonical LQT3 mutation delKPQ (in the cardiac NaV 1.5 sodium channel, encoded by SCN5A) is modeled in both tissue types (as described previously, by increasing entry into a bursting mode of channel gating, producing substantial late non-inactivating inward current). Marked APD prolongation is confirmed in both tissue types, exacerbated by slow stimulation rates or pauses in pacing. Simulation of another SCN5A mutation, F1473C, which clinically produces severe QT prolongation and heavy arrhythmia burden, is shown to have a markedly larger effect on PF cells than ventricular myocytes (including a propensity for repetitive early afterdepolarizations), owing to a depolarizing shift in the mutant channel availability and lower plateau potential in PF. Finally, the interactions between PF and ventricular cells at the tissue level are investigated in the context of these mutations in a cable model representing a section of ventricular wall. In conclusion, the biophysical alterations induced by LQT mutations may have significant tissue-specific consequences, with important implications for arrhythmia and its therapy.

Primary Ablation for Ventricular Tachycardia: When and How?

Catheter ablation of ventricular tachycardia (VT) has improved arrhythmia-free survival in patients with multiple VT episodes refractory to antiarrhythmic drugs. Recent studies have evaluated the role of early intervention with catheter ablation in patients experiencing a single episode of life-threatening ventricular arrhythmias and undergoing secondary prevention defibrillator implantation. Such “primary VT ablation” strategy has proven effective in reducing the VT recurrence rate compared with standard medical therapy (no antiarrhythmic drug). This article summarizes the evidence on primary VT ablation and discusses its clinical indications and outcomes compared with standard catheter ablation of drug-refractory recurrent VT (ie, secondary VT ablation).

Predictors of sustained ventricular arrhythmia episodes in patients with primary ICD indication

Implantable cardioverter-defibrillators (ICD) reduce mortality in patients with severely impaired left ventricular function. In randomized studies, female patients are underrepresented and data on ICD therapy is limited. Atrial fibrillation (AF) is a determinant of poor prognosis but has not been consistently evaluated. We evaluated the risk factors for the occurrence of ventricular arrhythmia episodes in patients with primary ICD prophylaxis. Consecutive patients after ICD implantation for primary prophylaxis were followed. During follow-up, detected sustained episodes of ventricular arrhythmia were documented. Multivariate analysis controlled for propensity score was used to evaluate the correlation between gender, history of AF, and the occurrence of ventricular arrhythmia episodes. A total of 400 patients (19.8% female; n = 79) were included. During follow-up, 64 patients (16%) had appropriate ICD therapy episodes. Men (18%) had significantly more often episodes than women (8%; p = 0.025). Patients with a history of AF (102, 25.5%) had significantly more often episodes (30%) compared to patients without a history of AF (11%; p < 0.001). In a multivariate model, only gender (p = 0.02) and history of AF (p < 0.001) were significantly associated predictors of the occurrence of appropriate ICD therapies during follow-up. Based on the propensity score model, the adjusted hazard ratio for male gender was 2.7 (p = 0.02) and 2.6 (p = 0.0004) for history of AF. Male gender and history of AF are independent predictors for the occurrence of sustained ventricular arrhythmia in primary ICD prophylaxis. Further studies need to evaluate whether history of AF in female patients might be an indicator for higher risk of sudden cardiac arrhythmic death.

Implantable Cardioverter-Defibrillator Patients Who Are Upgraded and Respond to Cardiac Resynchronization Therapy Have Less Ventricular Arrhythmias Compared With Nonresponders

The purpose of this study was to evaluate the impact of upgrading implantable cardioverter-defibrillator (ICD) therapy to cardiac resynchronization therapy (CRT) combined with defibrillator (CRT-D) on the occurrence of ventricular arrhythmia (VA) and appropriate ICD therapies. CRT has been shown to improve left ventricular (LV) systolic function and induce reverse LV remodeling. In addition, it has been hypothesized that CRT may reduce the incidence of VA. Heart failure patients receiving an upgrade from ICD to CRT-D were evaluated. Patients were considered responders to CRT if LV end-systolic volume reduced ≥15% at 6 months of follow-up. Episodes of VA, triggering device therapy (anti-tachycardia pacing and shocks) were recorded before and after upgrade for the overall population. In addition, these outcomes were compared between CRT responders and nonresponders during the follow-up period after CRT response was assessed. One hundred fifteen patients (93 males [81%], age 65 ± 12 years) were evaluated during a mean follow-up of 54 ± 34 months before CRT-D upgrade and 37 ± 27 months after upgrade. In CRT responders (n = 70), the frequency of VA requiring appropriate device therapy demonstrated a trend toward a decrease from 0.51 ± 0.79 to 0.30 ± 0.59 per patient per year after CRT-D upgrade (p = 0.052). In CRT nonresponders (n = 45), the frequency of VA requiring appropriate device therapy significantly increased from 0.40 ± 0.69 to 1.21 ± 2.53 per patient per year after CRT-D upgrade (p = 0.014). After upgrade from ICD to CRT-D, nonresponders to CRT showed a significant increase in VA burden requiring appropriate device therapy.