Triggers Of Ventricular Fibrillation Research Articles

Trigger and Substrate Mapping and Ablation for Ventricular Fibrillation in the Structurally Normal Heart.

Sudden cardiac death (SCD) represents approximately 50% of all cardiovascular mortality in the United States. The majority of SCD occurs in individuals with structural heart disease; however, around 5% of individuals have no identifiable cause on autopsy. This proportion is even higher in those <40 years old, where SCD is particularly devastating. Ventricular fibrillation (VF) is often the terminal rhythm leading to SCD. Catheter ablation for VF has emerged as an effective tool to alter the natural history of this disease among high-risk individuals. Important advances have been made in the identification of several mechanisms involved in the initiation and maintenance of VF. Targeting the triggers of VF as well as the underlying substrate that perpetuates these lethal arrhythmias has the potential to eliminate further episodes. Although important gaps remain in our understanding of VF, catheter ablation has become an important option for individuals with refractory arrhythmias. This review outlines a contemporary approach to the mapping and ablation of VF in the structurally normal heart, specifically focusing on the following major conditions: idiopathic ventricular fibrillation, short-coupled ventricular fibrillation, and the J-wave syndromes-Brugada syndrome and early-repolarization syndrome.

PO-02-174 CHARACTERIZATION OF PAPILLARY MUSCLE ABLATION WITH OPTICAL MAPPING AT DIFFERENT TRANSMURAL PENETRATION DEPTHS IN LIVE HUMAN HEART

Papillary muscles (PMs) are known triggers of ventricular arrhythmia, especially nonsustained ventricular tachycardia (VT) and sustained recurrent VT, and may play a role as triggers of ventricular fibrillation. Catheter ablation of PM is challenging and results in high VT recurrence rates. Clinical characterization of PM electrophysiology is challenging due to the limited spatial resolution of electrode arrays, motion, and distal fields. Thus, ablation procedures are limited in two ways: inaccurate determination of target ablation zones and inaccurate characterization of lesion profiles. Characterization of PM before and after ablation can be accomplished with deep infrared optical mapping toward a better understanding of the role of the PM. Using optical mapping and near-infrared voltage-sensitive fluorescent dyes, transmembrane potentials were recorded from the endocardial side of a live explanted human right ventricle free-wall (transplant recipient). We paced the myocardium at different cycle lengths (CLs) before and after ablation, and transmembrane potential maps were obtained using excitation light bands of different penetration depths to characterize the ablated zones transmurally. The PM exhibited alternans in action potential duration (APD) at longer CLs than wall tissue in non-ablated tissue, indicating a highly heterogeneous myocardium. The figure shows relative conduction velocity maps for subsequent beats before and after ablation. While dissection of the tissue appeared to show a transmural burn, optical mapping with different penetration depths, from green (surface) and near-infrared (NI, transmural) illumination, revealed that the transmural electrophysiology profile was ablated, only at the surface. The presence of conduction velocity alternans using NI light indicated incomplete ablation at the deeper subsurfaces, even though it appeared burnt during dissection. Contemporary electro-mapping systems used in clinics often achieve limited electrophysiological characterization in the depth of ablated areas. Such measurements would yield results similar to optical mapping with the green light excitation band (surface only), suggesting successful ablation that may be incomplete and may result in recurrent VT. We demonstrate that optical mapping with NI light is a useful tool for quantitative characterization of ablation parameters.

Catheter Ablation of Ventricular Fibrillation.

Ventricular fibrillation (VF) is a common cause of sudden cardiac death (SCD) and is unfortunately without a cure. Current therapies focus on prevention of SCD, such as implantable cardioverter-defibrillator (ICD) implantation and anti-arrhythmic agents. Significant progress has been made in improving our understanding and ability to target the triggers of VF, via advanced mapping and ablation techniques, as well as with autonomic modulation. However, the critical substrate for VF maintenance remains incompletely defined. In this review, we discuss the evidence behind the basic mechanisms of VF and review the current role of catheter ablation in patients with VF.

Hypothermia and Cold Injury in Children.

Hypothermia and Cold Injury in Children.

Radiofrequency ablation in Brugada syndrome.

Radiofrequency ablation in Brugada syndrome.

Purkinje triggers of ventricular fibrillation in patients with hypertrophic cardiomyopathy.

Ventricular fibrillation (VF) is the main mechanism of sudden cardiac death in patients with hypertrophic cardiomyopathy (HCM). The origin of VF and the success of catheter ablation to eliminate recurrent episodes in this population are poorly understood. From 2010 to 2014, five patients with HCM (age 21 ± 9 years, three female) underwent invasive electrophysiological studies and ablation at our center after resuscitation from recurrent (9 ± 7) episodes of VF. Ventricular premature beats (VPBs), seen to initiate VF in certain cases, were recorded noninvasively before the ablation procedure. Postprocedural computed tomography (CT) was performed to correlate ablation sites with myocardial hypertrophy in three patients. Outcomes were assessed by clinical follow-up and implantable cardioverter-defibrillator interrogations. VPB triggers were localized invasively to the distal left Purkinje conduction system (left posterior fascicle [2], left anterior fascicle [1], and both fascicles [2]). All targeted VF triggers were successfully eliminated by radiofrequency ablation in the left ventricle. Among patients with postablation CT imaging, 93 ± 12% of ablation sites corresponded to hypertrophied segments. Over 50 ± 38 months, four of five patients were free from primary VF without antiarrhythmic drug therapy. One patient who had 13 episodes of VF before ablation had a single recurrence. In our study of patients with HCM and recurrent VF, VF was not initiated from the myocardium but rather from Purkinje arborization. These sources colocalized with the hypertrophic substrate, suggesting electromechanical interaction. Focal ablation at these sites was associated with a marked reduction in VF burden.

Advances in Mapping and Ablation of Ventricular Fibrillation

Catheter ablation of ventricular fibrillation (VF) is challenging due to the difficulty in interpreting fibrillatory electrograms and the complete hemodynamic collapse with VF precluding detailed mapping. Successful ablation can be performed by eliminating triggers of VF. We review the contemporary advances in VF ablation, especially targeting the substrate for VF. Strategies to map and eliminate the substrate for VF can be applied generally, even in the absence of a reliable trigger. VF substrate can be mapped during sinus rhythm with signature low-voltage, fractionated, and late electrograms. Such substrate can be harbored within regions of scar in structural heart disease, or localized as epicardial microstructural abnormality in Brugada syndrome, inferolateral J-wave syndrome, and unexplained VF. Ablation of such substrate is an effective antiarrhythmic strategy. Furthermore, innovations in expeditious panoramic mapping techniques have generated interest in directly mapping and ablating drivers that sustain VF. Advances in understanding of ablation targets and innovations in mapping techniques are enabling successful ablation of VF in the electrophysiology laboratory. Beyond ablation of VF triggers in a subset of patients, progress is being made in ablating the substrate for VF in patients afflicted by this lethal arrhythmia.

Pro- and anti-arrhythmic effects of TRPM4 inhibition on ventricular fibrillation trigger and substrate mechanisms

Ventricular Fibrillation (VF) is a major cause of sudden cardiac death. Purkinje fibers (PF) are known to play an important role in triggering and maintaining VF. Previous studies have highlighted the role of TRPM4 channels in repolarization properties of PFs, but their potential impact on arrhythmogenesis and VF dynamics remains unknown. To investigate the role of TRPM4 channels in Purkinje-mediated trigger and substrate mechanisms. Endocardial optical mapping experiments were performed in sheep perfused left ventricular wedge preparations using a high-resolution CMOS camera. Purkinje-Muscle Junctions (PMJ) were localized through PF stimulation and identification of the breakthrough sites. Arrhythmias were induced either by isoprenaline perfusion (ISO; 1 μM; n = 7) or by endocardial burst pacing (10 Hz; n = 6) and their spatiotemporal dynamics quantified with or without 9-Phenanthrol (9PHE; 45 μM), a known TRPM4 inhibitor. ISO perfusion provoked focal tachy-arrhythmias originating from the PFs confirmed by the co-localization of the exit sites with previously identified PMJs. 9PHE reduced the rate of spontaneous focal activity and activation patterns were no longer correlated to the PMJs. However, following burst pacing, inhibition of TRPM4 led to a higher propensity of VF than ventricular tachycardia (VT). For the induced VT episodes, we observed a significant increase of DF (3.7 ± 0.7 Hz vs. 4.8 ± 0.8 Hz) and a significant decrease of regularity index (0.94 ± 0.05 vs. 0.84 ± 0.07) at the PMJs after 9PHE perfusion, while a significant increase in long lasting rotors was observed ( P = 0.044; for rotor number and P = 0.005; for rotor duration). A significant increase in focal activity (15 ± 2 μpixel/ms vs. 30 ± 9 μpixel/ms) was found during VF episodes. These results suggest that TRPM4 inhibition has anti-arrhythmic effects by preventing VF triggers from PFs, while at the same time increasing the complexity of induced ventricular arrhythmias.

Mapping and Ablation of Ventricular Fibrillation Associated With Early Repolarization Syndrome.

We conducted a multicenter study to evaluate mapping and ablation of ventricular fibrillation (VF) substrates or VF triggers in early repolarization syndromes (ERS) or J-wave syndrome (JWS). We studied 52 patients with ERS (4 women; median age, 35 years) with recurrent VF episodes. Body surface electrocardiographic imaging and endocardial and epicardial electroanatomical mapping of both ventricles were performed during sinus rhythm and VF for localization of triggers, substrates, and drivers. Ablations were performed on VF substrates, defined as areas that had late depolarization abnormalities characterized by low-voltage fractionated late potentials, and VF triggers. Fifty-one of the 52 patients had detailed mapping that revealed 2 phenotypes: group 1 had late depolarization abnormalities predominantly at the right ventricular (RV) epicardium (n=40), and group 2 had no depolarization abnormalities (n=11). Group 1 can be subcategorized into 2 groups: Group 1A included 33 patients with ERS with Brugada electrocardiographic pattern, and group 1B included 7 patients with ERS without Brugada electrocardiographic pattern. Late depolarization areas colocalize with VF driver areas. The anterior RV outflow tract/RV epicardium and the RV inferior epicardium are the major substrate sites for group 1. The Purkinje network is the leading underlying VF trigger in group 2 that had no substrates. Ablations were performed in 43 patients: 31 and 5 group 1 patients had only VF substrate ablation and VF substrates plus VF trigger, respectively (mean, 1.4±0.6 sessions); 6 group 2 patients and 1 patient without group classification had only Purkinje VF trigger ablation (mean, 1.2±0.4 sessions). Ablations were successful in reducing VF recurrences (P<0.0001). After follow-up of 31±26 months, 39 (91%) had no VF recurrences. There are 2 phenotypes of ERS/J-wave syndrome: one with late depolarization abnormality as the underlying mechanism of high-amplitude J-wave elevation that predominantly resides in the RV outflow tract and RV inferolateral epicardium, serving as an excellent target for ablation, and the other with pure ERS devoid of VF substrates but with VF triggers that are associated with Purkinje sites. Ablation is effective in treating symptomatic patients with ERS/J-wave syndrome with frequent VF episodes.

Mitral Valve Prolapse, Ventricular Arrhythmias, and Sudden Death.

Despite a 2% to 3% prevalence of echocardiographically defined mitral valve prolapse (MVP) in the general population, the actual burden, risk stratification, and treatment of the so-called arrhythmic MVP are unknown. The clinical profile is characterized by a patient, usually female, with mostly bileaflet myxomatous disease, mid-systolic click, repolarization abnormalities in the inferior leads, and complex ventricular arrhythmias with polymorphic/right bundle branch block morphology, without significant regurgitation. Among the various pathophysiologic mechanisms of electrical instability, left ventricular fibrosis in the papillary muscles and inferobasal wall, mitral annulus disjunction, and systolic curling have been recently described by pathological and cardiac magnetic resonance studies in sudden death victims and patients with arrhythmic MVP. In addition, premature ventricular beats arising from the Purkinje tissue as ventricular fibrillation triggers have been documented by electrophysiologic studies in MVP patients with aborted sudden death. The genesis of malignant ventricular arrhythmias in MVP probably recognizes the combination of the substrate (regional myocardial hypertrophy and fibrosis, Purkinje fibers) and the trigger (mechanical stretch) eliciting premature ventricular beats because of a primary morphofunctional abnormality of the mitral valve annulus. The main clinical challenge is how to identify patients with arrhythmic MVP (which imaging technique and in which patient) and how to treat them to prevent sudden death. Thus, there is a necessity for prospective multicenter studies focusing on the prognostic role of cardiac magnetic resonance and electrophysiologic studies and on the therapeutic efficacy of targeted catheter ablation and mitral valve surgery in reducing the risk of life-threatening arrhythmias, as well as the role of implantable cardioverter defibrillators for primary prevention.

Efficacy of Endocardial Ablation of Drug-Resistant Ventricular Fibrillation in Brugada Syndrome: Long-Term Outcome.

Background Both endocardial trigger elimination and epicardial substrate modification are effective in treating ventricular fibrillation (VF) in Brugada syndrome. However, the primary approach and the characteristics of patients who respond to endocardial ablation remain unknown. Methods Among 123 symptomatic Brugada syndrome patients (VF, 63%; syncope, 37%), ablation was performed in 21 VF/electrical storm patients, the majority of whom were resistant to antiarrhythmic drugs. Results Careful endocardial mapping revealed that 81% of the patients had no specific findings, whereas 19% of the patients, who experienced the most frequent VF episodes with notching of the QRS in lead V1, had delayed low-voltage fractionated endocardial electrograms. Ablation of VF triggers followed by endocardial substrate modification was performed in the right ventricular outflow tract in 85% of the cases and in the right ventricle in 15%. VF triggers could not be completely eliminated in 1 patient and VF became noninducible in 14 (88%) patients among 16 patients who underwent VF induction with normalization of Brugada-type ECG in 3. During follow-up (56.14±36.95 months), VF recurrence was observed in 7 patients. Importantly, all patients who had nothing of QRS in lead V1 did not respond to endocardial ablation despite presence of VF-triggering ectopic beats during ablation. Conclusions With careful documentation of VF-triggering ectopic beats and detailed endocardial mapping, endocardial VF trigger elimination followed by endocardial substrate modification has an excellent long-term outcome, whereas presence of QRS notching in lead V1 was associated with high VF recurrence suggesting epicardial substrate ablation as effective initial approach.

Mechanisms and management of refractory ventricular arrhythmias in the age of autonomic modulation

Ventricular arrhythmias are responsible for hundreds of thousands of deaths every year. Catheter ablation of ventricular tachycardia (VT) is an essential component of the management of these life-threatening arrhythmias. However, in many patients, despite medical and interventional therapy, VT recurs. Furthermore, some VT substrates (mid-myocardial, left ventricular summit, and intraseptal) are not easily targeted because of limitations of currently available technology. In certain clinical settings, ventricular fibrillation (VF) episodes that have premature ventricular contraction triggers can also be targeted with catheter ablation. However, in most patients there is no clear VF trigger to target, and therefore polymorphic VT or VF cannot be adequately treated with catheter ablation. The autonomic nervous system plays a crucial role in all aspects of ventricular arrhythmias, yet interventions specific to the cardiac neuronal axis have been largely underutilized. This underutilization has been most pronounced in patients with structural heart disease. However, there is a growing body of literature on the physiology and pathophysiology of cardiac neural control and the benefits of neuromodulation to treat refractory ventricular arrhythmias in these patients. We present case-based examples of neuromodulatory interventions currently available and a review of the literature supporting their use.

VALUE OF TESTING FOR MYOCARDIAL ISCHEMIA IN ISCHEMIC CARDIOMYOPATHY PATIENTS WITH RECURRENT VENTRICULAR ARRHYTHMIA IN A POPULATION BASED COHORT

New Myocardial ischemia is a common trigger for ventricular fibrillation (VF), however, ventricular tachycardia (VT) usually results from an underlying myocardial scar. Current guidelines recommend ischemia testing to be considered in patients with monomorphic VT (MMVT) and to be strongly considered in patients with polymorphic VT (PMVT) or VF. To assess whether testing for myocardial ischemia in ischemic cardiomyopathy (ICM) patients presenting with appropriate implantable cardioverter defibrillator (ICD) therapy would change clinical management. The patient population was derived from a provincial ICD registry in Nova Scotia. Medical records were examined retrospectively to determine if testing for myocardial ischemia with myocardial perfusion scan or cardiac catheterization was performed. All patients with ischemic cardiomyopathy and appropriate ICD therapy were included. The outcomes were the rate of coronary revascularization and mortality. A total of 288 patients were eligible for inclusion; 118 patients (41%) were tested for myocardial ischemia. Patients tested for myocardial ischemia were younger (63.3 ± 9.5 vs 67.3 ± 9.8, P=0.0007), had less heart failure (59.3% vs 71.2%, P=0.04) and were more likely to have been revascularized in the past (70.3% vs 55.9%, P=0.01). The reason for testing was MMVT/PMVT/VF in 71 patients (49 MMVT, 22 PMVT/VF) while 42 patients were tested for acute coronary syndrome or heart failure; cause of testing was not clear in 5 patients. In the ventricular arrhythmia group; 5 patients had coronary revascularization (2/49 (4.1%) with MMVT, 3/22 (13.6%) with PMVT/VF, p=0.33), compared to 5 patients in the ACS/HF group (p=0.5). After adjusting for age, gender, ejection fraction and NYHA class; there was no significant difference in mortality between patients who were tested for ischemia and those not tested (HR 0.75 (0.47, 1.21); P=0.24). In ICM patients with appropriate ICD therapy for MMVT; testing for myocardial ischemia rarely led to coronary intervention. In patients with PMVT/VF; testing had a higher chance of impact on clinical management. Testing for ischemia was not associated with a mortality difference in our cohort.

Sites of Successful Ventricular Fibrillation Ablation in Bileaflet Mitral Valve Prolapse Syndrome.

Although the vast majority of mitral valve prolapse (MVP) is benign, a small subset of patients, predominantly women, with bileaflet prolapse, complex ventricular ectopy (VE), and abnormal T waves comprise the recently described bileaflet MVP syndrome. We compared findings on electrophysiological study in bileaflet MVP syndrome patients with and without cardiac arrest to identify factors that may predispose to malignant ventricular arrhythmia. Fourteen consecutive bileaflet MVP syndrome patients (n=13 women; median [limits], age at index ablation, 33.8 [21.0-58.7] years; ejection fraction, 60% [45%-67%]; all ≤ moderate mitral regurgitation; n=6 with previous cardiac arrest and implantable cardioverter defibrillator shocks for ventricular fibrillation; and n=8 without implantable cardioverter defibrillator although with symptomatic complex VE) were included. The 2 groups had similar baseline echocardiographic and electrocardiographic characteristics. All patients had at least 1 left ventricular papillary or fascicular VE focus. Purkinje origin VE was identified as the ventricular fibrillation trigger in 6 of 6 cardiac arrest patients (4 from papillary muscle) and Purkinje origin of dominant VE was seen in 5 of 8 (3 from papillary muscle) nonarrest patients. Acute success was seen in 17 of 19 procedures, and a ventricular fibrillation storm occurred within 24 hours of ablation in a single patient. Repeat ablation for recurrent symptomatic arrhythmia was performed in 6 patients. At 478 (39-2099) days of follow-up, 2 cardiac arrest patients received appropriate shocks. Symptoms from VE were reduced in 12 of 14. Bileaflet MVP syndrome is characterized by fascicular and papillary muscle VE that triggers ventricular fibrillation. Ablation of clinically dominant VE foci improves symptoms and reduces appropriate implantable cardioverter defibrillator shocks.

Ventricular arrhythmias and the His–Purkinje system

Ventricular arrhythmias are a major cause of sudden death, which accounts for approximately half of cardiac mortality. The His-Purkinje system is composed of specialized cells responsible for the synchronous activation of the ventricles. However, experimental studies show that the Purkinje system can be arrhythmogenic during electrolyte imbalance, after exposure to various drugs, and in myocardial ischaemia, during which Purkinje cells can survive in anaerobic conditions. Purkinje cells can generate both automatic and triggered focal rhythms, and their network configuration can accommodate re-entrant circuits. In humans, a variety of monomorphic ventricular tachycardias can be sustained within the architecture of the Purkinje branches. Furthermore, discrete Purkinje sources can serve as critical triggers of ventricular fibrillation in a wide spectrum of patients with structural heart disease or with an apparently normal heart. In drug-resistant cases of monomorphic and polymorphic Purkinje-related ventricular tachycardias, catheter ablation is a very effective treatment. The specific transcriptional signatures and functional properties of Purkinje cells, including their intracellular calcium dynamics, underlie their extreme arrhythmogenicity. However, the identification of vulnerable individuals remains challenging, and the molecular mechanisms of Purkinje-related arrhythmias have to be characterized further to enable the development of interventions to prevent lethal cardiac arrhythmias.

Abstract 19422: Origin of Ventricular Fibrillation in Bileaflet Mitral Valve Prolapse Syndrome

Introduction: Although most patients with mitral valve prolapse (MVP) have a benign prognosis, there is a subgroup with bileaflet MVP syndrome (biMVPS) at increased risk of idiopathic ventricular fibrillation (VF). The phenotypic features of this syndrome include myxomatous bileaflet prolapse, complex ventricular ectopy (VE), T-wave inversion in inferolateral ECG leads, and female predominance. The mechanism of ventricular arrhythmia in these patients is unknown. Methods: We reviewed our center’s ablation experience of 14 consecutive patients with biMVPS patients between February 2007 and October 2013 (n=13 female, median [range] age at index ablation 33.8 [21.0 - 58.7] years, left ventricular ejection fraction [EF] 60 [45-67] %, all ≤ moderate mitral regurgitation [MR]). We compared findings from 6 with prior sudden cardiac arrest (SCA) and recurrent ICD shocks for drug refractory VF with 8 who had symptomatic drug-refractory complex VE but without prior SCA. Results: All patients with prior SCA had a predominant VE trigger for the VF. There was no difference between the two groups in EF, MR severity, VE burden, and number of different VE morphologies or foci ablated. Sites of successful VE ablation at index procedure were the LV papillary muscles (PM, n=6 anterior, 6 posterior), fascicular system (n=5 anterior, 4 posterior), mitral annulus (n=2), outflow tracts (3 RVOT, 1 LVOT), and coronary sinus (n=1). All patients had at least one LV papillary or fascicular VE focus. Purkinje origin VE was identified as the VF trigger in 6/6 SCA patients (3 from PM, 3 from LV fascicles) and only 4/8 (none from PM) non-SCA patients (p=0.04). Acute success was seen in 17/19 procedures with no complications. VF storm occurred within 24 hours of ablation in a single patient. At 310 (39 - 2099) days follow-up, 1 SCA patient received a single shock (p=0.031 compared to pre-ablation), and symptoms from VE were reduced in 12/14. Conclusions: BiMVPS is characterized by VE from the LV fascicles and papillary muscles that trigger VF. The VE is invariably multifocal and may also involve the outflow tracts and mitral annulus. Ablation of clinically dominant VE foci alleviates symptoms and reduces the number of VF-terminating ICD shocks.

Characteristics of ventricular tachycardia ablation in patients with continuous flow left ventricular assist devices.

Left ventricular assist devices (LVADs) are increasingly used as a bridge to cardiac transplantation or as destination therapy. Patients with LVADs are at high risk for ventricular arrhythmias. This study describes ventricular arrhythmia characteristics and ablation in patients implanted with a Heart Mate II device. All patients with a Heart Mate II device who underwent ventricular arrhythmia catheter ablation at 9 tertiary centers were included. Thirty-four patients (30 male, age 58±10 years) underwent 39 ablation procedures. The underlying cardiomyopathy pathogenesis was ischemic in 21 and nonischemic in 13 patients with a mean left ventricular ejection fraction of 17%±5% before LVAD implantation. One hundred and ten ventricular tachycardias (VTs; cycle lengths, 230-740 ms, arrhythmic storm n=28) and 2 ventricular fibrillation triggers were targeted (25 transseptal, 14 retrograde aortic approaches). Nine patients required VT ablation <1 month after LVAD implantation because of intractable VT. Only 10/110 (9%) of the targeted VTs were related to the Heart Mate II cannula. During follow-up, 7 patients were transplanted and 10 died. Of the remaining 17 patients, 13 were arrhythmia-free at 25±15 months. In 1 patient with VT recurrence, change of turbine speed from 9400 to 9000 rpm extinguished VT. Catheter ablation of VT among LVAD recipients is feasible and reasonably safe even soon after LVAD implantation. Intrinsic myocardial scar, rather than the apical cannula, seems to be the dominant substrate.

The Effect of Dobutamine on Susceptibility to Ischemia‐Induced Ventricular Fibrillation in the Isolated Rat Heart

Sudden cardiac death due to ventricular fibrillation (VF) continues to be a major cause of mortality, but the triggers of VF in ischemia remain poorly understood. Our hypothesis is that VF is triggered in myocardial ischemia as a result of ATP depletion, which causes ionic imbalance and electrical dysfunction that creates an arrhythmogenic substrate. The purpose of this study was to test this hypothesis by determining the effect of increasing cardiac ATP consumption on susceptibility to VF using a classical inotrope, dobutamine.Isolated rat hearts (n=12 per group) were perfused in the Langendorff mode with modified Krebs containing 3 mM K+. Dobutamine or vehicle was locally infused in a randomized and blinded manner to achieve a concentration of dobutamine of 3µM. After a further 15 min, regional ischemia was induced by coronary artery occlusion and maintained for 30 min. VF was determined from the ECG, and cardiac function was evaluated using an intraventricular balloon.Dobutamine increased heart rate and left ventricular developed pressure compared to controls as expected. The incidence of VF (75% vs 67%; P=NS) and time to onset of VF (892±68s vs 730±80s; P=NS) were similar in control and dobutamine groups respectively. Dobutamine reduced ischemic contracture, with end diastolic pressure 36±6 vs 15±3 mmHg after 25 min ischemia in control and dobutamine groups respectively (P&lt;0.05). Thus, although β1 stimulation by dobutamine increased cardiac work, it did not increase susceptibility to ischemic VF.

The Effect of Inhibition of Glycolysis on Susceptibility to Ischemia‐Induced Ventricular Fibrillation in the Isolated Rat Heart

Ventricular fibrillation (VF) is a major cause of sudden cardiac death but the triggers of VF in myocardial ischemia are poorly understood. We have previously proposed that ATP depletion may be the major trigger for development of VF in myocardial ischemia due to the consequent ionic and electrical dysfunction that creates an arrhythmogenic substrate. In the present study we determined the importance of ATP supplied by glycolysis to development of ischemia-induced VF by examining the effect of inhibition of glycolysis on the incidence and onset of VF. Isolated rat hearts (n=12 per group) were perfused in the Langendorff mode with modified Krebs solution, and then switched in randomized and blinded manner to one of three test solutions: Glucose Control (Krebs containing glucose + vehicle), Pyruvate Control (Krebs containing pyruvate + vehicle) or Pyrvuate + IAA (Krebs containing pyruvate + 100μM sodium iodoacetate, an irreversible inhibitor of glycolysis). After 15 min of perfusion with test solution, regional ischemia was induced by coronary occlusion and maintained for 30 minutes. Arrhythmias were determined from the ECG. The incidence of VF was 83%, 42% and 67% in the glucose control, pyruvate control and pyruvate + IAA groups respectively (P=NS). The mean time to onset of VF was 832±67 s, 823±76 s, and 671±67 s in the glucose control, pyruvate control and pyruvate + IAA groups respectively (P=NS). Thus, inhibition of glycolysis with pyruvate + IAA increased VF incidence and shortened the time to VF as a trend. We are increasing group size in order to avoid a Type II error when evaluating the effect of glycolytic inhibition on VF susceptibility. Supported by a Scientist Development Grant from the American Heart Association.

A case of a human ventricular fibrillation rotor localized to ablation sites for scar-mediated monomorphic ventricular tachycardia

Ventricular tachycardia (VT) and ventricular fibrillation (VF) are the most common causes of sudden cardiac death. Currently, knowledge of the reentrant mechanism of monomorphic VT circuits in relation to complex scar anatomy allows for various mapping techniques including electroanatomic and entrainment mapping to accomplish catheter ablation of VT.1, 2 Clinically, it may be observed that ablation to eliminate recurrent macro-reentrant VT may also eliminate recurrent VF, as defined for instance by electrograms from implanted cardioverter-defibrillators (ICD).3, 4 However, whether this represents elimination of the VT trigger for VF, or directly of the substrate for VF, is unclear since the mechanism of VF in relation to scar is not known. Recent work targeting localized rotors in atrial fibrillation ablation has shown promise,5 but its implications for VF are unknown. We report here a case where VT termination and a VF rotor occurred at spatially coincidental sites in a patient with ischemic cardiomyopathy, suggesting that VF rotors may localize to the same anatomic substrate that promotes VT.