John L. Sapp

Cardiac-Resynchronization Therapy for Mild-to-Moderate Heart Failure

BACKGROUND Cardiac-resynchronization therapy (CRT) benefits patients with left ventricular systolic dysfunction and a wide QRS complex. Most of these patients are candidates for an implantable cardioverter-defibrillator (ICD). We evaluated whether adding CRT to an ICD and optimal medical therapy might reduce mortality and morbidity among such patients. METHODS We randomly assigned patients with New York Heart Association (NYHA) class II or III heart failure, a left ventricular ejection fraction of 30% or less, and an intrinsic QRS duration of 120 msec or more or a paced QRS duration of 200 msec or more to receive either an ICD alone or an ICD plus CRT. The primary outcome was death from any cause or hospitalization for heart failure. RESULTS We followed 1798 patients for a mean of 40 months. The primary outcome occurred in 297 of 894 patients (33.2%) in the ICD-CRT group and 364 of 904 patients (40.3%) in the ICD group (hazard ratio in the ICD-CRT group, 0.75; 95% confidence interval [CI], 0.64 to 0.87; P<0.001). In the ICD-CRT group, 186 patients died, as compared with 236 in the ICD group (hazard ratio, 0.75; 95% CI, 0.62 to 0.91; P = 0.003), and 174 patients were hospitalized for heart failure, as compared with 236 in the ICD group (hazard ratio, 0.68; 95% CI, 0.56 to 0.83; P<0.001). However, at 30 days after device implantation, adverse events had occurred in 124 patients in the ICD-CRT group, as compared with 58 in the ICD group (P<0.001). CONCLUSIONS Among patients with NYHA class II or III heart failure, a wide QRS complex, and left ventricular systolic dysfunction, the addition of CRT to an ICD reduced rates of death and hospitalization for heart failure. This improvement was accompanied by more adverse events. (Funded by the Canadian Institutes of Health Research and Medtronic of Canada; ClinicalTrials.gov number, NCT00251251.).

Electrically Unexcitable Scar Mapping Based on Pacing Threshold for Identification of the Reentry Circuit Isthmus Feasibility for Guiding Ventricular Tachycardia Ablation

Background—We hypothesized that delineating electrically unexcitable scar (EUS) within low-voltage infarct regions will locate reentry circuit isthmuses by defining their borders. The pacing threshold and electrogram amplitude that best determines EUS is unknown. Methods and Results—The change in dimension of the virtual electrode was estimated in 11 patients and observed to increase by 4.4±2.5 mm as stimulus strength increases from threshold (2.9±1.8 mA) to 10 mA. EUS was defined as a threshold >10 mA. In 14 consecutive patients, mapping and ablation of ventricular tachycardia (VT) were performed using an electroanatomic mapping system. During sinus rhythm, unipolar pacing was performed at sites with bipolar electrogram amplitude <1.5 mV. EUS regions were marked on the maps. Reentry circuit isthmuses were identified by entrainment mapping or pace mapping, and ablation was performed. EUS was identified in the infarct in all 14 patients (11.8±13.9 cm2). All 20 VT circuit isthmuses identified were adjacent to EUS. Although electrogram amplitude correlated with pacing threshold (r =0.64, P <0.0001), many isthmuses had very low-amplitude electrograms, and EUS could not be identified from electrogram amplitude alone. RF ablation lines connecting selected EUS regions abolished all inducible VTs in 10 patients (71%); spontaneous VT was markedly reduced during follow-up (from 142±360 to 0.9±2.0 episodes per month, P =0.002). Conclusions—This new method of identifying EUS provides complimentary information to the electrogram amplitude in delineating potential reentry circuit paths, potentially facilitating ablation during sinus rhythm.

EHRA/HRS/APHRS expert consensus on ventricular arrhythmias.

Christian Torp Pedersen (EHRA Chairperson, Denmark), G. Neal Kay (HRS Chairperson, USA), Jonathan Kalman (APHRS Chairperson, Australia), Martin Borggrefe (Germany), Paolo Della-Bella (Italy), Timm Dickfeld (USA), Paul Dorian (Canada), Heikki Huikuri (Finland), Youg-Hoon Kim (Korea), Bradley Knight (USA), Francis Marchlinski (USA), David Ross (Australia), Frédéric Sacher (France), John Sapp (Canada), Kalyanam Shivkumar (USA), Kyoko Soejima (Japan), Hiroshi Tada (Japan), Mark E. Alexander (USA), John K. Triedman (USA), Takumi Yamada (USA), and Paulus Kirchhof (Germany)

Discerning the incidence of symptomatic and asymptomatic episodes of atrial fibrillation before and after catheter ablation (DISCERN AF): a prospective, multicenter study.

BACKGROUND The DISCERN AF study (Discerning Symptomatic and Asymptomatic Episodes Pre and Post Radiofrequency Ablation of Atrial Fibrillation) monitored atrial fibrillation (AF) using an implantable cardiac monitor (ICM) to assess the incidence and predictors of asymptomatic AF before and after catheter ablation. METHODS Patients with symptomatic AF underwent implantation of an ICM with an automated AF detection algorithm 3 months before and 18 months after ablation. Patients kept a standardized diary to record symptoms of arrhythmia, and ICM data were downloaded every 3 months. All episodes were blindly adjudicated and correlated with the diary. Asymptomatic recurrences were ICM episodes of 2 minutes or longer with no associated diary symptoms. RESULTS Fifty patients had 2355 ICM episodes. Of these, 69.0% were true AF/atrial flutter (AFL)/atrial tachycardia (AT); 16.0%, sinus with extrasystoles; 11.0%, artifact; and 4.0%, sinus arrhythmia. Total AF/AFL/AT burden was reduced by 86% from a mean (SD) of 2.0 (0.5) h/d per patient before to 0.3 (0.2) h/d per patient after ablation (P < .001), and 56.0% of all episodes were asymptomatic. The ratio of asymptomatic to symptomatic AF episodes increased after ablation from 1.1 to 3.7 (P = .002). By symptoms alone, 29 of 50 patients (58%) were free of AF/AFL/AT after ablation compared with 23 of 50 (46%) using ICM-detected AF/AFL/AT recurrence. Asymptomatic episodes were more likely AFL/AT and were significantly shorter and slower, with lower heart rate variability. However, the postablation state was the strongest independent predictor of asymptomatic AF. CONCLUSIONS The ratio of asymptomatic to symptomatic AF episodes increased from 1.1 before to 3.7 after ablation. Postablation state is the strongest predictor of asymptomatic AF. Symptoms alone underestimate postablation AF burden, with 12% of patients having asymptomatic recurrences only. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00745706.

Ventricular Tachycardia Ablation versus Escalation of Antiarrhythmic Drugs

BACKGROUND Recurrent ventricular tachycardia among survivors of myocardial infarction with an implantable cardioverter-defibrillator (ICD) is frequent despite antiarrhythmic drug therapy. The most effective approach to management of this problem is uncertain. METHODS We conducted a multicenter, randomized, controlled trial involving patients with ischemic cardiomyopathy and an ICD who had ventricular tachycardia despite the use of antiarrhythmic drugs. Patients were randomly assigned to receive either catheter ablation (ablation group) with continuation of baseline antiarrhythmic medications or escalated antiarrhythmic drug therapy (escalated-therapy group). In the escalated-therapy group, amiodarone was initiated if another agent had been used previously. The dose of amiodarone was increased if it had been less than 300 mg per day or mexiletine was added if the dose was already at least 300 mg per day. The primary outcome was a composite of death, three or more documented episodes of ventricular tachycardia within 24 hours (ventricular tachycardia storm), or appropriate ICD shock. RESULTS Of the 259 patients who were enrolled, 132 were assigned to the ablation group and 127 to the escalated-therapy group. During a mean (±SD) of 27.9±17.1 months of follow-up, the primary outcome occurred in 59.1% of patients in the ablation group and 68.5% of those in the escalated-therapy group (hazard ratio in the ablation group, 0.72; 95% confidence interval, 0.53 to 0.98; P=0.04). There was no significant between-group difference in mortality. There were two cardiac perforations and three cases of major bleeding in the ablation group and two deaths from pulmonary toxic effects and one from hepatic dysfunction in the escalated-therapy group. CONCLUSIONS In patients with ischemic cardiomyopathy and an ICD who had ventricular tachycardia despite antiarrhythmic drug therapy, there was a significantly lower rate of the composite primary outcome of death, ventricular tachycardia storm, or appropriate ICD shock among patients undergoing catheter ablation than among those receiving an escalation in antiarrhythmic drug therapy. (Funded by the Canadian Institutes of Health Research and others; VANISH ClinicalTrials.gov number, NCT00905853.).

Subxiphoid Surgical Approach for Epicardial Catheter-Based Mapping and Ablation in Patients With Prior Cardiac Surgery or Difficult Pericardial Access

Background—Percutaneous epicardial mapping and ablation are successful in some patients with ventricular epicardial reentry circuits but may be impossible when pericardial adhesions are present, such as from prior cardiac surgery. The purpose of this study was to evaluate the feasibility of direct surgical exposure of the pericardial space to allow catheter epicardial mapping and ablation in the electrophysiology laboratory when percutaneous access is not feasible. Methods and Results—In 6 patients with prior cardiac surgery or failed percutaneous pericardial access, a subxiphoid pericardial window was attempted. In all 6 patients, manual lysis of adhesions exposed the epicardial surface of the heart through a small subxiphoid incision and allowed placement of an 8F sheath into the pericardial space under direct vision. Access to the diaphragmatic surface of the heart with ablation catheters was achieved in all patients, and catheter manipulation to the lateral and anterior walls was possible in 4 patients. Three-dimensional electroanatomic voltage maps revealed low-amplitude regions in the inferior or posterior left ventricular epicardium. A total of 16 ventricular tachycardias were induced, and 14 were abolished by radiofrequency ablation. Ablation was limited by intrapericardial defibrillator patches adherent to the likely target region in 2 patients. All patients had chest pain consistent with pericarditis early after the procedure that resolved within a few days. There were no other complications. Conclusions—A direct surgical subxiphoid epicardial approach in the electrophysiology laboratory is feasible for patients with difficult pericardial access who require ablation of epicardial arrhythmia foci.

Initial Human Feasibility of Infusion Needle Catheter Ablation for Refractory Ventricular Tachycardia

Background— Ablation of ventricular tachycardia (VT) is sometimes unsuccessful when ablation lesions are of insufficient depth to reach arrhythmogenic substrate. We report the initial experience with the use of a catheter with an extendable/retractable irrigated needle at the tip capable of intramyocardial mapping and ablation. Methods and Results— Sequential consenting patients with recurrent VT underwent ablation with the use of a needle-tipped catheter. At target sites, the needle was advanced 7 to 9 mm into the myocardium, permitting pacing and recording. Infusion of saline/iodinated contrast mixture excluded perforation and ensured intramyocardial deployment. Further infusion was delivered before and during temperature-controlled radiofrequency energy delivery through the needle. All 8 patients included (6 male; mean age, 54) with a mean left ventricular ejection fraction of 29% were refractory to multiple antiarrhythmic drugs, and 1 to 4 previous catheter ablation attempts (epicardial in 4) had failed. Patients had 1 to 7 (median, 2) VTs present or inducible; 2 were incessant. Some intramyocardial VT mapping was possible in 7 patients. A mean of 22 (limits, 3–48) needle ablation lesions were applied in 8 patients. All patients had at least 1 VT terminated or rendered noninducible. During a median of 12 months follow-up, 4 patients were free of recurrent VT, and 3 patients were improved, but had new VTs occur at some point during follow-up. Two died of the progression of preexisting heart failure without recurrent VT. Complications included tamponade in 1 patient and heart block in 2 patients. Conclusions— Intramyocardial infusion-needle catheter ablation is feasible and permits control of some VTs that have been refractory to conventional catheter ablation therapy, warranting further study.

Contractile properties of myocardium are altered in dystrophin-deficient mdx mice

The objective of this study was to determine whether cardiac contractile force is altered in the dystrophin-deficient mdx mouse model of muscular dystrophy. Left atria from 12-14-week-old control and mdx mice were paced at 1 Hz in 1.25 mM external Ca2+ buffer. Twitch properties and effects of interposing intervals of 0.3 to 600 s on the force of subsequent beats (force-interval curves) were examined. Peak force and time-to-peak force were similar in both groups, but half-relaxation time was significantly prolonged in mdx heart. In control hearts, force-interval curves increased to an inflection point at about 1 s, then rose to a second peak near 60 s. In mdx heart, curves reached the early inflection more quickly, the second peak was diminished in magnitude and force was greatly depressed at long intervals. Curves were fitted to a four-parameter equation to quantify differences in shape. The parameter a, which reflects rate of rise to the first inflection, was significantly increased in mdx atria, while the parameter B, which reflects amplitude of the late peak, was significantly reduced. These differences in force production were more marked when external Ca2+ was raised to 2.5 mM. Results show contractile properties are markedly altered in atria from dystrophin-deficient mdx mice. These findings are consistent with the hypothesis that dystrophin deficiency affects cardiac contractile function, possibly through effects on SR function.

Single diagnostic pacing maneuver for supraventricular tachycardia

BACKGROUND Diagnostic supraventricular tachycardia (SVT) features and pacing maneuvers tend to be specific but insensitive. Therefore, diagnosis often requires the integration of multiple pieces of information and/or pacing maneuvers, which adds to the complexity of catheter ablation procedures. OBJECTIVE The purpose of this study was to determine if a single diagnostic pacing maneuver, namely, ventricular overdrive pacing including a basal pacing site near the earliest atrial activation, provides a definitive SVT diagnosis in nearly all patients. METHODS Sixty-seven consecutive patients with SVT undergoing catheter ablation at two institutions were prospectively studied. RESULTS Overdrive ventricular pacing provided the correct diagnosis in 91% of all patients and in 100% of patients when pacing accelerated the atrium to the pacing cycle length. Fusion due to wavefront collision in the ventricles or distal conduction system was 73% sensitive and 100% specific for accessory pathway-mediated SVT. Basal pacing was superior to pacing from the right ventricular apex for distinguishing accessory pathway-mediated SVT from AV nodal reentrant tachycardia. CONCLUSION Overdrive ventricular pacing is a highly effective single diagnostic pacing maneuver for sustained SVT. Basal pacing sites near the earliest atrial activation are superior to the right ventricular apex.

Inverse Solution Mapping of Epicardial Potentials Quantitative Comparison With Epicardial Contact Mapping

Background—Catheter ablation of ventricular tachycardia (VT) is still one of the most challenging procedures in cardiac electrophysiology, limited, in part, by unmappable arrhythmias that are nonsustained or poorly tolerated. Calculation of the inverse solution from body surface potential mapping (sometimes known as ECG imaging) has shown tremendous promise and can rapidly map these arrhythmias, but we lack quantitative assessment of its accuracy in humans. We compared inverse solution mapping with computed tomography–registered electroanatomic epicardial contact catheter mapping to study the resolution of this technique, the influence of myocardial scar, and the ability to map VT. Methods and Results—For 4 patients undergoing epicardial catheter mapping and ablation of VT, 120-lead body surface potential mappings were obtained during implantable defibrillator pacing, catheter pacing from 79 epicardial sites, and induced VT. Inverse epicardial electrograms computed using individualized torso/epicardial surface geometries extracted from computed tomography images were compared with registered electroanatomic contact maps. The distance between estimated and actual epicardial pacing sites was 13±9 mm over normal myocardium with no stimulus-QRS delay but increased significantly over scar (P=0.013) or was close to scar (P=0.014). Contact maps during right ventricular pacing correlated closely to inverse solution isochrones. Maps of inverse epicardial potentials during 6 different induced VTs indicated areas of earliest activation, which correlated closely with clinically identified VT exit sites for 2 epicardial VTs. Conclusions—Inverse solution maps can identify sites of epicardial pacing with good accuracy, which diminishes over myocardial scar or over slowly conducting tissue. This approach can also identify epicardial VT exit sites and ventricular activation sequences.Background— Catheter ablation of ventricular tachycardia (VT) is still one of the most challenging procedures in cardiac electrophysiology, limited, in part, by unmappable arrhythmias that are nonsustained or poorly tolerated. Calculation of the inverse solution from body surface potential mapping (sometimes known as ECG imaging) has shown tremendous promise and can rapidly map these arrhythmias, but we lack quantitative assessment of its accuracy in humans. We compared inverse solution mapping with computed tomography–registered electroanatomic epicardial contact catheter mapping to study the resolution of this technique, the influence of myocardial scar, and the ability to map VT. Methods and Results— For 4 patients undergoing epicardial catheter mapping and ablation of VT, 120-lead body surface potential mappings were obtained during implantable defibrillator pacing, catheter pacing from 79 epicardial sites, and induced VT. Inverse epicardial electrograms computed using individualized torso/epicardial surface geometries extracted from computed tomography images were compared with registered electroanatomic contact maps. The distance between estimated and actual epicardial pacing sites was 13±9 mm over normal myocardium with no stimulus-QRS delay but increased significantly over scar ( P =0.013) or was close to scar ( P =0.014). Contact maps during right ventricular pacing correlated closely to inverse solution isochrones. Maps of inverse epicardial potentials during 6 different induced VTs indicated areas of earliest activation, which correlated closely with clinically identified VT exit sites for 2 epicardial VTs. Conclusions— Inverse solution maps can identify sites of epicardial pacing with good accuracy, which diminishes over myocardial scar or over slowly conducting tissue. This approach can also identify epicardial VT exit sites and ventricular activation sequences.