Stephen R. Shorofsky

Dual-Chamber Versus Single-Chamber Detection Enhancements for Implantable Defibrillator Rhythm Diagnosis The Detect Supraventricular Tachycardia Study

Background— Delivery of inappropriate shocks caused by misdetection of supraventricular tachycardia (SVT) remains a substantial complication of implanted cardioverter/defibrillator (ICD) therapy. Whether use of optimally programmed dual-chamber ICDs lowers this risk compared with that in single-chamber ICDs is not clear. Methods and Results— Subjects with a clinical indication for ICD (n=400) at 27 participating centers received dual-chamber ICDs and were randomly assigned to strictly defined optimal single- or dual-chamber detection in a single-blind manner. Programming minimized ventricular pacing. The primary end point was the proportion of SVT episodes inappropriately detected from the time of programming until crossover or end of study. On a per-episode basis, 42% of the episodes in the single-chamber arm and 69% of the episodes in the dual-chamber arm were due to SVT. Mortality (3.5% in both groups) and early study withdrawal (14% single-chamber, 11% dual-chamber) were similar in both groups. The rate of inappropriate detection of SVT was 39.5% in the single-chamber detection arm compared with 30.9% in the dual-chamber arm. The odds of inappropriate detection were decreased by almost half with the use of the dual-chamber detection enhancements (odds ratio, 0.53; 95% confidence interval, 0.30 to 0.94; P=0.03). Conclusions— Dual-chamber ICDs, programmed to optimize detection enhancements and to minimize ventricular pacing, significantly decrease inappropriate detection.

Alterations in calcium handling in cardiac hypertrophy and heart failure

There is conflicting data concerning the effects of cardiac hypertrophy and failure on L-type Ca2+ channel density, the amplitude of the intracellular Ca2+ transients, and the characteristics of Ca2+ sparks. These discrepancies are probably due to multiple factors. First, the effects of cardiac hypertrophy on channel expression and cell adaptation are model dependent. Even within the same species, the mechanisms by which cardiac hypertrophy and heart failure are generated (genetic alteration, pressure overload, volume overload, high rate pacing, etc.) influence the results obtained. Second, with many animal models and diseased human hearts, the disease process is not uniformly distributed throughout the myocardium. Third, the effects on L-type Ca2+ channel behavior and SR function clearly depend on the extent of disease expression. Myocardial contractility increases with cardiac hypertrophy whereas it decreases with heart failure. Thus, it is difficult to compare results from different models of hypertrophy and heart failure at different stages of disease. More consistent data is likely to be obtained from longitudinal studies using a single animal model of disease. The challenge before us is to develop animal models that mimic human disease, which can be studied longitudinally during the progression of the disease process. This approach coupled with continued improvement in Ca2+ imaging and a greater understanding of normal E-C coupling, will enable us to identify precisely the abnormalities in E-C coupling that occur with the development of cardiac hypertrophy and heart failure and define the appropriate treatment modalities.

MRI-Guided ventricular tachycardia ablation: integration of late gadolinium-enhanced 3D scar in patients with implantable cardioverter-defibrillators.

Background— Substrate-guided ablation of ventricular tachycardia (VT) in patients with implanted cardioverter-defibrillators (ICDs) relies on voltage mapping to define the scar and border zone. An integrated 3D scar reconstruction from late gadolinium enhancement (LGE) MRI could facilitate VT ablations. Methods and Results— Twenty-two patients with ICD underwent contrast-enhanced cardiac MRI with a specific absorption rate of 0.05). ICD imaging artifacts were most prominent in the anterior wall and allowed full and partial assessment of LGE in 9±4 and 12±3 of 17 segments, respectively. In 14 patients with LGE, a 3D scar model was reconstructed and successfully registered with the clinical mapping system (accuracy, 3.9±1.8 mm). Using receiver operating characteristic curves, bipolar and unipolar voltages of 1.49 and 4.46 mV correlated best with endocardial MRI scar. Scar visualization allowed the elimination of falsely low voltage recordings (suboptimal catheter contact) in 4.1±1.9% of 2 mm resulted in >1.5-mV voltage recordings despite up to 63% transmural midmyocardial scar successfully ablated with MRI guidance. All successful ablation sites demonstrated LGE (transmurality, 68±26%) and were located within 10 mm of transition zones to 0% to 25% scar in 71%. Conclusions— Contrast-enhanced cardiac MRI can be safely performed in selected patients with ICDs and allows the integration of detailed 3D scar maps into clinical mapping systems, providing supplementary anatomic guidance to facilitate substrate-guided VT ablations.Background— Substrate-guided ablation of ventricular tachycardia (VT) in patients with implanted cardioverter-defibrillators (ICDs) relies on voltage mapping to define the scar and border zone. An integrated 3D scar reconstruction from late gadolinium enhancement (LGE) MRI could facilitate VT ablations. Methods and Results— Twenty-two patients with ICD underwent contrast-enhanced cardiac MRI with a specific absorption rate of <2.0 W/kg before VT ablation. Device interrogation demonstrated unchanged ICD parameters immediately before, after, or at 68±21 days follow-up (P>0.05). ICD imaging artifacts were most prominent in the anterior wall and allowed full and partial assessment of LGE in 9±4 and 12±3 of 17 segments, respectively. In 14 patients with LGE, a 3D scar model was reconstructed and successfully registered with the clinical mapping system (accuracy, 3.9±1.8 mm). Using receiver operating characteristic curves, bipolar and unipolar voltages of 1.49 and 4.46 mV correlated best with endocardial MRI scar. Scar visualization allowed the elimination of falsely low voltage recordings (suboptimal catheter contact) in 4.1±1.9% of <1.5-mV mapping points. Display of scar border zone allowed identification of excellent pace mapping sites, with only limited voltage mapping in 64% of patients. Viable endocardium of >2 mm resulted in >1.5-mV voltage recordings despite up to 63% transmural midmyocardial scar successfully ablated with MRI guidance. All successful ablation sites demonstrated LGE (transmurality, 68±26%) and were located within 10 mm of transition zones to 0% to 25% scar in 71%. Conclusions— Contrast-enhanced cardiac MRI can be safely performed in selected patients with ICDs and allows the integration of detailed 3D scar maps into clinical mapping systems, providing supplementary anatomic guidance to facilitate substrate-guided VT ablations.

Role of the transverse-axial tubule system in generating calcium sparks and calcium transients in rat atrial myocytes.

Cardiac atrial cells lack a regular system of transverse tubules like that in cardiac ventricular cells. Nevertheless, many atrial cells do possess an irregular internal transverse‐axial tubular system (TATS). To investigate the possible role of the TATS in excitation‐contraction coupling in atrial myocytes, we visualized the TATS (labelled with the fluorescent indicator, Di‐8‐ANEPPS) simultaneously with Ca2+ transients and/or Ca2+ sparks (fluo‐4). In confocal transverse linescan images of field‐stimulated cells, whole‐cell Ca2+ transients had two morphologies: ‘U‐shaped’ transients and irregular or ‘W‐shaped’ transients with a varying number of points of origin of the Ca2+ transient. About half (54 %, n=289 cells, 13 animals) of the cells had a TATS. Cells with TATS had a larger mean diameter (13.2 ± 2.8 μm) than cells without TATS (11.7 ± 2.0 μm) and were more common in the left atrium (n= 206 cells; left atrium: 76 with TATS, 30 without TATS; right atrium: 42 with TATS, 58 without TATS). Simultaneous measurement of Ca2+ sparks and sarcolemmal structures showed that cells without TATS had U‐shaped transients that started at the cell periphery, and cells with TATS had W‐shaped transients that began simultaneously at the cell periphery and the TATS. Most (82 out of 102 from 31 cells) ‘spontaneous’ (non‐depolarized) Ca2+ sparks occurred within 1 μm of a sarcolemmal structure (cell periphery or TATS), and 33 % occurred within 1 pixel (0.125 μm). We conclude that the presence of a sarcolemmal membrane either at the cell periphery or in the TATS in close apposition to the sarcoplasmic reticulum is required for the initiation of an evoked Ca2+ transient and for spontaneous Ca2+ sparks.

Complications associated with pectoral cardioverter-defibrillator implantation : Comparison of subcutaneous and submuscular approaches

OBJECTIVES The aim of this study was to compare complications in a large cohort of patients undergoing pectoral cardioverter-defibrillator implantation with a subcutaneous or submuscular approach. BACKGROUND Pectoral placement of implantable cardioverter-defibrillator (ICD) pulse generators is now routine because of downsizing of these devices. subcutaneous implantation has been advocated by some because it is a simple surgical procedure comparable to pacemaker insertion. Others have favored submuscular insertion to avoid wound complications. These surgical approaches have not been compared previously. METHODS The subjects for this study were 1,000 consecutive patients receiving a Medtronic Jewel ICD at 93 centers worldwide. Cumulative follow-up for all patients was 633.7 patient-years, with 64.9% of patients followed up for > or = 6 months. The complications evaluated were erosion, pocket hematoma, seroma, wound infection, dehiscence, device migration, lead fracture and dislodgment. RESULTS Subcutaneous implantation was performed in 604 patients and submuscular implantation in the remaining 396. The median procedural times were shorter for subcutaneous implantation (p = 0.014). In addition, the cumulative percentage of patients free from erosion was greater for subcutaneous implantations (p = 0.03, 100% vs. 99.1% at 6 months). However, lead dislodgment was more common with subcutaneous implantations (p = 0.019, 2.3% vs. 0.5% at 6 months) and occurred primarily during the first month postoperatively. Overall, there were no significant differences in cumulative freedom from complications between groups (4.1% vs. 2.5%, p = 0.1836). CONCLUSIONS Subcutaneous pectoral implantation of this ICD can be performed safely and has a low complication rate. This approach requires a simple surgical procedure and, compared with the submuscular approach, is associated with shorter procedure times and comparable overall complication rates. However, early follow-up is important in view of the increased lead dislodgment rate.

Comparison of Single- and Dual-Coil Active Pectoral Defibrillation Lead Systems

OBJECTIVES The purpose of this study was to compare defibrillation thresholds with lead systems consisting of an active left pectoral electrode and either single or dual transvenous coils. BACKGROUND Lead systems that include an active pectoral pulse generator reduce defibrillation thresholds and permit transvenous defibrillation in nearly all patients. A further improvement in defibrillation efficacy is desirable to allow for smaller pulse generators with a reduced maximal output. METHODS This prospective study was performed in 50 consecutive patients. Each patient was evaluated with two lead configurations with the order of testing randomized. Shocks were delivered between the right ventricular coil and either an active can alone (single coil) or an active can with the proximal atrial coil (dual coil). The right ventricular coil was the cathode for the first phase of the biphasic defibrillation waveform. RESULTS Delivered energy at the defibrillation threshold was 10.1+/-5.0 J for the single-coil configuration and 8.7+/-4.0 J for the dual-coil configuration (p < 0.02). Moreover, 98% of patients had low (<15 J) thresholds with the dual-coil lead system, compared with 88% of patients with the single-coil configuration (p=0.05). Leading edge voltage (p < 0.001) and shock impedance (p < 0.001) were also decreased with the dual-coil configuration, although peak current was increased (p < 0.001). CONCLUSIONS A dual-coil, active pectoral lead system reduces defibrillation energy requirements compared with a single-coil, unipolar configuration.

Enhanced detection of arrhythmia vulnerability using T wave alternans, left ventricular ejection fraction, and programmed ventricular stimulation: a prospective study in subjects with chronic ischemic heart disease.

Introduction: In previous studies, the prognostic value of T wave alternans (TWA) was similar to that of programmed ventricular stimulation (PVS). However, presently it is unclear if TWA and PVS identify the same patients or provide complementary risk stratification information. In addition, the effects of left ventricular ejection fraction (LVEF) on the prognostic value of TWA are unknown. The aim of this study was to determine if combined assessment of TWA, LVEF, and PVS improves arrhythmia risk stratification.

Exercise is Superior to Pacing for T Wave Alternans Measurement in Subjects with Chronic Coronary Artery Disease and Left Ventricular Dysfunction

Exercise vs Pacing for TWA Measurement. Introduction: T wave alternans (TWA) is a heart rate‐dependent marker of vulnerability to ventricular arrhythmias. Atrial pacing and exercise both are used as provocative stimuli to elicit TWA. However, the prognostic value of the two testing methods has not been compared. The aim of this prospective study was to compare the prognostic value of TWA measured during bicycle exercise and atrial pacing in a large cohort of high‐risk patients with ischemic heart disease and left ventricular dysfunction.

Advanced Rhythm Discrimination for Implantable Cardioverter Defibrillators Using Electrogram Vector Timing and Correlation

Electrogram Vector Timing and Correlation. Introduction: Discrimination of ventricular and supraventricular arrhythmias remains one of the major challenges for appropriate implantable defibrillator (ICD) therapy delivery. The electrogram vector timing and correlation (VTC) algorithm was developed for such rhythm discrimination. The VTC algorithm differentiates normally conducted supraventricular beats from abnormally conducted ventricular beats by comparing the timing and correlation of rate and shock channel electrograms.

Three-dimensional contrast-enhanced multidetector CT for anatomic, dynamic, and perfusion characterization of abnormal myocardium to guide ventricular tachycardia ablations.

Background—Advances in contrast-enhanced multidetector CT enable detailed characterization of the left ventricular myocardium. Myocardial scar and border zone (BZ), as the target of ventricular tachycardia ablations, displays abnormal anatomic, dynamic, and perfusion characteristics during first-pass CT. This study assessed how contrast-enhanced CT can predict voltage-defined scar and BZ and integrate its scar reconstructions into clinical mapping systems to guide ventricular tachycardia ablations. Methods and Results—Eleven patients with ischemic cardiomyopathy underwent contrast-enhanced CT before ventricular tachycardia ablation. Segmental anatomic (end-systolic and end-diastolic wall thickness), dynamic (wall thickening, wall motion), and perfusion (hypoenhancement) characteristics were evaluated. Receiver operating characteristic curves assessed the ability of CT to determine voltage-defined scar and BZ segments. Three-dimensional epi- and endocardial surfaces and scar borders were reconstructed, coregistered, and compared to voltages using a 17-segment model. Abnormal anatomic, dynamic, and perfusion data correlated well with abnormal (<1.5 mV) endocardial voltages (r=0.77). Three-dimensional reconstruction integrated into the clinical mapping system (registration accuracy, 3.31±0.52 mm) allowed prediction of homogenous abnormal voltage (<1.5 mV) in 81.7% of analyzed segments and correctly displayed transmural extent and intramural scar location. CT hypoperfusion correlated best with scar and BZ areas and encompassed curative ablations in 82% cases. Conclusions—Anatomic, dynamic, and perfusion imaging using contrast-enhanced CT allows characterization of left ventricular anatomy and 3D scar and BZ substrate. Integration of reconstructed 3D data sets into clinical mapping systems supplements information of voltage mapping and may enable new image approaches for substrate-guided ventricular tachycardia ablation.