Timothy W. Smith

Noninvasive Electroanatomic Mapping of Human Ventricular Arrhythmias with Electrocardiographic Imaging

Noninvasive imaging of cardiac electrical activity during ventricular arrhythmias enables superior diagnosis and treatment. A New View of the Beating Heart Just as a tree’s shadow is an oversimplification of branches and foliage, the electrocardiogram, a decades-old tool for measuring the electrical activity of the heart, captures only an approximate view of the heartbeat, distorted by the intervening tissues between the heart and the few electrodes on the skin. This poses a problem when trying to treat heart diseases such as dangerous ventricular arrhythmias, which destabilize the heartbeat and can lead to sudden cardiac death. Now, with a technique called electrocardiographic imaging (ECGI), Wang and colleagues have married multiple electrical recordings from the skin of patients who have ventricular tachycardia (VT) with detailed computerized axial tomography (CAT) scans of the anatomy of their torso. From these data, the authors can back calculate what is happening, electrically speaking, on the surface of the misbehaving hearts, yielding an individual portrait of that patient’s beating heart so that treatment can be more effectively deployed. Twenty-five patients with VT were scheduled to undergo electrical mapping of their hearts and then ablation of heart tissue to correct the electrical defect with an invasive catheter. The authors augmented this standard treatment by creating an image of their beating hearts with noninvasive ECGI, before the standard procedure. The ECGI and standard procedure identified the same origination point of the tachycardia in almost all of the patients, and ECGI was able to correctly categorize both focal and reentrant mechanisms of VT. The time resolution of ECGI enabled the authors to follow the response of the heart to different patterns of stimulation (or pacing), revealing presystolic activation near the site of origin. They could see variable beat-to-beat conduction patterns and showed that the abnormal conduction patterns often began in regions of scar tissue, relics of previous heart attacks. ECGI yields information comparable to the current procedure for mapping abnormal heart activity with a catheter-fed electrode, repeatedly placed on the heart surface. But it has significant advantages over the current approach: The spatial resolution of the ventricular arrhythmia on the heart surface is high, and it takes into account patient-to-patient variability in body size and shape. Further, it is noninvasive and can map single heartbeats, allowing unprecedented visualization of the anatomy of the electrical activation and beat-to-beat variability. These advantages should enable more effective diagnosis of VT and more appropriate drug or ablation therapy, which can now be directed to the specific characteristics of the patient’s heart instead of a simplified shadow. The rapid heartbeat of ventricular tachycardia (VT) can lead to sudden cardiac death and is a major health issue worldwide. Efforts to identify patients at risk, determine mechanisms of VT, and effectively prevent and treat VT through a mechanism-based approach would all be facilitated by continuous, noninvasive imaging of the arrhythmia over the entire heart. Here, we present noninvasive real-time images of human ventricular arrhythmias using electrocardiographic imaging (ECGI). Our results reveal diverse activation patterns, mechanisms, and sites of initiation of human VT. The spatial resolution of ECGI is superior to that of the routinely used 12-lead electrocardiogram, which provides only global information, and ECGI has distinct advantages over the currently used method of mapping with invasive catheter-applied electrodes. The spatial resolution of this method and its ability to image electrical activation sequences over the entire ventricular surfaces in a single heartbeat allowed us to determine VT initiation sites and continuation pathways, as well as VT relationships to ventricular substrates, including anatomical scars and abnormal electrophysiological substrate. Thus, ECGI can map the VT activation sequence and identify the location and depth of VT origin in individual patients, allowing personalized treatment of patients with ventricular arrhythmias.

Poor prognosis for patients with chronic kidney disease despite ICD therapy for the primary prevention of sudden death.

Introduction: Chronic kidney disease (CKD) has been independently associated with increased cardiovascular mortality. Little is known about the benefit of implantable cardioverter defibrillator (ICD) therapy for prevention of sudden death in this large, high‐risk population. We sought to evaluate the impact of CKD on survival in patients who received an ICD for primary prevention of sudden death.

Sudden cardiac death: Epidemiologic and financial worldwide perspective

The term sudden cardiac death (SCD) implies the sudden and unexpected loss of an active, productive member of the community. SCD is typically attributed to lethal ventricular arrhythmias; however, these arrhythmias are impossible to diagnose after the fact. Epidemiologic analyses, therefore, rely on inference of the cause of death. Estimates of the incidence of are SCD variable but it may be as high as 1 per 1,000 per year. The cost of SCD to society is incalculable. Current strategies for preventing SCD rely on risk assessment for cardiology patients and implantation of defibrillators (ICD) in high risk patients. Unfortunately, the absolute number of SCDs that occur in the general (relatively low-risk) population is large compared to the number of SCDs in the high risk population. Therefore, prevention of SCD in high risk populations is unlikely to prevent the majority of SCDs. Cost-effectiveness of ICD implantation for prevention of SCD has been studied; ICDs appear to meet U.S. and European criteria for cost-effectiveness if their benefit extends to at least 7–8 years. However, therapies considered cost-effective may nonetheless be too costly for most worldwide societies. Currently, investigators are focusing on refining risk stratification, partly in hopes of identifying patients for whom ICD implantation will not be useful.

The azygos defibrillator lead for elevated defibrillation thresholds: implant technique, lead stability, and patient series.

Background: Conventional insertion of implantable cardioverter‐defibrillator (ICD) includes an evaluation of the defibrillation threshold (DFT). Implanting an ancillary defibrillation lead in the azygos vein has been introduced as a therapeutic option in patients with “high” DFT. This study reports the efficacy and stability of azygos defibrillation coils implanted for elevated DFTs.

Reduction of RV pacing by continuous optimization of the AV interval

Background: In patients requiring permanent pacing, preservation of intrinsic ventricular activation is preferred whenever possible. The Search AV+ (SAV+) algorithm in Medtronic EnPulse™ dual‐chamber pacemakers can increase atrioventricular (AV) intervals to 320 ms in patients with intact or intermittent AV conduction. This prospective, multicenter study compared the percentage of ventricular pacing with and without AV interval extension.

Standard Right Atrial Ablation is Effective for Atrioventricular Nodal Reentry with Earliest Activation in the Coronary Sinus

Introduction: Reports suggest that coronary sinus (CS) or left atrial ablations may be necessary for treatment of AV nodal reentrant tachycardia (AVNRT) with earliest retrograde atrial activation in the CS. We assessed the efficacy of standard right atrial catheter ablation approaches in these tachycardias and determined the incidence of earliest activation in the CS in AVNRT.

Noninvasive Cardiac Radiation for Ablation of Ventricular Tachycardia

BACKGROUND Recent advances have enabled noninvasive mapping of cardiac arrhythmias with electrocardiographic imaging and noninvasive delivery of precise ablative radiation with stereotactic body radiation therapy (SBRT). We combined these techniques to perform catheter‐free, electrophysiology‐guided, noninvasive cardiac radioablation for ventricular tachycardia. METHODS We targeted arrhythmogenic scar regions by combining anatomical imaging with noninvasive electrocardiographic imaging during ventricular tachycardia that was induced by means of an implantable cardioverter–defibrillator (ICD). SBRT simulation, planning, and treatments were performed with the use of standard techniques. Patients were treated with a single fraction of 25 Gy while awake. Efficacy was assessed by counting episodes of ventricular tachycardia, as recorded by ICDs. Safety was assessed by means of serial cardiac and thoracic imaging. RESULTS From April through November 2015, five patients with high‐risk, refractory ventricular tachycardia underwent treatment. The mean noninvasive ablation time was 14 minutes (range, 11 to 18). During the 3 months before treatment, the patients had a combined history of 6577 episodes of ventricular tachycardia. During a 6‐week postablation “blanking period” (when arrhythmias may occur owing to postablation inflammation), there were 680 episodes of ventricular tachycardia. After the 6‐week blanking period, there were 4 episodes of ventricular tachycardia over the next 46 patient‐months, for a reduction from baseline of 99.9%. A reduction in episodes of ventricular tachycardia occurred in all five patients. The mean left ventricular ejection fraction did not decrease with treatment. At 3 months, adjacent lung showed opacities consistent with mild inflammatory changes, which had resolved by 1 year. CONCLUSIONS In five patients with refractory ventricular tachycardia, noninvasive treatment with electrophysiology‐guided cardiac radioablation markedly reduced the burden of ventricular tachycardia. (Funded by Barnes–Jewish Hospital Foundation and others.)

Residual Cx45 and its relationship to Cx43 in murine ventricular myocardium

Gap junction channels in ventricular myocardium are required for electrical and metabolic coupling between cardiac myocytes and for normal cardiac pump function. Although much is known about expression patterns and remodeling of cardiac connexin(Cx)43, little is known about the less abundant Cx45, which is required for embryonic development and viability, is downregulated in adult hearts, and is pathophysiologically upregulated in human end-stage heart failure. We applied quantitative immunoblotting and immunoprecipitation to native myocardial extracts, immunogold electron microscopy to cardiac tissue and membrane sections, electrophysiological recordings to whole hearts, and high-resolution tandem mass spectrometry to Cx45 fusion protein, and developed two new tools, anti-Cx45 antisera and Cre+;Cx45 floxed mice, to facilitate characterization of Cx45 in adult mammalian hearts. We found that Cx45 represents 0.3% of total Cx protein (predominantly 200 fmol Cx43 protein/μg ventricular protein) and colocalizes with Cx43 in native ventricular gap junctions, particularly in the apex and septum. Cre+;Cx45 floxed mice express 85% less Cx45, but do not exhibit overt electrophysiologic abnormalities. Although the basal phosphorylation status of native Cx45 remains unknown, CaMKII phosphorylates 8 Ser/Thr residues in Cx45 in vitro. Thus, although downregulation of Cx45 does not produce notable deficits in electrical conduction in adult, disease-free hearts, Cx45 is a target of the multifunctional kinase CaMKII, and the phosphorylation status of Cx45 and the role of Cx43/Cx45 heteromeric gap junction channels in both normal and diseased hearts merits further investigation.

Management of Arterial Injuries Caused by Laser Extraction of Indwelling Venous Pacemaker and Defibrillator Leads

The use of laser technology for the removal of pacemaker and defibrillator leads has decreased the lead extraction time and improved the success rate for complete lead removal when compared to traditional techniques. However, this extraction method may be associated with significant complications. This report documents two cases of iatrogenic arteriovenous fistula created by laser lead extraction. Endovascular repair of these fistulas provides an effective and less invasive alternative to open repair.

The classic elephant trunk technique for staged thoracic and thoracoabdominal aortic repair: Long-term results

OBJECTIVE The classic elephant trunk (ET) technique has become the standard approach for patients with diffuse aortic disease requiring a staged thoracic and thoracoabdominal aortic repair. The aim of this study was to assess long-term outcomes and predictors for survival after surgical repair of extensive thoracic aortic disease with the ET technique. METHODS Between 1984 and 2013, 248 consecutive patients were treated in our institution and analyzed retrospectively. Follow-up consisted of outpatient clinic visits including postoperative computed tomography imaging at 3 months and annually thereafter. Second-stage intervention was indicated if the diameter of the descending or thoracoabdominal aorta was greater than or equal to 60 mm, in case of a rapidly growing aneurysm and/or symptoms. RESULTS Mean age was 65 ± 10 years; 44% were male. After first-stage ET, in-hospital mortality was 8% and permanent neurologic deficits were observed in 2% of patients. Median follow-up after the first stage was 48 months (range, 1-210 months). One hundred twelve patients (45%) underwent second-stage ET. Overall survival after first-stage ET was 75% and 67% at 5 and 10 years, respectively. Survival in patients with second-stage ET was 87%, compared with 65% in the group who did not undergo second-stage ET at the 5-year follow-up (P < .001) and 67% compared with 36% at the 10-year follow-up (P < .001). Predictor for mortality was the absence of second-stage ET (P = .044). CONCLUSIONS A 2-stage approach for diffuse aortic disease is a safe method. The acceptable mortality at the first stage justifies the use of the classic ET technique and allows subsequent repair of the distal aorta. Long-term survival is increased when both stages are completed.