Juntang Lu

Intramyocardial Adiposity After Myocardial Infarction New Implications of a Substrate for Ventricular Tachycardia

Background— Collagen has been attributed as the principal structural substrate of ventricular tachycardia (VT) after myocardial infarction (MI), even though adiposity of myocardium after MI is well recognized histologically. We investigated the effects of intramyocardial adiposity compared with collagen on electrophysiological properties, connexin43 expression, and VT induction after MI. Methods and Results— Simultaneous left ventricular plunge-needle, noncontact mapping was performed in sheep without MI (MI−; n=5), with MI and inducible VT (MI+VT+; n=7), and with MI and no inducible VT (MI+VT−; n=8). Histological intramyocardial quantity of adipose and collagen and degree of discontinuity were coregistered with electrophysiological parameters (MI+; 290 specimens). Additional assessment of connexin43 expression was performed. Left ventricular scar contained a body mass–independent abundance of adipocytes (adipose:collagen=0.8). Increased adipose density and discontinuity contributed to a greater inverse correlation (r) with conduction velocity (r for adipose=0.39, r for discontinuity=0.45, r for collagen=0.26) and electrogram amplitude (r for adipose=0.73, r for contiguity=0.77, r for collagen=0.68) compared with collagen. Collagen density was similar between the MI+ groups (P>0.29). However, the MI+VT+ group demonstrated a significant (all P⩽0.01) increase in adipose (8%) and discontinuity (qualitative) and decrease in conduction velocity (13%) and electrogram amplitude (21%) at MI borders compared with the MI+VT− group. In scar, myocytes adjacent to fibrofatty interfaces demonstrated increased connexin43 lateralization. A gradient increase in adipose was observed at sites that supported preferential presystolic VT activation and exhibited attenuation of excitation wavelength (P<0.001). Conclusions— Intramyocardial adiposity, in association with myocardial discontinuity within left ventricular scar borders, is a significant factor associated with altered electrophysiological properties, aberrant connexin43 expression, and increased propensity for VT after MI.Background— Collagen has been attributed as the principal structural substrate of ventricular tachycardia (VT) after myocardial infarction (MI), even though adiposity of myocardium after MI is well recognized histologically. We investigated the effects of intramyocardial adiposity compared with collagen on electrophysiological properties, connexin43 expression, and VT induction after MI. Methods and Results— Simultaneous left ventricular plunge-needle, noncontact mapping was performed in sheep without MI (MI−; n=5), with MI and inducible VT (MI+VT+; n=7), and with MI and no inducible VT (MI+VT−; n=8). Histological intramyocardial quantity of adipose and collagen and degree of discontinuity were coregistered with electrophysiological parameters (MI+; 290 specimens). Additional assessment of connexin43 expression was performed. Left ventricular scar contained a body mass–independent abundance of adipocytes (adipose:collagen=0.8). Increased adipose density and discontinuity contributed to a greater inverse correlation ( r ) with conduction velocity ( r for adipose=0.39, r for discontinuity=0.45, r for collagen=0.26) and electrogram amplitude ( r for adipose=0.73, r for contiguity=0.77, r for collagen=0.68) compared with collagen. Collagen density was similar between the MI+ groups ( P >0.29). However, the MI+VT+ group demonstrated a significant (all P ≤0.01) increase in adipose (8%) and discontinuity (qualitative) and decrease in conduction velocity (13%) and electrogram amplitude (21%) at MI borders compared with the MI+VT− group. In scar, myocytes adjacent to fibrofatty interfaces demonstrated increased connexin43 lateralization. A gradient increase in adipose was observed at sites that supported preferential presystolic VT activation and exhibited attenuation of excitation wavelength ( P <0.001). Conclusions— Intramyocardial adiposity, in association with myocardial discontinuity within left ventricular scar borders, is a significant factor associated with altered electrophysiological properties, aberrant connexin43 expression, and increased propensity for VT after MI. # Clinical Perspective {#article-title-48}

Bipolar Ablation of the Interventricular Septum is More Efficient at Creating a Transmural Line than Sequential Unipolar Ablation

Introduction: Post infarct ventricular tachycardia (VT) often involves the interventricular septum (IVS) and requires transmural septal ablation. The purpose of this study was to compare the efficacy of bipolar ablation (BIA) versus sequential unipolar ablation (SUA) in creating a transmural ablation line along the IVS scar border.

Comparison of Electroanatomic Contact and Noncontact Mapping of Ventricular Scar in a Postinfarct Ovine Model With Intramural Needle Electrode Recording and Histological Validation

Background—Substrate-based ablation is useful for nonhemodynamically tolerated postinfarct ventricular tachycardia. We assessed the accuracy of the CARTO contact and EnSite noncontact systems at identifying scar in a chronic ovine model with intramural plunge needle electrode recording and histological validation. Methods and Results—Scar mapping was performed on 8 male sheep with previous percutaneous-induced myocardial infarction. Up to 20 plunge needles were inserted into the left ventricle of each animal in areas of dense scar, scar border, and normal myocardium. A simultaneous CARTO map and EnSite geometry were acquired using a single catheter, and needle electrode locations were registered. A dynamic substrate map was constructed using ratiometric 50% peak negative voltage. The scar percentage around each needle location was quantified histologically. Analysis was performed on 152 plunge needles and corresponding histological blocks. Spearman correlation with histology was 0.690 (P<0.001) for needle electrode peak-to-peak voltage (PPV), 0.362 (P<0.001) and 0.492 (P<0.001) for CARTO bipolar and unipolar PPV, and 0.381 (P<0.001) for EnSite dynamic substrate map (≤40 mm from array). The area under the receiver operator characteristics curve (<50% and ≥50% scar) was 0.896 for needle electrode PPV, 0.726 and 0.697 for CARTO bipolar and unipolar PPV, and 0.703 for EnSite dynamic substrate map (≤40 mm from array). Conclusions—Both the CARTO contact and EnSite noncontact systems were moderately accurate in identifying postinfarct scar when compared with intramural electrodes and confirmed with histology. The EnSite dynamic substrate map was comparable to the CARTO contact bipolar PPV when points >40 mm from the array were excluded.

Evolution of Ventricular Tachycardia and Its Electrophysiological Substrate Early After Myocardial Infarction: An Ovine Model

Background— Sudden arrhythmic death after myocardial infarction (MI) is most frequent in the first month. Early programmed ventricular stimulation (within 1 week) post-MI has been able to identify long-term ventricular tachycardia (VT) occurrence. We aimed to determine the timing of development and stabilization of VT circuits after MI and how the evolution of the underlying substrate differs with VT inducibility. Methods and Results— MIs were induced in 36 sheep. The 21 survivors underwent serial electroanatomic mapping and programmed ventricular stimulation. Animals were classified as VTpos (inducible VT) or VTneg (noninducible VT) at day 8. Forty-three percent of MI survivors were VTpos on day 8 (9/21), and all remained inducible on day 100 with 1.5 (1.0–2.0) and 1.0 (1.0–2.0) morphologies per animal on days 8 and 100, respectively. Twelve-lead electrocardiogram matched in 15 of 19 VTs between days 8 and 100. The earliest presystolic ventricular activations during VT circuits were in similar locations at the 2 time points. The 12 VTneg animals remained noninducible on day 100. There was no difference in voltage or velocity substrate with time or inducibility. The area with fractionated signals increased with time and VT inducibility. VTpos animals had more linear regions of slowed conduction forming conducting channels. Conclusions— The inducibility and earliest presystolic endocardial activation sites of VT as well as voltage and velocity substrate on day 8 predicted those on day 100 postinfarct, indicating early formation and stabilization of the arrhythmogenic substrate. VT inducibility was influenced by the distribution of conducting channels and increased complex fractionated signals.

Simultaneous biventricular noncontact mapping and ablation of septal ventricular tachycardia in a chronic ovine infarct model.

Background—We assessed a novel simultaneous biventricular mapping and ablation approach for septal ventricular tachycardia (VT) in a chronic ovine infarct model. Methods and Results—In 8 sheep with inducible VT, mapping and ablation were performed 9±3 months after percutaneously induced myocardial infarction, with left ventricular ejection fraction 23±8%. Scar was identified by EnSite Dynamic Substrate Mapping plus CARTO voltage mapping. Thirty VT episodes (cycle length, 235±42 ms) were mapped with simultaneous analyses using EnSite arrays deployed in both the left ventricle and the right ventricle. Short ablation lines were created perpendicular to the breakout pathway along the scar border in the ventricle with earliest activity. If septal VT was still inducible, this line was extended before ablation in the second chamber. The end point of noninducibility of VT was achieved in all animals. The mean difference in delay in noncontact breakout timing between the ventricles was shorter for VT with (n=18) than without (n=12) septal breakout (32±7.8 ms, P<0.001). In 5 of 6 animals, after ablation in one ventricle, septal VT was still inducible with a common breakout site in the second ventricle. After septal ablation in the second ventricle, VT was no longer inducible. In the 6 animals in which septal VT had been ablated, transmural septal ablation was identified at the scar border, with overlapping left ventricular and right ventricular ablation lesions present in 5 of 6 (septal thickness 8 to 17 mm) and left ventricular endocardial ablation being transmural in 1 of 6 (6 mm). Conclusions—Biventricular scar and VT activation mapping correctly localizes septal VT pathways, directing ablation from one or both septal endocardial aspects. Creation of a transmural septal lesion at the scar border interrupting VT exit points is highly effective at ablating septal VT.

In vivo evaluation of virtual electrode mapping and ablation utilizing a direct endocardial visualization ablation catheter.

Visualization Catheter with Virtual Electrode Ablation. Background: Radiofrequency (RF) ablation utilizing direct endocardial visualization (DEV) requires a “virtual electrode” to deliver RF energy while preserving visualization. This study aimed to: (1) examine the virtual electrode RF ablation efficacy; (2) determine the optimal power and duration settings; and (3) evaluate the utility of virtual electrode unipolar electrograms.

Revised non-contact mapping of ventricular scar in a post-infarct ovine model with validation using contact mapping and histology

AIMS Identification of arrhythmogenic scar using non-contact (NC) sinus rhythm (SR) mapping is limited. Dynamic substrate mapping (DSM) overcomes these limitations but is less accurate than plunge needle electrode mapping. We developed a revised method for calculating DSM which was validated using detailed histological analysis and compared with conventional mapping modalities. METHODS AND RESULTS Mapping was performed in eight sheep, >9 weeks post-myocardial infarction. Twenty multielectrode needles were deployed at thoracotomy in the left ventricle within and surrounding scar, and located using Ensite. Simultaneous catheter, needle, and NC electrograms were recorded during SR and multisite pacing. Dynamic substrate mapping maps were calculated as the maximum local peak negative voltage (PNV). Absolute mean DSM (AMDSM) maps, based on peak-peak voltage (P-PV), were calculated to minimize local pacing effects and take into account anisotropic influence. Dynamic substrate mapping and AMDSM maps were normalized based on global maximum voltages attained. Histologically quantified scar and mapping criteria were compared using Spearmans correlation and receiver operator curves (area under the curve, AUC) using 50% scar cut-off. For unipolar mapping, needles had greatest sensitivity at identifying scar which was better for P-PV (AUC; needle = 0.90, catheter = 0.70, NC = 0.66) than for PNV (AUC; needle = 0.79, NC = 0.38). AMDSM (AUC = 0.75) had superior scar discrimination than either catheter (AUC; unipolar = 0.70, bipolar = 0.71) or DSM (AUC = 0.67). Absolute mean DSM accuracy was improved when valvular geometries were excluded (AUC = 0.77). CONCLUSION Absolute mean DSM was comparably accurate in identifying scarred myocardium as PNV needle mapping but was superior to conventional catheter and NC mapping.

Percutaneous microwave ablation with a long side-firing antenna array can successfully treat a nonsurgical chronic ovine atrial flutter model.

Introduction: Long side‐firing microwave (MW) arrays can deliver energy uniformly over its length without the need for intimate endocardial contact. We hypothesize that a novel 6 Fr 20 mm long percutaneous high‐efficiency MW antenna array ablation catheter can rapidly create long, continuous, and transmural linear ablation lesions.

Primary Radiofrequency Ablation of Ventricular Tachycardia Early After Myocardial Infarction Evaluation in an Ovine Model

Background—Ventricular tachycardia (VT) is a significant complication of myocardial infarction. Radiofrequency ablation for postinfarct VT is reserved for drug refractory VT or VT storms. Our hypothesis is that radiofrequency ablation in the early postinfarct period could abolish or diminish late recurrences of VT. Methods and Results—Myocardial infarct was induced by balloon occlusion of the left anterior descending artery in 35 sheep. The 25 survivors underwent programmed ventricular stimulation and electroanatomical mapping 8 days postinfarct. Animals with inducible VT (12 out of 25 animals) underwent immediate radiofrequency ablation. Further VT inductions were performed 100 and 200 days postinfarct. At day 8, 3.0±0.9 VT morphologies per animal were inducible. All were successfully ablated with 24±6 applications of radiofrequency energy. All had ablations on the left ventricular endocardium, and 67% had ablations on the right ventricular aspect of the interventricular septum. All targeted arrhythmias were successfully ablated acutely. One animal was euthanized because of hypotension from a serious pericardial effusion. The other 11 survived and remained arrhythmia free on subsequent inductions on the 100th and 200th days (P<0.001). The 13 animals without inducible VT remained noninducible at the subsequent studies. A historical control arm of 9 animals with inducible VT at day 8 remained inducible at day 100. Conclusions—Radiofrequency ablation on the eighth day after infarction abolished inducibility of VT at late induction studies ⩽200 days in an ovine model. Early identification and ablation of VT after infarction may prevent or reduce late ventricular arrhythmias but needs to be validated in clinical studies.

Investigating the utility of in vivo bio-impedance spectroscopy for the assessment of post-ischemic myocardial tissue

Increased myocardial structural heterogeneity in response to ischemic injury following myocardial infarction (MI) is purported as the mechanism of ventricular arrhythmogenesis. Current modalities for in vivo assessment of structural heterogeneity for identification of arrhythmogenic substrate are limited due to the complex nature of the structural microenvironment post-MI. We investigated the utility of in vivo bio-impedance spectroscopy (BIS) in a large post-infarct animal model for differentiation between normal and infarcted tissue. We also investigated the quantitative effects of adipose and collagen on BIS assessment of myocardium. The results indicate that the degree of myocardial injury following chronic post-infarction remodeling could be reliably quantified (performed in triplicates) using BIS. Furthermore, the presence of intramyocardial adipose tissue that develops in conjunction with collagen within the infarct zone had a greater and significant influence on BIS then collagen tissue alone. These preliminary results indicate a potential role of BIS for quantitative assessment and characterization of complex arrhythmogenic substrates in ischemic cardiomyopathy.