Early Reperfusion During Acute Myocardial Infarction Affects Ventricular Tachycardia Characteristics and the Chronic Electroanatomic and Histological Substrate
Background— Reperfusion therapy during acute myocardial infarction results in myocardial salvage and improved ventricular function but may also influence the arrhythmogenic substrate for ventricular tachycardia (VT). This study used electroanatomic mapping and infarct histology to assess the impact of reperfusion on the substrate and on VT characteristics late after acute myocardial infarction.
Methods and Results— The study population consisted of 36 patients (32 men; age, 63±15 years) referred for treatment of VT 13±9 years after acute myocardial infarction. Fourteen patients with early reperfusion during acute myocardial infarction were compared with 22 nonreperfused patients. Spontaneous and induced VTs and the characteristics of electroanatomic voltage maps were analyzed. Twenty-seven patients were treated by radiofrequency catheter ablation. Ten patients (6 nonreperfused) were treated by ventricular restoration with intraoperative cryoablation in 9. During surgery, biopsies were obtained from the resected core of the infarct. VT cycle length of spontaneous and induced VTs was shorter in reperfused patients (reperfused, 299±52/270±58 ms; nonreperfused, 378±77/362±74 ms; P=0.01). An electroanatomic patchy scar pattern was present in 71% of reperfused and 14% of nonreperfused patients (P=0.004). The proportion of electroanatomic dense scar was smaller in reperfused patients (24±18% versus 45±21%; P=0.02). Histological assessment in 10 patients revealed thick layers of surviving myocardium in 75% of reperfused but in none of the nonreperfused patients.
Conclusions— Scar size and pattern defined by electroanatomic mapping are different between VT patients with and without reperfusion during acute myocardial infarction. Less confluent electroanatomic scars match with thick layers of surviving myocardium on histology. Early reperfusion and less confluent electroanatomic scar are associated with faster VTs.
Received July 7, 2009; accepted March 1, 2010.
Catheter ablation is an important therapeutic option for controlling recurrent ventricular tachycardia (VT) late after acute myocardial infarction (AMI). Mapping studies have shown that reentry circuit locations and VT characteristics vary greatly among patients and are influenced by the 3-dimensional geometry of infarcted areas.1–3 In animal models, the duration of coronary artery occlusion determines the size, transmurality, and geometry of myocardial fibrosis after AMI.4,5 Thus, it seems likely that early reperfusion, which has become the standard treatment of AMI, will influence the nature of the VT substrate. Recently, methods have been developed to characterize the VT substrate that are based on bipolar electrogram characteristics during sinus or paced rhythm. These methods have been applied to ablation of VTs that are not stable for mapping during VT, targeting the substrate with linear radiofrequency lesions at the electrophysiological scar border zone.2,3,6 Animal studies to validate this substrate-based ablation approach were performed in a chronically occluded infarct-related artery (IRA) model resulting in a homogeneous dense scar surrounded by a small scar border zone.7
Editorial see p 1881
Clinical Perspective on p 1895
We hypothesized that early reperfusion during AMI results in smaller and less homogeneous scars on electroanatomic voltage maps and faster spontaneous and inducible VT compared with nonreperfused patients late after MI. To further evaluate the effect of early reperfusion on the VT substrate, the results of electroanatomic voltage maps were compared with infarct histology according to the reperfusion strategy in a subgroup of patients undergoing cardiac surgery.
The population comprised 36 consecutive patients late after AMI referred for catheter ablation or surgical treatment of sustained monomorphic VT without contraindications for left ventricular (LV) mapping and without evidence of reversible ischemia. Clinical evaluation consisted of careful history taking relative to the reperfusion strategy during the index MI and consecutive ischemic events, arrhythmias, and symptoms of heart failure. All patients underwent echocardiography, coronary angiography, and nuclear myocardial perfusion imaging to detect ischemia. The results, including the functional status, presence of an LV aneurysm, concomitant valvular disease, and residual coronary artery disease, were evaluated by a team of cardiologists, electrophysiologists, and cardiothoracic surgeons according to the institutional protocol. Patients with significant coronary artery stenosis and reversible ischemia on nuclear perfusion imaging, with a mobile LV thrombus, or with New York Heart Association heart failure class IV symptoms were excluded from the study.
Patients presenting with symptoms of heart failure and a dilated or aneurysmatic LV after anterior AMI were considered candidates for a combined surgical approach of ventricular restoration comprising of an endoventricular circular patch plasty and intraoperative VT ablation.8 Radiofrequency catheter ablation was offered to the remaining patients.
All available coronary angiograms obtained during and after the index AMI were reviewed by an interventional cardiologist to assess the effect of the early reperfusion strategy. From these results, patients were classified as either acutely reperfused with documented open IRA or not reperfused. The Thrombolysis in Myocardial Infarction scoring system was used to determine the patency of the IRA.9 Patients were considered reperfused when Thrombolysis in Myocardial Infarction grade 3 flow was present after reperfusion therapy.
After giving informed consent, all patients underwent electrophysiological evaluation, including electrical programmed stimulation (EPS) and LV electroanatomic voltage mapping. Studies were performed in the postabsorptive, nonsedated state. Antiarrhythmic drugs were discontinued for 5 half-lives except amiodarone, which was continued in 14 patients. The EPS protocol consisted of 3 drive cycle lengths (600, 500, and 400 ms) and ≤3 ventricular extrastimuli from 2 right ventricular sites and burst pacing. Twelve-lead ECGs and intracardiac electrograms were recorded simultaneously with a 48-channel acquisition system (Cardio-Laboratory 4.1, Prucka Engineering, Houston, Tex). The positive end point of EPS was reproducible induction of a sustained monomorphic VT lasting ≥30 seconds or requiring termination because of hemodynamic compromise. When catheter ablation was performed, the entire protocol was repeated until all inducible VTs were eliminated or until the procedure was classified as ablation failure in the judgment of the physician. Sinus rhythm electroanatomic voltage mapping (CARTO XP EP System, Biosense Webster Inc, Diamond Bar, Calif) of the LV was performed with a 3.5-mm-tip quadripolar mapping catheter with interelectrode spacing of 2, 5, and 2 mm (NaviStar ThermoCooled, Biosense Webster Inc) by a retrograde aortic approach. Bipolar voltage maps with a spatial resolution of <15 mm were created. Electric scar in the IRA-provided area was defined by voltage criteria. Electrogram amplitudes ≤0.5 mV were defined as dense scar; voltages >0.5 and ≤1.5 mV,2,7 as scar border zone. A “patchy pattern” of electroanatomic scar was defined as ≥2 low-voltage areas separated by areas of preserved voltage (>1.5 mV). For each map, the surface of the total scar, the scar border zone, and the dense scar were measured with software provided with the CARTO system.
VT was defined as IRA related if the reentry circuit isthmus site was located within the area supplied by the IRA. A reentry circuit isthmus site was defined by either activation and entrainment mapping for tolerated VT or by pace mapping (≥11/12 lead match between VT QRS and paced QRS morphology and a stimulus-to-QRS interval >40 ms) in patients with poorly tolerated VTs or who were scheduled for operation. In the latter, the potential reentry circuit isthmus site was marked by a single radiofrequency application to facilitate ablation during surgery.
Radiofrequency catheter ablation was performed at isthmus sites during VT for stable VTs and during sinus rhythm for unstable VTs with an open irrigated tip catheter. Radiofrequency power was applied to a maximum of 50 W, provided that the temperature recorded from the electrode remained <50°C for 60 seconds. All inducible monomorphic VTs were targeted and radiofrequency energy was applied if a potential isthmus site could be identified.
Cryoablation concomitant to surgery was performed with a Surgifrost cryoprobe (Cryocath, Montreal, Quebec, Canada). Overlapping applications, up to −150°C during 90 seconds, were applied to the endocardial scar border as identified by the surgeon. The epicardial surface was inspected for the extent of the scar, identified as a white discoloration of the muscular tissue. After opening of the LV, the endocardial surface was inspected for the extent of the scar. Next, the thickness of the LV wall was assessed by palpation; a distinction between the normal thickness of the LV wall and the scar could be identified in every patient. In most patients, the border at which the ventricular wall changes thickness coincided with the endocardial extension of the visible scar, except for the septal extension. The area for endocardial cryoablation was based on visible extension of the scar tissue or, in rare cases when no visual identification was possible, on the change in wall thickness.10 Care was taken that the VT reentry circuit isthmus site marked during catheter mapping was included in the ablation line. The encircling cryoablation line coincided with the suture line of encircling endoventricular patch plasty performed after ablation. VTs with a morphology corresponding to 12-lead surface ECG documentation of a spontaneous VT were considered clinical, and VTs with a cycle length corresponding to the cycle length of a VT documented in the internal cardiac defibrillator were considered presumptive clinical VTs.11 Complete ablation success was defined as the absence of any inducible monomorphic VT after the ablation procedure. Partial success was defined as successful ablation of ≥1 clinical/presumptive clinical VTs but other VTs remained inducible. Ablation failure was defined as continued inducibility of the clinical/presumptive clinical VT. Acute success was tested immediately after radiofrequency catheter ablation in patients who underwent catheter ablation and during a second EPS before hospital discharge in patients who underwent surgery.
In patients treated with surgical ablation and/or ventricular restoration, transmural biopsies were taken from the removed central part of the LV scar and were systematically assessed by a pathologist blinded to clinical history and mapping findings. Routine hematoxylin and eosin stains were performed on 5-μm formalin-fixed paraffin-embedded sections. All sections were analyzed for the presence and distribution of myocardial fibrosis. Assessment included visual scoring for density, location (predominance of subendocardial or subepicardial fibrosis), and extent of fibrosis and evaluation of the maximum percentage of transmurality. The identified area of the most extensive fibrosis was further analyzed morphometrically for total wall thickness, thickness of the remaining viable myocardium, and ratio of remaining myocardium thickness to total wall thickness. In addition, the spatial relation between viable myocardium and fibrous tissue was assessed and scored for each section and compared with the electroanatomic mapping results of the core infarct region.
Continuous variables are expressed as mean±SD, and categorical variables are given as frequency (%). The Mann-Whitney U test and Fisher exact test were used to compare data when appropriate. Mean VT cycle length was compared after first averaging the VT cycle length of individual patients and subsequently performing analyses. All statistical analyses were performed with SPSS software (version 16, SPSS Inc, Chicago, Ill). For all tests, a value of P≤0.05 was considered significant.
The 36 patients (age, 63±15 years; 32 men) were referred for treatment of VT 13±9 years after AMI. Fourteen patients (38%) had undergone acute reperfusion therapy. Reperfusion was achieved by percutaneous coronary intervention in 8 patients and thrombolysis in 5. In 1 patient with an occluded left anterior descending artery, collateral flow to the IRA (Rentrop grade 3) was present at the time of acute infarction. This was considered spontaneous reperfusion of the infarcted area. The time from onset of symptoms to presentation was available in 12 patients. All patients were admitted within 6 hours after onset of symptoms. The median time from symptom onset to presentation was 2 hours 45 minutes (interquartile range, 1 hour to 5 hours 40 minutes). The median estimated time to needle and time to balloon were 45 minutes (interquartile range, 36 minutes to 1 hour) and 1 hour (interquartile range, 30 minutes to 2 hours), respectively, resulting in a median time from symptom onset to balloon/needle of 3 hours 30 minutes (interquartile range, 2 hours 6 minutes to 6 hours 6 minutes). Twenty-two patients did not undergo early reperfusion therapy. Twenty-two (60%) had anterior wall infarction, 11 (31%) had inferior wall infarction, 2 had (6%) posterior wall infarction, and 3 (8%) had >1 infarct location. In these 3 patients, the IRAs were the left anterior descending and right coronary arteries; 1 patient subsequently underwent successful thrombolysis of the left anterior descending and right coronary arteries and was classified as reperfused. The remaining 2 patients had chronic occlusion of the left anterior descending and right coronary arteries and were classified as nonreperfused. At referral, the IRA was patent in all patients who had undergone early reperfusion and occluded in 17 nonreperfused patients. In 5 nonreperfused patients, the IRA was patent as a result of late percutaneous coronary intervention in 4 and late spontaneous reperfusion in 1.
After evaluation, 9 patients (25%) were offered a combined approach of surgical ventricular restoration and intraoperative VT ablation. In 1 patient, surgical ventricular restoration without cryoablation was performed after initial catheter ablation. The baseline characteristics of the patients are summarized in Table 1.
Fifty-five different spontaneous VTs were registered during the 4.7±5 months preceding referral. The number of different VTs did not differ between reperfused and nonreperfused patients (1.4±1.3 versus 1.7±1.1; P=0.4). Twenty VTs were documented on 12-lead surface ECGs and 35 on local electrograms stored in the internal cardiac defibrillator. In the latter group, a difference in VT cycle length of >30 ms was considered a different VT. The VT cycle length was significantly shorter in reperfused patients compared with nonreperfused patients (299±52 versus 378±77 ms; P=0.01; Figure 1). To correct for the effect of antiarrhythmic drugs, specifically amiodarone, on VT cycle length, the mean cycle lengths of VTs registered without any antiarrhythmic drugs and without amiodarone were compared. There was a nonsignificant tendency to a shorter VT cycle length without antiarrhythmic drugs and a significantly shorter VT cycle length without amiodarone in reperfused compared with nonreperfused patients (Table 1).
VT was inducible in all patients with a total of 80 different induced VTs. The cycle length of the first induced VT (the positive end point of EPS) was significantly shorter in reperfused patients (278±80 versus 391±109 ms; P=0.002). A similar difference was found for the mean VT cycle length (270±58 versus 362±74 ms; P=0.001; Figure 1).
Fast VTs with a cycle length <250 ms were inducible in 71% of the reperfused patients compared with 23% of the nonreperfused patients (P=0.003). After exclusion of patients on amiodarone during EPS, the induced VT cycle length remained significantly shorter in reperfused patients (254±51 versus 334±65 ms; P=0.006).
LV voltage mapping was performed with a mean number of 214±43 mapping points. The total scar surface area (bipolar voltage <1.5 mV) was comparable in reperfused and nonreperfused patients (65±48 versus 85±46 cm2). However, the surface area of dense scar (bipolar voltage <0.5 mV) and the percentage of dense scar in relation to total scar were significantly smaller in the reperfused group (21±25 cm2 and 24±18% in reperfused versus 42±32 cm2 and 45±21% in nonreperfused; P=0.02 and P=0.002, respectively).
A patchy scar pattern in the IRA-related area was found in 13 patients (36%). Ten of 14 reperfused patients (71%) but only 3 nonreperfused patients (14%) had a patchy pattern (P=0.001; Figure 2).
In patients who underwent primary percutaneous coronary intervention, the differences compared with nonreperfused patients were even more pronounced. In these patients, the average cycle lengths of clinical and induced VTs were 270±23 and 239±24 ms, respectively (Figure 1). The average absolute surface area of dense scar was 11±12 cm2; the mean percentage of dense scar was 14±12%; and 7 (88%) had a patchy scar pattern.
The targeted reentry circuit sites of VT were located within the scar area supplied by the IRA in 33 patients. In 3 patients, no reentry circuit isthmus site could be identified on the basis of the criteria defined above. However, the VT QRS morphology was compatible with an exit site located in the area supplied by the IRA. The results of the electrophysiological evaluation are summarized in Table 2.
Catheter ablation was performed in 24 of 27 patients. In 3 patients, all after early reperfusion with nontolerated VT (average cycle length, 227±7 ms) and a patchy scar pattern, no potential VT isthmus site could be identified. In 2 nonreperfused patients, epicardial catheter ablation was performed after endocardial ablation failure, which was successful in 1 patient. In none of the reperfused patients was an epicardial ablation approach considered appropriate. No procedure-related complications were observed.
Ten patients were treated by surgery after electrophysiological evaluation. Nine patients (3 reperfused [21%], 6 nonreperfused [27%]) were treated by surgical cryoablation and surgical ventricular restoration. One patient underwent surgical ventricular restoration without cryoablation after catheter ablation. There was 1 perioperative death caused by heart failure. One patient refused postoperative EPS. Outcome after ablation did not differ between reperfused and nonreperfused patients (Table 3).
Histological assessment was performed in the subpopulation of 10 patients undergoing a surgical intervention (4 reperfused, 6 nonreperfused). In all nonreperfused patients, focal, transmural fibrosis was found; in contrast, 3 of 4 patients with early reperfusion had only nontransmural fibrosis (Figure 3A and 3B). The average wall thickness of the infarcted area was 1.4±0.7 mm. The average wall thickness was significantly greater in reperfused patients than in nonreperfused patients (2.0±0.6 versus 1.0±0.5 mm; P=0.03; Figure 3C). The average thickness of viable myocardium even in the most severely fibrotic area was 1.0±0.8 mm in reperfused patients, translating to a ratio of viable myocardium to total wall thickness of 0.5±0.3. In the patients (4 reperfused, 1 nonreperfused) with a patchy pattern of electroanatomic scar, the average wall thickness was greater than in patients with a homogeneous electroanatomic scar (1.9±0.5 versus 0.8±0.2 mm; P=0.01). The extent to which viable myocytes were interspersed with fibrosis was categorized (Figure 4). Five dominant histological patterns were identified: contiguous areas of viable myocardium, small confluent areas of fibrosis surrounded by viable myocardium, confluent areas of fibrosis containing only strands of viable cardiomyocytes, confluent areas of fibrosis containing solitary viable cardiomyocytes, and transmural confluent fibrosis. The first 2 patterns were found in only 3 patients after reperfusion and matched a patchy pattern of electroanatomic scar in the core infarct region. In 2 patients with a patchy electroanatomic pattern of scar (1 reperfused, 1 nonreperfused), transmural fibrosis with solitary viable cardiomyocytes was found at histological assessment. However, in these 2 patients, the core infarct region that was resected consisted of dense scar at mapping (patient 5 in Figure 4). In the 5 nonreperfused patients with a homogeneous scar on mapping, no contiguous areas of viable myocardium were found. Three representative examples of electroanatomic maps (patients 1, 5, and 6) were incorporated into the figure. The assumed area that was resected by the surgeon is indicated on the maps.
The present study evaluates the effect of early reperfusion of the IRA on VT characteristics and the VT substrate by EPS, 3-dimensional electroanatomic voltage mapping, and histology in patients who present with VT late after AMI. The main finding of the study is that characteristics of low-voltage scars after AMI are different in patients with and without reperfusion therapy. Early reperfusion is associated with less dense and less confluent electroanatomic scars that appear to give rise to faster spontaneous and inducible VTs. The electrophysiological findings match the histological assessment demonstrating that the LV core infarct area consists of at least 50% viable myocardium in reperfused patients. To the best of our knowledge, this is the first study to report on differences in electroanatomic ventricular voltage maps between post-AMI patients with and without successfully reperfused IRA and their potential impact on clinical arrhythmias.
Reperfusion and Myocardial Scar
Early reperfusion during AMI results in myocardial salvage and reduced mortality during follow-up.12 Animal studies showed that the duration of coronary artery occlusion is related to infarct size and extent of transmural necrosis.4,5 Early reperfusion resulted in necrosis of the inner third of the wall extending toward the midmyocardium, whereas late reperfusion or permanent occlusion resulted in a uniform transmural necrosis.5 Similar results were found in human autopsied hearts with acute MI after treatment with thrombolysis.13 These findings from the acute phase of AMI are supported and extended by our data because biopsies were taken in the chronic healing phase 13±9 years after the index MI in 10 studied patients (28%). Likely as a result of transmural necrosis, the core infarct consisted of transmural fibrosis in nonreperfused patients, whereas the majority of early reperfused patients showed no transmural fibrosis at all with thick layers of viable myocardium even in the core infarct region.
The current gold standard in electrophysiology to define scars after MI is based on electroanatomic voltage criteria. Mapping studies in a porcine model of healed MI after chronic occlusion of the IRA revealed large, homogeneous areas of very low voltages surrounded by only a small scar border zone.7 These very low-voltage areas, arbitrarily defined as <0.5 mV, are likely to reflect dense, transmural scar typical of chronic occlusion of the IRA without collateral circulation, whereas the surrounding border zone may reflect nontransmural scar areas that are partly supplied by non-IRAs. A similar pattern of a central homogeneous dense scar area surrounded by the electroanatomic border zone was found in the majority of nonreperfused patients in this study.
Total infarct size, defined as areas of electrograms <1.5 mV, was similar in reperfused and nonreperfused patients. However, acute reperfusion with a median time from symptom onset to balloon/needle of 3 hours 30 minutes does not completely abort MI but resulted in nontransmural scars as confirmed by histology in a subgroup of patients and contributed to total infarct size using an electroanatomic cutoff value of <1.5 mV.
Of importance, the total area of electrograms <0.5 mV was significantly smaller and the scar border zone defined by electrograms between 0.5 and 1.5 mV was significantly larger in reperfused patients. This finding is in line with the histological findings demonstrating only nontransmural scar in the majority of reperfused patients.
In addition, reperfused patients had less confluent electroanatomic scar in which areas of lower voltage were frequently interspersed with areas that show relatively preserved or normal bipolar electrograms. These electrograms do not exclude intramural fibrosis as demonstrated by histology. The electroanatomic findings likely reflect an inhomogeneous distribution of viable myocardium and fibrosis. Preserved voltage areas are more likely to contain predominantly viable myocardium interspersed with fibrous tissue, whereas dense electroanatomic scar likely reflects confluent areas of fibrosis containing only strands of viable cardiomyocytes (Figure 3).
Arrhythmia and Electroanatomic Scar
Preconditioning for scar-related VT is slow conduction through narrow bundles of surviving myocytes bound by fibrous tissue.14 VT cycle length is determined by circuit path length and conduction velocity. Increasing isthmus length contributes to circuit path length with consecutive longer VT cycle length.15 In a canine infarct model, zones of slow conduction and lines of block bordering the protected isthmus coincided with areas where the border zone of viable myocardium was thinnest and the local gradient in border-zone thickness was maximal. In contrast, regions of fast conduction coincided with areas of thicker border zones with minimal gradients.1,16
Tachycardia-related slow-conducting channels have been identified within dense electroanatomic scar areas in the majority of patients with monomorphic VT after AMI. The mean length of these channels was 23±11 mm, and the mean cycle length of the channel-related VT was 365±77 ms, similar to the VT cycle length found in nonreperfused patients in our study.17
The larger and confluent dense scar areas found in patients without reperfusion are more likely to contain longer protected slow-conducting channels, which may explain the observed longer arrhythmia cycle length.15 In contrast, in reperfused patients, small areas of dense scars are interspersed with areas of preserved voltages and likely preserved conduction velocity referred to as a patchy pattern. Small areas of dense scar and thicker infarct border zones may result in shorter isthmus length, faster conduction, and therefore shorter VT cycle length (an example is provided in the online-only Data Supplement).
The present study has demonstrated significant differences in the electroanatomic and histological substrate between early reperfused patients and patients with a chronically occluded IRA. In addition, among post-AMI patients who underwent early reperfusion, a shift seems to occur toward faster arrhythmias likely because of the reperfusion-induced change in the substrate. Previous studies providing insights into the underlying substrate of reentry circuits of VT and the importance of the scar border zone were performed in patients with chronically occluded IRAs.
Currently, radiofrequency catheter ablation of fast and unstable VT requires a substrate-based approach that targets the border zone of scar relying on voltage mapping and pace mapping. This substrate-based approach was validated in an animal model of a chronic occluded IRA with large homogeneous electroanatomic scars surrounded by a small border zone. The larger border zone in reperfused patients with only small areas of dense scar on mapping and histology, however, may require a different mapping approach. Pace mapping to define VT exit sites might be less reliable or not applicable if pacing is performed within short protected isthmuses. Whether a patchy pattern of electroanatomic scar after reperfusion will pose a challenge in substrate-based mapping and ablation needs further evaluation. Studies in animal models that reflect the anatomic substrate in the reperfusion era are warranted to reevaluate the relationship of the VT circuit and the architecture of the scar, which might influence the concept of substrate-based ablation.
Reperfused patients accounted for one third of the studied population. These patients presented on average 7.7 years earlier than nonreperfused patients. There might be an ascertainment bias; eg, the nonreperfused patients may represent a subgroup of long-term survivors. In addition, alterations in the anatomy of the VT substrate over time that may occur as a result of increased wall stress, ischemia, hypertension, or medication or because of gradual changes after infarct healing cannot be excluded as potential confounders of the presented results. However, the difference in presentation time might reflect advances in recognition and reperfusion strategies of ST-segment elevation AMI in our patient population. The observational nature and relatively small sample size of the study limit the further identification of possible confounders. Because all patients in the present study were referred for ablation of VT, larger studies in a general population of patients after MI are warranted to further elucidate the effect of early reperfusion on arrhythmogenesis and characteristics of VTs.
All biopsies were taken from the central part of the infarcted area as identified by the surgeon. The scar areas were not completely resected; therefore, small areas of transmural fibrosis in the core infarcted area in reperfused patients might be missed. In addition, transmural biopsies were available only from the small subgroup of patients who underwent surgery.
There are marked differences in electroanatomic scar size and pattern between patients with and without successful reperfusion at the time of MI. Less confluent electroanatomic scars match layers of surviving myocyte bundles on biopsy. Early reperfusion and less confluent electroanatomic scar are associated with faster VTs, which might influence substrate-based ablation strategies.
We thank Dr W.G. Stevenson for helpful suggestions on the manuscript.
Source of Funding
Dr von der Thüsen is a recipient of a Dutch Heart Foundation stipend (Dutch Heart Foundation Junior Staff Member Fellowship No. 2008T050).
Ciaccio EJ, Ashikaga H, Kaba RA, Cervantes D, Hopenfeld B, Wit AL, Peters NS, McVeigh ER, Garan H, Coromilas J. Model of reentrant ventricular tachycardia based on infarct border zone geometry predicts reentrant circuit features as determined by activation mapping. Heart Rhythm. 2007; 4: 1034–1045.
Marchlinski FE, Callans DJ, Gottlieb CD, Zado E. Linear ablation lesions for control of unmappable ventricular tachycardia in patients with ischemic and nonischemic cardiomyopathy. Circulation. 2000; 101: 1288–1296.
Verma A, Marrouche NF, Schweikert RA, Saliba W, Wazni O, Cummings J, Abdul-Karim A, Bharqava M, Burkhardt JD, Kilicaslan F, Martin DO, Natale A. Relationship between successful ablation sites and the scar border zone defined by substrate mapping for ventricular tachycardia post-myocardial infarction. J Cardiovasc Electrophysiol. 2005; 16: 465–471.
Reimer KA, Lowe JE, Rasmussen MM, Jennings RB. The wavefront phenomenon of ischemic cell death, 1: myocardial infarct size vs duration of coronary occlusion in dogs. Circulation. 1977; 56: 786–794.
Miyazaki S, Fujiwara H, Onodera T, Kihara Y, Matsuda M, Wu DJ, Nakamura Y, Kumada T, Sasayama S, Kawai C. Quantitative analysis of contraction band and coagulation necrosis after ischemia and reperfusion in the porcine heart. Circulation. 1987; 75: 1074–1082.
Soejima K, Suzuki M, Maisel WH, Brunckhorst CB, Delacretaz E, Blier L, Tung S, Khan H, Stevenson WG. Catheter ablation in patients with multiple and unstable ventricular tachycardias after myocardial infarction: short ablation lines guided by reentry circuit isthmuses and sinus rhythm mapping. Circulation. 2001; 104: 664–669.
Reddy VY, Wrobleski D, Houghtaling C, Josephson ME, Ruskin JN. Combined epicardial and endocardial electroanatomic mapping in a porcine model of healed myocardial infarction. Circulation. 2003; 107: 3236–3242.
Sheehan FH, Braunwald E, Canner P, Dodge HT, Gore J, Van NP, Passamani ER, Williams DO, Zaret B. The effect of intravenous thrombolytic therapy on left ventricular function: a report on tissue-type plasminogen activator and streptokinase from the Thrombolysis in Myocardial Infarction (TIMI Phase I) trial. Circulation. 1987; 75: 817–829.
Aliot EM, Stevenson WG, Almendral-Garrote JM, Bogun F, Calkins CH, Delacretaz E, Della BP, Hindricks G, Jais P, Josephson ME, Kautzner J, Kay GN, Kuck KH, Lerman BB, Marchlinski F, Reddy V, Schalij MJ, Schilling R, Soejima K, Wilber D. EHRA/HRS Expert consensus on catheter ablation of ventricular arrhythmias: developed in a partnership with the European Heart Rhythm Association (EHRA), a registered branch of the European Society of Cardiology (ESC), and the Heart Rhythm Society (HRS); in collaboration with the American College of Cardiology (ACC) and the American Heart Association (AHA). Heart Rhythm. 2009; 6: 886–933.
Matsuda M, Fujiwara H, Onodera T, Tanaka M, Wu DJ, Fujiwara T, Hamashima Y, Kawai C. Quantitative analysis of infarct size, contraction band necrosis, and coagulation necrosis in human autopsied hearts with acute myocardial infarction after treatment with selective intracoronary thrombolysis. Circulation. 1987; 76: 981–989.
De Bakker JM, van Capelle FJ, Janse MJ, Wilde AA, Coronel R, Becker AE, Dingemans KP, van Hemel NM, Hauer RN. Reentry as a cause of ventricular tachycardia in patients with chronic ischemic heart disease: electrophysiologic and anatomic correlation. Circulation. 1988; 77: 589–606.
Ciaccio EJ. Dynamic relationship of cycle length to reentrant circuit geometry and to the slow conduction zone during ventricular tachycardia. Circulation. 2001; 103: 1017–1024.
Peters NS, Coromilas J, Severs NJ, Wit AL. Disturbed connexin43 gap junction distribution correlates with the location of reentrant circuits in the epicardial border zone of healing canine infarcts that cause ventricular tachycardia. Circulation. 1997; 95: 988–996.
Arenal A, del Castillo S, Gonzalez-Torrecilla E, Atienza F, Ortiz M, Jimenez J, Puchol A, Garcia J, Almendral J. Tachycardia-related channel in the scar tissue in patients with sustained monomorphic ventricular tachycardias: influence of the voltage scar definition. Circulation. 2004; 110: 2568–2574.
Reperfusion therapy during acute myocardial infarction results in myocardial salvage. The duration of coronary artery occlusion and early reperfusion have been shown to affect the size and geometry of fibrosis after myocardial infarction. The 3-dimensional scar geometry influences reentry circuit location and ventricular tachycardia (VT) characteristics. Current substrate-based catheter ablation strategies for VT after myocardial infarction are based predominantly on studies in patients and animals with a chronically occluded infarct-related artery resulting in large homogeneous scars. In the present study, we demonstrate that early reperfusion influences the characteristics of post–acute myocardial infarction scars assessed by electroanatomic voltage mapping and by histology after myocardial infarction compared with patients without reperfusion therapy. Early reperfusion was associated with less dense and less confluent electroanatomic scars consisting of thicker layers of viable myocardium that appear to give rise to faster spontaneous and inducible VTs. These findings may have important implications for the management of patients in the reperfusion era who present with VTs. Poorly tolerated VT requires a substrate-based ablation approach. However, current substrate-based techniques relying on voltage and pace mapping to target the scar border zone may not be applicable for smaller, less dense, and less confluent scar. Whether these changes in the electroanatomic VT substrate of reperfused patients will pose a challenge in ablation needs further evaluation. Studies in animal models more realistic in the reperfusion era are warranted to reevaluate the relationship of the VT circuit and the architecture of the scar and to reassess substrate-based ablation concepts.
The online-only Data Supplement is available with this article at http://circ.ahajournals.org/cgi/content/full/CIRCULATIONAHA.109.891242/DC1.