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Published online before print October 2, 2007, 10.1148/radiol.2452061615
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(Radiology 2007;245:712-719.)
© RSNA, 2007

Cardiac Imaging

Enhanced Infarct Border Zone Function and Altered Mechanical Activation Predict Inducibility of Monomorphic Ventricular Tachycardia in Patients with Ischemic Cardiomyopathy1

Verônica Rolim S. Fernandes, MD, PhD, Katherine C. Wu, MD, Boaz D. Rosen, MD, André Schmidt, MD, PhD, Albert C. Lardo, PhD, Nael Osman, PhD, Henry R. Halperin, MD, Gordon Tomaselli, MD, Ronald Berger, MD, PhD, David A. Bluemke, MD, PhD, Eduardo Marbán, MD, PhD, and João A. C. Lima, MD

1 From the Division of Cardiology, Johns Hopkins Hospital, 600 N Wolfe St, Blalock 524, Baltimore, MD 21287 (V.R.S.F., K.C.W., B.D.R., A.S., A.C.L., H.R.H., G.T., R.B., E.M., J.A.C.L.); and Departments of Biomedical Engineering (A.C.L.), Radiology (A.C.L., N.O., D.A.B., J.A.C.L.), and Surgery (A.C.L.), Johns Hopkins University, Baltimore, Md. Received September 18, 2006; revision requested November 17; revision received December 22; accepted January 23, 2007; final version accepted April 2. Supported by the Donald W. Reynolds Foundation and by grant RO1-HL64795 from the National Institutes of Health. V.R.S.F. supported by a research grant from CAPES, Ministry of Education of the Brazilian Government. Address correspondence to J.A.C.L. (e-mail: jlima{at}jhmi.edu).


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ADVANCES IN KNOWLEDGE
 IMPLICATIONS FOR PATIENT CARE
 References
 
Purpose: To prospectively determine whether mechanical behavior of left ventricular wall segments that contain different degrees of scar tissue and are located at different distances from the interface between infarcted and noninfarcted myocardial tissue can help predict inducibility of monomorphic ventricular tachycardia (VT) in patients with ischemic cardiomyopathy.

Materials and Methods: This HIPAA-compliant study was institutional review board approved; written informed consent was obtained from all patients. Forty-six patients (36 men, 10 women; mean age ± standard deviation, 61.6 years ± 11.9) with prior myocardial infarction (MI) and left ventricular dysfunction were referred for defibrillator implantation and underwent an electrophysiologic examination and tagged contrast-enhanced magnetic resonance (MR) imaging. Peak circumferential shortening strain (Ecc) and time to peak Ecc were measured in 12 segments from short-axis sections. Remote, adjacent, and border zones were defined according to increasing proximity to the MI. Patients in whom monomorphic VT could be induced (ie, inducible patients) were considered positive for inducibility. Relationships between inducibility of monomorphic VT, peak Ecc, and time to peak Ecc were analyzed with one-way analysis of variance and Bonferroni test.

Results: Inducible patients had more infarcted and border zone sectors and a shorter time to peak Ecc than did noninducible patients in the border zone and adjacent and infarcted regions (P < .001). Peak Ecc in the border zone of inducible patients (–11.42% ± 0.46 [standard error]) was greater than that in noninducible patients (–10.18% ± 0.38; P < .05). Ratio of Ecc in border zone and in remote regions was greater (P < .05) in inducible patients than in noninducible patients (1.31 ± 0.27 vs 0.64 ± 0.13, respectively).

Conclusion: Enhanced border zone function defined as greater Ecc and earlier time to peak Ecc showed positive correlation to VT inducibility in patients with prior MI and left ventricular dysfunction.

© RSNA, 2007


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ADVANCES IN KNOWLEDGE
 IMPLICATIONS FOR PATIENT CARE
 References
 
Left ventricular dysfunction has been identified as a marker of risk for sudden death in patients with coronary artery disease, and strategies to decrease the risk of sudden cardiac death in these patients are currently being studied (1–3). The Multicenter Automatic Defibrillator Implantation Trial (MADIT) II study findings (4) demonstrate that the placement of an implantable cardioverter defibrillator (ICD) resulted in a substantial (31% relative and ~6% absolute) reduction in total mortality in patients after myocardial infarction (MI) with a left ventricular ejection fraction of less than 30%.

Further refinement of risk criteria for ICD implantation, however, is required because most patients in whom an ICD is placed never experience appropriate firing. In addition, many patients with previous MI die suddenly despite the preservation of global left ventricular function (5). In the past, approaches directed at identifying patients at greatest risk have been based on the electrophysiologic properties of noninfarcted myocardial tissue and the factors that trigger the induction of lethal arrhythmias in these patients (6,7). Conversely, few studies have been performed to assess the detailed mechanical characteristics of the failing left ventricle as a marker of risk for malignant arrhythmias in relationship to its anatomic substrate, that is, the interface between myocardial scar tissue and preserved myocardial tissue. Previous studies have demonstrated that reentrant ventricular tachycardia (VT) commonly originates at this interface or border zone, which, in turn, may precipitate cardiac arrest in the absence of active ischemia (6).

Myocardial scar tissue can be accurately defined and quantified with contrast material–enhanced magnetic resonance (MR) imaging (8–11). Moreover, MR imaging with tissue tagging can be used in the detailed analysis of regional mechanical contractile behavior with high spatial resolution in relation to the infarct border (12,13). Thus, the purpose of our study was to prospectively determine whether the mechanical behavior of left ventricular wall segments that contain different degrees of scar tissue and are located at different distances from the interface between infarcted and noninfarcted myocardial tissue can help predict the inducibility of monomorphic VT in patients with ischemic cardiomyopathy.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 ADVANCES IN KNOWLEDGE
 IMPLICATIONS FOR PATIENT CARE
 References
 
Study Group
One author (N.O.) is a shareholder in and is on the advisory board of Diagnosoft (Palo Alto, Calif).

The study protocol was reviewed and approved by the institutional review board, and written informed consent was obtained from all patients. Our study was conducted in accordance with Health Insurance Portability and Accountability Act regulations.

Forty-six consecutive patients (36 men, 10 women; mean age ± standard deviation, 61.6 years ± 11.9; eight African American patients) with ischemic cardiomyopathy after MI who were referred for ICD placement for primary prevention of sudden cardiac death were prospectively enrolled between August 2003 and March 2005. Selection and exclusion were based on MADIT I (2) (n = 10) or II (4) (n = 36) criteria. All patients underwent tagged and contrast-enhanced MR imaging to analyze regional left ventricular function and MI location, respectively. Patients in whom monomorphic VT was inducible at electrophysiologic study or during ICD placement (ie, inducible patients) were considered positive. The relationship between inducibility and regional left ventricular function was studied.

Electrophysiologic Study
After MR imaging, patients underwent programmed ventricular stimulation at ICD placement or as an independent study. The stimulation protocol consisted of up to three extrastimuli at two drive cycle lengths delivered from the right ventricular apex alone (if the study was performed during ICD placement) or from the right ventricular apex and outflow tract (if the electrophysiologic study was performed independently). Inducible VT was defined as monomorphic VT of more than 10 seconds duration or associated with hemodynamic compromise necessitating earlier intervention.

MR Imaging
All patients underwent MR imaging with a 1.5-T clinical unit (Signa CV/I; GE Medical Systems, Waukesha, Wis) and a phased-array receiver coil wrapped around the chest. After localization of the heart, eight to 10 contiguous short-axis sections were prescribed to cover the entire left ventricle from the base to the apex. Cine images were obtained by using a steady-state free precession pulse sequence. Imaging parameters were as follows: repetition time msec/echo time msec, 3.8/1.6; flip angle, 45°; section thickness, 8–10 mm; field of view, 360–400 mm; matrix, 256 x 160; and temporal resolution, 40 msec.

For tagged MR imaging, five to eight tagged equally spaced short-axis sections were acquired to cover the entire left ventricle from the base to the apex. Tags were prescribed as a grid matrix in orthogonal orientations (0° and 90°) by using an electrocardiographically triggered spoiled gradient-echo pulse sequence with spatial modulation of magnetization (14,15). The parameters for tagged MR imaging were as follows: 3.5–7.2/2.0–4.2; flip angle, 12°; section thickness, 8–10 mm; field of view, 40 cm; matrix, 256 x 96–140; four to nine phase-encoding views per segment; mean bandwidth, 49 MHz (range 24.9–62.5 MHz); temporal resolution, 15.6–60.0 msec; and tag spacing, 7 mm.

Delayed-enhancement images were obtained in locations identical to those used for tagged MR imaging 10–15 minutes after the injection of a bolus of 0.2 mmol of gadodiamide (Omniscan; Amersham Health, Princeton, NJ) per kilogram of body weight by using an inversion-recovery fast gradient-echo pulse sequence. Imaging parameters were as follows: repetition time msec/echo time msec/inversion time msec, 5.4/1.3/150–250 (adjusted to null the signal of normal myocardium); flip angle, 20°; section thickness, 8 mm; field of view, 36–40 cm; matrix, 256 x 192; and two signals acquired.

Data Analysis
All contrast-enhanced MR imaging postprocessing analyses were performed by using a software package (Cinetool; GE Healthcare Technologies, Waukesha, Wis). Cine images were used to measure left ventricular ejection fraction, volumes, and mass according to standard methods (16). Delayed-enhancement images were used for infarct characterization. Myocardial tissue for each patient was classified as hyperenhanced (scar tissue) or normally enhanced myocardium with the software tool after a trained observer (A.S., with 3 years of cardiac MR imaging experience), through manual interaction, defined a region of interest within remote noninfarcted territory. The endocardial and epicardial borders were also defined by manual interaction to avoid contamination from the left ventricular cavity signal. Hyperenhanced tissue (scar tissue) was defined as areas with a signal intensity of more than 2 standard deviations from the mean signal intensity measured in remote areas within the manually predefined region of interest.

To measure myocardial strain in the entire left ventricle, the left ventricular wall was divided into myocardial sections and each of these sections was divided into 12 segments around the left ventricular cavity. Circumferential shortening was measured in each of these 12 sectors of every myocardial short-axis section, and scar transmurality was determined as the percentage of sector area comprised by scar tissue for each of these sectors. The latter parameter, that is, the percentage of scar tissue area in the sector, was used to classify each sector into four topographic regions. The infarcted region comprised segments with more than 25% of its area occupied by scar tissue. The border region comprised segments that contained less than 25% of scar tissue area and was immediately contiguous (either circumferentially or longitudinally) to the infarcted region. The adjacent region was defined as segments adjacent to those in the border regions (either circumferentially or longitudinally) that did not contain scar tissue. Finally, remote segments that did not contain scar tissue were those located outside the adjacent region.

The short-axis tagged sections were analyzed with the Harmonic Phase method (Diagnosoft) (17) to assess strain (V.R.S.F., B.D.R.; 3 and 5 years of experience in cardiac MR imaging, respectively). Regional systolic circumferential strains (Ecc) and the time between end diastole (electrocardiographic R wave) and peak Ecc were determined in 12 left ventricular segments from the midwall layer (Fig 1). By convention, systolic strains are expressed as the percentage of negative fractions of changes in distance between two points and, therefore, increased negativity denotes enhanced function. Ecc curves were obtained by tracking tagged myocardium throughout systole as shown in Figure 1d, which displays two Ecc curves corresponding to tagged tissue within the infarcted and remote regions. Ratios of border to remote regions of peak Ecc were calculated for each patient. These ratios were obtained by dividing the average Ecc from all border zone segments by that of remote regions.


Figure 1A
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  		Figure 1a: Images in an inducible patient with an anterior MI. (a) Short-axis delayed-enhancement MR image (5.4/1.3) obtained in the middle of the left ventricle. (b) Short-axis tagged MR image (5.0/2.1) obtained at the middle of the left ventricle at end diastole. (c) Short-axis tagged MR image obtained in the left ventricle at end diastole with constructed mesh by using Harmonic Phase software (Diagnosoft). Blue line indicates the subepicardial layer; red line, the midwall; and green line, the subendocardial layer. (d) Graph shows systolic Ecc curves. Note that the contraction in the infarcted region is significantly reduced when compared with that in the remote region.

 

Figure 1B
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  		Figure 1b: Images in an inducible patient with an anterior MI. (a) Short-axis delayed-enhancement MR image (5.4/1.3) obtained in the middle of the left ventricle. (b) Short-axis tagged MR image (5.0/2.1) obtained at the middle of the left ventricle at end diastole. (c) Short-axis tagged MR image obtained in the left ventricle at end diastole with constructed mesh by using Harmonic Phase software (Diagnosoft). Blue line indicates the subepicardial layer; red line, the midwall; and green line, the subendocardial layer. (d) Graph shows systolic Ecc curves. Note that the contraction in the infarcted region is significantly reduced when compared with that in the remote region.

 

Figure 1C
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  		Figure 1c: Images in an inducible patient with an anterior MI. (a) Short-axis delayed-enhancement MR image (5.4/1.3) obtained in the middle of the left ventricle. (b) Short-axis tagged MR image (5.0/2.1) obtained at the middle of the left ventricle at end diastole. (c) Short-axis tagged MR image obtained in the left ventricle at end diastole with constructed mesh by using Harmonic Phase software (Diagnosoft). Blue line indicates the subepicardial layer; red line, the midwall; and green line, the subendocardial layer. (d) Graph shows systolic Ecc curves. Note that the contraction in the infarcted region is significantly reduced when compared with that in the remote region.

 

Figure 1D
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  		Figure 1d: Images in an inducible patient with an anterior MI. (a) Short-axis delayed-enhancement MR image (5.4/1.3) obtained in the middle of the left ventricle. (b) Short-axis tagged MR image (5.0/2.1) obtained at the middle of the left ventricle at end diastole. (c) Short-axis tagged MR image obtained in the left ventricle at end diastole with constructed mesh by using Harmonic Phase software (Diagnosoft). Blue line indicates the subepicardial layer; red line, the midwall; and green line, the subendocardial layer. (d) Graph shows systolic Ecc curves. Note that the contraction in the infarcted region is significantly reduced when compared with that in the remote region.

 
Statistical Analysis
Statistical analysis was performed with a standard statistical software package (SPSS, version 13.0; SPSS, Chicago, Ill). Data are presented as means ± standard deviations unless stated otherwise. The Pearson {chi}2 with asymptotic test was used to assess between-group statistical comparisons of clinical variables. Both time to peak Ecc and maximal Ecc were analyzed by using one-way analysis of variance models. After finding significant differences with generalized linear models, multiple comparisons were performed by applying the Bonferroni ad hoc test, considering Ecc or time to peak Ecc as the outcome variable on different transmurality regions. Various comparisons of interests were analyzed, including those within and between the inducible and noninducible groups of different tagged regions defined by the same or different levels of remoteness from the infarcted region. Hypothesis tests for strain and time to peak Ecc were performed between inducibile and noninducible patients for border zones and remote regions by using unpaired Student t tests, and multiple comparison methods were applied whenever the number of groups exceeded two. All tests were two tailed, and differences were considered significant when the P value was less than .05.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 ADVANCES IN KNOWLEDGE
 IMPLICATIONS FOR PATIENT CARE
 References
 
There were no statistically significant differences in sex and age distribution, drug therapy, or infarct location between the inducible and noninducible patients (Table 1). Importantly, the heart rates, left ventricular volumes and masses, and ejection fractions did not differ significantly between the two groups (Table 2). The MI mass was significantly larger in inducible patients than in noninducible patients (64.8 g vs 50.5 g, respectively; P < .05; Table 2). Noninducible patients, however, tended to be categorized in a higher New York Heart Association heart failure class than inducible patients, although the difference did not reach statistical significance (P = .09, Table 1). All patients had transmural MI.


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  		Table 1. Clinical Characteristics of Inducible and Noninducible Patients

 

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  		Table 2. Structural and Functional Parameters from Inducible versus Noninducible Patients

 
Transmurality of Delayed Enhancement according to Inducibility
It is interesting that inducible patients had a greater number of infarcted (47.0% vs 38.2%, P < .01) and border zone (23.1% vs 21.5%, P < .01) sectors when compared with noninducible patients (P < .01). Conversely, our results showed that noninducible patients had a greater number of remote (23.4% vs 14.3%, P < .0001) and adjacent (16.9% vs 15.5%, P < .0001) sectors when compared with inducible patients (Table 3).


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  		Table 3. Transmurality Regions of Delayed Enhancement according to Inducibility

 
Time to Peak Ecc and Inducibility of VT
The time to peak Ecc was shorter in the inducible patients than in the noninducible patients. On average, the time to peak Ecc was 42 msec (95% confidence interval: 29.2 msec, 55.6 msec) shorter in inducible patients than in noninducible patients. Moreover, when comparisons were made between inducibility groups (Table 4, Fig 2), the average time to peak Ecc was shorter in inducible patients than in noninducible patients in segments classified as adjacent regions (P < .001), border zone (P < .001), and infarcted regions (P < .001) but not in remote regions (P > .05).


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  		Table 4. Time-to-Peak Ecc for Myocardial Regions Classified according to Proximity to the Infarcted Region and Scar Tissue Transmurality in Inducible and Noninducible Patients

 

Figure 2
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  		Figure 2: Graph shows the mean time to peak Ecc in different myocardial regions in inducible and noninducible patients. Data are presented as mean value ± 1.96 (standard error). The time to peak Ecc was significantly shorter in noninducible patients than in all but the remote region in inducible patients (P < .05).

 
Conversely, when comparisons were made within the group of patients in whom monomorphic VT could be induced, time to peak Ecc was similar among the different regions (infarcted, border, adjacent, and remote). Similar results were also found for the group of patients in whom monomorphic VT could not be induced (Table 4, Fig 2).

Magnitude of Circumferential Shortening and Inducibility of VT
When contractile function indexed according to percentage of peak systolic shortening was compared between the two groups of patients classified according to inducibility of monomorphic VT, we found that, on average, border zone segments of inducible patients had greater systolic contractility (more negative greater function) than did those of noninducible patients (P < .05; Table 5, Fig 3). Differences in Ecc for segments located in other regions were not significant between the two groups. To further explore these between-group differences, we examined whether function in the border zone normalized to remote region function in the same heart was related to electrophysiologic inducibility. The ratio of Ecc in border zone and in remote regions (turned positive with the division of two negative numbers) was 1.31 ± 0.27 (mean ± standard error) for inducible patients and 0.64 ± 0.13 for noninducible patients (P < .05).


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  		Table 5. Peak Ecc for Myocardial Regions Classified according to Proximity to the Infarcted Region and Scar Tissue Transmurality in Inducible and Noninducible Patient Groups

 

Figure 3
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  		Figure 3: Graph shows the mean peak Ecc in the different myocardial regions in inducible and noninducible patients. Data are presented as mean value ± 1.96 (standard error). On average, the systolic contractability of border zone segments in noninducible patients was worse than that in inducible patients (P < .05).

 
In addition, when different regions were compared within the two groups categorized according to inducibility, the following results were obtained: In the group of inducible patients, the percentage of peak systolic shortening (Ecc) in the infarcted regions was significantly reduced (more positive, less function) when compared with that in other myocardial regions classified according to scar tissue content and spatial distance from the infarct interface: border zone, P = .001; adjacent region, P < .0001; and remote region, P < .0001 (Table 5, Fig 3). Contractile function, however, was similar among segments located in the latter three regions. Conversely, within the noninducible group of patients, peak Ecc (given as a percentage) was reduced in magnitude not only in the infarcted region when compared with myocardial segments located in the border zone (P < .0001) and the adjacent (P < .0001) and remote (P < .0001, Fig 3) regions, but also in the border zone when the latter was compared with the adjacent (P < .0001) and remote (P = .009) regions. Finally, Ecc was similar in adjacent and remote regions among noninducible patients.


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
ADVANCES IN KNOWLEDGE
 IMPLICATIONS FOR PATIENT CARE
 References
 
The results of our study demonstrate that enhanced border zone function indexed as greater myocardial shortening and earlier time to peak Ecc characterized as a shorter time to peak contraction are correlated with inducibility of monomorphic VT in patients with ischemic cardiomyopathy. To our knowledge, this is the first study that relates inducibility of ventricular tachyarrhythmias with mechanical metrics obtained from combined delayed contrast-enhanced MR imaging and myocardial tagging in patients with ischemic cardiomyopathy. These findings add to our current understanding of the anatomic and mechanical substrates that underlie monomorphic VT in patients after MI with severe left ventricular dysfunction.

In general, the time to peak systolic deformation was 29–56 msec earlier in inducible patients than in noninducible patients. These differences were secondary to shorter contraction times in myocardial segments that contained scar tissue (classified as infarcted or border segments) and those that contained no scar tissue but were adjacent to border segments. More importantly, these changes in mechanical activation were accompanied by enhanced systolic myocardial shortening in the regions comprising the infarct interface (border region), an area known for heightened mechanical stress (18–20), altered metabolism (21), increased inflammatory activity, and cell apoptosis (22) well beyond infarct healing. It is important that this is the region that most often serves as the substrate for reentrant VT in patients with ischemic heart disease and prior MI (23,24).

Although the exact mechanisms underlying the relationships reported in our study remain to be elucidated, one of the first potential factors that comes to mind relates to the possibility that different amounts (transmural extent), types (hypertrophic responses), and/or geometric distribution (subendocardial vs subepicardial) of viable myocardium in the border region of patients from the two groups help explain both the differences in function and the enhanced susceptibility to VT. Differences in the "viable to nonviable mix" in terms of quantity, quality, or spatial distribution of myocardium and scar tissue could foster reentry, disorganized propagation of electrical activation, or both, while at the same time producing greater shortening locally. In this regard, the relations of extent of mixed viable or nonviable myocardium as defined by contrast-enhanced MR imaging in the border region (gray zone) with susceptibility for malignant arrhythmias (25) and postinfarct mortality (26) have been documented previously. Furthermore, in patients with Chagas heart disease, the presence and distribution of scar tissue is directly related to the development of spontaneous VT (27). The findings of Rochitte et al (27) support the notion that MR imaging–detected myocardial scarring caused by ischemic injury (28) or secondary to other pathophysiologic processes (25) may represent markers of VT inducibility and, ultimately, sudden death. In addition, it has also been demonstrated recently that the presence of intramural scar tissue in patients with nonischemic cardiomyopathy portends greater propensity for inducible VT (29) and mortality (30). Our study extends this concept by providing evidence that altered mechanical behavior in the form of altered contractile function and activation may constitute additional parameters to better define the substrate for malignant arrhythmias.

This possibility, however, while attractive, does not explain the earlier overall mechanical activation documented in the inducible group. These alterations suggest the contribution of other more generalized factors that contribute to increased arrhythmogenesis and increased function at the local border zone level. A possible mechanism of the border zone functional enhancement and earlier time to peak Ecc in inducible patients is increased sympathetic tone, which is considered to be one of the most important determinants of life-threatening arrhythmias (31).

Previous investigators have demonstrated that sympathetic activity is markedly increased in patients who survive or have post-MI VT (32,33), as opposed to those who did not develop postinfarct VT (32). They have also demonstrated lower baroreflex sensitivity in post-MI patients who experienced hemodynamic deterioration during VT (32,34). Increased sympathetic tone has also been demonstrated before the onset of major arrhythmias in patients with internal defibrillators (35), a finding that supports the concept that adrenergic stimulation enhances the risk of VT perhaps by augmenting border region function and/or producing inhomogeneities of mechanical activation.

Other regional mechanistic possibilities involving increased adrenergic stimulation relate to the time course and spatial distribution of cardiac nerve sprouting and sympathetic hyperinnervation after myocardial injury and necrosis. This phenomenon has been extensively studied in animal models of MI and in humans (36–39). After nerve injury induced by MI, sympathetic nerve sprouting contributes to regionally heterogeneous myocardial hyperinnervation (39), which has been associated with augmented susceptibility to ventricular arrhythmias and sudden death (40,41). These alterations of sympathetic nerve ending regeneration could be associated with altered border zone function. Finally, it is possible that the functional alterations reported in our study are directly implicated in the differences of susceptibility to monomorphic VT between the two groups of patients. An increased magnitude of border zone mechanical activity and/or altered timing to peak systolic deformation among the various myocardial regions might confer an increased risk to develop malignant VT. In this regard, heterogeneous mechanical activation could directly enhance the propensity for increased wall stress with regional alterations in electrophysiologic properties through the action of stretch-activated ion channels and arrhythmogenicity. Finally, it is important to also have in mind that the mechanisms listed earlier are not mutually exclusive and might contribute to different extents in different individuals.

Our study has limitations. We studied only patients with ischemic as opposed to nonischemic cardiomyopathy, and the only outcome was inducibility of monomorphic VT. We excluded inducibility of ventricular fibrillation because this response might be less specific. In addition, our inclusion criteria were not exactly identical to those used in the MADIT II study. Our electrophysiology protocol included the performance of invasive, as well as noninvasive electrophysiologic studies performed during ICD placement. Moreover, although inducibility for monomorphic VT in patients with ischemic cardiomyopathy is a risk factor for the development of spontaneous VT and/or ventricular fibrillation or sudden death, there is not an absolute 1:1 relationship between inducibility to those events and spontaneous VT. Finally, although multiple comparisons should be interpreted with caution given the small sample size, one should also consider that the number of observations, that is, the number of tagged segments within each anatomic region, was much larger, enabling better estimates of the intrasubject correlations.

In conclusion, enhanced border zone function in areas that contain a mixture of viable and nonviable tissue at the infarct interface is related to inducibility of monomorphic VT in patients with ischemic cardiomyopathy. Moreover, earlier mechanical activation characterized by the time needed to reach maximal systolic shortening is also related to the inducibility of monomorphic VT in these patients. The results of this study support the use of contrast-enhanced MR imaging with tissue tagging for the complete characterization of the anatomic and functional substrate that underlies malignant arrhythmias in patients with ischemic heart disease. This may lead to an improved definition of the subgroup of patients who will benefit from ICD placement after MI.


   ADVANCES IN KNOWLEDGE
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ADVANCES IN KNOWLEDGE
IMPLICATIONS FOR PATIENT CARE
 References
 


   IMPLICATIONS FOR PATIENT CARE
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ADVANCES IN KNOWLEDGE
 IMPLICATIONS FOR PATIENT CARE
References
 


   ACKNOWLEDGMENTS
 
The authors thank the participants of the Reynolds study, the other investigators, and the staff of the Johns Hopkins Donald W. Reynolds Center for their valuable contributions to this work. In addition, the authors acknowledge the important help with statistical review of the manuscript by Benilton S. Carvalho, MSc, Johns Hopkins Bloomberg School of Public Health.


   FOOTNOTES
 

Abbreviations: Ecc = circumferential shortening strain • ICD = implantable cardioverter defibrillator • MADIT = Multicenter Automatic Defibrillator Implantation Trial • MI = myocardial infarction • VT = ventricular tachycardia

See Materials and Methods for pertinent disclosures.

Author contributions: Guarantors of integrity of entire study, V.R.S.F., B.D.R., J.A.C.L.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; manuscript final version approval, all authors; literature research, all authors; clinical studies, V.R.S.F., K.C.W., B.D.R., D.A.B., R.B., G.T., H.R.H., A.S., J.A.C.L.; statistical analysis, V.R.S.F.; and manuscript editing, all authors


   References
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ADVANCES IN KNOWLEDGE
 IMPLICATIONS FOR PATIENT CARE
 References
 

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