FOCUS ISSUE: HYPERTROPHIC CARDIOMYOPATHY: CLINICAL RESEARCH
Cardiac Magnetic Resonance Detection of Myocardial Scarring in Hypertrophic CardiomyopathyCorrelation With Histopathology and Prevalence of Ventricular Tachycardia
Deborah H. Kwon, MD*,
Nicholas G. Smedira, MD*,
E. Rene Rodriguez, MD ,
Carmela Tan, MD,
Randolph Setser, PhD ,
Maran Thamilarasan, MD*,
Bruce W. Lytle, MD*,
Harry M. Lever, MD* and
Milind Y. Desai, MD*,,*
* Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio
Department of Pathology, Cleveland Clinic, Cleveland, Ohio
Imaging Institute, Cleveland Clinic, Cleveland, Ohio
Manuscript received December 27, 2008;
revised manuscript received February 23, 2009,
accepted April 3, 2009.
* Reprint requests and correspondence: Dr. Milind Y. Desai, Director, Cardiac CT and MR, Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195 (Email: desaim2{at}ccf.org).
 |
Abstract
|
|---|
Objectives: In hypertrophic cardiomyopathy (HCM) patients undergoing surgical myectomy, we sought to determine the association between pre-operative cardiac magnetic resonance (CMR) findings, small intramural coronary arteriole dysplasia (SICAD) on histopathology, and ventricular tachycardia (VT).
Background: Myocardial scarring (fibrosis) and SICAD are frequently observed on histopathology in HCM patients. CMR measures wall thickness and detects scar.
Methods: Sixty symptomatic HCM patients (62% men; mean age 51 ± 14 years), with preserved ejection fraction (mean 64 ± 5%) and no angiographic coronary disease underwent CMR (cine and delayed post-contrast) using a Siemens 1.5 T scanner, followed by septal myectomy. Maximal basal septal thickness was recorded on cine CMR. Scar was determined (percentage of total myocardium) on delayed post-contrast CMR images and quantified as none, mild (0% to 25%), moderate (26% to 50%), or severe (>50%). VT was assessed using Holter monitoring. Degree of SICAD was determined (normal, mild, moderate, and severe) on histopathology of surgical specimen.
Results: SICAD and scar were seen in 45 (75%) and 38 (63%) patients, respectively. In 15 patients without SICAD, 12 (80%) had no scar; 23 (70%) patients with mild SICAD had mild scar on CMR. On multivariate analysis, degree of SICAD was independently associated with scar on CMR (Wald chi-square statistic: 6.8, p < 0.01). Patients with basal septal scar on CMR had higher VT frequency compared with those without (27% vs. 5%, p = 0.03).
Conclusions: A strong association exists between degree of SICAD and myocardial scarring seen on CMR.
Key Words: hypertrophic cardiomyopathy • small intramural coronary arteriole dysplasia • myocardial scarring • cardiac magnetic resonance
|
Abbreviations and Acronyms
| | CAD = coronary artery disease | | CI = confidence interval | | CMR = cardiac magnetic resonance | | DHE-MRI = delayed hyperenhancement magnetic resonance imaging | | HCM = hypertrophic cardiomyopathy | | LV = left ventricle/ventricular | | LVEF = left ventricular ejection fraction | | LVOT = left ventricular outflow tract | | ROC = receiver-operating characteristic | | SCD = sudden cardiac death | | SICAD = small intramural coronary arteriole dysplasia | | VT = ventricular tachycardia |
|
Multiple post-mortem studies have documented myocardial fibrosis (interstitial or replacement) in hypertrophic cardiomyopathy (HCM) patients that is distinct from the pattern observed in coronary artery disease (CAD) or patients with dilated cardiomyopathy (1,2). With the recent emergence of cardiac magnetic resonance (CMR), including delayed hyperenhancement magnetic resonance imaging (DHE-MRI), it is now possible to accurately detect areas of myocardial fibrosis/scarring in vivo with a high degree of sensitivity (3–5). Areas of delayed hyperenhancement on CMR have been shown to correlate with histologically proven myocardial scar (4,6).
In HCM patients, scarring, detected in vivo on DHE-MRI (Fig. 1), has been correlated with wall thickness (7–9), regional function (8), and ventricular tachyarrhythmias (10–12). The etiology of myocardial scarring in HCM patients is debated, and multiple potential factors have been proposed, including left ventricular (LV) hypertrophy and dynamic left ventricular outflow tract (LVOT) gradient, resulting in potential pressure necrosis causing small intramural coronary arteriole dysplasia (SICAD) (1). However, all such previous associations have been demonstrated in necropsy studies of HCM patients presenting with sudden cardiac death (SCD) (1,2) or patients who underwent cardiac transplantation (6), raising a concern for a selection bias in that only a high-risk population was studied. We sought to study the association between basal interventricular septal thickness, myocardial scarring (both detected by CMR), SICAD (demonstrated by histopathology), and ventricular tachyarrhythmia in HCM patients who underwent surgical myectomy.
View larger version (47K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 1 Delayed Hyperenhancement Cardiac Magnetic Resonance Images in a Patient With Hypertrophic Cardiomyopathy
Delayed hyperenhancement magnetic resonance image in a patient with symptomatic hypertrophic obstructive cardiomyopathy demonstrating areas of extensive scarring in the basal interventricular septum (arrow). Notice also the areas of patchy scarring in the posterior wall (arrow). The image on the left is a short-axis view and image on the right is a 3-chamber view. LV = left ventricle.
|
|
|
Methods
|
|---|
Population.
This was an observational study of 60 consecutive HCM patients with symptomatic LVOT obstruction, preserved left ventricular ejection fraction (LVEF), and no angiographic CAD who underwent comprehensive clinical, echocardiographic, CMR, and angiographic evaluation followed by surgical myectomy (generally within 30 days). These patients were subsequently entered into a registry. HCM was defined as hypertrophied and nondilated LV in absence of another cardiac or systemic disease that could result in a similar magnitude of hypertrophy (13–15). All patients were symptomatic at the time of surgery (100% in New York Heart Association functional class III) from LVOT obstruction at baseline (resting or provokable LVOT gradient  50 mm Hg), despite treatment with maximally tolerated medications. Criteria for study exclusion were: ejection fraction <55%, angiographic obstructive CAD (>30% in at least 1 epicardial coronary artery), history of myocardial infarction, or the presence of pacemakers, defibrillators, or aneurysm clips precluding CMR. Pre-operative clinical, echocardiographic, CMR, and angiographic findings, along with post-operative surgical histopathology findings, were recorded from the electronic medical record. The Social Security Death Index was queried, and survival was ascertained during follow-up. This retrospective registry is approved by the local institutional review board with a waiver of individual informed consent.
Echocardiography.
Transthoracic echocardiography was performed using commercially available HDI 5000 (Philips Medical Systems, Bothell, Washington) and Acuson Sequoia (Siemens Medical Solution USA, Malvern, Pennsylvania) machines. Resting LVOT peak velocity was measured by continuous-wave Doppler echocardiography, and resting LVOT pressure gradient was estimated by using a simplified Bernoulli equation (16). Care was taken to avoid contamination of the LVOT waveform by the mitral regurgitation jet (17). In patients with resting LVOT gradients <30 mm Hg, provocative maneuvers, including Valsalva and amyl nitrite were also used to measure a provokable LVOT gradient. Maximal LVOT gradient was defined as the highest recorded LVOT gradient (resting or provokable) in a patient.
Holter monitoring.
The subjects had pre-operative arrhythmia monitoring performed using a 48-h Holter monitor as part of their clinical workup. Presence of ventricular tachycardia (VT) (sustained or nonsustained), defined as 3 or more consecutive ventricular beats at a rate >120 beats/min, was documented (18).
CMR.
The CMR examinations were performed on 1.5 T MR scanners (Siemens Medical Solutions, Erlangen, Germany), either Sonata (40 mT/m maximum gradient strength, 200 T/m/s maximum slew rate) or Avanto (45 mT/m maximum gradient strength, 200 T/m/s maximum slew rate), using electrocardiographic gating. Scout images were acquired initially to identify the cardiac axes. Subsequently, balanced steady-state free precession images were acquired: echo time (TE) = 1.6 ms, repetition time (TR) = 3.3 ms, flip angle = 70°, temporal resolution = 68 ms, and slice thickness = 6 mm (long-axis images) or 8 to 10 mm (contiguous short-axis images encompassing the entire LV volume, from apex to base). For short-axis images, the matrix size varied from 140 to 180 in the x-direction (phase-encoding direction) and 256 in the y-direction. In long-axis images, the matrix size varied from 120 to 210 in the x-direction (phase-encoding direction) and 256 in the y-direction. For patients able to suspend respiration, breath-hold duration was 10 to 15 s, depending on the heart rate; otherwise, images were acquired using 3 signal averages. Subsequently, DHE-MRI images were obtained in the same long- and short-axis orientations as in the above-described balanced steady-state free precession images,  20 min after injection of 0.2 mmol/kg of gadolinium dimenglumine (Magnevist, Berlex Imaging, Wayne, New Jersey), using a phase-sensitive inversion recovery spoiled gradient echo sequence (19): TE = 4 ms, TR = 8 ms, flip angle = 30°, bandwidth = 140 Hz/pixel, 23 k-space lines acquired every other RR-interval, field of view (varied from 228 to 330 in the x-direction and 260 to 330 in the y-direction), and matrix size (varied from 140 to 180 in the x-direction and 256 in the y-direction). This gave a spatial resolution of 1.5 to 2.1 mm (x-direction) by 1.1 to 1.4 mm (y-direction).
LVEF and end-diastolic basal interventricular septal thickness were measured by standard off-line analysis of short-axis cine images, using Argus analytical software (Siemens Medical Solutions). The presence and amount of scar was assessed using phase-sensitive DHE-MRI (Fig. 1), evaluating only the anteroseptum at the basal and mid-ventricular levels to approximately correspond with the area removed on myectomy (as illustrated in Fig. 2). For quantitation of scar, inner and outer myocardial edges were manually delineated. Scar was determined semiautomatically (as a percentage of total myocardium) using a viability prototype software (Siemens Medical Solutions, Erlangen, Germany) and defined as having an intensity >2 SDs above normal myocardium (identified using a user-specified region of interest) (20,21). Any areas that were identified as scar by the software, but not deemed to be scar by the user, were excluded manually by the user. Such quantitative scar analysis has been shown to be highly reproducible in a previous study (20). The degree of scar was subsequently graded as follows: none, mild (1% to 25%), moderate (26% to 50%), and severe (>50%), as described in previous DHE-MRI studies (22,23). CMR assessment was blinded from all other analyses.
View larger version (56K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 2 Schematic Representation of the Portion of Basal Septum Removed During Myectomy
Schematic illustration of the basal interventricular septum removed during surgical myectomy (area within the dotted line) in a hypertrophic cardiomyopathy patient with symptomatic left ventricular outflow tract obstruction. AO = aorta; AV = aortic valve; IVS = interventricular septum; LA = left atrium; LV = left ventricle; MV = mitral valve; PM = papillary muscles.
|
|
Myectomy.
All patients underwent surgical myectomy without coronary revascularization using techniques as previously described (Fig. 2) (24,25).
Histopathology.
All specimens were fixed in 10% formalin and grossly examined by the cardiovascular pathology staff (E.R.R. and C.T.). Particular attention was placed in sectioning along longitudinally oriented fascicles of muscle during gross evaluation to allow for better assessment of myocyte disarray in the microscopic examination. The endocardium was always examined, and sections perpendicular to areas of thickened endocardium were taken. Formalin-fixed tissue was routinely processed for paraffin embedding. Sections were stained with hematoxylin-eosin and Movat pentachrome stains. Histologic sections were evaluated for the presence of myocyte disarray, fibrosis, and SICAD. SICAD was defined by the presence of intimal and/or medial thickening with smooth muscle proliferation and disorganization (Fig. 3). The severity of SICAD was assessed based on the frequency that abnormal vessels were found and graded semiquantitatively as follows: absent (none to only a single affected artery), mild (1% to 25% of arteries affected), moderate (26% to 50%), and severe (>50%). This grading has been adapted at our institution, based upon previous work (1,2). Similarly, degree of myocardial fibrosis was assessed as normal, mild, moderate, and severe, as previously described (1). Histopathologic analysis was blinded from all other analyses.
View larger version (86K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 3 Small Intramural Dysplastic Coronary Arteriole in a Patient With Hypertrophic Cardiomyopathy
Histopathologic analysis of the basal septal specimen removed during surgical myectomy of a patient with hypertrophic obstructive cardiomyopathy. (A) Dysplastic intramural coronary arteries with narrowed lumen due to disordered medial smooth muscle hyperplasia or (B) intimal hyperplasia with increased mucopolysaccharide and collagen deposition. Scarring is also present in the media and adventitia (Movat pentachrome stain, x200).
|
|
Statistics.
Baseline demographics, risk factors, and clinical variables are descriptively summarized. Continuous variables are expressed as mean ± SD and/or median. Categorical data are presented as percentage frequency. Differences between groups were compared with the use of the Student t test or analysis of variance (for parametric variables) and Mann-Whitney test (for nonparametric variables) for continuous variables. The chi-square test was used for categorical variables. The Pearson correlation coefficient method was utilized to test for association between continuous variables. Receiver-operator characteristic (ROC) curve analysis was performed to discriminate between patients with or without SICAD, based upon the degree of basal septal hypertrophy. An area under the curve with a 95% confidence interval (CI) was calculated. A cutoff with best sensitivity and specificity is reported. Univariate and forward stepwise multivariate logistic regression analyses were performed to test the association between dependent and multiple independent variables. For multivariate analysis, only those variables with a p value  0.1 on univariate analysis were entered into the model. Data assembly and basic statistical comparisons were performed with JMP Software version 6.0.2 (SAS Institute, Cary, North Carolina). Advanced statistical analysis was performed using SPSS version 11 (SPSS Inc., Chicago, Illinois). A p value <0.05 was considered significant.
|
Results
|
|---|
The baseline data of the entire study population is shown in Table 1. There have been no deaths or cardiac transplantation in the follow-up period (308 ± 180 days) in this group. Of the study group, 53 (88%) patients had Holter monitoring, of which 10 (19%) had VT. Only 2 patients had an automated implantable defibrillator placed during the follow-up period.
Histopathologic data.
In the study group, 15 (25%) patients had no SICAD, 33 (55%) had mild, 10 (17%) had moderate, and 2 (3%) had severe SICAD. Based upon the presence or absence of SICAD, patients were divided into 2 groups: group A: SICAD (n = 45) and group B: no SICAD (n = 15); and the characteristics of these groups are shown in Table 1. Also, the classification based on fibrosis on histopathology was as follows: 19 (32%) patients with a normal pattern of fibrosis, 33 (55%) with mild, and 8 (13%) with moderate fibrosis.
Imaging data versus histopathology.
As demonstrated in Table 1, the mean LVEF and LVOT gradients (both resting as well as provokable) were similar in groups A and B. However, basal interventricular septal thickness on CMR was significantly higher in group A compared with group B. Median basal interventricular septal thickness in the patient population was 1.9 cm (range 1.5 to 3.9 cm). On ROC curve analysis, basal interventricular septal thickness had a significant association with presence or absence of SICAD (area under the curve = 0.76, p < 0.001, 95% CI: 0.62 to 0.88). For our population, based on ROC curve analysis, at a basal interventricular septal thickness cutoff of 1.95 cm, the sensitivity and specificity for predicting the presence of SICAD were 58% and 80%, respectively.
The distribution of basal interventricular septal scarring on DHE-MRI was as follows: none (22, or 37%), mild (33, or 55%), moderate (4, or 7%), and severe (1, or 2%). On chi-square testing, there was a strong association between degree of scarring noted on DHE-MRI, and fibrosis reported on histopathology (p < 0.001), as follows. Of the 22 patients with no scar on DHE-MRI, 19 had normal fibrosis reported on histopathology. Similarly, 33 patients had evidence of mild fibrosis (on histopathology) and scar (on DHE-MRI). There was a weak correlation between basal interventricular septal thickness and scar percentage, measured on CMR (r = 0.30, p = 0.02). The distribution of patients, based upon presence or absence of scar on DHE-MRI is shown in Table 2. As demonstrated in Table 2, the mean basal interventricular septal thickness was significantly higher in patients with DHE-MRI scarring compared with those without. Also, a greater percentage of patients with scarring seen on DHE-MRI had evidence of VT on Holter monitoring (27% vs. 5%, p = 0.03).
As shown in Table 1, a greater percentage of patients with SICAD had evidence of myocardial scarring on DHE-MRI as compared with those without SICAD. Figure 4
demonstrates the significant association between different degrees of scarring, seen on DHE-MRI and SICAD. Of the 15 patients without SICAD, 12 (80%) had no scar on DHE-MRI, whereas 23 (70%) with mild SICAD had evidence of mild scar. On ROC analysis, scar percentage on DHE-MRI was a significant predictor of the presence of SICAD (area under the curve: 0.77, p = 0.002, 95% CI: 0.63 to 0.92). Subsequently, we performed univariate and multivariate logistic regression analysis to test the association between myocardial scarring noted on DHE-MRI and multiple potential clinical and imaging variables. The results are shown in Table 3. Based on the logistic regression analysis, the odds of having myocardial scarring on DHE-MRI was significantly higher in presence of SICAD (odds ratio [OR]: 14 [95% CI: 3 to 60], p = 0.009), as compared to septal thickness less than the median (OR: 6 [95% CI: 2 to 19], p = 0.05).
View larger version (20K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 4 Association Between Degree of Myocardial Scarring on DHE-MRI and SICAD
Association between degree of myocardial scarring on delayed hyper-enhancement cardiac magnetic resonance (DHE-MRI) and small intramural coronary arteriole dysplasia (SICAD) in the study population.
|
|
View this table:
[in this window]
[in a new window]
|
Table 3 Univariate and Multivariate Logistic Regression Analysis Testing the Association Between Myocardial Scarring and Various Parameters
|
|
|
Discussion
|
|---|
To the best of our knowledge, this is the first in vivo study to demonstrate an independent association between presence (and degree) of SICAD by histopathology and myocardial scarring detected by DHE-MRI in a series of HCM patients. We demonstrate, using CMR, that there is a significant association between maximal basal interventricular thickness, myocardial scarring (both evaluated by CMR), and SICAD (described on histopathology) in the myectomy specimen that is removed at surgery in HCM patients who underwent surgical myectomy for symptomatic LVOT obstruction. No patient had evidence of significant epicardial CAD on pre-operative angiography, and all patients had preserved LVEF. We further demonstrate that the association between degree of SICAD and presence of DHE-MRI scarring was independent of other factors including age, sex, hypertension, LVOT gradient, and myocyte disarray. It also appears that the association of DHE-MRI scarring with SICAD is much stronger than with basal septal thickness. Previous studies have performed quantitative/semiquantitative analysis of the degree of SICAD and scar in a necropsy setting on the entire heart (2). However, in our study, only basal septal tissue removed during myectomy was available. Thus, a semiquantitative estimation of scar and SICAD (as percentage of the myocardial portion removed at myectomy) was performed.
The scar assessment and quantification was performed in a semiautomatic fashion using DHE-MRI. For the purpose of this study, we specifically recorded the presence of DHE-MRI scar in the basal anteroseptum at the basal and mid-ventricular levels to approximately correspond with the area removed on myectomy (Fig. 2). With the recent emergence of DHE-MRI, it is now possible to precisely detect areas of myocardial fibrosis/scarring in vivo with a high degree of sensitivity (3–5). Areas of delayed hyper-enhancement have been shown to correlate with histologically proven myocardial scar (4,6). Hence, we can have a detailed "in vivo" evaluation of myocardial scarring, which, in the past was only done in histopathologic specimens.
As demonstrated in recent studies (10–12), there was a significant association between scarring seen on DHE-MRI and occurrence of VT. However, longer-term follow-up data will be required to conclusively demonstrate the association between SICAD, scarring, and increased risk for sudden death (not just VT). Previous observations demonstrating the association between scarring and SICAD were derived from autopsy studies of HCM patients who died suddenly (1,2). These studies have the potential for a selection bias as only a high-risk sudden-death phenotype was studied.
Previous histopathologic studies have reported an increased frequency of SICAD, particularly in the interventricular septum, in HCM patients (1). That study also suggested that besides increased intramyocardial wall tension, there are other potential factors in the pathogenesis of SICAD, including the underlying cardiomyopathy itself (1). The observation of a strong association between SICAD and increased septal thickness suggests that these findings may occur later in the HCM disease process. Another association that needs further exploration is that between SICAD and genetics. Indeed, in the current study, significantly more patients with SICAD had a positive family history of HCM, compared to those without SICAD. Irrespective of the etiology and duration, it is well documented using CMR and positron emission tomography that HCM patients have evidence of microvascular dysfunction (26,27). In a CMR study of 35 HCM patients with a mean LVEF of 74 ± 9%, the authors demonstrated that the resting myocardial blood flow was similar to controls; however, following vasodilator challenge, the hyperemic blood flow was substantially lower in HCM patients (27). Thus, it is conceivable that HCM patients with SICAD have microvascular dysfunction resulting in repeated episodes of ischemia leading to myocardial scarring. Based on the current study, it appears that SICAD can be seen in HCM patients even when the basal septum is <2 cm in thickness.
Aside from ischemia, there could be other potential reasons for development of myocardial scarring in HCM. Although HCM is caused by mutation in genes encoding sarcomere components, an important component of its phenotypic expression is associated with increased myocardial connective tissue, a principal component of which is collagen (28,29). Different patterns of scarring have been observed (30). There may be a generalized increase in the normal structural skeletal framework of the myocardium, or in extreme cases, individual myocytes may become encased in collagen. Myocardial scarring in HCM has been demonstrated in minimally symptomatic individuals, patients with increased frequency of ventricular arrhythmias, and individuals at high risk of sudden death or myocardial thinning and dilation (8–12).
Clinical implications.
In light of the associations demonstrated in the current study, it could be potentially important to assess whether HCM patients with SICAD (and scar) have long-term worse outcomes compared to those without. Also, in light of emerging associations between myocardial scarring and VT in HCM patients, we likely need to evaluate the continued role of beta-blockers following the surgical relief of LVOT obstruction. An interesting study would be to prospectively evaluate the impact of continued beta-blocker use on outcomes in HCM patients with significant myocardial scarring (assuming a high prevalence of coronary dysplasia) following surgical relief of LVOT obstruction.
Study strengths and limitations.
The study is limited by a small sample size. There is a selection bias because our patient population consisted of HCM patients deemed symptomatic due to LVOT obstruction who underwent septal myectomy. Also, only those patients who were able to undergo CMR were included in the study. However, unlike previous autopsy reports, this is a relatively lower-risk HCM population, as no patients had SCD or LV systolic dysfunction. Also, the majority of patients in the current study population had mild scarring and mild SICAD. We do not have data on stress CMR to demonstrate that these patients indeed had functionally significant microvascular dysfunction. Because of the relatively small sample size, there is potential for over-fitting in statistical analysis. The current observational study only tests associations and does not prove causality. However, scar assessment by DHE-MRI can be considered a form of in vivo histologic assessment, with the additional advantage that it can be performed in patients with any HCM phenotype with global myocardial coverage with a potential to serially monitor disease progression.
|
Conclusions
|
|---|
HCM patients with no epicardial CAD and preserved LVEF, undergoing myectomy due to symptomatic LVOT obstruction, have an increased frequency of histopathologically proven SICAD and myocardial scarring (seen on DHE-MRI) in the interventricular septum. There is a strong association between degree of SICAD and myocardial scarring, independent of age, sex, risk factors, and LVOT gradient. Although myocardial scarring is associated with VT, longer-term longitudinal studies are required to conclusively ascertain the association between scarring and sudden death.
|
Acknowledgments
|
|---|
The authors thank Dr. Thomas O'Donnell (Siemens Research) for providing scar analysis software.
|
Footnotes
|
|---|
The institution receives modest research support from Siemens Medical Solutions.
|
References
|
|---|
1. Maron BJ, Wolfson JK, Epstein SE, Roberts WC. Intramural ("small vessel") coronary artery disease in hypertrophic cardiomyopathy J Am Coll Cardiol 1986;8:545-557.[Abstract]2. Varnava AM, Elliott PM, Sharma S, McKenna WJ, Davies MJ. Hypertrophic cardiomyopathy: the interrelation of disarray, fibrosis, and small vessel disease Heart 2000;84:476-482.[Abstract/Free Full Text] 3. Wu E, Judd RM, Vargas JD, Klocke FJ, Bonow RO, Kim RJ. Visualisation of presence, location, and transmural extent of healed Q-wave and non-Q-wave myocardial infarction Lancet 2001;357:21-28.[CrossRef][Web of Science][Medline] 4. Kim RJ, Fieno DS, Parrish TB, et al. Relationship of MRI delayed contrast enhancement to irreversible injury, infarct age, and contractile function Circulation 1999;100:1992-2002.[Abstract/Free Full Text] 5. Fieno DS, Kim RJ, Chen EL, Lomasney JW, Klocke FJ, Judd RM. Contrast-enhanced magnetic resonance imaging of myocardium at risk: distinction between reversible and irreversible injury throughout infarct healing J Am Coll Cardiol 2000;36:1985-1991.[Abstract/Free Full Text] 6. Moon JC, Reed E, Sheppard MN, et al. The histologic basis of late gadolinium enhancement cardiovascular magnetic resonance in hypertrophic cardiomyopathy J Am Coll Cardiol 2004;43:2260-2264.[Abstract/Free Full Text] 7. Moon JC, Mogensen J, Elliott PM, et al. Myocardial late gadolinium enhancement cardiovascular magnetic resonance in hypertrophic cardiomyopathy caused by mutations in troponin I Heart 2005;91:1036-1040.[Abstract/Free Full Text] 8. Choudhury L, Mahrholdt H, Wagner A, et al. Myocardial scarring in asymptomatic or mildly symptomatic patients with hypertrophic cardiomyopathy J Am Coll Cardiol 2002;40:2156-2164.[Abstract/Free Full Text] 9. Moon JC, McKenna WJ, McCrohon JA, Elliott PM, Smith GC, Pennell DJ. Toward clinical risk assessment in hypertrophic cardiomyopathy with gadolinium cardiovascular magnetic resonance J Am Coll Cardiol 2003;41:1561-1567.[Abstract/Free Full Text] 10. Teraoka K, Hirano M, Ookubo H, et al. Delayed contrast enhancement of MRI in hypertrophic cardiomyopathy Magn Reson Imaging 2004;22:155-161.[CrossRef][Web of Science][Medline] 11. Kwon DH, Setser RM, Popovic ZB, et al. Association of myocardial fibrosis, electrocardiography and ventricular tachyarrhythmia in hypertrophic cardiomyopathy: a delayed contrast enhanced MRI study Int J Cardiovasc Imaging 2008;24:617-625.[CrossRef][Web of Science][Medline] 12. Adabag AS, Maron BJ, Appelbaum E, et al. Occurrence and frequency of arrhythmias in hypertrophic cardiomyopathy in relation to delayed enhancement on cardiovascular magnetic resonance J Am Coll Cardiol 2008;51:1369-1374.[Abstract/Free Full Text] 13. Martin RP, Rakowski H, French J, Popp RL. Idiopathic hypertrophic subaortic stenosis viewed by wide-angle, phased-array echocardiography Circulation 1979;59:1206-1217.[Free Full Text] 14. Henry WL, Clark CE, Griffith JM, Epstein SE. Mechanism of left ventricular outlfow obstruction in patients with obstructive asymmetric septal hypertrophy (idiopathic hypertrophic subaortic stenosis) Am J Cardiol 1975;35:337-345.[CrossRef][Web of Science][Medline] 15. Pollick C, Rakowski H, Wigle ED. Muscular subaortic stenosis: the quantitative relationship between systolic anterior motion and the pressure gradient Circulation 1984;69:43-49.[Abstract/Free Full Text] 16. Nakatani S, Marwick TH, Lever HM, Thomas JD. Resting echocardiographic features of latent left ventricular outflow obstruction in hypertrophic cardiomyopathy Am J Cardiol 1996;78:662-667.[CrossRef][Web of Science][Medline] 17. Maron MS, Olivotto I, Betocchi S, et al. Effect of left ventricular outflow tract obstruction on clinical outcome in hypertrophic cardiomyopathy N Engl J Med 2003;348:295-303.[CrossRef][Web of Science][Medline] 18. Anderson KP, DeCamilla J, Moss AJ. Clinical significance of ventricular tachycardia (3 beats or longer) detected during ambulatory monitoring after myocardial infarction Circulation 1978;57:890-897.[Free Full Text] 19. Kellman P, Arai AE, McVeigh ER, Aletras AH. Phase-sensitive inversion recovery for detecting myocardial infarction using gadolinium-delayed hyperenhancement Magn Reson Med 2002;47:372-383.[CrossRef][Web of Science][Medline] 20. Setser RM, Bexell DG, O'Donnell TP, et al. Quantitative assessment of myocardial scar in delayed enhancement magnetic resonance imaging J Magn Reson Imaging 2003;18:434-441.[CrossRef][Web of Science][Medline] 21. Kolipaka A, Chatzimavroudis GP, White RD, O'Donnell TP, Setser RM. Segmentation of non-viable myocardium in delayed enhancement magnetic resonance images Int J Cardiovasc Imaging 2005;21:303-311.[CrossRef][Web of Science][Medline] 22. Kwon DH, Halley CM, Carrigan TP, et al. Extent of left ventricular scar predicts outcomes in ischemic cardiomyopathy patients with significantly reduced systolic function: a delayed hyperenhancement cardiac magnetic resonance study J Am Coll Cardiol Img 2009;2:34-44.[Abstract/Free Full Text] 23. Roes SD, Kelle S, Kaandorp TA, et al. Comparison of myocardial infarct size assessed with contrast-enhanced magnetic resonance imaging and left ventricular function and volumes to predict mortality in patients with healed myocardial infarction Am J Cardiol 2007;100:930-936.[CrossRef][Web of Science][Medline] 24. Heric B, Lytle BW, Miller DP, Rosenkranz ER, Lever HM, Cosgrove DM. Surgical management of hypertrophic obstructive cardiomyopathy. Early and late results. J Thorac Cardiovasc Surg 1995;110:195-206.[Abstract/Free Full Text] 25. Smedira NG, Lytle BW, Lever HM, et al. Current effectiveness and risks of isolated septal myectomy for hypertrophic obstructive cardiomyopathy Ann Thorac Surg 2008;85:127-133.[Abstract/Free Full Text] 26. Lorenzoni R, Gistri R, Cecchi F, et al. Coronary vasodilator reserve is impaired in patients with hypertrophic cardiomyopathy and left ventricular dysfunction Am Heart J 1998;136:972-981.[CrossRef][Web of Science][Medline] 27. Petersen SE, Jerosch-Herold M, Hudsmith LE, et al. Evidence for microvascular dysfunction in hypertrophic cardiomyopathy: new insights from multiparametric magnetic resonance imaging Circulation 2007;115:2418-2425.[Abstract/Free Full Text] 28. Shirani J, Pick R, Roberts WC, Maron BJ. Morphology and significance of the left ventricular collagen network in young patients with hypertrophic cardiomyopathy and sudden cardiac death J Am Coll Cardiol 2000;35:36-44.[Abstract/Free Full Text] 29. Kitamura M, Shimizu M, Ino H, et al. Collagen remodeling and cardiac dysfunction in patients with hypertrophic cardiomyopathy: the significance of type III and VI collagens Clin Cardiol 2001;24:325-329.[Web of Science][Medline] 30. Anderson KR, Sutton MG, Lie JT. Histopathological types of cardiac fibrosis in myocardial disease J Pathol 1979;128:79-85.[CrossRef][Web of Science][Medline]
Related Article
-
Inside This Issue
J. Am. Coll. Cardiol. 2009 54: A24.
[Full Text]
[PDF]
This article has been cited by other articles:
|
|
|
|
 
J. A. White, N. M. Fine, L. Gula, R. Yee, A. Skanes, G. Klein, P. Leong-Sit, H. Warren, T. Thompson, M. Drangova, et al.
Utility of Cardiovascular Magnetic Resonance in Identifying Substrate for Malignant Ventricular Arrhythmias
Circ Cardiovasc Imaging,
January 1, 2012;
5(1):
12 - 20.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Appelbaum, B. J. Maron, S. Adabag, T. H. Hauser, J. R. Lesser, T. S. Haas, A. B. Riley, C. J. Harrigan, F. N. Delling, J. E. Udelson, et al.
Intermediate-Signal-Intensity Late Gadolinium Enhancement Predicts Ventricular Tachyarrhythmias in Patients With Hypertrophic Cardiomyopathy
Circ Cardiovasc Imaging,
January 1, 2012;
5(1):
78 - 85.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. C. Y. To, A. Dhillon, and M. Y. Desai
Cardiac Magnetic Resonance in Hypertrophic Cardiomyopathy
J. Am. Coll. Cardiol. Img.,
October 1, 2011;
4(10):
1123 - 1137.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Amano, M. Takayama, Y. Fukushima, M. Kitamura, and S. Kumita
Delayed-enhancement MRI of apical hypertrophic cardiomyopathy: assessment of the intramural distribution and comparison with clinical symptoms, ventricular arrhythmias, and cine MRI
Acta Radiol,
July 1, 2011;
52(6):
613 - 618.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Minami, K. Kajimoto, Y. Terajima, B. Yashiro, D. Okayama, S. Haruki, T. Nakajima, N. Kawashiro, M. Kawana, and N. Hagiwara
Clinical Implications of Midventricular Obstruction in Patients With Hypertrophic Cardiomyopathy
J. Am. Coll. Cardiol.,
June 7, 2011;
57(23):
2346 - 2355.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. K. Shah, H. V. Schaff, M. D. Abel, and B. J. Gersh
Ventricular Tachycardia in Hypertrophic Cardiomyopathy With Apical Aneurysm
Ann. Thorac. Surg.,
April 1, 2011;
91(4):
1263 - 1265.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Y. Desai, S. R. Ommen, W. J. McKenna, H. M. Lever, and P. M. Elliott
Imaging Phenotype Versus Genotype in Hypertrophic Cardiomyopathy
Circ Cardiovasc Imaging,
March 1, 2011;
4(2):
156 - 168.
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Mewton, C. Y. Liu, P. Croisille, D. Bluemke, and J. A. C. Lima
Assessment of Myocardial Fibrosis With Cardiovascular Magnetic Resonance
J. Am. Coll. Cardiol.,
February 22, 2011;
57(8):
891 - 903.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. P. Leong, P. L. Madsen, and J. B. Selvanayagam
Non-invasive evaluation of myocardial fibrosis: implications for the clinician
Heart,
December 15, 2010;
96(24):
2016 - 2024.
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. I. Fishman, S. S. Chugh, J. P. DiMarco, C. M. Albert, M. E. Anderson, R. O. Bonow, A. E. Buxton, P.-S. Chen, M. Estes, X. Jouven, et al.
Sudden Cardiac Death Prediction and Prevention: Report From a National Heart, Lung, and Blood Institute and Heart Rhythm Society Workshop
Circulation,
November 30, 2010;
122(22):
2335 - 2348.
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. Bruder, A. Wagner, C. J. Jensen, S. Schneider, P. Ong, E.-M. Kispert, K. Nassenstein, T. Schlosser, G. V. Sabin, U. Sechtem, et al.
Myocardial Scar Visualized by Cardiovascular Magnetic Resonance Imaging Predicts Major Adverse Events in Patients With Hypertrophic Cardiomyopathy
J. Am. Coll. Cardiol.,
September 7, 2010;
56(11):
875 - 887.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. O'Hanlon, A. Grasso, M. Roughton, J. C. Moon, S. Clark, R. Wage, J. Webb, M. Kulkarni, D. Dawson, L. Sulaibeekh, et al.
Prognostic Significance of Myocardial Fibrosis in Hypertrophic Cardiomyopathy
J. Am. Coll. Cardiol.,
September 7, 2010;
56(11):
867 - 874.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. J. Chun, S. I. Choi, K. N. Jin, H. J. Kwag, Y. J. Kim, B. W. Choi, W. Lee, and J. H. Park
Hypertrophic Cardiomyopathy: Assessment with MR Imaging and Multidetector CT
RadioGraphics,
September 1, 2010;
30(5):
1309 - 1328.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. A. Austin, Z. B. Popovic, D. H. Kwon, M. Thamilarasan, T. Boonyasirinant, S. D. Flamm, H. M. Lever, and M. Y. Desai
Aortic stiffness independently predicts exercise capacity in hypertrophic cardiomyopathy: a multimodality imaging study
Heart,
August 1, 2010;
96(16):
1303 - 1310.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
Top
Abstract
Methods