CLINICAL RESEARCH: HYPERTROPHIC CARDIOMYOPATHY
Occurrence and Frequency of Arrhythmias in Hypertrophic Cardiomyopathy in Relation to Delayed Enhancement on Cardiovascular Magnetic Resonance
A. Selcuk Adabag, MD, MS*,*,
Barry J. Maron, MD ,
Evan Appelbaum, MD , ,
Caitlin J. Harrigan, BA,
Jacqueline L. Buros, BA,
C. Michael Gibson, MD, MS,,
John R. Lesser, MD,
Constance A. Hanna, RN,
James E. Udelson, MD||,
Warren J. Manning, MD, and
Martin S. Maron, MD||
* Division of Cardiology, Veterans Affairs Medical Center, Minneapolis, Minnesota
Hypertrophic Cardiomyopathy Center, Minneapolis Heart Institute Foundation, Minneapolis, Minnesota
Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts
PERFUSE Core Laboratory and Data Coordinating Center, Harvard Medical School, Boston, Massachusetts
|| Hypertrophic Cardiomyopathy Center, Division of Cardiology, Tufts-New England Medical Center, Boston, Massachusetts.
Manuscript received August 2, 2007;
revised manuscript received November 2, 2007,
accepted November 26, 2007.
* Reprint requests and correspondence: Dr. A. Selcuk Adabag, Section of Cardiology (111 C), Veterans Affairs Medical Center, One Veterans Drive, Minneapolis, Minnesota 55417. (Email: adaba001{at}umn.edu).
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Abstract
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Objectives: Our aim was to determine whether myocardial fibrosis, detected by cardiovascular magnetic resonance (CMR), represents an arrhythmogenic substrate in hypertrophic cardiomyopathy (HCM).
Background: Myocardial fibrosis is identified frequently in HCM; however, the clinical significance of this finding is uncertain.
Methods: We studied prevalence and frequency of tachyarrhythmias on 24-h ambulatory Holter electrocardiogram (ECG) with regard to delayed enhancement (DE) on contrast-enhanced CMR in 177 HCM patients (age 41 ± 16 yrs; 95% asymptomatic or mildly symptomatic).
Results: Premature ventricular contractions (PVCs), couplets, and nonsustained ventricular tachycardia (NSVT) were more common in patients with DE than those without DE (PVCs: 89% vs. 72%; couplets: 40% vs. 17%; NSVT: 28% vs. 4%; p < 0.0001 to 0.007). Patients with DE also had greater numbers of PVCs (202 ± 655 vs. 116 ± 435), couplets (1.9 ± 5 vs. 1.2 ± 10), and NSVT runs (0.4 ± 0.8 vs. 0.06 ± 0.4) than non-DE patients (all p < 0.0001); DE was an independent predictor of NSVT (relative risk 7.3, 95% confidence interval 2.6 to 20.4; p < 0.0001). However, extent (%) of DE was similar in patients with and without PVCs (8.2% vs. 9.1%; p = 0.93), couplets (8.5% vs. 8.4%; p = 0.99), or NSVT (8.3% vs. 8.5%; p = 0.35).
Conclusions: In this large HCM cohort with no or only mild symptoms, myocardial fibrosis detected by CMR was associated with greater likelihood and increased frequency of ventricular tachyarrhythmias (including NSVT) on ambulatory Holter ECG. Therefore, contrast-enhanced CMR identifies HCM patients with increased susceptibility to ventricular tachyarrhythmias.
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Abbreviations and Acronyms
| | CMR = cardiovascular magnetic resonance | | DE = delayed enhancement | | ECG = electrocardiogram | | HCM = hypertrophic cardiomyopathy | | ICD = implantable cardioverter-defibrillator | | LV = left ventricular/ventricle | | NSVT = nonsustained ventricular tachycardia | | PVC = premature ventricular contraction | | ROC = receiver-operating characteristic | | SVT = supraventricular tachycardia |
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Hypertrophic cardiomyopathy (HCM) is the most common cause of sudden cardiac death in the young (1–4). The mechanism of sudden death in HCM is ventricular tachyarrhythmia emanating from a structurally abnormal myocardium, which often includes areas of fibrosis (5–10). Myocardial scars create a potentially arrhythmogenic substrate and increase susceptibility to ventricular tachycardia/fibrillation (11,12). Indeed, gross macroscopic scarring is frequently present on post-mortem examination in HCM patients who have died suddenly, suggesting a possible causal association between fibrosis and sudden death in this disease (8–10).
Cardiovascular magnetic resonance (CMR) with delayed enhancement (DE) imaging after gadolinium infusion, has the capability of identifying myocardial fibrosis in vivo in patients with structural heart disease (13–15). In both ischemic and dilated cardiomyopathy, the presence of DE is an independent predictor of cardiovascular mortality, including sudden cardiac death (16–19). Although DE is found commonly on contrast-enhanced CMR in HCM patients (20–22), currently there is no direct evidence that this finding is associated with arrhythmias, particularly nonsustained ventricular tachycardia (NSVT), an established risk factor for sudden death in HCM (23,24). Therefore, the objective of the present study was to assess the relationship between DE and ventricular and supraventricular tachyarrhythmias evident on 24-h ambulatory Holter electrocardiogram (ECG) in a large cohort of HCM patients.
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Methods
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Study patients.
From April 2003 to January 2007, 204 HCM patients were evaluated with contrast-enhanced CMR and 24-h ambulatory Holter ECG in the HCM centers of the Minneapolis Heart Institute Foundation and Tufts-New England Medical Center (Boston). Of the 204 patients, 27 were excluded on the basis of more than a 10-month time period between CMR and the Holter ECG. The final study population included 177 HCM patients. Median interval between the 2 studies was 1 month ( 3 months in 81%, 6 months in 98%).
Diagnosis of HCM was based on the demonstration of a hypertrophied left ventricle (LV; wall thickness  13 mm in adult patients or the equivalent wall thickness relative to body surface area in children) associated with a nondilated LV in the absence of another cardiac or systemic disease that could produce the magnitude of hypertrophy evident (25).
CMR.
The CMR (Philips Gyroscan ACS-NT 1.5T, Best, Netherlands; or Siemens Sonata 1.5-T, Erlangen, Germany) was performed using steady-state free-precession breath-hold cines in 3 long-axis planes and contiguous 10-mm short-axis slices (no gap) from the atrioventricular ring to the apex. The DE images were acquired 15 min after the intravenous administration of 0.2 mmol/kg gadolinium-DTPA (Magnevist, Schering, Berlin, Germany) with a breath-hold 2-dimensional segmented inversion-recovery sequence (TI 240 to 300 ms), acquired in the same orientation as the cine images.
Ventricular volumes, function, mass, and ejection fraction were measured for the LV using standard techniques (26), and analyzed with a commercial workstation (Qmass MR version 6 1.6, Medis Medical Imaging Systems, the Netherlands). The LV mass index (g/m2) was calculated by dividing myocardial mass by body surface area. Maximal LV wall thickness was taken as the greatest dimension determined automatically by the Mass software at any site within the LV wall.
To assess DE, all short-axis slices from base to apex were inspected visually to identify areas of normal (completely nulled) myocardium. Mean signal intensity (and standard deviation [SD]) was derived and a threshold of 6 SD exceeding the mean was used to define areas of DE (15,27–29). Summing the planimetered areas of DE in all short-axis slices yielded the total volume (g), which was also expressed as a proportion of total LV myocardium (% DE). The DE analysis was performed by 1 experienced reader and reviewed and confirmed by a second expert reader with both of the independent observers blinded to patient identity and clinical profile. Any discrepancies in analysis between the 2 readers was then adjudicated by a senior observer with >10 years of CMR experience. All CMR analyses were performed by observers blinded to the clinical and the 24-h ECG data.
Ambulatory Holter ECGs.
Ambulatory Holter ECG recordings were obtained in a standard fashion with a portable tape recorder and modified V1 and V5 leads. Holter ECG recordings were scanned on a DelMar Reynolds AccuPlus (model 403) Holter Analysis System (Del Mar Reynolds Medical, Irvine, California). Arrhythmia frequency was normalized to 24 h in recordings which did not include a complete 24-h period of uninterrupted and interpretable rhythm, owing to noise or loss of signal. In patients with >1 Holter ECG, the study closest in time to the CMR was analyzed. Nonsustained ventricular tachycardia and supraventricular tachycardia (SVT) was defined as 3 or more consecutive premature complexes with a heart rate of 100 beats/min (12,24).
Statistical analyses.
Data are expressed as mean ± SD. Clinical and demographic characteristics of the DE and non-DE groups were compared using the Mann-Whitney U test for continuous variables, and the chi-square test for noncontinuous variables expressed as proportions (or the Fisher exact test for subgroups containing 5 observations). Predictors of NSVT were assessed with logistic regression analysis. The multivariable regression model included DE, age, and maximal LV wall thickness, selected on the basis of univariate predictors of NSVT with p < 0.1 in the study population.
The ability of DE to discriminate patients who did or did not have NSVT on Holter ECG was assessed using the area under the receiver-operating characteristic (ROC) curve (c-index) with 95% confidence interval (CI). A c-index equal to 0.5 indicates that the discrimination was no better than random, whereas a c-index equal to 1.0 indicates perfect discrimination. All comparisons were 2 tailed. p 0.05 was considered to be statistically significant. The SPSS software version 10.0 (SPSS Inc., Chicago, Illinois) was used for all analyses.
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Results
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Patient characteristics.
At CMR, study patients were 41 ± 16 years of age (range 8 to 75 years); 129 (73%) were male (Table 1). Of the 177 patients, 168 (95%) were asymptomatic or mildly symptomatic (New York Heart Association [NYHA] functional classes I and II) and the other 9 (5%) were severely symptomatic (NYHA functional class III). Maximum LV wall thickness was 21 ± 5 mm (range 10 to 36 mm), and 40 patients (23%) had LV outflow obstruction at rest (gradient 30 mm Hg; range 0 to 160 mm Hg) (Table 1). A total of 102 patients (58%) were taking beta-blockers, 39 (22%) calcium-channel blockers, and 3 (2%) disopyramide. No patients were taking other antiarrhythmic medications, including amiodarone. A similar proportion of patients in the DE and non-DE subgroups were taking cardioactive medications (Table 1).
CMR findings.
Delayed enhancement was evident in 72 (41%) of the 177 patients, occupying 8.5 ± 8% (range 0.6% to 37.6%) of LV myocardium. Areas of DE were transmural (75% of any segmental wall thickness) in 39 (54%) of the 72 patients and nontransmural DE in the other 33 (46%) patients in discrete (focal), multifocal, or confluent patterns. Areas of DE were localized to the ventricular septum (n = 6), LV free wall (n = 17), at the right ventricular insertion into the septum (n = 10), or in a combination of these locations (n = 39). Distribution of DE was subendocardial in 5 patients, midmyocardial in 8, epicardial in 6, or a combination of these in 53.
Ambulatory Holter ECG.
Over 24 h of Holter ECG, 138 (78%) of the 177 study patients had ventricular arrhythmias, including 136 (77%) with premature ventricular contractions (PVCs) (range 1 to 4,800, mean 189), 47 (27%) with couplets (range 1 to 99, mean 5.5), and 24 (14%) with runs of NSVT. Number of NSVT runs in 24 h was 1 to 5 (mean 1.4), with 3 to 52 beats in the longest burst (mean 8.4 ± 10), and at ventricular rates of 132 ± 23 beats/min. Runs of SVT were present in 40 patients (23%, range 1 to 93, mean 4.7). Also, 47 patients (26%) had periods during which ST-segment depression (1 mm) was evident.
Patients with NSVT were older than those without NSVT (47 ± 12 years vs. 39.5 ± 17 years; p = 0.04). There was no statistically significant association between NSVT on Holter ECG and maximal LV thickness, LV outflow gradient at rest, NYHA functional class, or a history of syncope. There was no significant relationship between NSVT and the presence of ST-segment depression.
Relation of arrhythmias to DE.
Ventricular tachyarrhythmias were significantly more common in patients with DE than in those without DE (p < 0.0001 to 0.007) (Fig. 1). In particular, patients with DE had a 7-fold higher risk of NSVT than non-DE patients (relative risk 7.3, 95% CI 2.6 to 20.4; p < 0.0001). In multivariate analysis, after adjustment for age and maximal LV thickness, DE was the sole independent predictor of NSVT (p < 0.0001). Area under the ROC curve, generated to assess the capability of DE to discriminate patients with and without NSVT, was 0.77 (95% CI 0.67 to 0.87) (Fig. 2).
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Figure 1 Prevalence of Arrhythmias on 24-h Holter ECG With Respect to DE in 177 HCM Patients
DE = delayed enhancement; ECG = electrocardiogram; HCM = hypertrophic cardiomyopathy; NSVT = nonsustained ventricular tachycardia; PVC = premature ventricular contraction; SVT = supraventricular tachycardia.
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Figure 2 ROC Curve to Assess Ability of DE to Discriminate Patients With and Without NSVT on Holter ECG
Area under the curve is 0.77 (95% confidence interval 0.67 to 0.87). ROC = receiver-operating characteristic; other abbreviations as in Figure 1.
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Patients with DE also had greater numbers of PVCs, couplets, and NSVT runs (202 ± 655, 1.9 ± 5, and 0.4 ± 0.8, respectively) than did patients without DE (116 ± 435, 1.2 ± 10, and 0.06 ± 0.4, respectively; p < 0.0001). There was no association between ventricular tachyarrhythmias and transmural distribution or location of DE. Also, occurrence of SVT was unassociated with DE.
Among the 72 HCM patients with evidence of DE on CMR, the percentage of LV myocardium occupied by DE was unassociated with the occurrence of ventricular tachyarrhythmias (i.e., PVCs, couplets, and NSVT). Indeed, % DE on CMR was similar among patients with and without either PVCs (8.2% vs. 9.1%; p = 0.93), couplets (8.5% vs. 8.4%; p = 0.99), or NSVT (8.3% vs. 8.5%; p = 0.35) (Fig. 3).
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Figure 3 Cardiovascular Magnetic Resonance Image From a 36-Year-Old Hypertrophic Cardiomyopathy Patient
Relatively discrete areas of delayed enhancement (arrows), shown on long-axis (A) and short-axis (B) views, and comprising 4.3% of LV myocardium. In the same patient, a 12-beat run of nonsustained ventricular tachycardia was present on 24-h ambulatory Holter electrocardiogram (C). LA = left atrium; LV = left ventricle; VS = interventricular septum.
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Discussion
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These data show that the presence of DE (by contrast-CMR), representing areas of myocardial fibrosis, is independently associated with ventricular tachyarrhythmias on ambulatory Holter ECG in a largely asymptomatic or mildly symptomatic cohort of HCM patients. Indeed, DE was associated with a 7-fold increase in the risk of NSVT and was the sole independent predictor of this arrhythmia. These findings may have implications for the risk stratification of HCM patients, because NSVT is generally regarded to be an independent determinant of increased risk of sudden death in this disease (2,3,23,24,30,31).
Risk stratification strategy in HCM (based on the current primary prevention risk factors) is likely incomplete, owing largely to the heterogeneity of clinical and phenotypic expression and the low event rate observed in this disease (31,32). Therefore, identification of additional reproducible risk markers is essential to achieve more precise selection of patients for primary prevention of sudden cardiac death with the implantable cardioverter-defibrillator (ICD) (33–36). Moon et al. (21) proposed DE as a pre-disposing factor for disease progression and sudden death in HCM using clinical risk factors as surrogates for clinical end points (21). Teraoka et al. (37) and Dimitrow et al. (38) found DE to be most common in HCM patients with NSVT. However, prospective data correlating actual sudden death events with CMR findings (i.e., DE) are not yet available. In this regard, the present data linking DE to NSVT, and by inference to increased sudden death risk, provide some preliminary evidence that DE could ultimately prove to be a new risk marker in HCM.
In the present analysis, the prevalence and frequency of ventricular arrhythmias was unrelated to % DE, suggesting that the presence of DE (independent of its extent) represents a marker for increased arrhythmic risk in HCM. Although this lack of association between extent of DE and susceptibility to ventricular arrhythmias may seem counterintuitive (39), this observation is perhaps not unlike that recently reported in other forms of cardiovascular disease (17,27). For example, in patients suspected of coronary heart disease, Kwong et al. (17) demonstrated that small areas of DE were associated with an increased risk of cardiac events, including sudden death and appropriate ICD discharges. Furthermore, in patients with nonischemic cardiomyopathy, inducibility of ventricular arrhythmias during programmed electrical stimulation is largely unrelated to the extent of DE (27). Therefore, it is likely that the propensity of an abnormal myocardial substrate, comprising fibrosis, to generate ventricular arrhythmias is influenced substantially by factors other than absolute scar size (12,40). In this regard, the present data from a large cohort of HCM patients support the idea that even small areas of DE may be sufficient to promote arrhythmias.
Although our cross-sectional data suggest an association between DE and ventricular arrhythmias in HCM, prospectively designed studies in large patient populations are required to definitively establish DE as causally related to sudden death risk. Therefore, at present, it is premature to regard DE as a primary risk factor for HCM patients. Nevertheless, the data presented here may be relevant to clinical decision-making and considerations for prophylactic ICD therapy in individual patients. The findings suggest that DE, representing an abnormal myocardial substrate, may have some role in increasing arrhythmic risk mediated by NSVT. Therefore, in selected patients, it is possible that some weight can be given to areas of DE as an arbitrator in reaching recommendations for prophylactic ICDs when ambiguity remains concerning individual patient risk of sudden death after assessing the conventional risk factors (2,3,31,34). However, we wish to emphasize that it is not our intent to promote a strategy of ICD implantation in all HCM patients with DE (with or without NSVT). Rather, such ambiguous management decisions involving DE should be carried out with patient autonomy considerations and the desires of the fully informed patient contributing to the resolution (34).
In this analysis, we defined DE by using a cutoff of 6 SD above the mean signal intensity of normal myocardium. At present, there is no general consensus on this strategy or criterion (particularly in nonischemic cardiomyopathy), and earlier investigators have used a number of different approaches for the identification of DE, including visual assessment (without threshold) (29,41) as well as 2-SD (29,41) and 6-SD thresholds (15,27–29,41). In our experience, the amount of DE quantified with the 6-SD technique most closely approximates that assessed by visual inspection, with the cutoff of 2 SD yielding 22% greater amounts of DE than a cutoff of 6 SD. Our decision to use a threshold of 6 SD was based on the understanding that it provides the highest specificity for detection and quantification of myocardial fibrosis (15,28,29).
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Conclusions
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Among largely asymptomatic or mildly symptomatic patients with HCM, DE was associated with increased occurrence and frequency of ventricular tachyarrhythmias on ambulatory Holter ECG monitoring. Consequently, contrast-enhanced CMR likely identifies areas of myocardial fibrosis which represent a substrate for ventricular tachyarrhythmias in HCM and a subgroup of patients with increased susceptibility to potentially life-threatening arrhythmias. These data support the necessity for future longitudinal follow-up studies to clarify whether DE should be established as an independent risk predictor for sudden death in HCM.
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Footnotes
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Dr. Adabag is supported in part by the Veterans Administration Clinical Science Research and Development Service (grant no. 04S-CRCOE 001), Washington, DC.
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References
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1. Maron BJ. Sudden death in young athletes N Engl J Med 2003;349:1064-1075.[Free Full Text]2. Maron BJ, McKenna WJ, Danielson GK, et al. ACC/ESC clinical expert consensus document on hypertrophic cardiomyopathy: a report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents and the European Society of Cardiology Committee for Practice Guidelines (Committee to Develop an Expert Consensus Document on Hypertrophic Cardiomyopathy) J Am Coll Cardiol 2003;42:1687-1713.[Free Full Text] 3. Elliott P, McKenna WJ. Hypertrophic cardiomyopathy Lancet 2004;363:1881-1891.[CrossRef][Web of Science][Medline] 4. Maron BJ, Shirani J, Poliac LC, Mathenge R, Roberts WC, Mueller FO. Sudden death in young competitive athletes. Clinical, demographic, and pathological profiles. JAMA 1996;276:199-204.[Abstract/Free Full Text] 5. Maron BJ, Wolfson JK, Epstein SE, et al. Intramural ("small vessel") coronary artery disease in hypertrophic cardiomyopathy J Am Coll Cardiol 1986;8:545-557.[Abstract] 6. Tanaka M, Fujiwara H, Onodera T, Wu DJ, Hamashima Y, Kawai C. Quantitative analysis of myocardial fibrosis in normals, hypertensive hearts, and hypertrophic cardiomyopathy Br Heart J 1986;55:575-581.[Abstract/Free Full Text] 7. Factor SM, Butany J, Sole MJ, Wigle ED, Williams WC, Rojkind M. Pathologic fibrosis and matrix connective tissue in the subaortic myocardium of patients with hypertrophic cardiomyopathy J Am Coll Cardiol 1991;17:1343-1351.[Abstract] 8. Basso C, Thiene G, Corrado D, Buja G, Melacini P, Nava A. Hypertrophic cardiomyopathy and sudden death in the young: pathologic evidence of myocardial ischemia Hum Pathol 2000;31:988-998.[CrossRef][Web of Science][Medline] 9. Shirani J, Pick R, Roberts WC, Maron BJ. Morphology and significance of 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] 10. Varnava AM, Elliott PM, Baboonian C, Davison F, Davies MJ, McKenna WJ. Hypertrophic cardiomyopathy: histopathological features of sudden death in cardiac troponin T disease Circulation 2001;104:1380-1384.[Abstract/Free Full Text] 11. Hurwitz JL, Josephson ME. Sudden cardiac death in patients with chronic coronary heart disease Circulation 1992;85:I43-I49.[Medline] 12. Josephson ME. Recurrent ventricular tachycardiasIn: Josephson ME, editor. Clinical Cardiac Electrophysiology. Philadelphia, PA: Lippincott Williams & Wilkins; 2002. pp. 433-445. 13. Wu E, Judd RM, Vargas JD, Klocke FJ, Bonow RO, Kim RJ. Visualisation of presence, location, and transmural extent of healed Q-wave and nonQ-wave myocardial infarction Lancet 2001;357:21-28.[CrossRef][Web of Science][Medline] 14. 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] 15. Kim RJ, Wu E, Rafael A, et al. The use of contrast-enhanced magnetic resonance imaging to identify reversible myocardial dysfunction N Engl J Med 2000;343:1445-1453.[Abstract/Free Full Text] 16. Yan AT, Shayne AJ, Brown KA, et al. Characterization of the peri-infarct zone by contrast-enhanced cardiac magnetic resonance imaging is a powerful predictor of post-myocardial infarction mortality Circulation 2006;114:32-39.[Abstract/Free Full Text] 17. Kwong RY, Chan AK, Brown KA, et al. Impact of unrecognized myocardial scar detected by cardiac magnetic resonance imaging on event-free survival in patients presenting with signs or symptoms of coronary artery disease Circulation 2006;113:2733-2743.[Abstract/Free Full Text] 18. Mahrholdt H, Wagner A, Judd RM, Sechtem U, Kim RJ. Delayed enhancement cardiovascular magnetic resonance assessment of nonischaemic cardiomyopathies Eur Heart J 2005;26:1461-1474.[Abstract/Free Full Text] 19. Assomull RG, Prasad SK, Lyne J, et al. Cardiovascular magnetic resonance, fibrosis, and prognosis in dilated cardiomyopathy J Am Coll Cardiol 2006;48:1977-1985.[Abstract/Free Full Text] 20. 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] 21. 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] 22. Kim RJ, Judd RM. Gadolinium-enhanced magnetic resonance imaging in hypertrophic cardiomyopathy: in vivo imaging of the pathologic substrate for premature cardiac death? J Am Coll Cardiol 2003;41:1568-1572.[Free Full Text] 23. Adabag AS, Maron BJ. Implications of arrhythmias and prevention of sudden death in hypertrophic cardiomyopathy Ann Noninvasive Electrocardiol 2007;12:171-180.[CrossRef][Web of Science][Medline] 24. Adabag AS, Casey SA, Kuskowski MA, Zenovich AG, Maron BJ. Spectrum and prognostic significance of arrhythmias on ambulatory Holter electrocardiogram in hypertrophic cardiomyopathy J Am Coll Cardiol 2005;45:697-704.[Abstract/Free Full Text] 25. Klues HG, Schiffers A, Maron BJ. Phenotypic spectrum and patterns of left ventricular hypertrophy in hypertrophic cardiomyopathy: morphologic observations and significance as assessed by two-dimensional echocardiography in 600 patients J Am Coll Cardiol 1995;26:1699-1708.[Abstract] 26. Grothues F, Smith GC, Moon JC, et al. Comparison of interstudy reproducibility of cardiovascular magnetic resonance with two-dimensional echocardiography in normal subjects and in patients with heart failure or left ventricular hypertrophy Am J Cardiol 2002;90:29-34.[CrossRef][Web of Science][Medline] 27. Nazarian S, Bluemke DA, Lardo AC, et al. Magnetic resonance assessment of the substrate for inducible ventricular tachycardia in nonischemic cardiomyopathy Circulation 2005;112:2821-2825.[Abstract/Free Full Text] 28. Beek AM, Kuhl HP, Bondarenko O, et al. Delayed contrast-enhanced magnetic resonance imaging for the prediction of regional functional improvement after acute myocardial infarction J Am Coll Cardiol 2003;42:895-901.[Abstract/Free Full Text] 29. Bondarenko O, Beek AM, Hofman MB, et al. Standardizing the definition of hyperenhancement in the quantitative assessment of infarct size and myocardial viability using delayed contrast-enhanced CMR J Cardiovasc Magn Reson 2005;7:481-485.[Web of Science][Medline] 30. Spirito P, Watson RM, Maron BJ. Relation between extent of left ventricular hypertrophy and occurrence of ventricular tachycardia in hypertrophic cardiomyopathy Am J Cardiol 1987;60:1137-1142.[CrossRef][Web of Science][Medline] 31. Elliott PM, Poloniecki J, Dickie S, et al. Sudden death in hypertrophic cardiomyopathy: identification of high risk patients J Am Coll Cardiol 2000;36:2212-2218.[Abstract/Free Full Text] 32. Maron BJ. Contemporary considerations for risk stratification, sudden death and prevention in hypertrophic cardiomyopathy Heart 2003;89:977-978.[Free Full Text] 33. Maron BJ, Shen W-K, Link MS, et al. Efficacy of implantable cardioverter-defibrillators for the prevention of sudden death in patients with hypertrophic cardiomyopathy N Engl J Med 2000;342:365-373.[Abstract/Free Full Text] 34. Maron BJ, Spirito P, Shen W-K, et al. Implantable cardioverter-defibrillators and prevention of sudden cardiac death in hypertrophic cardiomyopathy JAMA 2007;298:405-412.[Abstract/Free Full Text] 35. Jayatilleke I, Doolan A, Ingles J, et al. Long-term follow-up of implantable cardioverter defibrillator therapy for hypertrophic cardiomyopathy Am J Cardiol 2004;93:1192-1194.[CrossRef][Web of Science][Medline] 36. Maron BJ, Estes III NAM, Maron MS, Almquist AK, Link MS, Udelson JE. Primary prevention of sudden death as a novel treatment strategy in hypertrophic cardiomyopathy Circulation 2003;107:2872-2875.[Free Full Text] 37. 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] 38. Dimitrow PP, Klimeczek P, Vliegenthart R, et al. Late hyperenhancement in gadolinium-enhanced magnetic resonance imaging: comparison of hypertrophic cardiomyopathy patients with and without nonsustained ventricular tachycardia Int J Cardiovasc Imaging 2008;24:77-83.[CrossRef][Web of Science][Medline] 39. Bello D, Fieno DS, Kim RJ, et al. Infarct morphology identifies patients with substrate for sustained ventricular tachycardia J Am Coll Cardiol 2005;45:1104-1108.[Abstract/Free Full Text] 40. Peters NS, Wit AL. Myocardial architecture and ventricular arrhythmogenesis Circulation 1998;97:1746-1754.[Free Full Text] 41. Amado LC, Gerber BL, Gupta SN, et al. Accurate and objective infarct sizing by contrast-enhanced magnetic resonance imaging in a canine myocardial infarction model J Am Coll Cardiol 2004;44:2383-2389.[Abstract/Free Full Text]
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2003 - 2010.
[Abstract]
[Full Text]
[PDF]
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M. S. Maron, B. J. Maron, C. Harrigan, J. Buros, C. M. Gibson, I. Olivotto, L. Biller, J. R. Lesser, J. E. Udelson, W. J. Manning, et al.
Hypertrophic cardiomyopathy phenotype revisited after 50 years with cardiovascular magnetic resonance.
J. Am. Coll. Cardiol.,
July 14, 2009;
54(3):
220 - 228.
[Abstract]
[Full Text]
[PDF]
|
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|
|
|
|
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D. H. Kwon, N. G. Smedira, E. R. Rodriguez, C. Tan, R. Setser, M. Thamilarasan, B. W. Lytle, H. M. Lever, and M. Y. Desai
Cardiac magnetic resonance detection of myocardial scarring in hypertrophic cardiomyopathy: correlation with histopathology and prevalence of ventricular tachycardia.
J. Am. Coll. Cardiol.,
July 14, 2009;
54(3):
242 - 249.
[Abstract]
[Full Text]
[PDF]
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|
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|
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|
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T. Boonyasirinant, P. Rajiah, R. M. Setser, M. L. Lieber, H. M. Lever, M. Y. Desai, and S. D. Flamm
Aortic stiffness is increased in hypertrophic cardiomyopathy with myocardial fibrosis: novel insights in vascular function from magnetic resonance imaging.
J. Am. Coll. Cardiol.,
July 14, 2009;
54(3):
255 - 262.
[Abstract]
[Full Text]
[PDF]
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|
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S. Bongioanni, P. Spirito, A. S. Masi, A. Chiribiri, R. Bonamini, and M. R. Conte
Extensive Myocardial Fibrosis in a Patient With Hypertrophic Cardiomyopathy and Ventricular Tachycardia Without Traditional High-Risk Features
Circ Cardiovasc Imaging,
July 1, 2009;
2(4):
349 - 350.
[Full Text]
[PDF]
|
|
|
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D. Wang, V. V. Patel, E. Ricciotti, R. Zhou, M. D. Levin, E. Gao, Z. Yu, V. A. Ferrari, M. M. Lu, J. Xu, et al.
Cardiomyocyte cyclooxygenase-2 influences cardiac rhythm and function
PNAS,
May 5, 2009;
106(18):
7548 - 7552.
[Abstract]
[Full Text]
[PDF]
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A. S. Flett, M. A. Westwood, L. C. Davies, A. Mathur, and J. C. Moon
The Prognostic Implications of Cardiovascular Magnetic Resonance
Circ Cardiovasc Imaging,
May 1, 2009;
2(3):
243 - 250.
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. F. Tops and J. J. Bax
The Year in Imaging Related to Electrophysiology
J. Am. Coll. Cardiol. Img.,
April 1, 2009;
2(4):
498 - 510.
[Full Text]
[PDF]
|
|
|
|
|
|
|
F Alpendurada, J Wong, and D J Pennell
Practical applications of cardiovascular magnetic resonance
Heart Asia,
March 31, 2009;
2009(3):
16 - 22.
[Abstract]
[Full Text]
[PDF]
|
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A. La Gerche, A. J. Taylor, and D. L. Prior
Athlete's Heart: The Potential for Multimodality Imaging to Address the Critical Remaining Questions.
J. Am. Coll. Cardiol. Img.,
March 1, 2009;
2(3):
350 - 363.
[Abstract]
[Full Text]
[PDF]
|
|
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|
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A. Attili, G. C. Mueller, and S. M. Day
AJR Teaching File: Asymptomatic Man with Giant Negative T Waves on ECG
Am. J. Roentgenol.,
March 1, 2009;
192(3_Supplement):
S57 - S61.
[Full Text]
[PDF]
|
|
|
|
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S. Nazarian, D. A. Bluemke, and H. R. Halperin
Applications of Cardiac Magnetic Resonance in Electrophysiology
Circ Arrhythm Electrophysiol,
February 1, 2009;
2(1):
63 - 71.
[Full Text]
[PDF]
|
|
|
|
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A. N. DeMaria, O. Ben-Yehuda, J. J. Bax, G. K. Feld, B. H. Greenberg, W. Y.W. Lew, J. A.C. Lima, A. S. Maisel, S. M. Narayan, D. J. Sahn, et al.
Highlights of the Year in JACC 2008.
J. Am. Coll. Cardiol.,
January 27, 2009;
53(4):
373 - 398.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Rudolph, H. Abdel-Aty, S. Bohl, P. Boye, A. Zagrosek, R. Dietz, and J. Schulz-Menger
Noninvasive detection of fibrosis applying contrast-enhanced cardiac magnetic resonance in different forms of left ventricular hypertrophy relation to remodeling.
J. Am. Coll. Cardiol.,
January 20, 2009;
53(3):
284 - 291.
[Abstract]
[Full Text]
[PDF]
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M. L. Chuang and W. J. Manning
Left ventricular hypertrophy and excess cardiovascular mortality is late gadolinium enhancement the imaging link?
J. Am. Coll. Cardiol.,
January 20, 2009;
53(3):
292 - 294.
[Full Text]
[PDF]
|
|
|
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M. S. Maron, J. J. Finley, J. M. Bos, T. H. Hauser, W. J. Manning, T. S. Haas, J. R. Lesser, J. E. Udelson, M. J. Ackerman, and B. J. Maron
Prevalence, Clinical Significance, and Natural History of Left Ventricular Apical Aneurysms in Hypertrophic Cardiomyopathy
Circulation,
October 7, 2008;
118(15):
1541 - 1549.
[Abstract]
[Full Text]
[PDF]
|
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P Elliott and P Spirito
Prevention of hypertrophic cardiomyopathy-related deaths: theory and practice
Heart,
October 1, 2008;
94(10):
1269 - 1275.
[Abstract]
[Full Text]
[PDF]
|
|
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A. Dhoble, S. R. Punnam, and G. S. Abela
Likelihood of Ventricular Arrhythmias Due to Myocardial Fibrosis in Hypertrophic Cardiomyopathy as Detected by Cardiac Magnetic Resonance Imaging
J. Am. Coll. Cardiol.,
September 9, 2008;
52(11):
969 - 969.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. S. Adabag, B. J. Maron, E. Appelbaum, C. J. Harrigan, J. L. Buros, C. M. Gibson, J. R. Lesser, C. A. Hanna, J. E. Udelson, W. J. Manning, et al.
Reply
J. Am. Coll. Cardiol.,
September 9, 2008;
52(11):
969 - 970.
[Full Text]
[PDF]
|
|
|
|
|
|
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N. Reichek and D. Gupta
Hypertrophic Cardiomyopathy: Cardiac Magnetic Resonance Imaging Changes the Paradigm
J. Am. Coll. Cardiol.,
August 12, 2008;
52(7):
567 - 568.
[Full Text]
[PDF]
|
|
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|
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|
|
S. Nazarian and J. A.C. Lima
Cardiovascular Magnetic Resonance for Risk Stratification of Arrhythmia in Hypertrophic Cardiomyopathy
J. Am. Coll. Cardiol.,
April 8, 2008;
51(14):
1375 - 1376.
[Full Text]
[PDF]
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Abstract
Methods