This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rickers, C. Articles by Maron, B. J. Search for Related Content PubMed PubMed Citation Articles by Rickers, C. Articles by Maron, B. J. Related Collections Cardiovascular imaging agents/Techniques Pediatric and congenital heart disease, including cardiovascular surgery Related Article

(Circulation. 2005;112:855-861.)
© 2005 American Heart Association, Inc.

Imaging

Utility of Cardiac Magnetic Resonance Imaging in the Diagnosis of Hypertrophic Cardiomyopathy

Carsten Rickers, MD; Norbert M. Wilke, MD; Michael Jerosch-Herold, PhD; Susan A. Casey, RN; Prasad Panse, MD; Neeta Panse, MD; Jochen Weil, MD; Andrey G. Zenovich, MSc; Barry J. Maron, MD

From the Department of Radiology (C.R., N.M.W., M.J.-H., P.P., N.P.), Fairview-University Medical Center, Minneapolis, Minn; Division of Pediatric Cardiology (J.W.), University of Hamburg-Eppendorf, Hamburg, Germany; and the Hypertrophic Cardiomyopathy Center (S.A.C., A.G.Z., B.J.M.), Minneapolis Heart Institute Foundation, Minneapolis, Minn.

Correspondence to Barry J. Maron, MD, Minneapolis Heart Institute Foundation, 920 E 28th St, Suite 60, Minneapolis, MN 55407. E-mail hcm.maron{at}mhif.org

Received September 17, 2004; revision received April 6, 2005; accepted April 26, 2005.

	Abstract

Top Abstract Introduction Methods Results Discussion References

 
Background— Two-dimensional echocardiography is currently the standard test for the clinical diagnosis of hypertrophic cardiomyopathy (HCM). The present study was undertaken to determine whether cardiac MRI (CMR) affords greater accuracy than echocardiography in establishing the diagnosis and assessing the magnitude of left ventricular (LV) hypertrophy in HCM.

Methods and Results— Forty-eight patients (age 34±16 years) suspected of having HCM (or with a confirmed diagnosis) were imaged by both echocardiography and CMR to assess LV wall thickness in 8 anatomic segments (total n=384 segments) and compared in a blinded fashion. Maximum LV thickness was similar by echocardiography (21.7±9.1 mm) and CMR (22.5±9.6 mm; P=0.21). However, in 3 (6%) of the 48 patients, echocardiography did not demonstrate LV hypertrophy, and CMR identified otherwise undetected areas of wall thickening in the anterolateral LV free wall (17 to 20 mm), which resulted in a new diagnosis of HCM. In the overall study group, compared with CMR, echocardiography also underestimated the magnitude of hypertrophy in the basal anterolateral free wall (by 20±6%; P=0.001), as well as the presence of extreme LV wall thickness (30 mm) in 10% of patients (P<0.05).

Conclusions— CMR is capable of identifying regions of LV hypertrophy not readily recognized by echocardiography and was solely responsible for diagnosis of the HCM phenotype in an important minority of patients. CMR enhances the assessment of LV hypertrophy, particularly in the anterolateral LV free wall, and represents a powerful supplemental imaging test with distinct diagnostic advantages for selected HCM patients.

Key Words: hypertrophy • cardiomyopathy • magnetic resonance imaging • echocardiography

	Introduction

Top Abstract Introduction Methods Results Discussion References

 
Hypertrophic cardiomyopathy (HCM) is a relatively common form of genetic heart disease and the most frequent cause of sudden cardiac death in the young.^1–6 The clinical phenotype is characterized by otherwise unexplained left ventricular (LV) hypertrophy and a myriad of patterns of wall thickening.⁷ Although the distribution of LV hypertrophy has shown little relation to clinical outcome,² the magnitude of LV wall thickness conveys prognostic significance, showing a direct relationship to the risk for sudden death.^3,4 Although 2D echocardiography is the standard imaging modality for clinical identification of the LV hypertrophy, a not inconsequential number of patients apparently affected by HCM fail to have their diagnosis resolved clinically with echocardiography for technical or other reasons, including some who are seemingly free of LV hypertrophy during at least a portion of their clinical course.^2,8–16

Cardiac MRI (CMR) has the capability of acquiring tomographic images of the hypertrophied LV chamber, with tissue contrast and border definition that are often superior to that achievable with echocardiography.^17–22 In the present study, we assessed a group of HCM patients with both CMR and 2D echocardiography to determine whether CMR provided diagnostic imaging information with respect to LV hypertrophy not accessible with standard echocardiography.

	Methods

Top Abstract Introduction Methods Results Discussion References

 
Patient Selection
Both 2D echocardiographic and CMR studies were performed prospectively over a 25-month period in 48 consecutively enrolled patients, in whom a diagnosis of HCM was either suspected or had been established. Each patient was first evaluated clinically with echocardiography in the Hypertrophic Cardiomyopathy Center of the Minneapolis Heart Institute Foundation, and subsequently, CMR studies were performed on the same day in the Department of Radiology at the Fairview-University Medical Center (University of Minnesota).

Patients were aged 8 to 69 years (mean 34±16 years); 34 (71%) were male. Twenty-five patients (52%) were asymptomatic (New York Heart Association functional class I), 18 (38%) were mildly symptomatic (class II), and 5 (10%) were severely limited by heart failure symptoms (classes III and IV). Thirteen patients (27%) had obstruction to LV outflow under resting conditions (gradient 30 mm Hg ranging to 150 mm Hg).

Diagnosis of HCM was based on the presence of LV hypertrophy without cavity dilatation (maximum wall thickness 15 mm in adults, or the equivalent relative to body surface area in children), in the absence of another cardiac or systemic disease capable of producing the magnitude of hypertrophy evident in that patient.^1,2,7 The study protocol was approved by an Institutional Review Board (Human Subjects Committee) at the University of Minnesota, and all patients signed an informed consent form before participation.

Echocardiography
Two-dimensional echocardiograms were obtained with commercially available instruments (Philips Agilent 5500) with 2.5- and 3.5-MHz transducers equipped with harmonic imaging. The extent and distribution of LV hypertrophy were assessed from 2D echocardiographic images in multiple cross-sectional planes, as described previously.⁷ Other cardiac dimensions were measured from the derived M-mode echocardiogram consistent with previous recommendations.⁷ Wall thicknesses were assessed directly from the television monitor with a calibration scale produced by the instrument. Locations of endocardial and epicardial borders were identified by viewing the pertinent portions of 0.5- or 0.75-inch format videotape in slow-motion freeze-frame and real-time modes. The greatest thickness measured at any site within the LV wall represented the maximum wall thickness. Peak instantaneous LV outflow gradient was estimated with continuous-wave Doppler under basal (resting) conditions.²³

Cardiac MRI
A 1.5-T dedicated CMR scanner (Sonata, Siemens Medical Systems) with a torso phased-array coil for cardiac imaging was used for all studies. Initially, scout images with a 4-chamber view were acquired to prescribe short-axis image planes from base to apex for cine imaging. True fast imaging with steady-state precession (with segmented acquisition of k-space lines) was applied for cine imaging, with breath holding by the patient for 15 cardiac cycle lengths.^24–26 The protocol/sequence parameters were as follows: repetition time (TR) for each 11-line k-space segment=35 ms; echo time (TE)=1.6 ms; receiver bandwidth=930 Hz/pixel; 256 readout points with oversampling; 165 phase encodings; 60° flip angle; a field of view with dimensions of 300 mm in the phase-encoding direction by 350 mm in the readout direction; and 15 phases per R-R interval. Contiguous cardiac images of 8-mm-thick slices with no interslice gap were acquired in both the long- and short-axis planes (10 to 15 per patient).

Analysis of Cine CMR
Cine CMR images were analyzed with validated image-processing software (MASS 4.0; Laboratory for Clinical and Experimental Image Processing; Leiden University, The Netherlands). End-diastolic and end-systolic images were identified with ECG, R-wave gating, and LV volume assessment. Contours of the endocardial and epicardial borders were manually delineated by 1 experienced observer (C.R.). The endocardial contour was drawn such that it averaged minor irregularities along the border (eg, including those presumably created by small trabeculae), as long as these morphological features did not exceed 2 mm in thickness (Figure 1). Larger overlying right ventricular structures, such as crista supraventricularis and papillary muscles, were routinely excluded from the measurement of LV wall thickness when necessary, integrating observations from the real-time cine mode and the static stop-frame images (on which the measurements were made). This methodology is depicted in Figure 1.

View larger version (121K): [in this window] [in a new window]   Figure 1. Method of LV wall thickness measurement by CMR. Chords are generated by computer segmentation, connecting endocardial and epicardial borders perpendicular to the myocardial centerline (automatically situated equidistant between endocardial and epicardial interfaces). Lengths of 100 LV chords define regional absolute wall thicknesses (in mm). In this patient, increased LV wall thicknesses (arrows) are predominantly in posterior ventricular septum (PVS) and extend into contiguous portion of anterior septum (AVS). RV indicates right ventricle.

LV wall thicknesses at end diastole were calculated by the centerline method from chords that connect the endocardial and epicardial boundaries and are perpendicular to an automatically determined myocardial centerline (located halfway between endocardial and epicardial borders; Figure 1).^27,28 The length of each chord was determined with the centerline algorithm in the MASS software, and the longest chord defined absolute wall thickness in each segment of LV (in millimeters).

LV Wall Thickness Comparisons
Echocardiography
The LV chamber was circumferentially divided into 4 anatomic segments in the parasternal short-axis plane (at end diastole): anterior and posterior ventricular septum; and anterolateral and posterior free wall (that portion between the papillary muscles).⁷ Specifically, the ventricular septum, the portion of LV wall situated between the 2 ventricular cavities (as defined anatomically by the insertion sites of right ventricular wall into septum), was divided into 2 segments, the anterior and posterior septum. In addition, in the parasternal long-axis plane (base to apex), the LV chamber was divided into 2 regions: proximal (basal) portion extending from the inferior margins of aortic valve to the distal extent of mitral leaflets, and the distal (apical) portion visualized beyond the mitral valve leaflet tips. Therefore, as described previously,⁷ in each patient, LV end-diastolic wall thickness was assessed in 4 proximal and 4 distal segments (n=8), for an overall total of 384 segments in the 48 study patients.

Measurement of LV wall thickness could be made with confidence in 384 (100%) of the segments by CMR and in 363 (95%) with echocardiography. LV wall thickness measurements by echocardiography have proved to be highly reproducible by prior intraobserver and interobserver variability analyses of patients with HCM and other conditions.^3,29,30

Cardiac MRI
Similarly, 8 LV segments were identified in each patient from the CMR image designed to correspond directly to those anatomic regions defined and analyzed in the echocardiographic studies. Maximum end-diastolic wall thickness in each LV segment was measured with CMR and echocardiography, independently by 2 investigators (C.R. for CMR and B.J.M. for echocardiography), both of whom were blinded to the wall thickness data obtained for the alternative imaging test.

CMR Observer Variability
Intraobserver variability was assessed for the measurement of LV wall thickness in each of the 8 segments in all 48 study patients (total of 384 segments). The initial measurements were those that constitute the data set included in the present report. The second set of measurements were made for the purpose of the reproducibility analysis 11 months later by the same observer (C.R.), without knowledge of the initial measurements.

Statistical Analysis
Data were expressed as mean±SD. Noncontinuous variables expressed as proportions were compared by ² test. Paired Student t tests were used for the comparison of normally distributed data. Intraobserver variability in comparative LV wall thickness measurements by CMR and echocardiography was assessed by calculating the coefficient of variation between the 2 measurements of LV wall thickness (by the same observer). Probability values were considered significant when 0.05.

	Results

Top Abstract Introduction Methods Results Discussion References

 
Patients Without HCM Diagnosis by Echocardiography
In 3 (6%) of the 48 patients (each a HCM family member), 2D echocardiograms showed normal wall thicknesses ( 12 mm) in all LV segments; the 3 patients were asymptomatic and without mitral valve systolic anterior motion or evidence of LV outflow obstruction. However, CMR identified LV hypertrophy confined to the anterolateral free wall in each of these 3 patients. Two were identical male twins, aged 13 years, with maximum LV thicknesses of 10 and 12 mm, respectively, by echocardiography, but 17 and 20 mm, respectively, by CMR (Table 1; Figure 2). The third patient was a 42-year-old woman with normal LV wall thickness of 12 mm by echocardiography but 17 mm by CMR (Table 1). Abnormal ECG patterns were present in each of these 3 patients and preceded recognition of LV hypertrophy by CMR in the twins.

View this table: [in this window] [in a new window]   TABLE 1. Echocardiographic and CMR Findings in Patients Without an HCM Diagnosis After Echocardiographic Examination

View larger version (117K): [in this window] [in a new window]   Figure 2. Diagnostic images from 13-year-old identical twin with nonobstructive HCM. Two-dimensional stop-frame echocardiogram (A) and comparative CMR (B) images acquired in short-axis plane in end diastole at mitral valve level, and 12-lead ECG (C). A, Echocardiogram shows normal thickness in all LV wall segments, including ventricular septum and contiguous portion of anterolateral free wall (*). Stop-frame image is representative of all cross-sectional planes obtained in this patient. B, CMR image showing segmental area of hypertrophy confined to anterolateral LV free wall (20 mm) and small portion of contiguous anterior septum (*), which was identified only with CMR, in same cross-sectional plane as echocardiogram shown in A. RV indicates right ventricle; AVS, anterior ventricular septum. C, Distinctly abnormal ECG showing Q waves in inferior leads II, III, AVF, and V6, deep S waves in right precordial leads, and diminished precordial R waves. Recorded at full standard, 1 mV=10 mm. Calibration marks in A and B are 1 cm apart; magnification of the images in the 2 panels is not identical.

Comparison of LV Wall Thickness With Echocardiography and CMR
Overall Study Group
LV end-diastolic wall thicknesses obtained by echocardiography and CMR were compared among the 48 study patients. Overall, maximum LV wall thickness did not differ significantly between the 2 imaging modalities, ie, 21.7±9.1 mm (range to 55 mm) with echocardiography and 22.5±9.6 mm (range to 53 mm) with CMR (P=0.21).

CMR imaging showed a broad spectrum of patterns and magnitude of LV hypertrophy, including patients in whom predominant wall thickness was most commonly in the anterior ventricular septum, but also patients with the most substantial hypertrophy in the posterior ventricular septum or the anterolateral free wall (Figure 3). When wall thicknesses measured by echocardiography and CMR were compared with respect to each of the individual LV segments, the 2 imaging tests yielded values that did not differ significantly, except for the anterolateral LV free wall (Table 2).

View larger version (110K): [in this window] [in a new window]   Figure 3. Diverse patterns of LV hypertrophy encountered in HCM shown in CMR short-axis images at end diastole. A, Anterolateral free wall (ALFW) hypertrophy (at 3 o’clock) with sharp transition to normal wall thickness in contiguous portions of anterior septum and posterior free wall. B, Moderate hypertrophy involving only anterior and posterior portions of ventricular septum (VS) equally. C, Predominant posterior ventricular septal hypertrophy (PVS) at 10 and 11 o’clock, also extending into contiguous anterior ventricular septum (AVS). D, Hypertrophy predominantly involving posterior portion of ventricular septum (PVS). E, Massive hypertrophy (wall thickness, 35 mm), largely confined to anterolateral free wall (ALFW) but also involving contiguous posterior free wall and anterior ventricular septum (AVS), with abrupt transition to normal wall thickness. Calibration marks are 1 cm apart.

View this table: [in this window] [in a new window]   TABLE 2. Magnitude of LV Wall Thickness in 8 Regions, Comparing CMR and Echocardiography in 48 HCM Patients

Notably, CMR measurements in the basal anterolateral LV free wall significantly exceeded those made with echocardiography (17±8 versus 13±6 mm; P=0.001), a difference of 20±6% (Figures 3A and 3B). The differences between echocardiographic and CMR measurements of the anterolateral LV free wall were most substantial when associated with the greatest magnitude of absolute LV wall thickness (P=0.001).

With regard to the power for detection of the HCM phenotype, both echocardiography and CMR were diagnostic in 45 patients, CMR alone in 3, and echocardiography alone in none. The site of predominant LV hypertrophy within the wall was most commonly the anterior ventricular septum on both echocardiogram (n=24 patients; 50%) and CMR (n=21; 43%; P=NS).

Patients With Extreme LV Hypertrophy
Of the 48 patients, 41 had maximum LV wall thickness <30 mm by echocardiography. However, in 6 of these 41 patients, CMR showed a more extreme degree of hypertrophy, with LV wall thickness 30 mm identifiable in anterolateral free wall (n=4), posterior septum (n=1), and anterior septum (n=1). In these 6 patients, maximum LV wall thickness was 32±1 mm with CMR compared with 24±3 mm on echocardiography (P<0.001). Conversely, of the 35 patients with maximum LV wall thickness <30 mm by CMR, only 1 had extreme hypertrophy identified with echocardiography (wall thickness 30 mm).

CMR Observer Variability
Intraobserver variability for LV wall thickness measured by CMR averaged 4.9% overall for the combined 8 LV segments. Variability for individual segments were as follows: anterior ventricular septum, basal 4.9%, apical 4.2%; posterior septum, basal 4.2%, apical 4.5%; anterolateral LV free wall, basal 4.9%, apical 5.0%; and posterior free wall, basal 7.2%, apical 4.1%.

	Discussion

Top Abstract Introduction Methods Results Discussion References

 
HCM is a heterogeneous cardiac disease in which clinical diagnosis is predicated on the demonstration of otherwise unexplained LV hypertrophy, which appears in a myriad of diverse patterns, and with a wide range in the magnitude of wall thickening, as documented in the present analysis.^1–3,7 Although the distribution of hypertrophy is often diffuse, it is also frequently segmental and confined to relatively small regions of the LV chamber.^1,2,7 Although the anterior portion of ventricular septum is the area of the wall most commonly involved in the hypertrophic process, localized wall thickening may preferentially involve posterior septum, apex, anterolateral, or even posterior free wall.^2,7,31,32

Two-dimensional echocardiography is generally regarded as the "gold standard" noninvasive diagnostic test for HCM.^1,2,7 However, echocardiography has certain technical limitations. Reliable quantitative delineation of LV wall thickness is dependent on adequate acoustic windows. Also, because the echocardiographic transducer is situated at a fixed point on the anterior chest wall, cross-sectional images are often unavoidably obtained with obliquity.^7,31,33

On the other hand, CMR provides the power of high-resolution, nonoblique images with excellent and uniform contrast at the endocardial borders, encompassing all levels and regions of the LV and permitting virtually complete reconstruction of the chamber.^{17–21,27,34} Therefore, CMR imaging has the potential to detect segmental wall thickening in any area of the LV wall, even when these regions are quite limited in size, and therefore can provide critical supplemental morphological information beyond that obtained from conventional and clinically adequate echocardiographic studies.

In this regard, the findings of the present study define a new subgroup of HCM patients and a novel diagnostic role for CMR imaging within the heterogeneous clinical and morphological spectrum of this disease.^1,2 This has not been delineated clearly in prior comparative CMR and echocardiographic studies in HCM.^18–20 Indeed, a relatively small (5%) but important patient subset had a HCM diagnosis confirmed solely by the morphological identification of segmental areas of hypertrophy confined to the anterolateral LV free wall that was provided only by CMR. Two of these patients were asymptomatic identical twins aged 14 years whose father had survived a sudden and unexpected HCM-related cardiac arrest triggered by vigorous physical activity at age 33 years (with residual cerebral damage and neurological deficit).

Both children had 5 serial 2D echocardiograms each (over 4 years) that were within normal limits and without evidence of wall thickening in any LV segment; however, over this time period, 12-lead ECGs consistently showed distinctly abnormal patterns involving right-axis deviation, as well as RSr' pattern in V₁, narrow deep Q waves, and deep S waves in these 2 patients, which raised a heightened suspicion that they harbored an HCM mutant gene and are affected family members,¹³ albeit with a phenotype that could not be confirmed with echocardiography. Indeed, as previously emphasized,^2,13 ECG abnormalities can be the initial and sole clinical clue to HCM, particularly in young family members.^2,13

However, in the present study, it was CMR that had a direct impact on diagnosis and clinical management, specifically in the twins. Given the appearance of the HCM phenotype (documented only by CMR) with maximum LV wall thicknesses of 17 and 20 mm, in conjunction with the high-risk profile created by their father’s cardiac arrest,^1,2,5 a cardioverter-defibrillator was implanted prophylactically in both children.^2,35 Finally, a 17-year-old symptomatic sibling of the twins with an abnormal ECG has recently been identified by CMR with similar anterolateral LV free wall hypertrophy associated with a normal echocardiogram.

Of particular note, in each of these 3 patients in whom CMR identified the HCM phenotype, the region of LV wall thickening did not involve the ventricular septum but was confined to a small portion of the LV chamber, specifically in the anterolateral LV free wall. This is a region of the LV, spatially removed from the center of the echocardiographic sector in the parasternal short-axis cross-sectional plane, in which it is frequently difficult to reliably assess the magnitude of wall thickening, ie, due to poor lateral resolution and often substantial image distortion that result in indistinct recognition of the epicardial border situated at the lateral margins of the sector.³³ Therefore, the detection by echocardiography of small segmental areas of hypertrophy by echocardiography in the anterolateral LV free wall is generally fraught with more substantial technical difficulties than is imaging of LV wall thickening in the anterior portion of ventricular septum (where superior axial resolution is operative). However, by utilizing high-resolution tomographic CMR imaging in patients in the present study, such technical limitations in epicardial (and endocardial) border recognition were largely resolved. The inherent capacity of CMR to image hypertrophied areas of the LV not readily identifiable by echocardiography has already been established in HCM patients with respect to apical wall thickening.³⁶

This principal was substantiated by 2 other analyses performed in this patient cohort. First, in the overall study group, we found that measurements of LV anterolateral free wall thickness were generally underestimated by 2D echocardiography (relative to CMR). Second, in an analysis of that subset of patients with the most extreme degrees of LV hypertrophy, a phenotypic expression of HCM to which increased risk for sudden death has been attributed,^1–5 echocardiography appeared to underestimate the absolute magnitude of LV wall thickening. Indeed, in 6 of the present study patients, echocardiography failed to completely identify massive degrees of hypertrophy (usually in the anterolateral free wall) recognized by CMR, which may have placed these patients in a higher-risk subgroup^2–5,37 as possible candidates for primary prevention of sudden death with an implantable defibrillator.³⁵

The latter observation creates a new clinical dilemma, because the available data in HCM relating risk of sudden death to extreme degrees of LV hypertrophy are based entirely on echocardiographic assessments of wall thickness. To somehow extrapolate and translate the available echocardiographic data to CMR-derived wall thicknesses will require future prospective clinical studies with substantial follow-up spanning many years (using CMR). Therefore, at present, the most prudent strategy for such patients (with LV wall thickness 30 mm only by CMR) will require a measure of individual clinical judgment that relies on an integrated assessment of the overall sudden death risk profile to determine the advisability of recommending an implantable defibrillator.

In addition to the value of CMR for the diagnosis of HCM described in this report and elsewhere,³⁶ other potential applications are likely. These include identification of the HCM phenotype when echocardiography is not of adequate diagnostic technical quality, as well as the recognition of delayed hyperenhancement after gadolinium infusion indicative of myocardial fibrosis.^37–39 It is also expected that the indications for CMR in HCM will expand as more data become available, thereby selectively justifying the additional healthcare costs involved.

In conclusion, the present data define distinctive advantages afforded by high-resolution CMR for the clinical diagnosis of HCM in selected patients. CMR imaging does not offer general superiority over echocardiography in all aspects regarding the morphological identification of the HCM disease phenotype, and at present, its use is not required in all HCM patients. Nevertheless, importantly, CMR is capable of establishing the diagnosis of HCM in some patients not reliably identifiable by conventional echocardiography.

	Footnotes

 
Dr Rickers is presently at Pediatric Heart Center, Universitätsklinikum Schleswig-Holstein, Kiel, Germany; Drs Wilke, Prasad Panse, and Neeta Panse are currently at Health Science Center, University of Florida, Jacksonville, Fla; and Dr Jerosch-Herold is currently at Advanced Imaging Research Center, Oregon Health and Science University, Portland, Ore.

	References

Top Abstract Introduction Methods Results Discussion References

 

1. Maron BJ. Hypertrophic cardiomyopathy: a systematic review. JAMA. 2002; 287: 1308–1320.[Abstract/Free Full Text]
   
2. Maron BJ, McKenna WJ, Danielson GK, Kappenberger LJ, Kuhn HJ, Seidman CE, Shah PM, Spencer WH, Spirito P, ten Cate FJ, Wigle ED; American College of Cardiology/European Society of Cardiology 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. Spirito P, Bellone P, Harris KM, Bernabo P, Bruzzi P, Maron BJ. Magnitude of left ventricular hypertrophy predicts the risk of sudden death in hypertrophic cardiomyopathy. N Engl J Med. 2000; 342: 1778–1785.[Abstract/Free Full Text]
   
4. Elliott PM, Poloniecki J, Dickie S, Sharma S, Monserrat L, Varnava A, Mahon NG, McKenna WJ. Sudden death in hypertrophic cardiomyopathy: identification of high risk patients. J Am Coll Cardiol. 2000; 36: 2212–2218.[Abstract/Free Full Text]
   
5. Maron BJ, Estes NAM III, Maron MS, Almquist AK, Link MS, Udelson J. Primary prevention of sudden death as a novel treatment strategy in hypertrophic cardiomyopathy. Circulation. 2003; 107: 2872–2875.[Free Full Text]
   
6. Maron BJ. Sudden death in young athletes. N Engl J Med. 2003; 349: 1064–1075.[Free Full Text]
   
7. 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]
   
8. Rosenzweig A, Watkins H, Hwang DS, Miri M, McKenna W, Traill TA, Seidman JG, Seidman CE. Preclinical diagnosis of familial hypertrophic cardiomyopathy by genetic analysis of blood lymphocytes. N Engl J Med. 1991; 325: 1753–1760.[Abstract]
   
9. Maron BJ, Niimura H, Casey SA, Soper MK, Wright GB, Seidman JG, Seidman CE. Development of left ventricular hypertrophy in adults with hypertrophic cardiomyopathy caused by cardiac myosin-binding protein C mutations. J Am Coll Cardiol. 2001; 38: 315–321.[Abstract/Free Full Text]
   
10. Seidman JG, Seidman CE. The genetic basis for cardiomyopathy: from mutation identification to mechanistic paradigms. Cell. 2001; 104: 557–567.[CrossRef][Medline] [Order article via Infotrieve]
    
11. 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]
    
12. Watkins H, McKenna WJ, Thierfelder L, Suk HJ, Anan R, O’Donoghue A, Spirito A, Matsumori A, Moravec SC, Seidman JG. Mutations in the genes for cardiac troponin T and -tropomyosin in hypertrophic cardiomyopathy. N Engl J Med. 1995; 332: 1058–1064.[Abstract/Free Full Text]
    
13. Panza JA, Maron BJ. Relation of electrocardiographic abnormalities to evolving left ventricular hypertrophy in hypertrophic cardiomyopathy during childhood. Am J Cardiol. 1989; 63: 1258–1265.[CrossRef][Medline] [Order article via Infotrieve]
    
14. Moolman JC, Corfield VA, Posen B, Nagumbela K, Seidman C, Brink PA, Watkins H. Sudden death due to troponin T mutations. J Am Coll Cardiol. 1997; 29: 549–555.[Abstract]
    
15. Konno T, Shimizu M, Ino H, Yamaguchi M, Terai H, Uchiyama K, Oe K, Mabuchi T, Kaneda T, Mabuchi H. Diagnostic value of abnormal Q waves for identification of preclinical carriers of hypertrophic cardiomyopathy based on a molecular genetic diagnosis. Eur Heart J. 2004; 25: 246–251.[Abstract/Free Full Text]
    
16. Shimizu M, Ino H, Yamaguchi M, Terai H, Hayashi K, Kiyama M, Sakata K, Hayashi T, Inoue M, Kaneda T, Mabuchi H. Chronologic electrocardiographic changes in patients with hypertrophic cardiomyopathy associated with cardiac troponin I mutation. Am Heart J. 2002; 143: 289–293.[CrossRef][Medline] [Order article via Infotrieve]
    
17. Grothues F, Smith GC, Moon JC, Bellenger NG, Collins P, Klein HU, Pennell DJ. Comparison of interstudy reproducibility of cardiovascular magnetic resonance with two-dimensional echocardiography in normal subjects and in patients with heart failure of left ventricular hypertrophy. Am J Cardiol. 2002; 90: 29–34.[CrossRef][Medline] [Order article via Infotrieve]
    
18. Devlin AM, Moore NR, Ostman-Smith I. A comparison of MRI and echocardiography in hypertrophic cardiomyopathy. Br J Radiol. 1999; 72: 258–264.[Abstract]
    
19. Pons-Llado G, Carreras F, Borras X, Palmer J, Llauger J, Bayes de Luna A. Comparison of morphologic assessment of hypertrophic cardiomyopathy by magnetic resonance versus echocardiographic imaging. Am J Cardiol. 1997; 79: 1651–1656.[CrossRef][Medline] [Order article via Infotrieve]
    
20. Posma JL, Blanksma PK, van der Wall EE, Hamer HP, Mooyaart EL, Lie KI. Assessment of quantitative hypertrophy scores in hypertrophic cardiomyopathy: magnetic resonance imaging versus echocardiography. Am Heart J. 1996; 132: 1020–1027.[CrossRef][Medline] [Order article via Infotrieve]
    
21. Nagel E, Lehmkuhl HB, Bocksch W, Klein C, Vogel U, Frantz E, Ellmer A, Dreysse S, Fleck E. Noninvasive diagnosis of ischemia-induced wall motion abnormalities with the use of high-dose dobutamine stress MRI: comparison with dobutamine stress echocardiography. Circulation. 1999; 99: 763–770.[Abstract/Free Full Text]
    
22. Lima JAC, Desai MY. Cardiovascular magnetic resonance imaging: current and emerging applications. J Am Coll Cardiol. 2004; 44: 1164–1171.[Abstract/Free Full Text]
    
23. Maron MS, Olivotto I, Betocchi S, Casey SA, Lesser JR, Losi MA, Cecchi F, Maron BJ. Effect of left ventricular outflow tract obstruction on clinical outcome in hypertrophic cardiomyopathy. N Engl J Med. 2003; 348: 295–303.[Abstract/Free Full Text]
    
24. Plein S, Bloomer TN, Ridgway JP, Jones TR, Bainbridge GJ, Sivananthan MU. Stead-state free precession magnetic resonance imaging of the heart: comparison with segmented k-space gradient-echo imaging. J Magn Reson Imaging. 2001; 14: 230–236.[CrossRef][Medline] [Order article via Infotrieve]
    
25. Moon JC, Lorenz CH, Francis JM, Smith GC, Pennell DJ. Breath-hold FLASH and FISP cardiovascular MR imaging: left ventricular volume differences and reproducibility. Radiology. 2002; 223: 789–797.[Abstract/Free Full Text]
    
26. Francois CJ, Fieno DS, Shors SM, Finn JP. Left ventricular mass: manual and automatic segmentation of true FISP and FLASH cine MR images in dogs and pigs. Radiology. 2004; 230: 389–395.[Abstract/Free Full Text]
    
27. Buller VG, van der Geest RJ, Kool MD, van der Wall EE, de Roos A, Reiber JH. Assessment of regional left ventricular wall parameters from short axis magnetic resonance imaging using a three-dimensional extension to the improved centerline method. Invest Radiol. 1997; 32: 529–539.[CrossRef][Medline] [Order article via Infotrieve]
    
28. Sheehan FH, Bolson EL, Dodge HT, Mathey DG, Schofer J, Woo HW. Advantages and applications of the centerline method for characterizing regional ventricular function. Circulation. 1986; 74: 293–305.[Abstract/Free Full Text]
    
29. Pelliccia A, Maron BJ, Culasso F, Spataro A, Caselli G. Athlete’s heart in women: echocardiographic characterization of highly trained elite female athletes. JAMA. 1996; 276: 211–215.[Abstract]
    
30. Maron BJ, Spirito P, Wesley YE, Arce J. Development and progression of left ventricular hypertrophy in children with hypertrophic cardiomyopathy. N Engl J Med. 1986; 315: 610–614.[Abstract]
    
31. Maron BJ, Gottdiener JS, Bonow RO, Epstein SE. Hypertrophic cardiomyopathy with unusual locations of left ventricular hypertrophy undetectable by M-mode echocardiography: identification by wide-angle, two-dimensional echocardiography. Circulation. 1981; 63: 409–418.[Abstract/Free Full Text]
    
32. Maron BJ, Gottdiener JS, Epstein SE. Patterns and significance of the distribution of left ventricular hypertrophy in hypertrophic cardiomyopathy: a wide-angle, two-dimensional echocardiographic study of 125 patients. Am J Cardiol. 1981; 48: 418–428.[CrossRef][Medline] [Order article via Infotrieve]
    
33. Weyman AE. Principals and Practice of Echocardiography. 2nd ed. Philadelphia, Pa: Lea & Febiger; 1994: 11–12.
    
34. Swingen C, Seethamraju RT, Jerosch-Herold M. An approach to the three-dimensional display of left ventricular function and viability using MRI. Int J Cardiovasc Imaging. 2003; 19: 325–336.[CrossRef][Medline] [Order article via Infotrieve]
    
35. Maron BJ, Shen W-K, Link MS, Epstein AE, Almquist AK, Daubert JP, Bardy GH, Favale S, Rea RF, Boriani G, Estes NAM III, Casey SA, Stanton MS, Betocchi S, Spirito P. 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]
    
36. Moon JC, Fisher NG, McKenna WJ, Pennell DJ. Detection of apical hypertrophic cardiomyopathy by cardiovascular magnetic resonance in patients with non-diagnostic echocardiography. Heart. 2004; 90: 645–649.[Abstract/Free Full Text]
    
37. 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: 1568–1572.[Free Full Text]
    
38. Moon JC, Reed E, Shepphard MN, Elkington AG, Ho SY, Burke M, Petrou M, Pennell DJ. 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]
    
39. Choudhury L, Mahrholdt H, Wagner A, Choi KM, Elliott MD, Klocke FJ, Bonow RO, Judd RM, Kim RJ. Myocardial scarring in asymptomatic or mildly symptomatic patients with hypertrophic cardiomyopathy. J Am Coll Cardiol. 2002; 40: 2156–2164.[Abstract/Free Full Text]
    

Related Article:

Issue Highlights
Circulation 2005 112: 777. [Full Text]

This article has been cited by other articles:

				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]

				S. Basavarajaiah, A. Boraita, G. Whyte, M. Wilson, L. Carby, A. Shah, and S. Sharma Ethnic differences in left ventricular remodeling in highly-trained athletes relevance to differentiating physiologic left ventricular hypertrophy from hypertrophic cardiomyopathy. J. Am. Coll. Cardiol., June 10, 2008; 51(23): 2256 - 2262. [Abstract] [Full Text] [PDF]

				G. K. Efthimiadis, S. Meditskou, G. E. Parcharidis, J. M. Galvin, J. R. Arnold, T. D. Karamitsos, S. E. Petersen, A. Pelliccia, and B. J. Maron Athletes with Repolarization Abnormalities N. Engl. J. Med., May 22, 2008; 358(21): 2296 - 2298. [Full Text] [PDF]

				I. S. Syed, S. R. Ommen, J. F. Breen, and A. J. Tajik Hypertrophic Cardiomyopathy: Identification of Morphological Subtypes by Echocardiography and Cardiac Magnetic Resonance Imaging J. Am. Coll. Cardiol. Img., May 1, 2008; 1(3): 377 - 379. [Full Text] [PDF]

				T. Germans and A. C van Rossum The use of cardiac magnetic resonance imaging to determine the aetiology of left ventricular disease and cardiomyopathy Heart, April 1, 2008; 94(4): 510 - 518. [Full Text] [PDF]

				E. Durand, E. Mousseaux, P. Coste, R. Pilliere, O. Dubourg, L. Trinquart, G. Chatellier, A. Hagege, M. Desnos, and A. Lafont Non-surgical septal myocardial reduction by coil embolization for hypertrophic obstructive cardiomyopathy: early and 6 months follow-up Eur. Heart J., February 1, 2008; 29(3): 348 - 355. [Abstract] [Full Text] [PDF]

				M. W. Hansen and N. Merchant MRI of Hypertrophic Cardiomyopathy: Part I, MRI Appearances Am. J. Roentgenol., December 1, 2007; 189(6): 1335 - 1343. [Abstract] [Full Text] [PDF]

				U Sechtem, H Mahrholdt, and H Vogelsberg Cardiac magnetic resonance in myocardial disease Heart, December 1, 2007; 93(12): 1520 - 1527. [Abstract] [Full Text] [PDF]

				R. G Assomull, D. J Pennell, and S. K Prasad Cardiovascular magnetic resonance in the evaluation of heart failure Heart, August 1, 2007; 93(8): 985 - 992. [Full Text] [PDF]

				R. A. Nishimura and S. R. Ommen Hypertrophic Cardiomyopathy, Sudden Death, and Implantable Cardiac Defibrillators: How Low the Bar? JAMA, July 25, 2007; 298(4): 452 - 454. [Full Text] [PDF]

				B. J. Maron, T. S. Haas, and J. R. Lesser Diagnostic Utility of Cardiac Magnetic Resonance Imaging in Monozygotic Twins With Hypertrophic Cardiomyopathy and Identical Pattern of Left Ventricular Hypertrophy Circulation, June 19, 2007; 115(24): e627 - e628. [Full Text] [PDF]

				B. J. Maron and A. Pelliccia The Heart of Trained Athletes: Cardiac Remodeling and the Risks of Sports, Including Sudden Death Circulation, October 10, 2006; 114(15): 1633 - 1644. [Full Text] [PDF]

				A. Pelliccia, F. M. Di Paolo, D. Corrado, C. Buccolieri, F. M. Quattrini, C. Pisicchio, A. Spataro, A. Biffi, M. Granata, and B. J. Maron Evidence for efficacy of the Italian national pre-participation screening programme for identification of hypertrophic cardiomyopathy in competitive athletes Eur. Heart J., September 2, 2006; 27(18): 2196 - 2200. [Abstract] [Full Text] [PDF]

				C. A. Dumont, L. Monserrat, R. Soler, E. Rodriguez, X. Fernandez, J. Peteiro, A. Bouzas, B. Bouzas, and A. Castro-Beiras Interpretation of electrocardiographic abnormalities in hypertrophic cardiomyopathy with cardiac magnetic resonance Eur. Heart J., July 2, 2006; 27(14): 1725 - 1731. [Abstract] [Full Text] [PDF]

				P. Spirito and C. Autore Management of hypertrophic cardiomyopathy. BMJ, May 27, 2006; 332(7552): 1251 - 1255. [Full Text] [PDF]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rickers, C. Articles by Maron, B. J. Search for Related Content