Cardiovascular magnetic resonance in hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy; magnetic resonance; diagnosis; prognosis

REVIEW ARTICLE

Cardiovascular magnetic resonance in hypertrophic cardiomyopathy

Afonso Akio Shiozaki^I; Raymond J. Kim^II; José Rodrigues Parga^I; Eduardo Marinho Tassi^III; Edmundo Arteaga^I; Carlos Eduardo Rochitte^I

^ICardiovascular Magnetic Resonance and Computed Tomography Sector of the Instituto do Coração of the Hospital das Clínicas – HCFMUSP - São Paulo, SP

^IIDuke Cardiovascular Magnetic Resonance Center, Durham, North Carolina - EUA

IIICardiovascular Magnetic Resonance and Computed Tomography Sector of the Diagnósticos da America S.A.- Rio de Janeiro, RJ

^{Mailing Address}

Key words: Hypertrophic cardiomyopathy; magnetic resonance; diagnosis; prognosis.

Hypertrophic cardiomyopathy (HCM) is the most frequent genetic cardiac disease that causes sudden death in young people, with an incidence of 1:500 adults.

The routinely used criteria for worst prognosis have limited sensitivity and specificity. Thus, the estimated risk of evolving to dilated cardiomyopathy or sudden death is somewhat inaccurate, leading to management uncertainty of HCM patients.

Therefore, an accurate noninvasive method for the diagnosis of HCM with prognostic value is of great importance.

In the last years, Cardiovascular Magnetic Resonance (CMR) emerged not only as a diagnostic tool, but also as a study with prognostic values, by characterizing myocardial fibrosis with great accuracy in HCM patients. Additionally, CMR identifies the types of hypertrophy, analyses the ventricular function, estimates the intraventricular gradient and allows the determination of differential diagnosis. Moreover, CMR can uniquely access myocardial fibrosis in HCM.

Introduction

Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disease which is the major responsible for sudden death among youth¹, with relatively frequent incidence of 1:500 in adults².

The polygenic character of the disease with over 200 mutations³, leads to an extremely varied phenotypic expression⁴. While some subjects remain asymptomatic for their whole lives, others present sudden death as the first presentation⁵.

The common risk factors used to stratify patients are: cardiac sudden death and family history of HCM; unexplained syncope; non-sustained ventricular tachycardia; abnormal blood pressure response during upright exercise testing in subjects < 40 years old; and presence of severe left ventricular hypertrophy (> 30 mm by echocardiogram). These criteria are very useful to physicians in guiding treatment of HCM subjects⁶.

However, the accuracy of these criteria is limited, leading to uncertainty about the real risk of sudden death.

Therefore, it is crucially important to have new diagnostic methods with enough prognostic power to identify potential subjects with higher risk of sudden death and ventricular dilatation form. This approach would allow more aggressive therapy with this group of subjects.

In the last few years cardiovascular magnetic resonance (CMR) has emerged as a very accurate tool in the diagnosis of HCM, even being considered as the first choice exam⁷. CMR evaluates several hypertrophic patterns, the ventricular function, the pressure gradient between the left ventricular outflow tract and aorta and is extremely useful for the differential diagnosis with other entities. Besides, for the first time, a non-invasive method identifies and quantifies the distribution of myocardial fibrosis found in this disease⁸.

The role of cardiovascular magnetic resonance in hypertrophic cardiomyopathy

Recently the European Society of Cardiology (Consensus Panel Report)⁷ and later the American College of Cardiology/American Heart Association (Clinical Competence Statement on Cardiac Imaging with Magnetic Resonance)⁹ indicated CMR as first choice exam or at least equivalent to other diagnostic methods in the approach of several cardiomyopathies, including HCM.

The excellent accuracy of CMR in anatomical and functional analysis of the left and right ventricles to quantify ventricular volume and mass^10-12 has increased the sensitivity and specificity of the diagnosis of HCM (Figure1). This has allowed precise identification of several forms of hypertrophy (Figures 2, 3, 4 and 5) and determination of differential diagnosis.

A comparative study of two-dimensional echocardiograms and CMR among HCM subjects demonstrated the greater accuracy of CMR in diagnosing and differentiating several patterns of hypertrophy. In cases where LV hypertrophy is more accentuated on the free wall, the echocardiogram did not permit diagnosis of HCM and among subjects with confined hypertrophy in anterolateral wall underestimated the thickness of the wall in relation to CMR¹³ (Figures 4 and 5).

Two other studies demonstrated that echocardiograms have lower sensitivity compared to that of CMRs. In the diagnosis of apical hypertrophic cardiomyopathy, echocardiograms did not properly evaluate the apical segment in up to 40% of HCM subjects^14,15 (Figure 2).

Recently, Petersen et al¹⁶ compared geometric LV indices by CMR in HCM subjects, healthy volunteers, competitive athletes with physiologic hypertrophy, aortic stenosis and hypertensive heart disease. These authors pointed to the low sensitivity in the classic measurements used in diagnosis of HCM, such as the maximal end-diastolic wall thickness over 13mm (40% sensitivity) and wall thickness ratio (28% sensitivity). However, when a new geometric index was applied using the maximal end-diastolic thickness-to-left ventricular end-diastolic volume index ratio, the results were promising. They compared this index among athletes participating in high-level competitive sports, which were principally rowing, swimming, running, and cycling for at least the previous 18 months with an average of 19.2 ± 6.8 hours of training per week for the last 8.5 ± 4.9 years with that of the HCM subjects. This index for healthy volunteers and athletes was lower than 0.15 mm x m² x ml.

Indices higher than 0.15mm x m² x ml was observed in all pathological hypertrophies and presented a sensitivity of 80%, specificity of 99%, negative predictive value of 94%, and positive predictive value of 95% in determining the differential diagnosis between HCM and the athletes’ hearts¹⁶.

One of the major contributions of CMR, besides the anatomical and functional data and geometric indices, is the delineation of myocardial fibrosis in HCM, which follows specific patterns⁸. The presence of myocardial fibrosis increases even more the diagnostic accuracy and provide an insight on the prognosis.

The technique that allows the identification of myocardial delayed enhancement (MDE) in ischemic heart disease was developed by Kim et al^17-21. They demonstrated a close correlation between myocardial fibrosis by CMR and the fibrosis seen in histology²². Moreover, a landmark study by Kim et al²³ defined a direct relationship between the extent of myocardial fibrosis by CMR and the potential for contractility recovery after revascularization. This data and other are the basis for considering CMR MDE as a gold-standard for myocardial viability in coronary artery disease²⁴.

The MDE technique uses contrast based agents that have extracellular distribution and accentuate the difference in tissue relaxation characteristics between infarcted and normal myocardium. Following intravenous administration, the contrast agent diffuses rapidly from the intravascular to the extracellular compartment. Several minutes after injection, gadolinium in the normal myocardial, which has small extracellular space, washes out rapidly, while slow wash out occurs within areas with enlarged extracellular space, such as areas of myocardial fibrosis or necrosis¹⁷.

Choudhury et al⁸ were the first to use the MDE technique to detect myocardial fibrosis areas in 81% of asymptomatic or mild symptomatic HCM subjects. Furthermore, these authors observed that the delayed enhancement pattern was very peculiar, with multiple foci standard. The myocardial hyperenhancement in HCM did not respect any specific coronary territory and in the majority of HCM subjects was found mostly at the junction between the interventricular septum and right ventricular free wall (Figure 6). This was previously demonstrated by HCM necropsy studies that showed myocardial disarray and highly accentuated fibrosis in these areas^8,24-26.

Once the fibrosis is visualized in the HCM by CMR, would the delayed enhancement have any prognostic implication?

In coronary artery disease, Bello et al ²⁷ showed that fibrosis measured by CMR in infarcted areas are better identifiers of patients who have a substrate for monomorphic ventricular tachycardia than LV ejection fraction.

Similar to ischemic cardiomyopathy, the probable origin of ventricular arrhythmias in HCM subjects²⁸ is the multiple areas of electrical abnormal conduction caused by myocardial fibrosis, which could lead to sudden death²⁹. Necropsy studies of HCM subjects demonstrated a higher fibrosis percentage in subjects who had sudden death when compared to those who died from non-cardiac causes³⁰.

Moon et al, in 2003³¹, demonstrated the presence of delayed enhancement representing myocardial fibrosis areas by CMR in 79% of HCM patients. Previous studies demonstrated that sudden death in HCM correlates to a number of risk factors³². The percentage of delayed enhancement was significantly higher when patients presented more than 2 risk factors for sudden death (15.7% vs. 8.6% p = 0.02). It was also significantly higher in patients who presented with progressive disease, in the form of ventricular dilatation (28.5% vs. 8.7% p < 0.001). This difference remained statistically significant when the subjects with more than 2 risk factors for sudden death or those with progressive dilated form were excluded.

These authors have also found the multiple foci delayed enhancement pattern previously related. Furthermore, they also observed 2 distinct patterns. The first pattern was denominated confluent hyperenhancement, a more localized and homogeneous pattern (Figure 6); the second, diffuse hyperenhancement, a more patchy and heterogeneous pattern (Figure 7). In the confluent pattern, there was a significant concentration of patients with lower risk for sudden death. (less than 2 risk factors), compared to the diffuse pattern, that was more frequent with higher risk (2 or more risk factors) for sudden death.

Thus, HCM subjects with diffuse delayed enhancement correlated to a higher percentage of fibrosis and to a worse prognosis for sudden death and left ventricular dilatation, while the HCM subjects with confluent delayed enhancement did not.

In conclusion, CMR provides a large amount of information on myocardial anatomy, function and tissue characterization that crucially improves HCM diagnosis. Of special importance is the singular CMR capability of detecting and quantifying myocardial fibrosis in HCM patients, which seems to be of great prognostic value.

Further studies will define if CMR can improve prediction of sudden death that will lead to changes in the current of management of HCM patients.

References

Received for publication on May 23, 2006; revised manuscript received June 18, 2006; accepted July 3, 2006

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Publication Dates

• Publication in this collection
  22 Mar 2007
• Date of issue
  Feb 2007

History

• Accepted
  03 July 2006
• Reviewed
  18 June 2006
• Received
  23 May 2006