dic ABC Imagem Cardiovascular Arq Bras Cardiol: Imagem cardiovasc. 2675-312X Sociedade Brasileira de Cardiologia 10.47593/2675-312X/20223504erer_15i Review Article Hypertrophic Cardiomyopathy: A Review Using Magnetic Resonance Imaging 0000-0003-1530-3795 Valério Raul Serra 1 Review conception and design, manuscript writing 0000-0002-3711-1754 Bittencourt Marcio Sommer 1 2 critical review of the manuscript for intellectual content 0000-0001-7302-7448 Uellendahl Marly M. 1 3 Review conception and design, manuscript writing, critical review of the manuscript for intellectual content DASA São Paulo SP Brazil DASA, São Paulo, SP, Brazil. Clinical and Epidemiological Research Center University Hospital University of São Paulo São Paulo SP Brazil Clinical and Epidemiological Research Center, University Hospital, University of São Paulo (USP), São Paulo, SP, Brazil. Federal University of São Paulo São Paulo SP Brazil Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil. Mailing Address: Marly M. Uellendahl • R. Joaquim Nabuco, 1560, Brooklyn Paulista, SP, Brazil, Postal Code: 04621-005. E-mail: mauellendahl@gmail.com

Conflict of interest

The authors have declared that they have no conflict of interest.

Editor responsible for the review: Daniela do Carmo Rassi Frota

 21 12 2022 2022 35 4 erer_15 29 9 2022 5 10 2022 20 10 2022 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract

Hypertrophic cardiomyopathy, the most common genetic cardiopathy in the general population, is characterized by asymmetric left ventricular hypertrophy. However, the phenotypic changes in this cardiomyopathy extend beyond ventricular hypertrophy and include changes in the mitral valve apparatus, papillary muscles, and right ventricle. Due to the difficult differential diagnosis among multiple causes of hypertrophy, cardiac magnetic resonance has played a fundamental role in its diagnostic and prognostic evaluation; magnetic cine-resonance in defining the location and extent of hypertrophy; late enhancement, in the detection of areas of myocardial fibrosis; more recent techniques such as T1 mapping that assesses interstitial fibrosis and extracellular volume; and finally tissue tracking in the analysis of myocardial deformation.

 Cardiomyopathy, Hypertrophic Magnetic Resonance Cardiac Imaging Techniques Introduction

Hypertrophic cardiomyopathy (HCM) was first described by the English pathologist Robert Donald Teare, who reported the presence of asymmetric myocardial hypertrophy postmortem in a series of eight patients, of whom seven had died of sudden cardiac death (SCD).1

The prevalence of HCM is 1:500 in the general population, making it the most common genetic cardiac pathology. It affects the sexes at similar frequencies, although women are more often underdiagnosed, tending to be older with more advanced cardiomyopathy at the initial evaluation.2-4

HCM is defined as an unexplained increase in the thickness of the left ventricular (LV) wall with hypertrophy ≥15 mm in end diastole and in any ventricular segment, with involvement restricted to the heart and in the absence of other pathologies that may cause similar hypertrophy.3,4 However, morphological changes in the mitral valve apparatus or papillary muscles and the presence of myocardial fibrosis and microvascular disease are also part of the spectrum of this disease.5

The LV hypertrophy (LVH) found in HCM has heterogeneous phenotypic patterns that can vary with LVH type (asymmetric, symmetric, focal, or diffuse) and ventricular wall location (ranging from the apex to the base). Other extremely important signs in the evaluation of HCM include LV outflow tract (LVOT) obstruction and LV ejection fraction (LVEF) changes.6-10

The myocardial hypertrophy in these patients is explained by characteristic histopathological findings, disorganized and hypertrophic myocardial fibers, and microvascular dysfunction with consequent silent ischemia and subsequent interstitial fibrosis.11

The life expectancy for most patients with HCM is similar to that of individuals without cardiomyopathy;12,13 however, a small proportion is at higher risk of cardiovascular events such as SCD, heart failure (HF), and stroke.13-15 Around 30–40% of patients with HCM are estimated to develop adverse events related to heart disease. Nonetheless, the current therapeutic arsenal, especially related to risk stratification and the use of implantable cardioverter-defibrillators (ICD), has reduced the mortality rate of these patients, even in the most severe cases, to less than 1% annually.4

 Genetics

HCM is an autosomal dominant genetic disease caused by mutations of different genes that encode cardiac sarcomere proteins.5,16

More than 1,500 mutations have been identified in more than 13 different genes that interfere with the coding of sarcomere contractile proteins. Numerous mutations are known, with the most prevalent being located in the beta-myosin heavy chain (MYH7) and myosin-binding protein C (MYBPC3) genes.4,5 Almost every patient with an HCM-related mutation will demonstrate phenotypic evidence until early adulthood, especially with increased myocardial thickness.17-20

Genetic testing can identify the mutation in up to 30–60% of patients with the HCM phenotype. However, a significant proportion of patients with phenotypic change resents no recognized genetic basis.4,21-23 Notably, genetic changes are not correlated with the subject’s phenotype, and similar genetic mutations may present as different cardiomyopathy phenotypes.24

The advantage of genetic confirmation is the opportunity to test first-degree relatives and, consequently, perform a cascade screening to enable early evaluation and follow-up, if indicated, for these patients.6,19,22,25 Relatives in whom the gene mutation is identified have a high probability of developing phenotypic changes at some point in life; therefore, follow-up with imaging tests is indicated. On the other hand, relatives not carrying the genetic mutation have no risk of developing the disease and require no clinical follow-up.22,23

 Phenotypic presentations of LVH

Different patterns of hypertrophy comprise this phenotype within the spectrum of HCM. The most common segment of LVH, involved in up to 70% of cases, is the confluence of the basal anterior septum with the contiguous anterior free wall, often the thickest segment.26-28 The second most common region of LVH is the posterior mid-apical LV septum.8,29

However, most phenotypes present hypertrophy in more than 50% of the total myocardium. On the other hand, some cases may present as focal hypertrophy, mainly in the basal anterior septum region or the basal anterior segment. These cases of focal hypertrophy may have a normal myocardial mass (up to 20%) despite a clinical diagnosis of HCM, constituting a greater diagnostic challenge, especially on echocardiography.7,26,28,30

Another extremely important but less frequent phenotype is midventricular hypertrophy, which, by causing dynamic LV obstruction, favors the onset of ventricular arrhythmias, myocardial necrosis, and apical aneurysms, causing thrombus and systemic embolic events.27,31

Apical ventricular hypertrophy, found in 5–25% of cases, is a heterogeneous HCM phenotype predominant in the apical segments that is often related to T-wave inversion on electrocardiography.32

Figure 1 shows the main hypertrophy patterns found in HCM cases.

Cardiac magnetic resonance imaging scan showing a longitudinal section (4C, 3C, 2C) with major hypertrophic cardiomyopathy (HCM) patterns. (A) HCM with septal predominance; (B) HCM with apical predominance; and (C) HCM with midventricular predominance.

Other phenotypic changes in HCM

HCM, in addition to typical LVH, has other cardiac presentations that, with the increased use of cardiac magnetic resonance (CMR), have become more evident and require consideration to reduce diagnostic failure.

Right ventricle

The use of CMR as a diagnostic method in cases of HCM demonstrated that up to one third of patients have right ventricular (RV) hypertrophy (considered if the thickness is ≥8 mm) associated with already known LVH. These patients may also progress with increased total RV mass.33

The main region of RV hypertrophy is at the insertion of the RV free wall in the anterior or posterior interventricular septum. In addition to ventricular hypertrophy, other phenotypic changes can be found in the RV, such as the presence of the supraventricular crest (muscle structure adjacent to the interventricular septum). This finding is important due to its location, as it may be erroneously included in the calculation of LV mass, leading to an overestimated total value.33

 LV apical aneurysms

LV apical aneurysms are another phenotypic HCM change that has increasing diagnostic importance with the greater use of CMR. The use of gadolinium-based contrast and late enhancement (LE) showed that these aneurysms are composed of fibrotic tissue and these changes are associated with increased risks of arrhythmias and SCD, with an important impact on treatment and ICD implantation evaluation. Therefore, it is necessary to investigate these aneurysms to ensure better patient follow-up and diagnostic guidance.34-36

 Mitral valve apparatus

Changes in the mitral valve apparatus are considered primary phenotypic presentations of HCM regardless of hypertrophy degree and other phenotypic findings, which suggests a more complex pathophysiology of this cardiomyopathy that extends beyond sarcomere-bound protein changes in the myocyte.33,37,38

Up to one third of patients with HCM may have elongated mitral leaflets, with an anterior mitral valve leaflet ≥ 30 mm and a posterior mitral valve leaflet ≥17 mm.33,37,38

This leaflet change plays an important role in the mechanisms responsible for LVOT obstruction, and, consequently, for the generated subaortic gradient, thereby also interfering with treatment options and strategies.33

 Trabeculations

Hypertrabeculation can be defined as a network of prominent trabeculations, particularly those involving the mid-apical region of the inferior and lateral LV wall. Its assessment is visual on short-axis images of the distal two-thirds of the LV and when trabeculations occupy >50% of the myocardial cavity or >50% of the endocardial perimeter.37

LV noncompaction, characterized by increased LV trabeculations, shares a genetic basis with some HCM genetic mutations; thus, the two pathologies can coexist and are described as being associations of different sarcomere gene mutations. Therefore, this may be a finding in patients diagnosed with HCM.39

 Papillary muscle

HCM can also present varied phenotypic disorders involving the papillary muscles. Up to 50% of cases present with a greater number of papillary muscles (three to four). Papillary muscle hypertrophy is also a disorder of HCM, including the presence of LE after the injection of gadolinium-based contrast.40,41

Another characteristic, especially on CMR, is anteriorization of the anterolateral papillary muscle. This change is identified on CMR in mid-basal sections of the LV short axis, where more than half of the anterolateral papillary muscle remains above an imaginary line dividing the left ventricular cavity into two equal parts starting from the RV junction in the posterior septum.37

Some HCM cases present with direct insertion of the papillary muscle into the mitral valve leaflets with complete or partial absence of the chordae tendineae.37

 Apical-basal accessory muscle

The apical-basal accessory muscle configures another secondary HCM change and corresponds to a muscle band connected to the ventricular apex that runs longitudinally in the ventricular cavity and close to the anterior septum, reaching the basal septum of the anterior wall. Its presence is first analyzed in section 3C and then reviewed in LV short-axis images.37

 Myocardial crypts

Congenital abnormalities are related to myocardial fibers and have been described in both healthy and HCM patients (<5%).26,39,42 The crypts are perpendicular to the LV long axis and must penetrate more than 50% of the compacted myocardium in end diastole and collapse in end systole. Multiple crypts are commonly located mainly in the basal and inferior inferoseptal wall of the LV at the junction with the RV.43,44

The differential diagnosis between LV crypts and trabeculations becomes important, with the latter, unlike crypts, being parallel to the endocardial border and not penetrating the compacted myocardium.43

 Left atrium

The left atrium (LA) is commonly enlarged in cases of HCM; its size is related to increased morbidity and mortality rates since it is a risk marker for cardiovascular events. The cause of atrial enlargement is multifactorial and not yet fully established; however, it may be related to increased ventricular filling pressures and mitral regurgitation as well as mitral valve systolic anterior motion (SAM).45

Figure 2 shows some phenotypical findings that can be seen in HCM cases.

Secondary phenotypic findings in hypertrophic cardiomyopathy. (A) Anterior anterolateral papillary muscle; (B) Apical-basal muscle accessory band; (C) Direct insertion of the papillary muscle into the anterior leaflet of the mitral valve; (D) Supraventricular right ventricular crest; (E) Crypts in the left ventricular lower basal wall; and (F) Left ventricular hypertrabeculation.

Functional changes

Together with the reported heterogeneous phenotypic changes, HCM also involves extremely important functional changes that require evaluation in this population.

Systolic function

Ventricular volumes are often reduced in HCM; therefore, LVEF is often overestimated (hyperkinetic LV). Thus, LVEF is often inadequate for evaluating the disease course and guiding therapy.5,26 However, advanced HCM (5–10% of cases) is characterized by ventricular remodeling and consequent ventricular wall thinning and cavity dilation. At this point, the LVEF decreases.46 About 75–100% of end-stage HF patients have extensive LE (≥25% of ventricular mass). These patients are at high risk of HF-related complications of about 10% per year.26,47

 LVOT obstruction

LVOT obstruction occurs due to a complex anatomical relationship of the cardiac structures involving the basal septum, LVOT, mitral valve apparatus, and papillary muscles.26,48 This obstruction is present in 70% of the classic phenotypic presentations of HCM and associated with increased cardiovascular risk and worse prognosis.5,26

Cine magnetic resonance imaging (cine-MRI) can effectively identify the presence of mitral valve SAM in the long- and short-axis view and signs of increased blood flow velocity in the LVOT.49 In these cases, an MRI flow velocity mapping sequence (phase-contrast) can be used to estimate the peak velocity and, therefore, the systolic gradient. However, this method has few studies and limited evaluations compared to Doppler echocardiography.49,50 In addition, it is performed at rest, and up to one-third of patients with HCM show signs of LVOT obstruction only on exertion.5

Video 1 below shows a CMRI with SAM.

3C and 4C systolic anterior motion.

Diastolic dysfunction

Unlike systolic function, diastolic function is among the first markers of HCM and related to myocardial fiber disarray and fibrosis, even in the absence of hypertrophy, being useful for evaluating cardiomyopathy.26,51

This evaluation is well studied and consolidated in echocardiography using several parameters, including mitral transvalvular Doppler.52

 Role of resonance in HCM

CMR is an important diagnostic method in cardiology practice, with a fundamental role in HCM. CMR provides a detailed characterization of different HCM phenotypes, being used as a diagnostic and prognostic tool.29 This method allows the formation of tomographic images with high temporal and spatial resolution without the need for iodinated contrast.53 Cine-MRI sequences (steady-state free precession imaging) enable a detailed analysis of the endocardial and myocardial contour with an accurate analysis of myocardial thickness and function.29 Moreover, CMR has none of the image acquisition limitations found in echocardiography, such as limited echocardiographic windows and oblique ventricular measurements.53

Added to this, CMR allows the identification and quantification of myocardial fibrosis through LE with gadolinium-based contrast, thus identifying patients at high risk of experiencing cardiac events.29 It also features promising techniques such as T1 mapping, a very useful tool in the differential diagnosis of ventricular hypertrophies and the identification of interstitial myocardial fibrosis and extracellular volume.

Consequently, CMR has garnered an important role in HCM, especially when echocardiographic images are inadequate or suboptimal, and has proven more sensitive than echocardiography for detecting some hypertrophy phenotypes such as apical predominance and secondary phenotypic changes. Therefore, CMR should be routinely used in such patients.54,55

Table 1 shows the main hypertrophy patterns found in HCM cases.

CMR indications in HCM defined by the American Heart Association/ American College of Cardiology, 2020.
Recommendation Evidence level Recommendation
I B-NR In patients with suspected HCM and inconclusive echocardiography findings, CMR is indicated for diagnostic clarification
I B-NR In patients with LVH, when alternative diagnoses such as infiltrative storage diseases and athlete’s heart are considered, CMR is helpful
I B-NR In patients with HCM who are not identified as at high risk of cardiovascular events or when the decision for ICD remains uncertain after clinical evaluation (including personal assessment/family history/echocardiogram/electrocardiogram), CMR is beneficial to assess maximum ventricular thickness, LVEF, apical aneurysms, and extension of the area of myocardial fibrosis by LE
1 B-NR In patients with obstructive HCM, when the anatomic mechanism of obstruction is inconclusive on echocardiography, CMR is indicated to assess septal reduction indication and planning
2b C-EO In patients with HCM, repeat CMR with periodic contrast (after 3–5 years) to re-stratify cardiovascular risk may be considered to evaluate LE and other morphologic changes, including LVEF, apical aneurysms, and LVH

Source: Ommen et al.4 NR: nonrandomized; CMR: cardiac magnetic resonance; EO: expert opinion; HCM: hypertrophic cardiomyopathy; ICD: implantable cardioverter defibrillator; LE: late enhancement; LVEF: left ventricular ejection fraction; LVH: left ventricular hypertrophy.

Late enhancement

Through a noninvasive evaluation, LE CMR has a unique ability to identify and quantify areas of fibrosis in the myocardium, thereby providing important diagnostic and prognostic information.55

The histopathology of HCM-related fibrosis is diffusely present in the myocardium and constitutes a substrate for tachyarrhythmias and SCD.47,56

 LE pattern and distribution in HCM

The presence of LE in HCM has various distributions and location patterns. However, it is not commonly related to a specific coronary territory.45 It frequently presents a multifocal, heterogeneous, and mesocardial enhancement pattern in about 30% of patients, but transmural LE can also be found.55,57 The most common LE sites are the interventricular septum and the LV free wall, occurring in more than 30% of patients. However, focal enhancement can also be found in the free wall, RV insertion, interventricular septum, and apex.

Other structures outside the LV may also present LE areas, including the RV and papillary muscles.58 There is a correlation between myocardial thickness and the presence of LE, according to which the greater the LV hypertrophy, the greater the chance of LE.58-60

The literature also shows a consistent relationship between LVEF and the presence of LE. An extensive LE area is observed in patients with an LVEF < 50%; on the other hand, patients with hyperdynamic systolic function have comparatively smaller LE areas.58-60

Patients with LVEF at the lower limit of normal present with LE and ventricular volumes closer to those of end-stage patients, suggesting the need for closer clinical follow-up and serial imaging.56

 LE quantification

Different methods and protocols quantify the LE area in HCM. The most widely used technique is based on semiautomatic algorithms that identify areas with increased signal intensity corresponding to regions with LE. A region of interest is selected in the annular myocardium and a gray scale is applied, with a standard deviation (SD) above the signal intensity of the signaled region of interest and selecting the areas corresponding to the enhancement. In some studies, the correlation between LE quantification and 6SD showed a greater correlation with the visual analysis of the area of fibrosis presented, proven as more reproducible in practice.33,61

An important study published in 2014 by Chan et al. demonstrated that fibrosis ≥ 15% in relation to total LV mass is useful for identifying patients with a preserved LVEF at risk of progression to HF and SCD.62,63

 Risk stratification for SCD by LE

Risk stratification for SCD in HCM patients has been studied for a long time and is extremely important. Today, several risk scores and guidelines aid the appropriate selection of patients who are indicated for ICD as primary prevention, a therapy that is the main determinant that reduces HCM-related mortality. Major factors in this stratification include a family history of SCD, unexplained syncope, non-sustained ventricular tachycardia, end-stage HCM (with systolic dysfunction), apical aneurysm on echocardiography or CMR, and the presence of LE in more than 15% of the ventricular mass. Therefore, as LE is considered a major risk factor for SCD, it must be detected and quantified in these patients (Figure 3).29,63-65

Late enhancement quantification in a patient with hypertrophic cardiomyopathy using a semiautomatic algorithm and showing extensive myocardial fibrosis (±30% of the myocardial mass).

T1 mapping

Histologically, HCM fibrosis is diffuse and global and not fully recognized on LE. In this case, T1 mapping is a new and promising tool that can analyze the entire extracellular content and thus provide a better evaluation of this fibrosis pattern.66,67

The T1 mapping sequence, which measures T1 longitudinal relaxation time, is used to identify the extent of increased extracellular content in patients with HCM and may be superior to the consolidated LE technique due to its ability to achieve the early detection of fibrosis.68,69

The native T1 mapping and extracellular volume fraction, which are high at times in patients with HCM, can be used in the early stages of HCM for the early detection of interstitial fibrosis and aid in the differential diagnosis of hypertrophies.

 Tissue tracking analysis (strain)

New CMR techniques have emerged for the evaluation of myocardial deformation, including tissue tracking (TT), a noninvasive post-processing technique used to evaluate myocardial strain.70,71

In HCM, fibrosis and hypertrophy contribute to mechanical abnormalities of the myocardium. Wall stress associated with relative endocardial ischemia and fibrosis help decrease strain values. Therefore, strain – mainly global longitudinal strain – may be useful in differentiating between hypertrophy types (pathological or physiological). Global longitudinal strain was also indirectly proportional to the fibrosis values, being a possible predictor of arrhythmic events. The endocardial dysfunction noted in HCM leads to a reduced radial strain. The literature showed a TT analysis with reduced longitudinal, radial, and circumferential strain values in patients with HCM versus the control group (Figure 4).70,71

(A) Bull’s eye analysis of global longitudinal strain by tissue tracking in a patient with hypertrophic cardiomyopathy; (B) Native T1 mapping analysis showing increased values in relation to normal; and (C) T1 parametric mapping.

Videos 2 and 3 show a tissue-tracking analysis using CMRI and 3D reconstruction.

Short-axis strain

3D LV strain

Differential diagnosis

LVH is a heterogeneous myocardial involvement with multifactorial causes related to several heart diseases that can be physiological as in athletes. Therefore, it is necessary to emphasize the importance of the differential diagnosis and diagnostic complexity of hypertrophy.

Infiltrative diseases

Although HCM is the main cause of unexplained LVH in adults, other infiltrative diseases such as amyloidosis, Fabry disease, and Danon disease have increased myocardial thickness as a phenotypic presentation37 and enter the differential diagnosis of hypertrophic phenotypes. Although morphological findings on CMR may suggest the etiology of ventricular hypertrophy and allow the differential diagnosis between infiltrative diseases and HCM, the hypertrophy pattern is not pathognomonic.23 On the other hand, although not definitive, LE may provide stronger differentiation data. Amyloidosis presents a characteristic LE pattern represented by subendocardial and subsequent transmural enhancement with difficult annulling due to extracellular glycoprotein deposits.55 T1 mapping, as already mentioned, can be an extremely useful tool in this differentiation since it allows the quantification of native myocardial T1. Native T1 values are higher in amyloidosis than in HCM but reduced in Fabry disease.55 Analysis of the data obtained by CMR associating morphological and functional criteria, RT, and T1 mapping are fundamental to a more accurate differentiation.

 Noncompaction myocardium

The higher spatial resolution of CMR tests showed that cases with a previous diagnosis of apical HCM presented significantly increased ventricular trabeculations rather than hypertrophy and were reclassified to noncompaction myocardium. These pathologies have a common genetic basis and may be associated.72,73

 Hypertensive heart disease

Patients exposed to arterial hypertension for the long term that is not adequately treated are reasonably likely to develop symmetrical LVH between the septum and the LV free wall (concentric hypertrophy). However, hypertensive heart disease is rarely associated with LVOT obstruction8 or the phenotypic findings described herein.

Thus, CMR may be important for detecting myocardial thickness changes after antihypertensive drug treatment, when hypertrophy regression favors the diagnosis of hypertensive heart disease.29

 Athlete’s heart

In clinical practice, the distinction between athlete’s physiological hypertrophy and pathological hypertrophy is a diagnostic challenge of important clinical relevance, with HCM causing one-third of SCD events in young competitive athletes.74

In this case, CMR can be useful for hypertrophy follow-up after physical deconditioning (16–18 months).74 In the athlete’s physiological hypertrophy, a regression of at least 2 mm in myocardial thickness is expected, while in HCM, the thickness is expected to remain the same. Another aspect is that LE is not expected to occur in patients with athlete’s heart. LE is a factor that corroborates the diagnosis of HCM.75

The athlete’s physiological hypertrophy does not usually progress with very increased thicknesses despite having similar ventricular mass values to those of other pathological hypertrophies (e.g., HCM, hypertensive heart disease) in addition to increased ventricular volumes and a decreased LVEF.74

Asymmetry is also a debatable differential diagnosis factor that affects up to 6% of patients with HCM and concentric hypertrophy.74 Maron et al. showed that 43% of athletes with SCD due to HCM had a normal septum/free wall ratio on autopsy.76

 Outlook

CMR techniques have showed remarkable advancement and evolution in recent years in addition to a growing role in the diagnostic and prognostic evaluation of the most diverse cardiomyopathies.

However, techniques such as TT for analyzing the myocardial infarction strain have not yet been fully applied in clinical practice and are currently used mainly for scientific research. Another technique with promising prospects is the 4D-flow analysis. This innovative technique provides a visual analysis of the blood flow, velocity, and pattern, allowing the choice of the correct plane to analyze the appropriate measurements with advantages in relation to the two-dimensional analysis performed by the phase-contrast technique already consolidated in resonance testing.77

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Prognostic value of quantitative contrast-enhanced cardiovascular magnetic resonance for the evaluation of sudden death risk in patients with hypertrophic cardiomyopathy. Circulation. 2014;130(6):484-95. doi: https://doi.org/10.1161/CIRCULATIONAHA.113.007094 Chan RH Maron BJ Olivotto I Pencina MJ Assenza GE Haas T et al Prognostic value of quantitative contrast-enhanced cardiovascular magnetic resonance for the evaluation of sudden death risk in patients with hypertrophic cardiomyopathy Circulation 2014 130 6 484 495 https://doi.org/10.1161/CIRCULATIONAHA.113.007094 64. Maron MS, Rowin EJ, Wessler BS, Mooney PJ, Fatima A, Patel P, et al. Enhanced American College of Cardiology/American Heart Association Strategy for Prevention of Sudden Cardiac Death in High-Risk Patients With Hypertrophic Cardiomyopathy. JAMA Cardiol. 2019;4(7):644-57. doi: https://doi.org/10.1001/jamacardio.2019.1391 Maron MS Rowin EJ Wessler BS Mooney PJ Fatima A Patel P et al Enhanced American College of Cardiology/American Heart Association Strategy for Prevention of Sudden Cardiac Death in High-Risk Patients With Hypertrophic Cardiomyopathy JAMA Cardiol 2019 4 7 644 657 https://doi.org/10.1001/jamacardio.2019.1391 65. Maron BJ, Rowin EJ, Maron MS. Paradigm of Sudden Death Prevention in Hypertrophic Cardiomyopathy. Circ Res. 2019;125(4):370-8. doi: https://doi.org/10.1161/CIRCRESAHA.119.315159 Maron BJ Rowin EJ Maron MS Paradigm of Sudden Death Prevention in Hypertrophic Cardiomyopathy Circ Res 2019 125 4 370 378 https://doi.org/10.1161/CIRCRESAHA.119.315159 66. Puntmann VO, Voigt T, Chen Z, Mayr M, Karim R, Rhode K, et al. Native T1 mapping in differentiation of normal myocardium from diffuse disease in hypertrophic and dilated cardiomyopathy. JACC Cardiovasc Imaging. 2013;6(4):475-84. doi: https://doi.org/10.1016/j.jcmg.2012.08.019 Puntmann VO Voigt T Chen Z Mayr M Karim R Rhode K et al Native T1 mapping in differentiation of normal myocardium from diffuse disease in hypertrophic and dilated cardiomyopathy JACC Cardiovasc Imaging 2013 6 4 475 484 https://doi.org/10.1016/j.jcmg.2012.08.019 67. Dass S, Suttie JJ, Piechnik SK, Ferreira VM, Holloway CJ, Banerjee R, et al. Myocardial tissue characterization using magnetic resonance noncontrast t1 mapping in hypertrophic and dilated cardiomyopathy. Circ Cardiovasc Imaging. 2012;5(6):726-33. doi: https://doi.org/10.1161/CIRCIMAGING.112.976738 Dass S Suttie JJ Piechnik SK Ferreira VM Holloway CJ Banerjee R et al Myocardial tissue characterization using magnetic resonance noncontrast t1 mapping in hypertrophic and dilated cardiomyopathy Circ Cardiovasc Imaging 2012 5 6 726 733 https://doi.org/10.1161/CIRCIMAGING.112.976738 68. Sado DM, White SK, Piechnik SK, Banypersad SM, Treibel T, Captur G, et al. Identification and assessment of Anderson-Fabry disease by cardiovascular magnetic resonance noncontrast myocardial T1 mapping. Circ Cardiovasc Imaging. 2013;6(3):392-8. doi: https://doi.org/10.1161/CIRCIMAGING.112.000070 Sado DM White SK Piechnik SK Banypersad SM Treibel T Captur G et al Identification and assessment of Anderson-Fabry disease by cardiovascular magnetic resonance noncontrast myocardial T1 mapping Circ Cardiovasc Imaging 2013 6 3 392 398 https://doi.org/10.1161/CIRCIMAGING.112.000070 69. Sado DM, Flett AS, Banypersad SM, White SK, Maestrini V, Quarta G, et al. Cardiovascular magnetic resonance measurement of myocardial extracellular volume in health and disease. Heart. 2012;98(19):1436-41. doi: https://doi.org/10.1136/heartjnl-2012-302346 Sado DM Flett AS Banypersad SM White SK Maestrini V Quarta G et al Cardiovascular magnetic resonance measurement of myocardial extracellular volume in health and disease Heart 2012 98 19 1436 1441 https://doi.org/10.1136/heartjnl-2012-302346 70. Jung HN, Kim SM, Lee JH, Kim Y, Lee SC, Jeon ES, et al. Comparison of tissue tracking assessment by cardiovascular magnetic resonance for cardiac amyloidosis and hypertrophic cardiomyopathy. Acta Radiol. 2020;61(7):885-93. doi: https://doi.org/10.1177/0284185119883714 Jung HN Kim SM Lee JH Kim Y Lee SC Jeon ES et al Comparison of tissue tracking assessment by cardiovascular magnetic resonance for cardiac amyloidosis and hypertrophic cardiomyopathy Acta Radiol 2020 61 7 885 893 https://doi.org/10.1177/0284185119883714 71. Neisius U, Myerson L, Fahmy AS, Nakamori S, El-Rewaidy H, Joshi G, et al. Cardiovascular magnetic resonance feature tracking strain analysis for discrimination between hypertensive heart disease and hypertrophic cardiomyopathy. PLoS One. 2019;14(8):e0221061. doi: https://doi.org/10.1371/journal.pone.0221061 Neisius U Myerson L Fahmy AS Nakamori S El-Rewaidy H Joshi G et al Cardiovascular magnetic resonance feature tracking strain analysis for discrimination between hypertensive heart disease and hypertrophic cardiomyopathy PLoS One 2019 14 8 e0221061 https://doi.org/10.1371/journal.pone.0221061 72. Kelley-Hedgepeth A, Towbin JA, Maron MS. Images in cardiovascular medicine. Overlapping phenotypes: left ventricular noncompaction and hypertrophic cardiomyopathy. Circulation. 2009;119(23):e588-9. doi: https://doi.org/10.1161/CIRCULATIONAHA.108.829564 Kelley-Hedgepeth A Towbin JA Maron MS Images in cardiovascular medicine. Overlapping phenotypes: left ventricular noncompaction and hypertrophic cardiomyopathy Circulation 2009 119 23 e588 e589 https://doi.org/10.1161/CIRCULATIONAHA.108.829564 73. Spirito P, Autore C. Apical hypertrophic cardiomyopathy or left ventricular non-compaction? A difficult differential diagnosis. Eur Heart J. 2007;28(16):1923-4. doi: https://doi.org/10.1093/eurheartj/ehm266 Spirito P Autore C Apical hypertrophic cardiomyopathy or left ventricular non-compaction? A difficult differential diagnosis Eur Heart J 2007 28 16 1923 1924 https://doi.org/10.1093/eurheartj/ehm266 74. Petersen SE, Selvanayagam JB, Francis JM, Myerson SG, Wiesmann F, Robson MD, et al. Differentiation of athlete’s heart from pathological forms of cardiac hypertrophy by means of geometric indices derived from cardiovascular magnetic resonance. J Cardiovasc Magn Reson. 2005;7(3):551-8. doi: https://doi.org/10.1081/jcmr-200060631 Petersen SE Selvanayagam JB Francis JM Myerson SG Wiesmann F Robson MD et al Differentiation of athlete’s heart from pathological forms of cardiac hypertrophy by means of geometric indices derived from cardiovascular magnetic resonance J Cardiovasc Magn Reson 2005 7 3 551 558 https://doi.org/10.1081/jcmr-200060631 75. Maron BJ. Distinguishing hypertrophic cardiomyopathy from athlete’s heart physiological remodelling: clinical significance, diagnostic strategies and implications for preparticipation screening. Br J Sports Med. 2009;43(9):649-56. doi: https://doi.org/10.1136/bjsm.2008.054726 Maron BJ Distinguishing hypertrophic cardiomyopathy from athlete’s heart physiological remodelling: clinical significance, diagnostic strategies and implications for preparticipation screening Br J Sports Med 2009 43 9 649 656 https://doi.org/10.1136/bjsm.2008.054726 76. Maron BJ, Roberts WC, McAllister HA, Rosing DR, Epstein SE. Sudden death in young athletes. Circulation. 1980;62(2):218-29. doi: https://doi.org/10.1161/01.cir.62.2.218 Maron BJ Roberts WC McAllister HA Rosing DR Epstein SE Sudden death in young athletes Circulation 1980 62 2 218 229 https://doi.org/10.1161/01.cir.62.2.218 77. Nordmeyer S, Riesenkampff E, Messroghli D, Kropf S, Nordmeyer J, Berger F, et al. Four-dimensional velocity-encoded magnetic resonance imaging improves blood flow quantification in patients with complex accelerated flow. J Magn Reson Imaging. 2013;37(1):208-16. doi: https://doi.org/10.1002/jmri.23793 Nordmeyer S Riesenkampff E Messroghli D Kropf S Nordmeyer J Berger F et al Four-dimensional velocity-encoded magnetic resonance imaging improves blood flow quantification in patients with complex accelerated flow J Magn Reson Imaging 2013 37 1 208 216 https://doi.org/10.1002/jmri.23793 10.47593/2675-312X/20223504erer_15p Artigo de Revisão Cardiomiopatia Hipertrófica: Uma Revisão pelo Olhar da Ressonância Magnética 0000-0003-1530-3795 Valério Raul Serra 1 Concepção e desenho da revisão, redação do manuscrito 0000-0002-3711-1754 Bittencourt Marcio Sommer 1 2 Concepção e desenho da revisão, Revisão crítica do manuscrito quanto ao conteúdo intelectual 0000-0001-7302-7448 Uellendahl Marly M. 1 3 redação do manuscrito, Revisão crítica do manuscrito quanto ao conteúdo intelectual Brasil DASA, São Paulo, SP, Brasil. Brasil Centro de Pesquisa Clínica e Epidemiológica do Hospital Universitário da USP, São Paulo, SP, Brasil. Brasil Universidade federal de São Paulo – UNIFESP, São Paulo, SP, Brasil. Correspondência: Marly M. Uellendahl • R. Joaquim Nabuco, 1560, Brooklyn Paulista, SP, Brasil, CEP: 04621-005. E-mail: mauellendahl@gmail.com

Conflito de interesses

Os autores declaram não terem conflitos de interesse.

Editor responsável pela revisão: Daniela do Carmo Rassi Frota

 Resumo

A cardiomiopatia hipertrófica é a cardiopatia genética mais frequente na população geral e é caracterizada por uma hipertrofia ventricular esquerda assimétrica. Entretanto, as alterações fenotípicas desta cardiomiopatia vão muito além da hipertrofia ventricular, e incluem alterações do aparato valvar mitral, dos músculos papilares e do ventrículo direito. Devido à dificuldade no diagnóstico diferencial entre as múltiplas causas de hipertrofia, a ressonância magnética cardíaca vem cumprindo um papel fundamental na avaliação diagnóstica e prognóstica desta cardiomiopatia. A cine-ressonância magnética na definição da localização e extensão da hipertrofia, o realce tardio, na detecção das áreas de fibrose miocárdica e técnicas mais recentes como o Mapa de T1 que avalia a fibrose intersticial e o volume extracelular; e finalmente o Tissue Tracking na análise da deformação miocárdica.

 Cardiomiopatia Hipertrófica Ressonância Magnética Técnicas de Imagem Cardíaca Introdução

A cardiomiopatia hipertrófica (CMH) foi descrita pela primeira vez pelo patologista inglês Robert Donald Teare, no relato de uma série de oito casos em que, post mortem, observou-se a presença de hipertrofia assimétrica miocárdica, sendo que sete desses casos apresentaram quadro de morte súbita (MS).1

A prevalência da CMH é de 1:500 indivíduos na população geral, sendo a patologia cardíaca de origem genética mais frequente. Apresenta acometimento semelhante entre os sexos, apesar de as mulheres serem mais subdiagnosticadas e apresentarem maior idade e cardiomiopatia mais avançada na avaliação inicial.2-4

O diagnóstico desta patologia é feito ao observar um aumento inexplicado da espessura da parede do ventrículo esquerdo (VE) – hipertrofia ≥15mm na diástole final e em qualquer segmento ventricular, com acometimento restrito ao coração e na ausência de outras patologias que possam provocar hipertrofia semelhante.3,4 No entanto, alterações morfológicas do aparato valvar mitral, dos músculos papilares, presença de fibrose miocárdica e doença microvascular também compõem o espectro dessa doença.5

A hipertrofia ventricular esquerda (HVE), encontrada na CMH, apresenta padrões fenotípicos heterogêneos, que podem cursar com variados tipos de HVE (assimétrica, simétrica, focal ou difusa) e em diferentes localidades da parede ventricular (do ápice à base do coração). Outras manifestações de extrema importância na avaliação dessa cardiomiopatia incluem a obstrução ao fluxo na via de saída do VE (VSVE) e alterações da fração de ejeção do VE (FEVE).6-10

A hipertrofia miocárdica nesses pacientes é explicada por achados histopatológicos característicos com hipertrofia das fibras miocárdicas, que mostram-se desorganizadas, assim como disfunção microvascular, com consequente isquemia silenciosa e posterior fibrose intersticial.11

A expectativa de vida nos portadores de CMH é, em sua maioria, semelhante à da população sem cardiomiopatia,12,13 porém pequena parcela possui maior risco de eventos cardiovasculares como MS, insuficiência cardíaca (IC) e acidente vascular encefálico (AVE).13-15 Estima-se que em torno de 30 a 40% dos pacientes portadores de CMH desenvolverão eventos adversos relacionados à cardiopatia. Entretanto, com o arsenal terapêutico existente hoje, especialmente relacionado à estratificação de risco e implante de cardiodesfibrilador implantável (CDI), a mortalidade nesses pacientes, mesmo nos quadros mais graves, reduziu-se a menos que 1% ao ano.4

 Genética

A CMH é uma doença genética, autossômica dominante, causada pela mutação em diferentes genes que codificam as proteínas do sarcômero cardíaco.5,16

Foram identificadas mais de 1.500 mutações, em mais de 13 genes diferentes, que interferem na codificação das proteínas contráteis do sarcômero. Apesar de inúmeras mutações conhecidas, as com maior prevalência estão localizadas nos genes da beta-miosina de cadeia pesada (MYH7) e na proteína C ligada a miosina (MYBPC3).4,5 Estima-se que quase todo paciente que apresenta alguma mutação relacionada à CMH demonstrará evidências fenotípicas, principalmente com aumento da espessura miocárdica, até o início da vida adulta.17-20

O teste genético pode identificar a mutação em até 30 a 60% dos pacientes com fenótipo de CMH. Porém, parte significativa dos pacientes com alteração fenotípica não apresenta base genética reconhecida.4,21-23

É importante ressaltar que a alteração genética não guarda correlação com fenótipo do indivíduo, podendo mutações genéticas semelhantes apresentarem fenótipos diferentes da cardiomiopatia.24

A vantagem da confirmação genética é a oportunidade de testar parentes de primeiro grau e, por consequente, um rastreamento em cascata, conseguindo-se, assim, realizar uma avaliação precoce e seguimento, se indicado, desses pacientes.6,19,22,25 Estima-se que, em parentes em que se identifique a mutação gênica, haja uma alta probabilidade de desenvolvimento das alterações fenotípicas em algum momento da vida, portanto, o seguimento com exames de imagem é indicado. Em contrapartida, parentes que não carregam a mutação genética, não apresentam risco futuro de manifestar a doença e não necessitam de seguimento clínico.22,23

 Apresentações fenotípicas das hipertrofias ventriculares esquerdas

Dentro do espectro da CMH existem diferentes padrões de hipertrofia que compõem esse fenótipo. O segmento mais comum de HVE, que está envolvido em até 70% dos casos, é a confluência do septo anterior basal com a parede livre anterior contígua, sendo frequente o segmento de maior espessura.26-28

Em seguida, a segunda região mais frequente de hipertrofia é o septo posterior médio-apical do VE.8,29

Porém, vale ressaltar que a maioria dos fenótipos apresentam hipertrofia em mais de 50% do miocárdio total. Por outro lado, alguns casos podem apresentar hipertrofia focal, principalmente nas regiões de septo anterior basal ou no segmento anterior basal. Nota-se que esses casos de hipertrofia focal podem apresentar massa miocárdica normal (até 20%) e, mesmo assim, ter o diagnóstico clínico de CMH, constituindo maior desafio diagnóstico, especialmente ao ecocardiograma.7,26,28,30

Outro fenótipo de extrema importância, porém menos frequente, é a hipertrofia da região médio-ventricular, que, por provocar uma obstrução dinâmica do VE, favorece o surgimento de arritmias ventriculares, necrose miocárdica e, principalmente, a formação de aneurisma apical, permitindo formação de trombos e eventos embólicos sistêmicos.27,31

A hipertrofia ventricular apical, encontrada em 5 a 25% dos casos, também é um fenótipo heterogêneo da CMH, com predomínio nos segmentos apicais e frequentemente relacionada à inversão das ondas T no eletrocardiograma.32

A Figura 1 mostra os principais padrões de hipertrofia encontrados nos casos de CMH.

Exame de RMC mostrando cortes longitudinais (4C, 3C, 2C) com os principais padrões de CMH. (A) CMH com predomínio septal; (B) CMH com predomínio apical; (C) CMH com predomínio médioventricular.

Outras alterações fenotípicas na CMH

A CMH, além da típica HVE, apresenta outras manifestações cardíacas que, com o aumento da utilização da ressonância magnética cardíaca (RMC), ficaram mais evidentes e precisam ser consideradas e destacadas, no sentido de se reduzir a falha no diagnóstico.

Ventrículo direito

Com a utilização da RMC como método diagnóstico nos casos de CMH, foi possível demonstrar que até um terço dos pacientes apresentam hipertrofia ventricular direita (considerada de espessura ≥8mm), associada à já conhecida HVE. Esses pacientes também podem evoluir com aumento da massa total do ventrículo direito (VD).33

A principal região de hipertrofia do VD é na inserção da parede livre do VD, no septo interventricular anterior ou posterior. Além da hipertrofia ventricular, outras alterações fenotípicas podem ser encontradas no VD, como a presença da crista supraventricular (estrutura muscular adjacente ao septo interventricular). Esse achado é importante, pois, devido à sua localização, pode, erroneamente, ser incluída no cálculo da massa ventricular esquerda e superestimar seu valor total.33

 Aneurismas apicais do ventrículo esquerdo

Os aneurismas apicais do VE constituem outra alteração fenotípica da CMH que teve um aumento diagnóstico importante com a maior utilização da RMC nesses pacientes. Além disso, com a utilização de contraste a base de gadolínio e com a técnica do realce tardio (RT), observa-se que esses aneurismas são compostos de tecido fibrótico, e essas alterações estão associadas ao maior risco de arritmias e MS, tendo importante impacto no tratamento e na avaliação de implante de CDI. Portanto, faz-se necessária a investigação desses aneurismas, para melhor acompanhamento e direcionamento diagnóstico desses pacientes.34-36

 Aparato valvar mitral

As alterações do aparato valvar mitral são consideradas manifestações fenotípicas primárias da CMH, independentes do grau de hipertrofia e de outros achados fenotípicos, o que sugere fisiopatologia mais complexa dessa cardiomiopatia, que vai além das alterações de proteínas ligadas ao sarcômero no miócito.33,37,38

Observa-se, na CMH, que até um terço dos pacientes podem apresentar folhetos mitrais alongados, com medidas do folheto anterior da valva mitral ≥30mm e do folheto posterior da valva mitral ≥17mm.33,37,38

Essa alteração dos folhetos tem papel contribuinte importante nos mecanismos responsáveis pela obstrução da VSVE e, consequentemente, do gradiente subaórtico gerado e, portanto, também tem interferência nas opções e estratégias de tratamento.33

 Trabeculações

A hipertrabeculação pode ser definida como uma rede de trabeculacões proeminentes, envolvendo, particularmente, a região médio-apical da parede inferior e lateral do VE. Sua avaliação é visual, feita nas imagens em eixo curto do VE nos dois terços distais e quando as trabeculações ocupam >50% da cavidade miocárdica ou >50% do perímetro endocárdico.37

A não compactação do VE, doença caracterizada por aumento das trabeculações do VE, tem base genética compartilhada com algumas mutações genéticas da CMH e, desse modo, as duas patologias podem coexistir e são descritas como sendo associações de diferentes mutações nos genes do sarcômero. Por isso, esse pode ser um achado encontrado em pacientes com diagnóstico de CMH.39

 Músculo papilar

A CMH também pode apresentar variadas alterações fenotípicas, envolvendo os músculos papilares. Em até 50% dos casos é possível observar maior número de músculos papilares (três a quatro papilares). A hipertrofia do músculo papilar também é alteração encontrada na CMH, inclusive com presença de RT, após a injeção de contraste a base de gadolínio.40,41

Outra característica encontrada, principalmente na RMC, seria a anteriorização do músculo papilar anterolateral. A identificação dessa alteração na RMC ocorre nos cortes médio-basais do eixo curto do VE, onde mais da metade do músculo papilar anterolateral permanece acima de uma linha imaginária traçada, dividindo a cavidade ventricular esquerda em duas partes iguais, a partir da junção do VD no septo posterior.37

É também possível observar, em alguns casos de CMH, a inserção direta do músculo papilar nos folhetos da valva mitral com completa ou parcial ausência das cordas tendíneas.37

 Músculo acessório apical basal

O músculo acessório apical basal configura outra alteração secundária da CMH e corresponde a uma banda muscular conectada ao ápice ventricular, que corre longitudinalmente na cavidade ventricular, perto do septo anterior, chegando no septo basal da parede anterior. Sua presença é primeiramente analisada no corte 3C e, depois, revista nas imagens de eixo curto do VE.37

 Criptas miocárdicas

São anormalidades congênitas relacionadas às fibras miocárdicas e descritas tanto em pacientes saudáveis como também pacientes com CMH (<5%).26,39,42 As criptas são perpendiculares ao eixo longo do VE e devem penetrar mais de 50% do miocárdio compactado na diástole final e colapsar na sístole final. É comum a presença de múltiplas criptas localizadas, principalmente, na parede inferosseptal basal e inferior do VE, na junção com o VD.43,44

Torna-se importante o diagnóstico diferencial entre as criptas e as trabeculações do VE, no qual as trabeculacões, diferentemente das criptas, são paralelas à borda do endocárdio e não penetram no miocárdio compactado.43

 Átrio esquerdo

O átrio esquerdo (AE) está comumente aumentado nos casos de CMH e seu tamanho está relacionado com o aumento da morbimortalidade, sendo um marcador de risco para eventos cardiovasculares. A causa do aumento atrial é multifatorial e ainda não é totalmente estabelecida, porém, pode estar relacionada a elevações das pressões de enchimento ventricular e ao refluxo mitral, estando relacionada ao movimento anterior sistólico (SAM) da valva mitral.45

A Figura 2 mostra algumas dos achados fenotípicos que podem ser encontradas nos casos de CMH.

Achados fenotípicos secundários na CMH. (A) Músculo papilar anterolateral anteriorizado; (B) Banda acessória muscular apicalbasal; (C) Inserção direta do músculo papilar no folheto anterior da valva mitral; (D) Crista supraventricular no VD; (E): criptas na parede inferior basal do VE; (F) hipertrabeculação do VE.

Alterações funcionais

Em conjunto com as heterogêneas alterações fenotípicas relatadas, a CMH também apresenta alterações funcionais de extrema importância, que necessitam ser avaliadas nessa população.

Função sistólica

Na CMH, os volumes ventriculares são frequentemente reduzidos e, portanto, a FEVE normalmente é superestimada (VE hipercinético). Dessa forma, a FEVE é, muitas vezes, inadequada para avaliação da evolução da doença e como guia terapêutico.5,26 Porém, as CMH avançadas (5 a 10% dos casos) são caracterizadas por remodelamento ventricular e consequente afilamento das paredes ventriculares e dilatação das cavidades. Nesse momento, ocorre a queda da FEVE.46 Em pacientes em estágio final, cerca de 75 a 100% apresentam RT de grande extensão (≥25% da massa ventricular). Esses pacientes apresentam risco elevado de complicações relacionadas à IC – próximo de 10% ao ano.26,47

 Obstrução da via de saída do ventrículo esquerdo

A obstrução da VSVE ocorre devido a uma relação anatômica complexa das estruturas cardíacas, envolvendo o septo basal, a VSVE, o aparato valvar mitral e os músculos papilares.26,48

Essa obstrução está presente em 70% das apresentações fenotípicas clássicas da CMH e associada ao aumento dos riscos cardiovasculares e pior prognóstico.5,26

A cinerressonância magnética (cine-RM) pode, de maneira eficaz, identificar a presença do SAM da valva mitral no eixo longo e no eixo curto e, também, identificar sinais de aumento da velocidade do fluxo sanguíneo na VSVE.49

Nesses casos, a sequência de mapeamento de velocidade de fluxo pela ressonância magnética (phase contrast) pode ser utilizada para estimar o pico de velocidade e, portanto, o gradiente sistólico. Porém, é um método com poucos estudos e avaliação limitada, se comparado ao estudo Doppler do ecocardiografia.49,50

Além disso, nota-se que é uma análise feita em repouso e até um terço dos pacientes com CMH apresentam sinais de obstrução da VSVE apenas ao esforço.5

O vídeo 1 demostra um exame de RMC com SAM.

Anterior sistólico 3C e 4C.

Disfunção diastólica

Diferente da função sistólica, a função diastólica é um dos primeiros marcadores da CMH e está relacionada ao desarranjo das fibras miocárdicas e à fibrose, mesmo na ausência de hipertrofia, sendo útil como avaliação da cardiomiopatia.26,51

Essa avaliação é bem estudada e consolidada na ecocardiografia, utilizando diversos parâmetros, entre eles o Doppler transvalvar mitral.52

 Papel da ressonância na cardiomiopatia hipertrófica

A RMC consolidou-se como importante método diagnóstico na prática cardiológica, com papel fundamental na CMH. A RMC propicia uma caracterização detalhada dos diversos fenótipos da CMH, sendo utilizada como ferramenta diagnóstica e prognóstica.29 Esse método permite a formação de imagens tomográficas com alta resolução temporal e espacial, sem a necessidade do uso de contraste iodado.53 É possível, por meio de sequências de cine-RM (steady-state-free-precession, SSFP), uma análise detalhada do contorno do endocárdio e do miocárdio, permitindo análise precisa das espessuras e da função miocárdica.29 Além disso, a RMC não apresenta as limitações encontradas no ecocardiograma relacionadas à obtenção da imagem, como janelas ecocardiográficas limitadas e medidas ventriculares oblíquas.53

Agregado a isso, a RMC permite a identificação e a quantificação da fibrose miocárdica, por meio da técnica do RT, com a utilização de contraste à base de gadolínio, podendo, dessa forma, identificar indivíduos com risco elevado de eventos cardíacos.29

Apresenta também técnicas promissoras, como o mapa de T1, ferramenta que pode ser muito útil no diagnóstico diferencial das hipertrofias ventriculares e na identificação de fibrose miocárdica intersticial e do volume extracelular.

Consequentemente, a RMC ganhou importante papel na CMH, especialmente quando as imagens ecocardiográficas são inadequadas ou subótimas, mostrando-se mais sensível que a ecocardiografia nas detecções de alguns fenótipos de hipertrofia (como a de predomínio apical), e nas detecções de alterações fenotípicas secundárias. Portanto, a RMC mostra-se método que deve ser considerado de uso rotineiro nestes pacientes.54,55

A Tabela 1 contempla as principais recomendações da utilização da RMC no contexto da CMH atualmente.

Indicações da RMC em CMH definidos pela AHA/ACC 2020.
Recomendação Nível Evidência Recomendação
I B-NR Para pacientes com suspeita de CMH e possuem ecocardiograma inconclusivo, RMC está indiciada para esclarecimento diagnóstico
I B-NR Para pacientes com HVE nos quais possuem diagnósticos alternativos considerados, como doenças infiltrativas de depósito e o coração do atleta, a RMC é útil.
I B-NR Para pacientes com CMH que não são identificados como alto risco de eventos cardiovasculares, ou, nos quais a decisão de CDI permanece incerta após avaliação clínica (inclui avaliação pessoal/ história familiar/ ecocardiograma/ eletrocardiograma), a RMC é benéfica para avaliar a espessura máxima ventricular, FEVE, aneurismas apicais e extensão de área de fibrose miocárdica pela técnica do realce tardio
1 B-NR Para pacientes com CMH obstrutiva no qual o mecanismo anatômico da obstrução é inconclusivo ao ecocardiograma, a RMC está indicada para avaliar a indicação e planejamento da redução septal
2b C-EO Para pacientes com CMH, a repetição de CMR com contraste periódica (3 a 5 anos) com propósito de reestratificar o risco cardiovascular pode ser considerada para avaliação do realce tardio e outras alterações morfológicas, incluindo FEVE, desenvolvimento de aneurismas apicais e da HVE

Fonte: Ommen et al.4 NR: não randomizado; RMC: ressonância magnética cardíaca; EO: opnião do especialista; CMH: cardiomiopatia hipertrófica; CDI: cardiodesfibrilador implantável; FEVE: fração de ejeção do ventrículo esquerdo; HVE: hipertrofia ventricular esquerda.

Realce tardio

Por meio de avaliação não invasiva, a RMC, utilizando a técnica do RT, tem capacidade única na identificação e quantificação de áreas de fibrose no miocárdio, além de fornecer importantes informações diagnósticas e prognósticas.55

A fibrose relacionada à CMH, em sua histopatologia, apresenta-se de forma difusa no miocárdio e compõe substrato para taquiarritmias e MS.47,56

 Padrão e distribuição de realce tardio na cardiomiopatia hipertrófica

A presença de RT na CMH possui padrões variados de distribuição e localização. Entretanto, comumente, não está relacionado a um território coronariano específico.45 Seu padrão mais frequente, encontrado em cerca de 30% dos pacientes, é um realce multifocal, heterogêneo e mesocárdico. Porém, RT com padrão transmural também pode ser encontrado nesses pacientes.55,57

O local mais encontrado de RT é no septo interventricular e na parede livre do VE, que ocorre em mais de 30% dos pacientes, porém, também é possível encontrar realces focais na parede livre, na inserção do VD, no septo interventricular e no ápex.

Além disso, outras estruturas fora do VE também podem apresentar áreas de RT, incluindo o VD e os músculos papilares.58

Existe correlação entre a espessura miocárdica e a presença de RT, segundo a qual, quanto maior a hipertrofia do VE, maior a chance de presença de RT.58-60

A literatura também mostra uma consistente relação entre a FEVE e a presença de RT. Observa-se, em pacientes com FEVE <50%, extensa área de RT e, por outro lado, em pacientes com função sistólica hiperdinâmica têm comparativamente áreas menores de RT.58-60

Tem-se também que pacientes que apresentam FEVE no limite inferior da normalidade apresentam RT e volumes ventriculares mais próximos aos pacientes em estágios finais, sugerindo que esses pacientes necessitam de acompanhamento clínico mais próximo e exames de imagens seriados para seguimento.56

 Quantificação do realce tardio

Existem diferentes maneiras e protocolos para quantificação da área de RT na CMH. A técnica mais amplamente utilizada é baseada em algoritmos semiautomáticos que são capazes de identificar áreas com intensidade de sinal aumentado, correspondente às regiões com RT. Seleciona-se uma área de interesse (ROI) no miocárdio anulado e aplica-se uma escala de cinza, com um desvio-padrão (DP) acima da intensidade do sinal da região de interesse sinalizada, selecionando as áreas correspondentes ao realce. Em alguns estudos, a correlação da quantificação do RT com 6DP apresentou maior correlação com a análise visual da área de fibrose apresentada, mostrando-se mais reprodutível na prática.33,61

Importante estudo publicado em 2014 por Chan et al. demostrou que um comprometimento de ≥15% de fibrose em relação à massa total do VE é útil em identificar pacientes com FEVE preservada que estão em risco de progressão para IC e MS.62,63

 Estratificação de risco de morte súbita pelo ralce tardio

A estratificação do risco de MS nos portadores de CMH é assunto de extrema importância e há muito estudado. Tem-se hoje diversos escores de risco e diretrizes para auxiliar na escolha certeira do paciente com indicação de CDIs como prevenção primária, terapia esta que se mostrou como principal determinante na diminuição da mortalidade por CMH. Fatores considerados maiores nessa estratificação incluem história familiar de MS, síncope inexplicada, taquicardia ventricular não sustentada, CMH em estágio final (com disfunção sistólica), aneurisma apical no ECO ou RMC e a presença de RT em mais de 15% da massa ventricular. Portanto, considerado fator de risco maior para MS nesses pacientes, fica clara a importância de detecção e quantificação do RT nestes pacientes.29,63-65 (Figura 3)

Quantificação do realce tardio em paciente com CMH, com algoritmo semiautomático, mostrando fibrose miocárdica extensa (±30% da massa miocárdica).

Mapa de T1

Histologicamente, a fibrose da CMH é difusa e global e não é toda reconhecida pela técnica de RT. Nesse caso, o mapa de T1 é ferramenta nova e promissora e pode fornecer análise de todo conteúdo extracelular e, assim, melhor avaliação desse padrão de fibrose.66,67

A sequência de mapa de T1, que mede o tempo de relaxamento longitudinal de T1, é utilizada para identificar a extensão do aumento de conteúdo extracelular nos pacientes com CMH e pode mostrar-se superior à técnica consolidada do RT, devido à capacidade de detecção precoce de fibrose.68,69

O mapa de T1 nativo e a fração de volume extracelular, que se encontram em tempos elevados na CMH, pode ser utilizado em fases iniciais da CMH, para detecção precoce de fibrose intersticial e auxiliar no diagnóstico diferencial de hipertrofias.

 Análise de tissue tracking (<italic>strain</italic>)

Na RMC, novas técnicas surgiram para a avaliação da deformação miocárdica, entre elas o tissue tracking (TT), uma técnica de pós-processamento não invasiva utilizada para avaliação do strain miocárdico.70,71

Na CMH, especificamente, tanto a fibrose como a hipertrofia contribuem para a anormalidade mecânica do miocárdio. O estresse da parede, em conjunto com a isquemia relativa do endocárdio e fibrose, contribui para a queda dos valores do strain. Portanto, o strain – principalmente o strain global longitudinal (SGL) – pode ser de boa utilidade para a diferenciação entre tipos de hipertrofias (patológicas ou fisiológicas). O SGL também se mostrou indiretamente proporcional aos valores de fibrose encontrados, sendo possível preditor de eventos arrítmicos. A disfunção endocárdica notada na CMH leva a uma redução do strain radial. Em dados da literatura, a análise do TT apresentou valores reduzidos de strain longitudinal, radial e circunferencial, nos pacientes com CMH, em comparação com o grupo controle.70,71(Figura 4)

(A) Bull’s eye da análise do strain longitudinal global pelo Tissue Tracking em paciente com CMH; (B) Análise do Mapa de T1 nativo, mostrando valores aumentados em relação a normalidade; (C) Mapa paramétrico T1.

Os vídeos 2 e 3 mostram a análise do tissue-tracking através da RMC e sua reconstrução em 3D.

Plano apical de 4 câmaras no repouso. MPR e PM normais.

Plano apical de 4 câmaras no repouso. MPR e PM normais.

Diagnóstico diferencial

A HVE é um acometimento miocárdico heterogêneo, de causa multifatorial e relacionado a diversas cardiopatias e até, como em atletas, fisiológica.

Portanto, faz-se necessário ressaltar a importância do diagnóstico diferencial das hipertrofias e sua complexidade diagnóstica.

Infiltrativas

Apesar de a CMH ser a principal causa de HVE não explicada em adultos, outras doenças infiltrativas como amiloidose, Fabry e Danon, também apresentam aumento da espessura miocárdica como manifestação fenotípica37 e entram no diagnóstico diferencial dos fenótipos hipertróficos. Embora os achados morfológicos da RMC possam sugerir a etiologia da hipertrofia ventricular e permitir o diagnóstico diferencial entre doenças infiltrativas e CMH, o padrão de hipertrofia não é patognomônico.23 Já o RT pode ser um dado de diferenciação mais forte, embora também não seja definitivo. A amiloidose apresenta um padrão característico de RT, representado por realce subendocárdico e, posteriormente transmural, com dificuldade de anulação decorrente do depósito extracelular de glicoproteínas.55 O mapa de T1, como já referido, pode ser uma ferramenta extremamente útil nessa diferenciação, uma vez que permite a quantificação do T1 nativo do miocárdio. Na amiloidose, os valores de T1 nativo encontram-se mais elevados em relação à CMH, enquanto na doença de Fabry, esses valores encontram-se reduzidos.55 A análise do conjunto de informações obtidas pela RMC, associando-se critérios morfológicos, funcionais, RT e mapa de T1 são fundamentais para essa diferenciação de forma mais acurada.

 Miocárdio não compactado

Com a maior resolução espacial nos exames de RMC, pode-se observar que casos com diagnóstico prévio de CMH apical apresentavam, no lugar da hipertrofia, aumento importante das trabeculações ventriculares e foram reclassificados para miocárdio não compactado. São patologias que guardam uma base genética em comum e podem estar associadas.72,73

 Cardiopatia hipertensiva

Pacientes expostos à hipertensão arterial por longo tempo e não tratada adequadamente apresentam chances razoáveis de apresentar HVE simétrica entre septo e parede livre do VE (hipertrofia concêntrica). Lembramos porém que a cardiopatia hipertensiva raramente está associada a obstruções na VSVE8 ou esteja associada aos achados fenotípicos descritos.

Nesse aspecto, a RMC pode ser importante em detectar as mudanças de espessura miocárdica após tratamento medicamentoso anti-hipertensivo, no qual a regressão da hipertrofia favorece o diagnóstico de cardiopatia hipertensiva.29

 Coração do atleta

Na prática clínica, a distinção da hipertrofia fisiológica do atleta e a hipertrofia patológica é desafio diagnóstico e de importante relevância clínica, sendo que a CMH é responsável por um terço das mortes súbitas em atletas jovens de competição.74

Neste caso, a RMC pode ser útil em realizar o segmento da hipertrofia após o descondicionamento físico (16 a 18 meses).74 Na hipertrofia fisiológica do atleta, espera-se uma regressão de pelo menos 2mm da espessura miocárdica, enquanto na CMH espera-se que a espessura se mantenha a mesma inicialmente observada. Outro aspecto é que não se espera encontrar RT nos pacientes com coração de atleta. A presença de RT é fator que corrobora o diagnóstico de CMH.75

Habitualmente a hipertrofia fisiológica do atleta não evoluiu com espessuras muito elevadas, apesar de apresentar valor de massa ventricular similares quando comparada com outras hipertrofias patológicas (como CMH ou cardiopatia hipertensiva), além de cursar com aumento dos volumes ventriculares e FEVE menores.74

Importante ressaltar que a assimetria também é um fator de diagnóstico diferencial discutível, devido à presença de até 6% dos pacientes com CMH e hipertrofia concêntricas.74 Maron et al. mostraram que 43% dos atletas que sofreram MS, devido à CMH, apresentavam relação septo/parede livre normais na autópsia.76

 Perspectivas

É notável o rápido avanço e evolução das técnicas da RMC nos últimos anos, além de seu crescente papel na avaliação diagnóstica e prognósticas das mais diversas cardiomiopatias.

Porém, técnicas como o TT para análise do strain miocárdico ainda não são totalmente aplicadas na prática clínica e são, hoje, utilizadas principalmente para pesquisa científica. Outra técnica com perspectiva promissora é a análise de fluxo 4D (4D-flow). Essa técnica inovadora possibilita a análise visual do fluxo sanguíneo, sua velocidade e padrões, permitindo escolher o plano correto para a análise das medidas adequadas, apresentando vantagens em relação a análise bidimensional realizada pela técnica do phase-contrast, já consolidada na prática da ressonância.77