 Hi everyone, I'm Dr. Vanti Gulhane. I specialize in cardiovascular imaging and this is an exhaustive tutorial on the role of cardiac MR in patients with hypertrophic cardiomyopathy. I have divided it into two parts. In the first part I'm going to discuss how a CMR study can be used to perform morphologic and functional assessment, as well as tissue characterization for identification and quantification of myocardial fibrosis in these patients of HCM. Further, there are several prognostic markers that can be established using CMR in these patients and I'm going to throw some light on it. Before we begin I just want to say I hope everyone back home is staying safe in this rather unfortunate time of the COVID pandemic and I also hope that you enjoy today's presentation. Thank you. The term hypertrophic cardiomyopathy implies an autosomal dominant genetic disease caused by mutations in the cardiac sarcoma protein genes. These patients have a higher prevalence of family history of HCM and sudden cardiac death. Hence, imaging is imperative in this condition and in an adult HCM is defined by a wall thickness more than 15 mm in one or more left ventricle myocardial segments as measured by any imaging technique or more than 30 mm in patients with a family history of hypertrophic cardiomyopathy that is not explained solely by loading conditions. In children, the diagnosis of HCM requires an LV wall thickness of more than two standard deviations greater than the predicted mean that is a Z score of more than two. It is important to note however that virtually any LV wall thickness even when within normal limits can be consistent with the presence of an HCM causing mutant gene. Here in this short axis CMR image the myocardial hypertrophy is clearly visible and the wall thickness measured was 45 mm. In this part one tutorial I'm going to review how cardiac MR is useful to understand various features of HCM and also review various prognostic factors of HCM that can be established on cardiac MR. Second part of the tutorial will focus on identifying differentials of myocardial hypertrophy such as infiltrative disorders, physiologic hypertrophy, hypertensive hypertrophy, mitochondrial disorders. First and foremost is morphological assessment of the cardiac for pattern of LV hypertrophy, popular remosal abnormalities, the mitral valve abnormalities and the left atrial dilatation. Various patterns of myocardial hypertrophy can be seen in HCM. The most common phenotype of HCM is asymmetric septal hypertrophy. As in this image we see that the basal intraceptal segment is grossly hypertrophied as compared to the anterior or the lateral wall. Other patterns include midventricular, apical, concentric, mass like hypertrophy. These are the examples. The first image on the upper left shows a concentric LV hypertrophy in the two chamber view. The upper right shows apical hypertrophy on the fourth chamber view. Lower images show on a fourth chamber view a mass forming hypertrophy involving the septum on the left image and a mass forming hypertrophy involving the lateral wall on the right image. Abnormalities are also common in the mitral valve and the subvalvular apparatus in patients with HCM. It has been reported that the mitral valve leaflet lens are longer in HCM patients as compared to the normal. Let us look at few examples. Image A is of an elderly man with an extraordinarily long anterior mitral leaflet measuring 33 mm. The posterior mitral leaflet is of normal length. Image F is of a 57-year-old man who had a preclinical HCM, had a genetic mutation, but a normal LV wall thickness of 9 mm and on careful examination are greatly elongated anterior mitral leaflet of 25 mm. The posterior mitral leaflet is of normal length. Again, it is not a rule that mitral valve would always be elongated in HCM. Here is an example of a 31-year-old woman who is showing a massive septal hypertrophy but a normal anterior mitral leaflet length. Then the subvalvular apparatus consists of the papillary muscles and cordy tendinge. A number of papillary muscle abnormalities can be noted in patients with HCM such as papillary muscle hypertrophy, accessory apical basal muscle bundle, antropycl papillary muscle displacement, double bipid morphology, hypermobile muscles. Papillary muscle hypertrophy is defined on CMR as a papillary muscle thickness of more than 11 mm or greater than the LV free wall thickness and the papillary muscle mass cut off of more than 7 grams per meter square has been proposed. Now the image labeled A shows the severe hypertrophy of the left ventricular septum and the hypertrophy of the papillary muscles. Image B is of another patient showing three papillary muscles which are hypertrophied. Now papillary muscle hypertrophy can also be present in systemic hypertension and is not unique to HCM. However, it is important to know that more often the hypertrophy of papillary muscle in hypertension is proportionate for the concentric LV hypertrophy as which is seen in this image here. Other anomalies of the subvalvular paratars are illustrated in this slide. The figure A shows an apical displacement of the papillary muscle resulting in leaflet slack and left ventricular outflow tract obstruction during systole. Image besides it shows an anomalous insertion of the cordy of the papillary muscle in the mid portion of the anterior mitral leaflet. The image on the lower right shows double bipid papillary muscles as an illustration and a CMR image. Further, the image on the left shows an anomalous direct insertion of the antrilateral papillary muscle to the anterior mitral leaflet without an intervening cordy tendinine in a patient with HCM. Image on the upper right shows an antropiical displacement of a papillary muscle which had a double bipid morphology. Myocardial crypts and hypertrabiculations are considered as sudden markers of the genetic disease in HCM. The image A is an echo as well as an illustration of a myocardial crypt. The image B shows a myocardial crypt at the arrowhead on this four-chamber CMR. Hypertrabiculations are when the trabeculian recess occupy either more than 50 percent of the LV cavity or more than 50 percent of the endocardial perimeter. So this completes the morphological assessment on CMR in patients with hypertrophic cardiomyopathy. Once the morphological assessment is done, functional assessment is the next step on CMR. LV systolic function can be accurately assessed on CMR using semi-automated functional assessment software. HCM is known to notoriously cause hyperdynamic systolic function in the early course of the disease but progress to systolic dysfunction later on. Other functional parameters of HCM includes the systolic anterior motion of the mitral leaflet, left ventricular outflow tract obstruction, cavity obliteration and mitral regurgitation. Let's look at it one by one. He is an example of three different patients with hyperdynamic as well as hypokinetic LV functions in patients with myocardial hypertrophy. First two patients had HCM, the last patient turned out to have an entirely different diagnosis. I will disclose this in the second part of my tutorial. Next here is this sine loop of a systolic anterior motion of mitral leaflet along with basal septal hypertrophy causing dynamic LVOT obstruction in a patient with HCM. Sometimes overt systolic anterior motion of the mitral leaflet may not be established but a bright signal of flow acceleration may be noted in LVOT on CMR as in this patient four chamber view on the right this can point to HCM. Then LVOT obstruction leads to secondary functional mitral regurgitation. On CMR the visualized regurgitan jet can be quantified by subtracting the forward aortic flow derived from phase contrast sequence from the LV stroke volume measured on the sine images. Left atrial dilatation is also common due to the restrictive physiology and mitral regurgitation. Left atrial size more than 45 mm is a consistent predictor for atrial fibrillation and stroke in patients with HCM. Then cavity obliteration is a specific sign of HCM and it is not seen in other conditions such as hypertension or athlete's heart. The three chamber cavity obliteration due to midwall hypertrophy in HCM. Patients with HCM also develop diastolic dysfunction which is usually defined on echocardiography. Diastolic dysfunction can also be assessed on CMR with various parameters. Simplest would be to look at the mitral inflow velocities and pulmonary vein flow which can be derived from phase contrast CMR. We can also calculate the pulmonary blood volume index on the first pass perfusion CMR which can differentiate between stages of diastolic dysfunction in patients with heart failure. Pulmonary blood volume index is also considered as a quantitative biomarker of hemodynamic congestion in HCM. Here is a method to evaluate the pulmonary transit time and pulmonary blood volume index on the first pass perfusion CMR. Two region of interest are drawn, one in the RV and the LV cavity. Signal intensity by time curves are plotted. Pulmonary transit time is defined by the time interval between the peaks of the two signal intensity by time curves for RV and LV respectively. The pulmonary blood volume index can be obtained by the product between the pulmonary transit time and the RV stroke volume index normalized by the RR interval. This method has been well described in the recent publication in the European Heart Journal and subscribers are encouraged to read through this part. I'm happy to share this with you in case you have trouble accessing it online. This completes the functional assessment of HCM on CMR. A very important application of CMR in HCM is tissue characterization for the presence of myocardial fibrosis, late gadolinium enhancement sequences obtained to identify myocardial fibrosis. In our study of about 100 HCM patients, various patterns of late gadolinium enhancement were found. The image A with RV insertion point enhancement, image B shows a diffuse myocardial enhancement, image C shows a mid-myocardial LV wall enhancement, image D shows a transmural enhancement in the interior wall, image E showing a mixed subendocardial mid-myocardial LV enhancement, image F showing the papillary muscle enhancement. Several studies are found that up to 65% have myocardial fibrosis and show late gadolinium enhancement. In case of diffuse myocardial fibrosis, supplementing T1 mapping is useful as in this case where late gadolinium enhancement could identify only superior and inferior RV insertion point fibrosis. Mid-myocardial fibrosis in the septum in this patient was identified on T1 mapping shown in image B and C as elevated native T1 time on the 1.5T scanner. Studies have shown that the extra cellular volume calculated by T1 mapping technique can be used to differentiate HCM from the athlete's remodelling. T2 mapping also shows promise. Presents of hyperintensity on T2 weighted CMR may represent advanced disease and higher T2 values of up to 61 milliseconds have been reportedly related to syncope in cases of asymmetric HCM when compared to the reference normal myocardial T2 value less than 50 milliseconds. Next, how do we establish prognosis in HCM using cardiac MR? Several clinical features that comprise high risk for sudden cardiac death in HCM includes a young age. Presents of non-sustained ventricular tachycardia. Maximum LV wall thickness of more than or equals to 30 mm. Family history of sudden cardiac death at a young age. Left atrial diameter of more than 45 mm. Presents of LVOD obstruction and a presence of abnormal exercise blood pressure response. Quantification of myocardial fibrosis is possible on CMR and myocardial fibrosis more than 50% of the LV mass on CMR has been shown to be associated with a two-fold increase in the risk of sudden cardiac death. This myocardial fibrosis serves as a prognostic feature on cardiac MR. Let me highlight issues with this. Different methods can be employed to quantify myocardial fibrosis on CMR such as manual contouring, two, three, five or six standard deviation techniques or full width at half maximum technique. However, quantification varies substantially with each of these techniques. For example, in this patient, manual quantification that is manually marking areas of fibrosis showed a calculated value of 22%. Using six standard deviation, myocardial fibrosis is found to be 29%. Using full width at half maximum technique, myocardial fibrosis was found to be 5% in the same patient. The six standard deviation work the best in our case. This is supported by studies that report six standard deviation techniques superior to other techniques to identify fibrosis in HCM patients, although this has not been histopathologically validated yet. To conclude, quantification of myocardial fibrosis can be done on CMR and the presence of more than 15% myocardial fibrosis on six standard deviation should be reported as it suggests a poor prognosis. Further, recently RV and LV long axis strain have been extensively studied on CMR as prognostic indicators. The study by Yang et al describes a simple method to calculate myocardial strain on the Cine images as the percentage change in the length between the epicardial board of LV apex and the midpoint of a line connecting the mitral and tricuspid annulus at endastelian and systeli respectively. The figure illustrates the contouring part. In the study published in the international journal of cardiology, the RV long axis strain was noted to be an independent predictor of adverse prognosis in HCM in addition to the RV ejection fraction. I have highlighted the increased strain measurements which were noted in both RV and LV in this study. Finally, it is possible to perform genotype phenotype analysis of HCM on CMR and patients with any genetic mutation are likely to demonstrate reverse curve HCM in comparison to sigmoidal HCM. The example on the left is of patient with MYPBC3 mutation showing reverse curvature HCM. Second patient also had a mutation or PKP2 mutation which maps to arrhythmogenic cardiomyopathy showing sigmoid curvature. Thus to conclude, CMR is a comprehensive assessment tool in patients with known or suspected HCM. CMR derived morphological and functional parameters as well as tissue characterization allows ascertaining the diagnosis also provides significant prognostic information and risk prediction for sudden cardiac death in patients with hypertrophic cardiomyopathy. This concludes the discussion on the role of CMR in HCM, the part 1. If you have any questions, feel free to contact me on avanti.gulane at penmedicine.upen.edu. Do follow me on Twitter. Also, do like this video, share and subscribe to our channel on youtubeindianradiologists.com. Thank you.