Coronary microvascular dysfunction in hypertrophic cardiomyopathy detected by Rubidium-82 positron emission tomography and cardiac magnetic resonance imaging

Journal of Nuclear Cardiology, Mar 2018

William E. Moody, Matthias Schmitt, Parthiban Arumugam

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Coronary microvascular dysfunction in hypertrophic cardiomyopathy detected by Rubidium-82 positron emission tomography and cardiac magnetic resonance imaging

Received Feb Coronary microvascular dysfunction in hypertrophic cardiomyopathy detected by Rubidium-82 positron emission tomography and cardiac magnetic resonance imaging William E. Moody 0 Matthias Schmitt 0 2 Parthiban Arumugam 0 0 Electronic supplementary material The online version of this article ( contains supplementary material, which is available to authorized users. Reprint requests: William E. Moody , PhD, MRCP , Department of Cardiology, Nuffield House, Queen Elizabeth Hospital Birmingham , Birmingham, B15 2TH , UK 1 Nuclear Medicine Centre, Manchester Royal Infirmary , Manchester , UK 2 Department of Cardiology, University Hospital of South Manchester NHS Foundation Trust , Wythenshawe, Manchester , UK 3 Department of Cardiology, Nuffield House, Queen Elizabeth Hospital Birmingham , Birmingham , UK CASE REPORT A 75-year-old South-East Asian man presented with exertional chest pain. Risk factors for coronary disease included hypertension, diabetes mellitus, hyperlipidaemia, and family history. High sensitivity Troponin was normal. An electrocardiogram (ECG) showed sinus rhythm with deep T wave inversion in leads I, aVL, V4V6 (Figure 1). Coronary angiography showed diffuse, non-obstructive disease (Figure 2). Rubidium-82 positron-emission tomography (PET) imaging demonstrated increased tracer uptake at rest, suggestive of left ventricular (LV) hypertrophy. There was adenosine stress-induced LV cavity dilation with reversible hypoperfusion in a left anterior descending artery territory (Figure 3A). The global myocardial perfusion reserve (MPR) was reduced at 1.22 ml/g/min (Figure 3B). In view of the resting ECG abnormality, high tracer uptake at rest and reduced global in the context of nonobstructed coronaries, cardiac magnetic resonance (CMR) imaging (3T Skyra) was performed to exclude a cardiomyopathy. This demonstrated marked regional variability in heart muscle thickness with a maximal wall thickness of 19 mm in the mid inferoseptum (Figure 4A). Left ventricular ejection fraction was supranormal (82%) with apical systolic cavity obliteration (see on-line Video A). Although there was only minimal late gadolinium enhancement seen involving the superior right ventricular insertion point (image not shown), native T1 was elevated at 1276 ms consistent with diffuse fibrosis (mid septum, normal range 1052 ± 23 ms; Figure 4B). Adenosine stress imaging demonstrated a circumferential epicardial-endocardial signal intensity gradient, most pronounced in areas of maximal myocardial thickness (Figure 4C, arrows; online Video B). DISCUSSION This case highlights the ability of both PET and CMR imaging to demonstrate impaired myocardial blood flow during vasodilator stress with adenosine in a patient with hypertrophic cardiomyopathy (HCM). In the absence of a coronary stenosis, these findings are consistent with microvascular dysfunction. Numerous pathophysiological factors have been implicated in the development of small vessel ischemia in HCM including thickening of intramural coronary arterioles, elevated regional wall stress associated with increased intracavity pressures resulting from outflow obstruction, disorganized cellular architecture with increased collagen deposition in the interstitium, and ventricular hypertrophy associated with a decrease in capillary density.1 In a study of 34 patients with HCM who underwent combined PET and CMR imaging, Sotgia et al. demonstrated a continuum of coronary microvascular ischemia ranging from those subjects with only mildly elevated wall thickness in whom hyperemic myocardial blood flow (MBF) is relatively preserved and late gadolinium enhancement absent, to those with greater hypertrophy, where MBF is increasingly impaired and replacement fibrosis more frequent and extensive.2 Similarly, pixel-wise quantitative CMR perfusion imaging in 35 HCM patients demonstrated an inverse association between hyperemic MBF and wall thickness, with a significantly lower probability of fibrosis in myocardial segments with increasing hyperemic MBF.3 These data provide support for the hypothesis that coronary microvascular dysfunction contributes to the development of myocardial fibrosis in HCM. Although in our case there was limited evidence of replacement fibrosis, T1-mapping was consistent with diffuse fibrosis, and this was associated with reduced hyperemic MBF and global MPR. We also demonstrated transient ischemic dilatation on PET which has been reported in up to half of HCM patients without epicardial coronary disease;4 this observation is also associated with reduced maximal global hyperemic MBF and MPR, as well as greater maximal wall thickness on echocardiography.4,5 More recently, PET imaging of 104 HCM patients demonstrated stressinduced LV cavity dilatation in 52% and this was associated with the stress trans-mural perfusion gradient, reduced global MPR and lower stress LV ejection fraction.6 The presence of microvascular dysfunction in patients with HCM has long been recognized as a strong predictor of clinical deterioration and mortality: in 2003, Cecchi et al. used PET to identify a stress MBF of \ 1.10 ml/g/min as the optimal cut-off for predicting adverse events.7 Further long-term outcome studies are required to clarify this threshold and to determine whether this phenomenon provides incremental prognostic utility beyond the factors already entered into the current HCM risk algorithm.8 Disclosure The authors have no conflicts of interest to declare. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 1. Maron MS , Olivotto I , Maron BJ , Prasad SK , Cecchi F , Udelson JE , Camici PG . The case for myocardial ischemia in hypertrophic cardiomyopathy . J Am Coll Cardiol . 2009 ; 54 : 866 - 75 . 2. Sotgia B , Sciagra R , Olivotto I , Casolo G , Rega L , Betti I , Pupi A , Camici PG , Cecchi F . Spatial relationship between coronary microvascular dysfunction and delayed contrast enhancement in patients with hypertrophic cardiomyopathy . J Nucl Med . 2008 ; 49 : 1090 - 6 . 3. Ismail TF , Hsu LY , Greve AM , Goncalves C , Jabbour A , Gulati A , Hewins B , Mistry N , Wage R , Roughton M , Ferreira PF , Gatehouse P , Firmin D , O'Hanlon R , Pennell DJ , Prasad SK , Arai AE . Coronary microvascular ischemia in hypertrophic cardiomyopathy - a pixel-wise quantitative cardiovascular magnetic resonance perfusion study . J Cardiovasc Magn Reson . 2014 ; 16 : 49 . 4. Bravo PE , Tahari A , Pozios I , Luo HC , Bengel FM , Wahl RL , Abraham MR , Abraham TP . Apparent left ventricular cavity dilatation during PET/CT in hypertrophic cardiomyopathy: Clinical predictors and potential mechanisms . J Nucl Cardiol . 2016 ; 23 : 1304 - 14 . 5. Bravo PE , Pinheiro A , Higuchi T , Rischpler C , Merrill J , Santaularia-Tomas M , Abraham MR , Wahl RL , Abraham TP , Bengel FM . PET/CT assessment of symptomatic individuals with obstructive and nonobstructive hypertrophic cardiomyopathy . J Nucl Med . 2012 ; 53 : 407 - 14 . 6. Yalcin H , Valenta I , Yalcin F , Corona-Villalobos C , Vasquez N , Ra J , Kucukler N , Tahari A , Pozios I , Zhou Y , Pomper M , Abraham TP , Schindler TH , Abraham MR . Effect of diffuse subendocardial hypoperfusion on left ventricular cavity size by (13)N-ammonia perfusion PET in patients with hypertrophic cardiomyopathy . Am J Cardiol . 2016 ; 118 : 1908 - 15 . 7. Cecchi F , Olivotto I , Gistri R , Lorenzoni R , Chiriatti G , Camici PG . Coronary microvascular dysfunction and prognosis in hypertrophic cardiomyopathy . N Engl J Med . 2003 ; 349 : 1027 - 35 . 8. Elliott PM , Anastasakis A , Borger MA , Borggrefe M , Cecchi F , Charron P , Hagege AA , Lafont A , Limongelli G , Mahrholdt H , McKenna WJ , Mogensen J , Nihoyannopoulos P , Nistri S , Pieper PG , Pieske B , Rapezzi C , Rutten FH , Tillmanns C , Watkins H. ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC) . Eur Heart J . 2014 ; 2014 (35): 2733 - 79 .

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William E. Moody, Matthias Schmitt, Parthiban Arumugam. Coronary microvascular dysfunction in hypertrophic cardiomyopathy detected by Rubidium-82 positron emission tomography and cardiac magnetic resonance imaging, Journal of Nuclear Cardiology, 2018, 1-5, DOI: 10.1007/s12350-018-1245-4