Shabana Kausar MD, Sibtain Jahangir MD
Rawalpindi Institute of Cardiology, Pakistan
Clinical History
A 48-year-old male normotensive, non-smoker, with no history of drug abuse presented in the emergency department with palpitations for last one hour and dyspnea of New York Heart Association (NYHA) class II for 5 months. He had similar episodes for past 6 years but with no definitive diagnosis. He has had diabetes for last 6 years controlled with oral hypoglycemics.He had first presented 5 years ago in the emergency department where diagnosis of ventricular tachycardia (VT) was made for which he was cardioverted pharmacologically. Again after 2 years he presented with same complaints, for which he was evaluated with echocardiography which showed normal dimensions with ejection fraction of 50%. Patient received medical treatment including beta blockers. There was no history of prolonged medical illness in the past or hospitalization, in addition no prior history of tuberculosis, radiation exposure or occupational exposure to any pathogen. For the latest complaints of VT, patient underwent electrical cardioversion in emergency department due to failed medical cardioversion. He was diagnosed with heart failure based on clinical signs and raised pro-B-type natriuretic peptide (pro-BNP) level up to 1270pg/ml (Normal reference 125pg/ml). The electrocardiogram (ECG) showed evidence of wide complex tachycardia at rate of 150bpm with atrioventricular (AV) dissociation with possible left free wall origin (Figure 1). His reverted ECG showed atrial fibrillation with singlet ventricular premature beats (Figure 2). Chest radiograph revealed cardiomegaly with fluffy calcific shadows over cardiac shadow (Figure 3).
 Figure 1: Wide complex tachycardia at rate of 150 bpm with AV dissociation. Leads I and AVL are negative suggestive of possible left free wall origin. |
 Figure 2: Twelve lead ECG with underlying atrial fibrillation with variable ventricular rate. Rare premature ventricular beat as a singlet. |
 Figure 3: Chest radiograph revealed cardiomegaly with fluffy calcific shadows over heart area. |
Echocardiogram shows dilated left atrium (LA) and right atrium (RA) and normal sized left ventricle (LV) with extensive echogenic foci at LV lateral wall, mitral annulus, posterior mitral leaflet and LA wall without significant valvular abnormalities (Figure 4 & Movie 1). LV systolic function appears moderately depressed on visual assessment.
 Movie 1: Apical 4 chamber view showing echogenic lateral LV wall, basal septum and mitral annular calcification (MAC) with tethering of lateral LV wall. Right heart is spared. |
 Figure 4: The figure shows various areas of hyperechoic foci basal septal calcification (as shown by white arrow). LV lateral wall calcium (indicated by blue arrow) and LA wall calcification (shown by yellow arrow). |
CMR Findings
CMR was planned after electrophysiology team opinion to determine possible arrhythmogenic substrate and tissue characterization. CMR was done on 3T Canon Vantage Titan scanner (Canon Medical Systems, Otawara, Tochigi, Japan) using steady state free precession (SSFP) cine imaging, T1 weighted (T1WI), T2 weighted (T2WI), T1 parametric mapping followed by gadolinium first pass perfusion, early and delayed late gadolinium enhancement (LGE) images. Cine images showed dilated LA with hypointense lesions involving lateral LV wall, basal inferior wall left AV groove. Severe LV systolic dysfunction due to akinetic tethering of lateral LV wall was noted. However, septal motion was spared, and right ventricle (RV) appeared normal in function and size (Movie 2, Figure 5). Quantitative evaluation of LV function showed LVEF of 36%. T2WI with fat saturation showed signal loss within myocardium indicated by arrows at various sections of LV stack (Figure 6). T1 maps revealed various hypointense foci within LV showing remarkably low T1 times of 92 ms and increased native T1 value of 1194 ms in the myocardium (Figure 7). The mitral regurgitation appeared mild with regurgitation fraction of 15% by indirect quantification method. The first pass perfusion at basal, mid and apical level showed areas of hypoperfusion, with possibility of caseous degeneration of calcium which appeared as bright areas within the core of hypoperfused lateral LV wall (Figure 8). LGE images showed scattered areas of low signal lesions in LV, LA and AV groove. LGE short axis images showed heterogenous enhanced core within hypoenhanced lesion in lateral LV wall, extensive LGE of non-ischemic pattern in mid and distal LV myocardium (Figure 9 and 10).
 Movie 2: Balanced SSFP cine four chamber (left), mid short axis (middle) and three chamber (right) showing dilated LA and hypointense lesions involving lateral LV wall, basal inferior wall, left AV groove areas. Severe LV systolic dysfunction due to akinesia of lateral LV wall, septal motion was spared. RV also appeared normal in function and size. |
 Figure 5: Balanced SSFP four chamber at peak systole showing dilated LA, possible dilated RA, normal sized LV with mild LV hypertrophy and hypointense lesion indicated by white arrow. |
 Figure 6: T2WI with fat saturation short axis stack showing signal loss within myocardium indicated by arrow at various sections. |
 Figure 7: Native T1 map at basal short axis slice of LV shows raised septal maps of 1211ms and markedly low maps of 92ms in anterolateral segment, areas of hypointense lesion. |
 Figure 8: Rest first pass perfusion at basal level showing areas of hypoperfusion (blue arrow). There is possible caseous degeneration of calcium which appears as brighter area within the core of hypoperfused lateral LV wall indicated by white arrow in this still image. |
 Figure 9: LGE images showing two chamber (left), four chamber (middle), and basal short axis (right) showing scattered areas of unenhanced lesion in LV, LA, and AV groove. |
 Figure 10: LGE short axis images showing heterogenic enhanced core within hypoenhanced lesion in lateral LV wall, there is extensive LGE of non-ischemic pattern in mid and distal LV. |
Conclusion
Patient subsequently underwent cardiac computed tomography (CT) to confirm suspicion of myocardial infiltration by calcium. Cardiac CT was performed on 64 slice Canon Aquilion scanner (Canon Medical Systems, Otawara, Tochigi, Japan). The non-contrast CT images showed extensive calcification (popcorn appearance) of LV, LA, AV groove and mitral annulus. There was no involvement of RV, coronaries and pericardium, the lung and mediastinal window also appeared normal and free of any calcium infiltration (Figure 12 & Movie 3).
Imaging features were suggestive of non-ischemic cardiomyopathy with infiltration by calcium. Patient was managed with standard heart failure medications as per guidelines including metoprolol, angiotensin receptor/neprilysin inhibitor (ARNI) 26/24 mg, spironolactone along with anticoagulant (apixaban). The search for the cause of his extensive myocardial calcification was made but no obvious cause was found. Despite thorough clinical evaluation and the use of multiple imaging modalities, the cause of the myocardial calcification remains idiopathic. All potential etiologies documented in the literature, such as ischemic heart disease, infiltrative cardiomyopathies (e.g. amyloidosis or sarcoidosis), and myocarditis, tuberculosis and hyperparathyroidism were systematically excluded based on the patient’s clinical history, imaging findings, and lack of suggestive features. His serum calcium levels and parathyroid hormone levels were within normal limits. However, due to socioeconomic constraints, we were unable to pursue genetic testing. Given the recurrent nature of the patient’s arrhythmias and the risk of sudden cardiac death, he was referred to the electrophysiology department for the placement of an implantable cardioverter-defibrillator (ICD). However, after looking at the details of cardiac imaging in this patient, ICD and medications may not be the cure of this disease and perhaps cardiac transplant would be required as a permanent solution.
 Figure 11: Non-contrast cardiac CT multiplanar reconstruction (MPR) images showing extensive popcorn shaped calcification in heart as shown by arrows. |
 Movie 3: Cranio-caudal of contrast enhanced axial cardiac CT showing extensive calcification of LV, LA, AV grooves and mitral annulus. There is no involvement of RV, coronaries, and pericardium. The lung window also appears normal. Also, noted is the aberrant right subclavian artery with a retro-esophageal course. |
Perspective
This case underscores the need for a multi-modal imaging approach in evaluating cardiac calcium and how it behaves on CMR. Cardiac calcification in coronaries, mitral annulus and pericardium are well known entities but massive myocardial calcification appearing as stone heart is a very rare finding. They may be classified in two principal forms: dystrophic and metastatic. However, idiopathic myocardial calcification is also mentioned in literature. The former represents the sequelae of local tissue damage like necrosis or degeneration, whereas the latter is the result of abnormal calcium-phosphate homeostasis due to renal failure, primary hyperparathyroidism, vitamin D deficiency and inflammatory process. It is also an uncommon complication of sepsis, usually found in patients with severe sepsis.[1] MAC is well known abnormality with its prevalence varies from 5% to 42% depending on the imaging modality used. Contrary to its name MAC is no more confined to MV annulus but studies examining surgical and autopsy samples have described extension of calcification into the LV, mitral leaflets, papillary muscle, chordae tendineae and left ventricular outflow tract (LVOT) with occasional continuous calcification of the aorto-mitral curtain extending up into the aortic valve. MAC is no longer regarded as a local, chronic and degenerative process resulting in precipitation of calcium and phosphate, but as an active and regulated molecular process that is related to lipid metabolism, hemodynamic stress, chronic kidney disease, bone and mineral metabolism and inflammation.[2] In this case there is extensive MAC, but the involvement of myocardium is the extension of MAC or MAC is secondary to myocardial disease, it is difficult to say. The case also highlighted the role of CT and CMR in excluding the differentials of MAC like tumor, thrombi and vegetation.
The common causes of myocardial calcification mentioned in literature are myocardial infarction, ventricular aneurysms, myocarditis, endomyocardial fibrosis, tuberculosis and systemic metabolic disease such as sarcoidosis and primary hyperoxaluria.[3] All these potential causes have been ruled out in this case based on clinical history and investigation profile. Tuberculosis being very prevalent in Asia and commonly involves lungs and pericardium with residual sequelae in organs affected, which is not found in this case. The presentation of myocardial calcification can vary from ventricular systolic dysfunction (heart failure reduced ejection fraction (HFrEF)), heart failure with preserved ejection fraction (HFpEF) or scar-related arrhythmias, although late-onset cardiomyopathy and associated ventricular arrhythmias due to diffuse myocardial calcifications has not been reported.[1] It can also be presented with isolated restrictive cardiomyopathy.[4]
As far as the management of myocardial calcification is concerned, it is challenging because of lack of response to medications and interventions like radiofrequency ablation. For instance, literature mentioned 19% of post-MI patients with myocardial calcification referred for VT ablation was associated with a high incidence of endocardial ablation failure.[5] There are no standardized imaging features available to classify specific subtypes of intra-myocardial calcifications. Cardiac CT and CMR imaging are important in confirming the diagnosis, and assessing the extent and location of myocardial calcium.[6]
A systemic review published in European Heart journal in 2024 reported that several medical conditions are associated with myocardial calcification but sepsis and myocarditis being most common (6). CT findings tend to reduce with time if underlying disease is treatable.[6] Little is known about the behavior of myocardial calcium on imaging especially CMR. This case provided insight into myocardial calcification features on various sequences of CMR and how multi-modality cardiac imaging helps in understanding the rare cardiac pathologies like myocardial calcification. However, CMR especially role of parametric mapping in differentiating myocardial calcium and fat needs to be further studied.
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References
- Lim A, Be KK, Wong C. A case report: extensive myocardial calcification and non-ischemic cardiomyopathy related to past sepsis. Eur Heart J Case Rep. 2021 Feb 18;5(2):ytaa564.
- Massera D, Kizer JR, Dweck MR. Mechanisms of mitral annular calcification. Trends Cardiovasc Med. 2020 Jul;30(5):289-295.
- Lippolis A, Buzzi MP, Romano IJ, Dadone V, Gentile F. Stone heart: An unusual case of heart failure with preserved ejection fraction due to massive myocardial calcification. J Cardiol Cases. 2020 Nov 19;23(4):145-148.
- Yang CC, Tsai CS, Tsai YT, Lin CY, Chen JL, Hsu PS. Restrictive cardiomyopathy caused by diffuse calcification of the left ventricle after 20 years of haemodialysis. Cardiovasc J Afr. 2022 Mar-Apr 23;33(2):95-97.
- de Riva M, Naruse Y, Ebert M, Watanabe M, Scholte AJ, Wijnmaalen AP, Trines SA, Schalij MJ, Montero-Cabezas JM, Zeppenfeld K. Myocardial calcification is associated with endocardial ablation failure of post-myocardial infarction ventricular tachycardia. Europace. 2021 Aug 6;23(8):1275-1284.
- Kido T, Tanimoto K, Watanabe T, Taira M, Narita J, Ishida H, Ishii R, Ueno T, Miyagawa S. Myocardial calcification: case reports and a systematic review. Eur Heart J Imaging Methods Pract. 2024 Jul 30;2(3):qyae079.
Case Prepared By:
Avanti Gulhane, MD, DNB, FSCMR
Editorial Board, Cases of SCMR
University of Washington
