Calcification in a Young Male With End-Stage Renal Disease: An Overlooked Complication

The saddle-shaped mitral annulus is a complex structure that plays a dynamic role in leaflet coaptation, and left atrial and left ventricular systole and diastole. Mitral annular calcification, a kind of dystrophic calcification, is associated with advanced age, female gender and coronary artery disease, and is one of the most common cardiac findings on autopsy.^1,2 However, a premature form of mitral annular calcification occurs in patients with end-stage renal disease (ESRD) and prevalence is estimated to be as high as 40% in this cohort.³ In an attempt to reiterate the importance of this oft-missed clinical entity, we present a case of accelerated mitral annular calcification in a young man with ESRD.

Case Report

A 37-year-old man with history of ESRD on hemodialysis, hypertension, hyperlipidemia, and subtotal parathyroidectomy 6 months prior due to refractory renal hyperparathyroidism was brought to the emergency department (ED) for chest pain.

The chest pain began 30 minutes before presentation while the patient was sitting on his couch playing video games. He described the pain as an 8 out of 10 and pressure-like. It was localized to his left breast and did not radiate. The pain was present at rest, non-positional, and associated with mild shortness of breath. It spontaneously terminated a few minutes after presenting to the ED, before the patient received sublingual nitroglycerine. He reported that he often missed medication doses and had been an active smoker for the past 15 years.

Vital signs on presentation included blood pressure of 188/125 mm Hg with no discordance between both arms, heart rate of 86 beats per minute, respiratory rate of 16/minute and SpO2 was 100% on room air. His body mass index was 24.6 kg/m². On examination, he was sitting comfortably with the head of the bed inclined at 45 degrees. The pain was not reproducible on palpation and the apex beat was localized to the 5th intercostal space in the mid-clavicular line. A III/VI holosystolic murmur was appreciated, loudest at the mitral area with radiation to the axilla. There was no friction rub. The lungs were clear to auscultation. Examination of the extremities revealed a normovolemic, regular pulse and an arterio-venous fistula on the left forearm with a palpable thrill. Pertinent investigations included an abnormal basic metabolic panel (sodium: 131 mmol/L, potassium 3.7 mmol/L, BUN 54 mg/dL, creatinine 12.2 mg/dL). Calcium corrected for albumin was 8.9 mg/dL and phosphorous was 7.5 mg/dL. Calculated calcium x phosphorous product was 66.75 mg²/dl² (Normal: <55 mg²/dl²). The patient was given aspirin, clopidogrel, and high-intensity atorvastatin. Initial troponin was 0.14 ng/mL. An electrocardiogram revealed left anterior fascicular block (old) and met criteria for left ventricular hypertrophy, but did not show acute ST-T wave changes. A chest x-ray revealed mitral annular calcification (Figure 1). The next troponin in 6 hours was 0.15 ng/mL and the patient was started on a heparin drip as per non-ST-elevation myocardial infarction (NSTEMI) protocol. The troponin reached a peak of 0.17 ng/mL in 24 hours, after which it trended down. Echocardiography showed a dilated left atrium (57 mm) and severe posterior annular calcification of the mitral valve with mildly restricted leaflet opening. Ejection fraction was 65% with concentric left ventricular hypertrophy and diastolic dysfunction. Mild posterior wall hypokinesis was also noted. Given that his TIMI risk score was 3, the patient was scheduled for a coronary angiography and transferred to a tertiary care facility.

The patient underwent coronary angiography, which revealed severe calcified left main coronary artery disease. The left anterior descending (LAD) artery had ostial calcification (Figure 2). The right coronary artery and the circumflex artery were both normal, with dominant right coronary circulation. Left ventriculography demonstrated an akinetic apex.

The patient underwent surgical bioprosthetic mitral valve replacement and coronary artery bypass graft with the left internal mammary artery grafted to the mid LAD and a saphenous graft vein to obtuse marginal artery (Figure 3).

The patient had an unremarkable post-operative hospital course. At his two-month follow-up visit, the patient reported good recovery, resolution of his angina symptoms, and an improvement in his functional capacity. His echo post-operatively showed an intact bioprosthetic mitral valve with no mitral regurgitation or mitral stenosis, and an ejection fraction of 50 to 55% with mild concentric left ventricular hypertrophy.

Discussion

The prevalence of mitral annular calcification is estimated at 40% in ESRD patients. Previously it was thought that this was a result of high ventricular systolic pressures associated with systemic hypertension and the resultant degenerative process. However, the etiology appears to be more intricate, with a strong link between prevalence and the systemic dysfunction in calcium-phosphorous metabolism typically seen in ESRD. It appears that a high calcium-phosphorous product (as seen in our patient) causes the precipitation of calcium in the vulnerable tissue of the mitral annulus.^4,5 There is no established therapy for the prevention of mitral annular calcification. Scant data are available about the effects of risk factor modification on disease progression.

Three-dimensional echocardiography studies have shed light on the anatomic and hemodynamic changes that occur in mitral annular calcification. Calcification follows the curve of the mitral annulus, with relative sparing of the anterior leaflet and the commissures — a feature that distinguishes it from rheumatic mitral disease. The annular diameter is increased (not decreased) in both systole and diastole, as compared with normal subjects. There is loss of systolic contraction along the anteroposterior diameter with no increase in saddle shape of the annulus usually seen in early systole. The normal decrease in leaflet tenting during systole is also blunted. The subsequent valvular dysfunction leads to increased leaflet stress and perturbation of efficient flow through the left ventricle.⁶

Mitral annular calcification is not a benign entity. It is a marker for atherosclerotic burden and may be associated with aortic valvulopathy.⁷ In addition, it carries the risk of complications, including arterial emboli, atrioventricular block and associated atrial arrhythmias, mitral regurgitation, infective endocarditis, and increased mortality.^8-10 

^aCardio Metabolic Institute, Somerset, New Jersey;
^bRobert Wood Johnson University Hospital, New Brunswick, New Jersey;
^cSt. Peter’s University Hospital, New Brunswick, New Jersey

Disclosures: The authors report no conflicts of interest regarding the content herein.

The authors can be contacted via Joseph Ibrahim, MSIV, at ibrahimj3@upmc.edu.

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