Hypocalcaemic Cardiomyopathy; the Relationship Between Myocardial Damage, Left Ventricular Function, Calcium and ECG Changes in a Patient with Idiopathic Hypocalcaemia

Abstract

Despite our knowledge of the importance of calcium ions in muscle function there is little documentation of the effect of hypocalcaemia on left ventricular function. In adults, left ventricular failure resulting from hypocalcaemia is rare and is mostly associated with primary hypoparathyroidism or surgical removal of the parathyroid glands 1–4. This is the first case to clearly demonstrate the relationship between serum calcium concentration (corrected for albumin), creatinine phosphokinase (CPK) levels, ECG changes and left ventricular ejection fraction in a patient with normal coronary arteries, who suffered a transient period of hypocalcaemia following parathyroidectomy. A 38 year-old man was admitted for a repeat parathyroidectomy in December 1998 as treatment for tertiary hyperparathyroidism secondary to end-stage-renal-disease (ESRD). The aetiology of the (ESRD) was reflux nephropathy and the patient had been placed on continuous ambulatory peritoneal dialysis (CAPD) in 1996. Alfacalcidol and phosphate binders had failed to suppress the secondary hyperparathyroidism that occurs in renal failure. Medical therapy failed to prevent the progression to symptomatic tertiary hyperparathyroidism with parathyroid levels reaching 1450 ng/l (normal 10–65). An initial parathyroidectomy in January 1998 was unsuccessful resulting in the necessity for a re-exploration one year later. Before the second operation the patient received loading doses of alfacalcidol in an attempt to prevent post-operative hypocalcaemia resulting from an influx of calcium into the skeleton (hungry bone syndrome). Despite large doses of additional post-operative intravenous calcium and oral supplements the patient remained hypocalcaemic for 3 weeks. During this period the patient complained of atypical chest pain associated with generalised aches, pains and malaise. The CPK measured 2500 IU/l and an ECG showed repolarisation changes throughout the antero-lateral leads mimicking a non-Q wave myocardial infarction (Fig. 1). CKMB/CK index 0.5% (Normal 0–3.5) echocardiography revealed a slightly dilated left ventricle with globally reduced function producing an ejection fraction (EF) of 39%. This was supported by radionuclide angiography using a multi-gated acquisition (MUGA) scan, which calculated an EF of 37%. When these investigations were repeated 3 months later there had been a marked improvement in left ventricular function as evidenced visually on the echocardiogram. The MUGA now also calculated the EF to be 57%(Fig. 2). Once the serum-calcium levels corrected for albumin, were stabilised the patient's myalgia resolved, the CPK normalised (Fig. 3, Table 1) and the T-wave changes on the ECG returned to normal (Fig. 4). He was therefore able to undergo an exercise tolerance test in which he completed seven minutes of the Bruce protocol stopping due to fatigue. A maximum heart rate of 178/min was achieved (98% max. predicted) and no ECG changes were seen throughout the test. The patient continued to experience atypical chest pains that were sharp and unrelated to exercise. Consequently coronary angiography was carried out, this demonstrated normal coronary arteries. Intracellular calcium plays an important role in the movement of actin and myosin filaments in relation to each other resulting in muscle contraction 5. The increased levels of calcium within the myofibrils is thought to be necessary for the increased force of myocardial contractions. The detrimental effect of low calcium levels on myocytes has previously been observed 6 and it follows that because of its dependence on this particular cation, the heart will suffer to a greater degree than skeletal muscle in hypocalcaemic states. In this patient, cardiac damage is indicated by a CPKMB value of 40.3-μg/l (normal 0–5), however as an index compared with total CPK it remains within the normal range reflecting the greater mass of damaged skeletal muscle. This is not the first report of hypocalcaemic cardiomyopathy. Left ventricular impairment in the presence of normal coronary arteries has been previously recorded but was thought to be associated with chronic rather than acute hypocalcaemia 7,8. Combinations of previous heart disease and the administration of medication have complicated other case studies attempting to demonstrate a relationship between hypocalcaemia and left ventricular function 9. The T-wave inversion seen in our case has appeared in all of these previous reports and appears to be a characteristic of the condition. Despite the documented drop in cardiac ejection fraction, the patient displayed no signs or symptoms of heart failure. This may in part be due to the ability of his peritoneal dialysis to off-load the failing ventricle. This patient suffered acute hypocalcaemia, was receiving no medication other than calcium supplements and had normal coronary arteries. Stabilisation of serum-calcium levels was therefore the only intervention that occurred and allows a direct comparison with the cardiac investigations. The elevated CPK levels, T-wave changes on the ECG and the drop in left ventricular ejection fraction clearly correspond to the lowest corrected calcium recordings and show resolution when these levels normalised. Although the Q-T interval on this patient's ECG remained less than 0.39 s it is important to note that by comparison with the patient's normal ECG's there was a considerable increase during the hypocalcaemic episode which is likely to be significant. This is the first time that such comparisons have been documented in this manner in a patient with no other complicating factors. Hypocalcaemia is an important, reversible and easily overlooked cause of cardiomyopathy. This case highlights the importance of routine measurements of serum-calcium levels in the investigation of patients in whom the aetiology of their cardiomyopathy is unknown. The condition can occur acutely and may mimic a myocardial infarction with inverted T-waves, left ventricular failure and raised cardiac enzymes. All these changes can be expected to resolve with correction of the serum-calcium levels.