Hypocalcemia Mimicking Acute Myocardial Infarction
The case of a 25-year-old woman presenting with chest pain, ECG changes, and laboratory findings suggestive of myocardial infarction is reported. Cardiac catheterization showed impaired left ventricular performance but otherwise normal coronary arteries. Laboratory analyses revealed primary hypoparathyroidism, and supplementation with calcium and vitamin [D.sub.3] was initiated. There was subsequent improvement in laboratory findings as well as echocardiographically determined left ventricular performance. Thereafter, the patient remained asymptomatic. Apart from some persisting ECG repolarization disturbances, there was complete normalization of the initial changes. This ease demonstrates a combination of clinical, blood biochemical, and ECG findings mimicking acute myocardial infarction.
(CHEST 2000; 118:260-262)
Key words: ECG changes; hypocalcemia; hypoparathyroidism
Abbreviations: CK = creatine kinase; FS = fractional shortening; LDH = lactate dehydrogenase
A 25-year-old woman was admitted to a hospital because of loss of consciousness, and clonic and tonic seizures. One and one-half years prior to the current admission, the patient was found to have hypocalcemia (1.5 mmol/L; normal range, 2.2 to 2.65 retool/L) coincidentally at the time of a cesarean section, but without further diagnostic or therapeutic workup. Other than episodes of nocturnal dyspnea 4 months earlier, the patient was asymptomatic. During the last few days before this admission, she complained of dull pain in the extremities. The serum calcium concentration was 0.85 mmol/L. On regaining consciousness, she developed chest pain that was not relieved by short-acting nitrates. On transfer to our service, the initial ECG was suggestive for acute or evolving myocardial infarction, with ST-segment elevation in leads I and aVL, and concurrent ST-segment depression in leads III, aVR, aVF, [V.sub.1], and [V.sub.3]-[V.sub.5] (Fig 1, top, A). In addition, the QTc interval on admission as calculated using Bazett's correction (in which the raw interval from beginning of QRS complex to the apex of the T wave is divided by the square root of the R-R interval) was 0.480 [s.sup.0.5]. Blood chemistry at admission revealed a lactate dehydrogenase (LDH) activity of 549 IU/L (normal range, 120 to 240 IU/L); an aspartate-aminotransferase (glutamate-oxalacetate-transaminase) activity of 26 IU/L (normal range, 0 to 15 IU/L); an alanine-aminotransferase (glutamate-pyruvate-transaminase) activity of 14 IU/L (normal range, 0 to 19 IU/L); a creatine kinase (CK) activity of 1,290 IU/L (normal range, 0 to 80 IU/L); and a CK-MB activity of 13 IU/L (normal range, 0 to 8 IU/L). Although the latter were presumably due to the patient's seizures, an acute cardiac event could not be ruled out. Consequently, cardiac catheterization was performed that revealed an impaired left ventricular ejection fraction but otherwise entirely normal coronary arteries. The differential diagnoses included a prior coronary artery embolism, coronary spasm, cardiomyopathy, or myocarditis. Parathyroid hormone was found to be [is less than] 1 pg/mL (normal range, 6 to 50 pg/mL), with a concomitantly reduced 25-hydroxyvitamin-D3 concentration of 6 ng/mL (normal range, 20 to 100 ng/mL), consistent with the diagnosis of primary hypothyroidism. Determination of serum electrolytes revealed 3.39 mmol/L (normal range, 3.8 to 5.0 mmol/L) for potassium; 0.5 mmol/L (normal range, 0.8 to 1.0 mmol/L) for magnesium; 7.8 mg/dL (normal range, 2.5 to 5.0 mg/dL) for phosphorus; and 45.4% (normal range, 51 to 64%) of serum proteins for serum albumin (total serum protein, 7.9 g/dL). Analysis of thyroid function revealed normal levels of free thyroxine (1.88 ng/dL), free triiodothyronine (3.97 pg/mL), as well as thyroid-stimulating hormone (2.2 [micro]U/mL). Sex hormone status, as expressed by lutropine (0.5 IU/L), follitropine (3.4 IU/L), and 17-[Beta]-estradiol (55.0 pg/mL), was unremarkable, and there was no clue to the presence of any other endocrine imbalance. Supplementation with calcium as well as vitamin [D.sub.3] was begun. Subsequently, the initial calcium concentration of 0.85 mmol/L rose to 1.51 mmol/L, and the increased CK values at admission decreased to 88 IU/L within 2 weeks, as did LDH activity (211 IU/L). Echocardiographic follow-up revealed a moderately diminished left ventricular systolic performance as expressed by means of left ventricular fractional shortening (FS) due to impaired motion of the anterior and lateral walls (FS, 11%). There was an improvement on calcium supplementation within a few days (FS, 29%). The ECG changes also showed a tendency to revert to normal: both ST-segment elevation and depression abated, and other than nonspecific changes in repolarization in leads I, aVR, aVF, and [V.sub.1]-[V.sub.3], none of the initial abnormalities persisted (Fig 1, bottom, B). Similarly, the QTc interval decreased to 0.372 [s.sup.0.5] (ie, to 77.5% of its initial value). On treatment of her hypoparathyroidism by means of continued oral supplementation with calcium and vitamin [D.sub.3], the patient remained asymptomatic and was discharged from the hospital a few days later.
[Figure 1 ILLUSTRATION OMITTED]
ECG changes were twofold: ST-segment elevation and prolongation of the QT interval. The latter is known to be due to the fact that hypocalcemia prolongs the duration of phase two of the action potential of cardiac muscle. In addition, calcium channel function and calcium influx during phase two are modulated by the rate of change of extracellular calcium, all of which impact on the QT interval.[1,2] The more abrupt the changes in calcium concentration occur, the more marked are the subsequent QT-interval changes. Accordingly, coronary spasm due to hypocalcemia must be viewed as the most likely cause of the QT-interval changes, as well as the clinical and invasive findings. Calcium ions are necessary for both contraction and relaxation; they are essential in both the cardiac and systemic vasculature.[4,5] Furthermore, spasms are known to be a sequel of hypomagnesemia, which, in turn, is often associated with hypocalcemia. Indeed, in our patient at the time of admission, magnesium depletion was also found (0.5 mmol/L), which, within a few days, returned to normal when clinical and ECG findings had resolved. Thus, coronary spasm in the clinical setting of hypocalcemia appears the most likely cause of the chest pain at admission, mimicking acute myocardial infarction. In contrast, both the initial clinical findings and the course of the disease rule out differential diagnostic considerations, such as prior coronary artery embolism, cardiomyopathy, or myocarditis.
There is controversy regarding the relationship between calcium concentration[2,5] and left ventricular function, as well as the rapidity of reversal on elimination of the underlying electrolyte imbalance.[2-4,7,8] Experimental data suggest more extensively depressed ventricular function with lower calcium concentrations. However, depression of left ventricular ejection does not appear to be a matter of extracellular calcium concentrations only. It also appears to be related to the duration of the imbalance, during which organic alterations may be incurred, to concomitant or underlying heart diseases, as well as to the rapidity of calcium concentration changes.[1,2.5,7] If, as in the case of chronic heart failure, [Beta]-adrenergic-receptor down-regulation renders [Beta]-agonists ineffective, the contractile state may become almost exclusively dependent on extracellular calcium concentration. This, in turn, leads to rapid changes of left ventricular performance following acute changes of calcemia. On the other hand, isolated chronic hypocalcemia due to endocrine disorders leads to organic changes that need not be reversible, but leaves the [Beta]-adrenoceptor-dependent cardiac contractile state unaltered.[2,7] Accordingly, little, if any, acute change in cardiac performance can be expected on repletion of calcium stores. This concept is also in keeping with the fact that clinically manifest heart failure is rarely observed in the setting of isolated hypocalcemia.[2,4,8]
Other than the electrolyte disturbances described, blood chemistry studies showed elevations of LDH and CK at hospital admission. The latter are known to occur in hypocalcemia, which leads to lowered cell membrane potentials and, consequently, increased cell membrane permeability with subsequent leakage of cytoplasmic proteins from muscle cells. Both were completely reversible on supplementation of calcium and vitamin [D.sub.3]. This argues in favor of hypocalcemia as the cause, although muscular damage following the seizures immediately prior to hospital admission must be taken into consideration as well.
In summary, in this case, an exacerbation of long-standing hypocalcemia led to suspicion of an acute or evolving myocardial infarction. There was no history of factors such as sepsis, acute pancreatitis, administration of radiocontrast media, cardiopulmonary bypass, transfusion of citrated blood, hemodialysis, or (para)thyroidectomy, all of which are known to have the potential to lower the calcium concentration. Accordingly, in this patient and others, management of the emergency situation will not only remain dependent on the rapidity with which complete blood chemistry results are available, but also the urgency with which severe cardiac disease must be confirmed or ruled out.
 Davis TME, Singh B, Choo KE, et al. Dynamic assessment of the electrocardiographic QT interval during citrate infusion in healthy volunteers. Br Heart J 1995; 73:523-526
 Vered I, Vered Z, Perez JE, et al. Normal left ventricular performance documented by Doppler echocardiography in patients with long-standing hypocalcemia. Am J Med 1989; 86:413-416
 Reddy CVR, Gould L, Gomprecht RF. Unusual electrocardiographic manifestations of hypocalcemia. Angiology 1974; 25:764 -768
 Bashour T, Basha HS, Cheng TO. Hypocalcemic cardiomyopathy. Chest 1980; 78:663-665
 Lang RM, Fellner SK, Neumann A, et al. Left ventricular contractility varies directly with blood ionized calcium. Ann Intern Med 1988; 108:524-529
 Khardori R, Cohen B, Taylor D, et al. Electrocardiographic finding simulating acute myocardial infarction in a compound metabolic aberration. Am J Med 1985; 78:529-532
 Kudoh C, Tanaka S, Marusaki S, et al. Hypocalcemic cardiomyopathy in a patient with idiopathic hypoparathyroidism. Intern Med 1992; 31:561-568
 Levine SN, Rheams CN. Hypocalcemic heart failure. Am J Med 1985; 78:1033-1035
(*) From the Deutsches Herzzentrum Munchen and I. Med. Klinik, Klinikum rechts der Isar der Technischen Universitat Munchen, Munich, Germany.
Manuscript received August 17, 1999; revision accepted December 8, 1999.
Correspondence to: Gunter Lehmann, MD, Deutsches Herzzentrum Munchen, Lazarettstra[Beta]e 36, D - 80636 Munchen, Germany; e-mail: firstname.lastname@example.org
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