a b s t r a c t

Characteristic ECG changes with hypercalcemia include shortening of the QoT, QaT, and QeT intervals which are measured from the beginning of the QRS complex to the origin (O), apex (A), and end (E) of the T wave respec- tively. At very high serum calcium levels ECG changes include slight prolongation of the PR and QRS intervals, T wave flattening or inversion, and the appearance of a J wave at the end of the QRS complex. We present a case of a 22 year-old male, who had been bedbound for 5 months following a severe motor vehicle collision, presenting with shortening of the QoT and QaT intervals leading to anterior ST elevation mimicking acute myocardial infarc- tion. Cardiac Troponin testing was negative, however, laboratory testing revealed a serum calcium level of 15 mg/dL (normal 7.3-10.5 mg/dL). We review the published literature regarding the link between hypercalce- mia and the appearance of ST elevation.

(C) 2017

1. Case

A 22 year-old bedbound male presented to the Emergency Depart- ment (ED) with worsening and possibly infected sacral decubiti ulcers. He had been involved in a significant motor vehicle collision five months prior, which had resulted in multiple sacral, pelvic, and femur fractures. Following hospital discharge, the patient remained bedridden at home and was unable to fully participate in home Physical therapy secondary to pain.

On exam, the patient had a BP 144/92 mm Hg, HR 115 bpm, RR 18/ min, T 37.3 ?C, and SpO2 98% on RA. He was 190.5 cm in height and 100 kg in weight with a BMI of 27.5 kg/m². His exam was notable for multiple sacral and heel decubiti ulcers with serosanguinous drainage. He was unable to walk, sit, roll-over without assistance secondary to pelvic girdle pain. His cardiopulmonary exam was normal with the ex- ception of an elevated heart rate.

In addition to laboratory and radiologic investigations, an ECG was obtained (Fig. 1). This was noted to have a sinus rhythm with concave ST segment elevation in V1-V4, Q waves with ST segment elevation in lead I and aVL, ST segment depressions in lead III and aVF, and biphasic T wave in leads V4-V6. The QT was measured at 324 ms and was calcu- lated to be 422 ms when adjusted for heart rate. The QoTc and QaTC were measured at 80 ms and 160 ms and calculated to be 110 ms and 210 ms when adjusted for heart rate.

A pelvic x-ray demonstrated patchy osteopenia or both hips and pel- vis. This patient’s labs were notable for mild leukocytosis and mildly

* Corresponding author at: Department of Emergency Medicine, Oregon Health & Sciences University, 3181 SW Sam Jackson Park Rd, Portland, OR 97239, United States.

E-mail address: duraned@ohsu.edu (E. Durant).

elevated lactate as a well as serum calcium of 15 mg/dL (normal 7.3- 10.5 mg/dL), magnesium 1.4 mg/dL (normal 1.6-2.6 mg/dL), phospho- rus 1.6 mg/dL (normal 2.3-4.7 mg/dL), and a serum albumin of 3.7 g/dL (normal 3.5-5.0 g/dL). Cardiac troponin I was undetectable (b 0.10 ng/mL).

Given the ECG findings, a cardiology consult was obtained and con- cluded the ST elevations noted on the ECG were most likely due to shortening of the QoT and QaT intervals resulting from hypercalcemia. No additional cardiology testing was recommended and a repeat ECG was not performed after treatment of hypercalcemia. The patient was admitted for wound care/infection and had an unremarkable hospital stay prior to being transferred to an inpatient rehabilitation facility.

1. Discussion

Calcium ion concentration has long been known to affect the cardiac action potential and surface electrocardiogram. Characteristic ECG changes with hypercalcemia include shortening of the QoT, QaT, and QeT intervals, which are measured from the beginning of the QRS com- plex to the origin (O), apex (A), and end (E) of the T wave respectively. A reduction in the duration of the QoTc and QaTc intervals is considered to be a more accurate reflection of hypercalcemia compared to measure- ments using the overall QTc interval [1-3]. The combination of short QoTc (b 180 ms) and QaTc (b 300 ms) had the highest specificity for hy- percalcemia in one series [3]. In our patient the QTc was normal at 420 ms, however the QoTc and QaTc were both reduced at 110 ms and 210 ms respectively.

Sonada et al., reported several ECG changes with hypercalcemia after performing a case-control study that compared the ECG findings in 89 patients with hypercalcemia to 267 age- and sex-matched controls

http://dx.doi.org/10.1016/j.ajem.2017.02.005

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Fig. 1.. ECG demonstrating ST segment elevations in leads V1 – V4, I, and avL, ST segment depressions in leads III and avF, and biphasic T waves in leads V4 – V6. QT, QTc, QoTc, ad QaTC are 324 ms, 422 ms, 80 ms, and 160 ms, respectively. Serum calcium was 15 mg/dL.

with normocalcemia [4]. In this series, hypercalcemia was associated with slight prolongation of the PQ interval (160 ms vs. 148 ms, p b 0.001), QRS duration (99 ms vs. 92 ms, p b 0.001), QT interval (354 ms vs. 378 ms, p b 0.001), and QTc (396 ms vs. 406 ms, p = 0.01). ST segment/T wave abnormalities were seen in 33% of patients with hypercalcemia vs. 4% in the control group (p b 0.001). J point ele- vation, identified either as a QRS slurring or a notching >= 0.1 mV in >= 2 consecutive leads, was noted in 30% of patients with hypercalcemia vs. 9% of controls (p b 0.001). Of the patients with J point elevation, over 50% also had ST elevation in two or more anatomic leads.

J point elevation and ST segment abnormalities have been reported in multiple case reports (Table 1) and one case series of patients with moderate/severe hypercalcemia. The majority of these patients

Table 1

Findings from Littmann L, Taylor III L, Brearley Jr. WD. ST-segment elevation: a common

finding in severe hypercalcemia. J Electrocardiol. Vol 40 2007:60-62.

Clinical history	Ca	QTc	ECG
62 yo male	16.5 mg/dL	0.258	STE V3-V4
52 yo male	15.8 mg/dL	0.402	STE V2-V3
49 yo male	17.0 mg/dL	0.420	STE V2-V5, I, aVL
39 yo male	12.9 mg/dL	0.415	STE V2-V6, I, II
23 yo male	14.7 mg/dL	0.418	STE V2-V6
44 yo male	18.5 mg/dL	0.383	STE V2
72 yo male	15.1 mg/dL	0.336	STE V2-V3, II, III, aVF
70 yo female	14.8 mg/dL	0.399	STE V2, I, aVL
45 yo female	20.2 mg/dL	0.326	STE V1-V3
48 yo male	10.9 mg/dL	0.360	STE V2-V5, I, aVL
35 yo male	13.3 mg/dL	0.408	STE V1-V2
43 yo male	11.4 mg/dL	0.382	STE V2-V4
50 yo male	11.1 mg/dL	0.393	STE V2-V5
48 yo female	15.0 mg/dL	0.418	STE V2-V6, II, III, aVF
86 yo male	11.4 mg/dL	0.400	STE V2-V4
36 yo female	10.5 mg/dL	0.352	STE V1-V4

presented with Nonspecific complaints, although several had chest, ab- dominal, back or shoulder pain. ST elevation occurs most often in the anterior leads and can be accompanied by regional ST depression. Serial cardiac enzymes, echocardiography, or cardiac catherization ruled out acute myocardial infarction. Littmann et al. published the largest case series of patients with hypercalcemia and ST elevation [5] (Table 1). Over a period of 14 years, 16 cases of hypercalcemia in which the ECG demonstrated ST-segment elevation that mimicked acute myocardial infarction were reviewed. The authors note ST elevation can occur in any anatomic configuration, but most commonly occurs in the anterior chest leads. The ST segments were reported to have a “scooped” appear- ance and were not followed by distinct T waves. According to Littmann, “ST-segment elevation is not a rare curiosity, but in fact may be the least well documented but most consistent electrocardiographic finding in patients with hypercalcemia.” [5]

Most authors hypothesize that ST elevation occurs as an artifact due to shortening of the interval between the S wave and the end of the T wave. Calcium channels act mainly in Phase 2 of the myocardial action potential. This is the plateau phase, consisting primarily of calcium in- flux and potassium efflux. During phase 3, calcium influx terminates and potassium efflux predominates as the myocyte repolarizes. Thus, the effect of hypercalcemia is confined to the ST segment with very little effect on the T wave (which occurs during phase 3). As the T wave moves closer to the QRS complex, the ST segment that connects the QRS wave to the T wave can appear to be elevated (and scooped) com- pared to the ECG baseline. This process may be accompanied by the ap- pearance of a J wave (Table 2).

Interestingly, Severe hypocalcemia has also been associated with ST elevation that can mimic an acute myocardial infarction [6-10].

1. Conclusion

The ECG changes of hypercalcemia include shortening of the QoTc (b 180 ms) and QaTc (b 300 ms) intervals as well as ST segment/T wave abnormalities that may mimic acute myocardial infarction.

Table 2

E. Durant, A. Singh / American Journal of Emergency Medicine 35 (2017) 1033.e3–1033.e6

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Hypercalcemia and ST elevation case reports.

Year	Author	Title	Journal	Clinical history	Ca	QTc	QoTc	QaTc	ECG	AMI excluded by	Notes
1984	Douglas	Extreme hypercalcemia and electrocardiographic	Am J	44 yo male with weakness,	21.8 mg/dL	0.330	0.140	0.220	STE V1-V5, II, III	Improved with
		changes	Cardiol	polyuria, polydipsia for						treatment
				3 weeks.
2003	Ashizawa	Hypercalcemia due to vitamin D intoxication with	Intern Med	78 yo male with nausea,	16.2 mg/dL	0.345	0.098	0.234	STE V1-V4; subtle	(-)Cath
		clinical features mimicking acute myocardial infarction		fatigue, and anorexia for 10					STD II, III, aVF
				days
2003	Topsakal	Electrocardiographic J wave as a result of	Jpn Heart J	67 yo female with nausea,	18.5 mg/dL	NR			STE V3-V6, II, III, aVF;	(-)Echo
		hypercalcemia aggravated by Thiazide diuretics in a		vomiting, weakness, and					STD I, aVL, V2
		case of primary hyperparathyroidism		constipation
2005	Turhan	ST segment elevation mimicking acute myocardial	Heart J	56 yo male with prolonged	16.2 mg/dL	0.362			STE V1-V6	(-)Enzymes/echo
		infarction in hypercalcemia		burning, crushing chest pain
2006	Nishi	Hypercalcemia-induces ST-segment elevation	J	31 yo male with nausea,	17.8 mg/dL	0.415			STE V1-V6	(-)Cath
		mimicking acute myocardial infarction	Electrocard	vomiting, lethargy,
				abdominal pain radiating to
				precordium
2009	Wesson	Severe hypercalcemia mimicking acute myocardial	Clin Med	69 yo female s/p syncopal	20.4 mg/dL	NR			STE V1-V5	(-)Enzymes
		infarction		event with vague chest pain
				and lethargy
2010	Donovan	Hypercalcemia mimicking STEMI on	Case Report	39 yo male with abdominal	23.0 mg/dL	NR			STE V2-V3, II, aVF	Clinically	2010
		electrocardiography	Med	pain, vomiting, and weakness						improved with
										supportive care
2010	Madampage	Hypercalcemia due to multiple myeloma with clinical	Chest	54 yo male with shoulder	17.1 mg/dL	“Normal”			STE II, III, aVF	(-)Cath
		features mimicking acute myocardial infarction		pain, fatigue, and weight loss
2010	Fang	Acute myocardial infarction mimicking squamous cell	Chin Med J	52 yo male with intermittent	16.0 mg/dL	“Normal”			STE V1-V3	(-)Enzymes/echo
		Lung cancer with bone metastases due to		substernal chest pain over
		hypercalcemia: A case report		2 weeks
2011	Hajsadeghi	A rare electrocardiographic manifestation of a rare form	Acta	60 yo male with epigastric	20.5 mg/dL	0.310	0.150	0.250	STE aVR, V1, STD II, III,	(-)Echo	*Patient died b24 h
		of multiple electrolyte disturbances: Hyperparathyroid	Medica	pain, vomiting, associated					aVF, ??? Precordial
		crisis	Iranica	fatigue/weakness for					leads (not included)
				1 month
2013	Huan	Bones, groans, stones, and STEMI overtones	OHSU	68 yo male with syncopal	17.6 mg/dL	NR			STE V2-V6, subtle	(-)Enzymes/echo
				event					STD III, aVF
2013	Cheng	Hypercalcemia-induced new onset left bundle branch	Acta Cardiol	78 yo female with vague	12.8 mg/dL	NR			STE V1-V4	(-)Enzymes/echo
		block mimicking acute myocardial infarction in a	Sin	chest pain and lethargy for
		patient with primary hyperparathyroidism		3 h
2013	Kukla	Hypercalcemia mimicking acute coronary syndrome	Kardiologia	69 yo female with chest pain	17.9 mg/dL	0.375		0.250	STE V1-V6, I, aVL	(-)Enzymes	*Translated from Polish
			Polska
2013	Chhabra	Milk Alkali syndrome: an electrocardiographic	Heart	46 yo male with severe	16.0 mg/dL	0.322			STE V3-V6, I, aVL, II,	(-)Enzymes
		masquerader for non-hypothermic Osborn		heartburn/Epigastric pain					III
		phenomenon
2014	Schutt	Severe hypercalcemia mimicking ST-segment elevation	Methodist	65 yo female with	N 14 mg/dL	0.420		0.240	STE V1-V3	(-)Enzymes/echo
		myocardial infarction	Debakey	near-syncope, vomiting, and
			Cardiovasc J	fatigue
2015	Patnaik	Just hypercalcemia or acute ST elevation myocardial	BMJ Case	79 yo male with lethargy and	19.4 mg/dL	NR		0.200	STE V1-V4	(-)Enzymes
		infarction – A review of hypercelcemia-related	Rep	confusion for 1 day
		electrocardiographic changes
2015	Braun	Suspected hypercalcemia induced ST segment elevation	Mil Med	55 yo male with shortness of	13.0 mg/dL	“Normal”			STE V1-V5	(-)Cath
		in a patient with sarcoidosis		breath and fatigue for 6 h
2015	Strand	Not all ST-segment changes are myocardial infarction:	BMJ Case	83 yo male with progressive	14.2 mg/dL	0.418			STE V1-V4, STD	(-)Enzymes/echo
		Hypercalcemia-induced ST-segment elevation	Reports	shortness of breath and leg					V5-V6
				swelling
2016	Nahass	Hypercalcemia-induced pancreatitis presenting with	Am J Emerg	32 yo male with sharp	17.0 mg/dL	NR			STE V1-V5	(-)Enzymes/echo
		acute ST-elevations mimicking a myocardial infarction	Med	epigastric pain radiating to
				the back and vomiting for
											(continued on next page)

1033.e6 E. Durant, A. Singh / American Journal of Emergency Medicine 35 (2017) 1033.e3–1033.e6

Table 2 (continued)

Year Author

Title

Journal

Clinical history

1 day

51 yo female with epigastric pain and exertional dyspnea for 1 week

Ca

2016 Manne

STriking resemblance: Calcium-alkali syndrome

Am J Med

Excluded 1993 Harris

Non-Hodgkin’s lymphoma – An unusual cause of myocardial infarction and hypercalcemia

Clin Oncology

66 yo male with vomiting, dehydration, and confusion

References

*Patient developed anterior chest pain/dyspnea/sweating

1. Nierenberg DW, Ransil BJ. Q-aTc interval as a clinical indicator of hypercalcemia. Am

J Cardiol 1979:243-8.

1. Saikawa T, Tsumabuki S, Nakagawa M, Takakurma T, Tamurama M, Maeda T, et al. QT intervals as an index of high serum calcium in hypercalcemia. Clin Cardiol 1988;11:75-8.

Notes

1. Ahmed R, Hashiba K. Reliability of QT intervals as indicators of clinical hypercalce- mia. Clin Cardiol 1988;11:395-400.
2. Sonoda K, Watanabe H, Hisamatsu T, Ashihara T, Ohno S, Hayashi H, et al. High fre- quency of early repolarization and Brugada-type electrocardiograms in hypercalce- mia. Ann Noninvasive Electrocardiol 2016;21:30-40.

AMI excluded by

(-)Enzymes

1. Littmann L, Taylor III L, Brearley Jr WD. ST-segment elevation: a common finding in severe hypercalcemia. J Electrocardiol 2007;40:60-2.

(+)AMI at

autopsy

1. Reddy CV, Gould L, Gomprecht RF. Unusual Electrocardiographic manifestations of hypocalcemia. Angiology 1974;25:764-8.
2. Lehmann G, Deisenhofer I, Ndrepepa G, Schmitt C. ECG changes in a 25-year-old woman with hypocalcemia due to hypoparathyroidism. Hypocalcemia mimicking acute myocardial infarction. Chest 2000;118:260-2.

STE V1-V5,STD II, III,

aVF

1. Eleftheriadis D, Fourla E, Vrizidis P. Acute myocardial infarction in a young male pa- tient with combined hormonal disorder. Chest 2002:2265-6.

STE V4-V6

1. Ilveskoski E, Sclarovsky S, Nikus K. Severe hypocalcemia simulating ST-elevation myocardial infarction. Am J Emerg Med 2012;30:256.e253-6.
2. Gomez-Dominguez R, Hidalgo R, Garcia-Rubira JC. Severe hypocalcemia masquerad- ing as acute coronary syndrome. J Emerg Med 2013;45:715-7.

QTc

QoTc

QaTc

ECG

16.3 mg/dL

0.440

17.5 mg/dL