Reversible Heart Failure

in a Hypocalcemic Patient

Chin-Sheng Lin,1 Shih-Hua Lin,2 Shu-Meng Cheng,1 Shih-Ping Yang1 and Tien-Ping Tsao1

Hypocalcemia is a less-recognized but reversible cause of heart failure. We report a 56-year-old gentleman with

chronic kidney disease, coronary artery disease and hypertension, presenting with exertional dyspnea, orthopnea,

and bilateral lower legs edema for one week. His jugular venous pulses were elevated. Cardiac examination revealed

regular heart beat and an S3 gallop without murmurs. Pertinent laboratory data revealed plasma creatinine 4.2 mg/dL

and elevated creatinine kinase (585 IU/L). Electrocardiography showed normal sinus rhythm with nonspecific ST-T

changes and a corrected QT (QTc) interval of 0.7 seconds (normal 0.36-0.43 seconds). Echocardiography

demonstrated generalized hypokinesia of the left ventricle with ejection fraction of 20-25�. Aggressive therapy

with carvedilol, spironolactone, intravenous nitroglycerin and furosemide failed to ameliorate the patient’s clinical

symptoms. Later, marked hypocalcemia (plasma total calcium 4.28 mg/dL) was noted, and a normalization of serum

calcium concentration improved the heart failure dramatically. Early recognition of hypocalcemia as a precipitating

factor of congestive heart failure will promote the rapid initiation of effective therapy.

Key Words: Hypocalcemia � Congestive heart failure � Hypoparathyroidism

INTRODUCTION

Clinical manifestations of hypocalcemia vary from

very mild and asymptomatic biochemical abnormality to

severe life-threatening disorders, such as laryngeal

spasm, tetany, and seizures. In addition to neuromu-

scular disorders, cardiovascular manifestations, such as

prolonged QT interval, ventricular arrhythmia, and heart

failure, can also occur in hypocalcemia.1 Many clini-

cians may be unaware of hypocalcemia associated with

heart failure, since it is often ignored or only briefly

mentioned in standard internal medicine. Furthermore, in

the presence of coexisting factors leading to heart fail-

ure, such as coronary artery disease with ischemic

cardiomyopathy, the hidden cause of heart failure due to

hypocalcemia may be easily overlooked. We describe a

patient featuring refractory heart failure due to unrecog-

nized hypocalcemia. The decompensated heart failure

was rapidly reversed by aggressive calcium supplement-

ation. The previously reported cases of hypocalcemic

heart failure (HHF) are also reviewed.

CASE REPORT

A 56-year-old man presented with exertional dy-

spnea, orthopnea, and bilateral lower leg edema for one

week. He had a history of hypertension and type 2 diabe-

tes under medication for 20 years, and more recently, he

had been receiving carvedilol, doxazocin, and insulin in-

jection to control hypertension and diabetes. One year

prior to this hospitalization, he was admitted because of

congestive heart failure with left ventricle (LV) ejection

47 Acta Cardiol Sin 2009;25:47�51

Case Report Acta Cardiol Sin 2009;25:47�51

Received: January 15, 2008 Accepted: April 25, 20081Division of Cardiology, Department of Medicine; 2Division of

Nephrology, Department of Medicine, Tri-Service General Hospital,

National Defense Medical Center, Taipei, Taiwan, R.O.C.

Address correspondence and reprint requests to: Dr. Tien-Ping Tsao,

Division of Cardiology, Department of Medicine, Tri-Service General

Hospital, Number 325, Section 2, Cheng-Kung Road, Neihu 114,

Taipei, Taiwan. Tel: 886-2-8792-7161; Fax: 886-2-6601-2656; E-

mail: denis.tsao@msa.hinet.net

fraction (EF) of 30-35�. Coronary artery disease (CAD)

with triple-vessel disease was diagnosed, and percu-

taneous coronary intervention (PCI) was performed.

Hypocalcemia (plasma total calcium level 7.3 mg/dL)

was noted during that hospitalization. The heart failure

got improvement, with LV EF increased to 40-45� after

PCI and medication with intravenous nitrate and furo-

semide. The plasma calcium level returned to normal

(8.6 mg/dL) after calcium supplementation. The patient

was discharged with the diagnosis of CAD with conges-

tive heart failure and received regular outpatient fol-

low-up. Additionally, the patient also suffered from pso-

riasis vulgaris.

On this most recent admission, his blood pressure

was 140/80 mmHg, heart rate 96 beats/min, respiratory

rate 22/min, body temperature 36.8 �C, and oxygen satu-

ration 94� on room air. Cardiac examination revealed

regular heart beat and an S3 gallop without murmurs. Bi-

lateral basilar moist crackles were heard on chest auscul-

tation. There were jugular venous distention, mild hepa-

tomegaly, and edema of his legs & scrotum. Chvostek’s

and Trousseau’s signs were negative. Psoriasis vulgaris

was noted as multiple sharply-demarcated and erythe-

matous plaques with silvery scales over his trunk, arms,

buttocks and abdomen.

Pertinent laboratory studies showed renal failure,

with blood urea nitrogen 92 mg/dL (8-25 mg/dL),

creatinine 4.2 mg/dL (0.7-1.2 mg/dL), and normal plas-

ma magnesium level (2.1 mEq/L) (Table 1). Elevated

creatinine kinase (585 IU/L) with normal creatinine

kinase-MB (23 IU/L) level was also noticed. Chest radi-

ography revealed cardiomegaly with pulmonary conges-

tion. The patient’s electrocardiography (ECG) showed

normal sinus rhythm, intraventricular conduction delay,

and a corrected QT (QTc) interval of 0.7 seconds (nor-

mal 0.36-0.43 seconds) (Figure 1A). Echocardiography

demonstrated generalized hypokinesia of LV with EF of

20-25� (Figure 2A). CAD with congestive heart failure

was tentatively diagnosed.

Standard medications for heart failure including

carvedilol 12.5 mg daily, spironolactone 25 mg daily, in-

travenous furosemide 80 mg every 8 hours, nitroglycerin

10 �g/min, and oxygen supplement failed to ameliorate

his cardiac symptoms. The plasma biochemistry data

showed profound hypocalcemia (plasma total calcium

level 4.28 mg/dL). Intravenous 10� calcium gluconate

was started at a dosage of 1 gram every 6 hours. The pa-

tient became normocalcemic (8.28 mg/dL) after calcium

supplementation for 6 days, and electrocardiographic

QTc interval returned to normal limit (0.43 seconds)

(Figure 1B). The LV EF increased to 45-50� (Figure

2B). The cardiac symptoms, skin lesions, and renal func-

tion much improved in three weeks. Both extreme

hypocalcemia and a low concentration of parathyroid

hormone (PTH, 7.9 pg/mL) indicated primary hypopara-

thyroidism. The patient was discharged under stable con-

dition and received oral calcitriol 0.5 �g daily, and cal-

cium citrate 950 mg three times daily. He did well, and

repeated electrocardiography showed no prolongation of

QTc during two years’ follow-up.

DISCUSSION

Calcium ions play a crucial role in contraction of

cardiac myocytes. Depolarization of the sarcolemma re-

sults in calcium influx and release of calcium ions from

the sarcoplasmic reticulum. Interaction of calcium ions

with troponin C results in initiation of cross-bridging be-

tween actin and myosin. The increase in cross-bridging

is proportional to the increase in intracellular calcium

concentration. Calcium is subsequently rapidly taken up

by the sarcoplasmic reticulum, leading to the relaxation

of cardiac myocytes until the arrival of another depolar-

Acta Cardiol Sin 2009;25:47�51 48

Chin-Sheng Lin et al.

Table 1. Biochemical studies in a patient with hypocalcemic

heart failure

Plasma Normal range Day 1 Day 7

Hemoglobin (13-16 g/dL) 12.4 11.8

Glucose (65-109 mg/dL) 213 114

Na+ (135-142 mmol/L) 137 144

K+ (3.5-5.0 mmolL) 4.5 4.1

Cl- (96-108 mmol/L) 193 104

HCO3- (23-25 mmol/L) 25.4 24.2

Total calcium (8.0-10.4 mg/dL) 4.28 8.28

Free calcium (4.4-5.6 mg/dL) 1.92 4.12

Phosphorus (2.5-4.5 mg/dL) 6.2 5.2

Mg2+ (1.3-2.2 mEq/L) 2.1 1.6

Urea (8-25 mg/dL) 92 33.6

Creatinine (0.7-1.2 mg/dL) 4.2 1.8

Albumin (3.5-4.8 g/dL) 3.8 3.5

Creatinine kinase (38-174 IU/L) 585 49

Creatinine kinase-MB (7-25 IU/L) 23 17

Parathyroid hormone (10-60 pg/mL) 7.9 -

ization wave, and the cycle continues.

This patient with previous CAD, chronic renal fail-

ure, and hypertension developed recurrent heart failure

with prolonged QT interval. The echocardiographic evi-

dence of generalized left ventricular hypokinesia and

documented hypocalcemia achieved a diagnosis of HHF,

further supported by improved heart function with cal-

cium and oral calcitriol supplements because the heart

failure was refractory to standard medication. Primary

hypoparathyroidism, which caused hypocalcemia in this

patient, was confirmed by low plasma parathyroid hor-

mone level.2

A total of 27 cases of HHF, including our patient,

have been reported in the literature. There were 17 fe-

males and 10 males.3-6 The etiologies of HHF include id-

iopathic hypoparathyroidism (13/27, 48�), status post

subtotal thyroidectomy (22�) and parathyroidectomy

(18�) with hypoparathyroidism, chronic renal failure

(3�), and nutritional osteomalacia (3�). The HHF can

be precipitated by coexisting hypomagnesemia and un-

derlying organic heart disease. Plasma total calcium

level at the onset of HHF is extremely low, with range of

4-6 mg/dL after correction for plasma albumin. Patients

with HHF can also present with variable neurological

49 Acta Cardiol Sin 2009;25:47�51

Hypocalcemia and Heart Failure

Figure 1. A. Electrocardiography on admission showed normal sinus rhythm, intraventricular conduction delay, and a corrected QT (QTc) interval

of 0.7 seconds. B. normal QTc of 0.43 seconds after correction of hypocalcemia

symptoms, such as extremity paresthesia, muscle cramp,

carpopedal spasm, weakness and seizure, although some

patients manifest with HHF alone. After aggressive cal-

cium supplementation, the HHF can be recovered com-

pletely within 3-4 weeks.

Elevation of plasma creatinine kinase (CK), electro-

cardiographic evidence of ST-T wave changes, and

echocardiographic evidence of myocardial dysfunction,

which mimics acute myocardial infarction in emergency

setting, can also develop in hypocalcemic patients with

normal coronary anatomy.7 Hypocalcemia lowers cell

membrane potentials, resulting in increased cell mem-

brane permeability and leakage of cytoplasmic proteins

from muscle cells, causing elevation of plasma CK

level.8 With persistent normal MB fraction, the plasma

CK level returned to normal during calcium supple-

mentation, and there was a significant improvement of

left ventricular function after correction of this meta-

bolic disorder. Hypocalcaemia, rather than coronary ar-

tery disease, was likely responsible for the cardiac

myopathic feature in our patient.

Generalized psoriasis precipitated by various factors

could be associated with hypocalcemia.9 Hypocalcemia

in these patients is usually caused by malabsorption, sur-

gical or idiopathic hypoparathyroidism. It was suggested

that hypocalcemia might damage cell adhesion mole-

cules, such as cadherins, which depend on calcium.10

Mineral metabolism abnormalities and reduced levels of

vitamin D metabolites in hypocalcemia had been also

postulated. Correcting the hypocalcemia with calcium

and vitamin D could completely cure such skin lesions.

Furosemide should be cautiously used in heart fail-

ure patients with hypocalcemia. Since furosemide may

induce hypocalcemia by increasing urine calcium wast-

ing, the usual therapeutic measures for heart failure

without calcium replenishment may not achieve satisfac-

tory response. In this case, severe hypocalcemia might

have been induced by furosemide during initial heart

failure treatment, resulting in worsening clinical signs

and hemodynamics.

This case report reminds clinicians to be aware of

hypocalcemia as a possible cause of decompensated

heart failure. Once hypocalcemia is recognized, it should

be treated and the possible cause of hypocalcemia should

be sought and treated as well. This will ultimately im-

prove the patient’s outcome.

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tongue, and double vision. Lancet 1997;349:1516.

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Acta Cardiol Sin 2009;25:47�51 50

Chin-Sheng Lin et al.

Figure 2. A. M-mode parasternal long-axis views of the left ventricle

(LV) in a patient with hypocalcemic heart failure. A, generalized

hypokinesia of LV with EF of 20-25�. B. the LV EF increased to

45-50� after correction of hypocalcemia.

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51 Acta Cardiol Sin 2009;25:47�51

Hypocalcemia and Heart Failure