A reversible form of cardiomyopathy.
SM Kini, SJ Pednekar, ST Nabar, P Varthakavi
Department of Medicine and Endocrinology, Topiwala National Medical College and B.Y.L. Nair Charitable Hospital, Dr. A. L. Nair Road, Mumbai Central, Mumbai-400 022, India., India
S M Kini
Department of Medicine and Endocrinology, Topiwala National Medical College and B.Y.L. Nair Charitable Hospital, Dr. A. L. Nair Road, Mumbai Central, Mumbai-400 022, India.
|How to cite this article:|
Kini S M, Pednekar S J, Nabar S T, Varthakavi P. A reversible form of cardiomyopathy. J Postgrad Med 2003;49:85-7
|How to cite this URL:|
Kini S M, Pednekar S J, Nabar S T, Varthakavi P. A reversible form of cardiomyopathy. J Postgrad Med [serial online] 2003 [cited 2021 Oct 21 ];49:85-7
Available from: https://www.jpgmonline.com/text.asp?2003/49/1/85/919
A 30 years old female, mother of a three-year-old child, presented with breathlessness and chest pain for four days and orthopnoea for last two days. She had no past history of cardiac, renal or thyroid disease. On examination, she was orthopnoeic, with a respiratory rate of 44/minute and pulse rate of 150/minute, which was regular in rhythm. The blood pressure was 110/70mmHg. The jugular venous pressure was raised. There was no pallor, cyanosis or oedema. The hyperdynamic apex impulse was situated in the 6th intercostal space 2.5 cm lateral to the left midclavicular line. Chest auscultation revealed bilateral basal crepitations and S3 gallop rhythm. There was no cardiac murmur or pericardial rub.
At this point what are the possible differential diagnoses?
A provisional diagnosis of acute left ventricular failure due to acute myocarditis was made on the basis of short duration history of breathlessness and findings of cardiomegaly with S3 gallop. Apart from viral myocarditis, chronic rheumatic heart disease like mitral stenosis or regurgitation which had decompensated, or acute or acute on chronic renal failure were possibilities.
An electrocardiogram showed sinus tachycardia. Arterial blood gas analysis showed hypoxia and respiratory alkalosis. She was transferred to the intensive cardiac care unit. Her chest x-ray showed cardiomegaly. Her electrocardiograms showed prolonged QTc interval of 0.52 seconds. The 2D-echo showed generalised hypokinesia, with a dilated left ventricle with poor function (ejection fraction: 20%); moderate mitral regurgitation, mild pulmonary hypertension; mild tricuspid regurgitation; mild right atrial and ventricular enlargement. Creatine phosphokinase-MB fraction was 28 units/L (normal:0 to 25 units/L). The blood sugar was 70mg/ dl, haemoglobin 12.3 gm%, serum sodium (134 mEq/ l), potassium (4.2 mEq/L), chlorides (102 mEq/L), creatinine (0.9mg/dl), AST (24 IU/ dl) and ALT (22 IU/ dl) were within normal limits. She was treated with dopamine, dobutamine, furosemide and digoxin. She responded to therapy with disappearance of signs of cardiac failure. The inotropes were tapered off. However, her exercise tolerance was so poor that she was breathless on walking a few steps. She had bilateral immature cataract. Chvostek’s sign and Trousseau’s sign were positive. The serum calcium was 0.98 mmol/L (normal range: 2.2-2.6 mmol/L), albumin: 36g/L (normal range: 35-55g/L) and phosphorus: 2mmol/L (normal range: 1.0-1.4 mmol/L).
Why should one measure serum calcium and albumin simultaneously?
The concentration of serum proteins is an important determinant of calcium ion concentration; most calcium is bound to albumin. If ionic calcium cannot be measured, certain approximations can be made to estimate protein-bound and ionised fractions.
% protein-bound Ca = 0.8 x albumin (g/L) + 0.2 x globulin (g/L) + 3
A simplified correction when serum albumin is low: to add 0.8 mg/dL to the serum calcium level for every 1 gm/dL by which the serum albumin is below 4 gm/dL.
On enquiry, she admitted to have a history of carpopedal spasm intermittently and tingling of all extremities for the last 15 years. Her symptoms had worsened while lactating her child 3 years back. She had a progressive decline in vision over the last 3 years. She had dyspnoea on exertion NYHA class I-II for the last 3 months. She had no deformities, bony pain, fractures or vitiligo. Her child did not have neonatal tetany. There was no history suggestive of malabsorption, thyroid dysfunction, alcohol abuse, previous neck surgery or family history of similar illness.
* Critically ill with severe sepsis or burns.
* Acute renal failure
* Extensive transfusion with citrated blood.
* Medication with protamine or heparin.
* Hypoalbuminaemia can lower total calcium concentration.
* Acute pancreatitis with extensive fat necrosis.
* Vitamin D deficiency due to poor nutrition, low sun light
exposure, defective metabolism due to long term ingestion of anticonvulsants as phenytoin or phenobarbitone, intestinal malabsorbtion or obstructive jaundice.
* Chronic renal failure.
* Hereditary or acquired hypoparathyroidism.
* Hypomagnesemia. 
What conditions can cause hypocalcemia in a 30-year old female?
Arterial blood gases were normal; urinary pH was normal; serum parathormone (PTH): 3.8 pg/ml (normal: 12 to 72 pg/ml); serum 25-(OH) vitamin D: 19.3 ng/ml (normal: 9.9 to 41.5 ng/ml); serum magnesium: 0.71 mmol/L; alkaline phosphatase: 3.14 KA units/ml and albumin: 30 g/L.
How does one explain worsening of symptoms during pregnancy and lactation?
Relief of tetany has been reported to occur in women suffering from hypoparathyroidism during both pregnancy and lactation. This may be secondary to a rise of PTH-related peptide concentration. So there may be a reduced need for vitamin D therapy during this time. But in our country, deficiency states of calcium and vitamin D are highly prevalent. Also, hypoparathyroidism itself can reduce the formation of active vitamin D. These factors may be responsible for worsening of symptoms during pregnancy and lactation.2
How does one explain lack of hypocalcaemia in a newborn baby despite the mother having significant hypocalcaemia?
Mineralisation of the fetal skeleton is provided for by active calcium transport from mother to foetus across the placenta. Maternal hypocalcaemia results in reduced calcium delivery to the foetus. This stimulates foetal parathyroid secretion and maintains normal calcium levels postpartum.3
What should be your approach to a case of chronic hypocalcaemia?
A pattern of low calcium with high phosphorus in the absence of renal failure or massive tissue destruction almost invariably means hypoparathyroidism or pseudohypoparathyroidism. A low calcium with low phosphorus points to absent or ineffective vitamin D, which impairs the action of PTH on calcium metabolism but not on phosphate clearance. There are exceptions to these rules: Chronic alcoholics with nutritional hypomagnesaemia have hypoparathyroidism. Yet, phosphate levels are low. Patients with chronic renal failure often have hypocalcaemia and hyperphosphataemia despite having secondary hyperparathyroidism.
In hereditary or acquired hypoparathyroidism and in severe hypomagnesemia PTH levels are either undetectable or are within normal range. With ineffective PTH action due to abnormalities in vitamin D action, even mild hypocalcaemia is associated with elevated PTH levels. A low or low normal 25(OH)D level indicates vitamin D deficiency due to lack of sun light, inadequate vitamin D intake or intestinal malabsorption. A low level of 1,25(OH)2D in the presence of elevated concentrations of PTH suggests ineffective PTH action in disorders such as chronic renal failure, severe vitamin D deficiency, vitamin D – dependent rickets type I, and PHP. The presence of mild hypocalcemia, rickets, and hypophosphatemia related to anticonvulsant therapy can be identified from the history.1
An ophthalmologic evaluation revealed bilateral zonular cataract and no evidence of papilloedema. CT scan brain showed supra- and infra-tentorial neuroparenchymal calcification. Thyroid function tests were normal and anti-microsomal antibodies were negative.
Oral calcium supplements (4gms/day) were started. However, even after four weeks of admission, she had hypocalcaemia (serum calcium 1.03 mmol/ L and serum phosphorus 1.67 mmol/L). The 24-hour urinary calcium excretion was 0.58mmol/ day (normal: <7.5 mmol/day). Her exercise tolerance would markedly improve with injection calcium gluconate. Addition of vitamin D therapy helped maintain her serum calcium levels. Daily oral elemental calcium (3 g) and weekly oral vitamin D (6 lakh units) normalised serum levels (serum calcium: 2.08 mmol/L, phosphorus: 1.1 mmol/L, magnesium: 0.67 mmol/L). Within a week of this therapy she could walk on a level ground without dyspnoea.
On discharge, (2 weeks after this therapy) she could climb a flight of stairs easily. She was never put on ACE inhibitors. Subsequently, she conceived. Throughout the pregnancy, serum calcium and phosphorus were maintained between 1.81-1.96 mmol/L and 1.1-1.4 mmol/L, respectively. She delivered a full term healthy male child.
How should this patient monitored in order to prevent complications of therapy?
Serum calcium is monitored 2-3 times per week till the dose of vitamin D and calcium are stable, then 6 monthly. 24 hour urinary calcium is checked monthly for 3 months, then 6 monthly. If it is more than 300 mg/day with serum calcium <2 mmol/L, oral thiazide is added to reduce hypercalciuria.Serum Phosphorus is checked 2-3 times per week till the dose of vitamin D and calcium are stable, then 6monthly.If calcium normal and phosphorus >1.93 mmol/L, add non absorbable antacid to reduce gut absorption of phosphorus to prevent metastatic calcification.5
She came 40 months later for follow-up. She had been regularly on 2 gms of calcium per day with 6 lakh units of vitamin D weekly in the intervening period and had also undergone surgery for cataract. She was asymptomatic, but 2D-echocardiography still showed a dilated cardiomyopathy with global hypokinesia with an ejection fraction that had improved from 20% to 35%. Her serum calcium was 2.13mmol/L and phosphorus 1.1mmol/L. Both her babies had normal levels of serum calcium.
How does hypoparathyroidism lead to the development of cardiomyopathy?
The mechanisms6 for the development of cardiomyopathy in patients with hypoparathyroidism include hypocalcaemia (the most important), hypomagnesaemia, decreased levels of circulating parathormone, other metabolic changes due to hypoparathyroid state and coexisting myocardial disease.
Calcium plays an important role in myocardial function. As sarcoplasmic reticulum is unable to sequester a sufficient quantity of calcium ion to initiate contraction a supplemental extra-cellular source of calcium ions is required. The strength of the contraction is influenced by the magnitude of influx of extra-cellular calcium.
At renal level, a rise in cytosolic free calcium level in renal tubular cells will promote natriuresis.7 Conversely, a fall in cytosolic calcium may increase renal sodium reabsorbtion. Thus sodium retention during hypocalcaemia may be a factor in the pathogenesis of cardiac failure.
The resolution of congestive cardiac failure associated with hypoparathyroidism with treatment of the metabolic abnormalities induced by hypoparathyroidism, strongly supports the causal relationship between hypocalcaemia and the cardiomyopathy.
Which conditions can cause a reversible form of dilated cardiomyopathy?
• Alcohol abuse
• Selenium deficiency
• Thyroid disease
• Cocaine use
• Chronic, uncontrolled tachycardia3
|1||Braunwald E, Fausi AS, Kasper DL. et al. eds. Harrison’s Principles of Internal Medicine. 15th edn. McGraw-Hill: 2001.|
|2||Rude RK. Hypocalcaemia and hypoparathyroidism. In Bardin CW, ed. Current therapy in Endocrinology and Metabolism: Mosby publications; 1997. 6th edn. pp. 546-51.|
|3||Mimouni FB, Wroot A. Disorders of Calcium Metabolism in the Newborn. In Sperling MA ed. Pediatric Endocrinology. Philadelphia: WB Saunders;1996. pp. 95-115.|
|4||Favus MJ, ed. Primer on the Metabolic Bone Disease and Disorders of Mineral Metabolism. 3rd edn. 1996. Appendix p. 454. |
|5||Goltzman D, Cole DEC. Hypoparathyroidism. In Primer on the Metabolic Bone Disease and Disorders of Mineral Metabolism. 3rd edn. 1996. pp. 220-23. |
|6||Brenton DP, Gonzales J, Pollard AB. Hypocalcemic cardiac failure. Postgrad Med J 1978;54:633-6.|
|7||Breslau NA. Calcium, magnesium and phosphorus:renal handling and urinary excretion. In Primer on the Metabolic Bone Disease and Disorders of Mineral Metabolism. 3rd edn. 1996. pp. 49-6.|