Left ventricular function in patients with chronic hypophosphatemia

April,

796

Brief

Communications

American

1984

Heart Journal

position and major coarsesystolic fluttering of the leaflets as its echocardiographiccorrelate. We speculatethat the ejected blood acting upon the shaggy and incompetent free border of the leaflets may have been the underlying mechanism. Caution should be exercised in attributing mild systolic flutter to bioprosthetic valve tear. Serial major coarsefluttering in associationwith appearanceof an aortic diastolic murmur should, however, suggestthe diagnosisof xenograft dysfunction. REFERENCES

1. Cohn LH, Koster J, Mee RBB, Collins JJ Jr: Long-term follow-up of the Hancock bioprosthetic heart valve: A 6-year review. Circulation 6O(suppl):I-87, 1979. 2. Lakier JB, Khaja F, Magilligan DJ Jr, Goldstein S: Porcine xenograft valves: Long term (60-89 month) follow-up. Circulation 62:313, 1980. 3. Carpentier A, Deloche A, Relland J, Fabiani JN, Forman J, Camilleri JP, Soyer R, Dubost C: Six-year follow up of glutaraldehyde-preserved heterografts. With particular reference to the treatment of congenital valve malformations. J Thorac Cardiovasc Surg 68:771, 1974. 4. McIntosh CL, Michaelis LL, Morrow AG, Itscoitz SB, Redwood DR, Epstein SE: Atrioventricular valve replacement with the Hancock porcine xenograft: A five-year clinical experience. Surgery 78:768, 1975. 5. Alam M, Madrazo AC, Magilligan DJ, Goldstein S: M-mode and two dimensional echocardiographic features of porcine valve dysfunction. Am J Cardiol 43:502, 1979. 6. Harrison EE, Sbar S, Spoto E, Jr, Clark P: Echocardiogram in porcine mitral valve dysfunction (letter). Am J Cardiol 45:908, 1980. 7. Alam M, Goldstein S: Echocardiogram in porcine mitral valve dysfunction (Reply to letter). Am J Cardiol 45:908, 1980. 8. Cunha CL, Giuliani ER, Callahan JA, Pluth JR: Echophono-

cardiographic findings in patients with prosthetic heart valve malfunction. Mayo Clin Proc 55:231, 1980. 9. Bloch WN Jr, Felner JM, Schlant RC, Symbas PN, Jones EL: The echocardiogram of the porcine aortic aortic position. Chest 72:640, 1977.

bioprosthesis

Left ventricular function in patients chronic hypophosphatemia

in the

with

Zvi Vered, M.D., Alexander Battler, M.D., Michael Motro, M.D., Menachem Frank, M.D., Ram Inbar, M.D., and Henry N. Neufeld, M.D. Tel Hashomer,

Israel

Several recent reports have suggested that marked hypophosphatemiamay be associatedwith left ventricular (LV) dysfunction and may produce congestive cardiomyopathy.‘*2 Darsee end Nutter’ described three patients with congestive cardiomyopathy appearing secondary to hypophosphatemiadue to ingestion of aluminum hydroxide, which was reversible after phosphate replacement. From the Heart Institute and Metabolic Unit, Chaim Sheba Medical ClX&!r. Reprint requests: Zvi Vered, M.D., Heart Institute, Chaim Sheha Medical Center, Tel Hashomer 52621, Israel.

SWT Fig. 1. Normal echocardiogram. LV = left ventricle; IVS = interventricular septum; SWT = systolic wall thickness; ES = end systole; ED = end diastole.

O’Connor et al.’ presentedsevencritically ill patients with hypophosphatemia, in whom hemodynamic studies showedimproved LV stroke work after administration of phosphate. We studied cardiac function in 10 patients with chronic hypophosphatemia using echocardiography and radionuclide ventriculography. Seven were malesand three were females; their mean age was 55.4 years, range 45 to 68 years.All patients underwent a metabolic workup. Serum parathyroid hormone (PTH) or urinary cyclic adenosine monophosphate (AMP) were measured only when parathryoidectomy was contemplated. In Table I the clinical and laboratory findings of these patients are summarized. Included

in our study were patients

with

mean serum

phosphate levels of 2.0 mg/dl or less during the last 2 years. At least three out of five most recent phosphate levelswere under 2 mg/dl (normal range in our laboratory is 2.5 to 4.5 mg/dl). Mean + SD phosphate level during the study was 1.89 t 0.18 mg/dl. M-mode echocardiographic studies were performed with a SmithKline Ekoline 20A Ultrascope equipped with a 2.25 MHz transducer. LV function wasevaluated by the following: (1) interventricular diastolic

septum and posterior wall motion, (2) enddimension, (3) end-systolic dimension, end (4)

calculated fractional shortening. Multigated equilibrium radionuclide ventriculography wasperformed after in vivo labeling of red blood cells with 20 to 30 mCi of technetium-99m (Tc-99m), es previously described.3Radionu-

elide ventriculography was performed at rest only. Mmodeechocardiographicstudiesrevealed normal LV function in all 10 patients

(Table

I end Fig. 1). Radionuclide

Volume Number

Table

107 4

Brief Communications

797

I. Clinical and laboratory data Echocardiographic

No.

Age fyr)

1 2 3 4 5 6 7 8 9 10

P Sex

(mgldl)

50 52 53 66 45 5'7 57 46 48

M M M M M M F M

1.6 2.0 1.5 1.8 2.0 2.0 2.0 1.9 2.0

9.7 9.7 9.0 9.9 9.5 10.0 9.2 11.3 12.2

68

F

2.0

12.1

F

(rnzdl)

Clinical

P = phosphorus;

Ca = calcium;

EDD

= end-diastolic

EDD (cm)

ESD

4.3 3.8 3.8 5.0 5.0 5.3 5.2 4.3 4.0

2.6 2.8 2.5 3.7 3.2 3.0 3.0 3.0 2.8

39 26 34 26 36 41 30 30 30

4.6

3.2

30

4.53 * 0.57

2.98 k 0.34

33.5 + 6.07

picture

Idiopathic, nephrolithotomy, left nephrectomy Idiopathic, bilateral nephrolithotomy Idiopathic, bilateral ureteronephrolithotomy Idiopathic, right ventricular dysfunction Idiopathic, right ureterolithotomy Idiopathic, right pylolithotomy Hyperparathyroidism, parathyroidectomy Hyperparathyroidism Hyperparathyroidism, right ventricular dysfunction Hyperparathyroidism, parathyroidectomy, anginal syndrome, myxedema, right ventricular dysfunction Mean dimension;

ESD

+ SD

= end-systolic

ventriculographic studiesrevealed normal LV global function in all 10 patients. Mean ejection fraction was 62 f 6%. In two patients LV regional dysfunction was observed.One presentedtypical clinical and ECG features of old myocardial infarction in the samearea. The other gave a typical history of anginal syndrome, but the ECG was normal. In two patients right ventricular global function was diminished, right ventricular ejection fraction being 437%and 46% , respectively, and in an additional patient right ventricular regional dysfunction was observed. Various systemshave been described to be affected by hypophosphatemia.4The possible mechanism that has been suggested is a diminished amount of adenosine triphosphate (ATP) in the cell due to hypophosphatemia.5,6 This condition may be seenin situations such as diabetes, alcohol withdrawal, after burns, in respiratory alkalosis,or causedby phosphatebinding subjects,aswell as in casesof hyperalimentation.7 The systems involved are striated muscles,red blood cells,5-7white cells,8and thrombocyte@; even respiratory failure hasbeendescribed asreversible after phosphate replacement.‘OIn one study” induced hypophosphatemia caused myocardial dysfunction in dogs, reversible after the administration of phosphate. Surprisingly little data exist on the effect of hypophosphatemiaon cardiac function in humans.In one publication,’ chronic ingestion of aluminum hydroxide caused hypophosphatemia and the clinical picture of congestive cardiomyopathy in three patients, reversible after phosphate replacement. In another report,2 hemodynamic studies showed improved stroke work in seven critically ill patients associated with improvement in hypophosphatemia after phosphate replacement. Our patients presented with pure, long-standing, clinically significant hypophosphatemia, and in all LV function was found to be normal. A possibleexplanation for

dimension;

results

FS = fractional

(cm)

Percent

FS

shortening.

the discrepancy between our results and the previously described data is the difference in the severity of hypophosphatemia. The patients described by Darsee and Nutter’ and by O’Connor et al.2 had mean serum phosphate level of 0.4 mg/dl and just below 1 mg/dl, respectively, while our phosphatelevels ranged between 1 and 2 mg. Many of the signs and symptoms of hypophosphatemia tend to appear with serumphosphatelevelsbelow 1 mg/dl, but these severe casesare seldom observed in clinical practice. Serum phosphatelevelsof 1 to 2 mg/dl, which are still significant, are much more common.We can conclude that in this group of patients hypophosphatemiaalonedid not causeLV dysfunction. In none of our patients was hypophosphatemiacausedby the ingestion of aluminum hydroxide, and all were in good health during the study. Since LV function wasnormal in all 10 patients, administration of phosphate seemed not to be justified. An interesting finding was right ventricular dysfunction in three patients. None of them had a history of hypertension or coronary disease, that have been reported as causing right ventricular dysfunction,” but two of them had a past medical history of heavy smoking and it is possible that right ventricular dysfunction was due to obstructive lung disease,as described previously.13None of these patients had right ventricular dilatation on echocardiographic evaluation. Our results suggest that long-standing, clinically significant hypophosphatemia due to primary hyperparathyroidism or idiopathic hypophosphatemia is not necessarily associatedwith LV dysfunction. REFERENCES

1. Darsee JR, Nutter DO: Reversible severe congestive cardiomyopathy in three cases of hypophosphatemia. Ann Intern Med 89~867, 1978. 2. O’Connor LR, Wheeler WS, Bethune JE: Effect of hypophos-

April,

798

<7 .

4. 5.

6.

7.

8.

9.

10.

11.

12. 13.

Brief

Communications

American

nhatemia on myocardial performance in man. N Engl J Med i97:901, 1977. Bodenheimer MM, Banka VS, Helfant RH: Radionuclide angiographic assessment of left ventricular contraction. Uses, limitations and future directions (Review). Am J Cardiol 453:661. 1980. Lotz M, Zisman E, Bartter FC: Evidence for phosphorus depletion syndrome in man. N Engl J Med 278:409, 1968. Young JA, Lichtman MA, Cohen J: Reduced red cell 2, 3 diphosphoglycerate and adenosine triphosphate, hypophosphatemia, and increased hemoglobin-oxygen affinity after cardiac surgery. Circulation 47:1313, 1973. Lichtman MA, Miller DR, Freeman RB: Erythrocytes adenosine triphosphate depletion during hypophosphatemia in a uremic subject. N Engl J Med 74:562, 1971. Travis ST, Sugerman HJ, Ruberg RL, Dudrick SJ, DeliovoriPapadopoulos M, Miller LD, Oski FA: Alteration of red cell glycolytic intermediates and oxygen transport as a consequence of hypophosphatemia in patients receiving intravenous hyperalimentation. N Engl J Med 285:763, 1971. Craddock PR, Yawata Y, Silvis S, Jacob H: Phagocyte dysfunction induced by intravenous hyperalimentation (abstr). Clin Res 21:597, 1973. Knochel JP: The pathophysiology and clinical characteristics of severe hypophosphatemia. Arch Intern Med 137:203, 1977. Newman JH, Neff TA, Ziporin P: Acute respiratory failure associated with hypophosphatemia. N Engl J Med 296:1101, 1977. Fuller TJ. Nichols WW, Brenner BJ, Peterson dC: Reversible depression in myocardial contractility in the dog with experimental phosphorus deficiency (abstr). Clin Res 26:32A, 1978. Ferlinz J: Right ventricular performance in essential hypertension. Circulation 61:156, 1980. Slutsky R, Hooper W, Gerber K, Battler A, Froelicher J, Ashburn W, Karliner D: Assessment of right ventricular function at rest and during exercise in patients with coronary heart disease. A new approach using equilibrium radionuclide angiography. Am J Cardiol 45:63, 1980.

Mild myocardial inflammation as congestive cardiomyopathy to immunosuppression

presenting responsive

Jeffrey G. Shanes,M.D., Ronald J. Krone, M.D., Cheng C. Tsai, M.D., Keith Fischer, M.D., and George A. Williams, M.D. St. Louis, MO.

The prognosisfor patients with a congestive cardiomyopathy is extremely poor. However, someof these patients, those with an inflammatory myocarditis, may respond to immunosuppressivetherapy. Mason et al.’ have shownthe From the Division of Cardiology and the Department Jewish Hospital of St. Louis, Washington University; Cardiology and the Department of Pathology, St. Louis Center. Reprint requests: Jeffrey G. Shanes, M.D., Division of sity of Illinois at Chicago, P.O. Box 6998, Chicago, IL

of Radiology, The and the Division of University Medical Cardiology, 60680.

Univer-

A-

-’

--.-...

y-&z __

‘.. _

Heart

1984 Journal

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6 -

1. M-mode echocardiogram before therapy. A, Mitral valve level. B, Left ventricular level. Note dilatation (left ventricular internal dimension, diastolic [LVIDd] = 7.3 cm; left ventricular internal dimension, systolic [LVIDs] = 6.0 cm) and left ventricular dysfunction (increased e point [arrow] to septal separation and ejection fraction = 44%). There are alsofrequent multifocal ventricular premature contractions. Fig.

usefulnessof endomyocardial biopsy for the specific diagnosisof inflammatory myocarditis. They have emphasized that in order to make such a diagnosisand justify the risks of treatment with immunosuppressive therapy, heavy lymphocytic infiltration must be found.* We describe a casein which only a mild-to-moderate lymphocytic infiltrate wasdocumented by endomyocardial biopsy, yet the responseto high-dose immunosuppressivetherapy was dramatic. W.P., a 24-year-old white man, was transferred to The Jewish Hospital of St. Louis for the evaluation of congestive heart failure (CHF). He had been in excellent health until 6 months prior to admission,when he noted effortrelated precordial discomfort. At the time of admissionhe presented with pulmonary edema, atria1 fibrillation, and complex ventricular arrhythmias. There wasno history of alcohol abuse or viral illness. Physical examination was remarkable for marked cardiomegaly, elevated jugular