Cardiac involvement in bone marrow transplantation: serial changes in left ventricular size, mass and performance

Abstract

Forty-five consecutive adult patients with haematological malignancies were studied prospectively to evaluate cardiac involvement in bone marrow transplantation (BMT). Echocardiography and measurement of systolic time intervals were performed before conditioning with cyclophosphamide (CY) (120 mg kg-1) and total body irradiation (10-12 Gy), and repeated 1 month and 1 year after BMT. The left ventricular (LV) changes at the 1-month study included increases in mass index (85.1 +/- 4.0 g m-2 vs: 76.1 +/- 3.3 g m-2, mean +/- SE; P less than 0.001) and in the pre-ejection period/ejection time ratio (0.46 +/- 0.01 vs. 0.36 +/- 0.01, P less than 0.001), and decreases in fractional shortening (24.9 +/- 1.0% vs. 27.9 +/- 0.8%, P less than 0.01) and in the peak normalized diameter lengthening rate (2.2 +/- 0.1 s-1 vs. 2.6 +/- 0.1 s-1, P less than 0.01). Four patients developed congestive heart failure. Twenty-four patients were alive and relapse-free 1 year after BMT. The LV measurements were then no longer different from the pre-transplant readings. Thus BMT that is preceded by conditioning with CY and total body irradiation results in increased LV mass and impaired systolic and diastolic LV function. These changes are mostly subclinical, and are also reversible if the recipient survives the initial months after transplantation.

Cardiac toxicity of high-dose chemotherapy

“…Since its initial description 30 years ago, 11 it has been reported by many others, 10,[12][13][14][15][16][17][18][19][20][21][22][23] with a wide spectrum of incidence, manifestation and severity. 10,[12][13][14][15][16][20][21][22][23] On the basis of postmortem examination, [10][11][12]14,15,20,21,24 the pathophysiology of HD cyclophosphamide-associated cardiac toxicity is thought to depend upon toxic endothelial damage followed by extravasation of toxic metabolites with resultant myocyte damage and interstitial hemorrhage and edema. HD cyclophosphamide-associated cardiotoxicity occurs during or soon after (within 3 weeks) administration.…”

“…Following administration of HD cyclophosphamide, nonspecific and transient electrocardiogram (ECG) abnormalities 10,15,18,21 and left ventricular ejection fraction (LVEF) drops 10,15,23 have been recorded with no predictive value for the subsequent development of clinically relevant cardiotoxicity. These alterations are expected to return toward baseline within a few days or weeks in most cases.…”

“…These alterations are expected to return toward baseline within a few days or weeks in most cases. 8,10,15,18,21,23 Therapy with diuretics should be started in the first instance. The addition of an angiotensin-converting enzyme inhibitor in case of ECG and/or two-dimensional echocardiogram (2D echo) evidence of impaired left ventricular contraction, the patient not being hypotensive, should be considered according to established guidelines.…”

Assessment of cardiotoxicity during haemopoietic stem cell transplantation with plasma brain natriuretic peptide

“…4,30,32 Data suggest that dosing may be an important risk factor. 5 Echocardiographic abnormalities develop in over half of paediatric patients 1 week after and persist for several weeks beyond high-dose cyclophosphamide administration.…”

“…The toxic effects of cyclophosphamide on the myocardium have been documented in HSCT patients using other methods including serial ECGs, 7 echocardiography, 30 PET scanning 31 and, in severe cases, autopsy findings of haemorrhagic myocardial necrosis. 4,30,32 Data suggest that dosing may be an important risk factor.…”