Early Left Ventricular Dysfunction and Chelation Therapy in Thalassemia Major

Freeman, Anthony; Giles, R.; Berdoukas, Vasilios; Walsh, Warren F.; Choy, Daniel S.J.; Murray, Provan C.

doi:10.7326/0003-4819-99-4-450

Cited by 81 publications

(41 citation statements)

References 24 publications

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“…15,[29][30][31][32] In this paper, we have observed LVEF changes over a median period of 6 years, with 25% of the patients being observed between 12 and 20 years. It is clear that detectable changes in systolic function precede the development of clinical heart failure sufficiently early for a useful intervention strategy to be adopted.…”

Section: Discussionmentioning

confidence: 94%

“…47 Furthermore, a wide overlap between LVEF responses of subjects with angiographically normal hearts and those with coronary artery disease is now recognized, 48 whereas invariable increases in LVEF had been reported initially. 49 Exercise LVEF testing using MUGA with a follow up of 1 to 4 years was reported by Freeman et al 29,31 in 23 thalassemia major patients receiving subcutaneous DFO. Although a minority of patients had abnormal resting LVEF values, most showed abnormal exercise responses, suggesting an increased sensitivity of exercise compared with resting LVEF.…”

Section: Discussionmentioning

confidence: 99%

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Value of sequential monitoring of left ventricular ejection fraction in the management of thalassemia major

Davis

O’Sullivan

Jarritt

et al. 2004

Blood

157

133

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Regular monitoring of left ventricular ejection fraction (LVEF) for thalassemia major is widely practiced, but its informativeness for iron chelation treatment is unclear. Eighty-one patients with thalassemia major but no history of cardiac disease underwent quantitative annual LVEF monitoring by radionuclide ventriculography for a median of 6.0 years (interquartile range, 2-12 years). Intraobserver and interobserver reproducibility for LVEF determination were both less than 3%. LVEF values before and after transfusion did not differ, and exercise stress testing did not reliably expose underlying cardiomyopathy. An absolute LVEF of less than 45% or a decrease of more than 10 percentage units was significantly associated with subsequent development of symptomatic cardiac disease (P < .001) and death (P ‫؍‬ .001), with a median interval between the first abnormal LVEF findings and the development of symptomatic heart disease of 3.5 years, allowing time for intervention. In 34 patients in whom LVEF was less than 45% or decreased by more than 10 percentage units, intensified chelation therapy was recommended (21 with subcutaneous and 13 with intravenous deferoxamine). All 27 patients who complied with intensification survived, whereas the 7 who did not comply died (P < .0001). The KaplanMeier estimate of survival beyond 40 years of age for all 81 patients is 83%. Sequential quantitative monitoring of LVEF is valuable for assessing cardiac risk and for identifying patients with thalassemia major who require intensified chelation

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Value of sequential monitoring of left ventricular ejection fraction in the management of thalassemia major

Davis

O’Sullivan

Jarritt

et al. 2004

Blood

157

133

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“…'-4 In patients with normal systolic function at rest, a subnormal ejection fraction response to exercise has been identified by radionuclide angiography. 25,26 Left ventricular diastolic filling has never been investigated systematically in patients with thalassemia major. A restriction to ventricular diastolic filling, however, has been described in some patients with idiopathic hemochromatosis.5-7 In the present study, we used Doppler echocardiography to assess left ventricular diastolic filling in a relatively large group of patients with thalassemia major who were free of cardiac symptoms and had normal left ventricular systolic function and diastolic cavity dimension.…”

Section: Discussionmentioning

confidence: 99%

Restrictive diastolic abnormalities identified by Doppler echocardiography in patients with thalassemia major.

et al. 1990

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The consequences of transfusional iron overload on left ventricular diastolic filling have never been investigated systematically in patients with thalassemia major. In the present study, the pattern of left ventricular filling was assessed by Doppler echocardiography in 32 patients with thalassemia major (age, 17±5 years) who had not experienced symptoms of heart failure and had normal left ventricular systolic function. Data were compared with those obtained in 32 age-matched and sex-matched normal subjects. An abnormal Doppler pattern of left ventricular filling with increased flow velocity at mitral valve opening followed by an abrupt and premature decrease of flow velocity in early diastole was identified in the patients with thalassemia. Peak flow velocity in early diastole was increased in patients compared with controls (90±10 vs. 81+ 15 cm/sec; p<0.01), and rate of deceleration of flow velocity after the early diastolic peak and the ratio between the early and late (atrial) peaks of flow velocity were also increased (1,050±325 vs. 762±+193 cm/sec2 and 2.7±0.7 vs. 2.2+0.5, respectively;p<0.001) whereas flow velocity deceleration time was reduced (97±22 vs. 119±19 msec; p<0.001). This Doppler pattern of diastolic filling is usually described as "restrictive" and reflects a decrease in left ventricular chamber compliance. A restrictive pattern of left ventricular filling was also identified in the subgroup of 16 study patients who had undergone optimal iron chelation therapy with deferoxamine. Rate of deceleration of flow velocity after the early diastolic peak was increased, and flow velocity deceleration time was reduced in these 16 patients (1,080+±356 cm/sec2 and 94±19 msec) compared with controls (795±214 cm/sec2 and 118+19 msec, respectively; p<0.01). The results of this investigation demonstrate that left ventricular filling is altered in patients with thalassemia major and that diastolic abnormalities develop in an early phase of cardiac involvement, when symptoms of heart failure are absent and systolic function is normal. The findings of this study also suggest that chelation therapy with deferoxamine does not completely protect patients with thalassemia from myocardial danmage due to iron-related cardiac toxicity. (Circulation 1990;82:88-94) In patients with thalassemia major, long-terrn transfusion therapy, extravasal hemolysis, and increased intestinal absorption of iron result in systemic iron overload; the deposition of iron in the inyocardium causes left ventricular dysfunction.1-2 Although hemochromatosis of the heart is generally described as a dilated cardiomyopathy with increased left ventricular diastolic cavity dimension and depressed systolic function1-4 a restrictive cardiomyopathy with impaired left ventricular filling has also been reported in some patients with idiopathic hemochromatosis.5 7 Diastolic filling, however, has never been systematically investigated in patients with thalassemia major.Doppler echocardiography has been extensively used to assess left ventricular dias...

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“…The significance of this observation could be a lower stroke volume on exercise in adults than in children. LV dysfunction during exercise has been proposed as an early marker of cardiac impairment in thalassaemia [24], followed by moderate ventricular dilatation and LV dysfunction at rest later in the course of the disease [7,25]. Other authors have described an abnormal contraction and relaxation of the posterior LV wall [26].…”

Section: Discussionmentioning

confidence: 99%

Lung function and exercise capacity in thalassaemia major

Cracowski¹,

Wuyam²,

Klein³

et al. 1998

Eur Respir J

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Lung function abnormalities in thalassaemia major are various and complex; however, patients still die from cardiac lesions. This study aimed to investigate pulmonary and cardiac involvement at an early stage in thalassaemic patients and study their respective implications at rest and during exercise. Ten patients (five adults and five children) with thalassaemia major were investigated by echocardiography, lung function and exercise testing a few days after transfusion. All have had regular transfusions and chelation with deferoxamine and none had chronic pulmonary disease symptoms. Minor lung function abnormalities were found: two patients had moderate obstructive syndrome and two had a decreased carbon monoxide transfer factor. Hypoxaemia was never found at rest and no desaturation was observed at the end of exercise. Echocardiographic abnormalities were also moderate. Peak oxygen consumption (V'O2) was decreased in three adults and was lower in adults than children (means 27.7+/-4.6 and 41.1+/-4.8 mL.kg(-1).min(-2) respectively). The V'O2/cardiac frequency slope was lower in adults than children (0.25+/-0.06 versus 0.42+/-0.10 mL.kg(-1).min(-2)), whereas end-exercise breathing reserve was >40% maximal voluntary ventilation for all patients. In conclusion, none of the patients had ventilatory limitations but older patients had cardiac limitations assessed by the relationship between oxygen consumption and cardiac frequency. Exercise testing may detect cardiac impairment in thalassaemia major earlier than investigations at rest.

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Early Left Ventricular Dysfunction and Chelation Therapy in Thalassemia Major

Cited by 81 publications

References 24 publications

Value of sequential monitoring of left ventricular ejection fraction in the management of thalassemia major

Value of sequential monitoring of left ventricular ejection fraction in the management of thalassemia major

Restrictive diastolic abnormalities identified by Doppler echocardiography in patients with thalassemia major.

Lung function and exercise capacity in thalassaemia major

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