Survival in Thalassaemia Major Patients  Prognostic Value of Doppler-Demonstrated Left Ventricular Restrictive Filling Pattern

Efthimiadis, Georgios K.; Hassapopoulou, Helen P.; Tsikaderis, Dimitrios; Karvounis, Haralambos; Giannakoulas, George; Parharidis, Georgios E.; Louridas, Georgios E.

doi:10.1253/circj.70.1037

Cited by 24 publications

(8 citation statements)

References 29 publications

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“…Two long-term observational studies following consecutive patients with TDT showed that survival was significantly improved for patients with better compliance to deferoxamine [28,29]. In the first study (N=257; duration 30 years), Gabutti and Piga found that patients with >70% compliance (58% of patients) had a survival rate of 98% compared with a survival rate of 46% for poorly chelated patients ( p <0.000001) [28].…”

Section: Adherence To Ictmentioning

confidence: 99%

“…In the first study (N=257; duration 30 years), Gabutti and Piga found that patients with >70% compliance (58% of patients) had a survival rate of 98% compared with a survival rate of 46% for poorly chelated patients ( p <0.000001) [28]. In the second study (N=45; duration 15 years), Efthimiadis and colleagues found that patients with excellent compliance (20% of patients; ICT 6–7 days/week) had a 15-year cumulative survival of 100% compared with 52% survival for patients with poor compliance (47% of patients; ICT ≤3 days/week; p =0.018) [29]. In an analysis using a Markov model based on multiple data sources, including the observational study from Gabutti and Piga mentioned above, adequate compliance to deferoxamine was associated with a decreased risk of complications, including cardiac disease (60% vs 96%), diabetes (9% vs 54%), hypogonadism (47% vs 81%), and hypothyroidism (14% vs 28%) compared with typical compliance (i.e., compliance observed in clinical practice) [30].…”

Section: Adherence To Ictmentioning

confidence: 99%

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Advances in iron chelation therapy: transitioning to a new oral formulation

Shah

2017

DIC

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Iron overload is a concern for patients who require repeated red-blood-cell transfusions due to conditions such as sickle cell disease, thalassemia, or myelodysplastic syndromes. The recommended treatment for removing excess iron in these patients is iron chelation therapy. Currently available iron chelators include deferoxamine, which is administered by injection, and deferasirox and deferiprone, both of which are administered orally. Adherence to iron chelator therapy is an important consideration and may be affected by side effects. A new formulation of deferasirox, a film-coated tablet (FCT), has the potential to improve adherence by offering greater flexibility in administration compared with the original formulation of deferasirox, a dispersible tablet (DT) for oral suspension. This review provides an overview of the currently available iron chelator formulations, with a focus on a comparison between deferasirox DT for oral suspension and deferasirox FCT. The new formulation may be associated with fewer side effects and has increased bioavailability. In addition, alternative strategies for iron chelation, such as combining two different iron chelators, will be discussed.

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Section: Adherence To Ictmentioning

confidence: 99%

Section: Adherence To Ictmentioning

confidence: 99%

Advances in iron chelation therapy: transitioning to a new oral formulation

Shah

2017

DIC

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“…In one report of 45 patients with 15 years of follow-up, 11 patients died, and restrictive LV filling was predictive of death. 153 …”

Section: Diastolic Function and Compliancementioning

confidence: 99%

Cardiovascular Function and Treatment in β-Thalassemia Major

Pennell¹,

Udelson²,

Arai³

et al. 2013

Circulation

324

172

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This aim of this statement is to report an expert consensus on the diagnosis and treatment of cardiac dysfunction in β-thalassemia major (TM). This consensus statement does not cover other hemoglobinopathies, including thalassemia intermedia and sickle cell anemia, in which a different spectrum of cardiovascular complications is typical. There are considerable uncertainties in this field, with a few randomized controlled trials relating to treatment of chronic myocardial siderosis but none relating to treatment of acute heart failure. The principles of diagnosis and treatment of cardiac iron loading in TM are directly relevant to other iron-overload conditions, including in particular Diamond-Blackfan anemia, sideroblastic anemia, and hereditary hemochromatosis. Heart failure is the most common cause of death in TM and primarily results from cardiac iron accumulation. The diagnosis of ventricular dysfunction in TM patients differs from that in nonanemic patients because of the cardiovascular adaptation to chronic anemia in non–cardiac-loaded TM patients, which includes resting tachycardia, low blood pressure, enlarged end-diastolic volume, high ejection fraction, and high cardiac output. Chronic anemia also leads to background symptomatology such as dyspnea, which can mask the clinical diagnosis of cardiac dysfunction. Central to early identification of cardiac iron overload in TM is the estimation of cardiac iron by cardiac T2* magnetic resonance. Cardiac T2* <10 ms is the most important predictor of development of heart failure. Serum ferritin and liver iron concentration are not adequate surrogates for cardiac iron measurement. Assessment of cardiac function by noninvasive techniques can also be valuable clinically, but serial measurements to establish trends are usually required because interpretation of single absolute values is complicated by the abnormal cardiovascular hemodynamics in TM and measurement imprecision. Acute decompensated heart failure is a medical emergency and requires urgent consultation with a center with expertise in its management. The first principle of management of acute heart failure is control of cardiac toxicity related to free iron by urgent commencement of a continuous, uninterrupted infusion of high-dose intravenous deferoxamine, augmented by oral deferiprone. Considerable care is required to not exacerbate cardiovascular problems from overuse of diuretics or inotropes because of the unusual loading conditions in TM. The current knowledge on the efficacy of removal of cardiac iron by the 3 commercially available iron chelators is summarized for cardiac iron overload without overt cardiac dysfunction. Evidence from well-conducted randomized controlled trials shows superior efficacy of deferiprone versus deferoxamine, the superiority of combined deferiprone with deferoxamine versus deferoxamine alone, and the equivalence of deferasirox versus deferoxamine.

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“…Thus, the main concern is to detect early markers of cardiac function with prognostic impact on survival. In a previous work we have found that left ventricular (LV) restrictive filling pattern (RFP) is an important predictor of cardiac mortality in 45 asymptomatic transfusion‐dependent patients with TM 4 . The 15‐year cumulative survival rate was 58% in patients with LV RFP and 88% in patients with LV non‐RFP (log‐rank statistic = 6.02, P = 0.014).…”

mentioning

confidence: 93%

Prognostic Value of Doppler‐Demonstrated Left versus Biventricular Restrictive Filling Pattern in Thalassemia Major

Efthimiadis¹,

Giannakoulas²,

Hassapopoulou³

et al. 2008

Echocardiography

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ongestive heart failure is the main cause of death in transfusion-dependent homozygous-thalassaemia (thalassaemia major (TM)) patients. When symptoms of heart failure appear, death usually occurs within 1 year. 1,2 Although cardiac death is the most common cause of death in patients with TM, early markers of cardiac function with prognostic impact on survival have not yet been adequately defined. Deposition of iron in the heart is the major determinant of survival in these patients. 3,4 Left ventricular (LV) restrictive filling pattern (RFP), as assessed by Doppler-echocardiography, is a well-recognized feature of TM patients with normal LV systolic function, 5 although debated by some authors. 6,7 LVRFP, as assessed by Doppler-echocardiography, is characterized by an increase of the peak early to peak late filling velocity ratio (>2) and/or shortened deceleration time of early filling (<150 ms) because of impaired ventricular compliance. 8,9 Doppler-demonstrated LVRFP is an ominous sign in a variety of cardiac diseases with concomitant systolic heart failure, 10-13 but the clinical significance of restrictive physiology in TM patients has not yet been well established. The purpose of this longitudinal study was to investigate the impact of the Doppler-demonstrated LV filling pattern and also the impact of compliance with chelation therapy on survival in a cohort of asymptomatic TM adult patients with normal LV systolic function throughout a 15-year observation period. Methods Patients and Study Protocol All patients gave written informed consent and the protocol of this study was reviewed and approved by the institutional review board. Sixty-five consecutive TM patients, who were followed-up in the Thalassaemia Unit, were considered candidates for the analysis. All patients initially underwent clinical evaluation, chest X-ray, 12-lead ECG and Doppler-echocardiography from May 1989 to August 1989, in order to obtain baseline data, and then they were examined periodically by clinical examination and Doppler-echocardiography up to the end of the data collection (May 2004). The endpoint of the study was death from cardiovas-cular causes. Patients' inclusion criteria were: (1) age ≥14 years at the initial examination, (2) normal LV end-diastolic diameter (=55 mm) and normal LV systolic function (frac-tional shortening =30%), as assessed by echocardiography and (3) absence of any symptom of cardiac and/or pulmonary pathology. Among the 65 patients initially evaluated, 20 were excluded for the following reasons: 11 were <14 years of age; 4 had LV fractional shortening <30%; 5 died from non-car-Background The present study evaluated the prognostic significance of Doppler-demonstrated left ventricular (LV) restrictive filling pattern (RFP) in patients with thalassaemia major (TM), which carries an adverse cardio-vascular prognosis. Methods and Results The study group comprised 45 asymptomatic transfusion-dependent patients with TM and normal LV systolic function. All patients were chelated with desferrioxamine. They wer...

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Survival in Thalassaemia Major Patients Prognostic Value of Doppler-Demonstrated Left Ventricular Restrictive Filling Pattern

Cited by 24 publications

References 29 publications

Advances in iron chelation therapy: transitioning to a new oral formulation

Advances in iron chelation therapy: transitioning to a new oral formulation

Cardiovascular Function and Treatment in β-Thalassemia Major

Prognostic Value of Doppler‐Demonstrated Left versus Biventricular Restrictive Filling Pattern in Thalassemia Major

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