Lack of Heart Iron Overload in Patients with Thalassemia Intermedia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3822-3822
Author(s):  
Renzo Galanello ◽  
Mark Tanner ◽  
Gildo Matta ◽  
Susanna Barella ◽  
Patrizio Bina ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Ejection Fraction ◽  
Iron Overload ◽  
Thalassemia Major ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Cardiac Complications ◽  
Thalassemia Intermedia ◽  
Chronic Anemia ◽  
Parenchymal Cells

Abstract Iron loading in patients with thalassemia intermedia occurs slowly and is mainly due to increased gastrointestinal iron absorption secondary to chronic anemia, while in patients with thalassemia major iron overload is faster and secondary to the chronic transfusion therapy. Moreover, iron accumulation in thalassemia intermedia is prevalent in parenchymal cells, while in thalassemia major iron derived from red cell breakdown firstly accumulates in the reticulo-endothelial cells and subsequently in the parenchymal cells. Although heart disease represents the main determinant of survival in beta thalassemias, the cardiac complications are different in the two clinical forms, that are thalassemia major and thalassemia intermedia. In this study we evaluated liver and iron overload in patients with thalassemia intermedia. We have studied 8 patients with thalassemia intermedia with a mean age of 36 ± 12 years. All these patients were homozygotes for the beta zero 39 non-sense mutation (C→T) and were never transfused or had received only sporadic transfusions (less than 10 blood units throughout their life). Myocardial iron (heart T2*, Anderson et al 2001), echocardiographic left ventricular ejection fraction, serum ferritin (mean of the last 5 years) and hemoglobin (mean of the last 2 years) have been evaluated in each patient. Hepatic iron content was determined in 5 patients with atomic absorption after liver biopsy. Six patients were on chelation therapy with subcutaneous desferrioxamine (mean 2 ± 1 grams/week). Mean ferritin was 637 ± 497 ng/ml and mean hemoglobin 8.0 ± 1.0 g/dl. Heart T2* was normal in all patients (mean 46 ± 11 msec, range 36 – 62 msec). The mean left ventricle ejection fraction was 61 ± 6 % (range 51 – 70 %). Echocardiogram showed in all the patients a mild enlargement of both ventricles. Three patients had pulmonary hypertension and two had an extrasystolic arrhythmia. To our knowledge this is the first study reporting the results of heart T2* in thalassemia intermedia. As a consequence of the mechanism and rate of accumulation patients with thalassemia intermedia do not have heart iron overload, while liver iron concentration is quite relevant. Cardiac complications in thalassemia intermedia are mainly due to the hyperdynamic circulation associated with chronic anemia and to pulmonary hypertension.

scholarly journals Impact of a Ten-Year National Italian Networking on Cardiac Complications in Patients with Thalassemia Major

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1055-1055
Author(s):  
Alessia Pepe ◽  
Laura Pistoia ◽  
Aurelio Maggio ◽  
Annamaria Carrà ◽  
Maria Grazia Roberti ◽  
...  
Keyword(s):  
Heart Failure ◽  
Iron Overload ◽  
Chelation Therapy ◽  
Thalassemia Major ◽  
Left Ventricular ◽  
Mean Difference ◽  
Left Ventricular Ejection ◽  
Cardiac Complications ◽  
Myocardial Iron ◽  
Number Of Patients

Abstract Introduction. The MIOT (Myocardial Iron Overload in Thalassemia) Network was a national Italian network constituted by thalassemia and magnetic resonance imaging (MRI) centers built in 2006. The main aim was to assure available, accessible homogeneous and standardized T2* MRI cardiac and liver iron overload assessments for a significant number of patients with emoglobinopathies. Moreover, the creation of a solid clinical-instrumental web based database allowed data exchange between centers and constituted a means of monitoring health care processes and outcomes. We describe the impact of this ten-year Network on cardiac complications in patients with thalassemia major (TM). Methods. Among the 2497 emoglobinopathies patients consecutively enrolled in the MIOT Network we considered the 1401 TM patients who performed an end-of-study MRI. Per protocol the MRI follow up was scheduled every 18±3 months. Myocardial iron overload (MIO) was quantified by the multislice multiecho T2* technique. Biventricular function was quantified by cine images. Results. At the last MRI significantly higher global heart T2* values (35.5±10.7 ms vs 29.2±12.0 ms; P<0.0001) and a significant lower number of patients with global heart T2*<20 ms (26.3% vs 12.0%; P<0.0001) were detected. Four patterns of MIO were identified: no MIO (all segments with T2*≥20 ms), heterogeneous MIO and global heart T2*≥20 ms, heterogeneous MIO and global heart T2*<20 ms, and homogeneous MIO (all segments with T2*<20 ms). Figure 1 shows the frequency of the 4 patterns at both scans. At the last MRI a significant higher frequency of patients with no MIO and a significant lower frequency for the other three patterns indicating MIO were detected. An improvement in MIO, that is a transition to a better risk class, was detected in the 68.4% of patients showing MIO at the baseline (at least one pathologic segment). In patients with significant baseline MIO (global heart T2*<20 ms) a significant increase in left ventricular ejection fraction (EF) (mean difference: 3.2±8.5 %, P<0.0001) as well as in right ventricular EF (mean difference: 1.2±8.9 %, P=0.002) were detected with a concordant improvement of MIO status. Based on MRI results the 75% of the patients changed the chelation therapy. At the last MRI the percentage of patients with an excellent/good compliance was significantly higher (94.7% vs 92.7%%; P=0.034). The 13.1% of the patients had a cardiac complication (heart failure, arrhythmias, pulmonary hypertension, myocardial infarction, angina, myo/pericarditis, and peripheral vascular disease) before the enrolment in the project. During the study, the frequency of cardiac complications was 7.9 %, significantly lower (P<0.0001). In particular, the frequency of heart failure was significantly lower (5.9% vs 1.7%, P<0.0001). Conclusion. Over a period of 10 years, the continuous monitoring of cardiac iron levels and a tailored chelation therapy allowed a reduction of MIO in the 70% of patients and a consequent improvement of cardiac function and reduction of heart failure. So, a national networking as the MIOT project was effective in improving the care and reducing cardiac outcomes of TM patients. Figure 1 Figure 1. Disclosures Pepe: Chiesi Farmaceutici S.p.A., ApoPharma Inc., and Bayer: Other: No profit support.

scholarly journals A Randomized, Placebo-Controlled, Double-Blind Trial of the Effect of Combined Therapy With Deferoxamine and Deferiprone on Myocardial Iron in Thalassemia Major Using Cardiovascular Magnetic Resonance

Circulation ◽  
2007 ◽  
Vol 115 (14) ◽  
pp. 1876-1884 ◽  
Author(s):  
M.A. Tanner ◽  
R. Galanello ◽  
C. Dessi ◽  
G.C. Smith ◽  
M.A. Westwood ◽  
...  
Keyword(s):  
Cardiovascular Magnetic Resonance ◽  
Magnetic Resonance ◽  
Ejection Fraction ◽  
Endothelial Function ◽  
Thalassemia Major ◽  
Iron Chelator ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Iron Loading ◽  
Myocardial Iron

Background— Cardiac complications secondary to iron overload are the leading cause of death in β-thalassemia major. Approximately two thirds of patients maintained on the parenteral iron chelator deferoxamine have myocardial iron loading. The oral iron chelator deferiprone has been demonstrated to remove myocardial iron, and it has been proposed that in combination with deferoxamine it may have additional effect. Methods and Results— Myocardial iron loading was assessed with the use of myocardial T2* cardiovascular magnetic resonance in 167 patients with thalassemia major receiving standard maintenance chelation monotherapy with subcutaneous deferoxamine. Of these patients, 65 with mild to moderate myocardial iron loading (T2* 8 to 20 ms) entered the trial with continuation of subcutaneous deferoxamine and were randomized to receive additional oral placebo (deferoxamine group) or oral deferiprone 75 mg/kg per day (combined group). The primary end point was the change in myocardial T2* over 12 months. Secondary end points of endothelial function (flow-mediated dilatation of the brachial artery) and cardiac function were also measured with cardiovascular magnetic resonance. There were significant improvements in the combined treatment group compared with the deferoxamine group in myocardial T2* (ratio of change in geometric means 1.50 versus 1.24; P =0.02), absolute left ventricular ejection fraction (2.6% versus 0.6%; P =0.05), and absolute endothelial function (8.8% versus 3.3%; P =0.02). There was also a significantly greater improvement in serum ferritin in the combined group (−976 versus −233 μg/L; P <0.001). Conclusions— In comparison to the standard chelation monotherapy of deferoxamine, combination treatment with additional deferiprone reduced myocardial iron and improved the ejection fraction and endothelial function in thalassemia major patients with mild to moderate cardiac iron loading.

scholarly journals Transitioning from Preclinical to Clinical Heart Failure with Preserved Ejection Fraction: A Mechanistic Approach

2020 ◽  
Vol 9 (4) ◽  
pp. 1110 ◽  
Author(s):  
Antoni Bayes-Genis ◽  
Felipe Bisbal ◽  
Julio Núñez ◽  
Enrique Santas ◽  
Josep Lupón ◽  
...  
Keyword(s):  
Heart Failure ◽  
Pulmonary Hypertension ◽  
Ejection Fraction ◽  
Right Ventricular ◽  
Left Atrial ◽  
Interstitial Fibrosis ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Preserved Ejection Fraction ◽  
Ventricular Ejection Fraction

To better understand heart failure with preserved ejection fraction (HFpEF), we need to better characterize the transition from asymptomatic pre-HFpEF to symptomatic HFpEF. The current emphasis on left ventricular diastolic dysfunction must be redirected to microvascular inflammation and endothelial dysfunction that leads to cardiomyocyte remodeling and enhanced interstitial collagen deposition. A pre-HFpEF patient lacks signs or symptoms of heart failure (HF), has preserved left ventricular ejection fraction (LVEF) with incipient structural changes similar to HFpEF, and possesses elevated biomarkers of cardiac dysfunction. The transition from pre-HFpEF to symptomatic HFpEF also involves left atrial failure, pulmonary hypertension and right ventricular dysfunction, and renal failure. This review focuses on the non-left ventricular mechanisms in this transition, involving the atria, right heart cavities, kidneys, and ultimately the currently accepted driver—systemic inflammation. Impaired atrial function may decrease ventricular hemodynamics and significantly increase left atrial and pulmonary pressure, leading to HF symptoms, irrespective of left ventricle (LV) systolic function. Pulmonary hypertension and low right-ventricular function are associated with the incidence of HF. Interstitial fibrosis in the heart, large arteries, and kidneys is key to the pathophysiology of the cardiorenal syndrome continuum. By understanding each of these processes, we may be able to halt disease progression and eventually extend the time a patient remains in the asymptomatic pre-HFpEF stage.

Prolongation of QTc Intervals and Risk of Sudden Death among Patients with Sickle Cell Diseases.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2249-2249
Author(s):  
Bharathi Upadhya ◽  
William Ntim ◽  
Joshua Dworkin ◽  
David Leedy ◽  
Francis X. O’Brien ◽  
...  
Keyword(s):  
Sudden Death ◽  
Ejection Fraction ◽  
Pulmonary Artery ◽  
Iron Overload ◽  
Sickle Cell ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Qtc Interval ◽  
Qtc Prolongation ◽  
Significant Difference

Abstract Unexplained sudden death is common among patients (pts) with sickle cell diseases (SCD). QTc prolongation is a risk factor for fatal arrhythmias among adults. Cardiovascular autonomic dysfunction has been proposed as a contributing cause for sudden death in SCD but QTc prolongation has only been described in isolated pediatric case reports. Purpose: To investigate the incidence of QTc prolongation among adults with SCD and the relationship between prolonged QTc interval and sudden death. Methods: We reviewed records of 180 consecutive adults with SCD from October 1996 to January of 2007. EKGs and echocardiograms (Echo) were independently reviewed by a cardiologist who was blinded to the patients’ clinical and laboratory data. Bazett’s formula was used to calculate QTc interval. In pts with more than one EKG, the longest QTc data was used for analysis. Results: SCD were divided into 3 groups: homozygous SS = 113 (67%), SC = 34 (20%), Sβthal = 21 (13%). Mean age was 35 years (range 25–45), 66 (58%) were females, 108 (96%) were African American and 4% were Mexican. Other medical problems were prior CVA in 17, congestive heart failure in 11, hypertension in 9, renal insufficiency in 13, and diabetes in 7. Medications included hydroxyurea in 41, methadone in 38, other narcotics in 41, ACE inhibitors in 16 and beta blockers in 16. Twenty five pts were receiving chronic exchange transfusions. EKGs were available in 113 (67%) and Echo in 95 (53%). Serum chemistries and ferritin were available in 110 pts within 24 hours of the EKG and in 3 pts within 48 hours. QTc intervals were prolonged (&gt;440 msec) in 74 pts (66%). Sixty six pts (47%) pts had more than one EKG with prolonged QTc. QTc intervals increased progressively over 4 years from a mean 434 msec (415–452) to mean 462 msec (446–487), (p=&lt;0.001). In univariate analysis, there was a positive correlation between QTc prolongation and the following: prolongation of QRS, increased left ventricular end diastolic dimension, decreased ejection fraction, elevated pulmonary artery systolic pressure, elevated ferritin, decreased creatinine clearance and methadone use. In multivariate analysis elevated ferritin levels had the most significant association (p= 0.008). Eighteen pts died over the 5 years (15.9%). Causes of death were pulseless electrical activity in 3, sepsis in 3 and unknown in 12. Identified risk factors for death were QTc prolongation (p=0.017), prolonged QRS (p=0.011), increased septal thickness (p=0.038), elevated pulmonary artery pressure (p=0.001), decreased left ventricular ejection fraction (p=0.001) and renal failure (p&lt;0.001). There was a significant difference in QTc interval between living and deceased pts with QTc of 452.5 msec (430–477) vs. 469(433.5–538.25) msec (p=0.017). Conclusions: Prolongation of QTc is common among adults with SCD and is associated with other cardiac abnormalities that are directly related to sudden death. Elevated ferritin (presumably from iron overload) appears to be the most significant factor associated with prolongation of QTc. These findings suggest that serial monitoring of EKG, electrolytes and ferritin should be part of the standard care in SCD pts. Exchange transfusions are preferable in stable conditions to minimize iron overload. Careful consideration should be given to the choice of analgesics and the use of drugs such as macrolide antibiotics and tricyclic antidepressants that could further prolonged the QTc and cause life threatening arrhythmias.

scholarly journals The transpulmonary ratio of endothelin 1 is elevated in patients with preserved left ventricular ejection fraction and combined pre- and post-capillary pulmonary hypertension

2017 ◽  
Vol 8 (1) ◽  
pp. 204589321774501 ◽  
Author(s):  
David F. Meoli ◽  
Yan Ru Su ◽  
Evan L. Brittain ◽  
Ivan M. Robbins ◽  
Anna R. Hemnes ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Left Ventricular Ejection Fraction ◽  
Ejection Fraction ◽  
Left Ventricular ◽  
Ventricular Ejection ◽  
Left Ventricular Ejection ◽  
Heart Catheterization ◽  
Ventricular Ejection Fraction ◽  
Endothelin 1 ◽  
Normal Lvef

Pulmonary hypertension complicating left heart disease (PH-LHD) is associated with increased morbidity and mortality, especially in patients who develop combined pre- and post-capillary PH (Cpc-PH). Mechanisms underlying PH-LHD are incompletely understood, particularly for individuals with preserved left ventricular ejection fraction (LVEF). We hypothesized that transpulmonary concentrations of biomarkers representing signaling pathways with known effects on the pulmonary circulation could provide insight into the molecular etiology of PH-LHD in patients with preserved LVEF. Blood samples were collected from the pulmonary artery (PA) and wedge positions of outpatients with normal LVEF referred for right heart catheterization. Hemodynamic tracings were reviewed to classify patients as “no PH” (n = 23) or “PH-LHD” (n = 22). A biomarker’s transpulmonary ratio (TPR) was calculated as the quotient of wedge and PA concentrations. The TPR of endothelin 1 (ET-1) was elevated in Cpc-PH (n = 10) compared to no PH or isolated post-capillary PH (Ipc-PH, n = 12); cAMP and cGMP TPRs were not different among groups. Higher ET-1 TPR in Cpc-PH was due to increased wedge ET-1 concentration. Pulmonary vascular resistance (PVR) strongly correlated with wedge ET-1 exclusively in Cpc-PH patients. In patients with normal LVEF and Cpc-PH, ET-1 TPR is higher, due to elevated wedge ET-1, compared to those without PH or with Ipc-PH. Strong correlation between PVR and wedge ET-1, observed only in the Cpc-PH group, may suggest increased pulmonary vascular responsiveness to ET-1 in these patients. These findings implicate elevated pulmonary ET-1 as a marker of, and a potential contributor to, development of Cpc-PH in this population.

Supportive care and chelation therapy in MDS: are we saving lives or just lowering iron?

Hematology ◽  
2009 ◽  
Vol 2009 (1) ◽  
pp. 664-672 ◽  
Author(s):  
Heather A. Leitch ◽  
Linda M. Vickars
Keyword(s):  
Iron Overload ◽  
Supportive Care ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Thalassemia Major ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Beta Thalassemia ◽  
Ventricular Ejection Fraction ◽  
The Impact

AbstractThe myelodysplastic syndromes (MDS) are characterized by cytopenias and risk of transformation to acute myeloid leukemia (AML). Although new treatments are available, a mainstay in MDS remains supportive care, which aims to minimize the impact of cytopenias and transfusion of blood products. Red blood cell (RBC) transfusions place patients at risk of iron overload (IOL). In beta-thalassemia major (BTM), IOL from chronic RBC transfusions inevitably leads to organ dysfunction and death. With iron chelation therapy (ICT), survival in BTM improved from the second decade to near normal and correlated with ICT compliance. Effects of ICT in BTM include reversal of cardiac arrhythmias, improvement in left ventricular ejection fraction, arrest of hepatic fibrosis, and reduction of glucose intolerance.It is not clear whether these specific outcomes are applicable to MDS. Although retrospective, recent studies in MDS suggest an adverse effect of transfusion dependence and IOL on survival and AML transformation, and that lowering iron minimizes this impact. These data raise important points that warrant further study. ICT is potentially toxic and cumbersome, is costly, and in MDS patients should be initiated only after weighing potential risks against benefits until further data are available to better justify its use. Since most MDS patients eventually require RBC transfusions, the public health implications both of transfusion dependence and ICT in MDS are considerable. This paper summarizes the impact of cytopenias in MDS and treatment approaches to minimize their impact, with a focus on RBC transfusions and their complications, particularly with respect to iron overload.

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