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(Chest. 2002;121:506-512.)
© 2002 American College of Chest Physicians

Left Ventricular Remodeling, Systolic Function, and Diastolic Function in Young Adults With ß-Thalassemia Intermedia*

A Doppler Echocardiography Study

Marco Vaccari, MD; Roberto Crepaz, MD; Monica Fortini, BD; Maria R. Gamberini, MD; Sabrina Scarcia, MD; Walter Pitscheider, MD and Giuliano Bosi, MD

* From the Pediatric Cardiology Unit (Drs. Vaccari, Scarcia, and Bosi), Section of Pediatrics, Department of Clinical and Experimental Medicine, University of Ferrara, Italy; Division of Cardiology (Drs. Crepaz and Pitscheider), Ospedale Regionale, Bolzano, Italy; and Division of Pediatrics (Ms. Fortini and Dr. Gamberini), Thalassemia Unit, Arcispedale S. Anna, Ferrara, Italy. This work was partially supported by a Grant of the "Associazione per la Lotta alla Talassemia," Section of Ferrara, Italy.

Correspondence to: Giuliano Bosi, MD, Associate Professor of Pediatric Cardiology, Pediatric Cardiology Unit, Department of Clinical and Experimental Medicine, University of Ferrara, Via Savonarola 9, 44100 Ferrara, Italy; e-mail: bsg{at}unife.it


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Background: The aim of this study was to investigate the left ventricular (LV) remodeling and function in 24 asymptomatic young adults affected by ß-thalassemia intermedia (TI), in order to compare the obtained data with that of 80 patients affected by ß-thalassemia major (TM) and 65 healthy subjects.

Methods: LV volumes and shapes, mass index, mass/volume ratio, systolic and diastolic function, stroke volume, and cardiac index were determined by two-dimensional and M-mode echocardiography.

Results: In the TM and TI groups, LV volumes, diastolic and systolic shapes were significantly different from the control subjects, but the ejection fraction was slightly reduced only in the TM group. The TI group had larger LV volumes than did the TM group (mean [± SD] end-diastolic volume index, 99.4 ± 21.9 vs 82.7 ± 21.5 mL/m2, respectively [p < 0.005]; mean end-systolic volume index, 42.8 ± 12.2 vs 36.1 ± 12.9 mL/m2, respectively [p < 0.05]). Both groups showed an increase of the LV mass index, but the mass/volume ratio did not differ from the control subjects. The systolic volume index and the cardiac index were increased in both groups, but the increase was more pronounced in the TI group. Fractional shortening (FS) and the mean velocity of circumferential shortening (mVCFc) were decreased in the TM group (FS, 33.6 ± 5.5% vs 36.9 ± 4.1, respectively [p < 0.001]; mVCFc, 1.06 ± 0.18 vs 1.17 ± 0.12 circumference per second, respectively [p < 0.0001]). The LV contractile state was depressed only in the TM group, and the preload index was normal in both. LV filling showed an increase in the total flow velocity integral due to increases in the peak E wave (E) and peak A wave (A) velocities and integrals, with an increase of the E/A ratio in the TM group and a slight decrease in the TI group. The isovolumic relaxation time was prolonged in both groups. There was no major derangement in the pulmonary venous flow.

Conclusions: Asymptomatic young adults with TI show significant increases in LV volumes, LV mass, and cardiac index that are more pronounced than those in TM patients. LV systolic function is preserved in the TI group but is slightly depressed in the TM group due to the increase of afterload and to reduced contractility. The hemodynamic and hematologic factors involved in the etiopathogenesis of these findings are discussed, such as the treatment strategy.

Key Words: color-Doppler echocardiography • left ventricle remodeling and function • thalassemia intermedia


   Introduction
TOP
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
Thalassemia syndromes often are complicated by cardiac involvement that is related mainly to iron tissue overload as a result of hemolysis, increased intestinal absorption, and multiple transfusions.1 2 3 4 Moreover, iron-induced cardiac disease is considered to be the primary cause of death in patients who have transfusion-dependent ß-thalassemia major (TM).5 Left ventricular (LV) mechanics have been studied in TM patients,6 7 8 9 10 11 12 13 while a very small amount of data is available on cardiac function in patients with ß-thalassemia intermedia (TI).2 4 14 15 In these patients, the myocardial derangement mainly has been related to the increased GI iron absorption associated with milder clinical symptoms, and so they have little or no need of blood transfusions.2 3 4

The aim of our study has been to investigate LV remodeling and function, as assessed by Doppler echocardiography, in a relatively large number of TI patients in order to compare the data obtained with those for TM patients and healthy control subjects.


   Materials and Methods
TOP
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
Study Population
Twenty-four of the 31 patients affected by TI (mean [± SD] age, 29.5 ± 10 years), and 80 transfusion-dependent TM patients (mean age, 27.2 ± 5.5 years) of the 273 who are regularly observed by the outpatient service of the Thalassemia Unit of Ferrara were enrolled in this study. At the time of the Doppler echocardiography examination, none of the enrolled TI patients were receiving or had received RBC transfusions, and, consequently, they had never been exposed to chelating agents. None of the patients had clinical signs of cardiac dysfunction or were receiving any cardioactive drugs. All patients had undergone splenectomies. The mean hemoglobin (Hb) level in the previous year was 8.81 ± 0.91 g/dL, and the mean serum ferritin value in the previous year was 940 ± 1374 ng/mL.

Similarly, at the time of the evaluation, none of the enrolled TM patients had clinical signs of cardiac involvement, and they were not receiving any cardiovascular medications. All patients had undergone splenectomies. Each TM patient was receiving an RBC transfusion every 2 to 3 weeks, together with adequate iron-chelation therapy (mean pretransfusional Hb level for the previous year, 8.99 ± 0.5 g/dL; mean serum ferritin value for the previous year, 1,131 ± 1,112 ng/mL). At the time of examination, the TM patients had received 814 ± 283 blood units, and the mean total amount of iron transfused was 188.7 ± 70.1 g (Tables 1 and 2 ). The control group consisted of 65 healthy young adults who were comparable in age and sex, had no cardiovascular disorders, and had normal findings on Doppler echocardiography examinations.


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  		Table 1.. Demographic Data of Patients With ß-TI, TM, and Control Subjects*

 
Doppler Echocardiography Examination
The Doppler echocardiography examinations were performed with a phased-array sector scan with a 3.5-MHz and/or a 2-MHz transducer. All echocardiographic measurements, which were performed by the same observer (MV), were obtained by averaging those taken from at least three cardiac cycles, according to the criteria of the American Society of Echocardiography.16 Intraobserver and interobserver reproducibility of the echocardiographic and Doppler measurements, based on the analysis of the same sets of cardiac cycles as in our laboratory, were 4.2 ± 3% and 5.1 ± 3.2%, respectively. Peak systolic BP and peak diastolic BP were monitored by a vital sign monitor (Dinamap; GE Medical Systems; Salt Lake City, UT) during the echocardiographic examination.

Analysis of LV Volume, Shape, and Mass
LV volumes and mass were estimated in the short-axis planes, measuring the long axes from the apical endocardium to the midpoint of the plane of the mitral valve in the apical four-chamber view and utilizing the area-length model.17 18 19 The ratio of LV end-diastolic mass/volume was used to evaluate the degree of adaptation of the wall thickness to changes in chamber size. The LV chamber shape was assessed using the long axis/minor axis ratio, which was obtained at end-diastole and end-systole.20 End-diastolic and end-systolic volumes were used to calculate the ejection fraction (EF), stroke volume, and cardiac index.

Analysis of LV Systolic Function, Afterload, Contractility, and Preload
From a parasternal short-axis cut of the LV, end-diastolic and end-systolic diameters, posterior wall thickness at end-diastole and end-systole, and septal thickness at end-diastole were obtained in order to calculate the following: (1) fractional shortening (FS) and mean velocity of circumferential shortening corrected by heart rate (mVCFc)16 21 ; (2) end-systolic meridional stress (ESSm) and end-systolic circumferential stress (ESSc) [ie, indexes of afterload]22 23 24 25 ; (3) peak systolic meridional (PSSm) and peak systolic circumferential stress (PSSc) [ie, indexes of appropriate hypertrophy]26 ; (4) stress-shortening index (SSI) and stress velocity index (SVI) [ie, indexes of the LV contractile state, sensitive and insensitive, respectively, to preload]27 28 ; and (5) the functional preload index (FPI) [FPI = SSI - SVI] as the difference between the SSI and SVI relationships (which reflects the functional consequence of preload).26 27 28

Analysis of LV Diastolic Function
The LV filling was evaluated by pulsed-Doppler sampling of the mitral valve inflow. The peak E-wave velocity of the mitral valve (E), the peak A-wave velocity of the mitral valve (A), the E/A ratio, and the deceleration time (DT) were obtained. Isovolumic relaxation time (IVRT) was measured as the time from the end of aortic flow to the onset of mitral flow. From the Doppler curve, the area under the total velocity curve (flow velocity integral [FVI]), E area (Ea), A area (Aa), and their ratios (Ea/FVI, Aa/FVI, and Ea/Aa) were obtained29 ; the E/FVI ratio (ie, the index of LV diastolic function, not dependent on heart rate and preload) also was obtained.30 The pulmonary venous flow was examined with the sample volume positioned just at the orifice of the right upper pulmonary vein. The following Doppler velocities were obtained: peak velocity during ventricular systole and peak velocity during ventricular diastole; the systole/diastole ratio; and the peak reverse flow due to atrial contraction. In case of biphasic systolic flow, the highest wave is taken as the maximal systolic velocity.31

Statistical Analysis
Data are presented as the mean ± SD. A two-sample Student’s t test was used to assess the differences in the means between patients and control subjects. Differences were considered to be statistically significant when p < 0.05.


   Results
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
Clinical Findings
The demographic data of the two groups of patients and of the control subjects are summarized in Table 1 . Although patients and control subjects were matched for age and gender, body surface area was significantly smaller in TI and TM patients than in the control subjects. Systolic and diastolic pressures were slightly lower in TM patients, and diastolic pressure was lower in TI patients when compared with the control subjects. Heart rate was significantly increased in both groups. The hematologic profiles are reported in Table 2 . The TI patients had a later diagnosis and a shorter follow-up in comparison with the TM patients. The average Hb level of 8.81 ± 0.91 g in TI patients was not significantly different from that of TM patients, and the mean ferritin level did not differ between the two groups as well.


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  		Table 2.. Hematologic Profile of Patients With ß-TI and TM*

 
Doppler Echocardiography Findings
LV volumes, diastolic shapes, and systolic shapes were significantly different, but EF was slightly reduced only in the TM patients when compared with the control subjects. The TI patients had larger LV volumes than did TM patients. Both groups showed an increase of the LV mass index, but the M/V ratio did not differ from that of the control subjects. Stroke volume and cardiac index were increased in both groups, but the increase was significantly pronounced in the TI group (Table 3 ).


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  		Table 3.. LV Geometry, Shape, and Cardiac Index in Patients With ß-TI, TM, and Control Subjects*

 
FS and mVCFc were decreased in the TM group in comparison with the TI patients and control subjects. ESSm was increased in both groups, however, PSSm was not different from that of the control subjects. ESSc was normal, and PSSc was slightly reduced in the TM patients. The LV contractile state was slightly depressed only in the TM patients, and the preload index was normal in both groups of patients (Table 4 ).


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  		Table 4.. LV Systolic Function, Afterload, Contractility, and Preload in Patients with ß-TI, TM, and Control Subjects*

 
LV diastolic function, which was assessed at mitral inflow, showed an increase in total FVI, due to an increase in peak early and late filling velocities and integrals, with an increase of the E/A ratio in the TM patients and a slight decrease in the TI group. The DT was slightly prolonged in TI patients, and the IVRT was slightly prolonged in both groups of patients (Table 5 ). In the TI group, there was no significant derangement in the pulmonary venous flow (Table 6 ).


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  		Table 5.. LV Diastolic Function from Mitral Valve Inflow in Patients With ß-TI, TM, and Control Subjects*

 

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  		Table 6.. LV Diastolic Function From Pulmonary Venous Inflow in Patients With ß-TI, TM, and Control Subjects*

 

   Discussion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
Little information regarding cardiac involvement in TI patients is available in the literature, being limited to the description of sporadic case reports.2 3 4 14 15 However, it is reasonable to expect a cardiac involvement in TI patients due to the presence of the following factors, which are known to play a role in the pathogenesis of so-called thalassemic cardiomyopathy: (1) chronic anemia, resulting in a high cardiac output state; and (2) iron overload, which is a late event occurring after the accumulation of iron in others organs such as the liver. Moreover, it is not known whether the susceptibility to infectious myocarditis, recently demonstrated for TM patients, also plays a role in TI patients.32 33 34

On this basis, we thought it appropriate to have a large series of TI patients undergo Doppler echocardiography examination in order to investigate LV remodeling and both systolic and diastolic function, and to compare the obtained data with that observed in a comparable group of TM patients.

It is important to emphasize that, at the time of the evaluation, both of our groups of patients had only mild iron overload and probably comparable iron stores. Both groups had similar Hb levels, and the mean ferritin level was < 2,500 ng/mL, which has been considered to be a safe level.35 However, there were significant differences between the two groups. First, the TM patients had been exposed, in the past, to a more severe iron overload due to RBC transfusions, and their iron stores had been greatly reduced only by the more recent introduction of intensive chelating therapy. In contrast, the TI patients have not received transfusions, except occasionally during surgical interventions for splenectomy and/or cholecystectomy. Consequently, their iron overload had never been severe. Second, the Hb levels in TI patients did not have significant variations in the course of the disease. In contrast, the Hb levels in TM patients, which were higher in the days following RBC transfusions than at the time of Doppler echocardiography examinations, were always measured just before blood transfusion, and showed significant variations according to the transfusion therapy.

The results of this study demonstrate that both TI and transfusion-dependent young adults with TM, who have no clinical signs of cardiac involvement, have significant abnormalities in volume, mass, and shape of the LV. In both groups, the observed decrease of systolic and diastolic BP seems related to a reduction of the systemic vascular resistance.

Our data are in agreement with those reported on TM patients.7 8 11 12 No comparison is possible concerning TI patients, because only a small amount of data is available in the literature.4 14 15 However, there were significant differences between the two groups. The LV remodeling was more pronounced in TI patients than in TM patients, whereas the systolic function and the contractile state were preserved in TI patients. The larger LV volumes and the increased stroke volume and cardiac index observed in the TI group probably could be explained by the presence of chronic anemia, which is associated with increased blood volume due to bone marrow expansion. The lower capacity of the blood to carry an adequate amount of oxygen to peripheral tissues was overcome by the higher cardiac output.36 37 38 The venous return was, therefore, increased, and this significant volume overload was carried out through the Frank-Starling mechanism and an increase of the heart rate, which was observed in both groups.

In the TM patients, we observed a slight decrease of LV systolic performance due to an increase of afterload and a reduced contractile state, which was probably secondary to the previous iron overload7 39 40 41

In transfusion-dependent TM patients, the filling pattern of the LV has been previously studied.11 13 42 In the early stage of the disease, no alteration of LV compliance has been reported by invasive studies.13 32 The filling pattern observed in our patients could be explained by an increased volume overload due to the hyperdynamic state, which was induced by chronic anemia.11 39 40 41 42 In contrast, a restrictive pattern of the mitral inflow has been reported in the final stage of the disease, which often is associated with symptoms of congestive heart failure, as can be seen in patients with dilated cardiomyopathies in the final stage of the disease.11 43 44 45 46 In agreement with the data on mitral inflow that has been reported by Kremastinos et al,11 we have documented an increase of early peak filling velocities and late filling velocities and integrals with an increase in E/A ratio in our TM patients. There was no major derangement in the pulmonary venous flow.

In our TI patients, we have observed a similar LV filling pattern but one with a more pronounced increase of the late filling velocity and a relative decrease of the E/A ratio.

In conclusion, the results of our study emphasize the primary role of chronically high cardiac output in the pathogenesis of LV remodeling, which is significantly more pronounced in TI patients. In other words, we think that iron toxicity does not play the main role in the pathogenesis of the described cardiac derangement, at least in the first stage of the disease, and especially in TI patients.

Treatment for patients with ß-TI has not been well-codified, and a conservative strategy usually is chosen. In fact, RBC transfusions usually are started after the patients have had a low Hb level for a long time.2 3 4 This approach inevitably leads to a state of high cardiac output, and this condition is not improved by their undergoing a splenectomy, as demonstrated by our findings. As suggested by Aessopos et al,15 this hemodynamic condition will in turn lead to pulmonary hypertension in the final stage of the disease, especially when it is associated with pulmonary vascular lesions that probably are related to iron deposits in the pulmonary vessels and to a hypercoagulable state with thrombotic obstructions. For this reason, these authors recommend the prescription of antithrombotic agents for patients who have undergone splenectomies.15

We suggest that the LV remodeling that was observed in TI patients may represent the first step in the failure of the LV, and, for this reason, we are strictly monitoring both groups of patients. On this basis, the strategy of treatment should be reconsidered and should consider the option of starting RBC transfusions and therapy with chelating agents earlier in the life of TI patients. A rise in the Hb level, together with adequate iron chelation, might prevent major cardiopulmonary derangement.47 48


   Acknowledgements
 
We are indebted to Professor Calogero Vullo for his precise and careful advice during the realization of this study.


   Footnotes
 
Abbreviations: A = peak A-wave velocity of the mitral valve; Aa = A-wave area; DT = deceleration time; E = E-wave velocity of the mitral valve; Ea = peak E-wave area; EF = ejection fraction; ESSc = end-systolic circumferential stress; ESSm = end-systolic meridional stress; FS = fractional shortening; FVI = flow velocity integral; Hb = hemoglobin; IVRT = isovolumic relaxation time; LV = left ventricle, ventricular; mVCFc = mean velocity of circumferential shortening corrected by heart rate; PSSc = peak systolic circumferential stress; PSSm = peak systolic meridional stress; SSI = stress-shortening index; SVI = stress velocity index; TI = thalassemia intermedia; TM = thalassemia major

Received for publication December 7, 2000. Accepted for publication June 6, 2001.


   References
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. Weatherall, DJ, Clegg, JB (1981) Thalassemia syndromes. Blackwell Scientific Publication Oxford, UK.
  2. Model, B, Berdoukas, V (1984) Thalassaemia intermedia. The clinical approach of thalassemia ,242-255 Grune & Stratton London, UK.
  3. Fosburg, MT, Nathan, DG (1990) Treatment of Cooley’s anemia. Blood 76,435-444[Free Full Text]
  4. Camaschella, C, Cappellini, MD (1995) Thalassemia intermedia. Haematologica 80,58-68[Abstract/Free Full Text]
  5. Zurlo, MG, De Stefano, P, Borga-Pignatti, C (1989) Survival and causes of death in thalassemia major. Lancet 2,27-30[ISI][Medline]
  6. Buja, LM, Roberts, WC (1971) Iron in the heart: etiology and clinical significance. Am J Med 51,209-221[CrossRef][ISI][Medline]
  7. Henry, WL, Nienhuis, AW, Wiener, M, et al (1978) Echocardiographic abnormalities in patients with transfusion-dependent anemia and secondary myocardial iron deposition. Am J Med 64,547-555[CrossRef][ISI][Medline]
  8. Lewis, BS, Rachmilewitz, EA, Amitai, N, et al (1978) Left ventricular function in ß-thalassemia and the effect of multiple transfusions. Am Heart J 96,636-645[CrossRef][ISI][Medline]
  9. Borow, KM, Propper, R, Bierman, FZ, et al (1982) The left ventricular end-systolic pressure-dimension relation in patients with thalassemia major: a new noninvasive method for assessing contractile state. Circulation 66,980-985[Free Full Text]
  10. Kremastinos, TD, Toutuzas, KP, Vissoulis, PG, et al (1985) Global and segmental left ventricular function in ß-thalassemia. Cardiology 72,129-139[ISI][Medline]
  11. Kremastinos, DT, Tsiapras, DP, Tsetsos, GA, et al (1993) Left ventricular diastolic Doppler characteristics in ß-thalassemia major. Circulation 88,1127-1135[Abstract/Free Full Text]
  12. Spirito, P, Lupi, G, Melevendi, C, et al (1990) Restrictive diastolic abnormalities identified by Doppler echocardiography in patients with thalassemia major. Circulation 82,88-94[Abstract/Free Full Text]
  13. Kremastinos, TD, Rentoukas, E, Mavrogeni, S, et al (1993) Left ventricular inflow pattern in ß-thalassemia major: a Doppler echocardiographic study. Eur Heart J 14,351-357[Abstract/Free Full Text]
  14. Mohamed, N, Jackson, N (1998) Severe thalassemia intermedia: clinical problems in the absence of hypertension. Blood Rev 12,163-170[CrossRef][ISI][Medline]
  15. Aessopos, A, Stamatelos, G, Skoumas, V, et al (1995) Pulmonary hypertension and right heart failure in patients with ß-thalassemia intermedia. Chest 107,50-54[Abstract/Free Full Text]
  16. Sahn, DJ, De Maria, A, Kisslo, J, et al (1978) Recommendations regarding quantitation in M-mode echocardiography: result of a survey of echocardiographic measurements. Circulation 58,1072-1080[Abstract/Free Full Text]
  17. . St. (1984) John Sutton M, Plappert TA, Hirshfeld JW, et al. Assessment of left ventricular mechanics in patients with asymptomatic aortic regurgitation: a two-dimensional echocardiographic study. Circulation 69,259-268[Abstract/Free Full Text]
  18. Schiller, NB (1989) Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. J Am Soc Echocardiogr 2,358-367[Medline]
  19. Park, SH, Shub, C, Nobrega, TP, et al (1996) Two-dimensional echocardiographic calculation of left ventricular mass as recommended by the American Society of Echocardiography: correlation with autopsy and M-mode echocardiography. J Am Soc Echocardiogr 9,119-128[CrossRef][Medline]
  20. Borow, KM, Lang, RM, Neumann, A, et al (1988) Physiologic mechanisms governing hemodynamic responses to positive inotropic therapy in patients with dilated cardiomyopathy. Circulation 77,625-637[Abstract/Free Full Text]
  21. Franklin, RCG, Wyse, RKH, Graham, TP, et al (1990) Normal values for noninvasive estimation of left ventricular contractile state and afterload in children. Am J Cardiol 65,505-510[CrossRef][ISI][Medline]
  22. Grossman, W, Jones, D, McLaurin, LP (1975) Wall stress and pattern of hypertrophy in the human left ventricle. J Clin Invest 56,56-62
  23. Borow, KM, Neumann, A, Wynne, J (1982) Sensitivity of end-systolic pressure-dimension and pressure-volume relations to the inotropic state in humans. Circulation 65,988-996[Abstract/Free Full Text]
  24. Mirski, I (1974) Review of various theories for evaluation of left ventricular wall stresses. Mirsky, I Chistoln, DN Sander, J eds. Cardiac mechanics: physiological, chemical and mathematical considerations ,381 Wiley New York, NY.
  25. Colan, SD, Parness, IA, Spevak, PJ, et al (1992) Developmental modulation of myocardial mechanics: age and growth-related alterations in afterload and contractility. J Am Coll Cardiol 19,619-627[Abstract]
  26. Colan, SD (1992) Noninvasive assessment of myocardial mechanics: a review of analysis of stress-shortening and stress-velocity. Cardiol Young 2,1-13
  27. Colan, SD, Borow, KM, Neumann, A (1984) Left ventricular end-systolic wall stress-velocity of fiber shortening relation: a load-independent index of myocardial contractility. J Am Coll Cardiol 4,715-724[Abstract]
  28. Colan, SD, Trowitzsch, E, Wernovsky, G, et al (1988) Myocardial performance after arterial switch operation for transposition of the great arteries with intact ventricular septum. Circulation 78,132-141[Abstract/Free Full Text]
  29. Snider, AR, Gidding, SS, Rocchini, AP, et al (1985) Doppler evaluation of left ventricular filling in children with systemic hypertension. Am J Cardiol 56,921-925[CrossRef][ISI][Medline]
  30. Bowman, LK, Lee, FA, Jaffe, CC, et al (1988) Peak filling rate normalized to mitral stroke volume: a new Doppler echocardiographic filling index validated by radionuclide angiographic techniques. J Am Coll Cardiol 12,937-943[Abstract]
  31. O’Leary, PW, Durongpisitkul, K, Cordes, TM, et al (1998) Diastolic ventricular function in children: a Doppler echocardiographic study establishing normal values and predictors of increased ventricular end-diastolic pressure. Mayo Clin Proc 73,616-628[ISI][Medline]
  32. Kremastinos, DT, Rentoukas, E, Mavrogeni, S, et al (1992) Myocarditis in ß-thalassemia major: a 5 year follow-up study [abstract]. J Am Coll Cardiol 19,803[Abstract]
  33. Kremastinos, DT, Tiniakos, G, Theodorakis, GN, et al (1995) Myocarditis in ß-thalassemia major: a cause of heart failure. Circulation 91,61-71
  34. Kremastinos, DT, Flevar, P, Spyropoulou, M, et al (1999) Association of heart failure in homozygous ß-thalassemia with the major histocompatibility complex. Circulation 100,2074-2078[Abstract/Free Full Text]
  35. Olivieri, NF, Nathan, DG, MacMillan, JH, et al (1994) Survival in medically treated patients with homozygous ß-thalassemia. N Engl J Med 331,574-578[Abstract/Free Full Text]
  36. Duke, M, Abelmann, WH (1969) The hemodynamic response to chronic anemia. Circulation 34,503-515[Free Full Text]
  37. Murray, JF, Escobar, E (1968) Circulatory effects of blood viscosity: comparison of methemoglobinemia and anemia. J Appl Phisiol 25,594-599
  38. Kumar, AE, Gupta, GD, Kumar, R, et al (1969) Pulmonary vascular adaptation to the hyperkinetic state of severe anemia. Clin Res 17,578-581
  39. Leon, MB, Borer, JS, Bacharach, SL, et al (1979) Detection of early cardiac dysfunction in patients with severe ß-thalassemia and chronic iron overload. N Engl J Med 301,1143-1148[Abstract]
  40. Aldouri, MA, Wonke, B, Hoffbrand, AV, et al (1990) High incidence of cardiomyopathy in ß-thalassemia patients receiving regular transfusion and iron chelation reversal intensified chelation. Acta Haematol 84,113-117[ISI][Medline]
  41. Nishimura, RA, Abel, MD, Housmans, PR, et al (1989) Mitral flow velocity curves as a function of different loading conditions: evaluation by intraoperative transesophageal Doppler echocardiography. J Am Soc Echocardiogr 2,79-87[Medline]
  42. Valdes Cruz, LM, Reinecke, C, Rutkowski, M, et al (1982) Preclinical abnormal segmental cardiac manifestations of thalassemia major in children on transfusion-chelation therapy: echocardiographic alterations of left ventricular posterior wall contraction and relaxation pattern. Am Heart J 103,505-511[CrossRef][ISI][Medline]
  43. Nody, AC, Bruno, MS, De Pasquale, NP, et al (1975) Fulminating idiopathic hemochromatosis presenting as constrictive pericarditis. Ann Intern Med 83,373-374
  44. Cutler, DJ, Isner, JM, Bracey, AW, et al (1980) Hemochromatosis heart disease: an unemphasized cause of potentially reversible restrictive cardiomyopathy. Am J Med 69,923-928[ISI][Medline]
  45. Appleton, CP, Hatle, LK, Popp, RL (1988) Demonstration of restrictive ventricular physiology by Doppler echocardiography. J Am Coll Cardiol 11,757-768[Abstract]
  46. Lavine, JS (1991) Left ventricular diastolic function in idiopathic cardiomyopathy: Doppler, hemodynamic correlations. Echocardiography 8,151-161
  47. Grisaru, D, Rachmilewitz, EA, Mosseri, M, et al (1990) Cardiopulmonary assessment in ß-thalassemia major. Chest 98,1138-1142[Abstract/Free Full Text]
  48. Du, ZD, Roguin, N, Milgram, E, et al (1997) Pulmonary hypertension in patients with thalassemia major. Am Heart J 134,532-537[CrossRef][ISI][Medline]



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 Am. J. Physiol. Heart Circ. Physiol.Home page
Y.-Q. Zhou, F. S. Foster, R. Parkes, and S. L. Adamson
Developmental changes in left and right ventricular diastolic filling patterns in mice
Am J Physiol Heart Circ Physiol, October 1, 2003; 285(4): H1563 - H1575.
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