Hemochromatosis

From Wikiecho
Jump to: navigation, search

Contents

Definition

Hemochromatosis, also known as hemosierosis or iron-storage disease results from iron overload of various parenchymal organs including the heart, liver, gonads and pancreas. Consecutive tissue damage and functional impairment leads to a classic pentad of symptoms: heart failure, cirrhosis, impotence, diabetes and arthritis. Iron overload cardiomyopathy occurs in 20-25% of patients, presenting as systolic and/or diastolic cardiac dysfunction with progressive congestive heart failure. Cardiac involvement is usually seen in advanced disease, although the degree of different organ iron overload is not always similar.

Etiology

The two most frequent clinical scenarios in which iron overload cardiomyopathy occurs are:

  • Hereditary (primary) hemochromatosis, an autosomal recessive disorder characterized by gene mutations involving iron metabolism, leading to increase iron uptake in the gastrointestinal tract.
  • Transfusional hemochromatosis secondary to chronic blood transfusions in patients with ineffective erythropoiesis (increased catabolism) as found in thalassemia or sickle cell anemia.

Diagnosis

  • The diagnosis of cardiac involvement is always made in clinical context
  • Clinical – patients most often present with congestive heart failure. Arrhythmias and conduction abnormalities are also noted.
  • Electrocardiography – 31% of patients have ST segment and T wave abnormalities and supraventricular arrhythmias.
  • Echocardiography – see below
  • Cardiac magnetic resonance imaging – by T2* time calculation, magnetic resonance imaging is able to detect and quantify myocardial iron load and to monitor response to treatment. T2* cardiac magnetic resonance is the recommended non-invasive tool for screening subclinical myocardial disease in hemochromatosis.
  • Evaluation of iron metabolism – increased plasma iron levels, serum ferritin, transferrin saturation and urinary iron; low total iron binding capacity.
  • Endomyocardial biopsy – may be useful for diagnosis and to guide treatment if other tests are equivocal, but can often give false-negative results (patchy iron deposition)[1].

Echocardiography features

  • Echocardiography plays a role in the diagnosis and follow up during treatment.
  • Findings are non-specific, with a restrictive or dilated cardiomyopathy profile.
  • Mild left ventricular dilatation, normal or mildly increased wall thickness, biatrial enlargement. Right ventricular involvement with normal size and increased wall thickness.
  • Left ventricular diastolic function – precedes systolic dysfunction. The degree of impairment correlates with the severity of iron overload, with a restrictive filling pattern in advanced stages Palka et al [2].
  • Left ventricular systolic function – usually preserved in early stages, with regional and global dysfunction in later stages, when iron overload reaches a critical level.
  • Tissue Doppler Imaging for subclinical myocardial involvement - studies have shown reduced longitudinal systolic and early diastolic velocities to be early signs of disease[3] [4] [5]. In addition, a reduced increase of basal septal systolic velocities during exercise was found when compared to normals[6].
  • Left atrial contractile function, particularly active emptying fraction, was studied as a very early echocardiographic sign of abnormal diastolic function in asymptomatic patients.Unfortunately, the results are conflicting [7] [8].
  • Increased pulmonary pressures at rest and during exercise due to elevated left ventricular filling pressures[9].

Treatment

  • Conventional - with dietary measures, repeated phlebotomies and chelating agents, i.e. desferrioxamine.
  • Novel therapies - still under research: calcium channel blockers, hepcidin (protein with major role in iron homeostasis), gene therapy and stem cell transplantation.

Prognosis

  • Myocardial dysfunction directly correlates with the amount of iron deposited in the heart.
  • Cardiac involvement accounts for one third of mortality in hemochromatosis patients
  • Timely treatment may prevent the occurrence of overt dilated cardiomyopathy and even reverse it in early stages.
  • In advanced cardiomyopathy cardiac transplantation can prolong survival[10].

References

  1. Cooper LT, Baughman KL, Feldman AM et al.The role of endomyocardial biopsy in the management of cardiovascular disease: a scientific statement from the American Heart Association, the American College of Cardiology, and the European Society of Cardiology. Endorsed by the Heart Failure Society of America and the Heart Failure Association of the European Society of Cardiology. J Am Coll Cardiol. 2007 ;50(19):1914-31.
  2. Davidsen ES, Omvik P, Hervig T, Gerdts E. Left ventricular diastolic function in patients with treated haemochromatosis. Scand Cardiovasc J. 2009;43(1):32-8.
  3. Davidsen ES, Hervig T, Omvik P, Gerdts E. Left ventricular long-axis function in treated haemochromatosis. Int J Cardiovasc Imaging 2009;25(3):237-47.
  4. Vogel M, Anderson LJ, Holden S, Deanfield JE, Pennell DJ, Walker JM. Tissue Doppler echocardiography in patients with thalassaemia detects early myocardial dysfunction related to myocardial iron overload. Eur Heart J 2003;24(1):113-9.
  5. Palka P, Macdonald G, Lange A, Burstow DJ. The role of Doppler left ventricular filling indexes and Doppler tissue echocardiography in the assessment of cardiac involvement in hereditaryhemochromatosis. J Am Soc Echocardiogr. 2002;15:884–90.
  6. Barbero U, Destefanis P, Pozzi R, Longo F, Piga A. Exercise Stress Echocardiography with Tissue Doppler Imaging (TDI) Detects Early Systolic Dysfunction in Beta-Thalassemia Major Patients without Cardiac Iron Overload. Mediterr J Hematol Infect Dis. 2012;4(1):e2012037.
  7. Shizukuda Y, Bolan CD, Tripodi DJ, Yau YY, Nguyen TT, Botello G, Sachdev V, Sidenko S, Ernst I, Waclawiw MA, Leitman SF, Rosing DR. Significance of left atrial contractile function in asymptomatic subjects with hereditary hemochromatosis. Am J Cardiol. 2006;98(7):954-9.
  8. Aggeli C, Felekos I, Poulidakis E, Aggelis A, Tousoulis D, Stefanadis C.Quantitative analysis of left atrial function in asymptomatic patients with b-thalassemia major using real-time three-dimensional echocardiography.Cardiovasc Ultrasound. 2011;9:38.
  9. Nihoyannopoulos P, Dawson D. Restrictive cardiomyopathies. Eur J Echocardiogr 2009;10(8):iii23-33.
  10. Gujja P, Rosing DR, Tripodi DJ, Shizukuda Y. Iron overload cardiomyopathy: better understanding of an increasing disorder. J Am Coll Cardiol 2010;56(13):1001-12.

Further reading

  1. Galiuto L, Badano L, Fox K, Sicari R, Zamorano JL. The EAE Textbook of Echocardiography. 1st edition. Oxford, Oxford University Press;2011.
  2. Libby P, Bonow R, Mann D, Zipes D. Braunwald's Heart Disease. 9the edition. Philadelphia, Saunders Elsevier; 2011.
  3. Bogaert J, Dymarkovski S, Taylor A, Muthurangu V. Clinical Cardiac MRI. 2nd edition. Berlin, Springer;2012.
Personal tools
Namespaces

Variants
Actions
Navigation
Toolbox