Clin Res Cardiol DOI 10.1007/s00392-015-0864-x
LETTER TO THE EDITORS
A patient with a rare cause of elevated troponin I Antonios Kilias1 • Karin Klingel2 • Meinrad Gawaz1 • Ulrich Kramer3 Peter Seizer1
•
Received: 15 February 2015 / Accepted: 23 April 2015 Ó Springer-Verlag Berlin Heidelberg 2015
Sirs: A 46-year-old male patient was admitted to our emergency room due to instable angina pectoris and progressive dyspnea. Relevant stenosis of coronary arteries was excluded by coronary angiography. MRI revealed septal linear late enhancement. Interestingly, the incidental finding of an abnormal ‘‘black’’ liver on cardiac MRI indicated an iron overload. Myocardial biopsy confirmed a significant myocardial iron deposition. Elevated serum transferrinsaturation index confirmed the diagnosis of an iron overload. Finally, genetic testing confirmed a homozygous C282Y mutation. Acute decompensated heart failure with troponin elevation is a rare first clinical presentation of hereditary hemochromatosis (HH). With the use of advanced diagnostic modalities (MRI, biopsy) and genetic testing, we confirmed our diagnosis. A 46-year-old male patient was admitted to our emergency room due to instable angina pectoris and progressive dyspnea (NYHA III). The patient was completely healthy until a week earlier, when he had an upper respiratory tract infection. The patient had no cardiovascular risk factors or
& Peter Seizer [email protected] 1
Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Eberhard Karls-Universita¨t Tu¨bingen, Tu¨bingen, Germany
2
Abteilung fu¨r Molekulare Pathologie, Institut fu¨r Pathologie, Universita¨tsklinikum Tu¨bingen, Tu¨bingen, Germany
3
Abteilung fu¨r Diagnostische und Interventionelle Radiologie, Eberhard Karls-Universita¨t Tu¨bingen, Tu¨bingen, Germany
other diseases up to unclear arthralgias. There was no family history of cardiac or hematological disease. The physical examination on admission revealed diminished breath sounds, expiratory crackles at both lung bases, and slight peripheral edema. A 12-lead electrocardiogram (ECG) showed T wave inversion in leads I, aVL, II, III, aVF and V3–V6 (Fig. 1a, b). Chest X-ray and additional computed tomography (CT) revealed a cardiomegaly, minimal pleural effusions, and pneumonia on both sides superimposed on pulmonary edema (Fig. 1c). A pulmonary artery embolism was excluded. Results of laboratory tests indicated elevated serum troponin I levels (0.05 lg/dl) and transaminases (GOT: 63 U/l, GPT: 61 U/l). Creatinine clearance and creatine kinase levels were within the normal range. Echocardiographic examination revealed a marginal dilatation of the left ventricle with a systolic dysfunction (ejection fraction about 40 % with global hypokinesia). A relevant valvular heart disease could be excluded. Due to elevated troponin levels, pathological ECG and systolic dysfunction, a coronary angiography, was performed [1–3]. Coronary angiography excluded the presence of relevant stenoses in the coronary arteries. Laevocardiography confirmed moderate global hypokinesia without significant mitral regurgitation. In order to clarify the cause of the underlying cardiomyopathy, a cardiac magnetic resonance imaging (MRI) was performed. Cardiac MRI revealed a septal linear late enhancement consistent with potential myocarditis or dilatative cardiomyopathy. Interestingly, the incidental finding of an abnormal ‘‘black’’ liver on MRI indicated a possible iron or copper overload (Fig. 1d, e). To finally clarify the underlying myocardial disease, a right ventricular endomyocardial biopsy was performed at the interventricular septum. Whereas no signs of myocarditis or dilatative cardiomyopathy could be detected, Prussian Blue staining of
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Clin Res Cardiol
Fig. 1 a, b 12-lead ECG at admission shows T wave inversion in leads I, aVL, II, III, aVF and V3–V6 (see arrows). c Chest X-ray at admission shows mild cardiomegaly and parahilary pulmonary edema. d, e Cardiac magnetic resonance imaging with midseptal
linear late enhancement and a ‘‘black liver’’. f, g Prussian Blue staining of granular pigment revealed an iron overload in cardiac myocytes (Prussian Blue Stain, 9400) and MHCII expression on activated macrophages
the myocardium showed a significant iron deposition (Fig. 1f, g). In addition, sonographic examination revealed a hepatomegaly with condensed parenchyma without signs of cirrhosis. An elevated serum transferrin-saturation index (94.1 %) confirmed the diagnosis of an iron overload. Serum ferritin level was also markedly increased (479 lg/ dl). In the case of suspected hereditary hemochromatosis (HH), a genetic testing detected that the patient was
homozygous for the C282Y mutation in the HFE (Hemochromatosis) gene. Thus, genetic, biochemical, and clinical markers determined the diagnosis of HH. We recommended a therapeutic phlebotomy by general practitioner, continuing medical heart failure therapy and screening of first-degree relatives. In addition, the patient was advised for an iron-reduced diet.
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Clin Res Cardiol
We report about a patient presenting in our emergency department with usual findings of an acute coronary syndrome [1–6]. Additional diagnostic tools like myocardial biopsy and cardiac MRI were necessary to reach the final diagnosis and thus the beginning of a suitable therapy [7, 8]. There are several reasons, which may lead to elevated troponin levels in our patient despite the absence of relevant stenoses in the coronary arteries: (i) iron deposition was accompanied by a low gradient inflammation according to an enhanced number of activated macrophages (see Fig. 1g), suggesting that single myocytes undergo apoptosis, (ii) acute decompensated heart failure of our patient [9], (iii) iron induced direct myocardial damage [10]. In our case, the clinical and biochemical markers (unclear cardiomyopathy, arthralgias, elevated transferring saturation values) were the first steps to evoke the diagnosis. Due to the clinical findings (pneumonia with cough, recent onset heart failure, elevated troponin), an acute myocarditis would be the suspected diagnosis after exclusion of a relevant coronary heart disease. With the help of advanced diagnostic modalities (MRI, biopsy), we demonstrated an iron overload in cardiac myocytes. Our case supports the importance of myocardial biopsy in patients with unclear reduced ejection fraction [11]. If no myocardial biopsy, but a liver biopsy, would have been performed in our patient, we could not exclude the additional presence of a dilatative cardiomyopathy or acute myocarditis beside the HH [12]. The last step was a simple genetic test. The detection of the C282Y homozygous mutation confirmed the diagnosis of HH with myocardial involvement. In our case, liver biopsy would not add further information or lead to further therapeutic consequences. Thus, liver biopsy was not performed in our patient. HH is an autosomal recessive disorder resulting from mutations in the HFE gene, usually manifesting in adults beginning in their 40 and 50 s. Approximately, 70–100 % of patients with a clinical diagnosis of HH are homozygous for the C282Y mutation [13]. HH is characterized by excessively high iron absorption from the gut resulting in an iron overload in a variety of organs such as liver, heart, and endocrine organs [13]. Although HH is the most common inherited disease of North Europeans with 1 in 200–400 affected [14], recent large studies suggest relatively low rates of clinical appearance and have failed to demonstrate a survival disadvantage [15]. However, in certain cases, HH can have a fatal prognosis. Liver cirrhosis, diabetes, liver cancer, and progressive heart failure are the most common causes of HH-related deaths [16, 17]. Early symptoms of iron accumulation are often nonspecific like unexplained fatigue, joint pain, abdominal pain, or loss of libido [18]. Biochemical tests play a crucial role for the early diagnosis of HH. Transferrin saturation is
generally regarded as the best single screening test for HH. Morning values of 60 % or higher in men and 50 % or higher in women have an approximate sensitivity of 92 %, specificity of 93 %, and positive predictive value of 86 % for detecting homozygous individuals with HH [19]. A low percentage of HH patients develop a cardiac hemochromatosis. HH can lead to a mixed dilated restrictive or dilated cardiomyopathy and conduction disturbances, such as atrial fibrillation or sick sinus syndrome [20]. The severity of myocardial involvement varies widely and does not correlate with the severity in other organs. In a few cases, arrhythmias and sudden cardiac death have been described [19, 21]. However, ventricular dysfunction can be reversible after venesection therapy or alternative chelation therapy [22]. Commonly, the easiest and most effective therapy is venesection. The efficacy of venesections is excellent resulting in a normalized survival rate, if neither cirrhosis nor diabetes were present at the time of diagnosis [23]. Patients with manifestations of late disease should receive treatment as well because some of the sequelae are reversible. The absence of liver cirrhosis and diabetes may predict a normal life expectance under venesection therapy in our patient. Three month after discharge left ventricular function was not improved significantly, however, based on reports in the literature ventricular dysfunction may recover with sufficient therapy within several months [24, 25]. Acknowledgments The study was supported in part by the Deutsche Forschungsgemeinschaft Klinische Forschergruppe KFO274. Conflict of interest On behalf of all authors, the corresponding author states that there is no conflict of interest.
References 1. Post F et al (2012) Pre- and early in-hospital procedures in patients with acute coronary syndromes: first results of the ‘‘German chest pain unit registry’’. Clin Res Cardiol 101(12):983–991 2. Theidel U et al (2013) Cost-effectiveness of ticagrelor versus clopidogrel for the prevention of atherothrombotic events in adult patients with acute coronary syndrome in Germany. Clin Res Cardiol 102(6):447–458 3. Jaguszewski M et al (2015) Acute coronary syndromes in octogenarians referred for invasive evaluation: treatment profile and outcomes. Clin Res Cardiol 104(1):51–58 4. Bestehorn K et al (2015) Coronary procedures in German hospitals: a detailed analysis for specific patient clusters. Clin Res Cardiol [Epub ahead of print] 5. Afzali D et al (2013) Impact of copeptin on diagnosis, risk stratification, and intermediate-term prognosis of acute coronary syndromes. Clin Res Cardiol 102(10):755–763 6. Zeymer U et al (2013) Intra-aortic balloon pump in patients with acute myocardial infarction complicated by cardiogenic shock: results of the ALKK-PCI registry. Clin Res Cardiol 102(3): 223–227
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Clin Res Cardiol 7. Steen H et al (2012) Clinical feasibility study for detection of myocardial oedema by a cine SSFP sequence in comparison to a conventional T2-weighted sequence. Clin Res Cardiol 101(2): 125–131 8. Seizer P et al (2013) Left ventricular site-directed biopsy guided by left ventricular voltage mapping: a proof of principle. Int J Cardiol 168(3):3113–3114 9. Peacock WF et al (2008) Cardiac troponin and outcome in acute heart failure. N Engl J Med 358(20):2117–2126 10. Ramm GA, Ruddell RG (2010) Iron homeostasis, hepatocellular injury, and fibrogenesis in hemochromatosis: the role of inflammation in a noninflammatory liver disease. Semin Liver Dis 30(3):271–287 11. Cooper LT et al (2007) 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. Eur Heart J 28(24):3076–3093 12. Seizer P et al (2013) EMMPRIN and its ligand cyclophilin A as novel diagnostic markers in inflammatory cardiomyopathy. Int J Cardiol 163(3):299–304 13. Feder JN et al (1996) A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nat Genet 13(4):399–408 14. Edwards CQ et al (1988) Prevalence of hemochromatosis among 11,065 presumably healthy blood donors. N Engl J Med 318(21):1355–1362
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15. Waalen J, Nordestgaard BG, Beutler E (2005) The penetrance of hereditary hemochromatosis. Best Pract Res Clin Haematol 18(2):203–220 16. Niederau C et al (1985) Survival and causes of death in cirrhotic and in noncirrhotic patients with primary hemochromatosis. N Engl J Med 313(20):1256–1262 17. Passen EL et al (1996) Images in cardiovascular medicine. Cardiac hemochromatosis. Circulation 94(9):2302–2303 18. McDonnell SM et al (1999) A survey of 2851 patients with hemochromatosis: symptoms and response to treatment. Am J Med 106(6):619–624 19. Tavill AS (2001) Diagnosis and management of hemochromatosis. Hepatology 33(5):1321–1328 20. Rivers J et al (1987) Reversible cardiac dysfunction in hemochromatosis. Am Heart J 113(1):216–217 21. Strobel JS et al (1999) Syncope and inducible ventricular fibrillation in a woman with hemochromatosis. J Interv Card Electrophysiol 3(3):225–229 22. Nielsen P et al (2003) Effective treatment of hereditary haemochromatosis with desferrioxamine in selected cases. Br J Haematol 123(5):952–953 23. Niederau C et al (1996) Long-term survival in patients with hereditary hemochromatosis. Gastroenterology 110(4):1107–1119 24. Gulati V et al (2014) Cardiac involvement in hemochromatosis. Cardiol Rev 22(2):56–68 25. Cecchetti G et al (1991) Cardiac alterations in 36 consecutive patients with idiopathic haemochromatosis: polygraphic and echocardiographic evaluation. Eur Heart J 12(2):224–230
LETTER TO THE EDITORS
A patient with a rare cause of elevated troponin I Antonios Kilias1 • Karin Klingel2 • Meinrad Gawaz1 • Ulrich Kramer3 Peter Seizer1
•
Received: 15 February 2015 / Accepted: 23 April 2015 Ó Springer-Verlag Berlin Heidelberg 2015
Sirs: A 46-year-old male patient was admitted to our emergency room due to instable angina pectoris and progressive dyspnea. Relevant stenosis of coronary arteries was excluded by coronary angiography. MRI revealed septal linear late enhancement. Interestingly, the incidental finding of an abnormal ‘‘black’’ liver on cardiac MRI indicated an iron overload. Myocardial biopsy confirmed a significant myocardial iron deposition. Elevated serum transferrinsaturation index confirmed the diagnosis of an iron overload. Finally, genetic testing confirmed a homozygous C282Y mutation. Acute decompensated heart failure with troponin elevation is a rare first clinical presentation of hereditary hemochromatosis (HH). With the use of advanced diagnostic modalities (MRI, biopsy) and genetic testing, we confirmed our diagnosis. A 46-year-old male patient was admitted to our emergency room due to instable angina pectoris and progressive dyspnea (NYHA III). The patient was completely healthy until a week earlier, when he had an upper respiratory tract infection. The patient had no cardiovascular risk factors or
& Peter Seizer [email protected] 1
Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Eberhard Karls-Universita¨t Tu¨bingen, Tu¨bingen, Germany
2
Abteilung fu¨r Molekulare Pathologie, Institut fu¨r Pathologie, Universita¨tsklinikum Tu¨bingen, Tu¨bingen, Germany
3
Abteilung fu¨r Diagnostische und Interventionelle Radiologie, Eberhard Karls-Universita¨t Tu¨bingen, Tu¨bingen, Germany
other diseases up to unclear arthralgias. There was no family history of cardiac or hematological disease. The physical examination on admission revealed diminished breath sounds, expiratory crackles at both lung bases, and slight peripheral edema. A 12-lead electrocardiogram (ECG) showed T wave inversion in leads I, aVL, II, III, aVF and V3–V6 (Fig. 1a, b). Chest X-ray and additional computed tomography (CT) revealed a cardiomegaly, minimal pleural effusions, and pneumonia on both sides superimposed on pulmonary edema (Fig. 1c). A pulmonary artery embolism was excluded. Results of laboratory tests indicated elevated serum troponin I levels (0.05 lg/dl) and transaminases (GOT: 63 U/l, GPT: 61 U/l). Creatinine clearance and creatine kinase levels were within the normal range. Echocardiographic examination revealed a marginal dilatation of the left ventricle with a systolic dysfunction (ejection fraction about 40 % with global hypokinesia). A relevant valvular heart disease could be excluded. Due to elevated troponin levels, pathological ECG and systolic dysfunction, a coronary angiography, was performed [1–3]. Coronary angiography excluded the presence of relevant stenoses in the coronary arteries. Laevocardiography confirmed moderate global hypokinesia without significant mitral regurgitation. In order to clarify the cause of the underlying cardiomyopathy, a cardiac magnetic resonance imaging (MRI) was performed. Cardiac MRI revealed a septal linear late enhancement consistent with potential myocarditis or dilatative cardiomyopathy. Interestingly, the incidental finding of an abnormal ‘‘black’’ liver on MRI indicated a possible iron or copper overload (Fig. 1d, e). To finally clarify the underlying myocardial disease, a right ventricular endomyocardial biopsy was performed at the interventricular septum. Whereas no signs of myocarditis or dilatative cardiomyopathy could be detected, Prussian Blue staining of
123
Clin Res Cardiol
Fig. 1 a, b 12-lead ECG at admission shows T wave inversion in leads I, aVL, II, III, aVF and V3–V6 (see arrows). c Chest X-ray at admission shows mild cardiomegaly and parahilary pulmonary edema. d, e Cardiac magnetic resonance imaging with midseptal
linear late enhancement and a ‘‘black liver’’. f, g Prussian Blue staining of granular pigment revealed an iron overload in cardiac myocytes (Prussian Blue Stain, 9400) and MHCII expression on activated macrophages
the myocardium showed a significant iron deposition (Fig. 1f, g). In addition, sonographic examination revealed a hepatomegaly with condensed parenchyma without signs of cirrhosis. An elevated serum transferrin-saturation index (94.1 %) confirmed the diagnosis of an iron overload. Serum ferritin level was also markedly increased (479 lg/ dl). In the case of suspected hereditary hemochromatosis (HH), a genetic testing detected that the patient was
homozygous for the C282Y mutation in the HFE (Hemochromatosis) gene. Thus, genetic, biochemical, and clinical markers determined the diagnosis of HH. We recommended a therapeutic phlebotomy by general practitioner, continuing medical heart failure therapy and screening of first-degree relatives. In addition, the patient was advised for an iron-reduced diet.
123
Clin Res Cardiol
We report about a patient presenting in our emergency department with usual findings of an acute coronary syndrome [1–6]. Additional diagnostic tools like myocardial biopsy and cardiac MRI were necessary to reach the final diagnosis and thus the beginning of a suitable therapy [7, 8]. There are several reasons, which may lead to elevated troponin levels in our patient despite the absence of relevant stenoses in the coronary arteries: (i) iron deposition was accompanied by a low gradient inflammation according to an enhanced number of activated macrophages (see Fig. 1g), suggesting that single myocytes undergo apoptosis, (ii) acute decompensated heart failure of our patient [9], (iii) iron induced direct myocardial damage [10]. In our case, the clinical and biochemical markers (unclear cardiomyopathy, arthralgias, elevated transferring saturation values) were the first steps to evoke the diagnosis. Due to the clinical findings (pneumonia with cough, recent onset heart failure, elevated troponin), an acute myocarditis would be the suspected diagnosis after exclusion of a relevant coronary heart disease. With the help of advanced diagnostic modalities (MRI, biopsy), we demonstrated an iron overload in cardiac myocytes. Our case supports the importance of myocardial biopsy in patients with unclear reduced ejection fraction [11]. If no myocardial biopsy, but a liver biopsy, would have been performed in our patient, we could not exclude the additional presence of a dilatative cardiomyopathy or acute myocarditis beside the HH [12]. The last step was a simple genetic test. The detection of the C282Y homozygous mutation confirmed the diagnosis of HH with myocardial involvement. In our case, liver biopsy would not add further information or lead to further therapeutic consequences. Thus, liver biopsy was not performed in our patient. HH is an autosomal recessive disorder resulting from mutations in the HFE gene, usually manifesting in adults beginning in their 40 and 50 s. Approximately, 70–100 % of patients with a clinical diagnosis of HH are homozygous for the C282Y mutation [13]. HH is characterized by excessively high iron absorption from the gut resulting in an iron overload in a variety of organs such as liver, heart, and endocrine organs [13]. Although HH is the most common inherited disease of North Europeans with 1 in 200–400 affected [14], recent large studies suggest relatively low rates of clinical appearance and have failed to demonstrate a survival disadvantage [15]. However, in certain cases, HH can have a fatal prognosis. Liver cirrhosis, diabetes, liver cancer, and progressive heart failure are the most common causes of HH-related deaths [16, 17]. Early symptoms of iron accumulation are often nonspecific like unexplained fatigue, joint pain, abdominal pain, or loss of libido [18]. Biochemical tests play a crucial role for the early diagnosis of HH. Transferrin saturation is
generally regarded as the best single screening test for HH. Morning values of 60 % or higher in men and 50 % or higher in women have an approximate sensitivity of 92 %, specificity of 93 %, and positive predictive value of 86 % for detecting homozygous individuals with HH [19]. A low percentage of HH patients develop a cardiac hemochromatosis. HH can lead to a mixed dilated restrictive or dilated cardiomyopathy and conduction disturbances, such as atrial fibrillation or sick sinus syndrome [20]. The severity of myocardial involvement varies widely and does not correlate with the severity in other organs. In a few cases, arrhythmias and sudden cardiac death have been described [19, 21]. However, ventricular dysfunction can be reversible after venesection therapy or alternative chelation therapy [22]. Commonly, the easiest and most effective therapy is venesection. The efficacy of venesections is excellent resulting in a normalized survival rate, if neither cirrhosis nor diabetes were present at the time of diagnosis [23]. Patients with manifestations of late disease should receive treatment as well because some of the sequelae are reversible. The absence of liver cirrhosis and diabetes may predict a normal life expectance under venesection therapy in our patient. Three month after discharge left ventricular function was not improved significantly, however, based on reports in the literature ventricular dysfunction may recover with sufficient therapy within several months [24, 25]. Acknowledgments The study was supported in part by the Deutsche Forschungsgemeinschaft Klinische Forschergruppe KFO274. Conflict of interest On behalf of all authors, the corresponding author states that there is no conflict of interest.
References 1. Post F et al (2012) Pre- and early in-hospital procedures in patients with acute coronary syndromes: first results of the ‘‘German chest pain unit registry’’. Clin Res Cardiol 101(12):983–991 2. Theidel U et al (2013) Cost-effectiveness of ticagrelor versus clopidogrel for the prevention of atherothrombotic events in adult patients with acute coronary syndrome in Germany. Clin Res Cardiol 102(6):447–458 3. Jaguszewski M et al (2015) Acute coronary syndromes in octogenarians referred for invasive evaluation: treatment profile and outcomes. Clin Res Cardiol 104(1):51–58 4. Bestehorn K et al (2015) Coronary procedures in German hospitals: a detailed analysis for specific patient clusters. Clin Res Cardiol [Epub ahead of print] 5. Afzali D et al (2013) Impact of copeptin on diagnosis, risk stratification, and intermediate-term prognosis of acute coronary syndromes. Clin Res Cardiol 102(10):755–763 6. Zeymer U et al (2013) Intra-aortic balloon pump in patients with acute myocardial infarction complicated by cardiogenic shock: results of the ALKK-PCI registry. Clin Res Cardiol 102(3): 223–227
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Clin Res Cardiol 7. Steen H et al (2012) Clinical feasibility study for detection of myocardial oedema by a cine SSFP sequence in comparison to a conventional T2-weighted sequence. Clin Res Cardiol 101(2): 125–131 8. Seizer P et al (2013) Left ventricular site-directed biopsy guided by left ventricular voltage mapping: a proof of principle. Int J Cardiol 168(3):3113–3114 9. Peacock WF et al (2008) Cardiac troponin and outcome in acute heart failure. N Engl J Med 358(20):2117–2126 10. Ramm GA, Ruddell RG (2010) Iron homeostasis, hepatocellular injury, and fibrogenesis in hemochromatosis: the role of inflammation in a noninflammatory liver disease. Semin Liver Dis 30(3):271–287 11. Cooper LT et al (2007) 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. Eur Heart J 28(24):3076–3093 12. Seizer P et al (2013) EMMPRIN and its ligand cyclophilin A as novel diagnostic markers in inflammatory cardiomyopathy. Int J Cardiol 163(3):299–304 13. Feder JN et al (1996) A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nat Genet 13(4):399–408 14. Edwards CQ et al (1988) Prevalence of hemochromatosis among 11,065 presumably healthy blood donors. N Engl J Med 318(21):1355–1362
123
15. Waalen J, Nordestgaard BG, Beutler E (2005) The penetrance of hereditary hemochromatosis. Best Pract Res Clin Haematol 18(2):203–220 16. Niederau C et al (1985) Survival and causes of death in cirrhotic and in noncirrhotic patients with primary hemochromatosis. N Engl J Med 313(20):1256–1262 17. Passen EL et al (1996) Images in cardiovascular medicine. Cardiac hemochromatosis. Circulation 94(9):2302–2303 18. McDonnell SM et al (1999) A survey of 2851 patients with hemochromatosis: symptoms and response to treatment. Am J Med 106(6):619–624 19. Tavill AS (2001) Diagnosis and management of hemochromatosis. Hepatology 33(5):1321–1328 20. Rivers J et al (1987) Reversible cardiac dysfunction in hemochromatosis. Am Heart J 113(1):216–217 21. Strobel JS et al (1999) Syncope and inducible ventricular fibrillation in a woman with hemochromatosis. J Interv Card Electrophysiol 3(3):225–229 22. Nielsen P et al (2003) Effective treatment of hereditary haemochromatosis with desferrioxamine in selected cases. Br J Haematol 123(5):952–953 23. Niederau C et al (1996) Long-term survival in patients with hereditary hemochromatosis. Gastroenterology 110(4):1107–1119 24. Gulati V et al (2014) Cardiac involvement in hemochromatosis. Cardiol Rev 22(2):56–68 25. Cecchetti G et al (1991) Cardiac alterations in 36 consecutive patients with idiopathic haemochromatosis: polygraphic and echocardiographic evaluation. Eur Heart J 12(2):224–230
