Cardiac fibrosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Niloofarsadaat Eshaghhosseiny, MD[2]


Synonyms and Keywords: Davies disease

Overview

Cardiac fibrosis refers to an abnormal thickening of the heart valves due to inappropriate proliferation of cardiac fibroblasts.Endomyocardial fibrosis(EMF) chareacterized by deposite of fibrous and thickening of the endocardium and myocardium ventricles that leading restrictive cardiomyopathy.It is a neglected disorder that usually prodominant in tropical areas of developing and low -income countries.

Historical Perspective

First description for endomyocardial fibrosis was in 1948 by Davies in Uganda.[1] Endomyocardial fibrosis was first discovered in 1984 in Ugenda.[1]

There have been several outbreaks of endomycardial fibrosis, including Africa,Asia,and South America.[1]

Classification

Myocardial fibrosis may be classified into two groups:interstitial fibrosis (diffuse),replacement fibrosis (scar) .[2] The interstitial fibrosis divided in to two subclasses:reactive and infiltrative.[3]

Pathophysiology

It is thought that cardiac fibrosis is the result of remodeling of extracellular and deposition of extracellular matrix that causes to impaired muscles function.[3] Also cardiac fibrosis is mediated by cardial fibrosis include Eosinophilia, Infectious such as toxoplasma, malaria,helminthic parasites,rheumatic fever,Environmental exposure such as cerium ,casava ,Immunologic and Genetic.[4][5][6] [7][8][9]

Causes

The most common cause of cardiac fibrosis is cardiac fibrotic scars that usually occure after myocardial infarction . other causes of cardiac fibrotic scars include , hypertensive heart disease,diabetic hypertrophic cardiomyopathy and ,idiopathic dilated cardiomyopathy.[3]

Differentiating ((Page name)) from other Diseases

cardiac fibrosis must be differentiated from other diseases that cause heart failure,premature death in children and adults.[10]

Epidemiology and Demographics

Endomyocardial fibrosis is the most cause of heart failure,that up 20% of cases are in endmic area.[10]

Recently the incidence of EMF has been decreased.[10]

In one of the researches in 2008 the prevalence of EMF was 19.8%.[11]

The incidence of EMF is approximately 10,000,000 people worldwide.[11]


The incidence of endomycardial fibrosis is more common in Africa,Asia and South America.[1]

The most cases in Uganda,Mozambique and some west of Africa are Endemic for EMF.[1] Although sporadic cases have been reported in Congo and Malawi.[1] In India the most cases are in rain forest area of Kerala State.[1] In china we can see the high frequency of EMF in Guanxi.[1] And in south of America , Brazil and Colombia are the most frequent area.[1]

Patients of all age groups may develop EMF butcommonly affects young adults between 10 to 30 years old with poor socioeconomic status.[1]

In some researches EMF affects men and women equally but prevalence of EMF in Uganda,is 2-fold higher in women of childbearing age .[1]

The majority of EMF cases are reported in Africa.[1]

Risk Factors

Common risk factors in the development of cardiac fibrosis may be occupational, environmental, genetic, and viral.[3]

Common risk factors in the development of cardiac fibrosis include Obesity, Metabolic dysfunction,DM,HTN.[12]

Screening

There is insufficient evidence to recommend routine screening for cardiac fibrosis but in high risk individuals or in endemic areas we can use echocardiography as screening.[13]

Natural History, Complications, and Prognosis

Common complications of cardiac fibrosis include stifness of left ventricle,heart failure,arrihythmias.[14]

Prognosis is very poor.[13]

Diagnosis

Diagnostic Study of Choice

The diagnosis and severity of cardiac fibrosis according to classification is made when we have 2 major criteria or 1 major criterion with 2 minor criteria.(table below)[1]

From Mocumbi AO, Ferreira MB, Sidi D, Yacoub MH.3 A population study of endomyocardial fibrosis in a rural area of Mozambique. N Engl J Med. 2008;359:43–49. Copyright © 2008 Massachusetts Medical Society.
criterion score
MAJOR CRITERIA
Endomyocardial plaques >2mm in thickness 2
Thin(<1mm) endomyocardial patches affecting >1 ventricular wall 3
Oblitration of the right ventricular or left ventricular apex 4
Thrombi or spontaneous contrast without sever ventricular dysfunction 4
Retraction of right venticular apex (right ventricular apical notch) 4
Atrioventricular valve dysfunction caused by adhession of the valvular apparatus 1-4
MINOR CRITERIA
Thin endomyocardial patches localized to 1 ventricular wall 1
Restrictive flow pattern across mitral or tricuspid valve 2
Pulmonary valve diastolic opening 2
Diffuse thickening of the anterior mitral leaflet 1
Enlarged atrium with normal-sized ventricle 2
M-movment of the interventricular septum and flat posterior wall 1
Enhanced density of the moderator or other intraventricular bands 1

History and Symptoms

EMF symptoms divided in to two phases:Acute , Chronic The most common symptoms of acute include febrile illness ,pancarditis,eosinophilia,dyspenea,itching, pericardial effusion. Symptoms of chronic phase deponds on biventricular or isolated right/left ventricular involvement(RV heart failure/LV heart failure).[1] In right ventricular involvement most common symptoms are :systemic venous HTN,facial edema,exophtalmos,jugular vein distention,gross hepatomegaly,splenomegaly and abdomonal swelling.[1]

Physical Examination

Patients with cardiac fibrosis usually appear ill. Common physical examination findings of cardial fibrosis causing heart failure include,facial and periorbital edema, acscites,jvp distention,fever,pericardial friction rub due to pericarditis and non specific signs in chronic phase are clubbing of digits,growth retardation ,testicular atrophy, cachexia.[1]

Laboratory Findings

Biomarkers of fibrosis can be detected in blood tests.[2] In 2015 Begon Lopez and teammates have been researched on using collagenouse biomarkers for diagnos of cardiac fibrosis. According to this article there is two type of collagen-derived serum peptids have been related to cardiac fibrosis: Carboxy-terminal propeptide of procollagen type 1(P1CP),Amino-terminal propeptide of procollagen type 3(P3NP).[15]

Electrocardiogram

An ECG may be helpful in the diagnosis of cardiac fibrosis. Findings on an ECG include RA abnormality,peaking and increased P wave amplitude, if right ventricle involved we will have R wave in lead V1, and AF is common in patients with cardiac fibrosis.[10]

X-ray

An x-ray may be helpful in the diagnosis of cardiac fibrosis. Findings on an x-ray include cardiomrgaly and may we have silhouette oligemic pulmonary fields.[10]

Echocardiography or Ultrasound

Findings on an echocardiography suggestive of endomyocardial fibrosis include small ventricle with obliteration of the apex with large atrium .[10] Oblitration by fibrosis at ventricular apex can change ventricular morphology,that called mushroom sign.[10]

CT scan

Cardiac calcifications or intracavitary thrombi may be finded in cardiac CT scan.[1]

MRI

Cardiac MRI may be helpful in the diagnosis of EMF. Findings on MRI diagnostic of EMF include small ventricles with hypertrophy in the apical,also shows hypoperfused myocardial areas and we can see fibrosis in late -gadolinium -enhancement images.[1][10]

Other Imaging Findings

There are no other imaging findings associated with cardiac fibrosis.

Other Diagnostic Studies

There are no other diagnostic studies associated with cardiac fibrosis.

Treatment

Medical Therapy

Supportive therapy of heart failure for EMF includes diuretics, angiotensin-converting enzyme inhibitors with combination therapy with asprin or anticoagulation.[1]

Surgery

Surgery is the mainstay of treatment for cardiac fibrosis. Compare with medical therapy , surgery can increase patients survival.Surgery of EMF include endocardiotomy and valve replacement or repair.[10]

Primary Prevention

There are no established measures for the primary prevention of cardiac fibrosis.

Secondary Prevention

Effective measures for the secondary prevention of cardiac fibrosis include screening echocardiography in endemic areas.[10]

References

  1. 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 1.16 1.17 1.18 Grimaldi A, Mocumbi AO, Freers J, Lachaud M, Mirabel M, Ferreira B; et al. (2016). "Tropical Endomyocardial Fibrosis: Natural History, Challenges, and Perspectives". Circulation. 133 (24): 2503–15. doi:10.1161/CIRCULATIONAHA.115.021178. PMID 27297343.
  2. 2.0 2.1 Espeland T, Lunde IG, H Amundsen B, Gullestad L, Aakhus S (2018). "Myocardial fibrosis". Tidsskr Nor Laegeforen. 138 (16). doi:10.4045/tidsskr.17.1027. PMID 30344312.
  3. 3.0 3.1 3.2 3.3 Hinderer S, Schenke-Layland K (2019). "Cardiac fibrosis - A short review of causes and therapeutic strategies". Adv Drug Deliv Rev. 146: 77–82. doi:10.1016/j.addr.2019.05.011. PMID 31158407.
  4. Weller PF, Bubley GJ (1994). "The idiopathic hypereosinophilic syndrome". Blood. 83 (10): 2759–79. PMID 8180373.
  5. Ijaola O, Falase AO (1990). "Distribution of antibodies against Coxsackie B viruses, arboviruses and Toxoplasma gondii among patients with endomyocardial fibrosis (EMF) compared with normal subjects from EMF endemic and non-endemic zones of Nigeria". Afr J Med Med Sci. 19 (2): 93–103. PMID 2165348.
  6. Valiathan SM, Kartha CC (1990). "Endomyocardial fibrosis--the possible connexion with myocardial levels of magnesium and cerium". Int J Cardiol. 28 (1): 1–5. doi:10.1016/0167-5273(90)90002-m. PMID 2194985.
  7. Sezi CL (1996). "Effects of cassava diet on Cercopithecus aethiops livers: a case for cassava as the cause of both tropical splenomegaly syndrome (TSS) and endomyocardial fibrosis (EMF)". East Afr Med J. 73 (5 Suppl): S24–8. PMID 8756024.
  8. Mocumbi AO, Latif N, Yacoub MH (2010). "Presence of circulating anti-myosin antibodies in endomyocardial fibrosis". PLoS Negl Trop Dis. 4 (4): e661. doi:10.1371/journal.pntd.0000661. PMC 2857887. PMID 20422043.
  9. Lowenthal MN (1978). "Endomyocardial fibrosis: familial and other cases from northern Zambia". Med J Zambia. 12 (1): 2–7. PMID 757895.
  10. 10.0 10.1 10.2 10.3 10.4 10.5 10.6 10.7 10.8 10.9 Duraes AR, de Souza Lima Bitar Y, Roever L, Neto MG (2019). "Endomyocardial fibrosis: past, present, and future". Heart Fail Rev. doi:10.1007/s10741-019-09848-4. PMID 31414216.
  11. 11.0 11.1 Mocumbi AO, Ferreira MB, Sidi D, Yacoub MH (2008). "A population study of endomyocardial fibrosis in a rural area of Mozambique". N Engl J Med. 359 (1): 43–9. doi:10.1056/NEJMoa0708629. PMID 18596273.
  12. Cavalera M, Wang J, Frangogiannis NG (2014). "Obesity, metabolic dysfunction, and cardiac fibrosis: pathophysiological pathways, molecular mechanisms, and therapeutic opportunities". Transl Res. 164 (4): 323–35. doi:10.1016/j.trsl.2014.05.001. PMC 4180761. PMID 24880146.
  13. 13.0 13.1 "Correction". Circulation. 131 (24): e535. 2015. doi:10.1161/CIR.0000000000000219. PMID 26078378.
  14. Ma ZG, Yuan YP, Wu HM, Zhang X, Tang QZ (2018). "Cardiac fibrosis: new insights into the pathogenesis". Int J Biol Sci. 14 (12): 1645–1657. doi:10.7150/ijbs.28103. PMC 6216032. PMID 30416379.
  15. López B, González A, Ravassa S, Beaumont J, Moreno MU, San José G; et al. (2015). "Circulating Biomarkers of Myocardial Fibrosis: The Need for a Reappraisal". J Am Coll Cardiol. 65 (22): 2449–56. doi:10.1016/j.jacc.2015.04.026. PMID 26046739.



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