Dilated cardiomyopathy

Not to be confused with hypertrophic cardiomyopathy or any other cardiomyopathy.
Dilated cardiomyopathy

Mouse heart slice showing dilated cardiomyopathy
Classification and external resources
Specialty Cardiology
ICD-10 I42.0
ICD-9-CM 425.4
OMIM 212110
DiseasesDB 3066
MedlinePlus 000168
eMedicine med/289 emerg/80 ped/2502
MeSH D002311
GeneReviews

Dilated cardiomyopathy or DCM is a condition in which the heart becomes enlarged and cannot pump blood efficiently. The decreased heart function can affect the lungs, liver, and other body systems.

DCM is one of the cardiomyopathies, a group of diseases that affect primarily the myocardium (the muscle of the heart). Different cardiomyopathies have different causes and affect the heart in different ways. In DCM a portion of the myocardium is dilated, often without any obvious cause. Left or right ventricular systolic pump function of the heart is impaired, leading to progressive cardiac enlargement and hypertrophy, a process called remodeling.[1]

Dilated cardiomyopathy is the most common form of non-ischemic cardiomyopathy. It occurs more frequently in men than in women, and is most common between the ages of 20 and 60 years.[2] About one in three cases of congestive heart failure (CHF) is due to dilated cardiomyopathy.[1] Dilated cardiomyopathy also occurs in children.

Signs and symptoms

Illustration of a Normal Heart vs. Heart with Dilated Cardiomyopathy

Dilated cardiomyopathy may not cause symptoms significant enough to impact on quality of life. A minority of people can experience significant symptoms. These might include:

A person suffering from dilated cardiomyopathy may have an enlarged heart, with pulmonary edema and an elevated jugular venous pressure and a low pulse pressure. Signs of mitral and tricuspid regurgitation may be present. A fast heart rate with no change during the respiratory cycle may also be found.

Causes

Although in many cases no cause is apparent, dilated cardiomyopathy is probably the result of damage to the myocardium produced by a variety of toxic, metabolic, or infectious agents. It may be due to fibrous change of the myocardium from a previous myocardial infarction. Or, it may be the late sequelae of acute viral myocarditis, such as with Coxsackie B virus and other enteroviruses[3] possibly mediated through an immunologic mechanism.[4] In cats, taurine deficiency is the most common cause of dilated cardiomyopathy.

Other causes include:

Autoimmune mechanisms are also suggested as a cause for dilated cardiomyopathy.[7]

Recent studies have shown that those subjects with an extremely high occurrence (several thousands a day) of premature ventricular contractions (extrasystole) can develop dilated cardiomyopathy. In these cases, if the extrasystole are reduced or removed (for example, via ablation therapy) the cardiomyopathy usually regresses.[8][9]

Although the disease is more common in African-Americans than in Caucasians,[10] it may occur in any patient population.

Genetics

About 25–35% of affected individuals have familial forms of the disease,[3] with most mutations affecting genes encoding cytoskeletal proteins,[3] while some affect other proteins involved in contraction.[11] The disease is genetically heterogeneous, but the most common form of its transmission is an autosomal dominant pattern.[3] Autosomal recessive (as found, for example, in Alström syndrome[3]), X-linked (as in Duchenne muscular dystrophy), and mitochondrial inheritance of the disease is also found.[12] Some relatives of those affected by dilated cardiomyopathy have preclinical, asymptomatic heart-muscle changes.[13]

Other cytoskeletal proteins involved in DCM include α-cardiac actin, desmin, and the nuclear lamins A and C.[3] Mitochondrial deletions and mutations presumably cause DCM by altering myocardial ATP generation.[3]

Pathophysiology

The progression of heart failure is associated with left ventricular remodeling, which manifests as gradual increases in left ventricular end-diastolic and end-systolic volumes, wall thinning, and a change in chamber geometry to a more spherical, less elongated shape. This process is usually associated with a continuous decline in ejection fraction. The concept of cardiac remodeling was initially developed to describe changes that occur in the days and months following myocardial infarction.[14]

Death is due to either congestive heart failure or ventricular tachy- or bradyarrhythmias.

Computational models

Cardiac dilation is a transversely isotropic, irreversible process resulting from excess strains on the myocardium.[15] A computation model of volumetric, isotropic, and cardiac wall growth predicts the relationship between cardiac strains (e.g. volume overload after myocardial infarction) and dilation using the following governing equations:

F = F^e \cdot F^g\,

where F^e is elastic volume stretch that is reversible and F^g is irreversible, isotropic volume growth described by:

F^g = \mathbb{I}+[\lambda^{g}-1]f_{0}\otimes f_{0} \,

where f_{0} is a vector, which points along a cardiomyocyte's long axis and \lambda^g is the cardiomyocyte stretch due to growth. The total cardiomyocyte growth is given by:

\lambda = \lambda^e \cdot F\lambda^g\,

The above model reveals a gradual dilation of the myocardium, especially the ventricular myocardium, to support the blood volume overload in the chambers. Dilation manifests itself in an increase in total cardiac mass and cardiac diameter. Cardiomyocytes reach their maximum length of 150 \mum in the endocardium and 130 \mum in the epicardium by the addition of sarcomeres.[16] Due to the increase in diameter, the dilated heart appears spherical in shape, as opposed the elliptical shape of a healthy human heart. In addition, the ventricular walls maintain the same thickness, characteristic of pathophysiological cardiac dilation.

Diagnosis

Generalized enlargement of the heart is seen upon normal chest X-ray. Pleural effusion may also be noticed, which is due to pulmonary venous hypertension.

Serial 12-lead ECGs from a 49-year-old black man with cardiomyopathy. (TOP): Sinus tachycardia (rate about 101/min) with LBBB accompanied by RAD (here about 108°). Frequent multifocal PVCs (both singly and in pairs) and left atrial enlargement. (BOTTOM): Same patient about 5 months later status-post orthotopic heart transplant.

The electrocardiogram often shows sinus tachycardia or atrial fibrillation, ventricular arrhythmias, left atrial enlargement, and sometimes intraventricular conduction defects and low voltage. When left bundle-branch block (LBBB) is accompanied by right axis deviation (RAD), the rare combination is considered to be highly suggestive of dilated or congestive cardiomyopathy.[17][18] Echocardiogram shows left ventricular dilatation with normal or thinned walls and reduced ejection fraction. Cardiac catheterization and coronary angiography are often performed to exclude ischemic heart disease.

Genetic testing can be important, since one study has shown that gene mutations in the TTN gene (which codes for a protein called titin) are responsible for "approximately 25% of familial cases of idiopathic dilated cardiomyopathy and 18% of sporadic cases."[19] The results of the genetic testing can help the doctors and patients understand the underlying cause of the dilated cardiomyopathy. Genetic test results can also help guide decisions on whether a patient's relatives should undergo genetic testing (to see if they have the same genetic mutation) and cardiac testing to screen for early findings of dilated cardiomyopathy.

Cardiac magnetic resonance imaging (cardiac MRI) may also provide helpful diagnostic information in patients with dilated cardiomyopathy.[20]

Treatment

Management and treatment of dilated cardiomyopathy has improved significantly in the last decade. Drug therapy can slow down progression and in some cases even improve the heart condition. Standard therapy may include salt restriction, ACE inhibitors, diuretics, and digitalis. Anticoagulants may also be used. Alcohol should be avoided.

There is some evidence for the benefits of coenzyme Q10 in treating heart failure.[21][22][23] Other supplements provided may include L-carnitine, taurine and D-ribose.

Surgery

Artificial pacemakers may be used in patients with intraventricular conduction delay, and implantable cardioverter-defibrillators in those at risk of arrhythmia. These forms of treatment have been shown to improve symptoms and reduce hospitalization.

In patients with advanced disease who are refractory to medical therapy, heart transplantation may be considered.

Reverse remodeling

This refers to reversing the remodeling that has occurred. Therapies that support reverse remodeling have been investigated, and this may suggests a new approach to the prognosis of cardiomyopathies (see ventricular remodeling).[14]

Other animals

Dilated cardiomyopathy is a heritable disease in some dog breeds, including the Boxer, Dobermann, Great Dane, Irish Wolfhound, and St Bernard.[24] Treatment is based on medication, including ACE inhibitors, loop diuretics, and phosphodiesterase inhibitors.

Dilated cardiomyopathy is also a disease affecting some cat breeds, including the Oriental Shorthair, Burmese, Persian, and Abyssinian. As opposed to these hereditary forms, non-hereditary DCM used to be common in the overall cat population before the addition of taurine to commercial cat food.

There is also a high incidence of heritable dilated cardiomyopathy in captive Golden Hamsters (Mesocricetus auratus), due in no small part to their being highly inbred. The incidence is high enough that several strains of Golden Hamster have been developed to serve as animal models in clinical testing for human forms of the disease.[25]

References

  1. 1 2 Jameson JN, Kasper DL, Harrison TR, Braunwald E, Fauci AS, Hauser SL, Longo DL. (2005). Harrison's principles of internal medicine (16th ed.). New York: McGraw-Hill Medical Publishing Division. ISBN 0-07-140235-7.
  2. ↑ Robbins SL, Kumar V, Cotran RS (2003). Robbins basic pathology (7th ed.). Philadelphia: Saunders. ISBN 0-7216-9274-5.
  3. 1 2 3 4 5 6 7 8 9 10 11 Mitchell, Richard Sheppard; Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson. Robbins Basic Pathology (8th ed.). Philadelphia: Saunders. ISBN 1-4160-2973-7.
  4. ↑ Martino TA, Liu P, Sole MJ (February 1994). "Viral infection and the pathogenesis of dilated cardiomyopathy". Circ Res. 74 (2): 182–8. doi:10.1161/01.res.74.2.182. PMID 8293557.
  5. ↑ http://www.merckmanuals.com/professional/cardiovascular_disorders/cardiomyopathies/dilated_cardiomyopathy.html
  6. ↑ Ritesh Agarwal,corresponding author Puneet Malhotra, Anshu Awasthi, Nandita Kakkar, and Dheeraj Gupta. Tuberculous dilated cardiomyopathy: an under-recognized entity? BMC Infect Dis. 2005; 5: 29. Published online 2005 Apr 27. doi: 10.1186/1471-2334-5-29
  7. ↑ San Martín MA, García A, Rodríguez FJ, Terol I (May 2002). "[Dilated cardiomyopathy and autoimmunity: an overview of current knowledge and perspectives]". Rev Esp Cardiol. (in Spanish) 55 (5): 514–24. doi:10.1016/s0300-8932(02)76644-x. PMID 12015932.
  8. ↑ Belhassen B (April 2005). "Radiofrequency ablation of "benign" right ventricular outflow tract extrasystoles: a therapy that has found its disease?". J. Am. Coll. Cardiol. 45 (8): 1266–8. doi:10.1016/j.jacc.2005.01.028. PMID 15837260.
  9. ↑ Shiraishi H, Ishibashi K, Urao N, et al. (November 2002). "A case of cardiomyopathy induced by premature ventricular complexes". Circ. J. 66 (11): 1065–7. doi:10.1253/circj.66.1065. PMID 12419942.
  10. ↑ Coughlin SS, Labenberg JR, Tefft MC (March 1993). "Black-white differences in idiopathic dilated cardiomyopathy: the Washington DC dilated Cardiomyopathy Study". Epidemiology 4 (2): 165–72. doi:10.1097/00001648-199303000-00013. PMID 8452906.
  11. ↑ Ross J (March 2002). "Dilated cardiomyopathy: concepts derived from gene deficient and transgenic animal models". Circ J. 66 (3): 219–24. doi:10.1253/circj.66.219. PMID 11922267.
  12. ↑ Schönberger J, Seidman CE (August 2001). "Many roads lead to a broken heart: the genetics of dilated cardiomyopathy". American Journal of Human Genetics 69 (2): 249–60. doi:10.1086/321978. PMC 1235300. PMID 11443548.
  13. ↑ Mahon NG, Murphy RT, MacRae CA, Caforio AL, Elliott PM, McKenna WJ (July 2005). "Echocardiographic evaluation in asymptomatic relatives of patients with dilated cardiomyopathy reveals preclinical disease". Annals of Internal Medicine 143 (2): 108–15. doi:10.7326/0003-4819-143-2-200507190-00009. PMID 16027452.
  14. 1 2 Pieske B (2004). "Reverse remodeling in heart failure – fact or fiction?". Eur Heart J Suppl. 6: D66–78. doi:10.1016/j.ehjsup.2004.05.019.
  15. ↑ Goektepe, Serdar; Abilez, Oscar John; Kuhl, Ellen (2010). "Generic approach towards finite growth with examples of athlete's heart, cardiac dilation, and cardiac wall thickening". Mechanics and Physics of Solids. doi:10.1016/j.jmps.2010.07.003.
  16. ↑ Goektepe, Serdar; Abilez, Oscar John; Parker, K; Kuhl, Ellen (2010). "A multiscale model for eccentric and concentric cardiac growth through sarcomerogenesis.". Theoretical Biology. doi:10.1016/j.jmps.2010.07.003.
  17. ↑ Nikolic G, Marriott HJ (Oct 1985). "Left bundle branch block with right axis deviation: a marker of congestive cardiomyopathy". J Electrocardiol 18 (4): 395–404. doi:10.1016/s0022-0736(85)80022-4. PMID 3906012.
  18. ↑ Childers R, Lupovich S, Sochanski M, Konarzewska H. (2000). "Left bundle branch block and right axis deviation: a report of 36 cases". J Electrocardiol 33 (Suppl): 93–102. doi:10.1054/jclc.2000.20326. PMID 11265743.
  19. ↑ Herman DS, Lam L, Taylor MR, Wang L, Teekakirikul P, Christodoulou D, Conner L, DePalma SR, McDonough B, Sparks E, Teodorescu DL, Cirino AL, Banner NR, Pennell DJ, Graw S, Merlo M, Di Lenarda A, Sinagra G, Bos JM, Ackerman MJ, Mitchell RN, Murry CE, Lakdawala NK, Ho CY, Barton PJ, Cook SA, Mestroni L, Seidman JG, Seidman CE (Feb 16, 2012). "Truncations of Titin causing dilated cardiomyopathy". N Engl J Med 366 (7): 619–628. doi:10.1056/NEJMoa1110186. PMID 22335739.
  20. ↑ Pennell DJ, Sechtem UP, Higgins CB, Manning WJ, Pohost GM, Rademakers FE, van Rossum AC, Shaw LJ, Yucel EK. (Nov 2004). "Clinical indications for cardiovascular magnetic resonance (CMR): Consensus Panel report". Eur Heart J 25 (21): 1940–1965. doi:10.1016/j.ehj.2004.06.040. PMID 15522474.
  21. ↑ Langsjoen PH, Langsjoen PH, Folkers K (1990). "A six-year clinical study of therapy of cardiomyopathy with coenzyme Q10". Int J Tissue React. 12 (3): 169–71. PMID 2276895.
  22. ↑ Folkers K, Langsjoen P, Langsjoen PH (January 1992). "Therapy with coenzyme Q10 of patients in heart failure who are eligible or ineligible for a transplant". Biochem Biophys Res Commun. 182 (1): 247–53. doi:10.1016/S0006-291X(05)80137-8. PMID 1731784.
  23. ↑ Baggio E, Gandini R, Plancher AC, Passeri M, Carmosino G (1994). "Italian multicenter study on the safety and efficacy of coenzyme Q10 as adjunctive therapy in heart failure. CoQ10 Drug Surveillance Investigators". Mol Aspects Med. 15 (Suppl): s287–94. doi:10.1016/0098-2997(94)90040-X. PMID 7752841.
  24. ↑ Oyama MA, Chittur S (July 2005). "Genomic expression patterns of cardiac tissues from dogs with dilated cardiomyopathy". Am J Vet Res 66 (7): 1140–55. doi:10.2460/ajvr.2005.66.1140. PMID 16111151.
  25. ↑ Nigro V, Okazaki Y, Belsito A, et al. (April 1997). "Identification of the Syrian hamster cardiomyopathy gene". Hum. Mol. Genet. 6 (4): 601–7. doi:10.1093/hmg/6.4.601. PMID 9097966.

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