Restrictive cardiomyopathy explained

Restrictive cardiomyopathy
Synonyms:	Obliterative cardiomyopathy, infiltrative cardiomyopathy, constrictive cardiomyopathy^[1]

Restrictive cardiomyopathy (RCM) is a form of cardiomyopathy in which the walls of the heart are rigid (but not thickened).^[2] Thus the heart is restricted from stretching and filling with blood properly. It is the least common of the three original subtypes of cardiomyopathy: hypertrophic, dilated, and restrictive.

It should not be confused with constrictive pericarditis, a disease which presents similarly but is very different in treatment and prognosis.

Signs and symptoms

Untreated hearts with RCM often develop the following characteristics:^[3]

• M or W configuration in an invasive hemodynamic pressure tracing of the RA
• Square root sign of part of the invasive hemodynamic pressure tracing Of The LV
• Biatrial enlargement
• Thickened LV walls (with normal chamber size)
• Thickened RV free wall (with normal chamber size)
• Elevated right atrial pressure (>12mmHg),
• Moderate pulmonary hypertension,
• Normal systolic function,
• Poor diastolic function, typically Grade III - IV Diastolic heart failure.

Those affected by RCM will experience decreased exercise tolerance, fatigue, jugular venous distention, peripheral edema, and ascites. Arrhythmias and conduction blocks are common.

Causes

RCM can be caused by genetic or non-genetic factors.^{[4] [5] [6]} Thus it is possible to divide the causes into primary and secondary.^[7] The common modern organization is into Infiltrative, storage diseases, non-infiltrative, and endomyocardial etiologies:^[8]

• Genetic
  • DES (desmin) ^[9]
  • CRYAB (alpha B Crystallin, HSPB5) ^[10]
  • FLNC (filamin C) ^[11]
• Infiltrative
  • Amyloidosis
  • Sarcoidosis
  • Primary hyperoxaluria
• Storage diseases
  • Fabry disease
  • Gaucher disease
  • Hereditary hemochromatosis
  • Glycogen storage disease
  • Mucopolysaccharidosis type I (Hurler syndrome)
  • Mucopolysaccharidosis type II (Hunter syndrome)
  • Niemann-Pick disease
• Non-infiltrative
  • Idiopathic
  • Diabetic cardiomyopathy
  • Scleroderma
  • Myofibrillar myopathies
  • Pseudoxanthoma elasticum
  • Sarcomeric protein disorders
  • Werner's syndrome
• Endomyocardial
  • Carcinoid heart disease
  • Endomyocardial fibrosis
  • Idiopathic
  • Hypereosinophilic syndrome
  • Chronic eosinophilic leukemia
  • Drugs (serotonin, methysergide, ergotamine, mercurial agents, busulfan)
  • Endocardial fibroelastosis
  • Consequence of cancer or cancer therapy
  • Metastatic cancer
  • Drugs (anthracyclines)
  • Radiation

The most common cause of restrictive cardiomyopathy is amyloidosis.

Mechanism

Rhythmicity and contractility of the heart may be normal, but the stiff walls of the heart chambers (atria and ventricles) keep them from adequately filling, reducing preload and end-diastolic volume. Thus, blood flow is reduced, and blood volume that would normally enter the heart is backed up in the circulatory system. In time, restrictive cardiomyopathy patients develop diastolic dysfunction and eventually heart failure.^[12]

Diagnosis

Diagnosis is typically made via echocardiography. Patients will demonstrate normal systolic function, diastolic dysfunction, and a restrictive filling pattern. 2-dimensional and Doppler studies are necessary to distinguish RCM from constrictive pericarditis. If a patient has restrictive cardiomyopathy, the Doppler study should present poorly maintained ventricular filling on the E-wave and little to no late ventricular filling on the A-wave leading to the dip and plateau pattern of the early diastolic pressure marks seen on the ECG.^[13] Cardiac MRI and transvenous endomyocardial biopsy may also be necessary in some cases. Reduced QRS voltage on EKG may be an indicator of amyloidosis-induced restrictive cardiomyopathy.

Treatment

Treatment of restrictive cardiomyopathy should focus on management of causative conditions (for example, using corticosteroids if the cause is sarcoidosis), and slowing the progression of cardiomyopathy. Salt-restriction, diuretics, angiotensin-converting enzyme inhibitors, and anticoagulation may be indicated for managing restrictive cardiomyopathy.^[14] As a consequence of reduced blood flow through the heart, there is an elevation in filling pressures, aimed at sustaining optimal blood circulation throughout the body. However, the excessive use of diuretics may lead to inadequate blood perfusion in body tissues and, consequently, tissue hypoperfusion due to a reduction in overall blood volume.^[15]

Calcium channel blockers are generally contraindicated due to their negative inotropic effect, particularly in cardiomyopathy caused by amyloidosis.^{[16] [17]} Digoxin, calcium channel blocking drugs and beta-adrenergic blocking agents provide little benefit, except in the subgroup of restrictive cardiomyopathy with atrial fibrillation.^[18] Vasodilators are also typically ineffective because systolic function is usually preserved in cases of RCM.

Heart failure resulting from restrictive cardiomyopathy will usually eventually have to be treated by cardiac transplantation or left ventricular assist device.^[14]

Epidemiology

Endomyocardial fibrosis is generally limited to the tropics and sub-saharan Africa. The highest incidence of death caused by cardiac sarcoidosis is found in Japan.^[19]

External links

• Overview at Merck Manual

Notes and References

1. Hancock. EW. Differential diagnosis of restrictive cardiomyopathy and constrictive pericarditis. Heart. September 2001. 86. 3. 343–9. 11514495. 1729880. 10.1136/heart.86.3.343.
2. Book: Pathophysiology of heart disease : a collaborative project of medical students and faculty. 2011. Wolters Kluwer/Lippincott Williams & Wilkins. Lilly, Leonard S., Harvard Medical School.. 978-1605477237. 5th. Baltimore, MD. 649701807.
3. Muchtar . E . Blauwet . L . Gertz . M . Restrictive Cardiomyopathy: Genetics, Pathogenesis, Clinical Manifestations, Diagnosis, and Therapy . Circulation Research . 2017 . 121 . 7 . 819–837 . 10.1161/CIRCRESAHA.117.310982 . 28912185 . free .
4. Brodehl. Andreas. Ferrier. Raechel A.. Hamilton. Sara J.. Greenway. Steven C.. Brundler. Marie-Anne. Yu. Weiming. Gibson. William T.. McKinnon. Margaret L.. McGillivray. Barbara. March 2016. Mutations in FLNC are Associated with Familial Restrictive Cardiomyopathy. Human Mutation. 37. 3. 269–279. 10.1002/humu.22942. 1098-1004. 26666891. 35455240. free.
5. Brodehl. Andreas. Gaertner-Rommel. Anna. Klauke. Bärbel. Grewe. Simon Andre. Schirmer. Ilona. Peterschröder. Andreas. Faber. Lothar. Vorgerd. Matthias. Gummert. Jan. The novel αB-crystallin (CRYAB) mutation p.D109G causes restrictive cardiomyopathy. Human Mutation. 38. 8. en. 947–952. 10.1002/humu.23248. 28493373. 1098-1004. 2017. 13942559. free.
6. Brodehl. Andreas. Pour Hakimi. Seyed Ahmad. Stanasiuk. Caroline. Ratnavadivel. Sandra. Hendig. Doris. Gaertner. Anna. Gerull. Brenda. Gummert. Jan. Paluszkiewicz. Lech. Milting. Hendrik. 2019-11-11. Restrictive Cardiomyopathy is Caused by a Novel Homozygous Desmin (DES) Mutation p.Y122H Leading to a Severe Filament Assembly Defect. Genes. en. 10. 11. 918. 10.3390/genes10110918. 31718026. 2073-4425. free. 6896098.
7. Book: Current diagnosis & treatment in cardiology. Crawford, Michael H.. Lange Medical Books/McGraw-Hill. 2003. 978-0-8385-1473-3. New York. 188. registration.
8. Muchtar. Eli. Blauwet. Lori A.. Gertz. Morie A.. 2017-09-15. Restrictive Cardiomyopathy: Genetics, Pathogenesis, Clinical Manifestations, Diagnosis, and Therapy. Circulation Research. en. 121. 7. 819–837. 10.1161/CIRCRESAHA.117.310982. 0009-7330. 28912185. free.
9. Brodehl. Andreas. Pour Hakimi. Seyed Ahmad. Stanasiuk. Caroline. Ratnavadivel. Sandra. Hendig. Doris. Gaertner. Anna. Gerull. Brenda. Gummert. Jan. Paluszkiewicz. Lech. Milting. Hendrik. 2019-11-11. Restrictive Cardiomyopathy is Caused by a Novel Homozygous Desmin (DES) Mutation p.Y122H Leading to a Severe Filament Assembly Defect. Genes. en. 10. 11. 918. 10.3390/genes10110918. 31718026. 6896098. 2073-4425. free.
10. Brodehl. Andreas. Gaertner-Rommel. Anna. Klauke. Bärbel. Grewe. Simon Andre. Schirmer. Ilona. Peterschröder. Andreas. Faber. Lothar. Vorgerd. Matthias. Gummert. Jan. Anselmetti. Dario. Schulz. Uwe. August 2017. The novel αB-crystallin (CRYAB) mutation p.D109G causes restrictive cardiomyopathy. Human Mutation. en. 38. 8. 947–952. 10.1002/humu.23248. 28493373. 13942559. 1059-7794. free.
11. Brodehl. Andreas. Ferrier. Raechel A.. Hamilton. Sara J.. Greenway. Steven C.. Brundler. Marie-Anne. Yu. Weiming. Gibson. William T.. McKinnon. Margaret L.. McGillivray. Barbara. Alvarez. Nanette. Giuffre. Michael. March 2016. Mutations in FLNC are Associated with Familial Restrictive Cardiomyopathy. Human Mutation. en. 37. 3. 269–279. 10.1002/humu.22942. 26666891. 35455240. free.
12. Web site: Restrictive Cardiomyopathy. The Lecturio Medical Concept Library . 28 June 2021.
13. Nihoyannopoulos, P and D Dawson. 2009. Restrictive cardiomyopathies. European Journal of Echocardiography, Volume 10, Issue 8, Pages iii23–iii33, https://doi.org/10.1093/ejechocard/jep156
14. Web site: Restrictive Cardiomyopathy Treatment & Management. 2015-06-10. 2014-12-18.
15. Muchtar, E, LA Blauwet and MA Gertz. 2017. Restrictive cardiomyopathy: genetics, Ppathogenesis, clinical manifestations, diagnosis, and therapy. Circulation Research. 121:819–837. https://doi.org/10.1161/CIRCRESAHA.117.310982
16. 10.1378/chest.104.2.618. 8339658. 0012-3692. 104. 2. 618–620. Pollak. A. Falk. R H. Left ventricular systolic dysfunction precipitated by verapamil in cardiac amyloidosis.. Chest. 1993-08-01. free.
17. 10.1016/0002-9149(85)90995-6. 0002-9149. 55. 13. 1645. Gertz. Morie A.. Falk. Rodney H.. Skinner. Martha. Cohen. Alan S.. Kyle. Robert A.. Worsening of congestive heart failure in amyloid heart disease treated by calcium channel-blocking agents. American Journal of Cardiology. 1985-06-01. 4003314.
18. 1092-8464. 2. 5. 431–438. Artz. Gregory. Wynne. Joshua. Restrictive Cardiomyopathy. Current Treatment Options in Cardiovascular Medicine. October 2000. 11096547. 10.1007/s11936-000-0038-6. 45162583.
19. Hulten. Edward. Aslam. Saira. Osborne. Michael. Abbasi. Siddique. Bittencourt. Marcio Sommer. Blankstein. Ron. February 2016. Cardiac sarcoidosis—state of the art review. Cardiovascular Diagnosis and Therapy. 6. 1. 50–63. 10.3978/j.issn.2223-3652.2015.12.13. 2223-3652. 4731586. 26885492.