Abstract
Background: Chronic progressive external ophthalmoplegia (CPEO), which includes Kearns‐Sayre syndrome, is a mitochondrial disorder with large deletions of mitochondrial DNA. Recently, mtDNA deletions in cardiac muscle cells were thought to be a cause of dilated cardiomyopathy. However, the cardiac involvement in patients with CPEO is generally considered to be limited to the cardiac conduction system.
Hypothesis: The purpose of this study was to evaluate left ventricular function in patients with CPEO.
Methods: We evaluated the cardiac function of five patients with CPEO by means of carotid pulse recording and Doppler echocardiography.
Results: The ratio of the pre‐ejection period to ejection time was increased to 0.67 in one patient and to 0.50 in another. Echocardiography showed left ventricular dilatation and diffuse hypokinetic wall motion in both cases. Left ventricular fractional shortening was decreased to 5 and 19%, respectively, and the mean rate of circumferential shortening was decreased to 0.12 and 0.63 circ/s, respectively. One of the two patients died of congestive heart failure 2 months after the study. The Doppler pattern of left ventricular filling in the three remaining patients showed a decrease in the ratio of peak flow velocity in early diastole to that in late diastole, with an increase in deceleration time.
Conclusion: Although cardiac involvement in patients with CPEO is generally considered to be limited to the cardiac conduction system, left ventricular dysfunction may be present and should receive more attention in the management of patients with CPEO.
Keywords: chronic progressive external ophthalmoplegia, mitochondrial myopathy, cardiac dysfunction
Full Text
The Full Text of this article is available as a PDF (632.4 KB).
References
- 1. Kearns TP, Sayre GP: Retinitis pigmentosa, external ophthalmoplegia and complete heart block. Unusual syndrome with histologic study in one of two cases. Arch Ophthalmol 1958; 60: 280–289. [PubMed] [Google Scholar]
- 2. DiMauro S, Bonilla E, Zeviani M, Nakagawa M, DeVivo DC: Mitochondrial myopathies. Ann Neurol 1985; 17: 521–538. [DOI] [PubMed] [Google Scholar]
- 3. Moraes CT, DiMauro S, Zeviani M, Lombes A, Shanske S, Miranda AF, Nakase H, Bonilla E, Werneck LC, Servidei S, Nonaka I, Koga Y, Spiro AJ, Brownell AKW, Schmidt B, Schotland DL, Zupanc M, DeVivo DC, Schon EA, Rowland LP: Mitochondrial DNA deletions in progressive external ophthalmoplegia and Kearns‐Sayre syndrome. N Engl J Med 1989; 320: 1293–1299. [DOI] [PubMed] [Google Scholar]
- 4. DiMauro S, Moraes CT: Mitochondrial encephalomyopathies. Arch Neurol 1993; 50: 1197–1208. [DOI] [PubMed] [Google Scholar]
- 5. Flier JS, Underhill LH: Mitochondrial DNA and disease. N Engl J Med 1995; 333: 638–644. [DOI] [PubMed] [Google Scholar]
- 6. Hattori K, Ogawa T, Kondo T: Cardiomyopathy with mitochondrial DNA mutations. Am Heart J 1991; 122: 866–869. [DOI] [PubMed] [Google Scholar]
- 7. Suomalainen A, Paetau A, Leinonen H, Majander A, Peltonen L, Somer H: Inherited idiopathic dilated cardiomyopathy with multiple deletions of mitochondrial DNA. Lancet 1992; 340: 1319–1320. [DOI] [PubMed] [Google Scholar]
- 8. Butler IJ, Gadoth N: Kearns‐Sayre syndrome. A review of a multisystem disorder of children and young adults. Arch Intern Med 1976; 136: 1290–1293. [DOI] [PubMed] [Google Scholar]
- 9. Roberts NK, Perloff JK, Kark RAP: Cardiac conduction in the Kearns‐Sayre syndrome (a neuromuscular disorder associated with progressive external ophthalmoplegia and pigmentary retinopathy). Am J Cardiol 1979; 44: 1396–1400. [DOI] [PubMed] [Google Scholar]
- 10. Charles R, Holt S, Kay JM, Epstein EJ, Rees JR: Myocardial ultra‐structure and the development of atrioventricular block in Kearns‐Sayre syndrome. Circulation 1981; 63: 214–219. [DOI] [PubMed] [Google Scholar]
- 11. Kawai H, Akaike M, Yokoi K, Nishida Y, Kunishige M, Mine H, Saito S: Mitochondrial encephalomyopathy with autosomal dominant inheritance: A clinical and genetic entity of mitochondrial diseases. Muscle & Nerve 1995; 18: 753–760. [DOI] [PubMed] [Google Scholar]
- 12. Lewis RP, Rittgers SE, Forester WF, Boudoulas H: A critical review of the systolic time intervals. Circulation 1977; 56: 146–158. [DOI] [PubMed] [Google Scholar]
- 13. Satin DJ, De Maria A, Kisslo J, Weyman A: The committee on M‐mode standardization of the American Society of Echocardiography. Recommendations regarding quantitation in M‐mode echocardiography: Results of a survey of echocardiographic measurements. Circulation 1978; 58: 1072–1083. [DOI] [PubMed] [Google Scholar]
- 14. Appleton CP, Hade LK, Popp RL: Relation of transmitral flow velocity patterns to left ventricular diastolic function: New insights from a combined hemodynamic and Doppler echocardiographic study. J Am Coll Cardiol 1988; 12: 426–440. [DOI] [PubMed] [Google Scholar]
- 15. Sato W, Tanaka M, Sugiyama S, Nemoto T, Harada K, Miura Y, Kobayashi Y, Goto A, Takada G, Ozawa T: Cardiomyopathy and angiopathy in patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes. Am Heart J 1994; 128: 733–741. [DOI] [PubMed] [Google Scholar]
- 16. Obayashi T, Hattori K, Sugiyama S, Tanaka M, Tanaka T, Itoyama S, Deguchi H, Kawamura K, Koga Y, Toshima H, Takeda N, Nagano M, Ito T, Ozawa T: Point mutations in mitochondrial DNA in patients with hypertrophic cardiomyopathy. Am Heart J 1992; 124: 1263–1269. [DOI] [PubMed] [Google Scholar]
- 17. Zeviani M, Gellera C, Antozzi C, Rimoldi M, Morandi L, Villani F, Tiranti V, DiDonato S: Maternally inherited myopathy and cardiomyopathy. Association with mutation in mitochondrial DNA tRNALeu(UUR) . Lancet 1991; 338: 143–147. [DOI] [PubMed] [Google Scholar]
- 18. Taniike M, Fukushima H, Yanagisawa I, Tsukamoto H, Tanaka J, Fujita H, Nagai T, Sano T, Yamaoka K, Inui K, Okada S: Mitochondrial tRNAIle mutation in fatal cardiomyopathy. Biochem Biophys Res Commun 1992; 186: 47–53. [DOI] [PubMed] [Google Scholar]
- 19. Schwartzkopff B, Frenzel H, Breithardt G, Deckert M, Lösse B, Toyka KV, Borggrefe M, Hort W: Ultrastructural findings in endomyocardial biopsy of patients with Kearns‐Sayre syndrome. J Am Coll Cardiol 1988; 12: 1522–1528. [DOI] [PubMed] [Google Scholar]
- 20. Kleber FX, Park JW, Hübner G, Johannes A, Pongratz D, König E: Congestive heart failure due to mitochondrial cardiomyopathy in Kearns‐Sayre syndrome. Klin Wochenschr 1987; 65: 480–486. [DOI] [PubMed] [Google Scholar]
- 21. Channer KS, Channer JL, Campbell MJ, Ree JR: Cardiomyopathy in the Kearns‐Sayre syndrome. Br Heart J 1988; 59: 486–490. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22. Tueskov C, Angelo‐Nielsen K: Kearns‐Sayre syndrome and dilated cardiomyopathy. Neurology 1990; 40: 553–554. [DOI] [PubMed] [Google Scholar]
- 23. Suzuki Y, Harada K, Miura Y, Sato W, Hayasaka K, Kawamura K, Takada G: Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke‐like episodes (MELAS) decreased in diastolic left ventricular function assessed by echocardiography. Pediatr Cardiol 1993; 14: 162–166. [DOI] [PubMed] [Google Scholar]
- 24. Hayashi J, Ohta S, Kikuchi A, Takemitsu M, Goto Y, Nonaka I: Introduction of disease‐related mitochondrial DNA deletion into HeLa cells lacking mitochondrial DNA results in mitochondrial dysfunction. Proc Natl Acad Sci USA 1991; 88: 10,614–10,618. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25. Obermaiser‐Kusser B, Müller‐Höcker J, Nelson I, Lestienne P, Enter Ch, Riedele Th, Gerbitz KD: Different copy numbers of apparently identically deleted mitochondrial DNA in tissues from a patient with Kearns‐Sayre syndrome detected by PCR. Biochem Biophys Res Commun 1990; 169: 1007–1015. [DOI] [PubMed] [Google Scholar]
- 26. Schon EA, Rizzuto R, Moraes CT, Nakase H, Zeviani M, DiMauro S: A direct repeat is a hotspot for large‐scale deletion of human mitochondrial DNA. Science 1989; 244: 347–349. [DOI] [PubMed] [Google Scholar]