deletion of mitochondrial dna in a patient with conduction block

3
550 Brief Communications February 1993 American Heart Journal Table I. Clinical and hemodynamic characteristics of four patients who underwent open heart, surgery after mitral balloon valvotomy _-. - Mitral value area (cm2) -- -- Follow-up Patient Age Technique and LA + Size After No. (yr) Sex size of balloons fmm)t Basal dilatation 6 mo 1 yr 3 yr 1 18 F Single balloon, 25 mm 45 0.5 3.2* 1.2 0.5 - 2 30 F Single balloon, 22 mm 40 1.1 1.65 1.7 1.3 0.6 3 33 F Double balloon, 15 mm + 18 mm 37 0.76 -. 4 25 F Double balloon, 18 mm + 18 mm 43 0.5 2.8* 2.8 - LA, Left atrium; L-R, left-to-right; MR, mitral regurgitation. *Doppler echocardiographic mitral valve area (measured a week after the procedure); the other values represent catheterization-derived mitral valve area (with the modified Gorlin formula). TMeasured by M-mode echocardiography. $Patient had cerebrovascular accident after the procedure and was hemodynamically unstable. patients, and the septumwasdilated with an 8 mm balloon catheter. In the two patients in whom a double balloon technique wasused,the deflated balloonswere withdrawn in tandem fashion across the septostomy on completion of the procedure. Most patients who undergo percutaneous balloon mitral valvotomy have small left-to-right atria1 shunts, which are undetectable by oximetry but detectable with more sensi- tive techniques such asindicator dilution curves,3 angiog- raphy, and transthoracic or transesophageal color Doppler echocardiography. The diameter of the defects decreases in most cases within 6 months, with a significant decrease in detectable atria1shunts.4 A smallerincrease in valve area after valvotomy, an absence of previous surgical commis- surotomy, presence of smaller left atria, and mitral valve calcification have been shown to predict the appearance of atrial shunting immediately after balloon mitral valvoto- my.3 Persistent atria1 shunts have been related to persis- tently elevated left atrial pressures, which are usually due to restenosis.3, 5All four of our patients had smallleft atria (<50 mm), and none had undergone a previous surgical commissurotomy. All had elevated left atria1 pressures (two because of restenosis and two because of severe valvular regurgitation). Yet careful inspection of the atria1 septum during surgery at a variable interval after the pro- cedure (range, 3 days to 3.5 years) revealed a healedscarin one patient (No. 2) and an intact healthy septum in the rest. We therefore believethat the development of an atria1 septal defect after balloon mitral valvotomy depends not only on the technique (i.e., the number of atria1 septosto- mies, the mode of transseptal balloon catheter delivery,6 and postvalvotomy hemodynamics3 as has been empha- sized previously) but also on the intrinsic elasticity of the atria1septum (fossa ovalis). This wasalsoshownin an ear- lier in vitro experiment, which was performed on fresh heart specimens in which the size of the atrial defect that wascreated by transseptal delivery of a balloon dilatation catheter was more diminutive than that predicted by the cross-sectional area of the inflated balloon.6 This may also explain why an atria1 septal defect does not develop in most. patients who undergo percutaneous balloon mitral valvot- omy, hemodynamicand technical factors notwithstanding. REFERENCES 1. 2. 3. 4. 5. 6. Vahanian A, Michel PL, Cormier B, et al. Results of percuta- neous mitral commissurotomy in 200 patients. Am J Cardiol 1989;63:847-52. Lock JE, Khalilullah M, Shrivatava S, Bahl V, Keane JF. Percutaneous catheter commissurotomy in rheumatic mitral stenosis. N Engl J Med 1985;313:1515-8. Cequier A, Bonan R, Serra A, et al. Left to right atrial shunt- ing after percutaneous mitral valvuloplasty: incidence and long term hemodynamicfollow up. Circulation 1990;81:1190-7. Yashida K, Yoshikawa J, Akasaka T, et al. Assessment of left to right atria1 shunting after percutaneous mitral valvulo- plasty by transesophageal color Doppler flow mapping. Circu- lation 1989;80:1521-6. Crawford MH. Iatrogenic Lutembacher’s syndrome revisited. Circulation 1990;81:1422-4. Fields CD, Slovenkai GA, Isner JM. Atria1 septal defect resulting from mitral balloon valvuloplasty: relation of defect morphology to transseptal balloon catheter delivery. AM HEART J 1990;119:568-76. Deletion of mitochondrial DNA in a patient with conduction block Wataru Sato,a Masashi Tanaka,b Satoru Sugiyama,b Kazuki Hattori,c Takayuki Ito,C Hideaki Kawaguchi,d Hisao Onozuka,d Hisakazu Yasuda,dKazunori Ito,e Goro Takada,” and Takayuki Ozawab Akita, Nagoya, and Sapporo, Japan From the Department of Pediatrics,” Akita University School of Medicine: the Departments of Biomedical Chemistryb and Internal Medicine,‘Faculty of Medicine, University of Nagoya; and the Departments of Cardiologyd and Neurology: Hokkaido University School of Medicine. Supported in part by grants-in-aid for General Scientific Research (62570128) and Scientific Research in Priority Areas (Bioenergetics 01617002) from the Ministry of Education, Science, and Culture of Japan, and by grant 01-02-39 from the Ministry of Health and Welfare of Japan. Reprint requests: Takayuki Ozawa, Department of Biomedical Chemistry, Faculty of Medicine, University of Nagoya, 65 Tsuruma-cho, Showa-ku, Nagoya 466, Japan. AMHEARTJ 1993;125:550 Copyright ” 1993 by Mosby-Year Book, Inc. 0002.8703/93/$1.00 + .lO 4/4/42618

Upload: wataru-sato

Post on 19-Oct-2016

215 views

Category:

Documents


2 download

TRANSCRIPT

Page 1: Deletion of mitochondrial DNA in a patient with conduction block

550 Brief Communications February 1993

American Heart Journal

Table I. Clinical and hemodynamic characteristics of four patients who underwent open heart, surgery after mitral balloon valvotomy

_-. - Mitral value area (cm2)

-- --

Follow-up

Patient Age Technique and LA + Size After No. (yr) Sex size of balloons fmm)t Basal dilatation 6 mo 1 yr 3 yr

1 18 F Single balloon, 25 mm 45 0.5 3.2* 1.2 0.5 - 2 30 F Single balloon, 22 mm 40 1.1 1.65 1.7 1.3 0.6 3 33 F Double balloon, 15 mm + 18 mm 37 0.76 -. 4 25 F Double balloon, 18 mm + 18 mm 43 0.5 2.8* 2.8 -

LA, Left atrium; L-R, left-to-right; MR, mitral regurgitation. *Doppler echocardiographic mitral valve area (measured a week after the procedure); the other values represent catheterization-derived mitral valve area (with the modified Gorlin formula). TMeasured by M-mode echocardiography. $Patient had cerebrovascular accident after the procedure and was hemodynamically unstable.

patients, and the septum was dilated with an 8 mm balloon catheter. In the two patients in whom a double balloon technique was used, the deflated balloons were withdrawn in tandem fashion across the septostomy on completion of the procedure.

Most patients who undergo percutaneous balloon mitral valvotomy have small left-to-right atria1 shunts, which are undetectable by oximetry but detectable with more sensi- tive techniques such as indicator dilution curves,3 angiog- raphy, and transthoracic or transesophageal color Doppler echocardiography. The diameter of the defects decreases in most cases within 6 months, with a significant decrease in detectable atria1 shunts.4 A smaller increase in valve area after valvotomy, an absence of previous surgical commis- surotomy, presence of smaller left atria, and mitral valve calcification have been shown to predict the appearance of atrial shunting immediately after balloon mitral valvoto- my.3 Persistent atria1 shunts have been related to persis- tently elevated left atrial pressures, which are usually due to restenosis.3, 5 All four of our patients had small left atria (<50 mm), and none had undergone a previous surgical commissurotomy. All had elevated left atria1 pressures (two because of restenosis and two because of severe valvular regurgitation). Yet careful inspection of the atria1 septum during surgery at a variable interval after the pro- cedure (range, 3 days to 3.5 years) revealed a healed scar in one patient (No. 2) and an intact healthy septum in the rest. We therefore believe that the development of an atria1 septal defect after balloon mitral valvotomy depends not only on the technique (i.e., the number of atria1 septosto- mies, the mode of transseptal balloon catheter delivery,6 and postvalvotomy hemodynamics3 as has been empha- sized previously) but also on the intrinsic elasticity of the atria1 septum (fossa ovalis). This was also shown in an ear- lier in vitro experiment, which was performed on fresh heart specimens in which the size of the atrial defect that was created by transseptal delivery of a balloon dilatation catheter was more diminutive than that predicted by the cross-sectional area of the inflated balloon.6 This may also explain why an atria1 septal defect does not develop in most.

patients who undergo percutaneous balloon mitral valvot- omy, hemodynamic and technical factors notwithstanding.

REFERENCES

1.

2.

3.

4.

5.

6.

Vahanian A, Michel PL, Cormier B, et al. Results of percuta- neous mitral commissurotomy in 200 patients. Am J Cardiol 1989;63:847-52. Lock JE, Khalilullah M, Shrivatava S, Bahl V, Keane JF. Percutaneous catheter commissurotomy in rheumatic mitral stenosis. N Engl J Med 1985;313:1515-8. Cequier A, Bonan R, Serra A, et al. Left to right atrial shunt- ing after percutaneous mitral valvuloplasty: incidence and long term hemodynamicfollow up. Circulation 1990;81:1190-7. Yashida K, Yoshikawa J, Akasaka T, et al. Assessment of left to right atria1 shunting after percutaneous mitral valvulo- plasty by transesophageal color Doppler flow mapping. Circu- lation 1989;80:1521-6. Crawford MH. Iatrogenic Lutembacher’s syndrome revisited. Circulation 1990;81:1422-4. Fields CD, Slovenkai GA, Isner JM. Atria1 septal defect resulting from mitral balloon valvuloplasty: relation of defect morphology to transseptal balloon catheter delivery. AM HEART J 1990;119:568-76.

Deletion of mitochondrial DNA in a patient with conduction block

Wataru Sato,a Masashi Tanaka,b Satoru Sugiyama,b Kazuki Hattori,c Takayuki Ito,C Hideaki Kawaguchi,d Hisao Onozuka,d Hisakazu Yasuda,d Kazunori Ito,e Goro Takada,” and Takayuki Ozawab Akita, Nagoya, and Sapporo, Japan

From the Department of Pediatrics,” Akita University School of Medicine: the Departments of Biomedical Chemistryb and Internal Medicine,‘Faculty of Medicine, University of Nagoya; and the Departments of Cardiologyd and Neurology: Hokkaido University School of Medicine. Supported in part by grants-in-aid for General Scientific Research (62570128) and Scientific Research in Priority Areas (Bioenergetics 01617002) from the Ministry of Education, Science, and Culture of Japan, and by grant 01-02-39 from the Ministry of Health and Welfare of Japan.

Reprint requests: Takayuki Ozawa, Department of Biomedical Chemistry, Faculty of Medicine, University of Nagoya, 65 Tsuruma-cho, Showa-ku, Nagoya 466, Japan.

AMHEARTJ 1993;125:550

Copyright ” 1993 by Mosby-Year Book, Inc. 0002.8703/93/$1.00 + .lO 4/4/42618

Page 2: Deletion of mitochondrial DNA in a patient with conduction block

556 Brief Communications

effective and alternative method to the conventional posi- tion.

REFERENCES

1.

2.

3.

4.

5.

6.

Daniel WG, Erbel R, Kasper W, Visser CA, Engberding R, Sutherland GR, Grube E, Hanrath P, Maisch B, Dennig K, Schartl M, Kremer P, Angermann C, Iliceto S, Curtius JM, Miigge A. Safety of transesophageal echocardiography: a mul- ticenter survey of 10,419 examinations. Circulation 1991; 83:817-21. Geibel A, Kasper W, Behroz A, Przewolka U, Meinertz T, Just H. Risk of transesophageal echocardiography in awake pa- tients with cardiac diseases. Am J Cardiol 198&62:337-g. Seward JB, Khandheria BK, Oh JK, Abel MD, Hughes RW, Edwards WD, Nichols BA, Freeman WK, Tajik AJ. Transe- sophageal echocardiography: technique, anatomic correla- tions, implementation, and clinical applications. Mayo Clin Proc 1988;63:649-80. Bansal RC, Shakudo M, Shah PM, Shah PM. Biplane transe- sophageal echocardiography: technique, image orientation, and preliminary experience in 131 patients. J Am Sot Echocar- diogr 1990;3:348-66. Fleischer DE, Goldstein SA. Transesophageal echocardiogra- phy: what the gastroenterologist thinks the cardiologist should know about endoscopy. J Am Sot Echocardiogr 1990;3:342-34. Erbel R, Rohmann S, Drexler M, Mohr-Kahaly S, Gerharz CD, Iversen S, Oeler H, Meyer J. Improved diagnostic value of echocardiography in patients with infective endocarditis by transesophageal approach: a prospective study. Eur Heart J 1988;9:43-53. Nellessen U, Schnittger I, Appleton CP, Masuyama T, Bolger A, Fischell TA, Tye T, Popp RL. Transesophageal two- dimensional echocardiography and color Doppler flow veloc- ity mapping in the evaluation of cardiac valve prostheses. Cir- culation 19&3;78:848-55. Stoddard MF, Arce J, Liddell NE, Peters G, Dillon S, Kuper- smith J. Two-dimensional transesophageal echocardiographic determination of aortic valve area in adults with aortic steno- sis. AM HEART J 1991;122:1415-22. Erbel R, Engberding R, Daniel W, Roelandt J, Visser C, Ren- nollet H. Echocardiography in diagnosis of aortic dissection. Lancet 1989;1:457-60.

Angioscopic and intravascular ultrasound imagings before and after percutaneous holmium-YAG laser coronary angioplasty

Akira Itoh, MD, Shunichi Miyazaki, MD, Hiroshi Nonogi, MD, Keizaburo Ozono, MD, Satoshi Daikoku, MD, Katsumi Saito, MD, Yoichi Goto, MD, and Kazuo Haze, MD Osaka, Japan

Coronary angiography is an established technique to eval- uate coronary artery stenosis and its severity. However, it

From the Division of Cardiology, Department of Internal Medicine, National Cardiovascular Center, Suita, Osaka.

Reprint requests: Kazuo Haze, MD, Division of Cardiology, Department of Internal Medicine, National Cardiovascular Center, 5-7-l Fujishirodai, Suita, Osaka 565, Japan.

AM HEART J 1993:125:556

February 1993

American Heart Journal

has a limitation in that the obtained information does not necessarily correlate to the pathologic changes because the images only show the silhouette of intraluminal changes.’ Coronary angioscopy can reveal the color and the surface plaque morphology of the coronary artery.2T 3 Intravascular ultrasound has the advantage of inspecting the entire ar- terial wall from the intima to the adventitia.4 By combin- ing these two modalities, it is expected that we may be able to understand the pathologic changes of the diseased cor- onary arterial wall in detail. Recently, holmium-yttrium- aluminum-garnet (Ho-YAG) laser coronary angioplasty was developed, and it has been available for the treatment of patients with angina as an investigational device.” Although the Ho-YAG laser-a pulsed wave laser--is reported to vaporize the atheromatous plaque experimen- tally, its effect on the atheromatous lesion has not been observed directly in vivo. We report the first case of com- bined observation with angiography, angioscopy, and in- travascular ultrasound before and after treatment with Ho-YAG laser angioplasty.

A 64-year-old male patient was referred to our hospital because of exertional chest discomfort and dyspnea. Cor- onary angiography revealed 90 % stenosis of the proximal left anterior descending coronary artery. Exercise thalli- um-201 scintigraphy showed anteroseptal myocardial is- chemia. The symptoms were not relieved despite maximal medical therapy. Because the angiographic morphology of the stenosis was extremely eccentric and the site was the branching portion of a major septal perforator, we applied Ho-YAG laser coronary angioplasty as an initial treatment of the vessel to avoid large coronary dissection and side branch occlusion. Available systems for coronary angios- copy were the VFS-1300 endoscopic system and the IF- 783V fiberoptic catheter (Nihon Kohden, Tokyo, Japan). The fiberoptic catheter is 0.68 mm in diameter and has 3000 pixels of imaging fiber with 50 bundles of lightening fiber. The double guiding catheter system (Inoue)2 was used to introduce the fiberoptic catheter. A hand injection or a compression bag was used for saline flush to obtain a clear viewing field. A 5F 30 MHz ultrasound imaging cath- eter (Cardiovascular Imaging Systems, Sunnyvale, Calif.) was used to obtain circumferential ultrasound images of the coronary arterial wall. It was introduced into the cor- onary artery over the guide wire, which had crossed the le- sion. Ultrasound images were obtained both during ante- grade passage and pullback of the catheter. Both angio- scopic and ultrasound images were recorded on S-VHS videotape for subsequent review and analysis. A Ho-YAG laser generator (Eclipse 2100, Eclipse Surgical Technolo- gies Inc., Palo Alto, Calif.) delivers a pulsed laser beam 250 msec in pulse length and 5 Hz in frequency. System spec- ifications are listed in Table I. We used a 1.75 mm “prime type” over-the-wire multifiber catheter system with 1.75 W of energy at the tip for this patient. After a 9F sheath was inserted into the right femoral artery, 5000 units of heparin and 500 mg of aspirin were administered intravenously. A 9F Superflow left Judkins catheter (Schneider Inc., Min- neapolis, Minn.) was advanced into the left coronary ostium. After baseline imaging with angiography, angios-

Copyright ‘?, 1993 by Mosby-Year Book, Inc. 0002-8703/93/$1.00 + .I0 4/4/42608

Page 3: Deletion of mitochondrial DNA in a patient with conduction block

552 Brief Communications February 1993

American HesIt Journal

Fig. 2. Detection of deleted mtDNA by primer-shift PCR method. A, PCR amplification with primers L820 and H1338. B, PCR amplification with primers L853 and H1338. Sizes of amplified fragments are indicated in kilo- base pairs. Only a single band was amplified from normal- sized mtDNA in control (C) muscle. Abnormal fragments derived from deleted mtDNA were found in both skeletal (S) and heart (H) muscle.

Fig. 1. Southern blot analysis of mtDNA digested with PvuII. In skeletal muscle (S), multiple fragments derived from deleted mtDNA were detected along with normal- sized mtDNA. No extra fragments were detected in either control (C) or heart (H) muscle.

mtDNA was smaller than the detection limit of the South- ern blot analysis. According to the reentry model proposed by Schmitt and Erlanger,4 cardiac conduction block is due to the presence of tissues with disparate electrophysiologic properties. Yamamoto and Nonaka5 reported that CCO- negative and CCO-positive portions were distributed seg- mentally even in a single skeletal muscle fiber in patients with mtDNA deletions. Three subunits of CC0 are en- coded by mtDNA. Accordingly the CCO-negative portions might represent segregation of defective mitochondria based on mtDNA mutations. It seems likely that similar segregation of defective mitochondria would also occur in the heart conduction system. Therefore we postulate that segmental distribution of mutant mtDNA is the cause of such an electrophysiologic difference within the specialized conduction system that generates cardiac arrhythmias or conduction blocks.

Chronic progressive external ophthalmoplegia has re- cently been categorized as a mtDNA disease, and Ozawa et al3 pointed out that mtDNA deletion in patients with chronic progressive external ophthalmoplegia is mater-

nally inherited.” We observed that mtDNA from the second son of the patient had a 6.0 Kb deletion, which was differ- ent from that of the patient. Although further investiga- tion, particularly mtDNA analysis of his family, is neces- sary to clarify the implication of mtDNA with deletion in the genesis of this pathologic condition, it is quite possible that the abnormality in molecular level might contribute to electrophysiologic disturbance.

REFERENCES

1.

2.

3.

4.

5.

Linnane AW, Marzuki S, Ozawa T, Tanaka M. Mitochondrial DNA mutations as an important contributor to ageing and degenerative diseases. Lancet 1989;1:642-5. Roberts NK, Perloff JK, Kark RAP. Cardiac conduction in Kearns-Sayre syndrome (a neuromuscular disorder associated with progressive external ophthalmoplegia and pigmentary retinopathy). Report of 2 cases and review of 17 published cases. Am J Cardiol 1979;44:1396-400. Ozawa T, Yoneda M, Tanaka M, Ohno K, Sato W, Suzuki H, Nishikimi M, Yamamoto M, Nonaka I, Horai S. Maternal in- heritance of deleted mitochondrial DNA in a family with mi- tochondrial myopathy. Biochem Biophys Res Commun 1988; 154:1240-7. Schmitt FO, Erlanger J. Directional differences in the con- duction of the impulse through heart muscle and their possi- ble relation to extrasystolic and fibrillatory contractions. Am J Physiol 1929;87:326-47. Yamamoto M, Nom&a I. Skeletal muscle pathology in chronic progressive external ophthalmoplegia with ragged-red fibers. Acta Neuropathol 1988;76:558-63.