Indications for pacemaker implantation in the Kearns-Sayre syndrome

The Kearns-Sayre syndrome is a rare condition, characterizedby progressive external ophthalmoplegia, retinal pigmentarydegeneration and progressive impairment of cardiac conduction,which mainly determines the prognosis. Two young patients (aged13 and 18 years) without symptoms of cardiac disease presentedwith an electrocardiogram showing sinus rhythm, a normal atrio-ventricularconduction time, right bundle branch block and a left anteriorfascicular block.Electrophysiologic investigation showed prolongationof His-ventricular interval at rest, which further increasedduring atrial pacing. Because of the potential progression ofthe conduction abnormalities and threatening sudden death, wedecided to implant a pacemaker in both patients. Ten monthslater one patient had become pacemaker-dependent. Prophylacticpacemaker therapy is advisable in patients suffering from theKearns-Sayre syndrome, who have bifascicular block on theprecordialelectrocardiogram.     

Indications and choices in pacemaker therapy

During their 33-year history of clinical use, cardiac pacemakers have evolved from devices primarily intended to save lives into complex systems designed to improve the cardiac patient's overall quality of life. To help physicians cope with this rapidly changing field, this review outlines current indications for pacemaker therapy and examines the wide range of options available. After describing the standard nomenclature for identifying the various systems, the author discusses pacemaker selection on the basis of cardiac rhythm alone, as well as rate-modulated therapy.     

Spontaneous Kearns-Sayre/chronic external ophthalmoplegia plus syndrome associated with a mitochondrial DNA deletion: a slip-replication model and metabolic therapy.

The muscle mitochondria of a patient with Kearns-Sayre/chronic external ophthalmoplegia plus syndrome were found to be completely deficient in respiratory complex I activity and partially deficient in complex IV and V activities. Treatment of the patient with coenzyme Q10 and succinate resulted in clinical improvement of respiratory function, consistent with the respiratory deficiencies. Restriction enzyme analysis of the muscle mtDNA revealed a 4.9-kilobase deletion in 50% of the mtDNA molecules. Polymerase chain reaction analysis demonstrated that the deletion was present in the patient's muscle but not in her lymphocytes or platelets. Furthermore, the deletion was not present in the muscle or platelets of two sisters. Hence, the mutation probably occurred in the patient's somatic cells. Direct sequencing of polymerase chain reaction-amplified DNA revealed a 4977-base-pair deletion removing four genes for subunits of complex I, one gene for complex IV, two genes for complex V, and five genes for tRNAs, which paralleled the respiratory enzymes affected in the disease. A 13-base-pair direct repeat was observed upstream from both breakpoints. Relative to the direction of heavy-strand replication, the first repeat was retained and the second repeat was deleted, suggesting a slip-replication mechanism. Sequence analysis of the human mtDNA revealed many direct repeats of 10 base pairs or greater, indicating that this mechanism could account for other reported deletions. We postulate that the prevalence of direct repeats in the mtDNA is a consequence of the guanine-cytosine bias of the heavy and light strands.     

Heart involvement in progressive external ophthalmoplegia (Kearns-Sayre syndrome): electrophysiologic, hemodynamic and morphologic findings

The Kearns-Sayre syndrome is combined with a progressive external ophthalmoplegia (PEO), retinal pigmentary degeneration and heart block. In some patients, progression of incomplete forms has been described and potentially fatal conduction disturbances may occur. The disease is considered as a systemic mitochondrial disorder. As part of an ongoing prospective study 6 patients (3 female, 3 male; age 32 +/- 9 years) with PEO and typical ultrastructural changes of a mitochondrial myopathy in their skeletal muscle were examined. The ECG disclosed atrio/intraventricular conduction defects in 5 patients: 1 patient had a third degree AV block which was treated by a pacemaker. Another patient had left anterior fascicular block with complete right bundle branch block. In 3 other patients an incomplete right bundle branch block was registered. In 1 patient, His-bundle electrography disclosed a block distal to His by atrial high rate pacing before and after i.v. injection of ajmaline; prophylactically a pacemaker was implanted. The mean HV-interval increased significantly under ajmaline by 44% in patients with sinus rhythm. Hemodynamic studies were normal in 5 patients at rest; only 1 patient was abnormal during exercise. Myocardial biopsy demonstrated mitochondrial abnormalities such as variability in shape and size. In 4 patients concentric cristae mitochondriales were seen. Our results suggest that atrioventricular conduction defects are common in patients with PEO. By means of endomyocardial catheterbiopsy a mitochondrial cardiomyopathy could be detected.     

Endocrine dysfunction in Kearns-Sayre syndrome

Kearns-Sayre syndrome (KSS) is a form of mitochondrial myopathy in which specific clinical features, namely progressive external ophthalmoplegia, pigmentary retinal degeneration and cardiac conduction defects, occur. KSS has also been associated with a variety of endocrine and metabolic disorders, in particular short stature, gonadal failure, diabetes mellitus, thyroid disease, hyperaldosteronism, hypomagnesaemia, and bone, tooth and calcification abnormalities. A case is described exhibiting all of these features. A survey of the literature was conducted to determine the prevalence of these conditions among reported cases. Cases with hypoparathyroidism were considered separately to see if they constituted a distinct subgroup with multiple endocrine dysfunction.
Short stature was common, being documented in 38% of cases. Gonadal dysfunction before or after puberty was also common (20% of cases) and affected both sexes equally. Diabetes mellitus was recorded in 13% of cases, half of which required insulin. Thyroid disease, hyperal-dosteronism and hypomagnesaemia were uncommon but were probably not looked for in many cases. Bone or tooth abnormalities and calcification of the basal ganglia were found both in those with and without hypoparathyroldism. While endocrine and metabolic dysfunction was found more commonly in those with hypoparathyroldism this is likely to be due to increased recognition rather than increased prevalence. No evidence of an autoimmune polyendocrine syndrome including hypoparathyroldism was found.     

Cardiac involvement in Kearns-Sayre syndrome

The mitochondrial cytopathies or oxidative-phosphorylation diseases are a diverse group of disorders that result from the structural, biochemical, or genetic derangement of mitochondria. Because mitochondrial dysfunction can affect the most highly energy-dependent organs, cardiac involvement is frequent in these diseases. To identify the clinical features of Kearns-Sayre syndrome, an entity associated with this group of diseases, we evaluated cardiac structure and function in 5 patients with Kearns-Sayre syndrome and followed the clinical course of these patients for 5 years.     

Cardiomyopathy in the Kearns-Sayre syndrome

The Kearns-Sayre syndrome is a mitochondrial myopathy characterised by ptosis, chronic progressive external ophthalmoplegia, abnormal retinal pigmentation, and cardiac conduction defects. A unique case is reported in which there was rapid development of progressive congestive cardiac failure that required cardiac transplantation. A review of published reports of mitochondrial myopathy shows that a minority of cases (less than 20%) have cardiac involvement. This had previously been limited to abnormalities of cardiac conduction with progressive heart block. Myocardial biopsy has, however, shown ultrastructural evidence of a generalised mitochondrial disorder which hitherto has not been associated with a functional deficit.     

Atrioventricular block in Kearns-Sayre syndrome

We report a case of a 17-year-old woman with Kearns-Sayre Syndrome who developed a high degree atrioventricular block. She had intraventricular conduction disturbances with normal atrioventricular conduction in previous electrocardiograms. The diagnosis criteria of this rare syndrome are commented on, and we describe the electrophysiological features, prognostic and treatment that atrioventricular conduction disturbances produce in these patients. We emphasize the necessary collaboration between neurologists and cardiologists in the early recognition of the conduction disturbances for implanting a prophylactic pacemaker.     

Endocrine dysfunction in Kearns-Sayre syndrome.

Kearns-Sayre syndrome (KSS) is a form of mitochondrial myopathy in which specific clinical features, namely progressive external ophthalmoplegia, pigmentary retinal degeneration and cardiac conduction defects, occur. KSS has also been associated with a variety of endocrine and metabolic disorders, in particular short stature, gonadal failure, diabetes mellitus, thyroid disease, hyperaldosteronism, hypomagnesaemia, and bone, tooth and calcification abnormalities. A case is described exhibiting all of these features. A survey of the literature was conducted to determine the prevalence of these conditions among reported cases. Cases with hypoparathyroidism were considered separately to see if they constituted a distinct subgroup with multiple endocrine dysfunction. Short stature was common, being documented in 38% of cases. Gonadal dysfunction before or after puberty was also common (20% of cases) and affected both sexes equally. Diabetes mellitus was recorded in 13% of cases, half of which required insulin. Thyroid disease, hyperaldosteronism and hypomagnesaemia were uncommon but were probably not looked for in many cases. Bone or tooth abnormalities and calcification of the basal ganglia were found both in those with and without hypoparathyroidism. While endocrine and metabolic dysfunction was found more commonly in those with hypoparathyroidism this is likely to be due to increased recognition rather than increased prevalence. No evidence of an autoimmune polyendocrine syndrome including hypoparathyroidism was found.     

Cardiomyopathy in the Kearns-Sayre syndrome.

The Kearns-Sayre syndrome is a mitochondrial myopathy characterised by ptosis, chronic progressive external ophthalmoplegia, abnormal retinal pigmentation, and cardiac conduction defects. A unique case is reported in which there was rapid development of progressive congestive cardiac failure that required cardiac transplantation. A review of published reports of mitochondrial myopathy shows that a minority of cases (less than 20%) have cardiac involvement. This had previously been limited to abnormalities of cardiac conduction with progressive heart block. Myocardial biopsy has, however, shown ultrastructural evidence of a generalised mitochondrial disorder which hitherto has not been associated with a functional deficit.     

Conduction disturbances in the Kearns-Sayre syndrome

The Kearns-Sayre syndrome is an uncommon disease, characterized by the triad of external ophthalmoplegia, retinitis pigmentosa, and heart block. Cardiac manifestations of this syndrome in a 31-year-old man are presented. Electrocardiogram revealed intermittent left bundle branch block and right bundle branch block with left anterior hemiblock. His bundle recording disclosed a prolonged HV interval. Clinical features of the syndrome are discussed and other published cases reviewed.     

Permanent pacemaker implantation. Indications and results

Clinical, laboratory and electrocardiographic data from 608 patients with permanent pacemakers implanted over a period of 8 years, were evaluated retrospectively. The number of implants was greater in males (56.5%) and in patients over 60 years of age (77.5%). Atherosclerosis was the most common disease found in this group (50%). Syncope occurred in 96.2% of the cases; and complete AV block was the most common electrocardiographic alteration (50.5%). Electrode displacement occurred in 32 patients (5.2%) and was the most commonly found early complication. Among the late complications, 10.3% of the patients had infections in the area of the generator. The total mortality was 7.7% due to the heart disease rather than pacemaker-related complication.     

Pathophysiology and management of syncope in Kearns-Sayre syndrome

A 20-year-old woman with known Kearns-Sayre syndrome was transferred to the emergency department due to syncopal episodes. The electrocardiogram on admission showed complete atrioventricular block. The diagnosis of mitochondrial encephalomyopathy was made when she was 14 years old. At the time of the initial diagnosis, she displayed a normal electrocardiogram pattern. At the age of 17, electrocardiogram recordings demonstrated right bundle branch block with left anterior fascicular block and a prolonged QTc interval of 485 milliseconds (Figure). She was taking coenzyme Q10, oral nicotinamide adenine dinucleotide (reduced), piribedil, amantadine, and primidone. Transthoracic echocardiography revealed normal wall motion of both ventricles and mitral valve prolapse without regurgitation. A permanent dual-chamber pacemaker was immediately implanted.