- Email: [email protected]
Cardiac involvement in the Kearns-Sayre syndrome
ALigusr 5, 1987
tion [electrocardiogram B]. Patient C was a 64-yearold man with persistent sinus arrest, in whom a VW pacemaker was implanted, and had no symptom of pacemaker syndrome. An’electrocardiogram showed absence of atria1 activity (electrocardiogram C). The other 2 patients with VW pacemakers had atrial fibrillation with complete atrioventriculqr block and had no symptom after the implantation. The results of the present study show that plasma ANP levels are elevated in many patients with bradyarrhythmias, and that correction of bradyarrhythmias by atrioventricular sequential pacing may decrease plasma ANP levels to normal. In contrast, plasma ANP levels were high in patients with VVI mode pacing, although 1 patient without atria1 contraction had a normal level. It is well knbwn that pacemaker syndrome may be associated with ventricular pacing.5 Regular atria1 echo beats through intact ventriculoatrial conduction (patient A] and a series of atrial contractions during ventricular systole in atrioventricular dissociation (patient B] produce adverse hemodynamic effect and predominance of vasodilatory reflex, which may cause pacemaker syndrome. In this state, atria contract against closed atrioventricular valves and empty in a retrograde direction into pulmonary and systemic vein, causing a marked increase in atria1 pressure .5 ANP secretion may be stimulated,
WE
AIVERICAi\i
JOiiRR;Aii
OF CAFlDlOiOGY
Volume
SO
385
since available evidence suggests that atria1 stretching due to increased atria1 pressure is at least one of the most important stimuli for AMP releases4 Injection of synthetic ANP causes vasodilation and decreases total peripheral resistance.6 Therefore, increased ANP secretion may play a causative role for occurrence of pacemaker syndrome by reducing total peripheral resistance despite low cardiac output in this condition. Further studies may be necessary to clarify the role of ANP in pacemaker syndrome. Acknowledgment: We thank Dr. Kazuhide Yamaoki for critical reading, Youko Morita for electrocardiographic recording and Noriko Yoshida for secretarial assistance in the preparation of this manuscript. 1. Yamaji T, Ishibashi M, Takaku F. Atria1 natriuretic factor in human blood. f Clin invest 1985;76:1705-1709. 2. Yamaji T, Ishibashi M, Nakaoka H, Imataka K, Amano M, Fujii J. Possible role for atria1 notriuretic peptide in polyuria associated with paroxysmal atria1 arrhythmias. Lancet 1985;1:1211. 3. Nakaoka H, Imataka K, Amano M, Fujii J, Ishibashi M, Yamaji T. Plasma levels of atria1 notriuretic factor in patients with congestive heart failure. N Engl J Med 1985;313:892-893. 4. Bates ER, Shenker Y, Grekin RJ. The relationship between plasma levels of immunoreactive atria1 natriuretic hormone and hemodynamic function in inon. Circulation 1986;73:1155-1161. 5. Ausubel K, Furman S. The pacemaker syndrome. Ann Intern Med 1985:103:420-429. 6. Hirata Y, Ishii M, Sugimoto T, Matsuoka H, Sugimoto T, Kangawa K, Matsuo H. The effects of human otrial28-amino acid peptide on systemic and renal hemodynamics in anesthetized rots. Circ Res i985;57:634-639.
Cardiac Involvement in the Kearns-Sayre Syndrome JOSE GALLASTEGUI, MD ROBERTJ. HARIMAN, MD BRUCE HANDLER, MD MAURICE LEV, MD SAROJA BHARATI, MD
K
earns-Sayre (K-S] syndrome is a multisystemic disorder initially described as chronic progressive external ophthalmoplegia associated with pigmentary degeneration of the retina (retinitis pigmentosa) and complete heart b1ock.l Apparently, this entity is caused by mitochondrial abnormalities that affect neuromuscular and cardiac conduction systems.2 The sequence in which this disorder affects the different organs varies, but usually cardiac involvement and From the University of Illinois, Chicago, Illinois, and the Congenital Heart and Conduction System Laboratory, Department of Pathology, Deborah Heart and Lung Center, Browns Mill, New Jersey. This study was aided by Grant HL 30558-04 from the National Institutes of Health, National Heart, Lung, and Blood Institute, Bethesda, Maryland. Manuscript received December 29, 1986; revised manuscript received and accepted February 9,1987.
FIGURE 1. Electrocardiogram of patient 1 showing sinus rhythm, right bundle branch block with left anterior fascicular block and possible inferior wall myocardial infarction of undetermined age.
388
BRIEF
REPORTS
FIGURE 2. reff, case 1. The branching bundle showing loss of fibers and degeneration of the initial portion of the left bundle branch (LBB) with marked fatty infiltration and degeneration of the right bundle branch (RBB). Weigert-van Gleson stain X 45. Rigbf, fibrosis of the second portion of the right bundle branch. Weigert-van Gieson stain X 90. Arrowspoint to the RBB. B = His bundle; V = ventricular septum.
atrioventricular (AV] block develop late.2 We report the clinical and pathologic findings of the heart and its conduction system in 2 patients with K-S syndrome. We performed detailed pathologic studies I$ the heart with special emphasis on the conduction system. The sinoatrial node and its approaches, the AV node and its approaches, the bundle of His and the beginning of the bundle branches were serially sectioned and every 26th (case I) or 16th [case 2) section was retained. The remainder of the bundle branches were likewise serially sectioned and every 40th (case 1) or 20th [case 2) section was retained. The atrial preferential pathways were serially sectioned and every 40th section was retained in both cases. The remainder of the heart was cut into blocks and 2 sections were taken from each block. These were consecutively stained with hematoxylin-eosin, Gomori trichrome and Weigert-van Gieson stains. In this manner, a total of 1,416 sections (case 1) and 1,773 sections (case 2) were examined. Case 1: The patient was a 36-year-old man who was referred for evaluation of bifascicular block (right bundle branch block and left anterior fascicular block)
detected on a routine electrocardiogram. The physical examination revealed bilateral ptosis and marked limitation of excursion of his extraocular movements. Funduscopic examination revealed choroidal atrophy and retinal pigmentary degeneration. Sz split widely. The electrocardiogram showed sinus rhythm, right bundle branch block with left anterior hemiblock, and possible inferior wall myocardial infarction of undetermined age (Fig. 1). The chest x-ray showed cardiomegaly. Cardiac catheterization revealed normal coronary arteries, decreased ejection fraction of 42%, and hypokinesia of inferior and anteroapical walls. Electrophysiologic evaluation showed a prolonged HV interval of 80 ms. Based on this finding, a permanent pacemaker was implanted. Ten days before death he was admitted to the hospital with an episode of pulmonary edema. On the 16th day of hospitalization ventricular tachycardia developed and degenerated to ventricular fibrillation. He died at age 37 years. At autopsy, the heart weighed 625 g. All 4 chambers were dilated. Considerable fatty infiltration of the anterior wall of the right ventricle was seen. The left ventricle showed moderate fibrosis in some sections of
August
4, 1987
THE
AMERICAN
JOURNAL
OF CARDIOLOGY
Volume
SO
387
FIGURE 3. reff, fatty infiltration of the branching bundle (8) and of the left bundle branch (LBB) with degeneration of left bundle branch. Weigert-van Gieson stain X 45. Right, fibrosis of the second portion of the right bundle branch. Gomori trichrome stain X 150. Arrowspoint to the right bundle branch. VS = ventricular septum.
the inner haIf of the anterior wall and marked fibrosis throughout the entire posterior wall. The sinoatrial node was normal. Its approaches showed hypertrophied myocardial cells, infiltrates of mononuclear cells with hemorrhage and fatty focal infiltration with early necrosis of myocardial cells. The atrial preferential pathways revealed marked fatty infiltration. The AV node, its approaches and the penetrating portions of the AV bundle showed fatty infiltration. The branching portion of the AV bundle at the beginning of the posterior radiation of the left bundle branch had lost most of its cells and was almost completely replaced by linear formations (Fig. 2, top). The anterior radiation of the left bundle branch showed marked fibrosis, and vacuolization. The right bundle branch revealed fibrosis, fatty infiltration and elastosis involving the proximal portions. The distal portions were completely replaced by connective tissue (Fig. 2, bottom]. Case 2: The patient was a 61-year-old man referred for evaluation of bifascicmar block (left bundle branch block with first-degree AV block] present since the age of 45 years. K-S syndrome was diagnosed at age 60 years. At evaluation, he was in mildly decompensated congestive heart failure. The chest x-ray showed
cardiomegaly. The electrocardiograi,r revealed left bundle branch block with first-degree AV block. Treatment with digoxin and diuretics resulted in improvement of his clinical condition. He remained in stable condition for 3 years until atrial fibrillation with slow ventricular response developed and precipitated worsening of his congestive heart failure. A permanent pacemaker was implanted, resulting in improvement of his clinical condition. Nevertheless, 2 weeks later the patient had an episode of pulmonary edema that led to cardiac arrest and death at age 64 years. At autopsy, the heart weighed 661 g. Ah 4 chambers were dilated. An old infarct of the posterior wall of the left ventricle was observed. Fatty infiltration of the right ventricle was also noted. The coronary arteries revealed mild-to-moderate atherosclerosis but no distinct narrowing. The sinoatrial node showed fatty infiltration with marked degeneration and cell necrosis. The approaches to the sinoatrial node and the atria1 preferential pathways revealed fatty infiltration with considerable fibrosis. The approaches to the AV node showed marked fatty infiltration with degeneration and necrosis of muscle cells. The AV node and the AV bundle in its penetrating and branching portions revealed marked fatty infihration and fibrosis (Fig. 3,
388
BRIEF
REPORTS
top). The left bundle branch in its initial part showed fibrosis and thickening bf the elastic tissue with destruction of cells. More’ distally, there was marked fibrosis with few Purkinje cells remhining. In the Purkinje nets, there was harked fatty infiltration with loss of Purkinje cells. The right bundle branch showed marked fibroelastosis and ‘fatty infiltration [Fig. 3, bottom]. Complete AV block is the cardiac component of the diagnostic triad of K-5 syndrome. It has been observed that the cardiac cpnduction disturbance in K-S syndrome isprogressive .3,4Thus, the patients may present inifially with minor conduction abnormalities that may progress to bifascicular, trifascicular and complete AV block.5 The time course of this progression is variable. Hbwever, in contrast to patients with ischemic disease, fascicular block in K-S apparently carries a high risk of early progression to complete AV block.3-5 There have been several reports on the electrophysiologic findings in this syndrome.3,4p6 All of them suggest an extensive involvement of the His-Purkinje system. This was manifested as prolonged HV interval, intra-Hisian block, distal His block or distal His block after atropine or pacing. There are few reports on pathologic findings in the heart of patients with K-S syndrome. These suggest that this disorder preferentially affects the conduction system.3s4 The involvement of the conduction system ranges from none4 to severe involvement of the distal
Effect of One Year of Thiazide Therapy on Plasma Volume, Renin, Aldosterone, lipids and Urinary Mbtanephrines in Systolic Hypixtension of Elderly Patients SUMAN VARDAN, MD MILTON H. DUNSKY, Mb NORMA E. HILL, RN KISHAN G. MEHROTRA, PhD SAKTIPADA MOOKHERJEE,MD, MRCP HAROLD SMULYAN, MD ROBERTA. WARNER, MD
and morI acreased cardiac and vascular morbidity tality are known to accompany systemic systolic hypertension of the elderly. We have reported on the hemoFrom the Cardiology, General Medicine, and Nuclear Medicine Sections, Department of Medicine, Veterans Administration Medical Center, and the Health Science Centers, State University of New York and School of Computer and Information Science, Syracuse University, Syracuse, New York. This work was supported by the Veterans Administration and by Grant RR-229 from the pivision of Research Resources, National Institutes of Health, Bethesda, Maryland. Manuscript received January 20,’ 1987; revised manuscript received and accepted April 7, 1987.
His bundle and bundle branches.3 Our findings are in agreement with these reports. We also observed degenerative myocardial changes. These findings may account for congestive heart failure in our patients. The clinical consequence of the pathologic inyolvement of the His-Purkinje system and the bundle branches is the tendency of patients with K-S syndrome to develop progressive infranodal block. Because of this tendency, these patients should be fol-. lowed at regular intervals with ‘electrocard‘iographic recordings. When there is evidence of development of bifascicular block, His bundle recording should be performed. Detection of a prolonged H-V interval or block below the His bundle upon atria1 pacing should prompt permanent pacemaker implantation even before development of complete AV block.4.5 1. Kearns TP, Sayre GP. Retinitis pigmentosa,‘external ophthalmoplegia and complete heart block. Arch Ophthalmol 1958;60:280-289. 2. Berenberg RA, Pellock JM, DiMauro S, Schotland DL, Bonilla E, Eastwood A, Hays A, Vicale CT, Behrens M, Chutorian A, Rowland LP. Lumping or splitting? “Ophtholmoplegia-Plus” or Kearns-Sayre syndrome? Ann Neural 1977;1:37-54. 3. Clark DS, Myerburg RJ, Morales A, Befeler B, Hernandez FA, Gelband H. Heart block in Kearns-Sayre syndrome. Electrophysiologic-pathologic correlation. Chest 1975;68:727-730. 4. Roberts NK, Perloff JK, Kark RAF. Cardiac conduction in the 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 r Cardiol 1979;44:1396-1400. 5. Charles R, Holt S, Kay JM, Epstein EJ, Rees JR. MyocardiaJ ultrastructure and the developmeni of atrioventricular block in Kearns-Sayre syndrome. Circulation 1981;63:214-219. 6. Morris JH, Eugster GS, Nora JJ, Pryor R. His bundle recording on progressive ophthalmoplegia. r Pediatr 1972;81:1167-1170.
dynamic benefit in this disorder after 1 month of’ therapy with a thiazide diuretic, and on the maintenance of improvement for 1 year.l In another group of patients with systolic hypertension we have reported on the changes in plasma volume, renin activity, and aldosterone, lipid and urinary metanephrine levels at 1 month of such therapy.2 This study extends these observations to 1 year of thiazide therapy and explores the relation between the hemodynamic and biochemical variables during this period. Twenty-one patients with primary systolic hypertension (systolic blood pressure [BP] 160 mm Hg or more and at least 2 times diastolic BP - 15]12 were followed for 1 year while they were taking hydrochlorothiazide, 50 mg/day. The following variables, Studied in the control state and at 1 month of therapy,2 were repeated at the end of 1 year: serum electrolytes, glucose, cholesteroL triglyceride, urjc acid, calcium, direct intraarterial BP, cardiac output, stroke volume, systemic vascular resistance, plasma volume, plasma aldosterone and plasma renin ‘activity and 24-hour urinary excretion of sodium, potassium and total metanephrines. At the end of 1 year, 8 patients could not be restudied: 5 were not available, 2 required additional antihypertensive therapy, and 1 with good BP control had hyperuricemia with symptomatic gout at the 10th month of therapy and needed another antihypertensive regimen. The other 13 patients (mean age 65 f 2.7 years [& standard error of the mean]) were available for this study.
tion [electrocardiogram B]. Patient C was a 64-yearold man with persistent sinus arrest, in whom a VW pacemaker was implanted, and had no symptom of pacemaker syndrome. An’electrocardiogram showed absence of atria1 activity (electrocardiogram C). The other 2 patients with VW pacemakers had atrial fibrillation with complete atrioventriculqr block and had no symptom after the implantation. The results of the present study show that plasma ANP levels are elevated in many patients with bradyarrhythmias, and that correction of bradyarrhythmias by atrioventricular sequential pacing may decrease plasma ANP levels to normal. In contrast, plasma ANP levels were high in patients with VVI mode pacing, although 1 patient without atria1 contraction had a normal level. It is well knbwn that pacemaker syndrome may be associated with ventricular pacing.5 Regular atria1 echo beats through intact ventriculoatrial conduction (patient A] and a series of atrial contractions during ventricular systole in atrioventricular dissociation (patient B] produce adverse hemodynamic effect and predominance of vasodilatory reflex, which may cause pacemaker syndrome. In this state, atria contract against closed atrioventricular valves and empty in a retrograde direction into pulmonary and systemic vein, causing a marked increase in atria1 pressure .5 ANP secretion may be stimulated,
WE
AIVERICAi\i
JOiiRR;Aii
OF CAFlDlOiOGY
Volume
SO
385
since available evidence suggests that atria1 stretching due to increased atria1 pressure is at least one of the most important stimuli for AMP releases4 Injection of synthetic ANP causes vasodilation and decreases total peripheral resistance.6 Therefore, increased ANP secretion may play a causative role for occurrence of pacemaker syndrome by reducing total peripheral resistance despite low cardiac output in this condition. Further studies may be necessary to clarify the role of ANP in pacemaker syndrome. Acknowledgment: We thank Dr. Kazuhide Yamaoki for critical reading, Youko Morita for electrocardiographic recording and Noriko Yoshida for secretarial assistance in the preparation of this manuscript. 1. Yamaji T, Ishibashi M, Takaku F. Atria1 natriuretic factor in human blood. f Clin invest 1985;76:1705-1709. 2. Yamaji T, Ishibashi M, Nakaoka H, Imataka K, Amano M, Fujii J. Possible role for atria1 notriuretic peptide in polyuria associated with paroxysmal atria1 arrhythmias. Lancet 1985;1:1211. 3. Nakaoka H, Imataka K, Amano M, Fujii J, Ishibashi M, Yamaji T. Plasma levels of atria1 notriuretic factor in patients with congestive heart failure. N Engl J Med 1985;313:892-893. 4. Bates ER, Shenker Y, Grekin RJ. The relationship between plasma levels of immunoreactive atria1 natriuretic hormone and hemodynamic function in inon. Circulation 1986;73:1155-1161. 5. Ausubel K, Furman S. The pacemaker syndrome. Ann Intern Med 1985:103:420-429. 6. Hirata Y, Ishii M, Sugimoto T, Matsuoka H, Sugimoto T, Kangawa K, Matsuo H. The effects of human otrial28-amino acid peptide on systemic and renal hemodynamics in anesthetized rots. Circ Res i985;57:634-639.
Cardiac Involvement in the Kearns-Sayre Syndrome JOSE GALLASTEGUI, MD ROBERTJ. HARIMAN, MD BRUCE HANDLER, MD MAURICE LEV, MD SAROJA BHARATI, MD
K
earns-Sayre (K-S] syndrome is a multisystemic disorder initially described as chronic progressive external ophthalmoplegia associated with pigmentary degeneration of the retina (retinitis pigmentosa) and complete heart b1ock.l Apparently, this entity is caused by mitochondrial abnormalities that affect neuromuscular and cardiac conduction systems.2 The sequence in which this disorder affects the different organs varies, but usually cardiac involvement and From the University of Illinois, Chicago, Illinois, and the Congenital Heart and Conduction System Laboratory, Department of Pathology, Deborah Heart and Lung Center, Browns Mill, New Jersey. This study was aided by Grant HL 30558-04 from the National Institutes of Health, National Heart, Lung, and Blood Institute, Bethesda, Maryland. Manuscript received December 29, 1986; revised manuscript received and accepted February 9,1987.
FIGURE 1. Electrocardiogram of patient 1 showing sinus rhythm, right bundle branch block with left anterior fascicular block and possible inferior wall myocardial infarction of undetermined age.
388
BRIEF
REPORTS
FIGURE 2. reff, case 1. The branching bundle showing loss of fibers and degeneration of the initial portion of the left bundle branch (LBB) with marked fatty infiltration and degeneration of the right bundle branch (RBB). Weigert-van Gleson stain X 45. Rigbf, fibrosis of the second portion of the right bundle branch. Weigert-van Gieson stain X 90. Arrowspoint to the RBB. B = His bundle; V = ventricular septum.
atrioventricular (AV] block develop late.2 We report the clinical and pathologic findings of the heart and its conduction system in 2 patients with K-S syndrome. We performed detailed pathologic studies I$ the heart with special emphasis on the conduction system. The sinoatrial node and its approaches, the AV node and its approaches, the bundle of His and the beginning of the bundle branches were serially sectioned and every 26th (case I) or 16th [case 2) section was retained. The remainder of the bundle branches were likewise serially sectioned and every 40th (case 1) or 20th [case 2) section was retained. The atrial preferential pathways were serially sectioned and every 40th section was retained in both cases. The remainder of the heart was cut into blocks and 2 sections were taken from each block. These were consecutively stained with hematoxylin-eosin, Gomori trichrome and Weigert-van Gieson stains. In this manner, a total of 1,416 sections (case 1) and 1,773 sections (case 2) were examined. Case 1: The patient was a 36-year-old man who was referred for evaluation of bifascicular block (right bundle branch block and left anterior fascicular block)
detected on a routine electrocardiogram. The physical examination revealed bilateral ptosis and marked limitation of excursion of his extraocular movements. Funduscopic examination revealed choroidal atrophy and retinal pigmentary degeneration. Sz split widely. The electrocardiogram showed sinus rhythm, right bundle branch block with left anterior hemiblock, and possible inferior wall myocardial infarction of undetermined age (Fig. 1). The chest x-ray showed cardiomegaly. Cardiac catheterization revealed normal coronary arteries, decreased ejection fraction of 42%, and hypokinesia of inferior and anteroapical walls. Electrophysiologic evaluation showed a prolonged HV interval of 80 ms. Based on this finding, a permanent pacemaker was implanted. Ten days before death he was admitted to the hospital with an episode of pulmonary edema. On the 16th day of hospitalization ventricular tachycardia developed and degenerated to ventricular fibrillation. He died at age 37 years. At autopsy, the heart weighed 625 g. All 4 chambers were dilated. Considerable fatty infiltration of the anterior wall of the right ventricle was seen. The left ventricle showed moderate fibrosis in some sections of
August
4, 1987
THE
AMERICAN
JOURNAL
OF CARDIOLOGY
Volume
SO
387
FIGURE 3. reff, fatty infiltration of the branching bundle (8) and of the left bundle branch (LBB) with degeneration of left bundle branch. Weigert-van Gieson stain X 45. Right, fibrosis of the second portion of the right bundle branch. Gomori trichrome stain X 150. Arrowspoint to the right bundle branch. VS = ventricular septum.
the inner haIf of the anterior wall and marked fibrosis throughout the entire posterior wall. The sinoatrial node was normal. Its approaches showed hypertrophied myocardial cells, infiltrates of mononuclear cells with hemorrhage and fatty focal infiltration with early necrosis of myocardial cells. The atrial preferential pathways revealed marked fatty infiltration. The AV node, its approaches and the penetrating portions of the AV bundle showed fatty infiltration. The branching portion of the AV bundle at the beginning of the posterior radiation of the left bundle branch had lost most of its cells and was almost completely replaced by linear formations (Fig. 2, top). The anterior radiation of the left bundle branch showed marked fibrosis, and vacuolization. The right bundle branch revealed fibrosis, fatty infiltration and elastosis involving the proximal portions. The distal portions were completely replaced by connective tissue (Fig. 2, bottom]. Case 2: The patient was a 61-year-old man referred for evaluation of bifascicmar block (left bundle branch block with first-degree AV block] present since the age of 45 years. K-S syndrome was diagnosed at age 60 years. At evaluation, he was in mildly decompensated congestive heart failure. The chest x-ray showed
cardiomegaly. The electrocardiograi,r revealed left bundle branch block with first-degree AV block. Treatment with digoxin and diuretics resulted in improvement of his clinical condition. He remained in stable condition for 3 years until atrial fibrillation with slow ventricular response developed and precipitated worsening of his congestive heart failure. A permanent pacemaker was implanted, resulting in improvement of his clinical condition. Nevertheless, 2 weeks later the patient had an episode of pulmonary edema that led to cardiac arrest and death at age 64 years. At autopsy, the heart weighed 661 g. Ah 4 chambers were dilated. An old infarct of the posterior wall of the left ventricle was observed. Fatty infiltration of the right ventricle was also noted. The coronary arteries revealed mild-to-moderate atherosclerosis but no distinct narrowing. The sinoatrial node showed fatty infiltration with marked degeneration and cell necrosis. The approaches to the sinoatrial node and the atria1 preferential pathways revealed fatty infiltration with considerable fibrosis. The approaches to the AV node showed marked fatty infiltration with degeneration and necrosis of muscle cells. The AV node and the AV bundle in its penetrating and branching portions revealed marked fatty infihration and fibrosis (Fig. 3,
388
BRIEF
REPORTS
top). The left bundle branch in its initial part showed fibrosis and thickening bf the elastic tissue with destruction of cells. More’ distally, there was marked fibrosis with few Purkinje cells remhining. In the Purkinje nets, there was harked fatty infiltration with loss of Purkinje cells. The right bundle branch showed marked fibroelastosis and ‘fatty infiltration [Fig. 3, bottom]. Complete AV block is the cardiac component of the diagnostic triad of K-5 syndrome. It has been observed that the cardiac cpnduction disturbance in K-S syndrome isprogressive .3,4Thus, the patients may present inifially with minor conduction abnormalities that may progress to bifascicular, trifascicular and complete AV block.5 The time course of this progression is variable. Hbwever, in contrast to patients with ischemic disease, fascicular block in K-S apparently carries a high risk of early progression to complete AV block.3-5 There have been several reports on the electrophysiologic findings in this syndrome.3,4p6 All of them suggest an extensive involvement of the His-Purkinje system. This was manifested as prolonged HV interval, intra-Hisian block, distal His block or distal His block after atropine or pacing. There are few reports on pathologic findings in the heart of patients with K-S syndrome. These suggest that this disorder preferentially affects the conduction system.3s4 The involvement of the conduction system ranges from none4 to severe involvement of the distal
Effect of One Year of Thiazide Therapy on Plasma Volume, Renin, Aldosterone, lipids and Urinary Mbtanephrines in Systolic Hypixtension of Elderly Patients SUMAN VARDAN, MD MILTON H. DUNSKY, Mb NORMA E. HILL, RN KISHAN G. MEHROTRA, PhD SAKTIPADA MOOKHERJEE,MD, MRCP HAROLD SMULYAN, MD ROBERTA. WARNER, MD
and morI acreased cardiac and vascular morbidity tality are known to accompany systemic systolic hypertension of the elderly. We have reported on the hemoFrom the Cardiology, General Medicine, and Nuclear Medicine Sections, Department of Medicine, Veterans Administration Medical Center, and the Health Science Centers, State University of New York and School of Computer and Information Science, Syracuse University, Syracuse, New York. This work was supported by the Veterans Administration and by Grant RR-229 from the pivision of Research Resources, National Institutes of Health, Bethesda, Maryland. Manuscript received January 20,’ 1987; revised manuscript received and accepted April 7, 1987.
His bundle and bundle branches.3 Our findings are in agreement with these reports. We also observed degenerative myocardial changes. These findings may account for congestive heart failure in our patients. The clinical consequence of the pathologic inyolvement of the His-Purkinje system and the bundle branches is the tendency of patients with K-S syndrome to develop progressive infranodal block. Because of this tendency, these patients should be fol-. lowed at regular intervals with ‘electrocard‘iographic recordings. When there is evidence of development of bifascicular block, His bundle recording should be performed. Detection of a prolonged H-V interval or block below the His bundle upon atria1 pacing should prompt permanent pacemaker implantation even before development of complete AV block.4.5 1. Kearns TP, Sayre GP. Retinitis pigmentosa,‘external ophthalmoplegia and complete heart block. Arch Ophthalmol 1958;60:280-289. 2. Berenberg RA, Pellock JM, DiMauro S, Schotland DL, Bonilla E, Eastwood A, Hays A, Vicale CT, Behrens M, Chutorian A, Rowland LP. Lumping or splitting? “Ophtholmoplegia-Plus” or Kearns-Sayre syndrome? Ann Neural 1977;1:37-54. 3. Clark DS, Myerburg RJ, Morales A, Befeler B, Hernandez FA, Gelband H. Heart block in Kearns-Sayre syndrome. Electrophysiologic-pathologic correlation. Chest 1975;68:727-730. 4. Roberts NK, Perloff JK, Kark RAF. Cardiac conduction in the 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 r Cardiol 1979;44:1396-1400. 5. Charles R, Holt S, Kay JM, Epstein EJ, Rees JR. MyocardiaJ ultrastructure and the developmeni of atrioventricular block in Kearns-Sayre syndrome. Circulation 1981;63:214-219. 6. Morris JH, Eugster GS, Nora JJ, Pryor R. His bundle recording on progressive ophthalmoplegia. r Pediatr 1972;81:1167-1170.
dynamic benefit in this disorder after 1 month of’ therapy with a thiazide diuretic, and on the maintenance of improvement for 1 year.l In another group of patients with systolic hypertension we have reported on the changes in plasma volume, renin activity, and aldosterone, lipid and urinary metanephrine levels at 1 month of such therapy.2 This study extends these observations to 1 year of thiazide therapy and explores the relation between the hemodynamic and biochemical variables during this period. Twenty-one patients with primary systolic hypertension (systolic blood pressure [BP] 160 mm Hg or more and at least 2 times diastolic BP - 15]12 were followed for 1 year while they were taking hydrochlorothiazide, 50 mg/day. The following variables, Studied in the control state and at 1 month of therapy,2 were repeated at the end of 1 year: serum electrolytes, glucose, cholesteroL triglyceride, urjc acid, calcium, direct intraarterial BP, cardiac output, stroke volume, systemic vascular resistance, plasma volume, plasma aldosterone and plasma renin ‘activity and 24-hour urinary excretion of sodium, potassium and total metanephrines. At the end of 1 year, 8 patients could not be restudied: 5 were not available, 2 required additional antihypertensive therapy, and 1 with good BP control had hyperuricemia with symptomatic gout at the 10th month of therapy and needed another antihypertensive regimen. The other 13 patients (mean age 65 f 2.7 years [& standard error of the mean]) were available for this study.