Lyle J. Olson

Sleep Apnea and Cardiovascular Disease

Sleep-related breathing disorders are highly prevalent in patients with established cardiovascular disease. Obstructive sleep apnea (OSA) affects an estimated 15 million adult Americans and is present in a large proportion of patients with hypertension and in those with other cardiovascular disorders, including coronary artery disease, stroke, and atrial fibrillation.1–14 In contrast, central sleep apnea (CSA) occurs mainly in patients with heart failure.15–19 The purpose of this Scientific Statement is to describe the types and prevalence of sleep apnea and its relevance to individuals who either are at risk for or already have established cardiovascular disease. Special emphasis is given to recognizing the patient with cardiovascular disease who has coexisting sleep apnea, to understanding the mechanisms by which sleep apnea may contribute to the progression of the cardiovascular condition, and to identifying strategies for treatment. This document is not intended as a systematic review but rather seeks to highlight concepts and evidence important to understanding the interactions between sleep apnea and cardiovascular disease, with particular attention to more recent advances in patient-oriented research. Implicit in this first American Heart Association/American College of Cardiology Scientific Statement on Sleep Apnea and Cardiovascular Disease is the recognition that, although holding great promise, this general area is in need of a substantially expanded knowledge base. Specific questions include whether sleep apnea is important in initiating the development of cardiac and vascular disease, whether sleep apnea in patients with established cardiovascular disease accelerates disease progression, and whether treatment of sleep apnea results in clinical improvement, fewer cardiovascular events, and reduced mortality. Experimental approaches directed at addressing these issues are limited by several considerations. First, the close association between obesity and OSA often obscures differentiation between the effects of obesity, the effects of OSA, and the effects of synergies between these conditions. Second, multiple comorbidities, …

Surgical Pathology of the Mitral Valve: A Study of 712 Cases Spanning 21 Years

The gross surgical pathologic features of the mitral valve were reviewed in 712 patients who had undergone mitral valve replacement at our institution during 1965, 1970, 1975, 1980, and 1985. Among the 452 cases of mitral stenosis, either with or without mitral insufficiency, 99% were attributable to postinflammatory disease and 1% were related to congenital mitral stenosis. Among the 260 cases of pure mitral regurgitation, the two most common causes were a floppy valve (38%) and postinflammatory disease (31%). Moreover, a floppy valve was observed in 73% of the 59 examples of chordal rupture and in 38% of the 16 cases of infective endocarditis. Women accounted for 73% of the 452 cases of mitral stenosis and for 72% of the 530 cases of postinflammatory disease. In contrast, men accounted for 58% of the 260 cases of pure mitral regurgitation, including 76% of the floppy valves and 69% of the infected valves. During the 21 years spanned by the study, the relative frequency of postinflammatory mitral insufficiency progressively decreased, whereas that of floppy mitral valves increased. It is unclear whether aging, heredity, environmental factors, changes in the frequency of acute rheumatic fever, or changes in patient referral practices may account for this observation.

Surgical Pathology of Pure Aortic Insufficiency: A Study of 225 Gases

The gross surgical pathologic features of the aortic valve were reviewed in 225 patients who had had clinically pure aortic insufficiency and aortic valve replacement at our institution during the years 1965, 1970, 1975, and 1980. The four most common causes of aortic regurgitation were postinflammatory disease (46%), aortic root dilatation (21%), incomplete closure of a congenitally bicuspid aortic valve (20%), and infective endocarditis (9%). Other causes of aortic incompetence in our study included ventricular septal defects (2%) and quadricuspid aortic valves (1%); the cause was indeterminate in 1%. The mean age of patients at valve replacement was approximately 50 years for all etiologic factors except a ventricular septal defect. All forms of aortic insufficiency were much more common in male than in female patients, except the postinflammatory and indeterminate types, which occurred approximately equally in both sexes. Moreover, the incidences of postinflammatory disease and aortic root dilatation changed appreciably with time. Before 1980, their incidences were 51% and 17%, respectively, but during 1980, they were 29% and 37%, respectively. Accordingly, aortic root dilatation is now the most common cause of pure aortic regurgitation in our surgical population. The decrease in the incidence of postinflammatory disease may be a result of the decreasing incidence of acute rheumatic fever reported in western countries.

Noncompaction of the Ventricular Myocardium

Noncompaction of the ventricular myocardium is a rare congenital cardiomyopathy resulting from an arrest in normal endomyocardial embryogenesis. The characteristic echocardiographic findings consist of multiple, prominent myocardial trabeculations and deep intertrabecular recesses communicating with the left ventricular cavity. The disease uniformly affects the left ventricle, with or without concomitant right ventricular involvement, and results in systolic and diastolic ventricular dysfunction and clinical heart failure. Noncompaction was initially described in children. However, recent studies have characterized this disease in the adult population, in whom this process may be more prevalent than currently appreciated. We describe an illustrative case of isolated noncompaction of the ventricular myocardium in a 57-year-old woman with the typical clinical and echocardiographic features of the disease. The literature on the topic is reviewed.

Myocardial dysfunction associated with brain death: clinical, echocardiographic, and pathologic features

BACKGROUND The sequelae of severe brain injury include myocardial dysfunction. We sought to describe the prevalence and characteristics of myocardial dysfunction seen in the context of brain-injury-related brain death and to compare these abnormalities with myocardial pathologic changes. METHODS We examined the clinical course, electrocardiograms, head computed tomography scans, and echocardiographic data of 66 consecutive patients with brain death who were evaluated as heart donors. In a sub-group of patients, we compared echocardiographic findings with pathologic findings. RESULTS Echocardiographic systolic myocardial dysfunction was present in 28 (42%) of 66 patients and was not predicted by clinical, electrocardiographic, or head computed tomographic scan characteristics. Ventricular arrhythmias were more common in the patients with, compared to those without, myocardial dysfunction (32% vs 0%; p < 0.001). Myocardial dysfunction was segmental in all 8 patients with spontaneous subarachnoid or intracerebral hemorrhage. In these patients, the left ventricular apex was often spared. Myocardial dysfunction was either segmental or global in 17 patients who suffered head trauma and in 3 patients who died of other central nervous system illnesses. In 11 autopsied hearts, we found poor correlation between echocardiographic dysfunction and pathologic findings. CONCLUSIONS Systolic myocardial dysfunction is common after brain-injury-related brain death. After spontaneous subarachnoid or intracerebral hemorrhage, the pattern of dysfunction is segmental, whereas after head trauma, it may be either segmental or global. We found poor correlation between the echocardiographic distribution of dysfunction and light microscopic pathologic findings.

The premortem recognition of systemic senile amyloidosis with cardiac involvement.

Abstract Purpose To recognize systemic senile amyloidosis involving the heart and to determine outcome. Patients and methods All patients with the diagnosis of amyloidosis at the Mayo Clinic from January 1, 1984 through May 1, 1992, were reviewed. Amyloid was confirmed histologically by sulfated alcian blue and alkaline Congo red staining. The labeled streptavidin-biotin immunoperoxidase method was used with antisera against Aκ, Aλ, Aa, transthyretin, and β 2 -microglobulin. Anti-P-component and antisera to albumin were used as controls. Chest radiographs, electrocardiograms, transthoracic echocardiograms, and cardiac catheterization data of all patients were reviewed. Serum and urine were examined with immunoelectrophoresis and immunofixation for the presence of a monoclonal protein. Lymphocyte DNA was examined for transthyretin mutations associated with familial amyloidosis. Results We identified 18 patients with myocardial tissue that stained positive for amyloid with sulfated alcian blue and Congo red and with transthyretin antisera. Congestive heart failure was present at diagnosis in 17 of the 18 patients. Atrial fibrillation was found in 11 patients. No monoclonal protein was found in the serum or urine. The echocardiographic findings were consistent with infiltrative cardiomyopathy due to amyloidosis in 16 patients. Right heart pressures were elevated in all 7 patients who had right-side heart catheterization. No transthyretin mutations were found in the leukocyte DNA from 12 patients. The actuarial median survival was 5 years; in contrast, the median survival was 5.4 months in 147 patients with primary amyloidosis (AL) who presented with congestive heart failure. Conclusion Patients with cardiac amyloid and no monoclonal protein in the serum or urine must have immunohistochemical staining for κ and λ light chains and transthyretin to distinguish between systemic senile amyloidosis, familial amyloidosis, and AL. Patients with systemic senile amyloidosis should not be treated with alkylating agents. Their survival is much longer than that of patients with AL (60 versus 5.4 months).

Surgical Pathology of Pure Aortic Stenosis: A Study of 374 Cases

The gross surgical pathologic features of the aortic valve were reviewed in 374 patients who had had clinically pure aortic stenosis and aortic valve replacement at our institution during the years 1965, 1970, 1975, and 1980. The most common cause of aortic stenosis, accounting for 46% of our cases, was calcification of a congenitally bicuspid valve. In the remainder, stenosis was produced by postinflammatory fibrocalcific disease (including rheumatic disease) in 35%, by degenerative calcification of an aging valve in 10%, and by calcification of a congenitally unicommissural valve in 6%. The cause of aortic stenosis was indeterminate in 4%. Valvular lesions included various degrees of dystrophic calcification, commissural fusion, and cuspid fibrosis. Calcification tended to occur more extensively and at a younger age in men than in women. Furthermore, it tended to produce stenosis and to necessitate valve replacement earliest in patients with unicommissural valves (mean age, 48 years), later in those with bicuspid or postinflammatory valves (mean age, 59 and 60 years, respectively), and latest in those with degenerative stenosis (mean age, 72 years). In our study, the relative incidence of postinflammatory aortic stenosis remained unchanged from 1965 to 1980, despite the steadily decreasing incidence of acute rheumatic fever reported in western countries. Our data suggest that (1) the incidence of chronic rheumatic heart disease has not yet begun to decrease appreciably, (2) many episodes of acute rheumatic fever may be subclinical, or (3) some forms of nonrheumatic aortic valve disease may produce gross alterations indistinguishable from those of classic chronic rheumatic valvulitis.

Angiotensin-Converting Enzyme Genotype Modulates Pulmonary Function and Exercise Capacity in Treated Patients With Congestive Stable Heart Failure

Background—The gene encoding ACE exhibits an insertion/deletion polymorphism resulting in 3 genotypes (DD, ID, and II), which affects serum and tissue ACE activity as well as other vasoactive substances. Pulmonary function is frequently abnormal in patients with congestive heart failure (CHF), the mechanism of which has not been completely characterized. ACE inhibition has been shown to improve diffusion across the alveolar-capillary membrane and to improve exercise capacity and gas exchange in CHF. The aim of the current study was to determine if ACE genotype is associated with altered pulmonary function and exercise intolerance in patients with treated CHF. Methods and Results—Fifty-seven patients (stratified according to ACE genotype as17 DD, 28 ID, 12 II) with ischemic and dilated cardiomyopathy, left ventricular ejection fraction (LVEF) <35%, and <10 pack-years of smoking history were studied. All patients were receiving standard therapy for left ventricular systolic dysfunction. Pulmonary function, LVEF, serum ACE, plasma angiotensin II, atrial natriuretic peptide, and brain natriuretic peptide were measured at baseline. Peak &OV0312;o2 and gas exchange measurements were assessed with graded exercise. Resting LVEF was similar among the genotype groups (25% to 28%), and no differences were observed in diastolic function or pulmonary artery pressures (P >0.05). Mean peak &OV0312;o2 and forced vital capacity (% Pred) were significantly reduced (P <0.05), whereas mean serum ACE activity and plasma angiotensin II concentration were highest in DD homozygotes. Subjects homozygous for the D-allele also demonstrated higher mean ventilatory equivalents for carbon dioxide (&OV0312;e/&OV0312;co2) during exercise (P <0.05). Conclusions—ACE DD genotype is associated with decreased exercise tolerance in CHF, possibly mediated by altered pulmonary function. Pharmacological strategies effecting more complete inhibition of serum and tissue ACE and/or potentiation of bradykinin may improve exercise capacity in patients with CHF and ACE DD genotype.

Endomyocardial biopsy in hemochromatosis: clinicopathologic correlates in six cases

Clinical and pathologic features of cardiac hemochromatosis diagnosed by endomyocardial biopsy in six men, aged 32 to 75 years (mean 52), are described. Echocardiography demonstrated left ventricular enlargement and marked global systolic dysfunction in five. Cardiac catheterization demonstrated normal coronary arteries, increased left ventricular end-diastolic pressure and decreased left ventricular systolic function in all five so studied. Stainable iron was present in all endomyocardial biopsy specimens from the five patients with decreased left ventricular systolic function. Histologically, iron was detected only within the sarcoplasm, and its extent varied inversely with ventricular function. Thus, cardiac hemochromatosis represents a storage rather than an infiltrative disease. These results indicate that stainable iron is consistently observed in endomyocardial biopsy specimens from patients with impaired left ventricular systolic function. Iron staining is recommended for endomyocardial biopsy specimens from patients with idiopathic cardiac dysfunction.

Dyssynchrony Indices To Predict Response to Cardiac Resynchronization Therapy A Comprehensive Prospective Single-Center Study

Background—Whether mechanical dyssynchrony indices predict reverse remodeling (RR) or clinical response to cardiac resynchronization therapy (CRT) remains controversial. This prospective study evaluated whether echocardiographic dyssynchrony indices predict RR or clinical response after CRT. Methods and Results—Of 184 patients with heart failure with anticipated CRT who were prospectively enrolled, 131 with wide QRS and left ventricular ejection fraction <35% had 6-month follow-up after CRT implantation. Fourteen dyssynchrony indices (feasibility) by M-mode (94%), tissue velocity (96%), tissue Doppler strain (92%), 2D speckle strain (65% to 86%), 3D echocardiography (79%), and timing intervals (98%) were evaluated. RR (end-systolic volume reduction ≥15%) occurred in 55% and more frequently in patients without (71%) than in patients with (42%) ischemic cardiomyopathy (P=0.002). Overall, only M-mode, tissue Doppler strain, and total isovolumic time had a receiver operating characteristic area under the curve (AUC) greater than the line of no information, but none of these were strongly predictive of RR (AUC, 0.63 to 0.71). In nonischemic cardiomyopathy, no dyssynchrony index predicted RR. In ischemic cardiomyopathy, M-mode (AUC, 0.67), tissue Doppler strain (AUC, 0.79), and isovolumic time (AUC, 0.76) -derived indices predicted RR (P<0.05 for all), although the incremental value was modest. No indices predicted clinical response assessed by Minnesota Living with Heart Failure Questionnaire, 6-minute walk distance, and peak oxygen consumption. Conclusions—These findings are consistent with the Predictors of Response to CRT study and do not support use of these dyssynchrony indices to guide use of CRT.