Impact of obstructive sleep apnea on left ventricular mass and diastolic function.

We wished to determine if obstructive sleep apnea (OSA) is associated with increased left ventricular mass (LVM) and impaired left ventricular diastolic function (LVDF) independently of coexisting obesity, hypertension (HTN), and diabetes mellitus (DM). Patients without primary cardiac disease, referred for evaluation of OSA (n = 533), had overnight polysomnography and Doppler echocardiography while awake. Patients were divided, according to the apnea-hypopnea index (AHI), into an OSA group (AHI > or = 5/h, n = 353) and a non-OSA group (AHI < 5/h, n = 180). In men, LVM was greater in the OSA group (98.9 +/- 25.6 versus 92.3 +/- 22.5 g/m, p = 0.023) despite exclusion of those with HTN and DM. A similar trend was noted in women. Regression analysis revealed that LVM was correlated with body mass index (BMI) (beta = 0.480, p < 0.0005), age (beta = 0.16, p = 0.001), and the presence of HTN (beta = 0.137, p = 0.003) in men and with BMI (beta = 0.501, p < 0.0005) in women, but not with AHI or oxygen saturation during sleep. The ratio of peak early filling velocity to peak late filling velocity (E/A), an index of LVDF, was similar in both groups (1.28 +/- 0.32 versus 1.34 +/- 0.31, p = 0.058); it was correlated with age (beta = -0.474, p < 0.0005), but not with AHI or oxygen saturation during sleep. We conclude that OSA is not associated with increased LVM or impaired LVDF independently of obesity, HTN, or advancing age.

The importance of age and obesity on the relation between diabetes and left ventricular mass.

OBJECTIVES: The study investigated the relation of age with diabetes, obesity and hypertension on left ventricular mass (LVM). BACKGROUND: Epidemiological studies demonstrate a general rise of LVM with aging, but whether this phenomenon is independent or a function of coexisting diseases that accompany the aging process is unclear. Although obesity, hypertension and diabetes often coexist and increase in prevalence with age, studies of LVM in diabetics have been reported in mostly nonobese populations, and with little regard to the age-hypertension-obesity interactions and effects on LVM. METHODS: We prospectively measured LVM in 875 consecutive, mostly obese individuals (673 men, 202 women). Clinical data were obtained by chart review and clinical history. Echocardiographic measurements of LVM (American Society of Echocardiography criteria) were calculated using the Devereux formula and corrected for height2.7 (LVM/Ht). RESULTS: Mean age was 49.3+/-12.3 years, body mass index 33.3+/-8.0 kg/m2, and LVM/Ht2.7 41.7+/-13.4 g/m2.7. Of the total cohort, 673 patients were men, 519 obese, 228 hypertensive, and 52 diabetic. Of the 519 obese, 183 were hypertensive and 44 were diabetic (22 of those were hypertensive). Of the 228 hypertensives, 183 were obese and 26 were diabetic. On multivariate analysis, obesity (p = 0.0001), age (p = 0.0001), hypertension (p = 0.0003) and diabetes (p = 0.62) were all independently associated with LVM/Ht2.7. Obesity was the most potent independent predictor of LVM/Ht2.7, associated with an increase of 8.1 g/m2.7 in LVM/Ht2.7. In diabetics, obesity had a synergistic effect on LVM/Ht2.7 (p = 0.006), which was further amplified by age (p = 0.03). CONCLUSIONS: Age, obesity, hypertension and diabetes are all independent determinants of LVM. The magnitude of the effect of diabetes on LVM is mainly consequent to a significant interaction of diabetes with obesity and age.

Effects of antihypertensive therapy on glucose and insulin metabolism and on left ventricular mass: A randomized, double-blind, controlled study of 21 obese hypertensives.

BACKGROUND: Glucose and insulin levels are associated with left ventricular mass (LVM) in insulin-resistant individuals. Antihypertensive drugs have different effects on glucose and insulin metabolism (GIM) and on LVM. To evaluate whether the effects of antihypertensive therapy on LVM are associated with its effects on GIM, we compared the effects of atenolol and perindopril on these parameters in a group of insulin-resistant, obese hypertensives. METHODS AND RESULTS: A total of 21 obese, nondiabetic hypertensives who were aged 55+/-12 years, had a body mass index of 32.8+/-5.0 kg/m(2), were free of coronary or valvular heart disease, and had normal LV function were randomized to treatment with atenolol (n=11) or perindopril (n=10). Echocardiographic LVM corrected for height (LVM/height) and GIM (3-hour intravenous glucose tolerance test) were measured after 4 to 6 weeks of washout and 6 months of treatment. Baseline characteristics were similar in both groups. Atenolol and perindopril effectively reduced blood pressure (from 149+/-13/98+/-4 to 127+/-8/82+/-6 mm Hg and from 148+/-9/98+/-4 to 129+/-9/82+/-6 mm Hg, respectively, for the atenolol and perindopril groups; P:=0.002). Atenolol significantly worsened GIM parameters, fasting glucose levels (5.3+/-0.9 to 6.0+/-1.5 mmol/L; P:=0.003), fasting insulin levels (121+/-121 to 189+/-228 pmol/L; P:=0.03), and most other relevant metabolic measures (P:<0.05 for all). Perindopril did not affect GIM. Atenolol did not affect LVM/height (119+/-12 to 120+/-17 g/m; P:=0.8), whereas perindopril significantly reduced LVM/height (120+/-13 to 111+/-19 g/m; P:=0.04). CONCLUSIONS: In obese, hypertensive individuals, adequate and similar blood pressure control was achieved with perindopril and atenolol. However, perindopril but not atenolol was associated with a more favorable GIM profile and led to a significant regression of LVM.

Glucose and insulin metabolism are important determinants of left ventricular mass in obese hypertensives.

BACKGROUND: Obesity and hypertension, the major modifiable clinical determinants of left ventricular mass, are both associated with a state of insulin resistance. OBJECTIVE: To determine the relationships between glucose and insulin metabolism and left ventricular mass in a group of obese, nondiabetic, hypertensive people. PATIENTS AND METHODS: Twenty-two obese, nondiabetic, hypertensive people (10 men), free of coronary or valvular heart disease, with normal left ventricular function were studied. The mean age was 55+/-12 years, body mass index 32.8+/-4.8 kg/m2, and systolic and diastolic blood pressures 149.0+/-11.0 mmHg and 98.0+/-4.0 mmHg, respectively. Left ventricular mass corrected for height (LVM/Ht) and glucose and insulin metabolism (3 h intravenous glucose tolerance test) were measured after a four- to six-week washout period of any antihypertensive medication. RESULTS: The mean LVM/Ht was 119.5+/-11.9 kg/m. The following metabolic measures correlated with LVM/Ht in a univariate analysis: total insulin integration area (r=0.54, P=0.008); fasting insulin (r=0.43, P=0.04); insulin at 90 min (r=0.54, P=0.013); and peak glucose levels (r=0.51, P=0.013). Stepwise multivariate linear regression analysis showed that only total insulin integration area (P=0.005) and peak glucose levels (P=0.01) correlated with LVM/Ht. CONCLUSION: In obese, nondiabetic, hypertensive people, left ventricular mass is associated with circulating glucose and insulin levels.

Pulmonary hypertension and cardiac function in adult cystic fibrosis: role of hypoxemia.

STUDY OBJECTIVES: To determine (1) the prevalence of pulmonary hypertension and cardiac dysfunction in adult cystic fibrosis (CF) patients with severe lung disease, (2) the relationship between these cardiovascular abnormalities and hypoxemia, and (3) the impact of subclinical pulmonary hypertension on survival. DESIGN: Single-blind, cross-sectional study. SETTING: Ambulatory clinic of the Adult CF program at a tertiary-level hospital. PATIENTS: Clinically stable patients with severe lung disease (FEV1 < 40% of predicted normal value) who were not receiving supplemental oxygen. A second cohort of patients in stable condition with less severe lung disease (FEV1 40 to 65% predicted) was also recruited to enable multivariate analysis for the determinants of pulmonary hypertension. MEASUREMENTS AND RESULTS: Eighteen patients with severe lung disease (FEV1 28 +/- 7% of predicted normal value) were initially studied. Each patient had overnight polysomnography, pulmonary function tests, and Doppler echocardiography. Arterial oxygen saturation (SaO2) was reduced during wakefulness (87.1 +/- 6.1%) and fell during sleep (84.0 +/- 6.6%) while transcutaneous PCO2 was normal during wakefulness (41.1 +/- 6.9 mm Hg) and increased during sleep (46.6 +/- 4.7 mm Hg). Left ventricular size, systolic function, and diastolic function were normal except in one patient who had had a previous silent myocardial infarction due to coronary artery disease. Qualitative assessment of right ventricular function was normal in all patients. Pulmonary artery systolic pressure (PASP) was increased (> 35 mm Hg) in seven patients without clinical evidence of cor pulmonale. Regression analysis was performed by combining these data with data from an additional 15 CF patients with moderately severe lung disease (FEV1 56.3 +/- 8.9% predicted normal) who were recruited to a modified study protocol that included overnight oximetry, pulmonary function tests, and Doppler echocardiography. None of these patients had evidence of hypoxemia and only three had mild elevation of PASP (36, 37, and 39 mm Hg). Linear regression analysis revealed that PASP was significantly correlated with FEV1 (r = -0.44; p = 0.013), and SaO2 during wakefulness (r =-0.60; p = 0.0003), during sleep (r = -0.56; p = 0.0008), and after 6 min of exercise (r = -0.75; p < 0.0001). Multivariate analysis revealed that awake SaO2 was a significantly better predictor of PASP than FEV1 (p = 0.0104). Clinical follow-up of the original cohort for up to 5 years revealed that mortality was significantly higher in those with pulmonary hypertension than those without pulmonary hypertension (p = 0.0129). CONCLUSIONS: In adult CF patients with severe stable lung disease, left and right ventricular function is well maintained in the absence of significant coronary artery disease; pulmonary hypertension develops in a significant proportion of patients and is strongly correlated with oxygen status, independent of lung function; and subclinical pulmonary hypertension is associated with an increased mortality.

Canadian consensus recommendations for the measurement and reporting of diastolic dysfunction by echocardiography: from the Investigators of Consensus on Diastolic Dysfunction by Echocardiography.

Abnormalities of diastolic filling are increasingly recognized as a cause of symptoms and predictors of outcome in patients with most forms of heart disease. Noninvasive assessment of diastolic filling is possible in almost all patients, but accurate evaluation must relate echocardiographic Doppler measurements to the complex physiologic and hemodynamic factors responsible for normal and abnormal filling. This evaluation has been facilitated by recent correlation of Doppler measurement of mitral and pulmonary venous inflow with hemodynamic studies. These studies have confirmed that when a careful, integrated approach is taken, Doppler flow patterns can document a progressive pattern of abnormality in many conditions. Impaired left ventricular (LV) relaxation is seen early and is recognized by a decrease in early transmitral LV filling and an increased proportion of filling during atrial contraction. As abnormalities progress, increasing LV chamber stiffness and elevated left atrial pressure lead to a "pseudonormal" filling pattern that previously has caused considerable confusion. This can be unmasked by careful evaluation of pulmonary venous inflow and the use of the Valsalva maneuver. When marked diastolic abnormalities are present, LV filling has restrictive features characterized by rapid early filling, a very stiff left ventricle with high filling pressures, and a poor prognosis. Routine measurement of indexes of diastolic filling have been hampered by uncertainty as to what should be measured, what techniques should be used, definition of normal values, and a clear method of reporting findings. This report represents the efforts of a Canadian consensus group to define a national standard for the performance and reporting of echocardiographic Doppler studies of diastolic filling.

Left atrial appendage thrombus in atrial flutter with no associated heart disease.

The risk of cardioembolic events and the role of anti-coagulation therapy in the management of patients with lone atrial flutter is not well defined in the medical literature. We report the case of an otherwise healthy 42-year-old man with chronic established atrial flutter, unassociated with any other heart disease or systemic illness, with transesophageal echocardiographic findings of a mobile left atrial appendage thrombus. The literature to date, potential mechanisms, and recommendations are discussed. The role of transesophageal electrocardiography and anticoagulation in atrial flutter may need to be considered more seriously, especially if atrial flutter has been present for a prolonged period of time.

Spontaneous iliopsoas hematoma in patients with unstable coronary syndromes receiving intravenous heparin in therapeutic doses.

OBJECTIVE: To identify the relationship between the use of anticoagulants, specifically heparin, and the development of iliacus and psoas muscle hematoma. Three patients with unstable angina who developed groin pain while on heparin anticoagulation are presented. Patients who are anticoagulated with heparin are at increased risk of developing iliacus or psoas hematoma, manifesting a wide range of symptoms from groin pain to massive bleeding and shock. Identification of these patients is crucial in cardiology practice. DATA SOURCES: MEDLINE searches under "iliacus', "psoas' and "iliopsoas hematoma' were conducted and cross-referenced with patients on anticoagulant therapy. Only English language articles were included. STUDY SELECTION: The search covered January 1966 to February 1995. Fifty-one articles were studied. DATA SYNTHESIS: The current literature suggests that anticoagulation can cause iliacus or psoas muscle hematoma and usually presents as femoral neuropathy. However, the presented case reports provide evidence that an earlier manifestation of this entity is the development of groin pain, and that early identification is crucial to improving patient morbidity and mortality. CONCLUSIONS: Patients who are on heparin anticoagulation should be carefully monitored for development of groin pain or leg weakness. In such cases, early recognition of possible iliacus or psoas hematoma should be by abdominal ultrasound or computed tomography, and heparin anticoagulation should be modified according to its clinical requirement.

Proximal narrowing of anomalous right coronary artery from the left coronary sinus: delineation by omniplane transesophageal echocardiogram.

Anomalous origin of the right coronary artery from the left sinus of Valsalva is a serious and potentially fatal, albeit rare, congenital abnormality. It can be associated with marked functional impairment and even sudden death. Transesophageal echocardiography can identify and confirm the course of aberrant coronary arteries and their relationship to the great vessels, as is demonstrated in this report of a 51-year-old female presenting with anomalous right coronary artery with narrowing of its proximal portion.

Left atrial enlargement in healthy obese: prevalence and relation to left ventricular mass and diastolic function.

BACKGROUND: Left atrial (LA) enlargement has been reported in the obese. However, its prevalence in the healthy obese, clinical correlates and relation to left ventricular (LV) mass and diastolic function have been little investigated. METHODS: Thirty-five consecutive, healthy, normotensive obese (body mass index greater than 28, mean +/- SD 34.2 +/- 2.3 kg/m2) and 35 nonobese subjects (body mass index 24.6 +/- 2.3 kg/m2) comparable in age and sex underwent echocardiographic measurements of LA posteroanterior (parasternal view), mediolateral and superoinferior (apical views) dimensions, aortic root diameter, LV mass and Doppler assessment of LV diastolic function. LA enlargement was defined as a posteroanterior dimension greater than 40 mm. A ratio of LA posteroanterior dimension to aortic root diameter greater than 1.4 was used as an index for disproportionate LA enlargement. RESULTS: LA enlargement was more frequent in the obese than in the nonobese (37% versus 6%, P<0.0001). Similarity, disproportionate LA enlargement was more frequent in the obese (34% versus 6%, P<0.0001). LA posteroanterior dimension correlated well with body mass index (r=0.52, P<0.0001) and LV mass (r=0.56, P<0.0001), and weakly with blood pressure (r=0.28, P<0.02). There was no significant correlation with LV diastolic function, age or sex. In multivariate analysis (multiple r=0.61, P<0.0001), LA posteroanterior dimension correlated significantly only with mass (P<0.005), and the association with body mass index and blood pressure became nonsignificant. Similar results were obtained when LA posteroanterior dimension was replaced with mediolateral or superoinferior dimensions. CONCLUSIONS: LA enlargement is frequent in the normotensive, otherwise healthy obese and correlates well with LV mass. It is not mediated through impairment of LV diastolic function, and likely reflects a physiological adaptation of the heart to the obese state. Further studies are needed to determine whether LA enlargement in the obese is associated with adverse long term outcome.

5-Fluorouracil related toxic myocarditis: case reports and pathological confirmation.

This report describes two cases of cardiotoxicity associated with the use of 5-fluorouracil (5-FU) in the treatment of neoplastic disease, and reviews the literature to date. The manifestations of cardiac toxicity were significant ventricular dysfunction during continuous infusion of 5-FU, accompanied by symptoms resembling cardiac ischemia in one case and irreversible cardiogenic shock in another. Detailed cardiac investigations and pathological findings provide convincing evidence that the development of acute myocarditis is the likely mechanism of 5-FU cardiotoxicity, rather than coronary insufficiency as has commonly been postulated. Although cardiotoxicity as a complication of 5-FU therapy remains rare, recognition of this entity is important as it may lead to serious hemodynamic compromise and may recur with drug rechallenge.

Insulin resistance is an important determinant of left ventricular mass in the obese.

BACKGROUND: Obesity in adults is associated with increased left ventricular (LV) mass. The mechanism for this is unclear, however. We tested the hypothesis that insulin resistance is an important independent contributing factor to LV mass in the healthy obese population. METHODS AND RESULTS: The study population consisted of 40 normotensive, nondiabetic, otherwise healthy obese subjects with body mass index (BMI) > 25 kg/m2. LV mass was echocardiographically determined according to the Penn convention, using the formula of Devereux and Reichek. Insulin resistance was assessed using indices derived from Intravenous Glucose Tolerance Test (IVGTT): insulin level at baseline, insulin level at 90 minutes of IVGTT (insulin-90), insulin integration over 90 minutes of IVGTT, and rate of glucose disposal (k value). Insulin-90 (r = .61, P = .0001), k value (r = .55, P = .003), insulin integration over 90 minutes (r = .46, P = .003), basal insulin (r = .44, P = .005), and BMI (r = .59, P = .0001) were all strongly correlated with LV mass by univariate analysis. No significant correlation was found with blood pressure or age. In multivariate regression analysis, only insulin-90 and k value correlated significantly with LV mass (P = .03, P = .02, respectively), accounting for 50% of the variance of LV mass, whereas the association with BMI became insignificant (P = .2). CONCLUSIONS: LV mass in the normotensive nondiabetic obese population is strongly associated with, and may be mediated by, the degree of insulin resistance and its associated hyperinsulinemia, independent of BMI and blood pressure.

ST-segment depression during sleep in obstructive sleep apnea.

It was hypothesized that obstructive sleep apnea may precipitate myocardial ischemia, reflected by ST-segment depression, in some patients during sleep. Overnight sleep studies and simultaneous 3-channel Holter monitoring were performed on 23 consecutive patients with obstructive sleep apnea without a history of coronary artery disease. Each patient was randomly assigned to nasal continuous positive airway pressure for the first half of the night. An episode of significant ST depression was defined as > 1 mm from baseline for > 1 minute. The total duration (minutes) of ST depression was indexed to the total sleep time (minutes per hour of sleep). Seven patients (30%) had ST depression during sleep. In all 7 patients the duration of ST depression decreased during nasal continuous positive airway pressure (30 +/- 18 vs 11 +/- 13 minutes per hour of sleep) in association with a reduction in the apnea-hypopnea index (65 +/- 35 vs 7 +/- 6/hour), arousal index (49 +/- 14 vs 6 +/- 4/hour) and the duration that oxygen saturation was < 90% (44 +/- 27 vs 12 +/- 23% total sleep time). When patients were not on nasal continuous positive airway pressure, the apnea-hypopnea and arousal indexes were higher during periods of ST depression than when ST segments were isoelectric, whereas oxygen saturation was not different. These 7 patients underwent exercise testing, which was positive for inducible myocardial ischemia in 1 patient. It is concluded that ST depression is relatively common in patients with obstructive apnea during sleep and that the duration of ST depression is significantly reduced by nasal continuous positive airway pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Ventricular function in snorers and patients with obstructive sleep apnea.

We hypothesized that intermittent hypoxemia and increased ventricular afterload due to obstructive apnea during sleep (OSA) would cause chronic left ventricular dysfunction. Overnight polysomnography, M-mode and two-dimensional echo-Doppler studies while awake were performed on 51 consecutive snorers, 30 with OSA and 21 without apnea. Patients with previous myocardial infarction, awake hypoxemia or hypercapnia, or other causes of nocturnal hypoxemia were excluded. Echo-Doppler measurements included end-diastolic right and left ventricular dimensions and wall thickness, indices of left ventricular systolic performance (fractional shortening, ejection fraction and ejection time and diastolic performance, (isovolumic relaxation time, ratio of peak early [E] to late [A] diastolic transmitral flow and mitral pressure half-time). Both OSA patients and nonapneic snorers were of similar age. Although OSA patients were heavier, had a greater apnea-hypopnea index, and significant nocturnal hypoxemia, their echo-Doppler measurements were within normal limits and were not significantly different from nonapneic snorers. It is concluded that isolated obstructive sleep apnea does not cause chronic left ventricular dysfunction.

Impairment of left ventricular diastolic function in systemic lupus erythematosus.

Left ventricular (LV) diastolic performance was evaluated with pulsed-wave Doppler echocardiography in a cross-sectional population of patients with systemic lupus erythematosus (SLE) in search of subclinical myocardial involvement. Such involvement is reported to occur infrequently, despite pathohistologic evidence of myocarditis in up to 70% of patients with SLE. Thirty-five consecutive patients with SLE were evaluated, 14 with active and 21 with inactive disease, and were compared with 30 age-matched healthy control subjects. Twenty-six patients were restudied at 7 months. All had normal LV systolic function, normal pericardial and valvular structures, and no significant valvular regurgitation on Doppler echocardiography. In SLE patients with active disease, indexes of LV diastolic function differed significantly from the inactive group and from control subjects, with marked prolongation of isovolumic relaxation time (104 +/- 18 vs 74 +/- 13 ms, p = 0.0001), as well as reduced peak early diastolic filling velocity (E) (0.69 +/- 0.19 vs 0.83 +/- 0.17 ms, p = 0.01), reduced ratio of early to late diastolic flow velocity (E/A) (1.15 +/- 0.53 vs 1.47 +/- 0.35, p = 0.02), and prolonged mitral pressure halftime (74 +/- 14 vs 65 +/- 8 ms p = 0.01). Similar significant differences were found between the active and inactive SLE patient groups. SLE patients with inactive disease differed from control subjects in only mild prolongation of mitral pressure halftime. Abnormal prolongation of isovolumic relaxation (greater than 100 ms) was found to be the most useful marker of diastolic impairment, being present in 64% of SLE patients with active disease and in 14% of patients with inactive disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Echocardiographic and Doppler studies in hypertrophic cardiomyopathy.

This article discusses the central role of cardiac ultrasonography-- two dimensional echocardiography, Doppler echocardiography, continuous-wave Doppler, pulsed-wave Doppler--in the clinical assessment and management of patients with hypertrophic cardiomyopathy.