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The effects of carbon monoxide on persistent changes in young rat heart: cardiomegaly, tachycardia and altered DNA content.

Newborn rat pups that inhale 500 ppm carbon monoxide (CO) for 32 days and develop increased heart mass (i.e. cardiomegaly) show persistent cardiomegaly and elevated resting heart rate as adults. Studies were carried out to explore the relationship of these phenomena to CO concentration and initial cardiomegaly using exposures of 350, 500 and 700 ppm CO. Initial cardiomegaly was greater in the right ventricle free wall (RV) than in the left ventricle plus interventricular septum (LV + S) at all three CO concentrations, and RV mass excess increased with CO concentration. Initial RV cardiomegaly was greater at 350 and 700 ppm CO in females than in males. Persistent cardiomegaly in the RV also increased with CO concentration, and was significantly greater in the females. Persistent cardiomegaly in the RV increased with initial cardiomegaly but at a decreasing rate at the higher CO concentrations, and when expressed as a percentage of initial cardiomegaly (i.e. 'efficiency'), the relative response was greatest at 500 ppm CO. For LV + S, efficiency of development of persistent cardiomegaly was greatest at 350 ppm CO. Persistent tachycardia increased with CO concentration in males but failed to do so in females, and was only weakly correlated with degree of persistent cardiomegaly. Thus, persistent cardiomegaly and persistent tachycardia (in males) are related to CO concentration. Myocardial DNA content of 32-day-old juveniles was significantly increased at 350 and 700 ppm CO. Adult DNA content of the RV was significantly elevated at 350 ppm CO (females) and continued to rise with CO concentration. DNA concentrations of the RV and LV were increased at 700 ppm CO.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Cardiomegaly on chest x-ray: prognostic implications from a ten-year cohort study of elderly subjects: a report from the Bronx Longitudinal Aging Study.

This report is from a 10-year cohort study of community-dwelling elderly men and women. Mean age at the time of entry into the study was 79 years. Annual chest x-ray studies were performed, and data are presented regarding prevalence, incidence, and prognosis of cardiomegaly. Cardiomegaly was defined as a transverse diameter of the cardiac silhouette greater than or equal to 50% of the transverse diameter of the chest (increased cardiothoracic ratio). At the time of entry into the study 110 subjects (23%) had cardiomegaly. After 10 years, 51% of the subjects with cardiomegaly at baseline died compared with 33% of the subjects without cardiomegaly (mortality rate = 9.1 vs 4.8/100 person-years respectively; p = 0.014). Cardiovascular disease incidence was also higher for those with preexisting cardiomegaly at baseline (rate 9.1 vs 6.1/100 person-years; p = 0.0001). According to the Cox proportional hazards regression analysis, age, cardiomegaly, diabetes, and prior evidence of myocardial infarction were independent predictors for death in this cohort. Similarly, the best predictive variables for cardiovascular disease were age, diabetes, prior evidence of myocardial infarction, and cigarette smoking. Of the 359 subjects without cardiomegaly at baseline, 108 (30%) showed evidence of new cardiomegaly, and their risk of cardiovascular disease was 1.8 times that of subjects whose test results were negative for cardiomegaly throughout the study (p = 0.003). Thus cardiomegaly, as defined by an increased cardiothoracic ratio on x-ray films, irrespective of cause, is associated with a poor prognosis in very elderly men and women.

Aged↗

Determinants and prognostic importance of cardiomegaly among new ESRD patients in the United States.

PURPOSE: Cardiomegaly is a radiographic abnormality of major prognostic importance in the general population. We explored the clinical correlations and mortality impact of cardiomegaly in new end-stage renal disease (ESRD) patients from the Dialysis Morbidity and Mortality Study Wave 2. METHODS: Radiographic data denoting the presence or absence of cardiomegaly were available for 97% (n=3908) of the entire cohort. Multivariate logistic regression explored relationships between potential uremic factors and known traditional cardiovascular disease (CVD) factors with cardiomegaly and Cox regression estimated the mortality risk associations over 2 years. RESULTS: The prevalence of cardiomegaly was 26%. Multivariate analysis identified: age (adjusted odds ratio [OR]=1.30 per 10 years older), black race (OR=1.33) diabetes (OR=1.26), hypertension (OR=1.28), tobacco use (OR=1.17), serum albumin (OR=1.36 per 1 g/dL lower), and extremes of body mass index (BMI) (OR=1.24 for BMI<21.1 and OR=1.10 for BMI>30.0 compared with referent [21.1-23.3 Kg/m2]) as significant correlates. The impact of cardiomegaly on mortality was greatest in the first 12 months (RR=1.56; CI, 1.33-1.83) and persisted for up to 2 years (RR=1.44; CI, 1.27-1.62). Interestingly, the likelihood of cardiomegaly was significantly lower for patients who received regular care during the pre-ESRD period (erythropoietin use [OR=0.79] and nephrology visits [OR=0.80 for > or =2 vs. less]). CONCLUSIONS: Traditional CVD risk factors were the predominant correlates of cardiomegaly in new ESRD patients. Vigorous CVD risk factor reduction strategies and frequent specialist care during the pre-ESRD period may be beneficial in reducing the prevalence of cardiomegaly and attenuating its impact on survival.

Adult↗

Significance of radiographic cardiomegaly in orthotopic heart transplant recipients.

OBJECTIVE: The purpose of this study is to evaluate the clinical significance of radiographic cardiomegaly in orthotopic heart transplant recipients and to identify causative anatomic and physiologic parameters. MATERIALS AND METHODS: We retrospectively compared the cardiothoracic ratio (CTR) measured using standard posteroanterior chest radiography with left ventricular end-diastolic diameter and left ventricular ejection fraction measured on two-dimensional echocardiography; right ventricular systolic pressure; and systolic, diastolic, and mean blood pressure measured at biopsy in 46 heart transplant recipients. RESULTS: Twenty-eight (61%) of the 46 patients had radiographic cardiomegaly. When we compared heart transplant recipients who had a CTR greater than 0.5 with recipients who had a CTR less than or equal to 0.5, we found no significant difference between their respective left ventricular end-diastolic diameters, left ventricular ejection fractions, right ventricular systolic pressures, systolic blood pressures, or mean blood pressures. A statistically significant difference existed between the mean values of diastolic blood pressure for transplant recipients with and without radiographic cardiomegaly. We found no significant correlation between CTR and left ventricular end-diastolic diameter, left ventricular ejection fraction, systolic blood pressure, diastolic blood pressure, or mean blood pressure. CONCLUSION: The statistically significant difference between the mean values of diastolic blood pressure of transplant recipients with and without radiographic cardiomegaly is clinically insignificant and unlikely to account for the finding of radiographic cardiomegaly. We conclude that radiographic cardiomegaly, which occurs frequently in heart transplant recipients, does not correlate with anatomic or physiologic parameters obtained under the same conditions. Radiographic cardiomegaly in heart transplant recipients does not connote allograft dysfunction or heart failure.

Adult↗

Postmortem cardiomegaly and echocardiographic measurements of left ventricular size and function in children infected with the human immunodeficiency virus. The Prospective P2C2 HIV Multicenter Study.

BACKGROUND: Cardiomegaly, seen postmortem in over 50% of HIV-infected children, may occur in the absence of clinical or histopathologic cardiac disease. Premortem echocardiography has also demonstrated clinical and subclinical cardiac disease, including increased left ventricular mass (LVM) and functional abnormalities. No studies have compared these echocardiographic measures of heart size and function with postmortem findings in this population. We sought to determine the postmortem prevalence, clinicopathologic relationships and importance of cardiomegaly in HIV-infected children. METHODS: We reviewed clinical and postmortem cardiac findings in 30 HIV-infected children who were part of the Prospective P(2)C(2) HIV Study. Postmortem heart weight was compared with clinical measures of heart size and function, with cardiac pathology and with clinical measures reflecting chronic effects of HIV disease. RESULTS: Postmortem cardiomegaly (heart weight z score >/=2) was identified in 53% of the children. Children with cardiomegaly had increased LVM, increased heart rate, more frequent clinical chronic heart disease and a higher prevalence of postmortem pericardial effusions compared to children without cardiomegaly (P</=.05). The association with LV end-diastolic dimension (LVEDD) did not reach statistical significance (P=.08). No association was found with LV posterior wall thickness (LVPWT), CD4(+) T-cell counts, HIV-1 viral load, hemoglobin, encephalopathy, myocardial histology or myocardial organisms. CONCLUSIONS: Postmortem cardiomegaly was associated with echocardiographic measures of increased LVM. The pathogenesis appears not to be related to chronic anemia, HIV viral load, the degree of immune suppression or encephalopathy. Autonomic dysregulation, reflected by chronically increased heart rate, may be of pathoetiologic significance.

Child↗

Prognostic role of cardiovascular risk factors for men with cardiomegaly (the Reykjavik Study).

The Reykjavik Study is a large population-based cohort study, starting in 1967. A total of 9,139 men, born in the years 1907 to 1934, have been followed for 4 to 24 years. Heart size was determined by chest roentgenogram in 2 planes and cardiomegaly, defined as a relative heart size exceeding 550 ml/m2, was detected in 517. Multivariate Cox regression analysis was used to estimate the independent contribution of variables measured at each participant's first visit to the risk of both all-cause and coronary artery disease (CAD) mortality. Cardiomegaly was detected in 3.7% of men aged < 40 years and in 21.2% of those > 75 years. One half of these men had hypertension, one third had manifestations of CAD, and 37% had neither. Among men with cardiomegaly, the presence of CAD had marked deleterious effect on prognosis. Serum total cholesterol and systolic blood pressure were significant independent risk factors of CAD mortality with risk ratio of 1.008 per mg/dl serum cholesterol (95% confidence interval 1.00 to 1.01; p = 0.004) and 1.015/mm Hg (95% confidence interval 1.000 to 1.300; p = 0.043), respectively. Smoking > 25 cigarettes/day carried a 2.3-fold risk (95% confidence interval 1.3 to 4.4; p = 0.008) of all-cause mortality. The traditional risk factors for CAD, serum cholesterol, high blood pressure, and smoking maintain their detrimental effect on prognosis among patients with cardiomegaly. These findings have implications for secondary prevention, signifying that in the presence of cardiomegaly, complacency is not justified in controlling major risk factors for CAD.

Adult↗

Effect of heart-size parameters computed from digital chest radiographs on detection of cardiomegaly. Potential usefulness for computer-aided diagnosis.

Heart size is an important and useful diagnostic parameter in chest radiographs. However, there is a large variation in the subjective judgment of cardiac enlargement (cardiomegaly). To reduce this subjective element, the authors are developing an automated system for quantitative analysis of heart size in digital chest radiographs. Four hundred chest radiographs were reviewed initially by two radiologists and were classified into two groups: those with and those without cardiomegaly. Another radiologist reviewed 47 images which were not classified consistently in the initial review. The authors used these radiographs to construct a database for determination of cardiomegaly. Numerous parameters related to heart size were obtained in a semiautomated analysis of these radiographs, and the use of each parameter for detection of cardiomegaly was evaluated by means of receiver operating characteristic analysis. The authors also examined whether the accuracy would be improved when they applied multivariate analysis to a pair of parameters. From the analyses of the individual parameters, the automatically determined cardiothoracic ratio was found to be the single most effective measure for detecting cardiomegaly in chest radiographs. However, multivariate analysis provided results superior to those with an individual parameter.

Cardiomegaly↗

The growth of the muscular and collagenous parts of the rat heart in various forms of cardiomegaly.

1. Cardiomegaly has been produced in rats by sideropenic anaemia, by isoprenaline or thyroxine or by the application of both drugs, by artificial increase in resistance to blood flow and by long-term adaptation to hypoxia and physical stress. The ratio of the growth of muscle to the growth of collagen in the heart has been studied.2. All possible variations in the ratio occurred depending on the type of stimulus used for inducing cardiomegaly and on the dynamics of the development of cardiomegaly. In cardiomegaly induced by sideropenia and by thyroxine the growth of muscle was not accompanied by the growth of collagen. Exposure to hypoxia or isoprenaline administration increased only the growth of collagen in the hypertrophic heart. In all other forms of cardiomegaly muscle and collagen formation were stimulated to the same extent.3. It is concluded that when certain organs hypertrophy during adult life several factors may determine the relative rapidity of growth of the muscular or parenchymal and the collagenous stromal components of the tissue.

Anemia, Hypochromic↗

Synergism between infarct-borne left ventricular dysfunction and cardiomegaly in increasing the risk of coronary bypass surgery.

The effect of cardiomegaly on operative and late mortality in patients with left ventricular dysfunction undergoing coronary bypass operation was investigated. The study group consisted of 178 patients whose left ventricular ejection fraction was below 45% and who were operated on from 1978 through 1985. Forty-five patients (group A) had severe left ventricular dysfunction (ejection fraction < 30%) and 133 (group B) had moderate dysfunction (30% > ejection fraction > 45%). Twenty-four of group A (53%) and 54 of group B (41%) patients had cardiomegaly (cardiothoracic ratio on chest x-ray films > 0.5). There were 10 (6%) hospital deaths, four in group A (9%) and six in group B (4.5%). All four deaths in group A and the six deaths in group B were patients who had cardiomegaly. Regardless of the severity of the left ventricular dysfunction, there was no operative death among patients with normal heart size (p < 0.001). Age over 65, bypass time longer than 2 hours, and incomplete revascularization emerged as risk factors. Follow-up ranged from 5 to 13 years (mean 7.8 years). Overall 5-year actuarial survival, including hospital mortality, was 80% +/- 3%. Reduced 5-year survival was observed in patients with cardiomegaly (67% +/- 5% versus 91% +/- 3%, p < 0.05). Five- and 10-year survival of patients from group A with cardiomegaly was 53% +/- 7% and 18% +/- 13%, respectively.

Cardiomegaly↗

Prognostic significance of radiographic cardiomegaly in patients with coronary heart disease.

To define the long term prognosis in patients with coronary heart disease (CHD) we have used criteria of radiographic cardiomegaly supplemented by M-mode echocardiography. 74 patients (Group A) with CHD and cardiomegaly were seen from 1980 to 1983 and have been compared to 121 patients (Group B) with normal cardiac size and prior myocardial infarction. Patients in Group A were defined by radiographic cardiomegaly with cardio-thoracic ratio of 0.50 or more. The groups were matched for age, sex and major coronary risk factors like hypertension, total cholesterol levels, smoking and diabetes. The echocardiographic diastolic left ventricular internal dimension of 6.16 +/- 0.34 cm was significantly more in Group A as compared to 4.94 +/- 0.26 cm in Group B (t = 2.03, p < 0.05). Actuarial analysis indicates that mortality or surgical option is significantly higher in patients with cardiomegaly (Logrank test = 59.72, p < 0.001) and the mortality is significantly more during the initial years. Thus, radiographic cardiomegaly indicates a bad prognosis in patients with CHD.

Actuarial Analysis↗

Cardiomegaly and abdominal mass in an acromegalic patient.

We herein report the case of a 53-year-old white acromegalic patient with an abdominal mass due to massive cardiomegaly. The patient suffered from long lasting acromegaly refractary to bromocriptine, transsphenoidal surgery and radiotherapy. He had been previously diagnosed as having systemic hypertension, ischemic chest pain and congestive heart failure with marked cardiomegaly. The present admission was due to asthenia, anorexia and weight loss that were finally attributed to adrenal insufficiency secondary to radiotherapy. Plain abdomen X-ray suggested the presence of supramesocolic mass. A large cold area in the left hepatic lobe was detected on the radionuclide liver scan. Radionuclide angiography surprisingly identified the cold area as a vascular structure corresponding to the heart. A body CT scan revealed the heart was expanding between stomach and liver. Two-dimensional echocardiography showed marked enlargement of left ventricle. Cardiomegaly was probably multifactorial (chronic hypertension, ischemic heart disease and acromegaly). To our knowledge, this is the first reported case of massive cardiomegaly behaving as an intraabdominal mass. This possibility must be considered when invasive intraabdominal diagnostic procedures are to be done, particularly in an acromegalic patient.

Abdomen↗

Hypertensive cardiomegaly caused by an aldosterone-secreting adenoma in a newborn.

A case of primary hyperaldosteronism and cardiomegaly due to a unilateral adrenal adenoma in a newborn is presented. Some peculiarities, most likely in relation to the onset of the disease during fetal life were evident: plasma cortisol was slightly increased before surgery, plasma renin activity was elevated 9 months after surgery and mineralcorticoid receptors remained suppressed 4 months after surgery. Unilateral adrenalectomy reversed both hypertension and cardiomegaly. We speculate that cardiomegaly was related to both hyperaldosteronism and hypertension and that individual factors are involved in the pathogenesis of cardiomegaly in hyperaldosteronism.

Adenoma↗

Accuracy of precordial percussion in detecting cardiomegaly.

STUDY OBJECTIVE: To assess the value of precordial percussion in detecting cardiomegaly, and to compare it with palpation of the apical impulse. DESIGN: Descriptive study. SETTING: Hospitals and clinics of a university medical center. PATIENTS: Light indirect percussion of the precordium was performed on 72 inpatients and 28 outpatients. All patients had a posteroanterior radiograph of the chest. Percussors were unaware of the clinical history and of chest roentgenogram results. MEASUREMENTS AND MAIN RESULTS: Thirty-six patients (36%) had cardiomegaly, defined as a cardiothoracic ratio of greater than 0.5 on chest roentgenogram. The cardiothoracic ratio was significantly correlated with percussion distance from the midsternal line in the left fourth (r = 0.35, p less than 0.0006), fifth (r = 0.65, p less than 0.00001), and sixth (r = 0.40, p less than 0.0001) intercostal spaces. After adjustment for clinical symptoms and systolic and diastolic blood pressures, percussion distance in the left fifth intercostal space remained a significant independent predictor of the cardiothoracic ratio. Percussion distance in the left fifth interspace discriminated cardiomegaly with a receiver-operating characteristic (ROC) area of 0.95. Percussion dullness more than 10.5 cm from the midsternal line in the left fifth interspace had a sensitivity of 94.4% (95% confidence interval [CI], 79.9% to 99.0%) and a specificity of 67.2% (CI, 54.2% to 78.1%). Distance of the apical impulse from the midsternal line discriminated with an ROC area of 0.95, but an impulse was palpated in only 40% of cases. CONCLUSIONS: Percussion in the left fifth intercostal space accurately discriminates patients with and without cardiomegaly, and adds information beyond that obtainable from the history and other parts of the physical examination.

Adolescent↗

Cardiomegaly in neonatal rats exposed to 500 ppm carbon monoxide.

Increased hemodynamic workload was induced in growing neonatal rats to study alterations in myocyte structure and number and to determine if carbon monoxide (CO) produced a volume-induced model of cardiomegaly. Newborn rats were exposed to 500 ppm CO for up to 32 days of age, at which time the remaining CO exposed rats and ambient air controls continued development in room air to 200 days of age. In the CO group, ventricular weight to body weight ratio was 26% greater than controls at 6 days of age, more than double at 15 days, and remained 47% greater at 28 days. Although absolute myocyte volumes were not different between the two groups at any time period, the CO group did have greater myocyte volume relative to body weight during the CO exposure period. Binucleated myocytes of both ventricles were longer than controls during the exposure period, but did not have increased width. By 200 days of age, myocytes from left ventricle plus septum of CO exposed rats were significantly shorter and CO exposed rats had more total myocytes than controls (36 x 10(6) versus 32 x 10(6) for controls, P less than 0.05). In this study, cardiomegaly induced by 500 ppm CO from birth to 32 days of age was primarily due to myocyte hypertrophy with myocytes having increased length to width ratios (i.e., alterations consistent with a volume-induced model). Following removal from CO exposure, there was regression of both cardiomegaly and myocyte hypertrophy. With increasing time after removal from CO, myocytes tended to become shorter and smaller compared to age matched controls. This trend was present at 105 days and statistically significant by 200 days of age, resulting in an increased number of myocytes in the myocardium long after removal of rats from CO exposure. We conclude that neonatal exposure to CO causes cardiomegaly by increase in cell length and cell volume, consistent with a volume overload model of cardiac hypertrophy.

Animals↗

The role of L-carnitine in the pathogenesis of cardiomegaly in patients with chronic hemodialysis.

Many reports have suggested that cardiac dysfunction with cardiomegaly is more often observed in patients with chronic hemodialysis. Moreover, cardiac dysfunction has been thought as one of the most important factors affecting the prognosis of these patients. In this study, in order to clarify the role of l-carnitine in the pathogenesis of cardiomegaly, 33 patients with chronic hemodialysis were studied using the multivariate analysis method. Among the factors which may affect cardiac function, the following 10 variables were examined. 1) age, 2) duration of dialysis, 3) plasma carnitine, 4) serum total cholesterol, 5) serum HDL-cholesterol, 6) triglyceride, 7) systolic blood pressure, 8) diastolic blood pressure, 9) left ventricular voltage on a electrocardiogram at rest and 10) hematocrit. The plasma carnitine levels in these patients were markedly reduced and inversely correlated with the cardiothoracic ratio (CTR) on the chest X-ray films (r = 0.38, p less than 0.05). In principal component analysis, the CTR was closely related to hematocrit and plasma carnitine levels. By multiregression analysis, both hypo-carnitinemia and anemia were independently shown to be important causes of cardiomegaly. Thus, it is suggested that the cardiomegaly in patients with chronic hemodialysis may be improved by supplemental therapy with l-carnitine, even in cases with severe anemia.

Adolescent↗