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Spectrum of dysautonomia in mitral valvular prolapse.

PURPOSE: Symptoms suggesting altered autonomic regulation of cardiovascular function have been noted in some patients with mitral valvular prolapse (MVP) but may also occur in patients with other disorders. We evaluated cardiovascular responses to autonomic stimuli in 118 patients with symptoms of dysautonomia, 78 of whom had MVP, and 40 of whom did not, to determine if unique patterns of these responses distinguished patients in one symptomatic subgroup from another. SUBJECTS AND METHODS: The responses of patients to standing, quantitated Valsalva maneuver, facial immersion in ice water, and administration of isoproterenol, phenylephrine, and tyramine were compared with those in 12 asymptomatic patients with MVP and 23 normal volunteers. RESULTS: Constitutional, cardiovascular, and neuropsychiatric symptoms occurred with similar frequency in the two symptomatic patient groups. The most common pattern of abnormal responses in symptomatic patients with or without MVP was (1) an increased heart rate and elevated plasma norepinephrine levels while supine and then while standing quietly for five minutes, (2) an exaggerated increase in heart rate during phase II of Valsalva, (3) a diminished bradycardic response during phase IV of Valsalva, and (4) an exaggerated heart rate response to administration of isoproterenol. The increased heart rate during Valsalva, but not the exaggerated sensitivity to isoproterenol, was correlated with the magnitude of the chronotropic response to standing only in symptomatic patients with MVP. Exaggerated hypertensive overshoot during phase IV of Valsalva was observed in only a few symptomatic patients. No consistent pattern of these abnormalities, however, was noted in any of the patient subgroups. Hemodynamic responses to autonomic stimuli in asymptomatic MVP patients were generally indistinguishable from those observed in normal subjects. CONCLUSION: These findings suggest that abnormal cardiovascular responses to autonomic stimuli may occur in any patient with symptoms of dysautonomia regardless of the presence or absence of MVP and that the pattern of these abnormal responses may be diverse. It is therefore important to characterize the pattern of altered autonomic regulation of cardiovascular function in each patient when considering mechanistic implications or making therapeutic decisions about these patients.

Adolescent↗

Abnormal interactions of embryonic mouse trisomy 16 heart fibroblasts with extracellular matrix components in vitro.

Trisomy 16 mice have cardiovascular abnormalities thought to arise from altered development and maturation of the cardiac cushions. Cell-cell and cell-extracellular matrix (ECM) interactions play critical roles in heart morphogenesis. To begin to examine the potential involvement of cell-ECM interactions in abnormal trisomy 16 heart development, fibroblasts were isolated from normal and trisomy 16 embryonic mouse hearts. Behavior of these cells was compared in bioassays involving cell-ECM interactions including cell attachment and collagen gel contraction. Significant differences in cell-ECM interactions were found between fibroblasts isolated from normal and trisomy 16 embryonic hearts. Trisomy 16 cells attached poorly to collagen and laminin compared to normal fibroblasts. Trisomy 16 heart fibroblasts also contracted collagen gels less effectively than normal heart fibroblasts. Cell-ECM interactions are largely mediated by ECM receptors of the integrin family. Expression of beta 1 integrins was examined at the mRNA and protein levels in normal and trisomy 16 fibroblasts. Analyses of integrin expression indicated the pattern of integrins produced by normal and trisomy 16 fibroblasts to be similar. These results indicate that fibroblasts isolated from embryonic trisomy 16 mouse hearts interact with several ECM components including collagen and laminin less efficiently than fibroblasts from normal mouse embryos. As cell-ECM interactions play significant roles in cardiac cushion development, abnormal interactions may contribute to defective atrioventricular septal morphogenesis in the trisomy 16 mouse.

Animals↗

Expanding the definition and classification of hypertension.

Cardiovascular abnormalities are frequently the cause, as well as the effect, of elevated blood pressure. As such, early cardiovascular disease (CVD) may be established before identifiable blood pressure thresholds are crossed. To identify individuals at risk for CVD at an earlier point in the disease process, as well as to avoid labeling persons as hypertensive who are at low risk for CVD, the Hypertension Writing Group proposes incorporating the presence or absence of cardiovascular risk factors, early disease markers, and target organ damage into the definition and classification scheme of hypertension. To describe both the complexity and progressive nature of hypertension, the following definition is proposed: "Hypertension is a progressive cardiovascular syndrome arising from complex and interrelated etiologies. Early markers of the syndrome are often present before blood pressure elevation is observed; therefore, hypertension cannot be classified solely by discrete blood pressure thresholds. Progression is strongly associated with functional and structural cardiac and vascular abnormalities that damage the heart, kidneys, brain, vasculature, and other organs and lead to premature morbidity and death." Classification of hypertension must involve assessing global cardiovascular risk to situate an individual's risk for CVD and events along a continuum. As knowledge of early CVD continues to evolve, the approach to classifying individuals along that continuum can be expected to evolve accordingly. The four categories currently used to classify hypertension are normal, prehypertension, and stages 1 and 2 hypertension. The population identified with prehypertension includes a subgroup with early CVD. We believe it would be preferable to classify all individuals as either normal or hypertensive, based on their cardiovascular evaluation, using the four categories of normal and stages 1, 2, and 3 hypertension.

Antihypertensive Agents↗

Cardiovascular risks to young persons on the athletic field.

Sudden cardiac deaths of young athletes, which are usually associated with physical exertion, continue to achieve high public visibility and generate considerable concern. Despite broad community participation in sports, such catastrophes are uncommon, occurring in about 1/200000 high school athletes per academic year. Various unsuspected congenital cardiovascular diseases are usually responsible; the most common lesions are hypertrophic cardiomyopathy and several congenital coronary artery anomalies. Selected reports suggest that arrhythmogenic right ventricular dysplasia may be a more common cause of these deaths than previously suspected. In some trained athletes with borderline increases in thickness of the left ventricular wall, mild morphologic expression of hypertrophic cardiomyopathy can often be distinguished from the physiologic consequences of athlete's heart by noninvasive clinical assessment and testing. In addition, the recognized cardiovascular risks of the athletic field are now extended to include cardiac arrest resulting from relatively modest, nonpenetrating chest blows produced by projectiles (such as baseballs) or bodily contact in the absence of underlying cardiac disease and without structural injury to the chest wall or heart. These uncommon but usually fatal events seem to result when chest impact occurs precisely during the vulnerable phase of repolarization, and they may be reduced by use of softer baseballs. Preparticipation screening for cardiovascular disease, consisting of standard history and physical examination, is customary practice for most high school and college athletes in the United States. Evidence suggests, however, that the present screening process for cardiovascular disease in high school athletes may be largely inadequate, given the content of the approved screening questionnaires (which serve as guidelines for the process) and the use of examiners with little cardiovascular training. This emphasizes the need for national standardization of preparticipation screening. The recommendations of the 26th Bethesda Conference for disqualification from competitive athletics are now a standard for management decisions when cardiovascular abnormalities are identified in trained athletes.

Cardiovascular Diseases↗

[Psoriasis and cardio-vascular disorders].

Psoriasis is one of the most frequent skin diseases. It occurs in adult people with a frequency 2-3%. Psoriasis is a systemic disease with immunologic and genetic determinants. Micro and macro vascular disorders are important for pathogenesis of psoriasis. Authors attempt to show a current scientific statement of pathogenetic mechanisms in psoriasis with special consideration of factors involving cardiovascular abnormalities. In consecutive steps described are associations between psoriasis and arterial hypertension from etiological, pathological and epidemiological point of view. In the same order are reviewed the junctions of psoriasis and lipid and carbohydrate metabolism disorders, as well as coagulative and heart valves abnormalities.

Cardiovascular Diseases↗

[The cardiovascular system and sports].

The article deals with the athlete's heart syndrome as well as the views on this phenomenon throughout this century. The basic diagnostic procedures for heart examination as a part of general medical examination are listed. The authors confront the position recommendations of American and European authors for determining eligibility for competition in athletes with cardiovascular abnormalities.

Cardiovascular Diseases↗

Echocardiography in the emergency room: is it feasible, beneficial, and cost-effective?

Echocardiography in the emergency room presents exciting practice possibilities that can facilitate prompt and reliable diagnostic evaluations in patients with suspected cardiovascular emergencies. Echocardiography has the diagnostic potentials to evaluate the entire spectrum of cardiovascular abnormalities short of delineating coronary anatomy and evaluation of the conduction system. By reliably assessing the global and regional function, visualizing the cardiovascular structures from multiple tomographic planes, and quantitating hemodynamic abnormalities, echocardiography should be able to assist emergency room physician's evaluation and triage of the patients with chest pain syndrome, unexplained dyspnea, hypotension, shock, chest trauma, and cardiac arrest, whereby hopefully minimizing the unnecessary admission to the hospital and facilitating inhospital evaluation of the admitted patients with echocardiographic information. However, the optimal echocardiography practice in the emergency room requires well trained sonographers and echocardiographers who can respond to the clinical needs at anytime. Whether an emergency room physician can perform and interpret echocardiographic examinations satisfactorily will depend on his/her level of training and continuing education in this area. Currently, there is no established guideline for performing echocardiography in the emergency room. Further clinical investigations are necessary to define the most optimal and economical utilization of this versatile imaging and hemodynamic diagnostic modality in the emergency room.

Algorithms↗

Effect of beta blockade on the neurohumoral and cardiopulmonary response to dynamic exercise in cardiac transplant recipients.

OBJECTIVE: To determine the effects of a small dose of beta blocker on neurohumoral and cardiopulmonary responses after cardiac transplantation. BACKGROUND: Cardiac transplant recipients have a reduced exercise capacity and abnormal cardiovascular responses to exercise. The sympathoadrenal response to exercise has been shown to be abnormal with high venous noradrenaline. The effect of beta blockade on these neurohumoral mechanisms has not been defined. METHODS: 10 non-rejecting cardiac transplant recipients were studied. Patients carried out graded exercise to a symptom limited maximum. Blood samples were taken during exercise. Concentrations of noradrenaline, adrenaline, and atrial natriuretic peptide and plasma renin activity were measured. The next day, the exercise and sampling procedure were repeated after an oral dose of propranolol (40 mg). RESULTS: Patients tolerated exercise poorly after beta blockade, which was reflected in the maximum workload reached. Heart rate and blood pressure were significantly higher at rest and during exercise before beta blockade. Although there was no significant difference when resting, mean (SEM) noradrenaline concentrations during peak exercise were higher after beta blockade (16.2 (2) v 23.6 (2.9) nmol/l, p = 0.001). Adrenaline concentrations at peak exercise were also greater after beta blockade (0.89 (0.31) v 1.18 (0.38) nmol/l, p = 0.055). Atrial natriuretic peptide concentrations tended to be higher after beta blockade (118.75 (50.2) v 169.79 (39.3) pmol/l, p = 0.36). There was no significant change in plasma renin activity. CONCLUSIONS: A small oral dose of a competitive beta blocker such as propranolol has an adverse effect on exercise tolerance and cardiovascular response to exercise in cardiac transplant recipients. There are also increased concentrations of circulating noradrenaline and therefore, sympathetic activity during exercise. beta blockers should be used with caution in cardiac transplant recipients.

Administration, Oral↗

Molecular cardiology: new avenues for the diagnosis and treatment of cardiovascular disease.

This review summarizes some of the major advances in the investigation of molecular mechanisms underlying both normal and abnormal cardiovascular function. Four major areas are highlighted including cardiac muscle, the blood vessel, atherosclerosis and thrombosis/thrombolysis. The remarkable strides in understanding multifactorial diseases such as atherosclerosis, and the development of innovative new therapies such as the use of thrombolytic agents produced by recombinant deoxyribonucleic acid (DNA) technology, are noted. Moreover, it is concluded that the past decade of basic research has provided a solid framework for improvements in the diagnosis and therapy of other forms of cardiovascular disease as well. An evaluation of current trends in basic cardiovascular research suggests that diagnostic and therapeutic approaches to disease will increasingly target specific molecular processes underlying the pathophysiologic state.

Animals↗

Hyperglycemia-induced vasculopathy in the murine vitelline vasculature: correlation with PECAM-1/CD31 tyrosine phosphorylation state.

Maternal diabetes mellitus is associated with an increased incidence of congenital abnormalities as well as embryonic and perinatal lethality. In particular, a wide range of cardiovascular abnormalities have been noted in children of diabetic mothers and in the offspring of diabetic animals. The vascular system is the first organ system to develop in the embryo and is critical for normal organogenesis. The organization of mesodermal cells into endothelial and hematopoietic cells and into a complex vascular system is, in part, mediated by a series of specific cell-cell, cell-extracellular matrix, and cell-factor interactions. PECAM-1 expression has been observed during the earliest stages of vasculogenesis, and changes in PECAM-1 tyrosine phosphorylation have been associated with endothelial cell migration, vasculogenesis, and angiogenesis both in vitro and in vivo. In this report we demonstrate that exposure to hyperglycemia during gastrulation causes yolk sac and embryonic vasculopathy in cultured murine conceptuses and in the conceptuses of streptozotocin-induced diabetic pregnant mice. In addition, we correlate the presence of yolk sac and embryonic vasculopathy with the failure of PECAM-1 tyrosine dephosphorylation during the formation of blood islands/vessels from clusters of extra-embryonic and embryonic angioblasts in the murine conceptus using both in vitro and in vivo models. The importance of these findings in the development of vasculopathy in the offspring of diabetic mothers and the potential effects and benefits of glucose regulation during the periods of vasculogenesis/angiogenesis in embryonic development are discussed.

Abnormalities, Multiple↗

Vascular abnormalities in congenital cutis laxa--report of two cases.

Two cases of Japanese girls with congenital cutis laxa associated with cardiovascular abnormalities are described. Case 1: A 12-year-old girl has been under our observation from the age of 6 months. Cardioangiogram revealed dilatation of the ascending aorta, meandering of the descending aorta and the coronary arteries, coiling of the carotid and innominate (brachiocephalic) arteries, and hypoplasia of the pulmonary arteries. Case 2: A 2.8/12-year-old girl died after our follow-up from the age of 3 months. The cause of death was congestive heart failure secondary to peripheral stenosis of the pulmonary arteries. In both cases, skin biopsy revealed a decreased number of elastic fibers and an increased amount of acidic mucopolysaccharides. The same histological features were observed in the pulmonary arteries and other arteries as well. Electron microscopic findings were diffuse thinning of elastic fibers and reduced elastic content. The high blood level of elastase (167.8 micrograms/l) in case 1 may cast a light on the unknown etiology of the disease.

Abnormalities, Multiple↗

[Cardiac involvement in systemic lupus erythematosus: anatomo-pathological study].

To study the cardiac involvement in systemic lupus erythematosus, the clinical and necroscopy records of 29 patients were analyzed. Of these, 28 were female and 1 was male with a mean age of 28.6 +/- 10.4 years. The mean duration of the disease was 23.8 +/- 20.1 months. Twenty patients had the diagnosis of renal failure, 11 of arterial hypertension and 8 of congestive heart failure. No valvular or coronary arterial disease was diagnosed in any patient. The most frequent cause of death was sepsis, followed by renal failure. Only one patient died of causes directly related to heart disease. At necroscopy, 12 patients had pericarditis and 10 had cardiomegaly. Nonspecific valvular abnormalities were observed in 2 patients, Libman-Sacks' endocarditis in 1 and bacterial endocarditis in 2. Cardiovascular abnormalities were absent in only 8 (7.5%) patients. It was concluded that although frequent and contributing to mortality in some patients, cardiovascular involvement in systemic lupus erythematosus is multifactorial and, usually, nonspecific.

Adolescent↗

White-coat hypertension as a cause of cardiovascular dysfunction.

BACKGROUND: The increasing use of 24 h ambulatory blood pressure monitoring has allowed diagnosis of white-coat hypertension, in which blood pressures are higher on clinic measurements than on ambulatory monitoring. Treatment is not generally thought to be necessary for this disorder. However, there is evidence that patients with white-coat hypertension develop renal impairment and left ventricular hypertrophy. We undertook this study to assess whether white-coat hypertension, in the absence of cardiovascular structural abnormalities, is associated with cardiovascular functional abnormalities. METHODS: Cardiovascular function was assessed by ultrasonography in three groups of patients classified as normotensive, persistently hypertensive, or white-coat hypertensive (23, 20, and 22 patients, respectively) on the basis of ambulatory blood pressure monitoring, carried out for 28 h with recordings taken every 15 min during the day and every 20 min during the night, and clinic measurements, made with a semi-automatic oscillometric device. RESULTS: Similar abnormalities of diastolic left ventricular function were identified in the patients with persistent hypertension and those with white-coat hypertension; both groups differed in these indices from the normotensive group (E/A ratios 0.94 [SD 0.23], 1.06 [0.21], and 1.24 [0.31] respectively; ANOVA p < 0.005). In addition, the white-coat and persistently hypertensive groups, when compared with the normotensive group, showed similar abnormalities of elasticity, compliance, and stiffness (stiffness index 4.32 [1.90], 4.53 [1.38], and 3.27 [0.95] respectively; ANOVA p < 0.05) of the large arteries. INTERPRETATION: Functional cardiovascular abnormalities were identified in white-coat hypertensive patients who had no identifiable structural abnormalities. Such functional abnormalities can be reversed by antihypertensive treatment. We propose that patients with white-coat hypertension might benefit from antihypertensive treatment as well as those with persistent hypertension. This hypothesis should be addressed in prospective clinical trials.

Aged↗

Differential effects of various treatment combinations on cardiovascular dysfunction in patients with Parkinson's disease.

OBJECTIVES: Patients with Parkinson's disease (PD) frequently suffer from cardiovascular dysfunction, which may be enhanced to various extents by different antiparkinsonian drugs. MATERIALS AND METHODS: We analysed electrocardiogram (ECG) abnormalities, cardiovascular reflexes (CVR) and orthostatic hypotension (OH) in 148 patients with idiopathic PD assigned to five different combination therapies of levodopa (LD) plus either bromocriptine (BRO), ropinirole (ROP), selegiline (SEL), anticholinergic (ACH) or amantadine (AMA) or to LD monotherapy before and after a 1-week washout of the add-on drug. Patients were matched for age and disease severity (Hoehn and Yahr stage 2-3). Rater-blinded cardiovascular testing was performed at baseline, and following a 1-week washout period of the add-on drugs. RESULTS: We found that the incidence of cardiovascular dysfunction was generally higher in patients receiving a combination therapy compared with patients on LD monotherapy. ECG abnormalities were found in 40-52% of patients in combination therapy, but in only 20% of the patients receiving LD monotherapy. After discontinuation of BRO and SEL, there were significant improvements in ECG, OH and CVR. After washout of ACH and AMA, a significant improvement was found only in the CVR score. AMA and ROP were the add-on drugs with the least adverse cardiovascular effects. CONCLUSION: We conclude that pre-existing cardiovascular autonomic dysfunction should be investigated and taken into account when deciding which combination therapy to choose in the treatment of parkinsonian patients.

Aged↗

Echocardiographic evaluation of patients with clinically suspected arterial emboli.

153 patients (mean age 42 years, range 16-60) who had arterial embolic events were examined prospectively by transthoracic and transoesophageal echocardiography. Patients older than 60 years and those with evidence of extracranial carotid artery occlusive disease were excluded. 84 patients had a cerebral ischaemic event, 50 patients had embolic events in an abdominal organ or limb, and 19 patients had acute retinal ischaemia. The transthoracic echocardiographic examination was normal in 92 patients (60%), whereas only 65 patients (42%) had normal findings after both transthoracic and transoesophageal examination (p less than 0.005). Intracardiac masses, including valvular vegetations, were found in 39 patients (25%), including 27% of patients with cerebral embolism and 32% of these with peripheral embolism, but in none of the patients with retinal ischaemia (p less than 0.001). 47 patients (31%) had valvular disease, 10 (7%) had wall motion abnormalities, 23 (15%) had abnormalities of the interatrial septum, and 9 patients (6%) had diseases of the thoracic aorta. Cardiovascular abnormalities were frequently found by echocardiography in patients with arterial emboli. The transesophageal technique significantly increased the chance of detecting such abnormalities, especially intracardiac masses.

Adolescent↗