Right ventricular diastolic function in systemic hypertension

Right (RV) and left ventricular (LV) diastolic function was evaluated in 50 patients with mild, uncomplicated essential hypertension using pulsed-wave Doppler echocardiography. Patients with pulmonary, valvular or coronary artery disease were excluded and antihypertensive drugs were discontinued for the 2 weeks preceding the study. Ten normotensive patients without heart disease acted as control subjects. In the hypertensive patients, RV peak velocity of atrial filling was higher (42 +/- 10 vs 31 +/- 7 cm/s, p less than 0.01) and deceleration half-time was prolonged (96 +/- 20 vs 83 +/- 10 ms, difference not significant); ratio of early/atrial filling velocity (1.1 +/- 0.3 vs 1.7 +/- 0.4, p less than 0.001) and peak filling rate corrected to stroke volume (3.6 +/- 0.7 vs 5.3 +/- 0.9 SV/s, p less than 0.001) were lower. LV filling parameters showed similar changes. RV filling parameters did not correlate with age, LV mass or septal thickness but correlated weakly with LV radius/thickness ratio. There was good correlation between RV and the following corresponding LV filling parameters: peak filling rate, r = 0.68, p less than 0.001; ratio of early/atrial filling, r = 0.88, p less than 0.0001; and deceleration half-time, r = 0.62, p less than 0.001. Data indicate that RV diastolic function is abnormal in essential hypertension and these abnormalities are closely related to those of LV diastolic function.     

Ventricular diastolic function of the heart in systemic hypertension

Abnormalities in left ventricular (LV) diastolic function in hypertension have been more extensively investigated in recent years because of the availability of reliable noninvasive methods applicable to this type of ventricular functional analysis. Moreover, such approaches allowed investigation of the factors influencing LV diastolic function indexes and permitted development of correction or normalization indexes. More research has been done recently aiming at understanding the physiologic importance of LV diastolic dysfunction in hypertension; the preliminary results in this area suggest that LV diastolic dysfunction may be linked to alterations in the regional cardiopulmonary dynamics and in cardiopulmonary receptor activity. More questions, however, need to be answered with regard to the relative and integrative role of the various aspects of LV diastolic function and about the sequential alterations in the various indexes of LV diastolic function in hypertension.     

Changes in vascular endothelium and its function in systemic arterial hypertension

The various functions of arterial endothelium may be altered during pulmonary and arterial hypertension. Changes in the endothelium (or function) associated with hypertension are described. In both acute and chronic hypertension, permeability of the endothelium is enhanced. During the acute phase of hypertension, hyperplasia (cell replication) of the endothelium occurs while cell hypertrophy (enlarged cell size) and an increase in homocellular tight junctions are associated with sustained elevations of blood pressure. Endothelium may contribute to the increase in smooth muscle mass or cell number reported with various models of hypertension. Increased endothelial uptake or metabolism of norepinephrine and serotonin occurs during hypertension. The biotransformation of adenine nucleotides and various peptides by the endothelium is not altered by hypertension. Synthesis of prostacyclin is enhanced in the spontaneously hypertensive and Goldblatt hypertensive rat. Metabolism of prostaglandin E2, prostaglandin F2 alpha and prostacyclin by prostaglandin 15-hydroxydehydrogenase is impaired in the genetic models. Responses to endothelium-dependent vasodilators are impaired in acute and chronic models of hypertension. Production of relaxing factor by the endothelium is not inhibited, but rather the vascular smooth muscle fails to respond. Acute, severe hypertension potentiates the response to serotonin, presumably by attenuating the release or response to relaxing factor(s). In the aorta of the spontaneously hypertensive rat, the endothelium releases a constricting factor in response to acetylcholine. Pulmonary arterial endothelium (and other vessels) releases a vasoconstrictor that is blocked by inhibitors of cyclooxygenase. It is not clear whether this pressor factor is thromboxane A2. Cultured endothelial cells release a polypeptide that contracts arteries; however, any relation to hypertension is not known.     

Cardiac involvement in hypertension

Despite improved patient detection and pharmacologic therapy, the effect of treatment of hypertension on mortality from coronary artery-related events remains unresolved. Left ventricular (LV) hypertrophy, a known consequence of hypertension, is associated with an excess mortality independent of other known cardiovascular risk factors. Recently, LV hypertrophy accompanying hypertension has been associated with ominous ventricular arrhythmias. However, it does not necessarily follow that regression of LV hypertrophy will reduce this increased mortality. Diastolic dysfunction, manifested by reduced ventricular distensibility of the hypertrophying left ventricle, appears to be an early characteristic of the hypertensive heart since echocardiographic techniques have demonstrated diastolic filling abnormalities in untreated essential hypertensives even before significant LV hypertrophy appears. Not all antihypertensive agents diminish LV mass and improve diastolic dysfunction. Certain sympatholytic agents, calcium antagonists, β-adrenergic blockers, and the angiotensin-converting enzyme inhibitors appear to diminish LV hypertrophy. However, future studies are needed to determine if these agents that appear to reverse findings of LV hypertrophy and improve diastolic dysfunction will also reduce risk of coronary artery disease and related events.     

Cardiac hypertrophy in hypertension

The time course of regression of left ventricular hypertrophy and changes in left ventricular function were followed in 52 middle-aged hypertensive patients divided into two groups: 30 treated with betablockers and 22 with methyldopa. In case of inadequate blood pressure control, diuretics and/or vasodilators were added in both groups. Blood pressure decreased significantly over a three-year follow-up period. The decrease was most pronounced during the first three months. The biggest decrease in posterior wall and interventricular septum thickness was detected by echocardiography also within the first three months. While complete regression of posterior wall hypertrophy was noted within the next three months, interventricular septum thickness decreased steadily over a period of two years. No significant change was seen in the septum in the third year of follow-up. Complete regression of hypertrophy was found in 30 (57.7%) of probands, with no change altogether observed in as few as two patients. Regression was incomplete in 20 (38.4%) obese patients with manifest hypertrophy at the start of the study. Regression of hypertrophy was not associated with left ventricular function deterioration and was observed even after vasodilator administration. There were no differences between the two groups of patients.     

Mechanisms in alcohol-associated carcinogenesis

This review represents an overview on some aspects of pathogenetic mechanisms in alcohol-associated carcinogenesis and is based on presentations held on the symposium "Mechanisms in alcohol-associated carcinogenesis" at the 2004 ISBRA Meeting in Heidelberg/Mannheim, Germany. The chairs were Nils Homann and Hiromasa Ishii. The presentations were (1) Genetic polymorphisms of alcohol and aldehyde dehydrogenases, mean corpuscular volume and cancer risk of the upper aerodigestive tract in Japanese by Akira Yokoyama; (2) Retinoids, alcohol and carcinogenesis by Xiang-Dong Wang; (3) Bacterial ethanol metabolism and cancer by Nils Homann; (4) The role of ethanol metabolism in alcohol-associated carcinogenesis by Helmut K. Seitz; (5) Alcohol and breast cancer: potential mechanisms by Keith W. Singletary.     

Cardiac load and function in hypertension. Ultrasonic and hemodynamic study.

On the basis of echocardiographic measurements, 46 patients with established, uncomplicated primary hypertension (diastolic pressure = 100 mm Hg) were classified as: those with a normal-sized heart (Group I, 13 patients); those with left ventricular concentric hypertrophy (Group II, 19 patients); and those with left ventricular hypertrophy and enlargement (Group III, 14 patients). Eighteen age-matched healthy subjects were investigated as the controls. The function of both the left and right ventricle, evaluated by the stroke index-filling pressure relation and by the mean rate of ejection, was maintained in Group I, augmented in Group II and reduced in Group III, in comparison with the controls. Left ventricular mean rate of circumferential fiber shortening (Vcf) was normal in Group I, significantly augmented in Group II and definitely reduced in Group III. It could not be established whether the divergent variation from normal of the Vcf in Groups II and III reflected opposite changes in ventricular contractility or in afterload (wall stress during ejection), or both. However, the parallel functional pattern of the right and left ventricle in these two groups suggests a functional interdependence of the two sides which cannot be interpreted in terms of afterload but is best explained by changes in the contractile state of the whole heart.     

Cardiac involvement in systemic sclerosis

Objective. To assess the incidence and extent of cardiac involvement in systemic sclerosis (SSc) patients with no apparent cardiac symptoms. Methods. Surface electrocardiography, ambulatory electrocardiography, radionuclide ventriculography, myocardial scintigraphy, and echocardiography were performed in 18 patients. Results. These studies demonstrated ventricular tachycardia in 1 patient, nonsustained ventricular tachycardia in 5, supraventricular tachycardia in 6, decreased left ventricular ejection fraction in 2, decreased right ventricular ejection fraction in 8, and stress-induced reversible myocardial perfusion abnormalities in 6. Conclusion. These observations demonstrate a high rate of cardiac abnormalities in SSc patients without cardiac symptoms.     

Cardiac manifestations in systemic sclerosis

Primary cardiac involvement, which develops as a direct consequence of systemic sclerosis(SSc), may manifest as myocardial damage, fibrosis of the conduction system, pericardial and, less frequently, as valvular disease. In addition, cardiac complications in SSc may develop as a secondary phenomenon due to pulmonary arterial hypertension and kidney pathology. The prevalence of primary cardiac involvement in SSc is variable and difficult to determine because of the diversity of cardiac manifestations, the presence of subclinical periods, the type of diagnostic tools applied, and the diversity of patient populations. When clinically manifested, cardiac involvement is thought to be an important prognostic factor. Profound microvascular disease is a pathognomonic feature of SSc, as both vasospasm and structural alterations are present. Such alterations are thought to predict macrovascular atherosclerosis over time. There are contradictory reports regarding the prevalence of atherosclerosis in SSc. According to some authors, the prevalence of atherosclerosis of the large epicardial coronary arteries is similar to that of the general population, in contrast with other rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus. However, the level of inflammation in SSc is inferior. Thus, the atherosclerotic process may not be as aggressive and not easily detectable in smaller studies. Echocardiography(especially tissue Doppler imaging), single-photon emission computed tomography, magnetic resonance imaging and cardiac computed tomography are sensitive techniques for earlier detection of both structural and functional scleroderma-related cardiac pathologies. Screening for subclinical cardiac involvement via modern, sensitive tools provides an opportunity for early diagnosis and treatment, which is of crucial importance for a positive outcome.     

Cardiac involvement in systemic sclerosis

Systemic sclerosis (SS) can involve the pericardium, myocardium, conduction system, and cardiac valves. The presence of overt clinical signs of cardiac disease is a poor prognostic sign. Clinical manifestations include dyspnea, palpitations, chest pain, syncope, and symptoms of right heart failure. Prevalence of clinically symptomatic pericardial disease is 5-16%. However, ecocardiographic prevalence is 5.4- 41% and at autopsy is 33-77.5%. Patchy fibrosis is the characteristic myocardial finding in SS. Contraction band necrosis is the typical pathological finding. Important complications of fibrosis include left ventricular hypertrophy, as well as systolic and diastolic dysfunction of both ventricles. Early detection of these abnormalities is very important, mainly of the diastolic dysfunction, since it occurs before the systolic dysfunction and can predict important cardiac damage. Association of skeletal myositis with myocardial disease has been described. Patients with skeletal myositis are more likely to develop congestive heart failure, sustained symptomatic arrythmias, and cardiac sudden death. Coronary arteries are normal in systemic sclerosis, but there is no endomyocardial vessel involvement. There is an increased prevalence of arrhytmias, mainly premature atrial and ventricular contractions, as well as conduction system disease. Cardiac valvular involvement is minor in systemic sclerosis; mitral valve is the most frequently affected. Other abnormalities described in this disease include peripheral large vessels stiffness and secondary cardiac involvement due to pulmonary and systemic arterial hypertension. Cardiac involvement confers a high morbi-mortality risk in systemic sclerosis.     

Celiprolol in systemic hypertension

The safety and efficacy of orally administered celiprolol, a new beta 1-selective adrenergic blocking drug with peripheral beta 2-agonist properties, were assessed in 91 patients with mild to moderate systemic hypertension (supine diastolic blood pressure [BP] 95 to 114 mm Hg without medication) using a placebo-controlled, double-blind, randomized, titration-to-effect study design. All patients received placebo for 4 weeks and were then randomized to receive placebo (n = 46) or once-daily celiprolol (n = 45), which was titrated every 2 weeks (200, 400, 600 mg/day) over a 6-week period to achieve a reduction in supine diastolic BP to less than or equal to 90 mm Hg. Plasma lipids and lipoproteins were also assessed at baseline, during placebo and after randomization to active therapy in a subgroup of patients. Compared with placebo, celiprolol reduced supine and standing BP (reduction of supine BP -0.4/-2.1 mm Hg with placebo, -5.7/-6.4 with celiprolol, p less than 0.05; reduction of standing BP -1.7/-1.0 with placebo, -7.2/-4.9 with celiprolol, p less than 0.05). Supine heart rate was reduced by 6.8 beats/min with celiprolol compared with 2.0 beats/min with placebo (p less than 0.05). No differences were seen when the effects of placebo and celiprolol on plasma lipoproteins were compared. Celiprolol is a safe, effective and well tolerated once-daily antihypertensive drug and has no detrimental effects on plasma lipids.     

Comparison of left ventricular function by tissue Doppler imaging in patients with diabetes mellitus without systemic hypertension versus diabetes mellitus with systemic hypertension

Because diabetes mellitus substantially increases the risk of development of heart failure, we sought to establish early alterations in left ventricular systolic and diastolic function in patients with diabetes mellitus with and without coexisting systemic hypertension. We studied 134 subjects using echocardiography comprising standard 2-dimensional and conventional Doppler as well as tissue Doppler imaging. Our study demonstrated the early appearance of both left ventricular systolic and diastolic dysfunction in diabetic patients at rest and the contributory effects of diabetes to myocardial impairment produced by hypertension, as well as the high usefulness of tissue Doppler imaging in detection and quantitation of myocardial dysfunction in diabetics. This method was superior to other echocardiographic techniques and plasma brain natriuretic peptide evaluation.     

Cardiac arrhythmias in arterial hypertension

Patients with arterial hypertension frequently manifest various cardiac rhythm disturbances, ranging from bradyarrhythmias to supraventricular premature beats, atrial fibrillation, or other supraventricular and ventricular tachyarrhythmias. These cardiac arrhythmias may either cause symptoms or be completely asymptomatic, depending on the underlying cardiac function. Degenerative electrical disease and left ventricular hypertrophy constitute the principal pathophysiological mechanisms. This review summarizes all important existing evidence on cardiac arrhythmia manifestation in the setting of arterial hypertension, and it highlights known underlying pathophysiological mechanisms and therapeutic considerations.     

Effects of intravenous verapamil administration on left ventricular diastolic function in systemic hypertension

The effects of intravenous verapamil administration (0.1 mg/kg as a bolus followed by an infusion of 0.007 mg/kg/min) were studied using high-temporal-resolution radionuclide angiography in 27 patients with hypertension. Verapamil administration increased heart rate from 69 ± 11 to 75 ± 12 beats/min (p < 0.001) and decreased systolic, diastolic and mean blood pressures (BPs) from 155 ± 21/102 ± 12 mm Hg (mean 119 ± 14) to 142 ± 19/95 ± 12 mm Hg (mean 109 ± 13) (p < 0.001 for all). Ejection fraction decreased significantly (from 65 ± 10% to 60 ± 11%, p < 0.005); peak filling rate, however, increased significantly only in patients in whom it was subnormal in the basal study (from 2.2 ± 0.4 to 3.0 ± 0.6 end-diastolic counts/s, p < 0.001). These latter patients had significantly higher values of left ventricular (LV) mass index than patients with normal or increased peak filling rate (129 ± 22 vs 112 ± 22 g/m², respectively, p < 0.05). The isovolumic relaxation period changes were inversely related to the baseline values (r = 0.83, p < 0.001). In the subgroup of patients in whom isovolumic relaxation period lengthened, time to end systole decreased (from 360 ± 31 to 329 ± 30 ms, p < 0.025) and time to onset of rapid filling increased (from 420 ± 31 to 451 ± 34 ms, p < 0.025), whereas these 2 intervals had opposite patterns in patients in whom isovolumic relaxation period decreased or did not change. The delay in end systole during verapamil administration in patients in whom isovolumic relaxation period increased is likely a consequence of improved LV synchrony, as the coefficient of variation computed on functional images of LV time to end systole decreased, but it did not change in the other subgroup (from 26 ± 5% to 20 ± 3% [p < 0.005] and from 24 ± 3% to 24 ± 4% [difference not significant]).     

Cardiac abnormalities in systemic lupus erythematosus

Abstracts

Cardiac abnormalities in systemic lupus erythematosus     

Improving the detection of pulmonary hypertension in systemic sclerosis using pulmonary function tests

Objective

To construct a readily applicable formula for selecting patients with systemic sclerosis (SSc) for right‐sided heart catheterization (RHC) based on the results of their pulmonary function tests (PFTs).

Methods

The diagnostic value of PFT variables was quantified in 386 patients with SSc against data obtained from RHC.

Results

We derived the following formula using data from 257 patients: predicted mPAP = 136 – SpO ₂ – 0.25 × DLCO % predicted, where mPAP is the mean pulmonary artery pressure, SpO ₂ is the oxygen saturation as measured by pulse oximetry, and DLCO is the diffusing capacity for carbon monoxide. We validated the formula in the remaining 129 SSc patients. The area under the curve was 0.75 (95% confidence interval [95% CI] 0.67, 0.84). Using a predicted threshold of 25 mm Hg, the sensitivity was 90.1% (95% CI 82, 96) and the specificity was 29.2% (95% CI 17, 44). When used as a screening procedure in a typical scleroderma patient population, it is projected that those with an mPAP below 25 mm Hg are unlikely to have pulmonary hypertension (PH; prevalence 4.4%), those with a predicted mPAP of 25–35 mm Hg are at average risk of having PH (prevalence of 11.3%), and those with a formula‐predicted mPAP above 35 mm Hg are likely to have PH (prevalence of 62.9%), thus justifying RHC. In patients with equivocal findings on echocardiography, a high formula‐predicted mPAP is strongly associated with the presence of PH.

Conclusion

We derived and validated an easily applied formula for determining pulmonary function in patients with SSc that identifies subgroups with a low, average, or high prevalence of PH. It provides information that is complementary to echocardiography and that should improve the selection of patients for RHC.