Left ventricular hypertrophy in patients with autonomic failure

BACKGROUND: In autonomic failure (AF), supine hypertension may predispose patients to end-organ damage. The pathophysiology of hypertensive heart disease in AF is not known. The aim of the present study was to evaluate the prevalence and predisposing factors of left ventricular hypertrophy (LVH) in patients with AF. METHODS: We studied 25 patients with AF (67 +/- 8 years); 80% were being treated for orthostatic hypotension. Twenty patients with essential hypertension (68 +/- 6 years) were considered as the control group. All subjects underwent echocardiography for measurement of left ventricular mass (LVM). The patients with AF underwent a 24-h BP monitoring and long-term blood pressure (BP) variability was calculated as standard deviation (SD) of the average of the half-hour mean values. RESULTS: The LVM is comparable in patients with AF and hypertensive controls (145 +/- 35 g/m2 v 127 +/- 32 g/m2, P = .07). The proportion of patients with LVH is similar in both populations (AF 80%, hypertensive 70%). The patients with AF were divided into two groups, with and without LVH. The SDs are significantly higher in AF patients with LVH than in those with normal LVM (SD 24-h systolic BP: 22 +/- 4 v 14 +/- 1 mm Hg, P = .001). CONCLUSIONS: A high proportion of patients with AF show LVH. The LVM values are comparable with those of patients with essential hypertension. The development of LVH seems to depend on high BP variability, characteristic of AF patients. Detection of LVH may help in the choice of treatment for orthostatic hypotension and in the prevention of heart failure.     

Hypertensive cardiovascular damage in patients with primary autonomic failure

Patients with primary autonomic failure have left-ventricular hypertrophy probably as a result of night-time hypertension.     

The role of vasodilator therapy in heart failure

This article has attemped to summarize the current status of the therapeutic use of vasodilator drugs in acute and chronic heart failure. It is apparent from the increasing number of publications in this area that this alternative to more standard forms of therapy is likely to find a permanent and important place in the management of patients with heart disease. It should also be apparent that ideal drugs for the therapy of chronic heart failure are not yet available. Nevertheless, it is probable that such drugs will emerge and become at least as important as the routine use of digitalis in such patients.     

Paradoxical hypertension after reversal of heart failure in patients treated with intensive vasodilator therapy

Hypertension is a major cause of heart failure, evolving from left ventricular hypertrophy to systolic and diastolic dysfunction. Although effective heart failure therapy has been associated with a lowering or no change in systemic arterial blood pressure in long-term follow-up, this study describes the symptomatic, clinical, and left ventricular functional response of a subgroup of heart failure patients with a prior history of hypertension who demonstrated a paradoxical hypertensive response despite high-dose vasodilator therapy.We prospectively identified 45 patients with a past history of hypertension who had become normotensive with symptomatic heart failure. Of these 45 heart failure patients, 12 became hypertensive while receiving therapy in follow-up, with systolic blood pressure ≥ 140 mm Hg (Group A). The remaining 33 patients did not have a hypertensive response to therapy (Group B).In the 12 Group A patients, 60 ± 10 years old, with symptomatic heart failure for 6.3 ± 4.3 years, vasodilator therapy was intensified in the 2.0 ± 0.5 years of follow-up, achieving final doses of enalapril 78 ± 19 mg and isosorbide dinitrate 293 ± 106 mg per day. New York Heart Association classification improved from 2.9 ± 0.8 to 1.3 ± 0.5 (P ≤> .0001), with a reduction in heart-failure–related hospitalizations. Left ventricular ejection fraction increased from 17 ± 6% to 40 ± 10% (P < .0001). Follow-up blood pressure at 1 to 3 months was unchanged. However, both systolic and diastolic blood pressure increased at final follow-up, rising from 116 ± 14 to 154 ± 13 mm Hg (P = .0001) and from 71 ± 9 to 85 ± 14 mm Hg (P = .004), respectively. Renal function remained unchanged. Although both groups had similar clinical responses, there were more blacks and women in the hypertensive Group A.Effectively, 12 of 45 (27%) heart failure patients with an antecedent history of hypertension demonstrated a paradoxical hypertensive response to vasodilator therapy. The recurrence of hypertension in a significant portion of patients successfully treated for heart failure has important clinical implications.     

The effect of body posture on exercise- and hyperventilation-induced asthma

Recent studies have shown that swimming is of relatively low asthmogenicity, even under conditions of high respiratory heat (and/or water) loss (RHL). It has been suggested that the horizontal body position may contribute to swimming's low asthmogenicity. We studied the effects of upright and prone body postures on pulmonary function following exercise (EIA) and after nonexercise hyperventilation (HIA). Twelve asthmatic boys (aged 12 to 16 years) underwent two 8-min exercise sessions of shoulder flexion-extension and two 8-min isocapnic hyperventilation treatments, in a counterbalanced order, either while lying prone or standing upright. All tests were carried out in a climatic chamber at 10 +/- 1 degree C and 31 +/- 2 percent relative humidity. Minute ventilation (VE) was kept constant at a predetermined individual level during all treatments. No differences were observed in pulmonary functions between the prone and upright postures following either exercise (FEV1 = -20.5 +/- 18.7 percent vs -22.2 +/- 18.7 percent, respectively) or hyperventilation (FEV1 = -29.6 +/- 19.0 percent vs -29.7 +/- 20.2 percent). We conclude that body posture on land has no meaningful effect on the severity of bronchoconstriction in asthmatic children; however, in view of some conceivable physiologic benefits of the prone position in water, an interactive effect on swimming-induced asthma (SIA) of body posture and water immersion cannot be ruled out.     

Renal vasodilator effect of parathormone

Parathyroid hormone (PTH) has been shown to decrease blood pressure in several animal species and to increase blood flow in different vascular beds. The aim of this work was to characterize and quantify the renal vasodilator effect of PTH on the isolated perfused kidney of the rat. The rat kidney was isolated and perfused in a closed circuit with a modified Krebs-Henseleit solution under non filtering conditions (BSA 10 g/100 ml, ligature of the ureter and perfusion pressure set on 70 mmHg). These conditions have been shown to avoid both glomerular filtration and PTH degradation. Vascular tone of the isolated kidney was restored by a continuous perfusion of prostaglandin F2 alpha (2 x 10(-8) mol/mn). The vasodilator responses to PTH were expressed as a percentage of the relaxation induced on each kidney preparation by 4.4 x 10(-4) M papaverine. PTH fragments [bovine PTH (1-34), NLe8.18Tyr34bPTH (1-34) amide and rat PTH (1-34)] induced concentration-dependent renal vasodilation. When tested at increasing cumulative concentrations, EC50 values ranged from 1 to 2 nM for all PTH fragments; maximal relaxation was obtained at 10(-8) M and only approached 40 p. 100 of the response induced by papaverine. Moreover, at concentrations higher than 10(-8) M, all three peptides induced lower vasodilator responses. Neither indomethacin nor phentolamine modified rPTH (1-34) induced renal response. When rPTH (1-34) was tested as a single concentration on each kidney preparation, a higher maximal response (60 p. 100 relaxation) was obtained. This suggested tachyphylaxis of the renal vasculature to repeated PTH administration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Physiologic basis of vasodilator therapy for heart failure

In congestive heart failure, an increase in impedance to left ventricular ejection appears to be an important factor in impairing left ventricular performance. Arteriolar narrowing and decreased arterial compliance will decrease the left ventricular ejection fraction, whereas reduction in venous capacitance will shift blood centrally and increase cardiac filling. These vascular events may result from activation of the sympathetic nervous system and the renin-angiotensin system. Vasodilator drugs, by relaxing the increased vascular tone, will reduce ventricular volume and increase stroke volume, and thus improve the patient's hemodynamic and myocardial metabolic state. Translation of this acute hemodynamic response into a therapeutic benefit from long-term therapy is an attractive but not yet entirely proved thesis. Long-term controlled trials must eventually establish the place of vasodilator drug therapy in the management of different types of congestive heart failure. Furthermore, additional insight is needed into the potential for selective therapy that is tailored to counteract specific mechanisms of vasoconstriction in individual patients.     

Chronic vasodilator therapy with flosequinan in congestive heart failure

This study was conducted to determine the long-term effect of flosequinan, a new orally administered arterial and venous dilator, on the clinical course of patients with moderate to severe congestive heart failure. Seventeen patients on chronic digitalis and diuretic therapy were randomized to receive either flosequinan (n = 9) or placebo (n = 8) in a double-blind fashion. Changes in symptomatology, exercise performance, and left ventricular function were assessed serially during the two-month treatment period. During the course of therapy, a modest improvement in the symptom scores and functional classification of the flosequinan-treated patients was observed. Flosequinan evoked a significant increase in maximal exercise capacity. While long-term flosequinan administration also effected a progressive increase in resting heart rate, it did not consistently improve indices of left ventricular systolic function. The addition of chronic vasodilator therapy with flosequinan to standard digitalis-diuretic regimens is capable of inducing clinical improvement in patients with moderate to severe chronic heart failure. Trials involving larger patient populations will be necessary to confirm the results of this preliminary study and to determine the extent of clinical improvement, subpopulations benefited, role in heart failure therapeutics, and so forth.     

Haemodynamic changes caused by alteration of autonomic activity in patients with heart failure

In 14 patients with heart failure (New York Heart Association class 2-3) and sinus rhythm the carotid sinus baroreceptors were stimulated to induce a reflex mediated decrease of sympathetic efferent activity and a simultaneous increase in vagal tone. Five patients were in severe heart failure (New York Heart Association class 3) with raised plasma concentrations of noradrenaline at rest (2.99 (0.86) nmol/l (mean (SD)) and nine patients had less severe heart failure (class 2.2 (0.2)) and normal plasma concentrations of noradrenaline at rest. The haemodynamic responses during arterial baroreceptor stimulation were different in both groups. In all five patients with severe heart failure cardiac output increased whereas in the nine patients with less severe heart failure it was unchanged or decreased. The increase of cardiac output in the group with severe heart failure was solely the result of a significant increase of stroke volume index (by 9 (2) ml/m2). In the nine patients with less severe heart failure stroke volume remained unchanged but heart rate decreased significantly by 7 (2) beats/min during baroreceptor stimulation. These data show that an integrated change of autonomic activity consisting of a decrease in sympathetic tone and an increase in vagal activity leads to an increase of stroke volume in patients with severe heart failure and hence to haemodynamic improvement.     

Diagnosis and treatment of supine hypertension in autonomic failure patients with orthostatic hypotension

Orthostatic hypotension is seen in various medical conditions. It can be secondary to medications or volume depletion. It can also be due to autonomic neuropathy secondary to other diseases, such as diabetes mellitus, or to primary degenerative processes of the autonomic nervous system. Orthostatic hypotension dominates the clinical picture of patients suffering from autonomic failure. Paradoxically, about one half of these patients also suffer from supine hypertension, which induces pressure natriuresis, worsening orthostatic hypotension. It also complicates the treatment of orthostatic hypotension. Supine hypertension is mediated by an increase in peripheral vascular resistance. This is due to residual sympathetic tone in patients with multiple system atrophy (Shy-Drager syndrome), but the cause is not known in patients with pure autonomic failure, who have increased vascular resistance despite very low levels or plasma norepinephrine and renin activity. The recent observation that patients with supine hypertension develop left ventricular hypertrophy suggests they should be treated. During the day, avoiding the supine position is often all that is required. Short-acting vasodilators (e.g., transdermal nitroglycerin) can be used during the night.