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The aim of the present study was to describe regional and global right ventricular (RV) function in a wide age range of healthy subjects of both sexes. We studied 255 (125 females) healthy individuals randomly selected from the Umeå General Population Register, age 58± 19 (range 22-89) years. RV function was studied using myocardial tissue Doppler imaging of the RV free wall. Isovolumic contraction (IVCv), systolic (Sv), early (Ev), and late (Av) diastolic velocities were measured. Furthermore, isovolumic periods and ejection time intervals were also measured. Conventional Doppler was used to study RV global filling properties. While systolic myocardial velocities were conserved over age, there was a decrease in myocardial E/A ratio with increasing age (r=-0.67, P< 0.001, for base) taken from the RV free wall. A similar age relation was found in RV global filling velocities with a reduced tricuspid E/A ratio (r=-0.57, P< 0.001). Furthermore, a significant correlation was found between global and regional E/A ratios at the basal (r= 0.58, P<= 0.001) and mid-segmental levels (r= 0.46, P<= 0.001). Systolic myocardial velocities behaved independent of age whereas regional as well as global E/A ratio were age-related. No relationship was found between regional isovolumic time intervals and age. Knowledge of these age-dependent relationships is fundamental when evaluating RV function in patients. (ECHOCARDIOGRAPHY, Volume 22, April 2005) [ABSTRACT FROM AUTHOR]

AIMS: Although pulmonary venous flow reversal (Ar) is useful in the evaluation of left ventricular (LV) diastolic function, it is often difficult to study with transthoracic echocardiography (TTE). We determined the relationship between Ar and left atrial (LA) mechanical function and sought to define surrogate measurements for Ar. METHODS AND RESULTS: A total of 130 healthy subjects, mean age 54.3+/-18.3 years, 62 women, were studied and classified into three groups: [young (Y), 25-44 years; n=44], [middle-age (M), 45-64 years; n=43] and [elderly (E), > or =65 years; n=43]. Pulmonary venous flow and LV inflow studies were performed by TTE and LV basal free-wall motion was studied by Doppler tissue imaging (DTI). All images were acquired with a superimposed electrocardiogram. RR interval was similar in all groups while LA dimension and PR interval were increased in Group E vs. Y (P<0.001). LA contraction (A(m)) on DTI, transmitral A-wave (A) and Ar were simultaneous and started 84ms after onset of P wave and this interval increased with age (P=0.02). Similarly, the time intervals from the same landmark to peak A(m), A, and Ar were prolonged with age (all, P<0.001). Despite this prolongation, peak A(m) coincided with peak Ar in every age group (r=0.97, P<0.001) and Ar acceleration and deceleration times were consistently equal. CONCLUSION: The timing of A(m) obtained by DTI can be used to accurately estimate corresponding measurements of Ar recorded by TTE in subjects without cardiac disease. [ABSTRACT FROM AUTHOR]

Aims: Assessment of right ventricular function is important. However, this is not easy to achieve due to the complex anatomy and geometry of the right ventricle, making the evaluation of its function limited. Therefore, a simple reliable and easy method is needed. This study was performed (1) to evaluate the use of right ventricular outflow tract fractional shortening obtained by M-mode echocardiography as a measure of right ventricular systolic function and (2) to determine the relationship between this parameter and other established measurements of right ventricular function such as long axis excursion.Methods and Results: Ninety-two consecutive patients referred for echocardiographic assessment of left and right ventricular function, age mean±SD was 68±14 years, were investigated. Twenty healthy controls, age 46±12 years were also studied. M-mode echocardiography was used to measure right ventricular outflow tract fractional shortening and right ventricular long axis excursion. Doppler echocardiography was used for the estimation of right ventricular–right atrial pressure drop and pulmonary artery acceleration time. Right ventricular outflow tract fractional shortening (P<0·0001), right ventricular long axis excursion (P<0·0001) and pulmonary acceleration time (P<0·0001) were reduced in patients compared to controls. Right ventricular outflow tract fractional shortening correlated with long axis excursion (r=0·66 P<0·0001), pulmonary artery acceleration time (r=0·80 P<0·0001) and right ventricular–right atrial pressure drop (r=−0·53 P<0·0001). Right ventricular long axis excursion correlated with right ventricular–right atrial pressure drop though to a lesser significance (r=−0·27P <0·001). Furthermore, right ventricular outflow tract fractional shortening was reduced in patients with pulmonary hypertension compared to patients without, this difference was not observed in the right ventricular systolic long axis excursion.Conclusion: Right ventricular outflow tract fractional shortening provides a simple and non-invasive measure of right ventricular systolic function. In combination with long axis excursion and Doppler velocities they should provide comprehensive assessment of right ventricular function. Copyright 2002 The European Society of Cardiology. Published by Elsevier Science Ltd. All rights reserved. [ABSTRACT FROM AUTHOR]

Background Much in the diagnosis of diastolic ventricular dysfunction is dependent upon the filling pattern, and most patients diagnosed with diastolic heart failure are elderly. Data from healthy asymptomatic individuals across a range of ages are rare. We sought to find an age-related variation in normal diastolic physiology, specifically the filling pattern and segmental myocardial longitudinal velocities.Methods and Results To assess the effect of normal ageing on left ventricular longitudinal function, we studied myocardial shortening and lengthening velocities using the tissue Doppler technique in 60 healthy subjects who were randomly selected from the Umeå (Sweden) General Population Register, which represents a wide range of ages (23–88 years). Myocardial velocities were documented at four left ventricular sites (anterior, left, posterior and septal) and at three levels (basal, mid-cavity and apical). Transmitral, transtricuspid and pulmonary venous flow velocities were recorded using pulsed-wave Doppler. While systolic myocardial velocities were conserved across ages, there was a marked decrease in early diastolic velocities with age (from 16cm.s−1at 30 years to 9cm.s−1at 80 years at the basal segment) and a corresponding significant increase in late diastolic velocities (from 10 to 16cm.s−1). Although these findings were most marked at the basal level, they were also clearly manifested at the apical level. Myocardial lengthening velocities were related to transmitral flow velocities, showing a correlation of 0·64 (P<0·0001) in early diastole and 0·68 (P<0·0001) in late diastole. Finally, diastolic pulmonary venous flow velocity was found to correlate with early diastolic myocardial velocities (at the basal level, r=0·53, P<0·0001).Conclusions Normal ageing causes a decrease in early diastolic and a substantial increase in late diastolic myocardial lengthening velocities. These changes explain the known trends in the transmitral flow pattern with age. In contrast, systolic myocardial velocities do not change significantly with age. These findings should be considered when evaluating diastolic function, especially in the elderly. [ABSTRACT FROM PUBLISHER]

Objective: The present study was performed to measure concentrations of plasma noradrenaline and neuropeptide-Y-like immunoreactivity in relation to cardiac function in patients with systemic sclerosis (SSc).Methods: Plasma noradrenaline was measured by high performance liquid chromatography and neuropeptide-Y by radioimmunoassay in 30 consecutive patients with SSc and 48 sex and age matched controls. Left ventricular (LV) function was evaluated by Echocardiography.Results: There were no significant differences between patients and controls in either plasma noradrenaline or plasma neuropeptide-Y. LV dysfunction and hypertrophy were common among patients. Plasma Neuropeptide-Y was related only to systolic function, while noradrenaline was related to both systolic and diastolic function as well as to LV hypertrophy.Conclusion: Patients with SSc develop different forms of myocardial dysfunction without activation of the sympathetic nervous system as evaluated by plasma noradrenaline and neuropeptide-Y; leaving vascular disease of the heart to be a main candidate. [ABSTRACT FROM AUTHOR]

Systemic sclerosis is a multisystemic disorder, also affecting the heart. To evaluate its influence on systolic left ventricular (LV) function, we investigated 30 consecutive patients (age 54.5 ±2.4 years, 15 men and 15 women) and 48 controls matched for age and sex. All subjects were investigated by phonocardiography, pulse curve recordings, M-mode echocardiography, and by pulsed and continuous wave Doppler. Heart rate, blood pressure and peripheral resistance did not differ, but patients weighed less than controls (P<0.01). Systolic time intervals indicated systolic impairment, with an increased pre-ejection period to LV ejection time (LVET) ratio (0.37±0.02 vs 0.30±0.01 P<0.001), and also an increased isovolumic contraction time to LVET ratio (0.17±0.02 vs 0.12±0.01, P<0.02). The latter difference remained when LVET was adjusted for heart rate. Echocardiographic E-point to septal separation was increased in patients (8.3± 1.3 vs 4.8±0.3mm, P = 0.001), also after adjustment for LV dimension (P = 0.0001), while septal fractional thickening was decreased (P<0.01). End systolic wall stress (P = 0.0002) and stress to volume ratio (P = 0.03) were lower in systemic sclerosis. Peak LV emptying rate was also lower in the patient group when measured by echocardiography (P = 0.03). There was no difference between groups regarding LV dimensions, fractional shortening or mean velocity of circumferential fibre shortening. While aortic Doppler peak emptying rate did not differ between groups, it occurred later in systole in the patient group (P<0.01) as did peak velocity (P = 0.0001). Cardiac output did not differ between the groups. In all, 18 of 30 patients (60%) had a systolic abnormality. However, only one patient had dilated cardiomyopathy, and two other patients had poor systolic function without L V dilatation. There was no relation between disease duration and systolic LV function. We conclude that, in a consecutive series of patients with systemic sclerosis, systolic LVfunction is frequently impaired. While time intervals, emptying rate, and wall fractional thickening are affected, cardiac output and LV cavity dimensions are usually not. [ABSTRACT FROM PUBLISHER]

An abstract of the article "Right Ventricular Hypertrophy and Diastolic Dysfunction in Patients With Systemic Sclerosis: An Isolated Phenomenon" by P. Lindqvist and colleagues is presented.

An abstract of the article "Effect of Age on the Right Ventricular Function. A Doppler Tissue Imaging Study: The Umeå General Population Heart Study" by P. Lindqvist and colleagues is presented.

An abstract of the article "Right Ventricular Diastolic Myocardial Performance Index and Pulmonary Artery Pressure" by P. Lindqvist and colleagues is presented.

An abstract of the article "Right ventricular function in hypertrophic cardiomyopathy" by S. Mörner, P. Lindqvist, E. Kazzam and A. Waldenstrom is presented.

An abstract of the article "Impaired diastolic heart function in familial amyloidotic polyneuropathy" by P. Lindqvist and colleagues is presented.

Background: Endocardial border detection is important for echocardiographic assessment of left-ventricular function. Second harmonic imaging of contrast agents enhances this border detection. We discovered that harmonic imaging improves tissue visualisation even before contrast injection. We therefore sought objectively to demonstrate the degree of enhancement of endocardial and myocardial visualisation.Methods: An ATL HDI-3000 scanner with software for contrast harmonic imaging was used to record short-axis images of the left ventricle in 27 patients with possible myocardial disease and 22 controls, in the fundamental mode and with harmonic imaging. A computer program measured the relative grey-scale values within six segments of the endocardium and myocardium. An Acuson Sequoia scanner equipped with software for tissue harmonic imaging was used to investigate the reproducibility of ejection-fraction calculations in 22 patients with ischaemic heart disease.Findings: Harmonic imaging produced brighter endocardium within each segment. Relative to the mean grey value of the total imaging sector, the values for harmonic and fundamental imaging were 171.5 vs 85.6% (p<0.0001) in end diastole and 194.1 vs 106.7% (p<0.0001) in end systole. Results for the myocardial segments were also significantly better for harmonic imaging. Structure enhancement of similar magnitude was seen among patients and healthy controls. Use of harmonic imaging reduced the proportion of unacceptable images by 14-46% in different views and improved the reproducibility of biplane ejection-fraction measurements.Interpretation: In comparison with fundamental imaging, the relative endocardial and myocardial brightness is enhanced by harmonic imaging. [ABSTRACT FROM AUTHOR]

The mechanism of anaphylactic shock (AS) remains incompletely understood. The potassium channel blocker 4-aminopyridine (4-AP), the inhibitors of cystathionine γ-lyase (ICSE), dl-propargylglycine (DPG) or β-cyanoalanine (BCA), and the nitric oxide (NO) synthase produce vasoconstriction and could be an alternative for the treatment of AS. The aim of this study was to demonstrate the ability of L-NAME, ICSE alone or in combination with 4-AP to restore blood pressure (BP) and improve survival in ovalbumin (OVA) rats AS. Experimental groups included non-sensitized Wistar rats ( n = 6); AS ( n = 6); AS ( n = 10 per group) treated i.v. with 4-AP (AS+4-AP), epinephrine (AS+EPI), AS+DPG, AS+BCA, or with L-NAME (AS+L-NAME); or AS treated with drug combinations 4-AP+DPG, 4-AP+BCA, 4-AP+L-NAME, or 4-AP+EPI. AS was induced by i.v. OVA (1 mg). Treatments were administered i.v. one minute after AS induction. Mean arterial BP (MAP), heart rate (HR), and survival were monitored for 60 min. Plasma levels of histamine, prostaglandin E2 (PGE2) and F2 (PGF2α), leukotriene B4 and C4, angiotensin II, vasopressin, oxidative stress markers, pH, HCO3, PaO2, PaCO2, and K+ were measured. OVA induced severe hypotension and all AS rats died. Moreover, 4-AP, 4-AP+EPI, or 4-AP+BCA normalized both MAP and HR and increased survival. All sensitized rats treated with 4-AP alone or with 4-AP+BCA survived. The time-integrated MAP "area under the curve" was significantly higher after combined 4-AP treatment with ICSE. Metabolic acidosis was not rescued and NO, ICSE, and Kv inhibitors differentially alter oxidative stress and plasma levels of anaphylactic mediators. The AS-induced reduction of serum angiotensin II levels was prevented by 4-AP treatment alone or in combination with other drugs. Further, 4-AP treatment combined with EPI or with BCA also increased serum PGF2α, whereas only the 4-AP+EPI combination increased serum LTB4. Serum vasopressin and angiotensin II levels were increased by 4-AP treatment alone or in combination with other drugs. Moreover, 4-AP alone and in combination with inhibition of cystathionine γ-lyase or EPI normalizes BP, increases serum vasoconstrictor levels, and improves survival in the Wistar rat model of AS. These findings suggest possible investigative treatment pathways for research into epinephrine-refractory anaphylactic shock in patients.

Objectives: Anaphylactic shock is associated with severe hypotension. Potassium channel blockers, such as 4-aminopyridine, induce vasoconstriction. The objective of this study was to test the ability of 4-aminopyridine to restore blood pressure and increase survival in anaphylactic shock., Design: Experimental study., Setting: Physiology laboratory., Subjects: Adult male Wistar rats., Interventions: Rats were sensitized with ovalbumin (1 mg SC), and anaphylactic shock was induced by IV injection of ovalbumin (1 mg). Experimental groups included non-allergic rats (NA) (n = 6); allergic rats (Controls) (n = 6); allergic rats treated with 4-aminopyridine (4-aminopyridine) (1 mg/kg) (n = 6); and allergic rats treated with epinephrine (EPI) (10 µg/kg) (n = 6). Treatments were administered 1 minute after induction of anaphylactic shock., Measurements and Main Results: Mean arterial blood pressure, heart rate, and survival were measured for 60 minutes. Plasma levels of histamine, leukotriene B4, prostaglandin E2, prostaglandin F2, pH, and HCO3 were measured. Mean arterial blood pressure was normal in the NA group; severe hypotension and high mortality were observed in controls; normalization of mean arterial blood pressure, heart rate, and increased survival were observed in 4-aminopyridine and EPI groups. All allergic 4-aminopyridine-treated rats survived after the induction of anaphylactic shock. Histamine level was higher in controls and the 4-aminopyridine group but reduced in the EPI group. Prostaglandin E2 increased in controls and EPI group and decreased in 4-aminopyridine group; prostaglandin F2 increased in controls but decreased in 4-aminopyridine and EPI groups. Leukotriene B4 decreased in 4-aminopyridine and EPI groups. Metabolic acidosis was prevented in the 4-aminopyridine group., Conclusions: Our data suggest that voltage-dependent K+ channel inhibition with 4-aminopyridine treatment restores blood pressure and increases survival in the Wistar rat model of anaphylactic shock. 4-aminopyridine or related voltage-dependent K channel blockers could be a useful additional therapeutic approach to treatment of refractory anaphylactic shock.

Background: The objective of this study was to provide for the first time data on plasma catecholamines, cortisol, glutathione and malondialdehyde after long term dehydration (20 days) in the presence and absence of angiotensin II (Ang II) AT1 receptor blocker (losartan) versus levels in time-matched, non-dehydrated control camels and to record the responses of glutathione and malondialdehyde activity in liver and kidney homogenates in control, dehydrated-losartan treated and dehydrated camels. Eighteen male camels were studied, six hydrated (control group), six dehydrated and treated with losartan (treated group) and six dehydrated not treated (dehydrated)., Results: Plasma levels of norepinephrine and dopamine were significantly increased (P < 0.01) in both treated and dehydrated groups compared to time matched control, whereas Plasma epinephrine level showed significant decrease (P < 0.05) in both treated and dehydrated groups compared to control. Plasma cortisol also showed significant increase (P < 0.01) in both treated and dehydrated groups compared to control. Glutathione levels in plasma, liver and kidney homogenates for both treated and dehydrated groups reveled significant increase (P < 0.05) Likewise, malondialdehyde levels in plasma, liver and kidney homogenates were substantially and significantly increased in both treated and dehydrated groups., Conclusion: In conclusion, the results of this study demonstrated that dehydration substantially increased the circulating levels of norepinephrine, dopamine and cortisol but decreased plasma epinephrine. Similarly, losartan showed similar effects to that of dehydration. In addition, this investigation showed dehydration alone or in combination with losartan induced significant increments in glutathione and malondialdehyde activities in plasma, liver and kidney homogenates, presumably in order to counteract the potentially damaging effects of free radicals. Blockade of angiotensin II AT1 receptors did not alter significantly the response of dehydration in any of these indices.

The objectives of this study were to investigate and compare the responses of atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) in the circulation of hydrated, dehydrated, and dehydrated losartan - treated camels; and to document the cardiac storage form of B-type natriuretic peptide in the camel heart. Eighteen male camels were used in the study: control or hydrated camels (n = 6), dehydrated camels (n = 6) and dehydrated losartan-treated camels (n = 6) which were dehydrated and received the angiotensin II (Ang II) AT-1 receptor blocker, losartan, at a dose of 5 mg/kg body weight intravenously for 20 days. Control animals were supplied with feed and water ad-libitum while both dehydrated and dehydrated-losartan treated groups were supplied with feed ad-libitum but no water for 20 days. Compared with time-matched controls, dehydrated camels exhibited a significant decrease in plasma levels of both ANP and BNP. Losartan-treated camels also exhibited a significant decline in ANP and BNP levels across 20 days of dehydration but the changes were not different from those seen with dehydration alone. Size exclusion high performance liquid chromatography of extracts of camel heart indicated that proB-type natriuretic peptide is the storage form of the peptide. We conclude first, that dehydration in the camel induces vigorous decrements in circulating levels of ANP and BNP; second, blockade of the renin-angiotensin system has little or no modulatory effect on the ANP and BNP responses to dehydration; third, proB-type natriuretic peptide is the storage form of this hormone in the heart of the one-humped camel.

Our objectives were to compare the levels of circulating electrolytes, hormones, and renal function during 20 days of dehydration in camels versus the level in non-dehydrated camels and to record the effect of blocking angiotensin II AT1 receptors with losartan during dehydration. Dehydration induced significant increments in serum sodium, creatinine, urea, a substantial fall in body weight, and a doubling in plasma arginine vasopressin (AVP) levels. Plasma aldosterone, however, was unaltered compared with time-matched controls. Losartan significantly enhanced the effect of dehydration to reduce body weight and increase serum levels of creatinine and urea, whilst also impairing the rise in plasma AVP and reducing aldosterone levels. We conclude that dehydration in the camel induces substantial increments in serum sodium, creatinine, urea and AVP levels; that aldosterone levels are altered little by dehydration; that blockade of angiotensin II type 1 receptors enhances the dehydration-induced fall in body weight and increase in serum creatinine and urea levels whilst reducing aldosterone and attenuating the rise in plasma AVP.

Background: Left ventricular function in hypertrophic cardiomyopathy (HCM) has been extensively studied, whereas right ventricular function is much less explored. The myocardial performance index (MPI) has been shown to be useful in functional assessment of both ventricles. Furthermore, right ventricular MPI was found to be of predictive value in heart failure due to dilated cardiomyopathy and ischemic heart disease. The aim of this study was, therefore, to evaluate the right ventricular MPI in patients with HCM., Methods: Fifty patients with HCM and 250 healthy controls were studied by conventional Doppler echocardiography and Doppler tissue imaging., Results: Patients showed increased global, 0.48 (0.15) vs. 0.21 (0.14), and regional, 0.71 (0.23) vs. 0.55 (0.17), right ventricular MPI, as compared to controls, p<0.001. Tricuspid annular plane systolic excursion and peak myocardial systolic velocities were also reduced. Patients with dyspnoea had increased global right ventricular MPI (0.53 vs. 0.36, p<0.05) as compared to those without dyspnoea., Conclusion: In the present study, patients with HCM showed evidence of both global and regional right ventricular dysfunction. Previous studies of the right ventricle in HCM have only shown evidence of diastolic dysfunction, contrary to our results, showing impairment of both systolic and diastolic function. This study suggests that HCM should not only be regarded as an isolated disease of the left ventricle, but rather as a biventricular disease. The predictive value of our findings in HCM needs to be assessed in a separate study with special reference to those with and without dyspnoea.

Systemic sclerosis (SSc) is frequently associated with interstitial lung disease (ILD) often leading to lung fibrosis. In this study we investigated whether matrix metalloproteinase 9 (MMP-9) and its natural inhibitor; the tissue inhibitor of matrix metalloproteinase 1 (TIMP-1), would be associated with remodelling in ILD in SSc. Levels of total MMP-9, pro-MMP-9 and TIMP-1 were measured in bronchoalveolar lavage (BAL) fluid from nine SSc patients with ILD, seven SSc patients without ILD and 16 age- and sex-matched healthy controls. Total MMP-9 and pro-MMP-9 levels were significantly elevated in SSc patients with ILD, compared to levels in SSc patients without ILD and healthy controls. In SSc patients with ILD calculated active MMP-9 levels were significantly higher than in SSc patients without ILD and tended to be higher than in healthy controls. TIMP-1 levels were elevated in both patient groups compared to healthy controls. Total-, pro- and active MMP-9 levels as well as pro-MMP-TIMP-1 and active MMP-9/TIMP-1 ratios were inversely associated with total lung capacity. The present study suggests that MMP-9 plays a pathophysiological role in the remodelling in ILD and lung fibrosis associated with SSc, and may represent a new therapeutic target in this condition.

Aims: Echocardiographic techniques have so far provided suboptimal estimates of myocardial contractility in humans. Longitudinal myocardial motion during the isovolumic contraction (IVC) phase, measured by colour tissue Doppler imaging (TDI), has recently been shown in experimental animal models to reflect the state of myocardial contractility. The aim of the present study was to investigate the relationship between left ventricular (LV) isovolumic contraction velocities (IVCv) using pulsed Doppler tissue imaging (DTI) and global LV contractility as measured during cardiac catheterization., Methods and Results: Cardiac catheterization and pulsed DTI were simultaneously performed in 16 consecutive patients (13 males, mean age 55+/-10years) with a variety of cardiac diseases. Relationships between the peak positive IVCv as measured at basal levels of the lateral, septal, anterior and posterior walls and the first derivative of LV pressure (+dP/dt(max)), were investigated. Peak IVCv measurements were obtainable in 81-100% of the four LV wall segments. Statistically significant linear relationships were found between IVCv and +dP/dt(max) at the lateral (r=0.58, P<0.05), septal (r=0.66, P<0.01), anterior (r=0.73, P<0.01) and posterior (r=0.81, P<0.001) segments of the LV., Conclusion: IVCv of the basal four LV walls correlates strongly with peak +dP/dt. IVCv is a readily obtainable non-invasive parameter, which correlates with the classical invasive measurement of global LV contractility. It appears likely that there are regional differences in wall motion when DTI is used to determine state of LV contractility.

The streptozotocin (STZ)-treated rat is a widely studied experimental model of diabetes mellitus (DM). Its pathophysiology includes hypoinsulinemia, hyperglycemia, cardiac hypertrophy, and a cardiomyopathy that is characterized by the presence of diastolic and/or systolic contractile dysfunction. As part of their endocrine function cardiomyocytes in the heart produce and secrete a family of related peptide hormones called the natriuretic peptides that include A-type natriuretic peptide (ANP) and B-type natriuretic peptide (BNP). ANP and BNP levels are variously augmented in patients with hypertension, cardiac overload, in the ventricles of failing or hypertrophied heart, in cardiac heart failure, in acute myocardial infarction (MI), and in some circumstances in DM. In this article, the effects of BNP on ventricular myocyte contraction and Ca2+ transport in STZ-induced diabetic rats have been investigated. BNP concentration was significantly increased in blood plasma and in atrial muscle in STZ-induced diabetic rats compared to age-matched controls. BNP was 11.9 +/- 0.9 ng/mL in plasma from diabetic rats compared to 6.7 +/- 1.6 ng/mL in controls and 15.8 +/- 2.0 ng/mg protein in diabetic atrial muscle compared to 8.5 +/- 1.0 ng/mg protein in controls. The heart weight to body weight ratio, an indicator of hypertrophy, was significantly increased in diabetic rat heart (4.3 +/- 0.1 mg/g) compared to controls (3.7 +/- 0.04 mg/g). The amplitude of shortening was not significantly altered in diabetic myocytes (10.3 +/- 0.4%) compared to controls (10.9 +/- 0.4%). BNP reduced the amplitude of shortening to a greater extent in diabetic myocytes (8.1 +/- 0.6%) compared to controls (10.1 +/- 0.4%). The time to peak (TPK) shortening was significantly prolonged in diabetic myocytes (254 +/- 8 ms) compared to controls (212 +/- 5 ms) and was not additionally altered by BNP. The time to half relaxation of shortening was also significantly prolonged in diabetic myocytes (131 +/- 8 ms) compared to controls (111 +/- 5 ms). BNP (10(-8) to 10(-6) M) normalized the time to half relaxation of shortening in diabetic myocytes to that of controls. Time to peak (TPK) shortening of Ca2+ was not different between diabetic and control rats. However, BNP (10(-7) M) increases TPK of Ca2+ significantly. The amplitude of the Ca2+ transient was significantly increased in diabetic myocytes (0.42 +/- 0.02 Ratio units [RU]) compared to controls (0.36 +/- 0.02 RU) and was not additionally altered by BNP. BNP may have a protective role in STZ-induced diabetic rat heart.

Vitamin D deficiency is common in Arab countries particularly among women. This is the result of a low dietary intake of the vitamin, limited exposure to sunlight (a paradox in view of the high sunshine figures), skin colour, obesity and high parity. Apart from its adverse effects on bone in women and their offspring, vitamin D deficiency has the potential to cause or exacerbate heart failure through a number of mechanisms including activation of the renin-angiotensin system and increased arterial pressure. Accordingly, we propose that ensuring adequate vitamin D levels in Arab women will have a much greater impact on health than just the prevention of bone disease. In particular, we suggest that prevention and correction of vitamin D deficiency will reduce the incidence of heart failure and, for Arab women with established heart failure and vitamin D deficiency, improve cardiac function.

Aims: Non-invasive assessment of pulmonary artery systolic pressure (PASP) has several limitations. As previously described by Burstin, the right ventricular (RV) isovolumic relaxation time (IVRt) is sensitive to changes in PASP. We therefore compared RV myocardial IVRt, derived by Doppler tissue imaging (DTI), with simultaneously measured invasive PASP., Methods and Results: Twenty-six consecutive patients (18 males, mean age 52 +/- 12 years, range 23-75) underwent a simultaneous Doppler echocardiography, including DTI, and cardiac catheterization examination for measurement of PASP and right atrial mean pressures. IVRt was measured using the myocardial velocities by pulsed DTI at both basal and mid cavity segments of the RV free wall. As diastolic time intervals are influenced by heart rate IVRt was corrected for heart rate (IVRt/RR%). A significant correlation was found between PASP and regional IVRt/RR% at both the basal (r = 0.42, P<0.05) and mid cavity segment (r = 0.71, P<0.001). Furthermore, when only patients with normal right atrial pressures (<7 mmHg) were taken into account, the correlation coefficient improved at both basal and mid cavity segments (r = 0.74, P<0.05 and r = 0.83, P<0.01)., Conclusion: Pulsed Doppler-derived IVRt correlates well with PASP. The use of pulsed DTI for measurement of IVRt is simple, reproducible and easy to obtain. We propose this method as an additional non-invasive tool in the assessment of PASP.

Aims: Echocardiographic techniques have not so far been able to provide a good estimation of myocardial contractility in humans. Myocardial motion during the isovolumic contraction phase, measured by Doppler tissue imaging, has only recently in experimental models been shown to describe myocardial contractility. The aim of the present clinical study was to investigate the relationship between right ventricular isovolumic contraction velocity and right ventricular state of contractility., Methods and Results: Doppler tissue imaging and cardiac catheterization were performed simultaneously in 26 consecutive patients with different cardiac diseases (18 males, mean age 52 +/- 12, range 23-75 years). Peak isovolumic contraction velocity was measured using Doppler tissue imaging at 2 levels of the right ventricular free wall. During cardiac catheterization, the first derivative of right ventricular pressure related to the pulmonary artery peak pressure (dP/dt/P(max)) was measured. Furthermore, right ventricular end diastolic pressure, right atrial mean pressure, pulmonary artery systolic pressure, and pulmonary artery resistance, were also measured. A significant relationship was found between isovolumic contraction velocity and dP/dt/P(max) (r = 0.59, p < 0.01). This relationship was strengthened after excluding patients with elevated right atrial pressures (r = 0.77, p < 0.001). Furthermore, a correlation was also found between basal and mid cavity isovolumic contraction velocity and right ventricular end diastolic pressure (r = -0.47, r = -0.49, p < 0.05) as well as right atrial mean pressure (r = -0.63, r = -0.55, p < 0.01)., Conclusion: Isovolumic contraction velocity is a reproducible and easily obtainable non-invasive parameter which correlates with invasive measurements of right ventricular state of contractility and right ventricular filling pressures.

Background: Cardiopulmonary involvement in patients with systemic sclerosis (SSc) carries a poor prognosis, mainly due to pulmonary hypertension and right-heart failure. To date, right ventricular (RV) involvement has not been studied in detail. We therefore assessed RV function in patients with SSc and related the findings to the clinical features of the disease., Method: Twenty-six consecutive patients (21 women) with SSc (mean age, 56 +/- 15 years [+/- SD]) and 25 healthy, age-matched control subjects (21 women) were studied. Doppler echocardiography including Doppler tissue imaging was used to evaluate cardiac function. Pulmonary function was also studied., Results: Compared with control subjects, RV free wall thickness (5.8 +/- 1.7 mm vs 3.7 +/- 1.1 mm, p < 0.001) and right atrial (RA) systolic area (15.9 +/- 3.7 cm2 vs 13.0 +/- 2.3 cm2, p < 0.01) were increased in patients with SSc, while the global early diastolic/atrial component velocity ratio was reduced (1.2 +/- 0.4 vs 1.7 +/- 0.6, p < 0.01). The global isovolumic relaxation time (IVRT) [64 +/- 23 ms vs 39 +/- 13 ms, p < 0.001] and regional IVRT (83 +/- 40 ms vs 46 +/- 24 ms, p < 0.001) were prolonged in patients vs control subjects, whereas the RV global filling time was reduced (454 +/- 122 ms vs 548 +/- 104 ms, p < 0.01). RV systolic function and pulmonary pressures at rest were similar in the two groups, but the pulmonary artery acceleration time was reduced (119 +/- 34 ms vs 141 +/- 29 ms, p < 0.05) in patients compared to control subjects. Left ventricular function did not differ between the two groups., Conclusion: Patients with SSc exhibit altered RV diastolic function together with an increase in RV wall thickness and RA area. These findings appear to be early markers of RV disturbance, probably in response to intermittent pulmonary arterial hypertension.

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In this study, we evaluate cardiac autonomic function in hypertrophic cardiomyopathy (HCM) by assessing heart rate variability (HRV), comparing a short-term laboratory method with an ambulatory (24-h) method, in patients with and without beta-blockade. Reduced HRV is a risk factor for adverse events in some cardiac diseases, but is not a proven risk indicator in HCM. Analysis of HRV has been based on either short- or long-term electrocardiographic recordings and previous studies in HCM have shown conflicting results. There is no consensus on which method to prefer, and we evaluate, for the first time, both short- and long-term analyses in patients with HCM. Long- and short-term HRV analyses were performed in 43 patients with HCM. They were divided in two groups, 22 patients on beta-blockade and 21 non-treated patients. As controls, 121 healthy subjects were used. Young patients without beta-blockade showed a reduction in HRV parameters reflecting parasympathetic function, both in the short- and long-term registrations, which was attenuated by beta-blockade. Parasympathetic autonomic regulation was found to be impaired in young patients with HCM. This may be of clinical relevance as abnormal autonomic function might be a substrate for malignant dysrhythmias. The impairment was attenuated by beta-blockade, which might indicate a clinically useful effect. We also show that short- and long-term methods yield similar results, suggesting that a short-term registration might be sufficient to assess HRV in patients with HCM.

Hypertrophic cardiomyopathy (HCM) is a heterogenous disease, with variable genotypic and phenotypic expressions, often caused by mutations in sarcomeric protein genes. The aim of this study was to identify the genotypes and associated phenotypes related to HCM in northern Sweden. In 46 unrelated individuals with familial or sporadic HCM, mutation analysis of eight sarcomeric protein genes was performed; the cardiac beta-myosin heavy chain, cardiac myosin-binding protein C, cardiac troponin T, alpha-tropomyosin, cardiac essential and regulatory myosin light chains, cardiac troponin I and cardiac alpha-actin. A total of 11 mutations, of which six were novel ones, were found in 13 individuals. Seven mutations were located in the myosin-binding protein C gene, two in the beta-myosin heavy chain gene and one in the regulatory myosin light chain and troponin I genes, respectively. This is the first Swedish study, where a population with HCM has been genotyped. Mutations in the cardiac myosin-binding protein C gene were the most common ones found in northern Sweden, whereas mutations in the beta-myosin heavy chain gene were less frequent than previously described. There are differences in the phenotypes mediated by these genes characterised by a more late-onset disease for the myosin-binding protein C gene mutations. This should be taken into consideration, when evaluating clinical findings in the diagnosis of the disease, especially in young adults in families with HCM, where penetrance can be expected to be incomplete in the presence of a myosin-binding protein C gene mutation.

Objective: To investigate the relationship between endothelium-dependent and endothelium-independent functions and the stiffness of conduit arteries as well as levels of endothelial activation markers in patients with systemic sclerosis (SSc)., Methods: Endothelium-dependent (i.e., flow-mediated) and endothelium-independent (i.e., nitroglycerin-induced) dilation of the brachial artery was measured as the percentage of change from baseline (FMD% and NTG%, respectively) in 24 SSc patients and 24 age- and sex-matched healthy controls by high-resolution ultrasound imaging. The maximum increase in systolic pressure per unit of time (dP/dt(max)), as a measure of arterial wall stiffness, was assessed in the radial artery by pulse applanation tonometry. Plasma nitrate, the most important metabolite of nitric oxide, and 24-hour urinary excretion of nitrate were measured by gas chromatography mass spectrometry. Soluble E-selectin and soluble vascular cell adhesion molecule 1 (sVCAM-1) were measured by enzyme-linked immunosorbent assay., Results: Brachial artery FMD% and NTG% did not differ between SSc patients and controls. Radial artery dP/dt(max) was significantly increased in the patients and correlated significantly with elevated levels of plasma nitrate and sVCAM-1. Twenty-four-hour urinary nitrate excretion tended to be elevated. Brachial artery NTG% was significantly inversely correlated with levels of plasma nitrate and soluble endothelial adhesion molecules., Conclusion: The ability of the brachial arteries to dilate in response to hyperemia and nitroglycerin challenge is preserved in SSc. Stiffness of the radial artery is increased, however. Endothelial activation seems to determine the extent of the brachial artery NTG% and the radial artery dP/dt(max). The data are compatible with the hypothesis that nitrate tolerance is present in the vascular smooth muscle cells of the brachial artery wall in SSc.

Chronic heart failure (CHF) studies investigating the clinical, hemodynamic, and therapeutic importance of endothelin-1 (ET-1), atrial natriuretic peptide (ANP), and brain natriuretic peptide (BNP) are largely based on resting plasma levels, which may vary with prior exertion and postprandial status. This study investigated the importance of peak-exercise plasma levels of ET-1, ANP, and BNP in the assessment of left ventricular (LV) systolic function. Thirty-six male-patients ages 58 +/- 10 (mean +/- SD ) with NYHA class I-IV CHF due to coronary artery disease or idiopathic dilated cardiomyopathy were enrolled. LV systolic function was assessed by echocardiography and radionuclide ventriculography. Resting and peak cardiopulmonary exercise venous blood sampling and treadmill exercise testing were performed in the fasting state. Resting plasma levels of ET-1, ANP, and BNP were elevated compared with reference laboratory normal values. Exercise induced significant (p < 0.0001) increase in plasma levels of ET-1, ANP, and BNP. On univariate analysis peak-exercise plasma levels of ET-1, ANP, and BNP were more closely related to echocardiographically determined LV end-diastolic diameter and end-systolic diameter than their resting values. Multiple step-wise regression models identified resting and peak-exercise plasma levels of ET-1 and ANP but only the resting BNP as independent predictors of LV dimensions and systolic function. Peak exercise plasma levels of ANP and ET-1 are potentially more reliable and important than their resting levels as markers of LV systolic dysfunction and LV dimensions in patients with heart failure.

Objective: To determine the relationship between vascular function and the inflammatory response in systemic sclerosis (SSc), and to investigate whether production of endothelial-derived nitric oxide (NO) is disturbed in this disease., Methods: We measured plasma nitrate, urinary excretion of both nitrate and cGMP, and soluble adhesion molecules of endothelial origin in patients with SSc and in age- and sex-matched controls and compared these levels between groups. Additionally, we performed correlation analysis to determine how these variables were related to one another. Plasma nitrate and 24-hour-urinary excretion of nitrate in patients and controls were measured after a 72-hour nitrate-free-diet, using a gas chromatography/mass spectrometric method. Soluble adhesion molecules intercellular adhesion molecule 1 (sICAM-1), vascular cell adhesion molecule 1 (sVCAM-1), and E-selectin and cytokines were measured by enzyme-linked immunosorbent assay. The expression of E-selectin was further investigated in skin biopsy specimens by immunoperoxidase staining, and the presence of inducible NO synthase by immunoblotting., Results: Plasma nitrate and 24-hour-urinary-excretion of cGMP were significantly elevated in patients compared with controls, while 24-hour-urinary-excretion of nitrate tended to be elevated in SSc patients. Levels of sICAM-1, sVCAM-1, and sE-selectin were significantly elevated in the patients. Levels of plasma nitrate in the patients correlated significantly with levels of sVCAM-1 (P = 0.020) and sE-selectin (P = 0.018) and approached a significant correlation with sICAM-1 (P = 0.055), suggesting that activated endothelial cells may produce plasma nitrate., Conclusion: NO synthesis is elevated in SSc patients, and the activated endothelial cell is a likely site of its production.

The cardiac troponin I gene has been described to be associated with hypertrophic cardiomyopathy. Until now, mutations in this gene have been found only in the Japanese population. We now present the first non-Japanese family, from northern Sweden, with a mutation in the cardiac troponin I gene. Clinical diagnose was based on echocardiography, with a maximum left ventricular wall thickness of >13 mm, or major electrocardiographic abnormalities, excluding subjects with other known causes of cardiac hypertrophy. Mutation screening was performed with a single-strand conformation polymorphism analysis and identification of mutation by direct DNA sequencing. We have identified a 33-bp deletion in exon 8 encompassing the stop codon. Nine individuals in three generations were tested, and four were carriers of this deletion. The mother was genetically affected and died of heart failure aged 90. Echocardiography at 71 years of age revealed no hypertrophy, but the electrocardiogram showed signs of left ventricular hypertrophy. Her two sons, also genetically affected, had left ventricular hypertrophy, with maximum wall thickness of 15 and 16 mm, respectively. One daughter and four grandchildren were clinically unaffected, but one of them, a 27-year-old woman with maximum wall thickness of 8 mm and normal electrocardiogram, was found to be genetically affected. In conclusion, we describe a non-Japanese family in which hypertrophic cardiomyopathy is due to a genetic defect in the cardiac troponin I gene. This mutation is a deletion of 33 bp in the last exon, whereas the previously described mutations in this gene are single nucleotide changes and a single codon deletion. The deletion of the C-terminal part of the cardiac troponin I protein, seems in this particular family to be associated with a mild phenotypic expression of familial hypertrophic cardiomyopathy., (Copyright 2000 Academic Press.)

We evaluated 30 consecutive patients and 48 age- and sex-matched controls to explore the possibility of a pathogenic contribution by plasma endothelin-1 in the cardiac expression of systemic sclerosis. Venous plasma endothelin-1 was measured by radio-immunoassay and left ventricular function by echocardiography. The patient group had elevated plasma endothelin-1 (2.6 +/- 0.2 vs. 1.8 +/- 0.1 pmol/1, P < 0.001), but endothelin-1 was not related to age, heart rate, blood pressure, total peripheral resistance, disease duration or systemic sclerosis score. Endothelin-1 was related to left ventricular hypertrophy in terms of septal thickness (r = 0.33, P < 0.01) and left ventricular mass index (r = 0.32, P < 0.01). Plasma endothelin-1 was further related to measures indicating reduced left ventricular filling; left atrial emptying index (r = -0.50, P < 0.0005), the first third filling fraction (r = -0.31, P < 0.05) and the time velocity integral of Doppler early/late filling velocity (r = -0.40, P < 0.001). Furthermore, circulating endothelin-1 was related to impaired left ventricular contractility as estimated by pre-ejection period/left ventricular ejection time (r = 0.32, P < 0.01) and end-systolic wall stress/volume index (r = -0.30, P < 0.05). We conclude that plasma endothelin-1 is elevated in relation to the degree of left ventricular hypertrophy, diastolic dysfunction and impaired contractility in systemic sclerosis. It may be of pathogenic importance to the cardiac involvement in systemic sclerosis which is not mediated via an increase in systemic blood pressure. It is not yet clear whether our findings are exclusive to systemic sclerosis patients or represent a generalized phenomenon in patients with impaired left ventricular function.

We related atrial natriuretic peptide (ANP) among 30 consecutive patients with systemic sclerosis (SScl) and 48 gender- and age-matched controls to the measurements of left ventricular (LV) function as evaluated by echocardiography and external pulse curves to determine possible causative factors for an increased level of plasma ANP. The patients had a markedly elevated plasma ANP level (239.4 +/- 59 vs. 178.2 +/- 36 pmol/l, p < 0.0005), which was not related to LV systolic function, heart rate, or blood pressure. Patients had LV hypertrophy and plasma ANP correlated directly to interventricular septal thickness (r = 0.41, p < 0.005), LV posterior wall thickness (r = 0.32, p < 0.01), and wall thickness to cavity dimension (r = 0.44, p < 0.0005), LV mass index (r = 0.40, p < 0.005). LV early filling properties were impaired, with reduction of atrial emptying index (p < 0.0005) and increased contribution of atrial contraction to LV filling. Plasma ANP correlated to atrial emptying index (r = 0.41, p < 0.0005) and to apex-cardiographic a wave (r = 0.28, p < 0.05). Plasma ANP was also related to left atrial dimension index (r = 0.27, p < 0.05), and was still related to atrial emptying index, but not to left atrial dimension, when considering the degree of LV hypertrophy in multivariate analysis. We conclude that ANP is elevated in patients with SScl. Reduced LV compliance, probably due to increased fibrosis, may cause changes in atrial pressure sufficient to stimulate ANP production without systolic dysfunction as a prerequisite.

To determine the relation between left ventricular filling properties and plasma atrial natriuretic peptide in systemic sclerosis, we evaluated 30 consecutive patients and 48 age- and sex-matched controls. The venous plasma atrial natriuretic peptide was measured by radio-immunoassay. Left ventricular involvement was evaluated by echocardiography and mitral regurgitation was evaluated by Doppler. The patient group had markedly elevated plasma atrial natriuretic peptide as compared to the matched controls, (239.4 +/- 59 vs. 178.2 +/- 36 pmol/l, P < 0.0005). We found signs of impaired left ventricular filling properties among the patients with an increase of the Doppler A-wave velocity and A/E ratio. A relative reduction of early filling was found in spite of some degree of mitral regurgitation in two-thirds of the patients. The plasma atrial natriuretic peptide concentration was related to the A-wave velocity (r = 0.44, P < 0.0005), the A/E ratio (r = 0.40, P < 0.005), and also to the degree of mitral regurgitation (r = 0.43, P < 0.005). The relationship to the A-wave velocity remained when considering possible confounding factors. We conclude that the previously observed fibrotic process in systemic sclerosis does not prevent production and liberation of plasma atrial natriuretic peptide in relation to factors distending the left atrium, such as altered left ventricular filling properties and the presence of mitral regurgitation. However, the moderate relationships between atrial natriuretic peptide and haemodynamic variables indicate that the peptide might also be an independent indicator of cardiac involvement in systemic sclerosis.

Objectives: Were to determine whether plasma atrial natriuretic peptide (ANP) is increased in patients with systemic sclerosis (SScl) and to evaluate its relation to cardiac dimensions and function., Methods: Using radio-immunoassay, plasma ANP was determined in 30 patients with SScl and 48 age and sex matched controls. The plasma ANP level was related to cardiac structure and function as determined by two-dimensional echocardiography (2-D echo)., Results: Plasma ANP was markedly elevated among patients as compared to controls (239,4 +/- 59 vs 178.2 +/- 36 pmpl/l, p < 0.0005). The left atrial long-axis and area were increased, and ANP was directly related to both measurements (r = 0.27, p < 0.05 and r = 0.40, p < 0.005, respectively). Plasma ANP was also related to the increased right atrial long-axis (r = 0.27, p < 0.05). The ANP level was not related to LV systolic function as estimated by ejection fraction, fractional area change and end-systolic wall stress, neither did these measures differ between patients and controls. However, there was an inverse correlation between ANP level and stroke volume (r = -0.35, p < 0.05), which was lower among the patients (p < 0.005). ANP displayed also an inverse relation to LV long axis diameter (r = -0.37, p < 0.005) and area (r = -0.42, p < 0.005) as well as to LV end-diastolic volume (r = -0.42, p < 0.005). Various measurements indicated LV hypertrophy among the SScl patients in spite of a small LV cavity. ANP was directly related to measures of LV hypertrophy, as interventricular septum thickness (r = 0.44, p < 0.005), LV posterior wall thickness (r = 0.34, p < 0.05), the wall thickness to cavity dimension ratio (r = 0.36, p < 0.05), and LV myocardial area (r = 0.36, p < 0.05). There was no relationship between ANP concentration and heart rate, blood pressure or total peripheral resistance., Conclusion: These results suggest that the ANP production is not reduced in SScl. Rather, circulating ANP is elevated in relation to the degree of LV hypertrophy. This implies that ANP may be useful for the identification of cardiac involvement in patients with SScl.

Impairment of left ventricular (LV) function has previously been reported in patients with systemic sclerosis (SScl). An intermittent vasospastic process in the myocardium may contribute to the development of myocardial dysfunction. Vasodilators may therefore be potentially useful in the treatment of cardiac dysfunction in patients with SScl. This study was designed to evaluate the long-term effects of captopril on the myocardial function of patients with SScl. Twenty-two patients with SScl (15 patients with diffuse scleroderma and 7 patients with CREST syndrome, i.e. calcinosis. Raynaud's phenomenon, oesophageal hypomotility, sclerodactyly, telangiectasia) were investigated by means of Doppler and echophonocardiography before and after treatment with captopril (1.3 mg kg-1 body weight d-1) for 11-15 months. There were no significant differences in heart rate, systolic and diastolic blood pressure, end-systolic blood pressure, total peripheral resistance or LV diameters before or after treatment. However, captopril treatment exerted significant effects on LV function: the pre-ejection period (PEP) and the ratio of pre-ejection period to LV ejection time decreased significantly (P less than 0.05). Mitral E-point septal separation decreased significantly (P less than 0.01), even after adjustment for LV end-diastolic diameter (P less than 0.01). The ejection fraction increased significantly (P less than 0.05), and the isovolumic relaxation time decreased (P less than 0.01). The left atrial emptying index increased (P less than 0.01). The Doppler peak late to early ventricular filling velocity decreased (P less than 0.05), and the isovolumic index was also reduced (P less than 0.05). We conclude that both systolic and diastolic LV function indices improved in patients with SScl after captopril treatment for a mean period of 1 year. The effects of captopril might be due to vasodilation of the myocardial vessels and/or a direct effect on the renin-angiotensin system of the heart.

To evaluate the left ventricular filling characteristics in systemic sclerosis, we examined 30 consecutive patients, 15 men and 15 women, and related the findings to those from 48 age- and sex-matched controls. All patients were investigated by pulsed and continuous wave mitral Doppler, and M mode echocardiography. We found the A wave of the mitral flow velocity as recorded by pulsed wave Doppler to be higher in patients (0.74 +/- 0.07 vs 0.54 +/- 0.02 m/sec, P less than 0.002), while the E wave did not differ. The high A/E ratio indicating reduced distensibility, correlated to interventricular septal thickness (r = 0.53, P less than 0.001), and atrial emptying index (r = -0.55, P less than 0.001). Early filling was impaired, with a prolonged pressure half time (99 +/- 6 vs 84 +/- 4 msec, P less than 0.05), and a reduced first third filling fraction (0.41 +/- 0.02 vs 0.48 +/- 0.01, P less than 0.001). Mitral regurgitation was found in 67% of systemic sclerosis patients and in 15% of controls (P less than 0.001). Doppler measures of left ventricular filling properties were not related to the presence of mitral regurgitation or systolic blood pressure. We conclude that left ventricular distensibility and early filling properties are impaired in systemic sclerosis and not related to blood pressure, but rather to left ventricular wall thickness and therefore probably secondary to myocardial fibrosis. Mitral regurgitation is a common finding in systemic sclerosis.

To evaluate the extent of left ventricular (LV) diastolic impairment in systemic sclerosis, we examined 30 consecutive patients (15 men and 15 women) with this condition, and compared the findings with the data for 48 age- and sex-matched randomly sampled controls. All patients were investigated by phonocardiography, pulse curve recording, and M-mode echocardiography. Twenty-three of 30 (77%) patients had LV hypertrophy and/or diastolic impairment. Interventricular septum (P = 0.0001), LV posterior wall (P less than 0.05), and the wall thickness to cavity dimension ratio (P less than 0.001) were increased in patients compared to controls, as was LV mass index (P less than 0.002). Five patients had asymmetric septal hypertrophy. LV end-diastolic dimension did not differ between groups. LV distensibility was impaired, as judged from apexcardiographic a/H ratio (P less than 0.05) and from an increased left atrial index (P less than 0.005). LV early filling was impaired, with a reduced left atrial emptying index (P = 0.0001), and a reduced rate of dimension increase in digitized M-mode (P less than 0.02). We found no evidence of impaired LV relaxation. Blood pressure did not differ between patients and controls. With longer duration of the disease, left atrial dimension appeared to increase (r = 0.42, P less than 0.05), while other variables were not related to disease duration. The impaired LV filling was not secondary to systolic dysfunction. We conclude that systemic sclerosis patients have an increased LV wall thickness, with impaired early filling properties and LV distensibility.

The effect of cold provocation on myocardial perfusion was studied in 21 patients with systemic sclerosis and 8 healthy controls. The cold provocation was designed not to cause a pain reaction, and no rise in heart rate/blood pressure product occurred during provocation. Myocardial perfusion was assessed by measurement of thallium uptake by imaged single photon emission computed tomography. No patient had clinical evidence of cardiac involvement, but abnormal electrocardiographic (ECG) findings were found in 5. In 12 patients cold-induced reversible perfusion defects were found; 9 of these also had permanent defects. A further 3 patients had permanent perfusion defects but no reversible defects. The permanent and/or reversible perfusion defects were not related to age among the patients and were not seen in any of the healthy controls, whose age distribution was similar. The reversible and permanent defects were not related to other features of systemic sclerosis, nor to the ECG findings. It is concluded that abnormalities in myocardial perfusion are common in systemic sclerosis and may be present without apparent clinical myocardial involvement. A cold-induced vasopastic process in the myocardial circulation might contribute to the development of the patchy myocardial fibrosis seen in patients with systemic sclerosis.