Circulating soluble adhesion molecules in patients with systemic sclerosis: correlation between circulating soluble vascular cell adhesion molecule-1 (sVCAM-1) and impaired left ventricular diastolic function

The objective of this paper is to investigate the relation between circulating soluble adhesion molecules and cardiac involvement, as assessed by echocardiography in patients with systemic sclerosis (SSc). Nineteen patients with SSc were submitted for assessment of serum levels of circulating soluble intercellular adhesion molecules (sICAM-1), and soluble vascular cell adhesion molecules-1 (sVCAM-1), and echocardiography. Abnormal left ventricular filling patterns (↓E/A ratio) were detected in ten patients (52.6%) with significant negative correlation with sVCAM-1 (r=−0.484, P < 0.05). It was also significantly correlated with age (r=−0.791, P < 0.01), age of onset (r=−0.468, P < 0.05), degree of dyspnea (r=−0.687, P < 0.01), and erythrocyte sedimentation rate (ESR) (r=−0.489, P < 0.05). Our findings suggest an important role for sVCAM-1 as a marker of disease severity and impaired left ventricular filling pattern in SSc. Received: 30 December 1999 / Accepted: 13 July 2000     

Tissue Doppler assessment of right ventricular function in female patients with limited form of systemic sclerosis

BackgroundCardiac involvement in systemic sclerosis (SSc) is often clinically occult. The aim of this study was the evaluation of early subclinical right ventricular (RV) involvement in patients with limited form of systemic sclerosis by tissue Doppler.MethodsTwenty female patients with limited cutaneous SSc and 20 control female subjects, matched for age were studied with transthoracic echocardiography and tissue Doppler imaging (TDI) to assess RV function. Patients with pulmonary hypertension, chronic renal failure, diabetes mellitus, hypertension, heart failure, left ventricular hypertrophy, ischemic or rheumatic heart disease were excluded.ResultsPatients with limited form SSc had significant lower tricuspid annulus peak systolic velocities (S_T) (9.95 ± 1.78 vs. 11.05 ± 1.53 cm/s, p < 0.044), early (E_T) (9.65 ± 1.30 vs. 12.50 ± 1.23 cm/s, p < 0.0001), late (A_T) diastolic velocity (12.60 ± 2.01 vs. 18.15 ± 1.81 cm/s, p < 0.0001), and tricuspid annular plane systolic excursion (TAPSE) (23.05 ± 3.50 vs. 26.50 ± 1.90, p < 0.001) compared to controls. Myocardial performance index (MPI) of the RV was higher in SSc patients compared to controls (0.41 ± 0.05 vs. 0.30 ± 0.02, p < 0.0001). There were significant correlations between disease duration and S_T and RV MPI (r = ?0.883, p < 0.0001; r = 0.686, p < 0.001, respectively).ConclusionsPatients with limited form of SSc present with pulsed-tissue Doppler imaging indices indicative of right ventricle dysfunction, which had significant correlations with disease duration. Tissue Doppler is a valuable non-invasive tool for detecting RV myocardial involvement in patients with limited SSc.     

Evaluation of left ventricular diastolic functions in patients with frequent premature ventricular contractions from right ventricular outflow tract

This study was sought to examine the effects of repetitive monomorphic premature ventricular contractions (PVCs) on left ventricular (LV) diastolic function. Thirty-three symptomatic patients (Study group, 10 males, mean age 40 ± 8 years) with normal LV systolic function and repetitive PVCs originating from the right ventricular outflow tract (RVOT-PVCs) on 24-h Holter monitoring, and 30 healthy controls (Control group, 9 males, mean age 37 ± 9 years) were enrolled in the study. None of the patients had structural heart disease. Diastolic function was assessed by echocardiographic mitral inflow pattern and tissue Doppler imaging. The study group displayed a lower E/A ratio, longer isovolumetric relaxation time (IVRT), and longer E-wave deceleration time (EDT). In the study group 13 patients showed impaired relaxation. While mean values of the systolic velocity (Sa), early diastolic velocity (Ea), and early/late diastolic velocity (Ea/Aa) ratio were significantly lower in the study group, the Aa velocity and E/Ea ratio were significantly higher. Ea velocity was <10 cm/s in 7 study patients. Mitral inflow pattern and Ea velocity was normal in all controls. Significant correlations were found between ventricular premature beats percentage and early to late transmitral flow velocity ratio, EDT, IVRT, Ea velocity, the Ea/Aa ratio, and the E/Ea ratio. In multivariate analysis, total PVC count and age were found to be independent predictors of impaired relaxation. These results suggest that repetitive monomorphic RVOT-PVCs lead to abnormalities of LV diastolic function that may contribute to clinical symptoms in patients with structurally normal hearts.     

Left ventricular aneurysms developed in a patient with systemic sclerosis

A 60-year-old woman with systemic sclerosis, lung fibrosis, and primary biliary cirrhosis was admitted to our hospital because of heart failure. Ventricular aneurysms were found in the apex and the posterior wall of the left ventricle by angiocardiography; however, there was no sign of coronary artery stenosis. A myocardial biopsy specimen revealed diffuse focal myocardial fibrosis. In this case, the patient with systemic sclerosis developed a rare complication of ventricular aneurysms without coronary disease.     

Left ventricular aneurysms developed in a patient with systemic sclerosis

Abstract

A 60-year-old woman with systemic sclerosis, lung fibrosis, and primary biliary cirrhosis was admitted to our hospital because of heart failure. Ventricular aneurysms were found in the apex and the posterior wall of the left ventricle by angiocardiography; however, there was no sign of coronary artery stenosis. A myocardial biopsy specimen revealed diffuse focal myocardial fibrosis. In this case, the patient with systemic sclerosis developed a rare complication of ventricular aneurysms without coronary disease.     

Hypocalcemia is related to left ventricular diastolic dysfunction in patients with chronic kidney disease

BackgroundLeft ventricular (LV) diastolic dysfunction in patients with chronic kidney disease (CKD) is of a complex nature and is the predominant cause of congestive heart failure in this group of patients. This work aimed to evaluate the potential effect of disturbances in calcium-phosphorus (Ca-P) metabolism in patients with CKD on LV diastolic function as assessed by echocardiography.Materials and methodsThe study group consisted of 81 ambulatory patients with CKD, stages 2–5, with preserved LV systolic function–LV ejection fraction >50% and with sinus rhythm. Standard echocardiography was performed in all patients with tissue Doppler echocardiography for the evaluation of the systolic velocity and both diastolic velocities of LV (EmLV and AmLV). The following laboratory parameters were measured: serum creatinine concentration, estimated glomerular filtration rate, and the levels of urea, P, Ca, parathormone, platelet count, hemoglobin level, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. Patients were divided into two groups according to the results of EmLV: group with LV diastolic dysfunction (EmLV < 8 cm/s) DF (+) and group with normal LV diastolic function DF (−), when EmLV was ≥8 cm/s.ResultsPatients in DF (+) group, as compared to DF (−) patients, manifested a lower serum Ca level and an elevated NT-proBNP level [9.03 ± 0.76 mg/dL vs 9.44 ± 0.78 mg/dL, p = 0.02, and 257.9 (32.6–12,633) pg/ml vs 149 (11.7–966) pg/ml, p = 0.035, respectively]. The area under the receiver operating characteristics (ROC) curve of Ca for diastolic dysfunction was 0.627, 95% CI (0.511–0.734), p = 0.04, whereas ROC derived Ca value of ≤9.82 mg/dL was characterized by a sensitivity of 91.8% and specificity of 38.1% for diagnosing LV diastolic dysfunction. The only independent variable predicting LV diastolic dysfunction as measured by a multivariate logistic regression analysis was Ca level ≤ 9.82 mg/dL with odds ratio = 8.81 (95% CI 1.49–51.82), p = 0.014.ConclusionsHypocalcemia is an independent predictive factor for LV diastolic dysfunction in patients with CKD.     

Regional diastolic function by tissue Doppler echocardiography in systemic sclerosis: correlation with clinical variables

The incidence of left ventricular (LV) diastolic dysfunction is increased in systemic sclerosis (SSc), while systolic dysfunction is present in a small percentage of patients. The aim of this study was to asses the LV “regional” diastolic abnormalities in SSc patients by the mean of Doppler tissue imaging (DTI). Echocardiographic echo-Doppler (DE) and DTI parameters were analyzed for 67 SSc patients: abnormal E/A ratio at DE was detected in 24, while abnormal e/a at DTI was observed in 41. A significant prevalence of DTI diastolic abnormalities in the segments reflecting longitudinal versus those reflecting radial LV motion was found. The segments of the basal regions of LV myocardium were significantly more involved than those of the middle portion. Linear correlation was observed between the extent of the diastolic abnormalities and the duration of disease. Longitudinal myocardial systolic velocities were significantly reduced in patients with abnormal e/a DTI.     

Early diastolic mitral annular velocity and color M-mode flow propagation velocity in the evaluation of left ventricular diastolic function in patients with Fabry disease

Fabry disease is an X-linked genetic disorder characterized by progressive intracellular accumulation of neutral glycosphingolipids. Cardiac involvement is frequent and left ventricular (LV) diastolic dysfunction is present in most of the affected subjects. Pulsed-wave tissue Doppler echocardiography (PW-TDE) and color M-mode are new Doppler methods for LV diastolic function evaluation. Their role in the assessment of Fabry disease-related cardiomyopathy remains to be established. In this study we aimed to determine the utility of PW-TDE and color M-mode-derived parameters in the assessment of LV diastolic function in patients with Fabry disease. Eighty-one echocardiographic examinations performed in 35 patients affected by Fabry disease were retrospectively analyzed. Early diastolic lateral mitral annular velocity (E_m) determined by PW-TDE and color M-mode flow propagation velocity (V_p) were measured and compared to LV filling patterns obtained using standard Doppler indexes. The receiver operating characteristics (ROC) curves method was used to determine the summary measure of relative accuracy for E_m and V_p. A comparison of ROC curves showed a significant difference for areas under the curve in favor of E_m (P < 0.001). Pseudonormal filling pattern, higher LV mass index, higher relative wall thickness, larger left atrial diameter, and older age were more frequent (all P < 0.001) in patients with incorrect diagnosis of normal LV diastolic function based on the measurement of V_p. E_m appears to be superior to V_p in the assessment of LV diastolic function in patients with Fabry disease. V_p fails to detect abnormal LV diastolic function in subjects with pronounced concentric LV remodeling and pseudonormal filling pattern.     

Non-invasive assessment of left ventricular diastolic function in patients with 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.     

Long-term survival in patients hospitalized with congestive heart failure: relation to preserved and reduced left ventricular systolic function.

AIMS: The purpose of this study was to evaluate the influence of left ventricular systolic function on the survival in a large consecutive cohort of patients hospitalized with congestive heart failure and to determine how left ventricular systolic function interacts with co-morbid conditions in terms of prognosis. METHODS AND RESULTS: Analysis of survival data from 5491 patients admitted for new or worsening heart failure to 34 departments of cardiology or internal medicine in Denmark from 1993-1996 was carried out. A standardized echocardiogram was available for 95% of the patients, and left ventricular systolic function was estimated using wall motion index score. Follow-up time was 5-8 years. Patients with preserved systolic function were older, more frequently female, and had less evidence of ischemia than patients with systolic dysfunction. After 1 year, 24% of the patients had died. Low wall motion index was a potent independent predictor of death (risk ratio for one unit increase, 0.60 (0.56-0.64)), and was of greater prognostic significance in younger patients and patients with a history of myocardial ischemia. However, even in patients with preserved systolic function, mortality was high (1 year mortality, 19%). CONCLUSION: In hospitalized heart failure patients, particularly in younger patients with ischemic heart disease, mortality risk is inversely related to left ventricular systolic function.     

Relationship between left ventricular diastolic dysfunction and six minute walk test in patients with systemic sclerosis

Objective: The six minute walk test (6MWT) is used for the assessment of functional capacity in pulmonary and cardiovascular diseases. Left ventricular diastolic dysfunction (LVDD) is the most common cardiac abnormality in systemic sclerosis (SSc). The aim of this study was to define the effect of LVDD on 6MWT parameters in patients with SSc. Methods: We studied 45 (female : male 40 : 5) SSc patients. Patients with obvious conditions that can affect 6MWT distance (6MWD) were excluded. All subjects were evaluated by 6MWT. Additionally, 6MWD of the participants was calculated as the percentage of normal predicted values. LVDD was assessed by using echocardiographic findings and classified into three categories: impaired relaxation, pseudonormal or restrictive. Results: There were 12 (27%) patients with LVDD. SSc patients with LVDD were older than SSc patients without LVDD (50 ± 12 years vs. 41 ± 10 years; P = 0.017). In all, the mean 6MWD was 487.9 ± 98.3 m. The 6MWD was shorter in SSc patients with LVDD as compared to those without LVDD (438.0 ± 94.7 m vs. 506.0 ± 94.5 m; P = 0.039). There was significant difference between the groups regarding the percentage of the predicted 6MWD (74.1 ± 10.1%vs. 82.8 ± 13.1%; P = 0.041). Conclusion: The presence of LVDD alters 6MWD in SSc patients. Reduction of 6MWD in a patient with SSc should prompt the investigation of LVDD.     

Chronic systemic inflammation accompanies impaired ventricular diastolic function, detected by Doppler imaging, in patients with newly diagnosed systolic heart failure (Hellenic Heart Failure Study)

We sought to evaluate the relationship between plasma cytokine levels (sCD14, tumor necrosis factor [TNF]-α, and interleukin [IL]-6) and tissue Doppler derived indices of left ventricular systolic and diastolic function in patients with newly diagnosed heart failure. We enrolled 101 consecutive patients (mean age 65 ± 13 years) with newly diagnosed heart failure who were hospitalized in our institute. Echocardiographic assessment was performed in all patients during the third day of their initial hospitalization. The pulsed tissue Doppler imaging (TDI) of the systolic and diastolic function of mitral annulus was characterized by the systolic wave Smv, and the diastolic waves: Emv and Amv. Left atrial kinetic energy (LAKE), an index of left atrial function, was calculated using the equation 1/2 × LASV × 1.06 × Amv²; where LASV is left atrial systolic volume. Furthermore the ratio E/Emv and the flow propagation velocity were also calculated; where E is the rapid mitral filling wave, detected by pulse Doppler. Soluble plasma levels of CD14, TNF-α, and IL-6 were measured in all patients during their third day of hospitalization. Linear regression analysis, after adjustment for sex, age, left ventricular ejection function, body mass index, arterial hypertension, smoking, physical activity, creatinine clearance, diabetes mellitus, and blood lipid levels, revealed that IL-6 levels were inversely associated with LAKE (b = − 5422.4 ± 2031.5, P = 0.03), Sm (b= −0.375 ± 0.1, P = 0.03), and flow propagation (b = −5.404 ±0.621, P = 0.001). CD14 levels were inversely associated with flow propagation (b = −17.655 ±2.6, P = 0.001), and positively associated with E/Emv ratio (b = 2.58 ± 3.6, P = 0.002) and A/Amv ratio (b = 0.629 ± 0.6, P = 0.04). TNF-α was inversely associated with Smv (b−1.189 ± 0.3, P = 0.005). This study reveals that increased plasma levels of CD14, IL-6 and TNF-α are associated with impaired left atrial function and more advanced left ventricular diastolic and systolic dysfunction, in patients with newly diagnosed heart failure.     

Assessment of left ventricular systolic function by tissue Doppler imaging in controlled versus uncontrolled type 2 diabetic patients

Aim

To detect and quantify early subtle left ventricular (LV) systolic dysfunction using Tissue Doppler Imaging in type 2 diabetic patients with apparently normal LV ejection fraction.

缺血性心肌病的左心室舒张功能障碍和预后

目的探讨缺血性心肌病(ischemiccardiomyopathy,ICM)左心室舒张功能不全与病死率的关系。方法应用多普勒超声测定ICM35例的二尖瓣和肺静脉血流频谱,分析11项参数与正常组进行比较。ICM组再分成非限制型和限制型充盈障碍亚组。对ICM病例进行8个月～5年的观察及死亡病因的调查。结果正常组与ICM组比较,二尖瓣E峰最大峰值(peakvelocityatearlydiastole,MV-E)、E/A比值(E/Aratio)、E峰减速时间(Ewavedecelerationtime,EDT);PV-S峰、D峰、S/DT、S/D比值,EPSS差异有统计学意义(P<0.05)。非限制型和限制型充盈障碍亚组比较,左心室射血分数差异无统计学意义(P>0.05),MV、PV指标,EPSS差异有统计学意义(P<0.05)。非限制型充盈障碍亚组病死率27%(4/15)。检查至死亡时间(24±8)个月;限制型充盈障碍亚组病死率55%(11/20)。检查至死亡时间(11±8)个月,心力衰竭是死亡主要原因。非限制型充盈障碍亚组与限制型充盈障碍亚组间差异有统计学意义(P<0.05)。结论左心室舒张功能不全是心力衰竭的一个重要表现。限制性充盈异常与重度收缩功能不全有关,是严重充血性心力衰竭的标志,病死率高。     

Morbidity and mortality of patients diagnosed with systemic sclerosis after the age of 75: a nested case-control study

This study aims to characterize the clinical features of a cohort of patients diagnosed with systemic sclerosis (SSc) after the age of 75 and compare them to a group diagnosed at a younger age. We record the review of 769 patients diagnosed with SSc over the past 16 years. Utilizing a nested case-control model, we compare demographics, disease severity, morbidity, and mortality data of all patients diagnosed after the age of 75 to sex- and disease-type-matched, randomly selected group of patients diagnosed with SSc before the age of 60. Twelve patients were diagnosed with SSc after the age of 75, seven with the diffuse, and five with the limited form. It took longer to diagnose SSc in the older patients, and comparison of disease severity revealed a worse pulmonary picture and a more frequent development of malignancy in the older patients as compared with the younger ones. During a mean follow-up of 36.2 months, our cohort of patients did not have worsening in their disease severity, though 6 months after the last follow-up, six patients died. We conclude that a diagnosis of SSc at an older age appears to be a poor prognostic indicator related to both disease severity and comorbidities. A higher clinical suspicion will lead to an earlier diagnosis and a potential decrease in morbidity and mortality.     

Left atrial velocity vector imaging for the detection and quantification of left ventricular diastolic function in type 2 diabetes

Left ventricular (LV) diastolic dysfunction (DD) is diagnosed by Doppler echocardiography (DE) and Tissue Doppler imaging (TDI). Velocity vector imaging (VVI) evaluates myocardial deformation (strain). We studied left atrial (LA) deformation and volumes by VVI in relation to established Doppler-derived indices of LV diastolic function in diabetic patients. MATERIAL: Using DE and TDI , 87 patients (males 49%; age 60+/-7 years) with type 2 diabetes mellitus were classified as having no (n=60), mild (n=13) or moderate (n=14) DD. RESULTS: LA volume was larger in moderate (72.3+/-22.4 ml) than in mild DD (58.8+/-16.1 ml; p=0.01) and no DD (57.9+/-16.0 ml; p=0.01). LA roof strain distinguished no DD from mild and moderate DD (p=0.0073). Systolic LA strain correlated to total emptying fraction (r=0.70, p<0.0001), and inversely to LA volume (r=-0.35, p=0.0009). A cross-validated analysis of no versus mild or moderate DD expressed by LA strain revealed a positive predictive value of 48% and negative of 84%. CONCLUSION: LA strain by VVI is impaired in patients with type 2 diabetes mellitus and mild or moderate LV DD. LA strain seems of value in distinguishing normal from abnormal diastolic function. VVI offers new information on regional LA function and LA volumes but has too limited discriminative power to detect early LV DD.     

Metabolic syndrome is associated with abnormal left ventricular diastolic function independent of left ventricular mass

Aim To characterize the extent to which metabolic syndrome criteriapredict left ventricular (LV) structure and function. Methods and results Metabolic syndrome criteria were assessedin 607 adults with normal LV function. The cohort was groupedaccording to the number of criteria satisfied: (1) Absent (0criteria, n = 110); (2) Pre-Metabolic Syndrome (1–2 criteria,n = 311); and (3) Metabolic Syndrome (3 criteria, n = 186).Echocardiography was used to assess LV structure (LV mass) andsystolic (LVEF, Vs) and diastolic function, by pulse-wave Doppler(E/A ratio) and tissue Doppler imaging (Ve). LV volumes andLVEF were similar between groups. However, LV mass increasedsignificantly and progressively (LVM/Ht^2.7, in g/m^2.7: 34.9± 6.7, 41.0 ± 9.5, 46.3 ± 11.0, P <0.001); LV relaxation decreased progressively (Ve_global', incm/s: 13.5 ± 2.8, 12.1 ± 3.0, 10.5 ± 2.2,P < 0.001) from Absent to Pre-Metabolic Syndrome to MetabolicSyndrome groups, respectively. Multiple variable analyses showedthat diastolic blood pressure, waist circumference, and triglyceridelevels were independent predictors of Ve after adjustment forLV mass. Conclusion Patients with metabolic syndrome have LV diastolicdysfunction independent of LV mass. These functional abnormalitiesmay partially explain the increased cardiovascular morbidityand mortality associated with metabolic syndrome.     

Assessment and impact of diastolic function by echocardiography in elderly patients

Doppler echocardiography is the gold standard for assessment of diastolic dysfunction, which is increasingly recognised as a cause of heart failure, especially in the elderly. Using a combination of Doppler echocardiography techniques, it is possible to identify grades of diastolic dysfunction, estimate left ventricular filling pressures and establish the chronicity of diastolic dysfunction. These physiologically-derived measures have been widely validated against invasive measurements of left heart pressures and have been shown to be prognostically valuable in a wide range of clinical settings. This review explores the mechanisms, and approaches to the assessment of diastolic dysfunction in the elderly. The challenge for clinicians is to identify pathophysiological changes from those associated with normal ageing. When used in combination, and taking age into account, Doppler echocardiographic parameters are helpful in the assessment of dyspnoea in older patients and provide prognostic insights.     

Mortality and survival in systemic sclerosis: Systematic review and meta-analysis

Objective

To determine the mortality, survival, and causes of death in patients with systemic sclerosis (SSc) through a meta-analysis of the observational studies published up to 2013.

Methods

We performed a systematic review and meta-analysis of the observational studies in patients with SSc and mortality data from entire cohorts published in MEDLINE and SCOPUS up to July 2013.

Results

A total of 17 studies were included in the mortality meta-analysis from 1964 to 2005 (mid-cohort years), with data from 9239 patients. The overall SMR was 2.72 (95% CI: 1.93–3.83). A total of 43 studies have been included in the survival meta-analysis, reporting data from 13,529 patients. Cumulative survival from onset (first Raynaud?s symptom) has been estimated at 87.6% at 5 years and 74.2% at 10 years, from onset (non-Raynaud?s first symptom) 84.1% at 5 years and 75.5% at 10 years, and from diagnosis 74.9% at 5 years and 62.5% at 10 years. Pulmonary involvement represented the main cause of death.

Conclusions

SSc presents a larger mortality than general population (SMR = 2.72). Cumulative survival from diagnosis has been estimated at 74.9% at 5 years and 62.5% at 10 years. Pulmonary involvement represented the main cause of death.