Attenuated post-exercise heart rate recovery in patients with systemic lupus erythematosus: the role of disease severity and beta-blocker treatment.

Objective Sinus tachycardia is frequently reported in systemic lupus erythematosus (SLE), while there are limited data on post-exercise ability to slow heart rate (i.e. heart rate recovery, HRR) in this group of patients. Methods We studied consecutive 70 patients with SLE and 30 healthy controls. All examined individuals underwent detailed clinical examination, echocardiography, Holter monitoring with heart rate variability and treadmill stress test using Bruce's protocol. HRR values were calculated as the difference between maximum HR during exercise and HR at the first (HRR1) and third (HRR3) minute of rest. Individuals with coronary artery disease, diabetes mellitus and suspected pulmonary hypertension were excluded from further analysis ( n = 15). Results Fifty-five SLE patients were eligible for this study: aged 41.5 ± 12.4 years, 87.3% women, SLICC/ACR-DI score 3.58 ± 1.85. In the SLE group 36.4% patients received beta-blockers, usually for previously detected sinus tachycardia and/or arterial hypertension. Mean HRR1 (36.9 ± 12.6 vs 49.5 ± 18.6, p = 0.0004) and HRR3 (55.5 ± 14.3 vs 69.2 ± 16.4, p = 0.0001) were significantly lower in SLE than in healthy individuals. Significantly negative correlations between SLICC/ACR-DI score and HRR1 ( r = -0.299, p = 0.01), HRR3 ( r = -0.361, p = 0.001) and exercise capacity ( r = -0.422, p < 0.0001) were revealed. Additionally, beta-blocker treatment was also revealed to alter significantly HRR1, HRR3 and exercise capacity in SLE. Conclusion Patients with SLE are characterized by attenuated HRR after exercise. In our study impaired HRR was associated with disease severity and beta-blocker treatment and probably with disease duration. The use of HRR assessment in SLE can be used as an additional marker of cardiac autonomic nervous system dysfunction.

Assessment of systemic and pulmonary arterial remodelling in women with systemic sclerosis.

OBJECTIVES: Systemic sclerosis (SSc) leads to pulmonary circulation dysfunctionand there are some indications of systemic circulation impairment. We evaluated the influence of SSc on the elastic properties of large systemic arterial walls and potential correlations between systemic and pulmonary circulation involvement. METHOD: We examined 75 consecutive women (mean age 53.13±10.1 years) with confirmed SSc [mean disease duration (DD) 7.1±9.1 years] and 21 age-matched female volunteers (mean age 52.6±8.3 years, ns). Pulse wave velocity (PWV) and transthoracic echocardiography were performed. SSc patients were divided into two groups according to the median of DD: ≤3 years (39 patients) and >3 years (36 patients). RESULTS: Patients with DD>3 years had higher PWV than those with DD≤3 years and controls (log PWV: 2.23±0.23 vs. 2.13±0.16 and vs. 2.11±0.16 m/s; p=0.028 and 0.029, respectively). In addition, echocardiographic indices showed impaired right ventricular (RV) function in the patients with DD>3 years. Also in these SSc patients, PWV correlated with clinical and echocardiographic parameters of pulmonary circulation: age (r=0.64, p<0.0001), acceleration time of pulmonary ejection (AcT; r=-0.38, p=0.021), and tricuspid regurgitation peak gradient (TRPG; r=0.34, p=0.04). Multiple linear regression analysis showed that PWV was independently associated with DD (ß=0.22, p==0.02), AcT (ß=-0.215, p=0.03), and age (ß=0.44, p<0.001). CONCLUSIONS: In patients with SSc lasting more than 3 years, the disease is characterized by increased stiffness of the large systemic arteries. Longer duration of SSc leads simultaneously to the increased stiffness of the large systemic arteries and to the progressive impairment of RV function and its coupling to the pulmonary arterial bed.

Antiendothelial cells antibodies in patients with systemic sclerosis in relation to pulmonary hypertension and lung fibrosis.

Although scleroderma is generally considered a fibrosing disease, it is now recognized that the underlying vascular pathology is playing a fundamental role in its pathogenesis. The present study was aimed at testing the prevalence of anti-endothelial cell antibodies (AECA) in systemic scleroderma (SSc) patients with and without pulmonary hypertension (PH) and in relation to the presence of pulmonary fibrosis. Fifty four SSc patients (50 females and 4 male, mean age 55.7 ± 16.3 years) were prospectively screened. All patients underwent transthoracic echocardiography with the estimation of pulmonary artery pressure (PAP) and tricuspid regurgitant peak gradient (TRPG). All patients suspected to have pulmonary hypertension were referred for right heart catheterization. Restrictive lung disease was confirmed by HRCT. A healthy control group included (n = 27; 7 men and 20 women, mean age 49.8 ± 12.1 years). The study of AECA was performed using the indirect immunofluorescence method on commercially available human umbilical vein endothelial cells. The HRCT scans in patients with suspected interstitial lung disease revealed signs of lung fibrosis in 15 (out of the 36 examined patients). TRPG at rest of 31 mmHg was demonstrated in 14 (21%) patients. During cardiac catheterization, arterial PH was found in two patients. Resting venous PH was found in one patient and an excessive post capillary PAP elevation at rest was demonstrated in 11 patients. At the baseline, 14/54 patients (26%) were positive for AECA. In the control group, the frequency of the antibodies was 3/27 (11%). No statistical correlation between antibody titter and the presentation of the disease existed. AECA were highly prevalent in a subgroup of patients suffering from interstitial pulmonary fibrosis. Out of the 15 patients suffering from lung fibrosis, 7 were AECA positive. The presence of AECA correlated very well with antinuclear antibodies (ANA), but was not related to the profile of ANA. Our findings support evidence that endothelial cell damage is involved in SSc, as there was increased prevalence of circulating AECA of the IgG isotype in SSc patients. AECA may also be related to the complications of SSc, like pulmonary fibrosis.

Pro- and antiangiogenic markers in patients with pulmonary complications of systemic scleroderma.

Systemic sclerosis (SSc) is an autoimmune disorder characterized by skin and internal organs fibrosis and concomitant vascular abnormalities. Although SSc is considered mainly fibrosing disease, underlying vascular pathology plays a fundamental role in its pathogenesis. We have focused on positive and negative serum markers of angiogenesis and fibrosis (pigment epithelium-derived factor [PEDF], vascular endothelial growth factor [VEGF], and soluble VEGF receptor [sVEGFR]), in progressive SSc patients at baseline and after follow-up in relation to cardiopulmonary complications (systemic hypertension [HT], pulmonary arterial hypertension [PAH] and pulmonary fibrosis [PF]). VEGF and PEDF but not sVEGFR were reciprocally regulated in SSc progression. Moreover, VEGF/PEDF ratio significantly increased during follow up suggesting that it might be used as a biomarker of disease progression. No correlation between the studied markers and cardiopulmonary complications was observed. In conclusion, VEGF and PEDF level, and the VEGF/PEDF ratio are significantly changed in the course of SSc progression and these markers can be used to assess SSc activity.

Long-term effects of acute pulmonary embolism on echocardiographic Doppler indices and functional capacity.

BACKGROUND AND HYPOTHESIS: Hemodynamic and functional consequences of acute pulmonary embolism (APE) are believed to be reversible with antithrombotic treatment. To verify this hypothesis, we reassessed our patients at least 1 year after an episode of APE. METHODS: We compared echo Doppler indices and 6-min walking test parameters (6-MWT) of 36 patients (13 men, 23 women, age 66 +/- 11 years), studied on average 3.1 +/- 2.2 years after an acute episode of pharmacologically treated massive or submassive APE, with data of 30 age-matched subjects (12 men, 18 women, age 67 +/- 12 years). RESULTS: At least 1 year after APE, right ventricular (RV) diameter remained increased in patients compared with controls (27 +/- 2 vs. 23 +/- 2 mm, p<0.001). Also, acceleration time of pulmonary ejection (AcT) was markedly shorter (97 +/- 19 vs. 123 +/- 19 ms, p<0.001) and the diameter of the pulmonary trunk was significantly larger in patients than in controls (21 +/- 2.6 vs. 18 +/- 2.2, p<0.001). Although the mean value of the tricuspid valve peak systolic gradient (TVPG) in the APE group at follow-up was similar to that in controls, TVPG>30 mmHg was recorded in three patients with APE (8.3%). There was no difference in the distance of 6-MWT between both groups; however, the mean desaturation after 6-MWT was higher in the APE group than in controls (3.04 +/- 2.08 vs. 1.45 +/- 0.69%, p=0.0005). CONCLUSIONS: Pharmacologic treatment of acute pulmonary embolism does not prevent mild persistent changes in morphology and function of the cardiovascular system. Despite normalization of pulmonary artery systolic pressure and similar exercise capacity, survivors of APE present signs suggesting RV dysfunction and/or its disturbed coupling to the pulmonary arterial bed, as well as ventilation to perfusion mismatch at exertion persisting long after the acute embolic episode.

Assessment of renal dysfunction improves troponin-based short-term prognosis in patients with acute symptomatic pulmonary embolism.

OBJECTIVE: Current risk stratification in acute pulmonary embolism (APE) includes assessment of clinical status, right ventricular overload and plasma troponin concentrations. As impaired renal function is one of the important predictors of mortality in cardiovascular diseases, we hypothesized that it is an independent early mortality marker in APE. MATERIAL AND METHODS: In prospective cohort study, we observed 220 consecutive patients (86M/134F, 64 +/- 18 years) with APE proven by spiral computed tomography (CT). On admission, echocardiography was performed and blood samples were collected for troponin and creatinine assays. RESULTS: The calculated glomerular filtration rate (GFR) differed significantly between 81 pts with low-, 131 pts with moderate- and 8 pts with high-risk APE [71 (19-181) vs. 55 (9-153) vs. 41 (14-68) mL min(-1); respectively P < 0.0001]. Twenty-three patients died during the 30-day observation. Importantly, GFR was lower in non-survivors than in survivors [35 (9-92) vs. 63 (14-181) mL min(-1), P < 0.0001]. The area under the curve (AUC) of the GFR receiver-operating characteristic (ROC) curve for predicting mortality was 0.760 (95% CI: 0.698-0.815). In multivariable analysis, independent mortality predictors were GFR, troponin, heart rate and history of chronic heart failure. In normotensive patients, the GFR and cardiac troponins (cTn) ROC curves for prediction of mortality showed no difference (AUC 0.789 and 0.781, respectively). However, Kaplan-Meier analysis showed an additive prognostic value of renal dysfunction. Thus, troponin-positive patients with a GFR < or = 35 mL mn(-1) showed 48% 30-day mortality, whereas troponin-positive patients with a GFR > 35 mL mn(-1) had 11% mortality, and troponin-negative patients with a GFR > 35 mL mn(-1) had good prognosis, P < 0.0001. CONCLUSION: Impaired kidney function, present in 47% of APE patients, is related to all-cause mortality. In initially normotensive patients, a GFR < 35 mL min(-1) predicts 30-day mortality. Moreover, GFR assessment can improve troponin-based risk stratification of APE.

A positive outcome in patient with massive acute pulmonary embolism and right atrial mobile thrombus fragmented during thrombolysis: a serial echocardiographic examination.

The case report presents a patient with acute, massive pulmonary embolism diagnosed by transthoracic echocardiography, with the mobile thrombus visualized in the right atrium. During the thrombolytic therapy the thrombus was fragmented and migrated to the pulmonary artery, with a rapid transient worsening of the clinical status of the patient. The continuation of thrombolysis led to the gradual improvement of the patient condition. In this case report the importance of serial echocardiographic examinations in revealing right heart masses, the right ventricle overloading and the effectiveness of treatment is shown.

Proximal pulmonary emboli modify right ventricular ejection pattern.

Analysis of the systolic flow velocity curve (SFVC) in the right ventricular outflow tract is considered as an alternative to the tricuspid valve pressure gradient (TVPG) method for echo-Doppler assessment of pulmonary arterial pressure (P(pa)). The present study checked whether or not SFVC is affected by the cause of pulmonary hypertension. Doppler recordings of 86 patients (39 female, aged 55.5+/-15.2 yrs) with acute (AP-PE) or chronic (CP-PE) proximal pulmonary embolism, chronic obstructive pulmonary disase (COPD) or primary pulmonary hypertension (PPH) were retrospectively analysed by two observers unaware of the purpose of the study. Despite having the lowest TVPG (48+/-13 mmHg), patients with AP-PE had the shortest acceleration time (t(acc); 56+/-15 ms) and time to midsystolic deceleration (t(msd); 105+/-16 ms). t(acc) <60 ms in patients with TVPG <60 mmHg had 98% specificity and 48% sensitivity for AP-PE. In PPH, SFVC was less abnormal (t(acc) 64+/-14 ms, t(msd) 125+/-25 ms, both p<0.03) despite having a TVPG twice as high (92+/-12 mmHg, p< 0.001). In contrast to t(acc), TVPG showed strong correlation with direct P(pa) measurements whenever performed (r=-0.43, p=0.02, versus r=0.80, p<0.001; n=30). There was no correlation between t(acc) and TVPG in a pooled study group and SFVC seemed strongly affected by the presence of both AP-PE and CP-PE. While potentially useful for evaluation of the true right ventricular afterload during pulsatile flow conditions, the systolic flow velocity curve does not provide a reliable estimate of pulmonary arterial pressure.