Peripheral Vascular Involvement Research Articles

P151 Nailfold capillaroscopy for prediction of novel severe organ involvement and mortality in systemic sclerosis

Abstract Background/Aims Nailfold capillaroscopy (NFC) has been suggested as a potential biomarker of disease severity in systemic sclerosis (SSc). Several studies report the association between capillary loss and disease severity however, the association of NFC abnormalities with novel severe organ involvement/progression and mortality in SSc has not been evaluated. We aim to evaluate the association of nailfold capillaroscopy (NFC) abnormalities with novel major organ involvement/progression and mortality in SSc. Methods Follow-up data from patients with SSc registered between 2000 and 2022 were analyzed. Patients underwent NFC at baseline. Baseline demographic data, antibody status, baseline pulmonary function, novel severe organ involvement/progression and mortality were registered. Novel organ involvement/progression was defined as new or progressive involvement of peripheral vasculature, lungs, heart, skin, gastrointestinal, kidney, musculoskeletal at 12 and 24 months of follow-up. The following NFC parameters were evaluated: capillary density, hemorrhages, enlarged and giant capillaries, avascular areas, organization of capillary architecture and scleroderma pattern (early/active/late). Logistic regression modelling was run to assess associations between NFC and clinical parameters, the occurrence of novel severe organ involvement and/or progression and mortality. Results 113 patients were included: 28 (25%) were male, 86 (76%) lcSSc and 27 (23%) dcSSc. 70 patients (61%) developed novel overall severe organ involvement/progression and 40 patients died (36%) during follow-up. Table 1 and table 2 summarizes the associations between NFC and novel severe organ involvement/progression and mortality during follow-up. Loss of capillary density was associated with overall severe organ involvement (p = 0.002), peripheral vascular involvement (p = 0.03), new ILD (p = 0.04) and skin progression (p = 0.01); avascular areas were associated with overall severe organ involvement (p = 0.03), new ILD (p = 0.03) and progression of ILD (p = 0.02) and scleroderma pattern was associated with overall severe organinvolvement (p = 0.03), peripheral vascular involvement (OR p = 0.04), new ILD (p = 0.004), progression of ILD (p = 0.03) and skin progression (p = 0.04). Mortality was associated with ILD (OR 2.56 CI 95% 1.5-7.2, p 0.04), DLCO <70% (2.34 CI 93% 1.42-6.23, p 0.03), a late pattern in NFC (3.42 95% CI 1.42-7.25, p 0.002), presence of hemorrhages (OR 1.77 95% CI 1.24-8.23, p0.034) and avascular zones (OR 6.22 95% CI 2.54-10.3, p 0.021). Survival rates from diagnosis at 10 years were lower in patients with NFC with active a late pattern (40% and 20%) compared with those with normal, unspecific and early pattern (100%, 90% and 70%) (p = 0.008 by log rank test) (figure 1). Conclusion NFC may be a potential biomarker in SSc for predicting novel severe organ involvement and/or progression and mortality. Abnormal capillary density, avascular areas and scleroderma pattern are predictors of overall severe organ involvement, peripheral vascular involvement, novel and progression of ILD and skin progression. Disclosure C. Sieiro Santos: None. P. Pérez García: None. J. Ordas Martínez: None. C. Álvarez Castro: None. E. Díez Álvarez: None.

Sustained vasodilation after cold pressor test is an independent predictor of poor survival in primary AL amyloidosis

Abstract Background Primary AL amyloidosis is a rare yet lethal systemic disorder. Dysfunction of the autonomous nervous system due to disease-related nerve infiltration is a common manifestation of AL amyloidosis. Previously published own work indicated that AL patients present sustained paradoxical vasodilation in response to sympathetic stimulus, as assessed by cold pressor test (CPT). The clinical relevance of this finding is unknown. Purpose We sought to investigate the relationship between CPT-induced vascular response and mortality in AL amyloidosis. Methods We consecutively recruited 97 newly diagnosed patients with AL amyloidosis. CPT of the brachial artery was performed before treatment initiation. All measurements were assessed using high resolution ultrasonography (14.0Mhz multifrequency linear array probe, Vivid 7 Pro; General Electric Healthcare, Milwaukee, Wisconsin, USA). The maximum vasodilation of the brachial artery was measured during the sympathetic stimulus and 3 minutes after withdrawal (sustained response). All-cause mortality was defined as the primary end-point of the study. Results Mean age was 66 years with prevalence of male gender. Sustained vasodilation (but not vasodilation during CPT) was associated with heart failure, NYHA stage, BNP and peripheral vascular involvement (p<0.05 for all). Sustained vasodilation after withdrawal of the sympathetic stimulus was significantly associated with mortality as assessed by Cox regression analysis (HR: 1.149, 95% CI 1.042–1.269, p=0.005). This association remained significant after adjustment for age, sex, systolic blood pressure (SBP), nerve involvement and Mayo stage (HR: 1.123, 95% CI 1.014–1.243, p=0.026). A sustained vasodilation ≥3.35% from pre-stimulus diameter was associated with shorter survival (log-rank test, p=0.022, Figure 1). No association between vasodilation during sympathetic stress and mortality was observed. Conclusions In AL amyloidosis, sustained paradoxical vasodilation in response to sympathetic stimulus was associated with poor survival. The clinical utility of this index of vascular autonomic dysfunction as a potential prognostic and therapeutic biomarker in AL amyloidosis merits further investigation. Funding Acknowledgement Type of funding sources: None.

Nailfold capillaroscopy in SSc: innocent bystander or promising biomarker for novel severe organ involvement/progression?

Nailfold videocapillaroscopy (NVC) plays a well-established role in differentiating primary from secondary RP due to SSc. However, the association of NVC with novel severe organ involvement/progression in SSc has never been evaluated in a multicentre, multinational study, which we now perform for the first time. Follow-up data from 334 SSc patients [265 women; 18 limited SSc (lSSc)/203 lcSSc/113 dcSSc] registered between November 2008 and January 2016 by seven tertiary centres in the EUSTAR-database, were analysed. Novel severe organ involvement/progression was defined as new/progressive involvement of the peripheral vasculature, lungs, heart, skin, gastrointestinal tract, kidneys, musculoskeletal system, or death, at the 12- or 24-month follow-up. NVC images at enrolment were quantitatively and qualitatively evaluated according to the standardized definitions of the EULAR Study Group on Microcirculation in Rheumatic Diseases. Uni- and multivariable logistic regression modelling (ULR, MLR) was performed. Of the 334 included SSc patients, 257 (76.9%) developed novel overall severe organ involvement/progression. Following MLR, normal capillary density was associated with less-frequent novel overall severe organ involvement/progression [odds ratio (OR) = 0.77, P < 0.001] and novel peripheral vascular involvement (OR = 0.79, P = 0.043); microhaemorrhages were associated with less novel pulmonary hypertension (OR = 0.47, P = 0.029); and a 'severe' (active/late) NVC pattern was associated with novel overall severe organ involvement/progression (OR = 2.14, P = 0.002) and skin progression (OR = 1.70, P = 0.049). Our results suggest that NVC may be a promising biomarker in SSc, certainly warranting further investigation. Despite the participation of tertiary centres, which follow their patients in a standardized way, we were underpowered to detect associations with infrequent severe organ involvement/progression.

Sex-related Differences in Systemic Sclerosis: A Multicenter Cross-sectional Study From the National Registry of the Italian Society for Rheumatology.

There is still a great deal to learn about the influence of sex in systemic sclerosis (SSc). In this respect, national registries provide large and homogeneous patient cohorts for analytical studies. We therefore investigated a wide-ranging and well-characterized SSc series with the aim of identifying sex differences in disease expression, with a special focus on demographic, clinical, and serological characteristics. A multicenter SSc cohort of 2281 patients, including 247 men, was recruited in the Italian Systemic sclerosis PRogression INvestiGation (SPRING) registry. Demographic data, disease manifestations, serological profile, and internal organ involvement were compared. The overall female/male ratio was 8.2:1. Female/male ratios for limited cutaneous SSc, diffuse cutaneous SSc, and SSc sine scleroderma subsets were 8.7:1, 4.9:1, and 10.7:1, respectively. A shorter time from onset of Raynaud phenomenon to SSc diagnosis, an increased prevalence of the diffuse cutaneous subset, renal crisis, and digital ulcers were found in males, whereas a significantly higher percentage of sicca syndrome, serum antinuclear antibodies, antiextractable nuclear antigens, anti-La/SSB, and anticentromere protein B was detected in the female group. Males exhibited lower left ventricular ejection fraction, as well as higher prevalence of conduction blocks, arrhythmias, ground glass, and honeycombing. Moreover, forced vital capacity and total lung capacity were medially lower in men than in women. Finally, males were more frequently treated with immunosuppressive drugs. Our study further supports the presence of several sex-related differences in patients with SSc. These differences were pronounced in the severity of cutaneous, peripheral vascular, and cardiopulmonary involvement for male patients, whereas an increased prevalence of sicca syndrome and a specific autoantibody profile characterized the female sex.

Peripheral vascular involvement in transthyretin cardiac amyloidosis. A comparative analysis with AL amyloidosis

Abstract Background The pattern of peripheral vascular involvement in the wild type transthyretin-related cardiac amyloidosis (ATTRwt) and its diagnostic utility in differentiating this infiltrating cardiomyopathy from light chain (AL) cardiac amyloidosis (AL-CA) and heart failure with preserved ejection fraction (HFpEF) of different origin have not been explored. Aims To characterize the pattern of peripheral vascular involvement in ATTRwt and evaluate its value in differentiating ATTRwt from AL-CA and HFpEF. Methods Newly diagnosed patients with ATTRwt (n=42) were consecutively recruited from our amyloidosis center. These patients were matched 1:1 for age and sex to patients with AL-CA (n=32) and subjects without amyloidosis (n=32) and also matched 2:1 to HFpEF patients (n=16). All subjects underwent a series of non-invasive vascular examinations for the assessment of: 1. subclinical carotid atherosclerosis with B-mode ultrasonography, 2. Arterial stiffness with measurement of carotid-femoral pulse wave velocity, 3. Reactive vasodilation with flow-mediated dilation (FMD) and 4. Aortic blood pressures and arterial wave reflections with augmentation index (AI) and return time of reflected wave (Tr). Results ATTRwt patients had lower peripheral (pBP) and aortic blood pressure (aBP) markers compared to non-AL controls (p<0.05 for all). ATTRwt grouping was an independent determinant of these markers, after adjustment for cardiovascular risk factors (CVRF), including history of hypertension, hyperlipidemia and diabetes, glomerular filtration rate, body mass index and smoking status (core model). ATTRwt had lower aDBP and increased Tr compared to AL subjects. In a comparison between ATTRwt and AL patients with cardiac involvement, AI and Tr were higher and FMD lower in ATTRwt patients. ATTRwt was an independent determinant of these markers, after adjustment for the core model (p<0.05 for all). Compared to HFpEF, patients with ATTRwt had lower peripheral and central BP and higher Tr (p<0.05 for all). By ROC analysis, Tr provided high diagnostic value for ATTRwt vs. AL-CA (Area Under the Curve, AUC=0.809, CI: 0.65–0.96) and for ATTRwt vs combined AL-CA and HFpEF (AUC=0.880, CI: 0.79–0.97). Finally, AI was closely correlated with posterior (Spearman's Rho=−0.30) and intraventricular wall thickness (Rho=−0.329) and left ventricular global longitudinal strain (Rho=−0.4) and lower cDBP with higher Gilmore and New York Heart Association stage (p<0.05). Conclusion ATTRwt patients present differential characteristics of peripheral vascular function and aortic hemodynamics as compared to AL, HFpEF and healthy controls. The clinical value of these characteristics merit further investigation since differential diagnosis among amyloidosis types is clinically challenging, while it may have prognostic implications. Funding Acknowledgement Type of funding sources: None.

WIDEFIELD FLUORESCEIN ANGIOGRAPHY IN THE DIAGNOSIS OF SUSAC SYNDROME.

To present the clinical manifestations and results of key diagnostic investigations in patients with Susac syndrome, with special emphasis on the principal role of fluorescein angiography (FA) of the peripheral retina. A retrospective analysis of medical records (collected 2000-2019) of 20 patients (15 women and five men), aged 20 to 51 years (mean age: 31.6 years) with complete or incomplete Susac syndrome diagnosed by an ophthalmic examination and widefield fluorescein angiography (WF-FA) by Spectralis and Optos Tx200. Fluorescein angiography abnormalities included vascular changes in the posterior pole in 64.7% and in the peripheral retina in 82.4%. Widefield FA abnormalities in the peripheral retina alone were seen in 35.3% and in the posterior pole, but without peripheral vascular involvement, in 17.6%. Secondary leakage from veins was noted in 58.8%. Widefield FA of the peripheral retina has a key role in cases of suspected Susac syndrome as it confirms the diagnosis and assesses disease activity. In addition to the characteristic findings, late-phase FA revealed leakage from veins which is not a typical sign. Patients experiencing migraine headaches may benefit from increasing awareness of neurologists and otologists who more promptly referred patients with suspected Susac syndrome for ophthalmologic evaluation and WF-FA of the peripheral retina.

OP0266 EFFICACY OF NINTEDANIB IN PATIENTS WITH SYSTEMIC SCLEROSIS-ASSOCIATED INTERSTITIAL LUNG DISEASE (SSC-ILD) AND INTERNAL ORGAN INVOLVEMENT: DATA FROM THE SENSCIS TRIAL

Background:SSc is a heterogeneous autoimmune disease characterised by fibrosis of the skin and internal organs. In most patients with SSc-ILD, organs other than the lungs are also affected. In the SENSCIS trial in patients with SSc-ILD, nintedanib reduced the rate of decline in forced vital capacity (FVC) (mL/year) over 52 weeks by 44% versus placebo.Objectives:We investigated the extent of organ involvement related to SSc at baseline in patients in the SENSCIS trial and the effect of nintedanib versus placebo on the rate of FVC decline in subgroups by internal organ involvement.Methods:The SENSCIS trial enrolled patients with SSc-ILD with first non-Raynaud symptom ≤7 years before screening, extent of fibrotic ILD ≥10% on high-resolution computed tomography (HRCT) and FVC ≥40% predicted. Patients with clinically significant pulmonary hypertension were excluded. Patients were randomised to receive nintedanib or placebo until the last patient reached week 52 but for ≤100 weeks. In post-hoc analyses, we analysed the rate of decline in FVC (mL/year) over 52 weeks in subgroups with and without different types of SSc-related internal organ involvement (upper gastrointestinal; lower gastrointestinal; cardiovascular [CV]; peripheral vascular; muscular; joint). These subgroups were defined based on patients’ SSc-related medical history as reported in the case report form. A random slope and intercept model was used to assess the rate of decline in FVC (mL/year) and an interaction test applied to assess potential heterogeneity in the treatment effect of nintedanib between the subgroups.Results:Of 576 patients, 96.9% had peripheral vascular involvement, 75.5% had upper gastrointestinal and 39.8% lower gastrointestinal involvement, 45.7% had CV involvement, 40.6% had joint involvement, and 27.1% had muscular involvement at baseline. In the placebo group, the rate of decline in FVC (mL/year) was numerically greater in patients with than without upper gastrointestinal involvement and in patients without than with joint involvement or muscular involvement (Figure). The exploratory interaction p-values did not indicate heterogeneity in the treatment effect of nintedanib versus placebo on reducing the rate of decline in FVC (mL/year) between the subgroups based on organ involvement (p>0.05 for all treatment-by-time-by-subgroup interactions) (Figure).Conclusion:Patients in the SENSCIS trial had diverse complications related to SSc. There was no evidence of a differential treatment effect of nintedanib on reducing the rate of decline in FVC based on gastrointestinal, CV, joint, or muscular involvement at baseline.Acknowledgements:The SENSCIS trial was funded by Boehringer Ingelheim. Medical writing support was provided by FleishmanHillard Fishburn, London, UK. The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE).Disclosure of Interests:Yannick Allanore Consultant of: Boehringer Ingelheim, Medsenic, Menarini and Sanofi, Grant/research support from: Alpine Pharmaceuticals, Anna-Maria Hoffmann-Vold Speakers bureau: Actelion, Boehringer Ingelheim, Lilly, MSD and Roche, Consultant of: Actelion, ARXX, Bayer, Boehringer Ingelheim, Lilly, Medscape, MSD and Roche, Grant/research support from: Boehringer Ingelheim, Maureen Mayes Consultant of: Paid consultant or member of Advisory Board/Steering Committee for Boehringer Ingelheim, Eicos, Galapagos and Mitsubishi Tanabe Pharma, Grant/research support from: Clinical trial research support from Boehringer Ingelheim, Corbus, Eicos and Galapagos, Madelon Vonk Speakers bureau: Boehringer Ingelheim, GlaxoSmithKline, Janssen and Roche, Consultant of: Boehringer Ingelheim and Janssen, Grant/research support from: Boehringer Ingelheim, Ferrer, Galapagos and Janssen, Corinna Miede Employee of: Currently an employee of mainanalytics GmbH, contracted by Boehringer Ingelheim, Margarida Alves Employee of: Currently an employee of Boehringer Ingelheim, Gabriela Riemekasten Speakers bureau: Actelion, Boehringer Ingelheim, Cellgene, GlaxoSmithKline, Janssen, Novartis and Roche, Consultant of: Actelion, Boehringer Ingelheim and Janssen, Grant/research support from: Janssen

Vascular Complications of Infective Endocarditis: Diagnosis and Management.

Introduction: The complications of infective endocarditis (IE) are frequent and severe. Our aim was to study the clinical and paraclinical profiles and prognosis of vascular complications, observed in a cardiology unit in Oujda, Morocco. Among 57 patients hospitalized for IE between 2015 and 2020 at the cardiology unit, 19 patients, or 33.3% of patients, had one or more vascular complications. We present here a retrospective analysis.Aim: Prevention, early diagnosis, and treatment of vascular complications are primordial to improving prognosis, following the guidelines of the European Society of Cardiology.Patients and methods: We retrospectively studied 57 patients hospitalized for IE. The diagnostic criteria for IE were modified from the Duke University criteria and we present all vascular complications among this cohort.Results: Nineteen patients presented with one or more vascular complications, 10 men and nine women, with a mean age of 49 years. IE had grafted on a mechanical prosthetic valve in four cases. Overall, we found 25 vascular lesions: six neurological complications, five cases of peripheral vascular involvement, nine splenic infarcts, and five recurrent septic pulmonary embolisms (SPEs). The vascular complications accrued after three to 14 days of antibiotherapy or on extension reports; blood cultures were positive in 17 (89.4%) cases; streptococcus was isolated in nine cases; Staphylococcus aureus in seven cases; and acinetobacter in one case.Conclusion: Vascular complications of IE are severe, the most common in our study being splenic infarct. Prevention and early diagnosis are essential to instituting optimal management.All the patients were followed up with a mean follow-up of three years. Late mortality involved one patient in connection with a hemorrhagic stroke secondary to an accident with vitamin K antagonists after its release in one month. No cases of recurrence of endocarditis were noted in this group.Data were collected from archived medical records and analyzed by Statistical Package for the Social Sciences.

Characterization and clinical implications of peripheral arterial involvement in transthyretin cardiac amyloidosis cardiomyopathy

Abstract Background The sporadic form of transthyretin amyloidosis cardiomyopathy (ATTR-CM) is underdiagnosed but its prevalence is increasing due to the aging population. Given the poor prognosis of ATTR-CM understanding the underlying pathophysiologic mechanisms of the disease is imperative in order to improve strategies for early diagnosis and risk stratification and to develop new effective therapeutic options. ATTR-CM is associated with hypotension and there is preliminary experimental evidence of vascular involvement but its presence and clinical significance remains unknown. Purpose To characterize peripheral arterial involvement and explore its clinical role in ATTR-CM. Methods We consecutively recruited 28 previously untreated patients with newly diagnosed ATTR-CM and 34 elderly controls >70 years old, without ATTR-CM or heart failure. In both groups, flow-mediated dilatation (FMD) and intima-media thickness (IMT) in the carotid arteries were measured by high-resolution ultrasonography as markers of peripheral vascular reactivity and of subclinical atherosclerosis, respectively. Carotid-femoral pulse wave velocity (PWV) was measured as a marker of arterial stiffness. Aortic blood pressure (BP) and augmentation index (AI) using applanation tonometry were measured as markers of arterial wave reflections, peripheral arterial resistance and central hemodynamics. Echocardiography was performed in all ATTR patients. All cardiovascular (CV) measurements were performed before administration of any ATTR-specific therapy. Results ATTR patients were older and had lower prevalence of hypertension and male gender (p<0.05 for all) than the control group. Aortic and peripheral BP (p=0.016–0.088) and AI (p=0.003) were lower in ATTR patients. IMT in the common (cc) and internal carotid (ic) as well as in the carotid bulb (cb) were significantly higher in ATTR patients (p=0.001–0.042). After multivariable adjustment for traditional CV disease (CVD) risk factors, the ATTR group was independently associated with AI and IMT in cc, cb and ic (p<0.05 for all). In a subgroup of subjects with similar age between groups (n=13 and n=33 and 74.5±2.9 vs. 75.6±3.6 years, for ATTR vs. controls, respectively) differences in AI and cbIMT remained significant. Interestingly, AI was strongly and inversely associated with interventricular wall thickness (IVwt) in ATTR patients (spearman rho=−0.651, p=0.001). After adjustment for traditional CVD risk factors this association remained significant. Conclusion ATTR-CM is associated with lower aortic wave reflections, which correlate with more advanced structural cardiac disease, as assessed by IVwt. Further, ATTR-CM patients present accelerated subclinical carotid atherosclerosis as compared to elderly control subjects. These findings suggest that in ATTR-CM there is disease-specific peripheral vascular involvement in parallel to cardiac involvement. The clinical significance of these findings merits further investigation. Funding Acknowledgement Type of funding source: None

Reactive Vasodilation Predicts Mortality in Primary Systemic Light-Chain Amyloidosis.

Rationale: Cardiac involvement and hypotension dominate the prognosis of light-chain amyloidosis (AL). Evidence suggests that there is also peripheral vascular involvement in AL but its prognostic significance is unknown. Objective: To evaluate vascular dysfunction in patients with AL as a potential future area of intervention, we assessed the prognostic utility of flow-mediated dilatation (FMD), a marker of vascular reactivity, which is augmented under conditions of hypotension and autonomic dysfunction. Methods and Results: We prospectively evaluated 115 newly diagnosed untreated AL patients in whom FMD was measured. FMD in AL patients was significantly higher than age-, sex- and risk factors-matched controls (4.0% versus 2.32%; P=0.006) and comparable with control groups at lower cardiovascular risk (P>0.1). Amyloidosis patients presented increased plasma and exhaled markers of the NO pathway while their FMD significantly correlated with augmented sustained vasodilatation after sympathetic stimulation. Increased FMD (≥4.5%) was associated with early mortality (hazard ratio, 4.36; 95% CI, 1.41-13.5; P=0.010) and worse survival (hazard ratio, 2.11; 95% CI, 1.17-3.82; P=0.013), even after adjustment for Mayo stage, nerve involvement and low systolic blood pressure. This finding was confirmed in a temporal validation AL cohort (n=55; hazard ratio, 4.2; 95% CI, 1.45-12.3; P=0.008). FMD provided significant reclassification value over the best prognostic model (continuous Net Reclassification Index, 0.61; P=0.001). Finally, better hematologic response was associated with lower posttreatment FMD. Conclusions: FMD is relatively increased in AL and independently associated with inferior survival with substantial reclassification value. Reactive vasodilation merits further investigation as a novel risk biomarker in AL.Visual Overview: An online visual overview is available for this article.

Large-vessel vasculitis diagnosed between 50 and 60 years: Case-control study based on 183 cases and 183 controls aged over 60 years.

Age at onset of large-vessel vasculitis (LVV) is commonly used to distinguish giant cell arteritis (GCA) and Takayasu arteritis (TA). However, LVV between age 50 and 60 years may be difficult to classify. We conducted a retrospective study including LVV aged between 50 and 60 years at onset (LVV50-60, cases) and compared them to LVV aged over 60 years (LVV>60, controls). LVV was defined histologically and/or morphologically. Controls fulfilled ACR 1990 criteria for GCA or presented isolated aortitis. We included 183 LVV50-60 and 183 gender-matched LVV>60. LVV50-60 had more frequent peripheral limb manifestations (23 vs. 5%), and less frequent cephalic (73 vs. 90%) and ocular signs (17 vs. 27%) than LVV>60. Compared to LVV>60, CT angiography and PET/CT scan were more frequently abnormal in LVV50-60 (74 vs. 38%, and 90 vs. 72%, respectively), with aorta being more frequently involved (78 vs. 47%). By multivariate analysis, absence of cephalic symptoms, presence of peripheral limb ischemia and aorta involvement, and increased CRP level were significantly associated with LVV50-60 presentation compared to LVV>60. At last follow-up, compared to LVV>60, LVV50-60 received significantly more lines of treatment (2 vs. 1), more frequent biologics (12 vs. 3%), had more surgery (10 vs. 0%), and had higher prednisone dose (8.8 vs. 6.5 mg/d) at last follow-up, CONCLUSION: LVV onset between 50 and 60 years identifies a subset of patients with more frequent aorta and peripheral vascular involvement and more refractory disease compared to patients with LVV onset after 60.

The Systemic Sclerosis Questionnaire (SySQ): Validation of the Translation of the Original German Version Into Spanish and Its Relationship to the Disease and to Quality of Life

ObjectiveTranslation, transculturation and validity of the self-administered questionnaire for functionality (Systemic Sclerosis Questionnaires [SySQ]) for use in Spanish patients with systemic sclerosis and its relationship to the severity of the disease and to quality of life. Patients and methodsWe conducted an observational analytical study to perform a cross-cultural validation of the self-administered questionnaire on functionality in scleroderma. The validity of the form and content was evaluated by an expert panel. The method included: (a) adaptation into Spanish of the construct for translation and back translation, and transculturation; (b) internal consistency with the SySQ (Cronbach's alpha), and (c) reproducibility was assessed taking into account all occasions in which the test was performed with Cohen's kappa. Additionally, we calculated the Spearman correlation coefficient with the Medsger severity scale, Health Assessment Questionnaire score and SF-36 score. ResultsWe included 70 patients with systemic sclerosis: age 17–78 (51±12) years, 65 (93%) were women, diffuse/limited subtype 64/36%, disease duration of .5–40 years. Optimal internal consistency for all categories of the final version of SySQ (Cronbach's α of .961) and intraobserver reliability in 2 tests over a 2-week interval (Cohen's kappa coefficient .618) and optimal interobserver reliability in 2 tests on the same day (Cohen's kappa coefficient .911). Moderate correlation between functionality by SySQ and by Health Assessment Questionnaire (r=.573, P<.0001). Inverse correlation between SySQ and quality of life mental health domain SF-36 (r=−.435, P<.001) and physical domain SF-36 (r=−.638, P<.001). Medsger severity scale (tendon, heart, lung, vascular) also showed significant correlation with SySQ. ConclusionsSySQ in this validated Spanish version is a suitable instrument to measure functional status in patients with systemic sclerosis. Reduced functionality is related to greater tendon and peripheral vascular involvement and to a poorer quality of life.

Gender differences in systemic sclerosis: relationship to clinical features, serologic status and outcomes.

There is a strong female preponderance reported in many connective tissue diseases and in almost all systemic sclerosis (SSc) case series. We compared gender differences in SSc patients in a large single-center cohort, including demographic features, disease subtype, environmental exposures, disease-specific serum autoantibodies, organ system involvement (frequency and severity) and survival. Adjustment for cutaneous subset (diffuse cutaneous [dc] and limited cutaneous [lc]) was performed. We identified key characteristics which distinguished female from male SSc patients. Females were more frequently younger at disease onset with a longer disease duration at the time of their first visit. Females more often had lcSSc and, if an overlap syndrome was present, it was most often systemic lupus erythematosus. In contrast, males more frequently had dcSSc and overlap with myositis. Females more frequently had peripheral vascular involvement but in males it was more often severe. Males were more often cigarette smokers and more frequently had environmental exposures. Males more frequently had interstitial lung disease (ILD or pulmonary fibrosis) which was more severe. Females had a significantly increased frequency of anti-centromere antibody and males anti-topoisomerase I and anti-U3RNP antibody. Males had significantly reduced survival (73% at 5 years and 45% at 10 years after onset of SSc). The most frequent causes of death were ILD in males and pulmonary hypertension in females. Gender differences may be important clues to understanding the natural history and pathogenesis of SSc.

29 Outcomes of PCI versus medical therapy in a surgically ineligible cohort from a single centre

Introduction There are limited data describing outcomes in patients who have been turned down for surgical revascularisation (CABG) on the basis of prohibitive risk. Methods We analysed cardiovascular outcomes (composite major adverse clinical event rate, MACE: all cause mortality; cardiac death, myocardial infarction, MI; repeat revascularisation; and stroke) in a retrospective cohort of patients turned down for elective CABG who were treated with PCI or medical therapy in a single centre over a 4 year period. Results Higher rates of cognitive impairment, chronic total occlusion, peripheral vascular disease (PVD) and atrial fibrillation were seen in the medical treatment group (n = 117). There was no difference between MACE rates in the PCI (n = 131) and medical groups at 30d however a significant difference emerged in MACE at 1 year, 2 year and 3 years due to a reduction in all cause death, cardiac death and MI in the PCI group. There was no difference between MACE rates in the high SYNTAX tertile, unless cases where residual SYNTAX was greater than 22 were excluded from the analysis. Independent predictors of MACE within the PCI group were SYNTAX score and diabetes, whereas peripheral vascular disease, haemodialysis and left main involvement were all associated with negative outcomes in the medical group. Conclusion Our data suggests a benefit from PCI revascularisation in patients ineligible for surgery at 1 year and a MACE-free survival benefit from PCI up to 3 years in patients within low and intermediate SYNTAX tertiles compared to medical therapy.

Inodilators in the Management of Low Cardiac Output Syndrome After Pediatric Cardiac Surgery.

Postoperative low cardiac output syndrome has been shown to have both a central and a peripheral vascular involvement. Therefore, inodilators which provide with a combination of positive inotropic and vasodilating therapy, conceptually should be an ideal form of treatment. However, contradictory data on these drugs exist. Phosphodiesterase inhibitors (e.g., milrinone) and more recently calcium sensitizers (e.g., levosimendan) have been most commonly used groups in the clinical setting. This review will summarize the pharmacology of inodilators with a special foccus on current clinical evidence. This article addresses the sixth of eight topics comprising the special issue entitled "Pharmacologic strategies with afterload reduction in low cardiac output syndrome after pediatric cardiac surgery".

SP0114 The Predictive and Prognostic Power of the Capillaroscopic Analysis

Next to its early diagnostic role, in discerning a primary from a secondary Raynaud's phenomenon (RP) due to systemic sclerosis (SSc), it is now evident a further critical role of...

SP0172 The Predictive and Prognostic Power of the Capillaroscopic Analysis

Next to its early diagnostic role, in discerning a primary from a secondary Raynaud's phenomenon (RP) due to systemic sclerosis (SSc), it is now evident a further critical role of...

C0520: Impairment of Peripheral Vascular Function in Systemic Lupus Erythematous Patients. Differences from the Vascular Pattern of Patients at High Cardiovascular Risk

Background: We investigated vascular function of peripheral arteries in Systemic Lupus Erythematous (SLE) patients, comparing results obtained in patients with acute coronary syndromes (less 1-year previous event) and in healthy control subjects (no cardiovascular events or autoimmune disease). Methods: In 170 patients (controls:76, ACS:74, SLE:20) peripheral arterial tonometry (PAT) and augmentation-index (Aix) by EndoPAT (Itamar, Caesarea, Israel), intima-media-thickness and pulse-wavevelocity at common carotid (c-IMT, c-PWv) and femoral arteries (f-IMT, f-PWv) by ultrasound technology (Esaote MyLab70) were assessed. Results: Among SLE group, 8 (40%) had a previous vascular event. ACS showed higher cardiovascular risk profile. ACS showed a marked atherosclerotic damage, because of higher cand f-IMT values in comparison to others (ACS: c-IMT= 1.9±0.6mm, f-IMT=1.7±0.8mm; SLE: c-IMT=1.6±0.8mm, f-IMT= 1.5±0.7mm; controls: c-IMT=1.3±0.9mm, f-IMT=1.2±0.4mm); SLE and ACS data did not significantly differ, but both resulted to be significantly higher than data found in controls (p = 0.02 and p=0.03, respectively). Vascular compliance was significantly impaired in SLE (c-PWv=10.5±2.6m/s, f-PWv=10.2±1.3m/s), in comparison to ACS (c-PWv=9.2±2.3m/s, f-PWv=9.4±3.1m/s; p < 0.05) and controls (c-PWv=7.1±2.1m/s, f-PWv=7.2±1.4m/s; p = 0.001). Aix was higher in SLE (17.2±6.3%), in comparison to ACS (15.3±1.4%, p = 0.2) and controls (8.1±4.2%; p =0.002). SLE showed a significantly lower endothelial function, expressed as natural logarithm of reactive hyperaemia index (LnRHI), (0.56±1.2), compared to controls (0.79±1.7; p = 0.03) and these values minimally differed between SLEs and ACS groups (0.50±2.3, p = 0.3). LnRHI and PWv values were significantly correlated with number of CRFs. At univariate and multivariate analyses, presence of SLE and a previous vascular event were significantly associated to endothelial dysfunction (p =0.02 and 0.03, respectively) and compliance impairment (p = 0.02 and 0.03, respectively). Conclusions: Our data suggested that SLE showed a marked atherosclerotic peripheral vascular involvement, similar to patients at very high CV as ACS, because of impairment of local compliance at common carotid and femoral arteries and a marked endothelial dysfunction.

Early Diagnostic and Predictive Value of Capillaroscopy in Systemic Sclerosis.

Nailfold microvascular impairment represents an early feature of systemic sclerosis (SSc) and its progression through different patterns of capillary damage and their validated scoring, is evaluable by nailfold videocapillaroscopy (NVC) in a safe and reliable manner. The presence of specific morphological microvascular alterations at the NVC (i.e., presence of giant capillaries) is fundamental and mandatory for the early diagnosis of SSc, together with the presence of the Raynaud's phenomenon. Furthermore, a recent longitudinal study showed a dynamic transition of microvascular damage through different NVC patterns of microangiopathy in almost 50% of SSc patients and clinical symptoms progressed in accordance with the NVC morphologic changes in 60% of the SSc patients. A pilot study was the first demonstrating an association between baseline NVC patterns and future severe, peripheral vascular and lung involvement with stronger odds according to worsening scleroderma patterns. Prognostic indexes for digital trophic lesions, especially for daily use in SSc clinics and simply limited to the mean score of capillary loss are now validated. Very recently, it has been described that efficacious potentially disease modifying therapies in SSc may interfere with progression of nailfold microvascular damage, as assessed by NVC, over long term at least in presence of digital ulcers. NVC is a safe and reliable tool for the early diagnosis of SSc and the different NVC scleroderma patterns have a predictive value for the clinical complications of the disease.

Increased risk for bone loss in women with systemic sclerosis: a comparative study with rheumatoid arthritis

To assess bone mass in women with systemic sclerosis (SSc) in comparison to age and sex-matched patients with rheumatoid arthritis (RA), and to evaluate factors influencing bone mineral density (BMD). Patients were consecutively recruited and assessed for BMD at the lumbar spine and hip by dual-energy X-ray absorptiometry (DEXA) using a densitometer. In SSc, the extent of skin involvement, modified Rodnan skin thickness score (mRSS) and Medsger disease severity index were assessed. Forty-three patients with SSc and 38 age-matched patients with RA were included. There was no difference in BMD measurements between patients with diffuse or limited SSc. Patients with SSc had similar risk factors associated with osteoporosis (OP) or low bone mass except for low body mass index (BMI) and low vitamin D levels compared to patients with RA. Lumbar spinal BMD and T score were similar between groups. Total hip and femoral neck BMD and T score at femoral neck and total hip were significantly lower in patient with SSc versus RA. There was significant association between mRSS, Medsger severity score (peripheral vascular involvement and skin) and femoral BMD. There is an increased risk for bone loss in patients with SSc and the risk of OP is associated with disease severity, prolonged menopause and disease duration. The complex pathophysiology of bone metabolism as well as complex pathogenesis of the SSc pose some difficulty reaching clear-cut conclusions on the causal relationship between SSc and bone loss.