G. Faganello

Combined Circumferential and Longitudinal Left Ventricular Systolic Dysfunction in Patients with Rheumatoid Arthritis without Overt Cardiac Disease

BACKGROUNDnPatients with rheumatoid arthritis have an increased risk for cardiovascular disease. Because of accelerated atherosclerosis and changes in left ventricular (LV) geometry, circumferential and longitudinal (C&L) LV systolic dysfunction (LVSD) may be impaired in these patients despite preserved LV ejection fraction. The aim of this study was to determine the prevalence of and factors associated with combined C&L LVSD in patients with rheumatoid arthritis.nnnMETHODSnOne hundred ninety-eight outpatients with rheumatoid arthritis without overt cardiac disease were prospectively analyzed from January through June 2014 and compared with 198 matched control subjects. C&L systolic function was evaluated by stress-corrected midwall shortening (sc-MS) and tissue Doppler mitral annular peak systolic velocity (S). Combined C&L LVSD was defined if sc-MS was <86.5% and S was <9.0xa0cm/sec (the 10th percentiles of sc-MS and S derived in 132 healthy subjects).nnnRESULTSnCombined C&L LVSD was detected in 56 patients (28%) and was associated with LV mass (odds ratio, 1.03; 95% CI, 1.01-1.06; Pxa0=xa0.04) and concentric LV geometry (odds ratio, 2.76; 95% CI, 1.07-7.15; Pxa0=xa0.03). By multiple logistic regression analysis, rheumatoid arthritis emerged as an independent predictor of combined C&L LVSD (odds ratio, 2.57; 95% CI, 1.06-6.25). The relationship between sc-MS and S was statistically significant in the subgroup of 142 patients without combined C&L LVSD (rxa0=xa00.40, Fxa0<xa00.001), having the best fitting by a linear function (sc-MSxa0=xa058.1xa0+xa03.34xa0×xa0peak S; r(2)xa0=xa00.19, Pxa0<xa0.0001), absent in patients with combined C&L LVSD.nnnCONCLUSIONSnCombined C&L LVSD is detectable in about one fourth of patients with asymptomatic rheumatoid arthritis and is associated with LV concentric remodeling and hypertrophy. Rheumatoid arthritis predictsxa0this worrisome condition, which may explain the increased risk for cardiovascular events in these patients.nnnNOTICE OF CLARIFICATIONnThe aim of this notice of clarification is to analyze in brief the similarities and to underline the differences between the current article (defined as paper J) and a separate article entitled Prevalence and Factors Associated with Subclinical Left Ventricular Systolic Dysfunction Evaluated by Mid-Wall Mechanics in Rheumatoid Arthritis (defined as paper E), which was written several months before paper J, and recently accepted for publication by the journal Echocardiography (Cioffi et al. http://dx.doi.org/10.1111/echo.13186). We wish to explain more clearly how the manuscript described in paper J relates to the paper E and the context in which it ought to be considered. Data in both papers were derived from the same prospective database, so that it would appear questionable if the number of the enrolled patients and/or their clinical/laboratory/echocardiographic characteristics were different. Accordingly, both papers reported that 198 patients with rheumatoid arthritis (RA) were considered and their characteristics were identical, due to the fact that they were the same subjects (this circumstance is common and mandatory among all studies in which the patients were recruited from the same database). These are the similarities between the papers. In paper E, which was written several months before paper J, we focused on the prevalence and factors associated with impaired circumferential left ventricular (LV) systolic function measured as mid-wall shortening (corrected for circumferential end-systolic stress). We found that 110 patients (56% of the whole population) demonstrated this feature. Thus, these 110 patients were the object of the study described in paper E, in which we specifically analyzed the factors associated with the impairment of stress-corrected mid-wall shortening (sc-MS). The conclusions of that paper were: (i) subclinical LV systolic dysfunction (LVSD) is detectable in more than half RA population without overt cardiac disease as measured by sc-MS, (ii) RA per se is associated with LVSD, and (iii) in RA patients only LV relative wall thickness was associated with impaired sc-MS based upon multivariate logistic regression analysis. Differently, in the paper J, we focused on the prevalence and factors associated with combined impairment of circumferential and longitudinal shortening (C&L) in 198 asymptomatic patients with RA. We found that 56 patients (28% of the whole population) presented this feature. Thus, these 56 patients were analyzed in detail in this study, as well as the factors associated with the combined impairment of C&L shortening. In paper J, we evaluated sc-MS as an indicator of circumferential systolic LV shortening, and we also determined the average of tissue Doppler measures of maximal systolic mitral annular velocity at four different sampling sites ( S) as an indicator of longitudinal LV systolic shortening. This approach clearly demonstrates that in paper J, we analyzed data deriving from the tissue Doppler analysis, which were not taken into any consideration in paper E. The investigation described in paper J made evident several original and clinically relevant findings. In patients with RA: (i) the condition of combined C&L left ventricular systolic dysfunction (LVSD) is frequent; (ii) these patients have comparable clinical and laboratory characteristics with those without combined C&L LVSD, but exhibit remarkable concentric LV geometry and increased LV mass, a phenotype that can be consider a model of compensated asymptomatic chronic heart failure; (iii) RA is an independent factor associated with combined C&L LVSD; (iv) no relationship between indexes of circumferential and longitudinal function exists in patients with combined C&L LVSD, while it is statistically significant and positive when the subgroup of patients without combined C&L LVSD is considered, having the best fitting by a linear function. All these findings are unique to the paper J and are not presented (they could not have been) in paper E. It appears clear that, starting from the same 198 patients included in the database, different sub-groups of patients were selected and analyzed in the two papers (they had different echocardiographic characteristics) and, consequently, different factors emerged by the statistical analyses as covariates associated with the different phenotypes of LVSD considered. Importantly, both papers E and J had a very long gestation because all reviewers for the different journals found several and important issues that merited to be addressed: a lot of changes were proposed and much additional information was required, particularly by the reviewers of paper E. Considering this context, it emerges that although paper E was written well before paper J, the two manuscripts were accepted at the same time (we received the letters of acceptance within a couple of weeks). Thus, the uncertainty about the fate of both manuscripts made it very difficult (if not impossible) to cite either of them in the other one and, afterward, we just did not think about this point anymore. Of note, the idea to combine in the analysis longitudinal function came therefore well after the starting process of revision of the paper E and was, in some way inspired by a reviewers comment. That is why we did not put both findings in the same paper. We think that our explanations provide the broad audience of your journal a perspective of transparency and our respect for the readers right to understand how the work described in the paper J relates to other work by our research group. Giovanni Cioffi On behalf of all co-authors Ombretta Viapiana, Federica Ognibeni, Andrea Dalbeni, Davide Gatti, Carmine Mazzone, Giorgio Faganello, Andrea Di Lenarda, Silvano Adami, and Maurizio Rossini.

Prevalence and factors related to left ventricular systolic dysfunction in asymptomatic patients with rheumatoid arthritis

BackgroundPatients with rheumatoid arthritis (RA) have a high risk for cardiovascular disease due to a chronic inflammatory state, accelerated atherosclerosis, and changes in left ventricular (LV) geometry. These conditions predispose patients to LV systolic dysfunction (LVSD). In this study we assessed whether RA is a condition associated with LVSD, and analyzed the prevalence and factors associated with LVSD in patients with RA.Patients and methodsEchocardiographic and clinical data from 198 patients with RA without presence or history of symptoms of cardiac disease were compared with 198 non-RA controls matched for cardiovascular risk factors. LVSD was identified withtissue Doppler echocardiography (TDE) when mitral annular peak systolic velocity (S’) was <u20099.0xa0cm/s.ResultsPatients with RA were 61u2009±u200912xa0years old and 71u2009% were female (disease duration 14u2009±u200910xa0years). LVSD was found in 89 patients with RA (45u2009%). By multiple regression analysis including both RA patients and controls, RA emerged as an independent condition associated with LVSD (exp β 3.89; CI: 1.87–8.08) together with higher E/E’ ratio (index of LV diastolic function) and diabetes mellitus. For the 198 patients with RA, the variables associated with LVSD were higher E/E’ ratio and systolic blood pressure.ConclusionsAlmost half of asymptomatic RA patients without history of cardiac disease have subclinical LVSD easily detectable with TDE. RA is closely related to LVSD. A higher degree of LV diastolic dysfunction and systolic blood pressure are associated with LVSD in these patients, whose risk for cardiovascular events could be better defined using such information in the asymptomatic stage of cardiac disease.ZusammenfassungHintergrundDas Vorliegen eines hohen Risikos für eine Herz-Kreislauf-Erkrankung ist bei Patienten mit rheumatoider Arthritis (RA) aufgrund chronischer Entzündungsprozesse, beschleunigter Arteriosklerose und Veränderungen der linksventrikulären (LV)-)Geometrie bekannt. Dies prädisponiert zu einer linksventrikulären systolischen Dysfunktion (LVSD). In der vorliegenden Studie untersuchten die Autoren, ob eine RA mit einer LVSD assoziiert ist sowie Prävalenz und Faktoren, die mit einer LVSD bei RA-Patienten einhergehen.MethodenEs wurden echokardiographische und klinische Daten von 198 Patienten ohne Bestehen oder Vorgeschichte von Symptomen einer Herzerkrankung mit 198 in Bezug auf kardiovaskuläre Risikofaktoren gematchte Kontrollen ohne RA verglichen. Eine LVSD wurde mittels Gewebedopplerechokardiographie (TDE) diagnostiziert, wenn die systolische Spitzengeschwindigkeit am Mitralring (S’) <u20099,0xa0cm/s war.ErgebnisseDie Patienten mit RA waren in einem Alter von 61u2009±u200912 Jahren, 71u2009% Frauen (Krankheitsdauer: 14u2009±u200910 Jahre). Eine LVSD wurde bei 89 RA-Patienten (45u2009%) festgestellt. Bei der multiplen Regressionsanalyse mit Einschluss sowohl der RA-Patienten als auch der Kontrollen erwies sich eine RA als unabhängige Erkrankung mit Assoziation zur LVSD [Expxa0β 3,89 (Konfidenzintervall, KI: 1,87–8,08)], zusammen mit einem höheren E/E’-Quotienten (Index der LV diastolischen Funktion) und Diabetes mellitus. Betrachtet man nur die 198 Patienten mit RA, waren die mit einer LVSD assoziierten Variablen ein höherer E/E’-Quotient und der systolische Blutdruck.SchlussfolgerungFast die Hälfte der asymptomatischen RA-Patienten ohne Vorgeschichte einer Herzerkrankung weisen eine subklinische LVSD auf, die mit der TDE leicht erkennbar ist. Die RA ist eng mit einer LVSD verknüpft. Ein höherer Grad einer LV diastolischen Dysfunktion und der systolische Blutdruck sind mit einer LVSD bei diesen Patienten assoziiert, deren Risiko für eine Herz-Kreislauf-Erkrankung besser bestimmt werden könnte, wenn solche Informationen im asymptomatischen Stadium der Herzerkrankung genutzt würden.

Cardiovascular risk stratification and management of patients with rheumatoid arthritis in clinical practice: the "EPIDAURO registry".

services are the major factors influencing pre-hospital delays in patients of acute ischemic stroke in China. Moreover, our study provides further evidence regarding the need for pre-hospital emergency care services among stroke patients. Therefore, the EMS system for stroke patients should be improved, especially in rural areas, and strong collaboration between hospital and community healthcare facilities should be encouraged.

Reasons why patients suffering from chronic heart failure at very high risk for death survive

BACKGROUNDnAn accurate prognostic stratification is essential for optimizing the clinical management and treatment decision-making of patients with chronic heart failure (HF). Among the best available models, we used the Cardiac and Comorbid Conditions HF (3C-HF) Score, to predict all-cause mortality in patients with CHF.nnnMETHODSnwe selected and characterized the subgroup of patients at very high risk with the worst mid-term prognosis belonging to the highest decile of 3C-HF score with the aim to assess predictors of survival in subjects with an expected probability of 1-year mortality near to 45%.nnnMETHODS AND RESULTSnWe recruited 1777 consecutive chronic HF patients at 3 Italian Cardiology Units. Median age was 76 ± 10 years, 43% were female, and 32% had preserved ejection fraction. Subjects belonging to the highest decile of 3C-HF score were 246 (13.8% of total population). During a median follow-up of 21 [12-40] months, 110 of these patients (45%) survived and 136 (55%) died. The variables that contributed to survival prediction emerged by Cox regression multivariate analysis were the lower degree of renal dysfunction and higher body mass index.nnnCONCLUSIONSnThe prognostic stratification of chronic HF patients allows in daily practice to select patients at different risk for death and identify prognosticators of survival in outliers at very high risk of death. The reasons why these patients outlive the matching part of subjects who expectedly die are related to the maintenance of a satisfactory renal function and body mass index.

Prognostic Role of Subclinical Left Ventricular Systolic Dysfunction Evaluated by Speckle-Tracking Echocardiography in Rheumatoid Arthritis

Background: Speckle‐tracking echocardiography allows early detection of subclinical left ventricular systolic dysfunction (LVSD) in patients with rheumatoid arthritis (RA). In this prospective study, we assessed the prevalence and the prognostic role of subclinical LVSD detected by speckle‐tracking echocardiography in RA patients. Methods: Two‐dimensional global longitudinal strain (GLS) and global circumferential strain (GCS) were measured in 209 RA patients without overt cardiac disease. LVSD was defined as low GLS (> −16.0%), low GCS (> −17.8%), or both. The primary end point was all‐causes hospitalization; the coprimary end point was hospitalization for cardiovascular causes. Results: The study population had a mean age of 58 ± 11 years; 67% were female, 52% had hypertension, and the RA duration was 14 ± 10 years. Low GLS was detected in 51 patients (24%), low GCS in 42 patients (20%), and combined low GLS and GCS in 18 patients (9%). During a median follow‐up time of 16 months (range, 10–21 months), a primary end point occurred in 50 patients (24%), and 25 patients were hospitalized for a cardiovascular event. Multiple Cox regression analyses revealed that combined low GLS and GCS was independently associated with the end point defined as all‐causes hospitalization together with higher aortic stiffness. Examined individually, neither low GCS nor low GLS showed an independent association with this typology of clinical outcome. Conversely, both low GCS and low GLS (examined individually or as combined low GLS and GCS) emerged as strong independent prognosticators of cardiovascular events. Conclusions: Subclinical LVSD defined as low GLS, GCS, or both is common in RA patients without overt cardiac disease and provides additional prognostic information in these individuals. HighlightsA significant proportion of asymptomatic rheumatoid arthritis patients without history of cardiac disease have subclinical left ventricular systolic dysfunction detected by speckle‐tracking echocardiography and defined as low global longitudinal strain (GLS) and/or low global circumferential strain (GCS).In rheumatoid arthritis subjects analyzed in primary prevention, all‐causes hospitalizations are independently related to the condition of combined low GLS and GCS.The combined low GLS and GCS status is characterized by older age, left ventricular diastolic dysfunction, and left ventricular hypertrophy, all of which are factors predisposing patients toward the development of overt heart failure.Low GCS, low GLS, and combined low GLS and GCS are strong independent predictors of cardiovascular events at mid‐term follow‐up.

The worrisome liaison between left ventricular systolic dysfunction and mitral annulus calcification in type 2 diabetes without coronary artery disease: data from the SHORTWAVE study.

BACKGROUND AND AIMnMitral annulus calcification (MAC) is a marker for coronary artery disease (CAD) and predicts poor outcome in the general population. No data are available on MAC in patients with type 2 diabetes. In these patients we assessed prevalence of MAC and the relation between MAC and left ventricular (LV) systolic function.nnnMETHODS AND RESULTSnAs many as 386 patients with type 2 diabetes without CAD were studied with Doppler echocardiography. LV systolic dysfunction was defined by analyzing 120 healthy subjects. Stress-corrected midwall shortening (sc-MS) and mitral annular peak systolic velocity (peak S) were considered as indexes of LV circumferential and longitudinal shortening and classified low if <89% and <8.5 cm/s, respectively (10th percentiles of controls). Patients who had MAC (107 = 28%) were older with longer duration of DM and were receiving more anti-hypertension medications than those who had not. At echocardiographic evaluation patients with MAC showed higher LV mass, larger left atrial volume (LAV), reduced sc-MS (88.4 ± 14.9 vs 92.6 ± 14.3%; p = 0.01) and peak S (8.9 ± 2.2 vs 10.0 ± 2.0 cm/s; p < 0.001) than patients without MAC. Multiple logistic regression demonstrated older age (OR 1.03 [IC 1.01-1.06], p = 0.009), larger LAV (OR 1.19 [IC 1.11-1.28], p < 0.001) and combined reduction in sc-MS and peak S (OR 3.00 [IC 1.57-5.72], p = 0.001) as independent factors associated with MAC.nnnCONCLUSIONSnMAC is detectable in one fourth of patients with type 2 diabetes without CAD and is mostly related to LV systolic dysfunction expressed as combined impairment of LV circumferential and longitudinal fibers, independent of age and LAV.

Echocardiographic markers of inducible myocardial ischemia at baseline evaluation preparatory to exercise stress echocardiography

BackgroundTissue Doppler Imaging (TDI) is a sensible and feasible method to detect longitudinal left ventricular (LV) systolic dysfunction (LVSD) in patients with diabetes mellitus, hypertension or ischemic heart disease. In this study, we hypothesized that longitudinal LVSD assessed by TDI predicted inducible myocardial ischemia independently of other echocardiographic variables (assessed as coexisting potential markers) in patients at increased cardiovascular (CV) risk.MethodsTwo hundred one patients at high CV risk defined according to the ESC Guidelines 2012 underwent exercise stress echocardiography (ExSEcho) for primary prevention. Echocardiographic parameters were measured at rest and peak exercise.ResultsExSEcho classified 168 (83.6xa0%) patients as non-ischemic and 33 (16,4xa0%) as ischemic. Baseline clinical characteristics were similar between the groups, but ischemic had higher blood pressure, received more frequently beta-blockers and antiplatelet agents than non-ischemic patients. The former had greater LV size, lower relative wall thickness and higher left atrial systolic force (LASF) than the latter. LV systolic longitudinal function (measure as peak S’) was significantly lower in ischemic than non-ischemic patients (8.7u2009±u20092.1 vs 9.7u2009±u20092.7xa0cm/sec, pu2009=u20090.001). The factors independently related to myocardial ischemia at multivariate logistic analysis were: lower peak S’, higher LV circumferential end-systolic stress and LASF.ConclusionsIn asymptomatic patients at increased risk for adverse CV events baseline longitudinal LVSD together with higher LV circumferential end-systolic stress and LASF were the factors associated with myocardial ischemia induced by ExSEcho. The assessment of these factors at standard echocardiography might help the physicians for improving the risk stratification among these patients for ExSEcho.

FRI0117 Analysis of risk for cardiovascular events and assessment of diagnostic and therapeutic management of patients with rheumatoid arthritis in clinical practice: the epidauro registry.

Background A number of studies have clearly documented a higher mortality rate in patients with rheumatoid arthritis (RA) than in general population, comparable to that found in patients with type 2 diabetes mellitus, mainly due to cardiovascular (CV) causes. No improvement in CV mortality over the last 50 years has been observed in recent meta-analyses in RA patients. Objectives The “EPIDAURO registry” (Registro sull’ EPIdemiologia Dell’Artrite reUmatoide e Rischio cardiOvascolare) collected information on the risk of CV events and on the clinical management (diagnostic tests and therapy for CV risk factors control) of RA patients to highlight possible reasons for lacking of reduction in CV mortality over time in these patients. Methods Anamnestic and clinical data of 721 patients with RA followed by 4 Italian Centers were retrospectively analyzed. The CV risk was graded according to the score of European Society of Cardiology. Subjects with a probability > 5% of CV events in the following 10 years were considered at increased CV risk. No exclusion criterion was considered for inclusion into the registry. Results Study patients had a mean age of 61±14 years, 29% was male, mean duration of AR was 11±8 years. The mean number of joints implicated was 5 per patient; the state of activity of the disease was high in 18% of patients. Hypertension coexisted in 48% of cases, dyslipidemia in 62%, diabetes 11%, smokers were 23%, known coronary artery disease 6%, previous myocardial infarction or heart failure 5% and 3%, respectively. 396 patients had multiple risk factors and were considered at increased risk independent of RA. Interestingly, information on physical activity was available in 40% of participants, waist circumference was measured in 41% of them and in only 39% were available all parameters allowing diagnosis of metabolic syndrome, serum vitamin D levels were measured in 19% (mean 27±5 ng/ml). Considering the diagnostic tests, an ECG was performed in 65% of patients, echocardiogram in 29%, exercise stress test in 6%, carotid ultrasound imaging in 13%, automatic 24 hours blood pressure or ECG monitoring in 19% and 9% respectively. In regards to the pharmacological therapy, beta-blockers were prescribed in 20% of patients, ACEi/ARBs in 30%, antiplatelet agents in 21% and statins in 20%. In patients who had an increased CV risk, echocardiography and exercise stress test were performed more frequently (36 vs 20% and 9 vs 4%, respectively; all p < 0.01) and beta-blockers and ACEi/ARBs were prescribed more commonly (27 vs 14% and 45 vs 11%, respectively, all p < 0.01) than patients who had not. Conclusions An increased CV risk is present in more than half of patients with RA examined in daily clinical practice. In these patients the available information essential for a complete CV evaluation including the presence of inducible myocardial ischemia and prognostic assessment are lacking in the vast majority of subjects and pharmacological treatment for managing CV risk factors is sub-optimal. Disclosure of Interest None Declared

12.8 ICD for primary and secondary prevention of sudden death in patients with dilated cardiomyopathy

Background and Aim: Although some patients (pts) with dilated cardiomyopathy (DC), also without history of sustained ventricular tachyarrhythmias, may be considered at high risk of sudden death (SD), the role of implantable defibrillator (ICD) for primary prevention remains uncertain. I P 481 HEALTH STATUS AND THE IMPACT OF ANXIETY ON