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Background 2D speckle tracking echocardiography (2DSTE) was proved to be accurate for the assessment of the RV function. However, normal values for RV strain refer mostly to 3- or 6-segment models, excluding the contribution of other RV walls to RV function. We analyze RV function by 2DSTE in a normal population, using parasternal two-(2C) and apical four-chamber (4C) RV views, and creating a new 12-segment model for a potential better definition of RV function. Methods We prospectively evaluated 100 normals using 2DE and STE. We assessed the RV systolic function from regional strain (basal, mid, and apical), and at the level of each wall: lateral (LS), septal (SS), inferior (IS), and anterior (AS), and also global strain for 4C (4CGS), and 2C (2CGS). Global systolic strain rate (SRs) was measured from 2C and 4C views. Diastolic function was assessed from early (SRe) and late global strain rate (SRl), for both views. Results A total of 70 healthy individuals (48±15 years, 34 men) were suitable for concomitant 4C and 2CRV analysis. Feasibility of the STE analysis was 87.8%. We found significantly lower SS by comparison with LS, AS, and IS (P

Aim The objective of this study was to evaluate the clinical presentation, inpatient management, and in-hospital outcome of patients hospitalized for acute heart failure syndromes (AHFS) and classified as pulmonary edema (PE). Methods The Romanian Acute Heart Failure Syndromes (RO-AHFS) study was a prospective, national, multicenter registry of all consecutive patients admitted with AHFS over a 12-month period. Patients were classified at initial presentation by clinician-investigators into the following clinical profiles: acute decompensated HF, cardiogenic shock, PE, right HF, or hypertensive HF. Results RO-AHFS enrolled 3224 patients and 28.7% (n = 924) were classified as PE. PE patients were more likely to present with pulmonary congestion, tachypnea, tachycardia, and elevated systolic blood pressure and less likely to have peripheral congestion and body weight increases. Mechanical ventilation was required in 8.8% of PE patients. PE patients received higher doses (i.e. 101.4 ± 27.1 mg) of IV furosemide for a shorter duration (i.e. 69.3 ± 22.3 hours). Vasodilators were given to 73.6% of PE patients. In-hospital all-cause mortality (ACM) in PE patients was 7.4%, and 57% of deaths occurred on day one. Increasing age, concurrent acute coronary syndromes, life-threatening ventricular arrhythmias, elevated BUN, left bundle branch block, inotrope therapy, and requirement for invasive mechanical ventilation were independent risk factors for ACM. Conclusions In this national registry, the PE profile was found to be a high-acuity clinical presentation with distinctive treatment patterns and a poor short-term prognosis. Advances in the management of PE may necessitate both the development of novel targeted therapies as well as systems-based strategies to identify high-risk patients early in their course.

Aims To explore the relationship between the mitral annular (MA) remodelling and dysfunction, mitral regurgitation (MR) severity, left ventricular (LV) and atrial (LA) size and function in patients with organic MR (OMR). Methods and results A total of 52 patients (57 ± 15 years, 31 men) with mild to severe OMR and 52 controls underwent 3D transthoracic echocardiography acquisitions of the mitral valve (MV), LA, and LV. MA geometry and dynamics, LV and LA volumes, LV ejection fraction (LVEF) and emptying fractions (LAEF) were assessed using dedicated software packages. LA and LV myocardial deformations were assessed using 2D speckle-tracking echocardiography. OMR patients presented larger and more spherical MA than controls during the entire systole ( P < 0.001). Although the MA non-planarity at early-systole was similar between OMR and controls (157 ± 13° vs. 153 ± 12°, P = NS), the MA became flatter from mid- to end-systole (153 ± 12 vs. 146 ± 10° and 157 ± 12 vs. 147 ± 8°, P < 0.01) in OMR. MA area fractional change was lower in patients with OMR (22 ± 5% vs. 28 ± 5%, P < 0.001), and correlated with the MR orifice and volume ( r = −0.52 and r = −0.55). MA fractional area change correlated with LA minimum and maximum volumes ( r = 0.77 and r = 0.70), total and active LAEF ( r = 0.72 and r = 0.76), and LA negative strain and strain rate ( r = 0.52 and r = 0.57), but not with the LVEF or LV global longitudinal strain. In a multivariate regression model using LAEF and LVEF, solely active LAEF correlated with the MA fractional area change ( β = 0.51, P = 0.005). Conclusion In patients with OMR, MA reduced function correlates with the MR severity and the LA size and function, but not with the LV function.

Background Left ventricular hypertrophy (LVH) and geometry patterns vary in different hemodynamic profiles The concentric hypertrophy (CH) pattern has been proved to have the worst prognosis. Objectives The aim of the study was to test the hypothesis that carotid artery stiffness, as a marker of vascular damage, is associated with CH, independently of other potential determinants such as demographic factors (age, sex, BMI), clinical parameters (smoking, diabetes, creatinine level) and hemodynamic variables (blood pressure, pulse pressure [PP]). Material and methods The study involved 262 subjects (89 men): 202 patients with hypertension (153 untreated, 49 on medication), aged 55.7 ± 10 years, and 60 age-matched normal controls. The subjects were examined by echocardiography and carotid ultrasound with a high-resolution echo-tracking system. Based on the left ventricular mass index (LVMI) and relative wall thickness (RWT), the patients with hypertension were divided into four patterns of LVH and geometry: normal geometry (N, n = 57), concentric remodeling (CR, n = 48), concentric hypertrophy CH (n = 62) and eccentric hypertrophy (EH, n = 35). Intima-media thickness (IMT) and the parameters of arterial stiffness were also assessed using the β stiffness index (β), Young elastic modulus (Ep), arterial compliance (AC), one-point pulse wave velocity (PWVβ) and the wave reflection augmentation index (AI). Results Univariate analysis showed that the following variables are significant in determining CH: β > 8.4, Ep > 136 kPa, PWVβ > 7.1 m/s, AI > 21.9%, systolic BP > 151 mm Hg, PP > 54, IMT > 0.56 and the presence of diabetes. However, by multivariate analysis only AI (OR 3.65, p = 0.003), PWVβ > 7.1 m/s (OR 2.86, p = 0.014), systolic BP (OR 3.12, p = 0037) and the presence of diabetes (OR 3.75, p = 0.007) were associated independently with the occurrence of CH. Conclusions Concentric hypertrophy in hypertension is strongly associated with carotid arterial stiffness and wave reflection parameters, independently of the influence of systolic blood pressure and diabetes.

Heart failure is a systemic and multiorgan syndrome with metabolic failure as a fundamental mechanism. As a consequence of its impaired metabolism, other processes are activated in the failing heart, further exacerbating the progression of heart failure. Recent evidence suggests that modulating cardiac energy metabolism by reducing fatty acid oxidation and/or increasing glucose oxidation represents a promising approach to the treatment of patients with heart failure. Clinical trials have demonstrated that the adjunct of trimetazidine to the conventional medical therapy improves symptoms, cardiac function and prognosis in patients with heart failure without exerting negative hemodynamic effects. This review focuses on the rationale and clinical benefits of trimetazidine by acting on cardiac metabolism in heart failure, and aims to draw attention to the readiness of this agent to be included in all the major guidelines dealing with heart failure.

We investigated associations between self-reported tooth loss and cardiovascular outcomes in a global stable coronary heart disease cohort.We examined 15,456 patients from 39 countries with stable coronary heart disease (prior myocardial infarction, prior revascularisation or multivessel coronary heart disease) in the STABILITY trial. At baseline, patients reported number of teeth (26-32 (all), 20-25, 15-19, 1-14 and no teeth) and were followed for 3.7 years. Cox regression models adjusted for cardiovascular risk factors and socioeconomic status, determined associations between tooth loss level (26-32 teeth: lowest level; no teeth: highest level) and cardiovascular outcomes.After adjustment, every increase in tooth loss level was associated with an increased risk of the primary outcome, the composite of cardiovascular death, non-fatal myocardial infarction and non-fatal stroke (hazard ratio 1.06; 95% confidence interval 1.02-1.10), cardiovascular death (1.17; 1.10-1.24), all-cause death (1.16; 1.11-1.22) and non-fatal or fatal stroke (1.14; 1.04-1.24), but not with non-fatal or fatal myocardial infarction (0.99; 0.94-1.05). Having no teeth, compared to 26-32 teeth, entailed a significantly higher risk of the primary outcome (1.27 (1.08, 1.49)), cardiovascular death (1.85 (1.45, 2.37), all-cause death (1.81 (1.50, 2.20)) and stroke (1.67 (1.15, 2.39)).In this large global cohort of patients with coronary heart disease, self-reported tooth loss predicted adverse cardiovascular outcomes and all-cause death independent of cardiovascular risk factors and socioeconomic status.

Background Covert vascular disease of the brain manifests as infarcts, white matter hyperintensities, and microbleeds on MRI. Their cumulative effect is often a decline in cognition, motor impairment, and psychiatric disorders. Preventive therapies for covert brain ischemia have not been established but represent a huge unmet clinical need. Aims The MRI substudy examines the effects of the antithrombotic regimens in COMPASS on incident covert brain infarcts (the primary outcome), white matter hyperintensities, and cognitive and functional status in a sample of consenting COMPASS participants without contraindications to MRI. Methods COMPASS is a randomized superiority trial testing rivaroxaban 2.5 mg bid plus acetylsalicylic acid 100 mg and rivaroxaban 5 mg bid against acetylsalicylic acid 100 mg per day for the combined endpoint of MI, stroke, and cardiovascular death in individuals with stable coronary artery disease or peripheral artery disease. T1-weighted, T2-weighted, T2*-weighted, and FLAIR images were obtained close to randomization and near the termination of assigned antithrombotic therapy; biomarker and genetic samples at randomization and one month, and cognitive and functional assessment at randomization, after two years and at the end of study. Results Between March 2013 and May 2016, 1905 participants were recruited from 86 centers in 16 countries. Of these participants, 1760 underwent baseline MRI scans that were deemed technically adequate for interpretation. The mean age at entry of participants with interpretable MRI was 71 years and 23.5% were women. Coronary artery disease was present in 90.4% and 28.1% had peripheral artery disease. Brain infarcts were present in 34.8%, 29.3% had cerebral microbleeds, and 93.0% had white matter hyperintensities. The median Montreal Cognitive Assessment score was 26 (interquartile range 23–28). Conclusions The COMPASS MRI substudy will examine the effect of the antithrombotic interventions on MRI-determined covert brain infarcts and cognition. Demonstration of a therapeutic effect of the antithrombotic regimens on brain infarcts would have implications for prevention of cognitive decline and provide insight into the pathogenesis of vascular cognitive decline.

WOS: 000438926500008, PubMed ID: 29980595, BACKGROUND: To describe the baseline characteristics of patients with heart failure and preserved left ventricular ejection fraction enrolled in the PARAGON-HF trial (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin Receptor Blocker Global Outcomes in HFpEF) comparing sacubitril/valsartan to valsartan in reducing morbidity and mortality. METHODS AND RESULTS: We report key demographic, clinical, and laboratory findings, and baseline therapies, of 4822 patients randomized in PARAGON-HF, grouped by factors that influence criteria for study inclusion. We further compared baseline characteristics of patients enrolled in PARAGON-HF with those patients enrolled in other recent trials of heart failure with preserved ejection fraction (HFpEF). Among patients enrolled from various regions (16% Asia-Pacific, 37% Central Europe, 7% Latin America, 12% North America, 28% Western Europe), the mean age of patients enrolled in PARAGON-HF was 72.7 +/- 8.4 years, 52% of patients were female, and mean left ventricular ejection fraction was 57.5%, similar to other trials of HFpEF. Most patients were in New York Heart Association class II, and 38% had >= 1 hospitalizations for heart failure within the previous 9 months. Diabetes mellitus (43%) and chronic kidney disease (47%) were more prevalent than in previous trials of HFpEF. Many patients were prescribed angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (85%), beta-blockers (80%), calcium channel blockers (36%), and mineralocorticoid receptor antagonists (24%). As specified in the protocol, virtually all patients were on diuretics, had elevated plasma concentrations of N-terminal pro-B-type natriuretic peptide (median, 911 pg/mL; interquartile range, 464-1610), and structural heart disease. CONCLUSIONS: PARAGON-HF represents a contemporary group of patients with HFpEF with similar age and sex distribution compared with prior HFpEF trials but higher prevalence of comorbidities. These findings provide insights into the impact of inclusion criteria on, and regional variation in, HFpEF patient characteristics., Novartis, The PARAGON-HF trial is funded by Novartis.

Carney complex (CNC) is a rare autosomal dominant syndrome. Spotty skin pigmentation is the major clinical manifestation of CNC, followed by cardiac myxomas, benign tumors that usually present with features from the classical triad of obstructive cardiac, embolic and non-specific constitutional symptoms (NCS). NCS are caused by the overproduction of interleukin-6 (IL-6), a pro-inflammatory cytokine which mediates the induction of intercellular adhesion molecule 1 (ICAM-1) and promotes endothelial dysfunction and atherosclerosis. Thus, myxomas may be directly linked to an increased risk of atherosclerotic events. We report here a case of a 74-year-old woman with left atrial myxoma, skin pigmentary abnormalities, thyroid disorder and extensive atherosclerosis, with non-embolic occlusion of infrarenal abdominal aorta.

Patients with atrial fibrillation (AF) often have multi-morbidity, defined as ≥3 comorbid conditions. Multi-morbidity is associated with polypharmacy, adverse events, and frailty potentially altering response to anticoagulation. We sought to describe the prevalence of multi-morbidity among older patients with AF and determine the association between multi-morbidity, clinical outcomes, and the efficacy and safety of apixaban compared with warfarin.In this post-hoc subgroup analysis of the ARISTOTLE trial, we studied enrolled patients age ≥ 55 years (n = 16,800). Patients were categorized by the number of comorbid conditions at baseline: no multi-morbidity (0-2 comorbid conditions), moderate multi-morbidity (3-5 comorbid conditions), and high multi-morbidity (≥6 comorbid conditions). Association between multi-morbidity and clinical outcomes were analyzed by treatment with a median follow-up of 1.8 (1.3-2.3) years.Multi-morbidity was present in 64% (n = 10,713) of patients; 51% (n = 8491) had moderate multi-morbidity, 13% (n = 2222) had high multi-morbidity, and 36% (n = 6087) had no multi-morbidity. Compared with the no multi-morbidity group, the high multi-morbidity group was older (74 vs 69 years), took twice as many medications (10 vs 5), and had higher CHAMulti-morbidity is prevalent among the population with AF; efficacy and safety of apixaban is preserved in this subgroup supporting extension of trial results to the most complex AF patients.

International audience; Aims - To obtain the normal ranges for echocardiographic measurements of left atrial (LA) function from a large group of healthy volunteers accounting for age and gender. Methods and results - A total of 371 (median age 45 years) healthy subjects were enrolled at 22 collaborating institutions collaborating in the Normal Reference Ranges for Echocardiography (NORRE) study of the European Association of Cardiovascular Imaging (EACVI). Left atrial data sets were analysed with a vendor-independent software (VIS) package allowing homogeneous measurements irrespective of the echocardiographic equipment used to acquire data sets. The lowest expected values of LA function were 26.1%, 48.7%, and 41.4% for left atrial strain (LAS), 2D left atrial emptying fraction (LAEF), and 3D LAEF (reservoir function); 7.7%, 24.2%, and -0.53/s for LAS-active, LAEF-active, and LA strain rate during LA contraction (SRa) (pump function) and 12.0% and 21.6% for LAS-passive and LAEF-passive (conduit function). Left atrial reservoir and conduit function were decreased with age while pump function was increased. All indices of reservoir function and all LA strains had no difference in both gender and vendor. However, inter-vendor differences were observed in LA SRa despite the use of VIS. Conclusion - The NORRE study provides contemporary, applicable echocardiographic reference ranges for LA function. Our data highlight the importance of age-specific reference values for LA functions.

Supplemental material 1 for Rationale, design, and baseline participant characteristics in the MRI and cognitive substudy of the cardiovascular outcomes for people using anticoagulation strategies trial by Mukul Sharma, Robert G Hart, Eric E Smith, Jackie Bosch, Fei Yuan, Amparo Casanova, John W Eikelboom, Stuart J Connolly, Gloria Wong, Rafael Diaz, Patricio Lopez-Jaramillo, Georg Ertl, Stefan Störk, Gilles R Dagenais, Eva M Lonn, Lars Ryden, Andrew M Tonkin, John D Varigos, Deepak L Bhatt, Kelley RH Branch, Jeffrey L Probstfield, Jae-Hyung Kim, Jong-Won Ha, Martin O’Donnell, Dragos Vinereanu, Keith AA Fox, Yan Liang, Lisheng Liu, Jun Zhu, Nana Pogosova, Aldo P Maggioni, Alvaro Avezum, Leopoldo S Piegas, Katalin Keltai, Matyas Keltai, Nancy Cook Bruns, Scott Berkowitz and Salim Yusuf in International Journal of Stroke

Supplemental material 2 for Rationale, design, and baseline participant characteristics in the MRI and cognitive substudy of the cardiovascular outcomes for people using anticoagulation strategies trial by Mukul Sharma, Robert G Hart, Eric E Smith, Jackie Bosch, Fei Yuan, Amparo Casanova, John W Eikelboom, Stuart J Connolly, Gloria Wong, Rafael Diaz, Patricio Lopez-Jaramillo, Georg Ertl, Stefan Störk, Gilles R Dagenais, Eva M Lonn, Lars Ryden, Andrew M Tonkin, John D Varigos, Deepak L Bhatt, Kelley RH Branch, Jeffrey L Probstfield, Jae-Hyung Kim, Jong-Won Ha, Martin O’Donnell, Dragos Vinereanu, Keith AA Fox, Yan Liang, Lisheng Liu, Jun Zhu, Nana Pogosova, Aldo P Maggioni, Alvaro Avezum, Leopoldo S Piegas, Katalin Keltai, Matyas Keltai, Nancy Cook Bruns, Scott Berkowitz and Salim Yusuf in International Journal of Stroke

Zofenopril is a lipophilic, sulfhydryl group-containing angiotensin-converting enzyme (ACE)-inhibitor, characterized by wide tissue distribution, long duration of action, and pleiotropic effects on endothelial dysfunction. Its clinical efficacy and safety have been described in the four randomized controlled trials of the SMILE program, which globally enrolled more than 3600 patients in post-acute myocardial infarction (AMI) setting. The SMILE-4 study specifically selected patients with left ventricular dysfunction at admission, and compared the effects of zofenopril or ramipril in combination with acetylsalicylic acid (ASA). Zofenopril demonstrated its superiority over ramipril in reducing the combined occurrence of death or hospitalization for cardiovascular causes both in the overall population included in the original study and in subgroups of patients at highest risk, namely hypertensive and diabetic subjects. The effects of the early treatment with zofenopril were sustained over time, and, after 5 years of follow-up, zofenopril increased the survival likelihood and reduced the hospitalization rate. Compared to ramipril, zofenopril was cost-effective with a number to treat of 13 and an incremental cost-effectiveness ratio (ICER) of 2125.45 euros for any additional event prevented. Furthermore, in real-world settings, zofenopril decreased the risk of death in patients with heart failure, particularly in men, and in subjects older than 76 years or with ejection fraction lower than 54%. These results support the early use of zofenopril immediately after AMI, even in the presence of comorbidities, and its maintenance over time to reduce the risk of heart failure. Funding: Menarini International Operations Luxembourg S.A.

BACKGROUND: Coronary artery disease is a major cause of morbidity and mortality worldwide, and is a consequence of acute thrombotic events involving activation of platelets and coagulation proteins. Factor Xa inhibitors and aspirin each reduce thrombotic events but have not yet been tested in combination or against each other in patients with stable coronary artery disease.METHODS: In this multicentre, double-blind, randomised, placebo-controlled, outpatient trial, patients with stable coronary artery disease or peripheral artery disease were recruited at 602 hospitals, clinics, or community centres in 33 countries. This paper reports on patients with coronary artery disease. Eligible patients with coronary artery disease had to have had a myocardial infarction in the past 20 years, multi-vessel coronary artery disease, history of stable or unstable angina, previous multi-vessel percutaneous coronary intervention, or previous multi-vessel coronary artery bypass graft surgery. After a 30-day run in period, patients were randomly assigned (1:1:1) to receive rivaroxaban (2·5 mg orally twice a day) plus aspirin (100 mg once a day), rivaroxaban alone (5 mg orally twice a day), or aspirin alone (100 mg orally once a day). Randomisation was computer generated. Each treatment group was double dummy, and the patients, investigators, and central study staff were masked to treatment allocation. The primary outcome of the COMPASS trial was the occurrence of myocardial infarction, stroke, or cardiovascular death. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants.FINDINGS: Between March 12, 2013, and May 10, 2016, 27 395 patients were enrolled to the COMPASS trial, of whom 24 824 patients had stable coronary artery disease from 558 centres. The combination of rivaroxaban plus aspirin reduced the primary outcome more than aspirin alone (347 [4%] of 8313 vs 460 [6%] of 8261; hazard ratio [HR] 0·74, 95% CI 0·65-0·86, pINTERPRETATION: In patients with stable coronary artery disease, addition of rivaroxaban to aspirin lowered major vascular events, but increased major bleeding. There was no significant increase in intracranial bleeding or other critical organ bleeding. There was also a significant net benefit in favour of rivaroxaban plus aspirin and deaths were reduced by 23%. Thus, addition of rivaroxaban to aspirin has the potential to substantially reduce morbidity and mortality from coronary artery disease worldwide.FUNDING: Bayer AG.

Statins are the most common drugs administered for patients with cardiovascular disease. However, due to statin-associated muscle symptoms, adherence to statin therapy is challenging in clinical practice. Certain nutraceuticals, such as red yeast rice, bergamot, berberine, artichoke, soluble fiber, and plant sterols and stanols alone or in combination with each other, as well as with ezetimibe, might be considered as an alternative or add-on therapy to statins, although there is still insufficient evidence available with respect to long-term safety and effectiveness on cardiovascular disease prevention and treatment. These nutraceuticals could exert significant lipid-lowering activity and might present multiple non–lipid-lowering actions, including improvement of endothelial dysfunction and arterial stiffness, as well as anti-inflammatory and antioxidative properties. The aim of this expert opinion paper is to provide the first attempt at recommendation on the management of statin intolerance through the use of nutraceuticals with particular attention on those with effective low-density lipoprotein cholesterol reduction.

Aortic diseases can become life-threatening conditions; therefore accurate imaging of the aorta has a major importance in clinical practice. Despite the advances represented by the most recently introduced techniques, such as computed tomography and magnetic resonance, echography remains essential for the detection of the aortic pathology and follow-up. It is rapid, cost-efficient, and with good accuracy. Meanwhile, it avoids irradiation and nephrotoxicity. Echography is mandatory for choosing and monitoring surgical or endovascular treatment, as well as for rapid detection of periprocedural complications. This chapter will focus on the role of echography for the assessment of aorta in normal and various pathological settings.

Aim & Methods One critical factor enhancing the implementation of successful diagnostic and therapeutic strategies into clinical practice is awareness among the lay public. We describe awareness in a contemporary, multinational convenience sample of subjects attending the Heart Failure Awareness (HFA) Day Initiatives in 2013. Results We analysed 2,438 subjects (Germany 33%, Lithuania 42%, Romania 8%, Slovenia 17%) : 53% were female, 58% were aged >60 years, 11% (had) worked in the medical sector, 82% heard about HF before. Shortness of breath and tiredness were correctly identified as symptoms of heart failure in 71% and 61%, but only 52% recognized swelling of feet and legs as a clinical sign; 31% considered heart failure a normal symptom of old age, and only 38% realized the particularly poor prognosis after a heart failure related hospitalization. Subjects who had heard about heart failure before had a lower prevalence of common misbeliefs about HF. Conclusion In subjects participating in the HFA Day initiative 2013, the level of awareness was unsatisfactory, and important misconceptions remain. The educational and awareness activities for both the population at large and also for decision makers should be broadened and intensified.

Growth hormone deficiency (GHD) in adults is associated with increased cardiovascular events, but detailed assessment of cardiac and vascular function is lacking. Thus we assessed cardiac, arterial, and endothelial functions, using conventional and speckle-tracking echocardiography, in adults with GHD compared with controls with similar cardiovascular risk.Fifty-two patients with GHD (47 ± 16 years; 34 men) and no cardiovascular disease or diabetes were enrolled prospectively and compared with 50 age- and sex-matched controls. Comprehensive echocardiography was performed in all participants. Regional left ventricular (LV) function was assessed from global longitudinal strain (GLS), global radial strain (GRS), and global circumferential strain (GCS), whereas LV torsion (LVtor) was calculated from basal (RotB) and apical (RotA) rotations. Arterial function was assessed from intima-media thickening, local wave speed, and beta index of stiffness, whereas endothelial function was assessed from flow-mediated dilation. Levels of pro-brain natriuretic peptide (proBNP) were measured.GLS and GCS were decreased more in patients with GHD than in controls (-17.2% ± 2.7% vs. -19.3% ± 3.3% and -15.9% ± 5.4% vs. -18.8% ± 3.5%; both P0.01), whereas GRS was similar. RotB and LVtor were also decreased in patients with GHD (-4.8° ± 2.6° vs. -6.2° ± 2.1°/cm and 1.8° ± 0.6° vs. 2.3° ± 1.1°/cm; both P0.05). ProBNP was increased in patients with GHD (61.0 ± 74 pg/dL vs. 24.7 ± 21 pg/dL; P = 0.002). Arterial and endothelial functions were similar between groups.In conclusion, adults with GHD had LV longitudinal dysfunction and increased proBNP levels compared with controls, suggesting intrinsic myocardial disease. Further studies are needed to assess if this cardiac impairment in adults with GHD is reversible after GH replacement.

Clinical outcomes and the effects of oral anticoagulants among patients with acute coronary syndrome (ACS) and either a history of or acute heart failure (HF) are largely unknown. We aimed to assess the relationship between prior HF or acute HF complicating an index ACS event and subsequent clinical outcomes and the efficacy and safety of apixaban compared with placebo in these populations.High-risk patients were randomly assigned post-ACS to apixaban 5.0 mg or placebo twice daily. Median follow-up was 8 (4-12) months. The primary outcome was cardiovascular death, myocardial infarction, or stroke. The main safety outcome was thrombolysis in myocardial infarction major bleeding.Heart failure was reported in 2,995 patients (41%), either as prior HF (2,076 [28%]) or acute HF (2,028 [27%]). Patients with HF had a very high baseline risk and were more often managed medically. Heart failure was associated with a higher rate of the primary outcome (prior HF: adjusted hazard ratio [HR] 1.73, 95% CI 1.42-2.10, P.0001, acute HF: adjusted HR 1.65, 95% CI 1.35-2.01, P.0001) and cardiovascular death (prior HF: HR 2.54, 95% CI 1.82-3.54, acute HF: adjusted HR 2.52, 95% CI 1.82-3.50). Patients with acute HF also had significantly higher rates of thrombolysis in myocardial infarction major bleeding (prior HF: adjusted HR 1.22, 95% CI 0.65-2.27, P = .54, acute HF: adjusted HR 1.78, 95% CI 1.03-3.08, P = .04). There was no statistical evidence of a differential effect of apixaban on clinical events or bleeding in patients with or without prior HF; however, among patients with acute HF, there were numerically fewer events with apixaban than placebo (14.8 vs 19.3, HR 0.76, 95% CI 0.57-1.01, interaction P = .13), a trend that was not seen in patients with prior HF or no HF.In high-risk patients post-ACS, both prior and acute HFs are associated with an increased risk of subsequent clinical events. Apixaban did not significantly reduce clinical events and increased bleeding in patients with and without HF; however, there was a tendency toward fewer clinical events with apixaban in patients with acute HF.

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Background Greater understanding of differences between men and women with coronary heart disease is needed. Methods and Results In this post hoc analysis of the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) trial, we described psychosocial factors, treatments, and outcomes of men versus women with stable coronary heart disease and explored the association of sex with psychosocial characteristics and cardiovascular risk. Cox proportional hazards models were used to assess the relationship between sex and outcomes. Interactions among sex, psychosocial factors, and the composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke were tested. Of 15 828 patients, 2967 (19%) were women. Among women, 21.2% felt often or always stressed at home (versus 9.8% of men), and 19.2% felt often or always sad or depressed (versus 10.1% of men; all P P =0.03) such that the lower risk in women varied by depressive symptom frequency, whereby women who were more depressed had a risk similar to men. Conclusions Female sex was independently associated with better long‐term clinical outcomes, although this was modified by frequency of depressive symptoms. This suggests that emotional state may be an important target for improving outcomes in patients with coronary heart disease, specifically in women. Clinical Trial Registration STABILITY ClinicalTrials.gov number (NCT00799903).

Rheumatoid arthritis (RA) causes frequently cardiovascular complications, probably determined by early atherosclerosis in connection to chronic systemic inflammation. Purpose of our study was to assess subclinical cardiac and vascular dysfunction, and to evaluate the mechanisms of ventriculo-arterial interaction, in patients with correctly treated RA vs. normal subjects.We evaluated 46 subjects (55±10 years, 2 men): 29 patients with seropositive treated RA (mean duration of 11±9 years), without documented cardiovascular or pulmonary disease, and 17 control subjects, matched for age, sex, and distribution of conventional major risk factors. All RA patients were under long-term treatment (more than 6 months) with Methotrexat + Sulfasalasine (22 patients) or Methotrexat + Sulfasalasine + Infliximab (7 patients). We determined biomarkers of inflammation (P-selectin, interleukines 1, 6, 10, 18, seric amiloid A, á-TNF, ã-interferon, C-reactive protein, anti-oxidated LDL antibodies), myocardial fibrosis (â-crosslaps) and ventricular overload (BNP). We assessed the parameters of cardiac function by standard and tissue Doppler echocardiography, intima-media thickness and arterial stiffness by "e-tracking" and "wave intensity analysis" (at the level of the right carotid artery), endothelial function by flow mediated dilation (FMD), and carotid-femoral pulse wave velocity by the Complior method.Biological parameters of inflammation, markers of myocardial fibrosis and of ventricular overload were not different between the 2 study groups. Also, parameters of subclinical cardiac and vascular function were similar between the two groups. RA patients had subclinical RV dysfunction, correlated to the duration of the disease. They also tended to have higher values of systolic pulmonary artery pressure than normals.Correctly treated patients with RA, with controlled systemic inflammation, have normal LV, endothelial and arterial function. However, in the absence of documented pulmonary disease, they do have subclinical RV dysfunction, correlated with the duration of disease. This suggests an intrinsic RV myocardial involvement but, since pulmonary artery pressure was also higher, a secondary mechanism might be also involved.

Cardiovascular diseases, particularly myocardial infarction, remain the leading cause of morbidity and mortality worldwide, even though pharmacological and interventional therapies improved significantly in the last years. Moreover, despite encouraging results of cell - based therapies in experimental myocardial infarction models, clinical trials showed inconsistent and modest efficiency. Therefore the next step should be the revealing of a new cell type, capable of regenerating the damaged myocardium. Telocytes (TCs), a relatively new type of interstitial cells, were described few years ago and are credited with important roles in regenerative therapies. In this paper we review their most important characteristics and functions, showing the evidences of their potential role in cardiac repair and regeneration. Our research leads to the conclusion that TCs might be a novel target for therapeutic strategies in myocardial infarction.

The occurrence of left ventricular free wall rupture in acute myocardial infarction decreased with the extent of interventional procedures of reperfusion, but it is still encountered in 1-2% of these patients. We are presenting the case of a 58 years old male with left ventricular free wall rupture occurred as a late complication of an inferior-lateral ST-elevated myocardial infarction. The aim of this case report is to underline the main clinical features, the diagnostic value of the echocardiographic exam and the importance of early surgical intervention in a rare, but very dangerous condition, with persistent high mortality rates. In this context, we will review the current prevalence, clinical forms and prediction factors of left ventricular free wall rupture.

International audience; Aims - To obtain the normal ranges for 2D echocardiographic (2DE) measurements of left ventricular (LV) strain from a large group of healthy volunteers accounting for age and gender. Methods and results - A total of 549 (mean age: 45.6 ± 13.3 years) healthy subjects were enrolled at 22 collaborating institutions of the Normal Reference Ranges for Echocardiography (NORRE) study. 2DE data sets have been analysed with a vendor-independent software package allowing homogeneous measurements irrespective of the echocardiographic equipment used to acquire the data sets. The lowest expected values of LV strains and twist calculated as ± 1.96 standard deviations from the mean were -16.7% in men and -17.8% in women for longitudinal strain, -22.3% and -23.6% for circumferential strain, 20.6% and 21.5% for radial strain, and 2.2 degrees and 1.9 degrees for twist, respectively. In multivariable analysis, longitudinal strain decreased with age whereas the opposite occurred with circumferential and radial strain. Male gender was associated with lower strain for longitudinal, circumferential, and radial strain. Inter-vendor differences were observed for circumferential and radial strain despite the use of vendor-independent software. Importantly, no intervendor differences were noted in longitudinal strain. Conclusion - The NORRE study provides contemporary, applicable 2D echocardiographic reference ranges for LV longitudinal, radial, and circumferential strain. Our data highlight the importance of age- and gender-specific reference values for LV strain.

Women with stable coronary artery disease have better clinical outcomes than men, but this association is modified by degree of depression : insights from the STABILITY trial

1.1. Cardiovascular disease and dyslipidemia: prevalence and global economic impact Cardiovascular diseases (CVDs) are the leading cause of mortality worldwide, reaching 31% of deaths in 2012 [1]. In particular, atherosclerosis and ischemic heart disease (IHD) are the main causes of premature death in Europe and are responsible for 42% of deaths in women and 38% in men under 75 years old [2]. The global economic impact of CVD is estimated to have been US $906 billion in 2015 and is expected to rise by 22% by 2030 [3]. Cardiovascular diseases also represent the major cause of disability in developed countries. It has been estimated that their growing burden could lead to a global increase in loss of disability-adjusted life years (DALYs), from a loss of 85 million DALYs in 1990 to a loss of ~150 million DALYs in 2020, becoming a major non-psychological cause of lost productivity [4]. Several risk factors contribute to the etiology and development of CVD; they are divided into those modifiable through lifestyle changes or by taking a pharmacologic treatment (e.g. for hypertension, smoking, diabetes mellitus, hypercholesterolemia) and those that are not modifiable (age, male gender, and family history) [5]. Elevated total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) blood concentrations are the major modifiable risk factors for coronary heart disease (CHD), whereas high concentrations of plasma high-density lipoprotein cholesterol (HDL-C) in certain conditions are considered protective [6]. Moreover, LDL-C remains a fundamental CV risk factor (and a main target of therapy) even when statins are largely used in the general population [7]. An examination of the data of 18 053 participants aged ≥ 20 years who participated in the National Health and Nutrition Examination Surveys (NHANES) from 1999 to 2006 showed that the unadjusted prevalence of hypercholesterolemia ranged from 53.2% to 56.1% in United States adults [8]. Differences related to gender and race or ethnicity were observed; in particular, a lower rate of control was found among women than men and lower rates of having a cholesterol check and being told about hypercholesterolemia were reported by African Americans and Mexican Americans than whites [8]. A recent report from the American Heart Association confirmed that in the US only 75.7% of children and 46.6% of adults present targeted TC levels (TC < 170 mg/dl for children and < 200 mg/dl for adults, in untreated individuals) [9]. The pattern is similar in other Western countries [10, 11].

Summary Background Oral anticoagulation is underused in patients with atrial fibrillation. We assessed the impact of a multifaceted educational intervention, versus usual care, on oral anticoagulant use in patients with atrial fibrillation. Methods This study was a two-arm, prospective, international, cluster-randomised, controlled trial. Patients were included who had atrial fibrillation and an indication for oral anticoagulation. Clusters were randomised (1:1) to receive a quality improvement educational intervention (intervention group) or usual care (control group). Randomisation was carried out centrally, using the eClinicalOS electronic data capture system. The intervention involved education of providers and patients, with regular monitoring and feedback. The primary outcome was the change in the proportion of patients treated with oral anticoagulants from baseline assessment to evaluation at 1 year. The trial is registered at ClinicalTrials.gov, number NCT02082548. Findings 2281 patients from five countries (Argentina, n=343; Brazil, n=360; China, n=586; India, n=493; and Romania, n=499) were enrolled from 48 clusters between June 11, 2014, and Nov 13, 2016. Follow-up was at a median of 12·0 months (IQR 11·8–12·2). Oral anticoagulant use increased in the intervention group from 68% (804 of 1184 patients) at baseline to 80% (943 of 1184 patients) at 1 year (difference 12%), whereas in the control group it increased from 64% (703 of 1092 patients) at baseline to 67% (732 of 1092 patients) at 1 year (difference 3%). Absolute difference in the change between groups was 9·1% (95% CI 3·8–14·4); odds ratio of change in the use of oral anticoagulation between groups was 3·28 (95% CI 1·67–6·44; adjusted p value=0·0002). Kaplan-Meier estimates showed a reduction in the secondary outcome of stroke in the intervention versus control groups (HR 0·48, 95% CI 0·23–0·99; log-rank p value=0·0434). Interpretation A multifaceted and multilevel educational intervention, aimed to improve use of oral anticoagulation in patients with atrial fibrillation and at risk for stroke, resulted in a significant increase in the proportion of patients treated with oral anticoagulants. Such an intervention has the potential to improve stroke prevention around the world for patients with atrial fibrillation. Funding Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, and Pfizer.

Multiple sclerosis (MS), neurologic disease affecting young population, may cause cardiovascular dysfunction, due to autonomous nervous dysfunction, physical invalidity, increased oxidative stress, and systemic inflammatory status. However, cardiovascular function is rarely evaluated in these patients. We assessed left and right ventricular (LV and RV) function by 2D, 3D, tissue Doppler, and speckle tracking echocardiography, and vascular function by remodeling, stiffness, and endothelial dysfunction parameters in patients with MS, compared to control subjects. 103 subjects (35 ± 10 years,70 women) were studied: 67 patients with MS and 36 control subjects. Patients with MS had decreased LV systolic function, confirmed by lower 2D and 3D ejection fraction, mitral annular plane systolic excursion, longitudinal myocardial systolic velocities, and 2D and 3D global longitudinal strain. The RV function was also decreased, as demonstrated by lower fractional area change, tricuspid annular plane systolic excursion, longitudinal systolic velocities, and longitudinal strain. Additionally, LV diastolic and left atrial (LA) function were decreased compared to controls. The parameters of arterial and endothelial function were similar between groups. Patients with MS have impaired biventricular function by comparison with normal subjects, with reduced LA function, but normal arterial and endothelial function. The noninvasive echocardiographic techniques might help to determine patients with MS at risk of developing cardiovascular dysfunction.

Purpose We assessed outcomes among anticoagulated patients with atrial fibrillation and a history of falling, and whether the benefits of apixaban vs warfarin are consistent in this population. Methods Of the 18,201 patients in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) study, 16,491 had information about history of falling–753 with history of falling and 15,738 without history of falling. The primary efficacy outcome was stroke or systemic embolism; the primary safety outcome was major bleeding. Results When compared with patients without a history of falling, patients with a history of falling were older, more likely to be female and to have dementia, cerebrovascular disease, depression, diabetes, heart failure, osteoporosis, fractures, and higher CHA 2 DS 2 -VASc (Congestive heart failure, Hypertension, Age ≥75 years, Diabetes mellitus, prior Stroke or TIA or thromboembolism, Vascular disease, Age 65-74 years, Sex category female) and HAS-BLED (Hypertension, Abnormal renal and liver function, Stroke, Bleeding, Labile international normalized ratio, Elderly, Drugs or alcohol) scores. Patients with a history of falling had higher rates of major bleeding (adjusted hazard ratio [HR] 1.39; 95% confidence interval [CI], 1.05-1.84; P = .020), including intracranial bleeding (adjusted HR 1.87; 95% CI, 1.02-3.43; P = .044) and death (adjusted HR 1.70; 95% CI, 1.36-2.14; P Conclusions Patients with atrial fibrillation and a history of falling receiving anticoagulation have a higher risk of major bleeding, including intracranial, and death. The efficacy and safety of apixaban compared with warfarin were consistent, irrespective of history of falling.

ST-segment elevation myocardial infarction (STEMI) remains a leading cause of morbidity and mortality worldwide. Primary percutaneous coronary intervention (pPCI) is the preferred therapy for STEMI if it is done within 120 min from the first medical contact, by an experienced team in a high-volume center. The aim of this study was to assess the clinical characteristics and predictors of in-hospital mortality of patients with STEMI treated by percutaneous coronary interventions (PCIs).We analyzed data from 15,076 STEMI patients enrolled in the RO-STEMI registry (ROmanian ST-Elevation Myocardial Infarction registry). Patients were divided into 2 groups: PCI (11.669; 77%) and conservative treated (3.407; 23%). PCI group includes both pPCI treated patients (84.3%), and patients undergoing rescue PCI (6.4%) and late PCI (9.3%).The mean age of STEMI patients was 62.7+/-12.7 years. 70% were males. Patients treated by PCI were younger (61.4+/-12.2 versus 67.2+/-13.3, p0.0001) and more often men (80% versus 71%, p0.0001). They were less likely to have acute heart failure (Killip class II-IV) at admission (p0.0001). During admission, patients treated by PCI received more often dual antiplatelet therapy (97.6% versus 90.8%, p0.0001), statins (96.3% versus 87.5%, p0.0001), beta-blockers (83.8% versus 73.2%, p0.0001), and RAAS blockers (82.6% versus 66.4%, p0.0001). Overall in-hospital mortality was 7.1%: 4.1% in the PCI group and 15.7% in the conservative treated group. Multivariate analysis showed that, after adjusting for all clinical variables, Killip class II-IV at admission (OR: 9.2; 95%CI: 6.2-13.6; p0.0001), LVEF35% (OR: 3.8; 95%CI: 2.6-5.4; p0.0001), age older than 65 years (OR: 2.2; 95%CI: 1.5-3.2; p0.0001), and anterior location of myocardial infarction (OR: 2.1; 95% CI: 1.5-3; p0.0001) remained independent predictors for in-hospital mortality for STEMI patients treated interventionally.Advanced Killip class, depressed LVEF, advanced age, and anterior location were the most powerful independent predictors of in-hospital mortality in STEMI patients who underwent interventional treatment.

Multiple sclerosis (MS) is a chronic neurological condition, characterized by recurrent episodes of inflammation and demyelination of the central nervous system called relapsing-remitting episodes, and continuous axonal degeneration that leads to irreversible progressive invalidity. Patients with multiple sclerosis present a higher mortality rate compared to the general population, and the excess of mortality may be explained by the increased cardiovascular risk and occurrence of cardiovascular disease. However, the exact pathways to cardiovascular dysfunction are not yet completely elucidated. This review focuses on the most important mechanisms of cardiovascular dysfunction in MS, such as the cardiomyocite structure alteration, the cardiovascular autonomous nervous system dysfunction, physical invalidity, oxidative stress and endothelial dysfunction, as well as the impact of cardiovascular risk factors in MS. The latest evidence about therapeutic approaches for MS, such as immunomodulatory treatment, vitamin D supplementation and statins are also discussed. There is little knowledge about the cardiovascular dysfunction in MS, and further research is required to improve the understanding of these complex mechanisms.