Asymptomatic LV Dysfunction and Heart Failure: Neurohumeral and metabolic aspects of Pharmacological intervention

Heart failure is a clinical syndrome, which develops as a result of impaired function of the heart. The response of the body to impaired cardiac function includes cardiac and extra cardiac factors, like cardiac remodeling, structural and functional changes in peripheral skeletal muscle and neurohumoral activation. The latter involves increased levels of catecholamines, activation of the renin-angiotensin system, release of ANP, aldosterone and vasopressin and plays a central role in regulating constriction of the peripheral circulation and causes structural and functional changes in the vascular waH, modulation of water and salt retention and sympathetic tone, thus influencing hemodynamic changes. The activated neurohonnones have both vasodilating and vasoconstrictive action and growth modulating and promoting actions

Abluminal biodegradable polymer biolimus-eluting versus durable polymer everolimus-eluting stent in patients with diabetes mellitus 5 years follow-up from the COMPARE II trial

_Background:_ Drug eluting stents with biodegradable polymers have been developed to address the risk of very late adverse events. Long-term comparison data between the biodegradable polymer-coated biolimus-eluting stent (BES; Nobori®) and the second-generation durable polymer-coated everolimus-eluting stent (EES; XIENCE V® or XIENCE PRIME® or PROMUS™) in diabetic patients are scarce. _Methods:_ The COMPARE II trial was an investigator-initiated, multicenter, open-label, randomized, all-comers trial which assigned patients undergoing percutaneous coronary intervention (PCI) in a 2:1 fashion to either BES or EES.We analyzed the safety and efficacy outcomes in diabetic patients at 5 year follow-up. The primary pre-specified composite endpoint major adverse cardiac event (MACE) was defined as cardiac death, non-fatal target-vessel myocardial infarction (TV-MI), or clinically indicated target vessel revascularization (CD-TVR). _Results:_ Out of 2707 study patients, 588 were diabetics of whom 391 were treated with BES and 197 with EES. At 5 years follow-up, MACE occurred in 87 patients in the BES group and in 34 patients in the EES group. Other safety and efficacy endpoints did not differ between stent groups. _Conclusions:_ At 5 years follow-up, no differences in terms of MACE as well as all analyzed safety and efficacy measures, including stent thrombosis, between the biodegradable polymer-coated BES and the durable polymercoated EES in diabetic patients were observe

Conventional hemodynamic resuscitation may fail to optimize tissue perfusion: An observational study on the effects of dobutamine, enoximone, and norepinephrine in patients with acute myocardial infarction complicated by cardiogenic shock

Aim: To investigate the effects of inotropic agents on parameters of tissue perfusion in patients with cardiogenic shock. Methods and Results: Thirty patients with cardiogenic shock were included. Patients received dobutamine, enoximone, or norepinephrine. We performed hemodynamic measurements at baseline and after titration of the inotropic agent until cardiac index (CI) ≥2.5 L.min-1.m-2 or mixed-venous oxygen saturation (SvO 2) ≥70% (dobutamine or enoximone), and mean arterial pressure (MAP) ≥70 mmHg (norepinephrine). As parameters of tissue perfusion, we measured central-peripheral temperature gradient (delta-T) and sublingual perfused capillary density (PCD). All patients reached predefined therapeutic targets. The inotropes did not significantly change delta-T. Dobutamine did not change PCD. Enoximone increased PCD (9.1 [8.9-10.2] vs. 11.4 [8.4-13.9] mm.mm-2; p10.3 mm.mm-2; mortality 72% vs. 17%, p = 0.003). Conclusion: This study demonstrates the effects of commonly used inotropic agents on parameters of tissue perfusion in patients with cardiogenic shock. Despite hemodynamic optimization, tissue perfusion was not sufficiently restored in most patients. In these patients, mortality was high. Interventions directed at improving microcirculation may eventually help bridging the gap between improved hemodynamics and dismal patient outcome in cardiogenic shock

Final 5-Year Follow-Up of a Randomized Controlled Trial of Everolimus- and Paclitaxel-Eluting Stents for Coronary Revascularization in Daily Practice the COMPARE Trial (A Trial of Everolimus-Eluting Stents and Paclitaxel Stents for Coronary Revascularization in Daily Practice)

Objectives This study sought to report the 5-year outcomes of everolimus-eluting stents (EES) and paclitaxel-eluting stents (PES) in an all-comers population undergoing percutaneous coronary intervention (PCI). Background The medium-term 1 and 2-year results of the prospective randomized COMPARE trial (A Trial of Everolimus-Eluting Stents and Paclitaxel-Eluting Stents for Coronary Revascularization in Daily Practice) showed superior clinical outcomes with EES compared with PES in an all-comers PCI population. Whether this benefit is sustained over longer-term follow-up is unknown. Furthermore, systematic long-term follow-up data on these metallic drug eluting stents with durable polymers are scarce. Methods We randomly assigned 1,800 patients undergoing PCI to EES or PES. The pre-specified composite primary endpoint was death, myocardial infarction (MI), or target vessel revascularization (TVR). Results Follow-up at 5 years was completed in 1,791 (99.5%) patients. Treatment with EES compared with PES led to a relative risk reduction of the primary endpoint by 27% (18.4% vs. 25.1%, p = 0.0005), driven by lower rates of MI (7.0% vs. 11.5%, p = 0.001) and TVR (7.4% vs. 11.4%, p = 0.003), but not with mortality (9.0% vs. 10.3%, relative risk 0.88, p = 0.36). Moreover, patients treated with EES compared with PES had lower rates of definite/probable stent thrombosis at 5 years (3.1% vs. 5.9%, p = 0.005). The hazard curves for TVR, MI, and stent thrombosis diverge over the first 3 years and, subsequently, progress in parallel. Conclusions The early- and medium-term superiority of EES over PES measured both by safety and efficacy endpoints is sustained at 5 years in this all-comer population. (A Trial of Everolimus-Eluting Stents and Paclitaxel-Eluting Stents for Coronary Revascularization in Daily Practice [COMPARE]; NCT01016041)

Endocrine disorders are prominent clinical features in patients with primary antibody deficiencies

Background: Primary antibody deficiencies (PADs) and anterior pituitary dysfunction are both rare conditions. However, recent studies have remarkably reported the occurrence of anterior pituitary dysfunction in PAD patients. Methods: In this cross-sectional, single-center study we evaluated the prevalence of endocrine disorders in adult PAD patients. Our study focused on common variable immunodeficiency (CVID), immunoglobulin G (IgG) subclass deficiency (IgGSD), and specific anti-polysaccharide antibody deficiency (SPAD). We assessed hormone levels, performed provocative tests and genetic testing in a subset of patients by direct sequencing of the nuclear factor kappa beta subunit 2 (NFKB2) gene and primary immunodeficiency (PID) gene panel testing by whole exome sequencing (WES). Results: Our results demonstrated that one out of 24 IgGSD/SPAD patients had secondary hypothyroidism and three out of 9 men with IgGSD/SPAD had secondary hypogonadism. Premature ovarian failure was observed in four out of 9 women with CVID and primary testicular failure in one out of 15 men with CVID. In two out of 26 CVID patients we found partial adrenal insufficiency (AI) and in one out of 18 patients with IgGSD/SPAD secondary AI was found. Moreover, in one out of 23 patients with CVID and in two out of 17 patients with IgGSD/SPAD severe growth hormone deficiency (GHD) was found, while one patient with IgGSD/SPAD showed mild GHD. Combined endocrine disorders were detected in two women with CVID (either partial secondary AI or autoimmune thyroiditis with primary hypogonadism) and in three men with IgGSD/SPAD (two with either mild GHD or secondary hypothyroidism combined with secondary hypogonadism, and one man with secondary AI and severe GHD). Genetic testing in a subset of patients did not reveal pathogenic variants in NFKB2 or other known PID-associated genes. Conclusion: This is the first study to describe a high prevalence of both anterior pituitary and end-organ endocrine dysfunction in adult PAD patients. As these endocrine disorders may cause considerable health burden, assessment of endocrine axes should be considered in PAD patients

The proton and deuteron F_2 structure function at low Q^2

Measurements of the proton and deuteron $F_2$ structure functions are presented. The data, taken at Jefferson Lab Hall C, span the four-momentum transfer range $0.06 < Q^2 < 2.8$ GeV$^2$, and Bjorken $x$ values from 0.009 to 0.45, thus extending the knowledge of $F_2$ to low values of $Q^2$ at low $x$. Next-to-next-to-leading order calculations using recent parton distribution functions start to deviate from the data for $Q^2<2$ GeV$^2$ at the low and high $x$-values. Down to the lowest value of $Q^2$, the structure function is in good agreement with a parameterization of $F_2$ based on data that have been taken at much higher values of $Q^2$ or much lower values of $x$, and which is constrained by data at the photon point. The ratio of the deuteron and proton structure functions at low $x$ remains well described by a logarithmic dependence on $Q^2$ at low $Q^2$.Comment: 3 figures, submitted pape

Predicting future left anterior descending artery events from non-culprit lesions:insights from the Lipid-Rich Plaque study

AIMS: The left anterior descending (LAD) artery is the most frequently affected site by coronary artery disease. The prospective Lipid Rich Plaque (LRP) study, which enrolled patients undergoing imaging of non-culprits followed over 2 years, reported the successful identification of coronary segments at risk of future events based on near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS) lipid signals. We aimed to characterize the plaque events involving the LAD vs. non-LAD segments. METHODS AND RESULTS: LRP enrolled 1563 patients from 2014 to 2016. All adjudicated plaque events defined by the composite of cardiac death, cardiac arrest, non-fatal myocardial infarction, acute coronary syndrome, revascularization by coronary bypass or percutaneous coronary intervention, and rehospitalization for angina with >20% stenosis progression and reported as non-culprit lesion-related major adverse cardiac events (NC-MACE) were classified by NIRS-IVUS maxLCBI4 mm (maximum 4-mm Lipid Core Burden Index) ≤400 or >400 and association with high-risk-plaque characteristics, plaque burden ≥70%, and minimum lumen area (MLA) ≤4 mm2. Fifty-seven events were recorded with more lipid-rich plaques in the LAD vs. left circumflex and right coronary artery; 12.5% vs. 10.4% vs. 11.3%, P = 0.097. Unequivocally, a maxLCBI4 mm >400 in the LAD was more predictive of NC-MACE [hazard ratio (HR) 4.32, 95% confidence interval (CI) (1.93-9.69); P = 0.0004] vs. [HR 2.56, 95% CI (1.06-6.17); P = 0.0354] in non-LAD segments. MLA ≤4 mm2 within the maxLCBI4 mm was significantly higher in the LAD (34.1% vs. 25.9% vs. 13.7%, P < 0.001). CONCLUSION: Non-culprit lipid-rich segments in the LAD were more frequently associated with plaque-level events. LAD NIRS-IVUS screening may help identify patients requiring intensive surveillance and medical treatment

Longitudinal-Transverse Separations of Structure Functions at Low Q2Q^{2} for Hydrogen and Deuterium

We report on a study of the longitudinal to transverse cross section ratio, $R=\sigma_L/\sigma_T$, at low values of $x$ and $Q^{2}$, as determined from inclusive inelastic electron-hydrogen and electron-deuterium scattering data from Jefferson Lab Hall C spanning the four-momentum transfer range 0.06 $< Q^{2} < 2.8$ GeV$^{2}$. Even at the lowest values of $Q^{2}$, $R$ remains nearly constant and does not disappear with decreasing $Q^{2}$, as expected. We find a nearly identical behaviour for hydrogen and deuterium.Comment: 4 pages, 2 gigure