Abstract
Aims
Tricuspid regurgitation (TR) is a frequent echocardiographic finding; however, its effect on outcome is unclear. The objectives of current study were to evaluate the impact of TR ...severity on heart failure hospitalization and mortality.
Methods and results
We retrospectively reviewed consecutive echocardiograms performed between 2011 and 2016 at the Tel-Aviv Medical Center. TR severity was determined using semi-quantitative approach including colour jet area, vena contracta width, density of continuous Doppler jet, hepatic vein flow pattern, trans-tricuspid inflow pattern, annular diameter, right ventricle, and right atrial size. Major comorbidities, re-admissions and all-cause mortality were extracted from the electronic health records. The final analysis included 33 305 patients with median follow-up period of 3.34 years (interquartile range 2.11–4.54). TR (≥mild) was present in 31% of our cohort. One-year mortality rates were 7.7% for patients with no/trivial TR, 16.8% for patients with mild TR, 29.5% for moderate TR, and 45.6% for patients with severe TR (P < 0.001). Univariate and multivariate analyses demonstrated a positive correlation between TR severity and overall mortality and rates of heart failure re-admission after adjustment for potential confounders. The proportional hazards method for overall mortality showed that patients with moderate hazard ratio (HR) 1.15, 95% confidence interval (CI) 1.02–1.3, P = 0.024 and severe TR (HR 1.43, 95% CI 1.08–1.88, P = 0.011) had a worse prognosis than those with no or minimal TR.
Conclusions
The presence of any degree of TR is associated with adverse clinical outcome. At least moderate TR is independently associated with increased mortality.
Risk stratification in Brugada syndrome remains a clinical challenge because the event rate is low but the presenting symptom is often cardiac arrest (CA). We review the data on risk stratification. ...A history of CA or malignant syncope is a strong predictor of spontaneous ventricular fibrillation (VF), whereas the prognostic value of a history of familial sudden death and the presence of a SCN5A mutation are less well defined. On the electrocardiogram, the presence of spontaneous type I electrocardiogram increases the risk for VF in all studies, whereas the presence of fragmented QRS complexes and early repolarization correlates with increased risk in several studies. Signal-averaged techniques using late potentials and microscopic T-wave alternans show some promising results in small studies that need to be confirmed. The value of electrophysiologic studies for predicting spontaneous VF remains controversial, and this includes programmed stimulation protocols that avoid a third extrastimuli or stimulation from the right ventricular outflow. Risk prediction is particularly challenging in children and women.
Abstract New generation of the most widely used devices for transcatheter aortic valve implantation (TAVI) have been recently introduced into practice. We compare the short term outcomes of TAVI with ...the Edwards SAPIEN S3 and the Medtronic Evolut-R. We performed a retrospective analysis from a single high volume tertiary center. Valve Academic Research Consortium (VARC)-2 criteria were used to define composite endpoints of device success and safety at 30 days. Study population included 232 patients implanted with the SAPIEN S3 (n=124) and Evolut-R (n=108). Device success reached 91.9% and 95.4% in the SAPIEN S3 and Evolut-R groups, respectively (p=0.289). Post-procedural echocardiography showed higher AV gradients (22.8±7 mmHg vs. 16±9 mmHg, p<0.001) among SAPIEN S3 group. Paravalvular leak of ≥ moderate severity was observed in 2.4% and 0% in the SAPIEN S3 and Evolut-R groups, respectively (p=0.251). Similar rates of in hospital complications, including major bleedings, vascular complications and pacemaker implantations were recorded in both groups. At 30 day follow-up, the combined-safety endpoint was reached in 5.6% and in 6.5% of patients in the SAPIEN S3 and Evolut-R groups, respectively (p=0.790). During follow up of 237±138 days, all-cause mortality was higher among patients implanted with Evolut-R compared to SAPIEN S3 (7 vs. 1 cases, respectively, p=0.006), however, cardiovascular mortality was not significantly different between groups. In conclusions, in a single-center comparative analysis, comparable rate of device success as well as safety profile and long term cardiovascular mortality were observed with the SAPIEN S3 and Evolut-R valves.
Vesicular Zn(2+) regulates postsynaptic neuronal excitability upon its corelease with glutamate. We previously demonstrated that synaptic Zn(2+) acts via a distinct metabotropic zinc-sensing receptor ...(mZnR) in neurons to trigger Ca(2+) responses in the hippocampus. Here, we show that physiological activation of mZnR signaling induces enhanced K(+)/Cl(-) cotransporter 2 (KCC2) activity and surface expression. As KCC2 is the major Cl(-) outward transporter in neurons, Zn(2+) also triggers a pronounced hyperpolarizing shift in the GABA(A) reversal potential. Mossy fiber stimulation-dependent upregulation of KCC2 activity is eliminated in slices from Zn(2+) transporter 3-deficient animals, which lack synaptic Zn(2+). Importantly, activity-dependent ZnR signaling and subsequent enhancement of KCC2 activity are also absent in slices from mice lacking the G-protein-coupled receptor GPR39, identifying this protein as the functional neuronal mZnR. Our work elucidates a fundamentally important role for synaptically released Zn(2+) acting as a neurotransmitter signal via activation of a mZnR to increase Cl(-) transport, thereby enhancing inhibitory tone in postsynaptic cells.
Zn(2+) is coreleased with glutamate from mossy fiber terminals and can influence synaptic function. Here, we demonstrate that synaptically released Zn(2+) activates a selective postsynaptic ...Zn(2+)-sensing receptor (ZnR) in the CA3 region of the hippocampus. ZnR activation induced intracellular release of Ca(2+), as well as phosphorylation of extracellular-regulated kinase and Ca(2+)/calmodulin kinase II. Blockade of synaptic transmission by tetrodotoxin or CdCl inhibited the ZnR-mediated Ca(2+) rises. The responses mediated by ZnR were largely attenuated by the extracellular Zn(2+) chelator, CaEDTA, and in slices from mice lacking vesicular Zn(2+), suggesting that synaptically released Zn(2+) triggers the metabotropic activity. Knockdown of the expression of the orphan G-protein-coupled receptor 39 (GPR39) attenuated ZnR activity in a neuronal cell line. Importantly, we observed widespread GPR39 labeling in CA3 neurons, suggesting a role for this receptor in mediating ZnR signaling in the hippocampus. Our results describe a unique role for synaptic Zn(2+) acting as the physiological ligand of a metabotropic receptor and provide a novel pathway by which synaptic Zn(2+) can regulate neuronal function.
Objective
Inflammation is associated with atherogenesis. Although a higher neutrophil count is associated with the plaque burden, the role of neutrophil activation is unclear. Human neutrophil ...peptides 1–3 (HNP1–3) are a risk factor for atherogenesis in bench models and are elevated in human atheromas. This study aimed to examine the association between skin HNP1–3 deposition and the severity of coronary artery disease (CAD), including long-term outcomes.
Methods
HNP1–3 levels were immunohistochemically quantified in skin biopsies, which were prospectively taken from 599 consecutive patients before clinically indicated coronary angiography. Established cardiovascular risk factors and blood markers for atheroinflammation were obtained. CAD severity and the incidence of repeat revascularization and mortality at 48 months of follow-up were assessed in relation to HNP1–3 levels.
Results
The risk of CAD was independently associated with age and HNP1–3 in the entire cohort (F = 0.71 and F = 7.4, respectively). Additionally, HNP1–3 levels were significantly associated with myocardial necrosis (R = 0.26). At the follow-up, high HNP1–3 levels negatively affected mortality (19.54%) and recurrent revascularization (8.05%).
Conclusion
HNP1–3 tissue deposition is positively associated with the severity of CAD, myonecrosis, and long-term sequelae. HNP1–3 levels may be suppressed using colchicine.
Objective
Subclinical myocardial dysfunction has been reported to occur early in systemic lupus erythematous (SLE). The study aim was to search for biomarkers of subclinical myocardial dysfunction ...which may correlate with disease activity in SLE patients.
Methods
This is a prospective, controlled, cross-sectional study of 57 consecutive patients with SLE and 18 controls. Serum samples were obtained to determine serum soluble ST2 (sST2), CXCL-10 and high-sensitivity troponin (hs-troponin) levels. All participants underwent an echocardiographic tissue Doppler study.
Results
sST2, CXCL-10 and hs-troponin levels were higher in patients with higher SLE disease activity (SLEDAI). sST2 and CXCL-10 levels were higher in patients with more disease damage as measured by the SLE damage index. Measures of diastolic dysfunction, as assessed by echocardiographic tissue Doppler negatively correlated with log CXCL-10: including E/A; E/e′lateral and E/e′septal, while E/e′ positively correlated with CXCL-10. Diastolic dysfunction parameters also correlated with log sST2 levels, a negative correlation was seen with E/e′lateral and a positive correlation was seen with E/e′. Systolic dysfunction parameters positively correlated with hs-troponin: LVED, LVES, IVS, LVMASS and LVMASS index. In a multivariate analysis, sST2 and CXCL-10 were found to be significantly different in SLE vs. healthy controls, independent of each other and independent of cardiovascular risk factors.
Conclusions
Soluble ST2 and CXCL-10 are markers of disease activity and accrued damage in SLE and may serve as sensitive biomarkers for detection of subclinical diastolic dysfunction, independent of traditional cardiovascular risk factors.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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