Environmental Tobacco Smoke and Cardiovascular Disease DiGiacomo, Sydne I; Jazayeri, Mohammad-Ali; Barua, Rajat S ...
International journal of environmental research and public health,
12/2018, Letnik:
16, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Environmental tobacco smoke (ETS) and its sequelae are among the largest economic and healthcare burdens in the United States and worldwide. The relationship between active smoking and ...atherosclerosis is well-described in the literature. However, the specific mechanisms by which ETS influences atherosclerosis are incompletely understood. In this paper, we highlight the definition and chemical constituents of ETS, review the existing literature outlining the effects of ETS on atherogenesis and thrombosis in both animal and human models, and briefly outline the public health implications of ETS based on these data.
Introduction
Catheter ablation (CA) can interfere with cardiac implantable electronic device (CIED) function. The safety of CA in the 1st year after CIED implantation/lead revision is uncertain.
...Methods
This single center, retrospective cohort included patients who underwent CA between 2012 and 2017 and had a CIED implant/lead revision within the preceding year. We assessed the frequency of device/lead malfunctions in this population.
Results
We identified 1810 CAs in patients between 2012 and 2017, with 170 CAs in 163 patients within a year of a CIED implant/lead revision. Mean age 68 ± 12 years (68% men). Time between the CIED procedure and CA was 158 ± 99 days. The CA procedures included AF ablation (n = 57, 34%), AV node ablation (n = 40, 24%), SVT ablation (n = 37, 22%), and PVC/VT ablations (n = 36, 21%). The cumulative frequency of lead dislodgement, significant CIED dysfunction, and/or CIED‐related infection following CA was (n = 1/170, 0.6%). There was a single atrial lead dislodgement (0.6%). There were no instances of power‐on‐reset or CIED‐related infection. Following CA, there was no significant difference in RA or RV lead sensing (p = 0.52 and 0.84 respectively) or thresholds (p = 0.94 and 0.17 respectively). The RA impedance slightly decreased post‐CA from 474 ± 80 Ohms to 460 ± 73 Ohms (p = 0.002), as did the RV impedance (from 515 ± 111 Ohms to 497 ± 98 Ohms, p < 0.0001).
Conclusions
CA can be performed within 1 year following CIED implantation/lead revision with a low risk of CIED/lead malfunction or lead dislodgement. The ideal time to perform CA after a CIED remains uncertain.
Introduction
Electromagnetic interference (EMI) from left ventricular assist devices (LVADs) can cause implantable cardioverter‐defibrillator (ICD) oversensing. We sought to assess the frequency of ...inappropriate shocks/oversensing due to LVAD‐related EMI and prospectively compare integrated (IB) versus dedicated bipolar (DB) sensing in patients with LVADs.
Methods
Single‐center study in LVAD patients with Medtronic or Abbott ICDs between September 2017 and March 2020. We excluded patients that were pacemaker dependent. Measurements were obtained of IB and DB sensing and noise to calculate a signal‐to‐noise ratio (SNR). Device checks were reviewed to assess appropriate and inappropriate sensing events.
Results
Forty patients (age 52 ± 14 years, 75% men, 38% ischemic cardiomyopathy) were included with the median time between LVAD implantation and enrollment of 6.7 months (2.3, 11.4 months). LVAD subtypes included: HeartWare (n = 22, 55%), Heartmate II (n = 10, 25%), and Heartmate III (n = 8, 20%). Over a follow‐up duration of 21.6 ± 12.9 months after LVAD implantation, 5% of patients (n = 2) had oversensing of EMI from the LVAD (both with HeartWare LVADs and Abbott ICDs) at 4 days and 10.8 months after LVAD implantation. Both patients underwent adjustment of ventricular sensing with resolution of oversensing and no further events over 5 and 15 months of further follow‐up. The SNR was similar between IB and DB sensing (50 29–67 and 57 41–69, p = 0.89).
Conclusion
ICD oversensing of EMI from LVADs is infrequent and can be managed with reprogramming the sensitivity. There was no significant difference in the R‐wave SNR with IB versus DB ICD leads.
Electromagnetic interference in patients with left ventricular assist devices and implantable cardioverter‐defibrillators
The effect of normalization of serum testosterone levels with testosterone replacement therapy (TRT) in patients with a history of myocardial infarction (MI) is unknown. The objective of this study ...was to determine the incidence of recurrent MI and all-cause mortality in subjects with a history of MI and low total testosterone (TT) with and without TRT. We retrospectively examined 1,470 men with documented low TT levels and previous MI, categorized into Gp1: TRT with normalization of TT levels (n = 755) Gp2: TRT without normalization of TT levels (n = 542), and Gp3: no TRT (n = 173). The association of TRT with all-cause mortality and recurrent MI was compared using propensity score-weighted Cox proportional hazard models. All-cause mortality was lower in Gp1 versus Gp2 (hazard ratio HR 0.76, confidence interval CI 0.64 to 0.90, p = 0.002), and Gp1 versus Gp3 (HR 0.76, CI 0.60 to 0.98, p = 0.031). There was no significant difference in the risk of death between Gp2 versus Gp3 (HR 0.97, CI 0.76 to 1.24, p = 0.81). Adjusted regression analyses showed no significant differences in the risk of recurrent MI between groups (Gp1 vs Gp3, HR 0.79, CI 0.12 to 5.27, p = 0.8; Gp1 vs Gp2 HR 1.10, CI 0.25 to 4.77, p = 0.90; Gp2 vs Gp3 HR 0.58, CI 0.08 to 4.06, p = 0.58). In conclusion, in a large observational cohort of male veterans with previous MI, normalization of TT levels with TRT was associated with decreased all-cause mortality compared with those with non-normalized TT levels and the untreated group. Furthermore, in this high-risk population, TRT was not associated with an increased risk of recurrent MI.
A number of recent technical solutions have led to significant advances in G protein-coupled receptor (GPCR) structural biology. Apart from a detailed mechanistic view of receptor activation, the new ...structures have revealed novel ligand binding sites. Together, these insights provide avenues for rational drug design to modulate the activities of these important drug targets. The application of structural data to GPCR drug discovery ushers in an exciting era with the potential to improve existing drugs and discover new ones. In this review, we focus on technical solutions that have accelerated GPCR crystallography as well as some of the salient findings from structures that are relevant to drug discovery. Finally, we outline some of the approaches used in GPCR structure based drug design.
Structural analysis of class B G-protein-coupled receptors (GPCRs), cell-surface proteins that respond to peptide hormones, has been restricted to the amino-terminal extracellular domain, thus ...providing little understanding of the membrane-spanning signal transduction domain. The corticotropin-releasing factor receptor type 1 is a class B receptor which mediates the response to stress and has been considered a drug target for depression and anxiety. Here we report the crystal structure of the transmembrane domain of the human corticotropin-releasing factor receptor type 1 in complex with the small-molecule antagonist CP-376395. The structure provides detailed insight into the architecture of class B receptors. Atomic details of the interactions of the receptor with the non-peptide ligand that binds deep within the receptor are described. This structure provides a model for all class B GPCRs and may aid in the design of new small-molecule drugs for diseases of brain and metabolism.
Background
Percutaneous left atrial appendage closure (LAAC) is a viable option for AF patients who are unable to tolerate long‐term oral anticoagulation (OAC).
Objective
We sought to assess the ...safety of two commonly used percutaneous devices for LAA closure in the United States by analysis of surveillance data from the FDA Manufacturer and User Facility Device Experience (MAUDE) database.
Methods
The MAUDE database was queried between May 1, 2006 and May 1, 2016 for LARIAT® (SentreHEART Inc., Redwood City, CA, USA) and WATCHMAN™ (Boston Scientific Corp., Marlborough, MA, USA) devices. Among 622 retrieved medical device reports, 356 unique and relevant reports were analyzed. The cumulative incidence of safety events was calculated over the study period and compared between the two devices.
Results
LAAC was performed with LARIAT in 4,889 cases. WATCHMAN was implanted in 2,027 patients prior to FDA approval in March 2015 and 3,822 patients postapproval. The composite outcome of stroke/TIA, pericardiocentesis, cardiac surgery, and death occurred more frequently with WATCHMAN (cumulative incidence, 1.93% vs. 1.15%; P = 0.001). The same phenomenon was observed when comparing the WATCHMAN pre‐ and postapproval experiences for the composite outcome, as well as device embolization, cardiac surgery, and myocardial infarction.
Conclusions
MAUDE‐reported data show that postapproval, new technology adoption is fraught with increased complications. Improved collaboration between operators, device manufacturers, and regulators can better serve patients through increased transparency and practical postmarket training and monitoring mechanisms.
The complement system is a crucial component of the host response to infection and tissue damage. Activation of the complement cascade generates anaphylatoxins including C5a and C3a. C5a exerts a ...pro-inflammatory effect via the G-protein-coupled receptor C5a anaphylatoxin chemotactic receptor 1 (C5aR1, also known as CD88) that is expressed on cells of myeloid origin. Inhibitors of the complement system have long been of interest as potential drugs for the treatment of diseases such as sepsis, rheumatoid arthritis, Crohn's disease and ischaemia-reperfusion injuries. More recently, a role of C5a in neurodegenerative conditions such as Alzheimer's disease has been identified. Peptide antagonists based on the C5a ligand have progressed to phase 2 trials in psoriasis and rheumatoid arthritis; however, these compounds exhibited problems with off-target activity, production costs, potential immunogenicity and poor oral bioavailability. Several small-molecule competitive antagonists for C5aR1, such as W-54011 and NDT9513727, have been identified by C5a radioligand-binding assays. NDT9513727 is a non-peptide inverse agonist of C5aR1, and is highly selective for the primate and gerbil receptors over those of other species. Here, to study the mechanism of action of C5a antagonists, we determine the structure of a thermostabilized C5aR1 (known as C5aR1 StaR) in complex with NDT9513727. We found that the small molecule bound between transmembrane helices 3, 4 and 5, outside the helical bundle. One key interaction between the small molecule and residue Trp213
seems to determine the species selectivity of the compound. The structure demonstrates that NDT9513727 exerts its inverse-agonist activity through an extra-helical mode of action.
Metabotropic glutamate receptors are class C G-protein-coupled receptors which respond to the neurotransmitter glutamate. Structural studies have been restricted to the amino-terminal extracellular ...domain, providing little understanding of the membrane-spanning signal transduction domain. Metabotropic glutamate receptor 5 is of considerable interest as a drug target in the treatment of fragile X syndrome, autism, depression, anxiety, addiction and movement disorders. Here we report the crystal structure of the transmembrane domain of the human receptor in complex with the negative allosteric modulator, mavoglurant. The structure provides detailed insight into the architecture of the transmembrane domain of class C receptors including the precise location of the allosteric binding site within the transmembrane domain and key micro-switches which regulate receptor signalling. This structure also provides a model for all class C G-protein-coupled receptors and may aid in the design of new small-molecule drugs for the treatment of brain disorders.
Background
Patients with left ventricular assist devices (LVAD) often tolerate ventricular arrhythmias (VA). We aim to assess the frequency and outcomes of ICD therapies averted by ultraconservative ...ICD programming (UCP) in LVAD patients.
Methods
This single center, retrospective cohort study included patients with LVADs and ICDs implanted from 2015 to 2019 that had UCP. The aim for UCP was to maximally delay VA treatments and maximize anti‐tachycardia pacing (ATP) prior to ICD shocks. VA events were reviewed after UCP and evaluated under prior conservative programming to assess for potentially averted events (that would have resulted in either ATP or defibrillation with prior programming).
Results
Fifty patients were included in the study with follow‐up of median 16 ± 10.2 months after UCP. The median time from LVAD implantation to reprogramming was 7 days (IQR 5–9 days). Fourteen patients (28%) had potentially averted VA events that would have been treated with their prior ICD programming (82 total events, median two events per patient, IQR 1–10 events). Treated VA events occurred in 15 patients (30%). Eleven of the 14 patients with potentially averted VAs had treated events as well. Only one patient reported definitive symptoms of self‐limited “dizziness” during a potentially averted event that did not result in hospitalization. No patients died of complications from or needed emergent care/hospitalization due a potentially averted VA.
Conclusions
UCP in LVAD patients likely prevented unnecessary VA treatments in many patients with minimal reported symptoms during these potentially averted events. Prospective studies are necessary to confirm these findings.
PDF
