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1.
Cardiol Clin ; 42(3): 339-350, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38910019

ABSTRACT

Electrosurgery has emerged as a groundbreaking tool in the field of structural cardiac interventions, revolutionizing the approach to complex cardiac conditions. This review delves into the core principles, procedural techniques, outcomes, and potential challenges associated with various electrosurgical procedures within the realm of structural cardiology. Five key electrosurgical procedures performed in complex structural interventions are highlighted in this review. They are the Transcaval Access, BASILICA, LAMPOON, ELASTIC/ELASTA-Clip, and SESAME procedures. While these electrosurgery procedures hold promise and have demonstrated positive outcomes, their technical intricacies, patient selection criteria, and the need for further research remain important considerations. As technology continues to evolve and more data becomes available, electrosurgery is poised to continue shaping the landscape of cardiac care, offering minimally invasive alternatives, and improving patient outcomes in complex structural cardiac interventions.


Subject(s)
Cardiac Surgical Procedures , Electrosurgery , Humans , Electrosurgery/methods , Cardiac Surgical Procedures/methods , Heart Diseases/surgery
2.
Struct Heart ; 8(2): 100228, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38481710

ABSTRACT

The SENTINEL Cerebral Protection System is one of the most commonly used devices for embolic protection during transcatheter aortic valve replacement. However, successful deployment of the SENTINEL device is often challenging in patients with a bovine aortic arch anatomy using the standard technique and requires extensive manipulation in the aortic arch increasing the risk of stroke. We describe a novel and simple technique of 2-filter deployment of SENTINEL device in patients with bovine arch anatomy. In this technique, after the deployment of the proximal filter, the device is hyperflexed on itself facing the lateral aspect of the ascending aorta instead of facing the descending aorta, with its tip pointing toward the common origin of the left common carotid artery (LCCA) and brachiocephalic trunk. The guidewire is then advanced to the LCCA. Since the guidewire can pass either anterior or posterior to the device shaft, the device needs to be untwisted either by clockwise or counterclockwise motion, before pulling the device shaft back to engage the LCCA, after which the distal filter can be deployed. Computed tomography scans obtained for planning transcatheter aortic valve replacement should be reviewed for the presence of bovine aortic arch anatomy so that this technique can be deployed directly, thereby reducing manipulations in the aortic arch, saving time, and not requiring additional equipment.

4.
Cureus ; 15(4): e37042, 2023 Apr.
Article in English | MEDLINE | ID: mdl-37143635

ABSTRACT

Introduction We sought to investigate the association between left-sided prosthetic valve dysfunction and gastrointestinal (GI) bleeding. Methods In a retrospective cohort of patients with left-sided prostheses, we identified those who experienced one or more GI bleeds. The latest or chronologically closest echocardiogram to the GI bleed was analyzed by a blinded investigator for prosthetic valve dysfunction. Results Among 334 unique patients, 166 had aortic prostheses, 127 had mitral prostheses, and 41 had both. A total of 58 (17.4%) subjects had GI bleeding events. Patients in the "GI Bleed" group had higher mean ejection fraction (56±14% vs. 49±15%; P = 0.003) and higher prevalence of hypertension, end-stage renal disease, and liver cirrhosis compared to the "No GI Bleed" group. There was a higher prevalence of moderate or severe prosthetic valve regurgitation in the GI Bleed vs. No GI Bleed group (8.6% vs. 2.2%; P = 0.027). Moderate or severe prosthetic valve regurgitation was independently associated with GI bleeding (odds ratio, 6.18; 95% confidence interval, 1.27-30.05; P = 0.024), after adjusting for ejection fraction, hypertension, end-stage renal disease and liver cirrhosis. Paravalvular regurgitation was associated with a higher incidence of GI bleeding compared to transvalvular regurgitation (35.7% vs. 11.9%; P = 0.044). The prevalence of prosthetic valve stenosis was similar between the GI Bleed and No GI Bleed groups (6.9% vs. 5.8%; P = 0.761). Conclusion In a cohort of patients with predominantly surgically placed prosthetic valves, moderate to severe left-sided prosthetic valve regurgitation was independently associated with GI bleeding.

5.
Cureus ; 15(3): e36002, 2023 Mar.
Article in English | MEDLINE | ID: mdl-37041923

ABSTRACT

Atrial fibrillation (AF) is a common heart rhythm disorder that increases the risk of stroke and other cardiovascular complications. The Watchman FLX device is a percutaneous device used for the closure of the left atrial appendage in patients with atrial fibrillation and prevents blood clots from forming, thereby decreasing the risk of stroke. However, device dislodgement during the procedure can occur and compromise the effectiveness of the device. In this case report, we present the experience of an 86-year-old man with a history of atrial fibrillation, coronary artery disease, hypertension, and recent gastrointestinal bleeding due to diverticulosis. During the procedure, the device became dislodged prior to the planned release from the shaft due to the difficult anatomy of the appendage, which caused the operator to over-torque and kink the delivery sheath. The kinked sheath prevented the transmission of torque to the appropriate region of the sheath and caused the device to unscrew prematurely. Fortunately, the device was self-deployed in a satisfactory position, and no further intervention was required. The patient did not experience any complications prior to discharge and follow-up echocardiography showed proper positioning of the device. This case highlights the importance of careful technique during the Watchman FLX procedure and the need to replace the delivery sheath if kinking is noted to prevent unintentional dislodgement of the device. In addition, the case was written with the aid of the artificial intelligence-powered language model ChatGPT and demonstrates its benefits as well as calls for caution while using it for medical writing.

6.
Cureus ; 15(2): e35172, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36949974

ABSTRACT

Purulent pericarditis is the infection of the pericardial space with pus formation. High mortality and morbidity can be explained by cardiac tamponade and septic shock in the acute phase, while chronically, it can lead to recurrent purulent pericarditis and constrictive pericarditis. We present two cases of purulent pericarditis treated with intrapericardial recombinant tissue plasminogen activator (r-tPA) for three consecutive days in addition to surgical pericardial drainage. In both instances, loculated effusions and re-accumulation of pericardial fluid persisted despite adequate antibiotic coverage and surgical drainage. Intrapericardial fibrinolysis was considered a less invasive alternative to extensive surgery to prevent constrictive pericarditis and improve clinical outcomes. Both patients had complete clinical recovery and there was no evidence of constrictive pericarditis during follow-up. There is scant literature regarding r-tPA therapy for purulent pericarditis, most of which is limited to case reports or case series. The most commonly used regimen is three doses of tPA administered into the pericardial space over three days. It is a safe and potentially effective therapy in preventing constrictive pericarditis and need of pericardiectomy.

7.
Am J Cardiovasc Drugs ; 22(6): 633-645, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35781867

ABSTRACT

BACKGROUND: Dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) with drug-eluting stent (DES) is typically continued for 6-12 months depending on clinical presentation. Recent studies have evaluated the safety of shorter durations of DAPT across stable and unstable coronary syndrome but are limited by smaller patient pools and varying indications. METHODS: The present study performed a systematic review and network meta-analysis comparing abbreviated (1-3 months) with standard (6-12 months) duration of DAPT. Both conventional and frequentist network meta-analyses with a random-effects model were conducted. RESULTS: Seventeen randomized controlled trials, nine of which included 1-3 months of DAPT, were selected. The risks of any bleeding (RR 0.68, 95% CI 0.54-0.85), major bleeding (RR 0.66, 95% CI 0.50-0.86), and net adverse clinical events (NACE) (RR 0.87, 95% CI 0.76-0.99) were lower with abbreviated (1-3 months) than standard-term (6-12 months) DAPT. No significant differences in the risk of myocardial infarction (RR 1.02, 95% CI 0.87-1.18), definite or probable stent thrombosis (RR 1.11, 95% CI 0.83-1.50), and major adverse cardiac events (MACE) (RR 0.96, 95% CI 0.86-1.06) were observed. Network meta-analysis demonstrated lower risk of any bleeding, major bleeding, and NACE with shorter durations of DAPT compared with 12 months. Risks of definite or probable stent thrombosis, myocardial infarction, and MACE were not significantly different. CONCLUSION: The results support the growing body of evidence that abbreviated duration (1-3 months) of DAPT may be considered to reduce the risk of bleeding without any differences in myocardial infarction, stent thrombosis, or MACE.


Subject(s)
Drug-Eluting Stents , Myocardial Infarction , Percutaneous Coronary Intervention , Thrombosis , Humans , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/methods , Drug-Eluting Stents/adverse effects , Platelet Aggregation Inhibitors/adverse effects , Network Meta-Analysis , Myocardial Infarction/epidemiology , Myocardial Infarction/drug therapy , Hemorrhage/chemically induced , Hemorrhage/epidemiology , Hemorrhage/drug therapy , Thrombosis/epidemiology , Thrombosis/etiology , Thrombosis/prevention & control , Treatment Outcome , Drug Therapy, Combination
8.
J Interv Card Electrophysiol ; 64(3): 763-771, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35258752

ABSTRACT

BACKGROUND: Landmark trials have shown superiority of ablative therapy over medical therapy in certain subpopulation with atrial fibrillation (AF). Previous studies have demonstrated an association between weight loss and reduced rates of recurrence of AF after ablation. The objective of this study is to determine if weight loss reduces the recurrence of AF after ablation. METHODS: An extensive literature search and systematic review of studies of weight loss on recurrence of AF after ablative therapy was performed. Risk ratio (RR) and 95% confidence intervals were measured for weight loss group versus control group in each study, and comparative analysis as well as subgroup analysis was made. RESULTS: Eight studies with a total of 1,425 patients were included. Overall, studies of patients who lost weight demonstrated lower recurrence of AF (RR 0.35; 95% CI 0.18-0.67). However, subgroup analysis of studies which included patients who lost ≥10% weight loss from baseline showed lower recurrence of AF (RR 0.18; 95% 0.03-0.89), whereas studies which included patients with <10% weight loss did not (RR 1.00; 95% 0.51-1.96). Studies of patients who had less than 12-month history of AF (RR 0.24; 95% CI 0.11-0.57) and those who lost weight prior to ablation (RR 0.40; 95% CI 0.20-0.79) also had lower recurrence of AF. CONCLUSION: Weight loss is associated with lower long-term recurrence of AF after ablative therapy. Studies of patients with ≥10% weight loss, less than 12-month history of AF, and weight loss prior to ablation experience lower recurrence of AF.


Subject(s)
Atrial Fibrillation , Catheter Ablation , Humans , Odds Ratio , Recurrence , Treatment Outcome , Weight Loss
9.
J Nucl Cardiol ; 28(6): 2799-2807, 2021 12.
Article in English | MEDLINE | ID: mdl-32383079

ABSTRACT

BACKGROUND: Data on the prognostic value of regadenoson SPECT myocardial perfusion imaging (MPI) is limited and based on small cohorts. METHODS AND RESULTS: We conducted a single-center, retrospective cohort study of 10,275 consecutive patients who underwent regadenoson SPECT-MPI. Among the study subjects, 28.7% had abnormal MPI and 25.5% had myocardial ischemia. Patients were followed for a mean of 2.4 ± 2.2 years for major adverse cardiac events (MACE), defined as cardiac death or myocardial infarction. There was a significant stepwise increase in MACE with an increasing burden of perfusion abnormality (P < .001) and myocardial ischemia (P < .001). Abnormal MPI (adjusted HR 1.52; 95% CI 1.21 to 1.91) and myocardial ischemia (adjusted HR 1.53; 95% CI 1.25 to 1.89) were associated with MACE, independent of and incremental to clinical covariates and left ventricular ejection fraction (LVEF). Moreover, post-stress LVEF, LVEF reserve, and left ventricular end-diastolic volume added significant prognostic information. Transient ischemic dilation ≥ 1.31 did not provide incremental prognostic value (adjusted HR 1.02; P = .906). CONCLUSION: In the largest cohort to date, we demonstrated that the presence and severity of perfusion abnormality and myocardial ischemia on regadenoson stress SPECT-MPI are associated with an independent increase in MACE.


Subject(s)
Myocardial Perfusion Imaging/methods , Purines , Pyrazoles , Tomography, Emission-Computed, Single-Photon/methods , Aged , Cohort Studies , Female , Humans , Male , Middle Aged , Myocardial Infarction/diagnostic imaging , Myocardial Ischemia/diagnostic imaging , Prognosis , Retrospective Studies
10.
Clin Med Insights Cardiol ; 14: 1179546820953416, 2020.
Article in English | MEDLINE | ID: mdl-32943967

ABSTRACT

BACKGROUND: Electrocardiogram (ECG) differentiation of wide complex tachycardia (WCT) into ventricular tachycardia (VT) and supraventricular tachycardia with aberration (SVT-A) is often challenging. OBJECTIVE: To determine if the presence of Q-waveforms (QS, Qr, QRs) in the inferior leads (II, III, aVF) can differentiate VT from SVT-A in a WCT compared to Brugada algorithm. We studied 2 inferior lead criteria namely QWC-A where all the inferior leads had a similar Q wave pattern and QWC-B where only lead aVF had a Q-waveform. METHODS: A total of 181 consecutive cases of WCT were identified, digitally separated into precordial leads and inferior leads and independently reviewed by 2 electrophysiologists. An electrocardiographic diagnosis of VT or SVT-A was assigned based on Brugada and inferior lead algorithms. Results were compared to the final clinical diagnosis. RESULTS: VT was the final clinical diagnosis in 24.9% of ECG cohort (45/181); 75.1% (136/181) were SVT-A. QWC-A and QWC-B had a high specificity (93.3% and 82.8%) and accuracy (78.2% and 71.0%), but low sensitivity (33.3% and 35.6%) in differentiating VT from SVT-A. The Brugada algorithm yielded a sensitivity of 82.2% and specificity of 68.4%. Area under the curve in ROC analysis was highest with Brugada algorithm (0.75, 95% CI 0.69-0.81) followed by QWC-A (0.63, 95% CI 0.56-0.70) and QWC-B (0.59, 95% CI 0.52-0.67). CONCLUSION: QWC-A and QWC-B criteria had poor sensitivity but high specificity in diagnosing VT in patients presenting with WCT. Further research combining this simple criterion with other newer diagnostic algorithms can potentially improve the accuracy of the overall diagnostic algorithm.

11.
Int J Impot Res ; 32(6): 623-627, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32862194

ABSTRACT

Microsurgical denervation of the spermatic cord (MDSC) is a treatment option in patients with chronic orchialgia. This procedure requires precise care to avoid any thermal damage to crucial adjacent tissues (arteries, veins, and lymphatics). Monopolar electrocautery is the standard ligation energy source, but may cause extensive collateral damage to the tissues. However, CO2 laser is known to produce a very predictable tissue penetration and minimal collateral spread. The goal of this study was to compare the extent of collateral thermal damage in both monopolar electrocautery and CO2 laser ablation in the spermatic cord during a robotic assisted MDSC (RMDSC) procedure as well as the feasibility for utilizing the flexible fiber-optic CO2 laser probe after "RMDSC" procedure. RMDSC was performed using standard monopolar electrocautery on the spermatic cord of one side of a fresh human male cadaver (randomly selected) and then compared to RMDSC using the CO2 laser on the contralateral spermatic cord. Nine histological cross-sections from each cord were measured for depth of collateral thermal/cautery injury. The mean collateral thermal injury with CO2 laser was 0.17 ± 0.031 mm (range: 0.15-0.25 mm), and with standard electrocautery 0.72 ± 0.046 mm (range: 0.60-0.75 mm). CO2 laser resulted significantly less collateral thermal injury than standard electrocautery (p < 0.0001). The CO2 laser probe was easy to manipulate with the Black Diamond micro-forceps (Intuitive Surgical, CA) and allowed for convenient tissue plane dissection. Human cadaveric targeted RMDSC using a flexible CO2 laser energy results in significantly decreased collateral thermal injury compared to standard monopolar electrocautery. These initial findings suggest potential advantages of the CO2 laser over traditional monopolar cautery in cases requiring minimal collateral tissue damage. Future studies are needed to assess its clinical potential in microsurgery.


Subject(s)
Robotic Surgical Procedures , Spermatic Cord , Carbon Dioxide , Denervation , Electrocoagulation/adverse effects , Humans , Lasers , Male , Prospective Studies , Spermatic Cord/surgery
12.
Curr Cardiol Rep ; 22(8): 76, 2020 07 06.
Article in English | MEDLINE | ID: mdl-32632540

ABSTRACT

PURPOSE OF REVIEW: To examine the utility and methods of coronary artery disease (CAD) assessment in patients with new-onset heart failure with reduced ejection fraction (HFrEF) of unclear etiology. Moreover, we sought to review the role and techniques of assessing myocardial viability to guide coronary revascularization in patients with established ischemic cardiomyopathy. RECENT FINDINGS: Data indicates that surgical coronary revascularization in patients with HFrEF due to ischemic cardiomyopathy leads to lower long-term all-cause mortality and cardiovascular hospitalizations. Thus, identifying ischemic heart disease in patients with new-onset HFrEF is essential. In addition to invasive coronary angiography (ICA), radionuclide myocardial perfusion imaging, coronary CT angiography (CCTA), and cardiac magnetic resonance (CMR) imaging have emerged as effective non-invasive tools in the assessment of CAD in this population. Viability testing remains an area of particular interest and debate and its full potential has not been fully addressed. We propose stepwise algorithms for CAD and viability assessment in this patient population. Non-invasive testing with radionuclide myocardial perfusion imaging, CCTA, and CMR is an alternative to ICA for CAD assessment in patients with new-onset HFrEF of unclear etiology. Several non-invasive imaging modalities have proved to be effective in detecting viable myocardium in patients with ischemic cardiomyopathy. The use of viability imaging to guide coronary revascularization should be individualized.


Subject(s)
Coronary Artery Disease , Heart Failure , Myocardial Ischemia , Myocardial Perfusion Imaging , Coronary Angiography , Humans , Ischemia , Stroke Volume
14.
Antioxidants (Basel) ; 8(7)2019 Jul 11.
Article in English | MEDLINE | ID: mdl-31336709

ABSTRACT

Atherosclerosis has long been known to be a chronic inflammatory disease. In addition, there is intense oxidative stress in atherosclerosis resulting from an imbalance between the excess reactive oxygen species (ROS) generation and inadequate anti-oxidant defense forces. The excess of the oxidative forces results in the conversion of low-density lipoproteins (LDL) to oxidized LDL (ox-LDL), which is highly atherogenic. The sub-endothelial deposition of ox-LDL, formation of foamy macrophages, vascular smooth muscle cell (VSMC) proliferation and migration, and deposition of collagen are central pathophysiologic steps in the formation of atherosclerotic plaque. Ox-LDL exerts its action through several different scavenger receptors, the most important of which is LOX-1 in atherogenesis. LOX-1 is a transmembrane glycoprotein that binds to and internalizes ox-LDL. This interaction results in variable downstream effects based on the cell type. In endothelial cells, there is an increased expression of cellular adhesion molecules, resulting in the increased attachment and migration of inflammatory cells to intima, followed by their differentiation into macrophages. There is also a worsening endothelial dysfunction due to the increased production of vasoconstrictors, increased ROS, and depletion of endothelial nitric oxide (NO). In the macrophages and VSMCs, ox-LDL causes further upregulation of the LOX-1 gene, modulation of calpains, macrophage migration, VSMC proliferation and foam cell formation. Soluble LOX-1 (sLOX-1), a fragment of the main LOX-1 molecule, is being investigated as a diagnostic marker because it has been shown to be present in increased quantities in patients with hypertension, diabetes, metabolic syndrome and coronary artery disease. LOX-1 gene deletion in mice and anti-LOX-1 therapy has been shown to decrease inflammation, oxidative stress and atherosclerosis. LOX-1 deletion also results in damage from ischemia, making LOX-1 a promising target of therapy for atherosclerosis and related disorders. In this article we focus on the different mechanisms for regulation, signaling and the various effects of LOX-1 in contributing to atherosclerosis.

15.
J Cardiovasc Pharmacol Ther ; 24(5): 428-434, 2019 09.
Article in English | MEDLINE | ID: mdl-31035795

ABSTRACT

BACKGROUND: Direct oral anticoagulants (DOACs) have been found to be similar or superior to warfarin in reducing ischemic stroke and intracranial hemorrhage (ICH) in patients with atrial fibrillation (AF). We sought to examine the anticoagulation prescription patterns in community since the advent of DOACs and also evaluate the outcomes in terms of gastrointestinal (GI) bleeding, ischemic stroke, and ICH in real-world patients with AF receiving anticoagulation. METHODS: This is a retrospective study comprising patients who were newly diagnosed with nonvalvular AF and were prescribed anticoagulants for stroke prevention. Prescription pattern of the anticoagulants based on CHA2DS2Vasc score was studied. Clinical outcomes of GI bleeding, ischemic stroke, and ICH were analyzed using a multivariate logistic regression model. RESULTS: Of the 2362 patients with AF on anticoagulation, 44.7% were prescribed DOACs. Patients with CHA2DS2VASc score of ≥3 received a prescription for warfarin more often than DOACs (P < .001). Multivariate logistic regression analysis revealed that the incidence of GI bleed (odds ratio [OR]: 0.91, 95% confidence interval [CI]: 0.62-1.35, P = .66) and stroke (OR: 0.77, 95% CI: 0.57-1.05, P = .10) was similar between warfarin and DOAC users. However, there was a trend toward lower ICH in the DOAC group (OR: 0.60, 95% CI: 0.36-1.01, P = .06). CONCLUSIONS: Prescription rate of DOACs for nonvalvular AF has increased significantly, with apixaban being the most commonly used agent. Patients with higher CHA2DS2-VASc score (≥3) are prescribed DOACs less often than warfarin. The reason for this discrepancy is unclear. Given the favorable risk-benefit profile of DOACs, further studies are needed to identify factors that determine anticoagulant selection in patients with AF with high thromboembolic risk.


Subject(s)
Anticoagulants/administration & dosage , Antithrombins/administration & dosage , Atrial Fibrillation/drug therapy , Brain Ischemia/prevention & control , Practice Patterns, Physicians'/trends , Stroke/prevention & control , Warfarin/administration & dosage , Administration, Oral , Aged , Aged, 80 and over , Anticoagulants/adverse effects , Antithrombins/adverse effects , Atrial Fibrillation/diagnosis , Atrial Fibrillation/epidemiology , Brain Ischemia/diagnosis , Brain Ischemia/epidemiology , Drug Utilization/trends , Female , Hemorrhage/chemically induced , Hemorrhage/epidemiology , Humans , Male , Retrospective Studies , Risk Factors , Stroke/diagnosis , Stroke/epidemiology , Time Factors , Treatment Outcome , Warfarin/adverse effects
16.
Crit Rev Food Sci Nutr ; 59(17): 2831-2838, 2019.
Article in English | MEDLINE | ID: mdl-29746786

ABSTRACT

Vitamin E is a lipid soluble vitamin comprising of eight natural isoforms, namely, α, ß, δ, γ isoforms of tocopherol and α, ß, δ, γ isoforms of tocotrienol. Many studies have been performed to elucidate its role in cancer. Until last decade, major focus was on alpha tocopherol and its anticancer effects. However, major clinical trials using alpha-tocopherol like SELECT trial and ATBC trial did not yield meaningful results. Hence there was a shift of focus to gamma-tocopherol, delta-tocopherol and tocotrienol. Unlike alpha-tocopherol, gamma-tocopherol and delta-tocopherol can scavenge reactive nitrogen species in addition to reactive oxygen species. Antiangiogenic effect, inhibition of HMG CoA reductase enzyme and inhibition of NF-κB pathway make the anti-cancer effects of tocotrienols unique compared to other vitamin E isoforms. Preclinical research on non-alpha tocopherol isoforms of vitamin E showed promising data on their anticancer effects. In this review, we deal with the current understanding on the potential mechanisms involved in the anticancer effects of vitamin E and the controversies in this field over last three decades. We also highlight the need to conduct further research on the anticancer effects of non-alpha-tocopherol isoforms in larger population and clinical setting.


Subject(s)
Antineoplastic Agents/pharmacology , Neoplasms , Vitamin E/pharmacology , Clinical Trials as Topic , Humans , Tocotrienols , alpha-Tocopherol , gamma-Tocopherol
17.
Curr Med Chem ; 26(9): 1693-1700, 2019.
Article in English | MEDLINE | ID: mdl-29737246

ABSTRACT

Oxidized LDL (ox-LDL) plays a central role in atherosclerosis by acting on multiple cells such as endothelial cells, macrophages, platelets, fibroblasts and smooth muscle cells through LOX-1. LOX-1 is a 50 kDa transmembrane glycoprotein that serves as receptor for ox-LDL, modified lipoproteins, activated platelets and advance glycation end-products. Ox- LDL through LOX-1, in endothelial cells, causes increase in leukocyte adhesion molecules, activates pathways of apoptosis, increases reactive oxygen species and cause endothelial dysfunction. In vascular smooth muscle cells and fibroblasts, they stimulate proliferation, migration and collagen synthesis. LOX-1 expressed on macrophages inhibit macrophage migration and stimulate foam cell formation. They also stimulate generation of metalloproteinases and contribute to plaque instability and thrombosis. Drugs that modulate LOX-1 are desirable targets against atherosclerosis. Many naturally occurring compounds have been shown to modulate LOX-1 expression and atherosclerosis. Currently, novel drug design techniques are used to identify molecules that can bind to LOX-1 and inhibit its activation by ox-LDL. In addition, techniques using RNA interference and monoclonal antibody against LOX-1 are currently being investigated for clinical use.


Subject(s)
Atherosclerosis/metabolism , Lipoproteins, LDL/metabolism , Scavenger Receptors, Class E/metabolism , Animals , Humans
19.
South Med J ; 111(4): 230-234, 2018 04.
Article in English | MEDLINE | ID: mdl-29719036

ABSTRACT

OBJECTIVES: Auscultation is an important clue to the presence of aortic stenosis (AS). We sought to assess the effect of symptom status, prior knowledge of diagnosis, and other patient factors on murmur detection. METHODS: Patients with moderate-to-severe AS by echocardiography at a single center between June 2015 and June 2016 were included. Five consecutive patient encounters (inpatient and outpatient) within 12 months before the echocardiogram were analyzed. RESULTS: Ninety-five patients (418 different clinician encounters) were studied. The murmur of AS was identified by only 39% of clinicians. In multivariate analysis, significant determinants of murmur detection were examination in outpatient setting (odds ratio [OR] 3.40, 95% confidence interval [CI] 1.75-6.61), known history of AS (OR 2.77, 95% CI 1.53-5.01), female sex (OR 1.97, 95% CI 1.07-3.60), and presence of symptoms (OR 1.91 95% CI 1.12-3.26). Compared with the murmur detection findings by clinicians in medicine, the findings of surgical specialty clinicians were significantly lower (OR 0.12, 95% CI 0.06-0.26, P < 0.001). CONCLUSIONS: In this real-world assessment, clinical context played an important role in the auscultation of AS murmur. The findings have important implications for the clinical diagnosis of asymptomatic advanced AS.


Subject(s)
Aortic Valve Stenosis , Asymptomatic Diseases/therapy , Auscultation/methods , Clinical Competence , Heart Murmurs , Aged , Aged, 80 and over , Aortic Valve Stenosis/diagnosis , Aortic Valve Stenosis/physiopathology , Arkansas , Clinical Competence/standards , Clinical Competence/statistics & numerical data , Echocardiography/methods , Female , Heart Murmurs/diagnosis , Heart Murmurs/etiology , Humans , Male , Middle Aged , Quality Improvement , Retrospective Studies , Severity of Illness Index
20.
J Card Fail ; 24(5): 321-329, 2018 May.
Article in English | MEDLINE | ID: mdl-29482028

ABSTRACT

BACKGROUND: Heart failure (HF) is a major global health problem. Clinical trials test efficacy, effectiveness, and safety of novel and emerging therapies in HF. We sought to determine the salient features of ongoing interventional clinical trials in HF. METHODS AND RESULTS: We accessed the ClinicalTrials.gov registry of the National Institutes of Health (NIH) and the International Clinical Trials Registry Platform of the World Health Organization on January 1, 2017, and extracted pertinent information on current HF clinical trials for systematic review. Of 794 HF trials that met our inclusion criteria, almost one-half (49.1%) evaluated clinical end points and one-third (32.8%) examined imaging end points as primary outcomes. One-fourth (24.8%) were industry sponsored and one-third (35.6%) were university sponsored. The NIH and other United States federal agencies funded only 14 trials (1.8% of all trials; 10.7% of trials in the US). Among 536 HF trials with specified left ventricular ejection fraction status, 434 (81.0%) focused on HF with reduced ejection fraction (HFrEF) and only 102 (19.0%) trials targeted HF with preserved ejection fraction (HFpEF). CONCLUSIONS: Ongoing HF trials are predominantly sponsored by nongovernmental funding agencies. Although HFpEF occurs as commonly as HFrEF in the community, the number of clinical trials targeting HFpEF is substantially lower compared with HFrEF.


Subject(s)
Clinical Trials as Topic/methods , Disease Management , Heart Failure/therapy , Registries , Stroke Volume/physiology , Heart Failure/physiopathology , Humans , United States
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