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1.
Am J Cardiol ; 208: 13-15, 2023 12 01.
Article in English | MEDLINE | ID: mdl-37806184

ABSTRACT

This retrospective study evaluates the prognostic value of pulmonary artery oxygen saturation (PA O2) among patients who undergo mechanical intervention for pulmonary embolism (PE). Patients who died within 90 days had less PA O2, and a greater percentage of patients with a PA O2 of <50 died within 90 days of intervention. Regression analysis revealed an association of PA O2 with mortality that held true despite accounting for Pulmonary Embolism Severity Index (PESI) score and type of endovascular intervention. Receiver operator curve testing revealed PA O2 <50% to be inferior to PESI score but superior to Bova score in predicting mortality after mechanical PE intervention, with the combination of PA O2 <50% and PESI outperforming PESI and PA O2 in predicting mortality. Our pilot evaluation suggests preintervention PA O2 <50% to be associated with increased risk of all-cause mortality and may help identify patients at greatest risk of deterioration.


Subject(s)
Pulmonary Artery , Pulmonary Embolism , Humans , Prognosis , Retrospective Studies , Risk Assessment , Oxygen Saturation , Predictive Value of Tests , Pulmonary Embolism/complications , Severity of Illness Index
2.
Catheter Cardiovasc Interv ; 101(1): 108-112, 2023 01.
Article in English | MEDLINE | ID: mdl-36403280

ABSTRACT

Coronary artery aneurysmal dilation is a rare finding with poorly understood mechanism of action that is found in small population of patients undergoing coronary angiography. Mycotic coronary aneurysm is an even rarer cause of coronary aneurysmal dilatation that develops as a potentially fatal complication of bacteremia. We present a case of mycotic right coronary artery aneurysm in a nonsurgical candidate with complex medical comorbidities treated with percutaneous coronary intervention via covered stents.


Subject(s)
Aneurysm, Infected , Coronary Aneurysm , Coronary Vessels , Percutaneous Coronary Intervention , Stents , Humans , Coronary Aneurysm/etiology , Coronary Aneurysm/surgery , Coronary Angiography/adverse effects , Coronary Vessels/diagnostic imaging , Percutaneous Coronary Intervention/adverse effects , Stents/adverse effects , Treatment Outcome , Aneurysm, Infected/etiology , Aneurysm, Infected/surgery
3.
J Interv Cardiol ; 2022: 5692964, 2022.
Article in English | MEDLINE | ID: mdl-35401062

ABSTRACT

Objectives: Evaluation of the safety and efficacy of the Penumbra device as an adjunct to percutaneous coronary intervention (PCI) in patients with myocardial infarction (MI) and a large thrombus burden that requires thrombectomy. Background: For patients with acute MI, PCI is the primary reperfusion method. Large thrombus burden has always been a limitation of successful reperfusion. However, the use of current aspiration devices has been associated with an increased incidence of stroke. Methods: We performed a retrospective chart review at the University Hospitals Medical Center in Cleveland. Our study included data from patients who underwent PCI for ST segment elevation myocardial infarction (STEMI) and non-ST segment elevation myocardial infarction (NSTEMI) assisted by the Penumbra Cat RX device (a wide-lumen thrombus aspiration catheter) between May 2019 and February 2021. The primary outcome was the final thrombolysis in myocardial infarction (TIMI) flow. The secondary endpoints were a composite of adverse cardiac events at 6 months. About 50% of the patients did undergo transfemoral PCI as per preference of individual operators. The Penumbra thrombectomy device can be used both by radial and femoral approach and does not need any different guide catheter use. Results: TIMI flow 3 was achieved in 111 patients (90.2%). The secondary endpoint occurred in 11 patients (8.9%, 3 MI, 8 heart failure hospitalizations). There were no stroke events or device-related complications. The door-to-balloon time was not affected by usage of the Penumbra device. Failure in the restoration of TIMI 3 flow was associated with the use of balloon angioplasty prior to the application of the Penumbra device, leading to distal embolization. Conclusions: The Penumbra Cat RX provides safe and effective thrombus removal with better clinical outcomes, even in high-risk patients with acute coronary syndrome.


Subject(s)
Coronary Thrombosis , Myocardial Infarction , Percutaneous Coronary Intervention , Stroke , Thrombosis , Coronary Angiography , Coronary Thrombosis/surgery , Humans , Myocardial Infarction/surgery , Retrospective Studies , Stroke/etiology , Stroke/therapy , Thrombectomy/adverse effects , Thrombosis/etiology , Treatment Outcome
4.
Indian Heart J ; 70(2): 323-325, 2018.
Article in English | MEDLINE | ID: mdl-29716715

ABSTRACT

BACKGROUND: Peripheral arterial disease (PAD) is an underdiagnosed illness often affecting the elderly population. Ankle brachial index (ABI) is a good diagnostic tool for PAD in outpatient practice, but remains underused. MATERIALS AND METHODS: Patients were recruited from an outpatient medical camp in rural India, and assessed for symptoms and pre-existing risk factors. Measured ABI≤0.9 was considered abnormal and considered PAD. RESULTS: Out of 100 patients recruited, PAD was diagnosed in 57 patients. Associated risk factors were like age >55years (67%), hypertension (66%), smoking (69%) and diabetes mellitus (35%) were common. CONCLUSION: PAD is a very common and underdiagnosed illness in rural India. A simple tool like ABI can help diagnosis in underserved areas.


Subject(s)
Ankle Brachial Index/methods , Blood Pressure/physiology , Mass Screening/methods , Peripheral Arterial Disease/diagnosis , Rural Population , Adolescent , Adult , Aged , Aged, 80 and over , Cross-Sectional Studies , Female , Humans , Incidence , India/epidemiology , Male , Middle Aged , Peripheral Arterial Disease/epidemiology , Peripheral Arterial Disease/physiopathology , Predictive Value of Tests , Risk Factors , Young Adult
5.
J Phys Condens Matter ; 29(38): 385302, 2017 Sep 27.
Article in English | MEDLINE | ID: mdl-28677587

ABSTRACT

The electronic states at graphene-SiO2 interface and their inhomogeneity is investigated using the back-gate-voltage dependence of local tunnel spectra acquired with a scanning tunneling microscope. The conductance spectra show two, or occasionally three, minima that evolve along the bias-voltage axis with the back gate voltage. This evolution is modeled using tip-gating and interface states. The energy dependent interface states' density, [Formula: see text], required to model the back-gate evolution of the minima, is found to have significant inhomogeneity in its energy-width. A broad [Formula: see text] leads to an effect similar to a reduction in the Fermi velocity while the narrow [Formula: see text] leads to the pinning of the Fermi energy close to the Dirac point, as observed in some places, due to enhanced screening of the gate electric field by the narrow [Formula: see text]. Finally, this also demonstrates STM as a tool to probe the density of interface states in various 2D Dirac materials.

6.
Cardiovasc Ther ; 35(4)2017 Aug.
Article in English | MEDLINE | ID: mdl-28423226

ABSTRACT

Low-density cholesterol (LDL) has been the prime target of currently available lipid-lowering therapies although current research is expanding the focus beyond LDL lowering and has included high-density cholesterol (HDL) also as the target. Bromo and extra-terminal (BET) proteins are implicated in the regulation of transcription of several regulatory genes and regulation of proinflammatory pathways. As atherosclerosis is an inflammatory pathway and studies showed that BET inhibition has a role in inhibiting inflammation, the concept of BET inhibition came in the field of atherosclerosis. RVX 208 is a novel, orally active, BET protein inhibitor and the only BET inhibitor currently available in the field of atherosclerosis. RVX 208 acts primarily by increasing apo A-I (apolipoprotein A-I) and HDL levels. RVX 208 has a novel action of increasing larger, more cardio-protective HDL particles. Post hoc analysis of Phase II trials also showed that RVX 208 reduced major adverse cardiovascular events (MACE) in treated patients, over and above that of apo A-I/HDL increasing action. This MACE reducing actions of RVX 208 were largely due to its novel anti-inflammatory actions. Currently, a phase III trial, BETonMACE, is recruiting patients to look for the effects of RVX 208 in patients with increased risk of atherosclerotic cardiovascular disease. So BET inhibitors act in multiple ways to inhibit and modulate atherosclerosis and would be an emerging and potential option in the management of multifactorial disease like coronary artery disease by inhibiting a single substrate. But we need long-term phase III trial data's to look for effects on real-world patients.


Subject(s)
Apolipoprotein A-I/biosynthesis , Lipoproteins, HDL/biosynthesis , Protein Synthesis Inhibitors/pharmacology , Proteins/antagonists & inhibitors , Quinazolines/pharmacology , Clinical Trials, Phase I as Topic , Clinical Trials, Phase II as Topic , Clinical Trials, Phase III as Topic , Humans , Quinazolinones
7.
J Patient Cent Res Rev ; 4(3): 104-113, 2017.
Article in English | MEDLINE | ID: mdl-31413977

ABSTRACT

PURPOSE: Multiple studies have shown pulse pressure (PP) to be a strong predictor of aortic calcification. However, no studies are available that correlate PP with aortic calcification at the segmental level. METHODS: We identified 37 patients with aortic PP measured during cardiac catheterization. Their noncontrast chest computed tomography scans were evaluated for the presence of calcium in different segments (ascending aorta, arch of aorta [arch], descending aorta) and quantified. Patients with calcification (Calcified Group A) were compared against patients without calcification (Noncalcified Group B) in terms of PP, calcification and compliance. RESULTS: The mean of the total calcium score was higher in the descending aorta than the arch or ascending aorta (691 vs 571 vs 131, respectively, P<0.0001). PP had the strongest correlation with calcification in the descending aorta (r=0.47, P=0.004). Calcified Group A had a much higher PP than Noncalcified Group B, with the greatest difference in the descending aorta (20 mmHg, P<0.0001), lesser in the ascending aorta (10 mmHg, P=0.12) and the least in the arch (5 mmHg, P=0.38). Calcified Group A patients also had much lower compliance than Noncalcified Group B patients, with the greatest difference among groups seen in the descending aorta (0.7 mL/mmHg, P=0.002), followed by the ascending aorta, then arch. CONCLUSIONS: These are the first data to evaluate the relative impact of aortic segments in PP. Finding the greatest amount of calcification along with greatest change in PP and compliance in the descending aorta makes a case that the descending aorta plays a major role in PP as compared to other segments of the thoracic aorta.

8.
J Clin Pharmacol ; 57(5): 547-557, 2017 05.
Article in English | MEDLINE | ID: mdl-27670133

ABSTRACT

Pulmonary arterial hypertension (PAH) is a relatively rare disease that, due to its chronic nature, has always been difficult to treat effectively. Selexipag is an oral prostacyclin (PGI2 ) agonist that was approved by US Food and Drug Administration (US FDA) in December 2015 for the treatment of PAH. After its success in phase 1 and phase 2 clinical trials regarding the convenient oral twice-daily dosing and low side-effect profile, selexipag raised the hope of controlling the disease progression in PAH patients. In the recently completed multicentered phase 3 study (GRIPHON), selexipag has been shown to reduce death and hospitalization due to PAH significantly, an effect that was consistent across different ranges of maintenance dose. In the same study selexipag use was also associated with an increase in 6-minute walk distance (a measure of symptom severity) from baseline, but no significant improvement in all-cause mortality could be observed. The results of the ongoing phase 3 studies (TRITON and TRANSIT-1) are expected to throw some more light on the safety and efficacy of this novel molecule across various treatment scenarios. Hence, our article aims to summarize all the available information from preclinical and clinical studies published to date on the pharmacodynamics, pharmacokinetics, efficacy, safety (in general and in scenarios such as hepatic and renal function impairment), significant drug interactions (with warfarin and antiretroviral drugs), and clinical significance of oral selexipag in patients with PAH.


Subject(s)
Acetamides/therapeutic use , Hypertension, Pulmonary/drug therapy , Pyrazines/therapeutic use , Acetamides/adverse effects , Acetamides/pharmacokinetics , Acetamides/pharmacology , Animals , Antihypertensive Agents/adverse effects , Antihypertensive Agents/pharmacokinetics , Antihypertensive Agents/pharmacology , Antihypertensive Agents/therapeutic use , Drug Interactions , Humans , Pyrazines/adverse effects , Pyrazines/pharmacokinetics , Pyrazines/pharmacology
9.
Cardiovasc Ther ; 35(1): 55-63, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27727514

ABSTRACT

Heart failure continues to be a widely prevalent disease across the world, affecting millions of Americans annually. Acute heart failure (AHF) has a substantial effect on rising healthcare costs and is one of the major causes of morbidity and mortality. The search for new drugs for symptom relief and to improve long-term outcomes in heart failure has led to development of serelaxin, a recombinant human relaxin-2 hormone. Relaxin was discovered in pregnancy, but eventually found to have a number of other physiological actions, not only in pregnancy, but also in nonpregnant women and men. The actions of serelaxin are primarily via nitric oxide, leading to the observed vasodilatory effects, and increase in renal plasma flow. It has also been found to increase expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)-2 and MMP-9. The antifibrotic and antiinflammatory effects of the drug also play a role in heart failure. In Phase II studies, serelaxin has shown reduction in pulmonary arterial pressure, pulmonary capillary wedge pressure, and NT-proBNP. The recently published results of the RELAX-AHF, a phase III clinical trial on serelaxin, has opened new avenues into our understanding of its effects in heart failure. The trial showed improvement in short-term dyspnea scores and 180-day mortality, but, interestingly, failed to show any improvement of the secondary endpoints of death or readmission at 60 days. Ongoing Phase III trials like RELAX-AHF-2 and RELAX-AHF-ASIA would explain these data better and improve understanding of the use of serelaxin in clinical practice. This article summarizes the most updated published preclinical and clinical study data on serelaxin, including pharmacokinetic, pharmacodynamic, safety studies in hepatic, renal impaired patients, Phase II and Phase III trials.


Subject(s)
Cardiovascular Agents/therapeutic use , Heart Failure/drug therapy , Relaxin/therapeutic use , Acute Disease , Animals , Cardiovascular Agents/adverse effects , Cardiovascular Agents/metabolism , Cardiovascular Agents/pharmacokinetics , Clinical Trials as Topic , Disease Models, Animal , Drug Evaluation, Preclinical , Heart Failure/metabolism , Heart Failure/physiopathology , Humans , Recombinant Proteins/adverse effects , Recombinant Proteins/metabolism , Recombinant Proteins/pharmacokinetics , Recombinant Proteins/therapeutic use , Relaxin/adverse effects , Relaxin/metabolism , Relaxin/pharmacokinetics , Signal Transduction/drug effects , Treatment Outcome
10.
Int J Cardiol ; 227: 556-564, 2017 Jan 15.
Article in English | MEDLINE | ID: mdl-27838121

ABSTRACT

Ranolazine was FDA approved for chronic angina in 2006. Since then, there has been extensive research involving this drug. The mechanism of action, debatable at the time of approval, has been demonstrated. Ranolazine acts via inhibition of late sodium channel current in the myocardium. This acts by lowering abnormally high cytosolic calcium levels. Other possible clinical applications of Ranolazine have also been explored. Out of many lines of investigation, its effects in atrial fibrillation, especially post-CABG and recurrent atrial fibrillation show promise. It has also shown definite HbA1c lowering effects when used in diabetics with coronary artery disease. Other possible indications for the drug include pulmonary arterial hypertension, diastolic dysfunction and chemotherapy-induced cardiotoxicity. This review aims to summarize major research regarding Ranolazine in potential applications beyond chronic angina. There are few dedicated large, randomized, phase III trials exploring the newer effects of Ranolazine. There are a few such trials underway, but more are needed.


Subject(s)
Angina Pectoris/drug therapy , Atrial Fibrillation/drug therapy , Diabetes Mellitus/drug therapy , Ranolazine/therapeutic use , Sodium Channel Blockers/therapeutic use , Aged , Angina Pectoris/diagnosis , Angina Pectoris/mortality , Atrial Fibrillation/mortality , Atrial Fibrillation/prevention & control , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/drug therapy , Cardiovascular Diseases/mortality , Chronic Disease , Diabetes Mellitus/diagnosis , Diabetes Mellitus/mortality , Female , Humans , Male , Middle Aged , Prognosis , Randomized Controlled Trials as Topic , Risk Assessment , Role , Survival Analysis , Treatment Outcome
11.
Int J Cardiol ; 224: 170-177, 2016 Dec 01.
Article in English | MEDLINE | ID: mdl-27657469

ABSTRACT

Heart failure (HF) is a burgeoning chronic health condition affecting more than 20million people worldwide. Patients with HF have a significant (17.1%) 30-day readmission rate, which invites substantial penalty in payment to hospitals from Centers for Medicare and Medicaid Services, as per the newly introduced Hospital Readmissions Reduction Program. Depression is one of the important risk factors for readmission in HF patients. It has a significant prevalence in patients with HF and contributes to the overall poor quality of life in them. Several behavioral (smoking, obesity, lack of exercise and medication noncompliance) and pathophysiological factors (hypercortisolism, elevated inflammatory biomarkers, fibrinogen, and atherosclerosis) have been found responsible for the adverse outcome in patients with HF and concomitant depression. Hippocampal volume loss noted in patients with acute HF exacerbations may contribute to the development of depressive symptoms in them. Screening for depression in HF patients continues to be challenging due to a considerable overlap in symptoms. Published trials on the use of antidepressants and cognitive behavioral therapy (CBT) have shown variable outcomes. Newer modalities like internet-based CBT have been tried in small studies, with promising results. A recent meta-analysis observed the beneficial role of aerobic exercise training in patients with HFrEF. Future long-term prospective studies may contribute to the formulation of a detailed screening and management guideline for patients with HF and depression. Our review is aimed to summarize the intricate relationship between depression and heart failure, with respect to their epidemiology, pathophysiological aspects, and optimal management approach.


Subject(s)
Depression , Heart Failure , Quality of Life , Depression/physiopathology , Depression/therapy , Disease Management , Heart Failure/psychology , Heart Failure/therapy , Humans
12.
J Invasive Cardiol ; 28(7): 265-70, 2016 Jul.
Article in English | MEDLINE | ID: mdl-27342202

ABSTRACT

OBJECTIVES: Recent studies have suggested that fractional flow reserve (FFR) measurement can be avoided by using similar ranges of baseline mean coronary pressure (Pd) to mean aortic pressure (Pa) ratio (0.88-0.95). Further studies have suggested that too many significant coronary stenoses are misclassified based on these ranges. We hypothesized that with a certain range of baseline Pd/Pa, 100% positive predictive value (PPV) and negative predictive value (NPV) can be achieved to avoid misclassification. METHODS: We retrospectively evaluated the pressure tracings of 555 consecutive intermediate coronary stenotic lesions that had undergone FFR measurement in the cardiac catheterization laboratory of a tertiary-care center. The baseline Pd/Pa was manually measured and correlated with final FFR. The operating test characteristics were calculated using an abnormal FFR of ≤0.80 as the criterion standard for the presence of hemodynamic, significant coronary stenosis. RESULTS: The area under the receiver-operating characteristics curve of baseline Pd/Pa for predicting FFR was 0.89, very similar to published results for instantaneous wave-free ratio and Pd/Pa. However, a significant number of lesions were mischaracterized (ie, using a baseline Pd/Pa of ≤0.88 to >0.95, there were 22 misclassifications, with 6 false-positive and 16 false-negative results). At a Pd/Pa of ≤0.86, 100% PPV was achieved, and 100% NPV was achieved at >1.00. CONCLUSION: A baseline Pd/Pa of ≤0.86 is associated with a PPV of 100%, which can avoid the misclassification errors seen in prior studies. This provides a more clinically useful application of baseline Pd/Pa.


Subject(s)
Coronary Stenosis , Coronary Vessels , Diagnostic Errors/prevention & control , Adenosine/administration & dosage , Aged , Arterial Pressure/physiology , Cardiac Catheterization/methods , Coronary Stenosis/diagnosis , Coronary Stenosis/physiopathology , Coronary Vessels/diagnostic imaging , Coronary Vessels/pathology , Coronary Vessels/physiopathology , Female , Fractional Flow Reserve, Myocardial/physiology , Hemodynamics , Humans , Hyperemia/physiopathology , Male , Middle Aged , Predictive Value of Tests , Retrospective Studies , Severity of Illness Index , Vasodilator Agents/administration & dosage
13.
J Cardiovasc Pharmacol ; 68(3): 183-90, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27092662

ABSTRACT

The aim of this comprehensive review article is to emphasize on the possible exploration of a new therapeutic approach in the management of heart failure (HF) and other cardiovascular diseases: the renin-angiotensin-aldosterone system-neprilysin combination inhibitors, also called angiotensin receptor neprilysin inhibitor, valsartan/sacubitril (LCZ696). Sacubitril is an inhibitor of neutral endopeptidase (NEP) which degrades vasoactive peptides such as atrial natriuretic peptide and brain natriuretic peptide. Valsartan is an angiotensin receptor blocker which is usually used in hypertension. Although HF has been a global health burden, for decades there has been lack of novel therapeutic options as many trials failed due to potential side effects. With the published results of the landmark trial Prospective comparison of ARNI with ACEI to Determine the Impact on Global Mortality and morbidity in HF (PARADIGM-HF), a new direction in the treatment of HF is anticipated. This trial showed that LCZ696 was able to reduce the primary composite end point of cardiovascular death or HF hospitalization, and similar reduction was observed for cardiovascular death. This review article also highlights the results of 4 published trials of LCZ696 in both HTN and HF. After the results of PARADIGM-HF trial, the major challenge will be outcome in regular clinical practice, as subjects in the trial were mostly stable New York Heart Association class II patients with no comorbidities. In addition, many trials are simultaneously in progress regarding the use of LCZ696 in patients with diabetes, renal failure, and hepatic impairment. To conclude, sacubitril/valsartan significantly improved morbidity and mortality in patients with chronic HF, but it will need meticulous attention when used in real outpatient practice.


Subject(s)
Aminobutyrates/administration & dosage , Angiotensin Receptor Antagonists/administration & dosage , Cardiovascular Diseases/drug therapy , Clinical Trials as Topic/methods , Neprilysin/antagonists & inhibitors , Renin-Angiotensin System/drug effects , Tetrazoles/administration & dosage , Biphenyl Compounds , Cardiovascular Diseases/metabolism , Drug Combinations , Drug Therapy, Combination , Humans , Neprilysin/metabolism , Renin-Angiotensin System/physiology , Valsartan
14.
Int J Cardiol ; 214: 292-8, 2016 Jul 01.
Article in English | MEDLINE | ID: mdl-27082776

ABSTRACT

The Vitamin K antagonist warfarin was the only oral anticoagulant available for decades for the treatment of thrombosis and prevention of thromboembolism until Direct Oral Anticoagulants (DOACs); a group of new oral anticoagulants got approved in the last few years. Direct thrombin inhibitor: dabigatran and factor Xa inhibitors: apixaban, rivaroxaban, and edoxaban directly inhibit the coagulation cascade. DOACs have many advantages over warfarin. However, the biggest drawback of DOACs has been the lack of specific antidotes to reverse the anticoagulant effect in emergency situations. Activated charcoal, hemodialysis, and activated Prothrombin Complex Concentrate (PCC) were amongst the nonspecific agents used in a DOAC associated bleeding but with limited success. Idarucizumab, the first novel antidote against direct thrombin inhibitor dabigatran was approved by US FDA in October 2015. It comprehensively reversed dabigatran-induced anticoagulation in a phase I study. A phase III trial on Idarucizumab also complete reversal of anticoagulant effect of dabigatran. Andexanet alfa (PRT064445), a specific reversal agent against factor Xa inhibitors, showed a complete reversal of anticoagulant activity of apixaban and rivaroxaban within minutes after administration without adverse effects in two recently completed parallel phase III trials ANNEXA-A and ANNEXA-R respectively. It is currently being studied in ANNEXA-4, a phase IV study. Aripazine (PER-977), the third reversal agent, has shown promising activity against dabigatran, apixaban, rivaroxaban, as well as subcutaneous fondaparinux and LMWH. This review article summarizes pharmacological characteristics of these novel antidotes, coagulation's tests affected, available clinical and preclinical data, and the need for phase III and IV studies.


Subject(s)
Anticoagulants/adverse effects , Antidotes/administration & dosage , Hemorrhage/drug therapy , Administration, Oral , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/therapeutic use , Anticoagulants/administration & dosage , Clinical Trials as Topic , Dabigatran/administration & dosage , Dabigatran/adverse effects , Factor Xa/administration & dosage , Factor Xa/adverse effects , Hemorrhage/chemically induced , Humans , Recombinant Proteins/administration & dosage , Recombinant Proteins/adverse effects
15.
Int J Cardiol ; 212: 29-36, 2016 Jun 01.
Article in English | MEDLINE | ID: mdl-27017118

ABSTRACT

Diabetes is a leading cause of morbidity and mortality worldwide. Management of diabetes is changing at a rapid pace. Three new classes of antidiabetic drugs including GLP-1 (Glucagon-like peptide 1), DPP-IV (Dipeptidyl peptidase IV) and SGLT2 (Sodium glucose cotransporter 2) inhibitors have been approved in the last few years. Treating diabetes with the antidiabetic drug does not always reduce the cardiovascular complications of diabetes. On the contrary, there was a huge controversy regarding the effect of rosiglitazone on cardiovascular risk reduction a few years ago. Since then, submission of postmarketing cardiovascular outcome study data has been mandated by US FDA and other drug regulatory agencies for newer antidiabetic medications. This is to avoid further premature claims regarding cardiovascular harm or safety of the newer classes. We already have some cardiovascular safety data available on DPP-IV and GLP-1 groups of medications. Dapagliflozin, canagliflozin, and empagliflozin are currently approved SGLT2 inhibitors. We do not have sufficient cardiovascular outcome data available for this novel class. However, this group of drugs, which act by increasing renal glucose excretion, have also shown some non-glycemic benefits including weight reduction, blood pressure control, diuretic action, renal protection, decrease in arterial stiffness and uric acid reduction. Empagliflozin, a new member of SGLT2 class, showed significant cardiovascular morbidity and mortality benefit in recently published EMPA-REG OUTCOME trial. The authors summarize all the published clinical and preclinical cardiovascular outcome data of SGLT2 inhibitors, including recently completed and ongoing major clinical trials in this comprehensive review.


Subject(s)
Cardiovascular Diseases/drug therapy , Cardiovascular Diseases/metabolism , Hypoglycemic Agents/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors , Sodium-Glucose Transporter 2/metabolism , Animals , Benzhydryl Compounds/pharmacology , Benzhydryl Compounds/therapeutic use , Cardiovascular Diseases/diagnosis , Clinical Trials as Topic/methods , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/metabolism , Drug Evaluation, Preclinical/methods , Glucosides/pharmacology , Glucosides/therapeutic use , Humans , Hypoglycemic Agents/pharmacology , Risk Factors , Treatment Outcome
16.
Phys Rev Lett ; 114(15): 157003, 2015 Apr 17.
Article in English | MEDLINE | ID: mdl-25933333

ABSTRACT

We demonstrate the role of the proximity effect in the thermal hysteresis of superconducting constrictions. From the analysis of successive thermal instabilities in the transport characteristics of micron-size superconducting quantum interference devices with a well-controlled geometry, we obtain a complete picture of the different thermal regimes. These determine whether or not the junctions are hysteretic. Below the superconductor critical temperature, the critical current switches from a classical weak-link behavior to one driven by the proximity effect. The associated small amplitude of the critical current makes it robust with respect to the heat generation by phase slips, leading to a nonhysteretic behavior.

17.
Pharmacotherapy ; 35(4): 388-95, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25884527

ABSTRACT

STUDY OBJECTIVES: To estimate periprocedural bleeding risk before elective percutaneous coronary intervention (PCI) by using a point-of-care bleeding risk calculator and to document changes in anticoagulant use and bleeding complications after implementation of use of this calculator. DESIGN: Prospective observational pilot study with a historical control cohort. SETTING: Tertiary care medical center. PATIENTS: The pilot cohort consisted of 100 patients undergoing ad hoc PCI during elective cardiac catheterization procedures between January and May 2013, whose bleeding risk and accompanying PCI anticoagulant recommendations were determined by the use of a pre-PCI point-of-care bleeding risk calculator. The historical control cohort consisted of all patients who underwent elective PCI at the same facility between April 1, 2011, and March 31, 2012, before implementation of use of the bleeding risk calculator. MEASUREMENTS AND MAIN RESULTS: The pre-PCI bleeding risk calculator distinguished patients in the pilot cohort as high risk (score 12 or higher) or low risk (lower than 12) for bleeding after a PCI procedure. The primary outcome was bivalirudin use in the pilot cohort compared with its use in the historical control cohort. Implementation of the bleeding risk calculator significantly decreased bivalirudin use compared with bivalirudin use in the historical control cohort (87% in the control cohort vs 60% in the pilot cohort, p<0.01). Bivalirudin use remained high in patients at high bleeding risk (82.2% in the pilot cohort vs 87.4% in the control cohort, p=0.3) and its use was decreased in patients at low bleeding risk (41.8% in the pilot cohort vs 87.1% in the control cohort, p<0.01). The incidence of bleeding complications in the pilot cohort was comparable with that in the control cohort (1% vs. 0.4%, p=0.37), although this pilot study was underpowered to potentially detect a significant change in the incidence of bleeding complications. CONCLUSION: A simple bleeding risk calculator can substantially reduce overall bivalirudin use by specifically decreasing its use among patients at low bleeding risk while maintaining its use among patients at high bleeding risk. The incidence of bleeding complications remained unchanged despite decreasing bivalirudin use among patients undergoing elective coronary catheterization who were at low risk for bleeding.


Subject(s)
Anticoagulants/therapeutic use , Hemorrhage/prevention & control , Percutaneous Coronary Intervention/adverse effects , Point-of-Care Systems , Aged , Aged, 80 and over , Female , Glomerular Filtration Rate , Health Care Costs , Hemorrhage/economics , Hirudins , Humans , Male , Peptide Fragments/therapeutic use , Pilot Projects , Prospective Studies , Recombinant Proteins/therapeutic use , Risk Assessment
18.
J Phys Condens Matter ; 27(1): 015601, 2015 Jan 14.
Article in English | MEDLINE | ID: mdl-25469688

ABSTRACT

Bi2Te3 is a member of a new class of materials known as topological insulators which are supposed to be insulating in the interior and conducting on the surface. However, experimental verification of the conductive qualities of the surface states has been hindered by parallel bulk conductions. We report low temperature magnetotransport measurements on single crystal samples of Bi2Te3. We observe metallic character in our samples and large and linear magnetoresistance from 1.5 K to 290 K with prominent Shubnikov-de Haas (SdH) oscillations whose traces persist up to 20 K. Even though our samples are metallic, we are able to obtain a Berry phase close to the value of π, which is expected for Dirac fermions of the topological surface states. This indicates that we have obtained evidence for the topological surface states in metallic single crystals of Bi2Te3. Other physical measurements obtained from the analysis of the SdH oscillations are also in close agreement with those reported for the topological surface states. The linear magnetoresistance observed in our sample, which is considered as a signature of the Dirac fermions of the surface states, lends further credence to the existence of topological surface states.

19.
Eur Heart J Acute Cardiovasc Care ; 4(6): 499-508, 2015 Dec.
Article in English | MEDLINE | ID: mdl-25515725

ABSTRACT

AIMS: While randomized clinical trials have compared clopidogrel with higher potency adenosine diphosphate (ADP) receptor inhibitors among patients with acute myocardial infarction, little is known about the frequency, effectiveness and safety of switching between ADP receptor inhibitors in routine clinical practice. METHODS AND RESULTS: We studied 11,999 myocardial infarction patients treated with percutaneous coronary intervention at 230 hospitals from April 2010 to October 2012 in the TRANSLATE-ACS study. Multivariable Cox regression was used to compare six-month post-discharge risks of major adverse cardiovascular events (MACE: death, myocardial infarction, stroke, or unplanned revascularization) and Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO)-defined bleeding between in-hospital ADP receptor inhibitor switching versus continuation of the initially selected therapy. Among 8715 patients treated initially with clopidogrel, 994 (11.4%) were switched to prasugrel or ticagrelor; switching occurred primarily after percutaneous coronary intervention (60.9%) and at the time of hospital discharge (26.7%). Among 3284 patients treated initially with prasugrel or ticagrelor, 448 (13.6%) were switched to clopidogrel; 48.2% of switches occurred after percutaneous coronary intervention and 48.0% at hospital discharge. Switching to prasugrel or ticagrelor was not associated with increased bleeding when compared with continuation on clopidogrel (2.7% vs. 3.3%, adjusted hazard ratio 0.96, 95% confidence interval 0.64-1.42, p=0.82). Switching from prasugrel or ticagrelor to clopidogrel was not associated with increased MACE (8.9% vs. 7.7%, adjusted hazard ratio 1.06, 95% confidence interval 0.75-1.49, p=0.76) when compared with continuation on the higher potency agent. CONCLUSIONS: In-hospital ADP receptor inhibitor switching occurs in more than one in 10 myocardial infarction patients in contemporary practice. In this observational study, ADP receptor inhibitor switching does not appear to be significantly associated with increased hazard of MACE or bleeding.


Subject(s)
Drug Substitution/statistics & numerical data , Myocardial Infarction/drug therapy , Percutaneous Coronary Intervention/methods , Purinergic P2Y Receptor Antagonists/therapeutic use , Adenosine/analogs & derivatives , Adenosine/therapeutic use , Aged , Clopidogrel , Drug Substitution/adverse effects , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Myocardial Infarction/surgery , Patient Discharge/statistics & numerical data , Platelet Aggregation Inhibitors/therapeutic use , Prasugrel Hydrochloride/therapeutic use , Proportional Hazards Models , Purinergic P2Y Receptor Antagonists/adverse effects , Ticagrelor , Ticlopidine/analogs & derivatives , Ticlopidine/therapeutic use
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