32 results on '"Borer, Jeffrey S"'
Search Results
2. Survival after Aortic Valve Replacement for Aortic Regurgitation: Prediction from Preoperative Contractility Measurement.
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Borer JS, Supino PG, Herrold EM, Innasimuthu A, Hochreiter C, Krieger K, Girardi LN, and Isom OW
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- Adult, Aged, Aortic Valve Insufficiency diagnostic imaging, Aortic Valve Insufficiency surgery, Censuses, Coronary Angiography, Disease Progression, Echocardiography, Female, Follow-Up Studies, Heart Valve Prosthesis Implantation, Humans, Male, Middle Aged, Proportional Hazards Models, Prospective Studies, Risk Factors, Survival, Treatment Outcome, United States epidemiology, Ventricular Function, Left, Young Adult, Aortic Valve Insufficiency mortality, Exercise Test methods, Myocardial Contraction physiology
- Abstract
Background: Noninvasive measurement of myocardial contractility (end-systolic wall stress-adjusted change in left ventricular ejection fraction from rest to exercise [ΔLVEF - ΔESS]) predicts heart failure, subnormal LVEFrest, and sudden death in asymptomatic patients with chronic severe aortic regurgitation (AR). Here we assess the relation of preoperative ΔLVEF - ΔESS to survival after aortic valve replacement (AVR)., Methods: Patients who underwent AVR for chronic, isolated, pure severe AR (n = 66) were followed for 13.0 ± 6.4 event-free years. Preoperative ΔLVEF - ΔESS (from combined echocardiographic and radionuclide cineangiographic data) enabled cohort stratification into 3 terciles (-1 to -11% [normal or mild] contractility deficit, -12 to -16% [moderate], and ≤-17% [severe], identical with segregation in our earlier study) to relate preoperative contractility to postoperative survival and to age- and gender-matched US census data., Results: Since AVR, 22 patients died (average annual risk [AAR] for all-cause mortality for the entire co hort = 3.15%). Preoperative ΔLVEF - ΔESS predicted postoperative survival (p = 0.009, log rank test). By contractility terciles, all-cause AARs were 1.44, 2.58, and 6.40%. Survival was lower than among US census comparators (p < 0.02), but the "mild" tercile was indistinguishable from census data (p = ns). By multivariable Cox regression, survival prediction by pre-AVR ΔLVEF - ΔESS was independent of, and superior to, prediction by age at surgery, gender, preoperative functional class, LVEFrest, LVEFexercise, change in LVEFrest to exercise, and LV diastolic or systolic dimensions (p ≤ 0.01, pre-AVR ΔLVEF - ΔESS vs. other covariates)., Conclusion: In severe AR, preoperative contractility predicts post-AVR survival and may be prognostically superior to clinical, geometric and performance descriptors, potentially impacting on patient selection for surgery., (© 2018 The Author(s) Published by S. Karger AG, Basel.)
- Published
- 2018
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3. Raymond John Lipicky, MD.
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Borer JS
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- 2018
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4. Impact of Beta-Blockade on Cardiac Events in Patients with Chronic Severe Nonischemic Mitral Regurgitation.
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Supino PG, Hai OY, Sharma A, Lampert J, Hochreiter C, Herrold EM, and Borer JS
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- Adrenergic beta-Antagonists therapeutic use, Adult, Chronic Disease, Female, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Mitral Valve surgery, Mitral Valve Insufficiency complications, Mitral Valve Insufficiency mortality, Prospective Studies, Risk Factors, Adrenergic beta-Antagonists adverse effects, Death, Sudden, Cardiac etiology, Heart Diseases etiology, Mitral Valve Insufficiency drug therapy
- Abstract
Objectives: The aim of this study was to examine the impact of beta-blockade on cardiac events among patients with initially asymptomatic chronic severe nonischemic mitral valve regurgitation (MR)., Methods: Data from 52 consecutive patients in our prospective natural history study of isolated chronic severe nonischemic MR were assessed post hoc over 19 years to examine the relation of chronic beta-blockade use to subsequent cardiac events (death or indications for mitral valve surgery, MVS). At entry, all patients were free of surgical indications; 9 received beta-blockers. Cardiac event rate differences were analyzed by Kaplan-Meier log rank comparison., Results: During follow-up, cardiac events included sudden death (1), heart failure (8), atrial fibrillation (6), left ventricular dimensions at systole ≥4.5 cm (11), left ventricular ejection fraction <60% (6), right ventricular ejection fraction <35% (2), and a combination of cardiac events (7). The cardiac event risk was 4-fold higher among patients receiving beta-blockers (average annual risk = 60.6%) versus those not receiving beta-blockers (average annual risk = 15.2%; p = 0.001). These effects remained statistically significant (p = 0.005) when analysis was adjusted for other baseline covariates., Conclusions: Beta-blockade appears to confer an increased risk of sudden cardiac death or indications for MVS among patients with chronic severe nonischemic MR. Randomized trials are needed to confirm these findings., (© 2017 S. Karger AG, Basel.)
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- 2018
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5. Efficacy Profile of Ivabradine in Patients with Heart Failure plus Angina Pectoris.
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Borer JS, Swedberg K, Komajda M, Ford I, Tavazzi L, Böhm M, Depre C, Wu Y, Maya J, and Dominjon F
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- Adult, Aged, Angina Pectoris complications, Female, Heart Failure, Systolic complications, Heart Failure, Systolic physiopathology, Heart Rate drug effects, Humans, Ivabradine, Male, Middle Aged, Stroke Volume, Angina Pectoris drug therapy, Benzazepines therapeutic use, Cardiovascular Agents therapeutic use, Heart Failure, Systolic drug therapy
- Abstract
Objectives: In the Systolic Heart Failure Treatment with the If Inhibitor Ivabradine Trial (SHIFT), slowing of the heart rate with ivabradine reduced cardiovascular death or heart failure hospitalizations among patients with systolic chronic heart failure (CHF). Subsequently, in the Study Assessing the Morbidity-Mortality Benefits of the If Inhibitor Ivabradine in Patients with Coronary Artery Disease (SIGNIFY) slowing of the heart rate in patients without CHF provided no benefit for cardiovascular death or nonfatal myocardial infarction (primary composite end point), with secondary analyses suggesting possible harm in the angina subgroup. Therefore, we examined the impact of ivabradine in the patients with CHF plus angina in SHIFT., Methods: SHIFT enrolled adults with stable, symptomatic CHF, a left ventricular ejection fraction ≤35% and a sinus rhythm with a resting heart rate ≥70 bpm. Outcomes were the SHIFT and SIGNIFY primary composite end points and their components., Results: Of 6,505 patients in SHIFT, 2,220 (34%) reported angina at randomization. Ivabradine numerically, but not significantly, reduced the SIGNIFY primary composite end point by 8, 11 and 11% in the SHIFT angina subgroup, nonangina subgroup and overall population, respectively. Ivabradine also reduced the SHIFT primary composite end point in all 3 subgroups., Conclusions: In SHIFT, ivabradine showed consistent reduction of cardiovascular outcomes in patients with CHF; similar results were seen in the subgroup of SHIFT patients with angina., (© 2016 S. Karger AG, Basel.)
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- 2017
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6. Use and Disuse of Observational Research: The Case of Remote Monitoring in Heart Failure.
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Tavazzi L, Borer JS, and Tavazzi G
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- Cardiac Resynchronization Therapy, Cardiac Resynchronization Therapy Devices, Defibrillators, Implantable, Electrocardiography, Ambulatory instrumentation, Humans, Randomized Controlled Trials as Topic, Telemedicine, Heart Failure diagnosis, Heart Failure physiopathology, Heart Failure therapy, Observational Studies as Topic standards
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- 2017
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7. Therapeutic Coronary Reperfusion and Reperfusion Injury: An Introduction.
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Borer JS and Lewis BS
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- Coronary Circulation, Coronary Vessels, Humans, Myocardial Reperfusion, Myocardial Reperfusion Injury
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- 2016
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8. Effect of Combining Ivabradine and β-Blockers: Focus on the Use of Carvedilol in the SHIFT Population.
- Author
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Bocchi EA, Böhm M, Borer JS, Ford I, Komajda M, Swedberg K, and Tavazzi L
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- Adrenergic beta-Antagonists adverse effects, Aged, Benzazepines adverse effects, Bisoprolol therapeutic use, Carbazoles adverse effects, Cardiovascular Agents adverse effects, Carvedilol, Double-Blind Method, Drug Therapy, Combination, Female, Hospitalization, Humans, Ivabradine, Male, Metoprolol therapeutic use, Middle Aged, Nebivolol therapeutic use, Propanolamines adverse effects, Proportional Hazards Models, Treatment Outcome, Adrenergic beta-Antagonists therapeutic use, Benzazepines therapeutic use, Carbazoles therapeutic use, Cardiovascular Agents therapeutic use, Heart Failure, Systolic drug therapy, Propanolamines therapeutic use
- Abstract
Objectives: We explored the prescription of β-blockers with ivabradine in patients with systolic heart failure, focusing on the most frequently coprescribed β-blocker, carvedilol., Methods: We analyzed outcomes in SHIFT patients with systolic heart failure who were prescribed β-blockers (carvedilol, bisoprolol, metoprolol, or nebivolol) with ivabradine or placebo. Analysis was by intention to treat in patients prescribed a β-blocker at the time of the event., Results: Data were available for 2,596 patients receiving carvedilol, 1,483 bisoprolol, 1,424 metoprolol, and 197 nebivolol. Mean treatment duration was 19 months. There was no difference in the effect of ivabradine on the primary composite endpoint of cardiovascular death or heart failure hospitalization between the various β-blockers [hazard ratios (HR) for risk reduction, 0.75-0.89; p for interaction=0.86]. Patients prescribed carvedilol with ivabradine had lower rates of primary composite endpoint (HR 0.80, 95% CI: 0.68-0.94), heart failure hospitalization (HR 0.73, 95% CI: 0.61-0.88), and cardiovascular hospitalization (HR 0.80, 95% CI: 0.69-0.92) versus carvedilol with placebo. The dosage of carvedilol had no detectable effect and there were no unexpected safety issues., Conclusions: Whatever β-blocker was coprescribed with ivabradine, there were improvements in cardiovascular outcomes in patients with systolic heart failure, especially with the most prescribed β-blocker--carvedilol., (© 2015 S. Karger AG, Basel.)
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- 2015
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9. Heart Rate, Life Expectancy and the Cardiovascular System: Therapeutic Considerations.
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Boudoulas KD, Borer JS, and Boudoulas H
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- Animals, Arterial Pressure, Cardiovascular Diseases drug therapy, Humans, Mice, Rats, Risk Factors, Cardiovascular Diseases mortality, Heart physiopathology, Heart Rate physiology, Life Expectancy
- Abstract
It has long been known that life span is inversely related to resting heart rate in most organisms. This association between heart rate and survival has been attributed to the metabolic rate, which is greater in smaller animals and is directly associated with heart rate. Studies have shown that heart rate is related to survival in apparently healthy individuals and in patients with different underlying cardiovascular diseases. A decrease in heart rate due to therapeutic interventions may result in an increase in survival. However, there are many factors regulating heart rate, and it is quite plausible that these may independently affect life expectancy. Nonetheless, a fast heart rate itself affects the cardiovascular system in multiple ways (it increases ventricular work, myocardial oxygen consumption, endothelial stress, aortic/arterial stiffness, decreases myocardial oxygen supply, other) which, in turn, may affect survival. In this brief review, the effects of heart rate on the heart, arterial system and survival will be discussed., (© 2015 S. Karger AG, Basel.)
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- 2015
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10. Relation of indirect vasodilator use to prognosis in patients with chronic severe mitral regurgitation.
- Author
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Supino PG, Khan N, Hai O, Herrold EM, Hochreiter C, and Borer JS
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- Atrial Fibrillation prevention & control, Chronic Disease, Death, Sudden, Cardiac prevention & control, Follow-Up Studies, Heart Failure prevention & control, Humans, Hypertension drug therapy, Male, Middle Aged, Mitral Valve Insufficiency physiopathology, Prospective Studies, Stroke Volume physiology, Treatment Outcome, Mitral Valve Insufficiency drug therapy, Vasodilator Agents therapeutic use
- Abstract
Objectives: The relation of indirect vasodilator use to cardiac events (CE) is undefined for chronic severe nonischemic mitral regurgitation (MR). The aim of this study was to resolve this knowledge deficiency., Methods: Data from 52 consecutive patients in our prospective natural history study with isolated chronic severe nonischemic MR were assessed post hoc over 19 years to examine the relation of indirect vasodilator use to subsequent CE (death or indications for valve surgery). At entry, no patient had surgical indications, 14% had hypertension (HTN) and 7 chronically received vasodilators (5 angiotensin-converting enzyme inhibitor, 1 receptor blocker and 1 α-adrenergic blocker). CE differences were assessed by log-rank comparison of Kaplan-Meier curves., Results: During follow-up, CE included sudden death (1 patient), heart failure (7 patients), atrial fibrillation (6 patients), left ventricular (LV) systolic dimension >4.5 cm (12 patients), LV ejection fraction (EF) <60% (7 patients), right ventricular EF <35% (2 patients) and combination CE (7 patients). Overall, vasodilator use did not predict CE (not significant). However, patients without HTN had higher CE rates with vasodilators than without (p = 0.007), while those with HTN and vasodilators had lower CE rates than those without vasodilators (p = 0.04)., Conclusion: Vasodilator use appears to confer no survival benefit in patients with chronic severe MR. The small number of patients with HTN precludes conclusions about modulation of vasodilator effect by HTN. Randomized trials are needed to conclusively evaluate this association.
- Published
- 2014
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11. Role of oral factor Xa inhibitors after acute coronary syndrome.
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Sharma A, Garg A, Borer JS, Krishnamoorthy P, Garg J, Lavie CJ, Arbab-Zadeh A, Mukherjee D, Ahmad H, and Lichstein E
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- Administration, Oral, Azepines administration & dosage, Benzamides administration & dosage, Humans, Morpholines administration & dosage, Pyrazoles administration & dosage, Pyridones administration & dosage, Rivaroxaban, Thiophenes administration & dosage, Treatment Outcome, Acute Coronary Syndrome drug therapy, Factor Xa Inhibitors administration & dosage
- Abstract
Despite an early invasive strategy and the use of dual antiplatelet therapy, patients with acute coronary syndrome (ACS) continue to be at substantial risk for recurrent ischemic events. It is believed that this risk is, at least in part, due to an intrinsic coagulation pathway that remains activated for a prolonged period after ACS. Earlier studies using warfarin showed a reduction in ischemic events, but the overall benefits were offset by increased bleeding complications. Recently, there has been increased interest in the potential role of new oral anticoagulants, some of which target factor Xa, after ACS. Factor Xa is important for the coagulation pathway and also plays a role in cellular proliferation and inflammation. It may thus be an attractive target for therapeutic intervention in ACS. Recently, various oral factor Xa inhibitors have been studied as potential treatment options for ACS. This review will focus on currently available data to evaluate the possible role of factor Xa inhibitors in the management of patients with ACS.
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- 2014
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12. Nonischemic mitral regurgitation: prognostic value of nonsustained ventricular tachycardia after mitral valve surgery.
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Olafiranye O, Hochreiter CA, Borer JS, Supino PG, Herrold EM, Budzikowski AS, Hai OY, Bouraad D, Kligfield PD, Girardi LN, Krieger KH, and Isom OW
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- Electrocardiography, Ambulatory, Female, Humans, Male, Middle Aged, Mitral Valve Insufficiency mortality, Mitral Valve Insufficiency physiopathology, Postoperative Complications etiology, Postoperative Complications physiopathology, Prognosis, Prospective Studies, Stroke Volume physiology, Tachycardia, Ventricular etiology, Tachycardia, Ventricular physiopathology, Ventricular Dysfunction, Left mortality, Ventricular Dysfunction, Left physiopathology, Mitral Valve Insufficiency surgery, Postoperative Complications mortality, Tachycardia, Ventricular mortality
- Abstract
Background: Nonsustained ventricular tachycardia (VT), frequent in unoperated severe mitral regurgitation (MR), confers mortality risk [sudden death (SD) and cardiac death (CD)]. The prognostic value of VT after mitral valve surgery (MVS) is unknown; we aimed to define this prognostic value and to assess its modulation by left (LV) and/or right (RV) ventricular ejection fraction (EF) for mortality after MVS., Methods: In 57 patients (53% females, aged 58 ± 12 years) with severe MR prospectively followed before and after MVS, we performed 24-hour ambulatory electrocardiograms approximately annually. LVEF and RVEF were determined within 1 year after MVS by radionuclide cineangiography., Results: During 9.52 ± 3.49 endpoint-free follow-up years, late postoperative CD occurred in 11 patients (7 SD, 4 heart failures). In univariable analysis, >1 VT episode after MVS predicted SD (p < 0.01) and CD (SD or heart failure; p < 0.04). Subnormal postoperative RVEF predicted CD (p < 0.04). When adjusted for preoperative age, gender, etiology or antiarrhythmics, both postoperative VT and RVEF predicted CD (p ≤ 0.05). When postoperative VT and RVEF were both in the multivariable model, only subnormal RVEF predicted CD (p < 0.04). Among those with normal RVEF, VT >1 episode predicted SD (p = 0.03)., Conclusion: Postoperative VT and subnormal RVEF predict late postoperative deaths in nonischemic MR. Their assessment may aid patient management., (Copyright © 2013 S. Karger AG, Basel.)
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- 2013
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13. Off-pump versus on-pump coronary artery bypass grafting in octogenarians: comparison of short-term outcomes and long-term survival.
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Lee DC, Ramirez SA, Bacchetta M, Borer JS, and Ko W
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- Aged, 80 and over, Coronary Artery Disease surgery, Female, Humans, Male, New York epidemiology, Perioperative Period, Retrospective Studies, Coronary Artery Bypass, Off-Pump mortality
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Off-pump coronary artery bypass (OPCAB) has gained increasing acceptance with potential benefits for high-risk elderly patients. We report a surgeon's operative outcomes in octogenarians with an OPCAB program. Retrospective, intention-to-treat analysis of 97 consecutive octogenarians who underwent coronary bypass by a single surgeon between 1997 and 2001 before and after initiation of a multi-vessel OPCAB program was performed. OPCAB was attempted in all octogenarians. The OPCAB cohort had higher serum creatinine (OPCAB vs. pre-OPCAB: 1.30 ± 0.79 mg/dl vs. 1.08 ± 0.27, p = 0.04) and ejection fractions (52 ± 14% vs. 45 ± 11%, p = 0.02) than the pre-OPCAB cohort. The OPCAB group was more likely to require urgent/emergency surgery (63 vs. 40%, p = 0.04) and to have chronic renal insufficiency (18 vs. 3%, p = 0.05). After programmatic change to OPCAB, significant postoperative improvements were observed in the length of hospital stay (17 ± 19 vs. 8 ± 4 days, p < 0.01), duration of inotropic requirement (47 ± 70 vs. 18 ± 39 h, p < 0.04), duration of ventilator support (51 ± 54 vs. 16 ± 27 h, p < 0.01) and incidence of tracheostomy (16 vs. 3%, p < 0.02). In-hospital mortalities (3.2 vs. 2.7%), strokes (3 per group) and 5-year survival did not differ significantly (57 vs. 67%, p = 0.50, NS). Despite some higher preoperative risks, the OPCAB program demonstrated clinical benefits in octogenarians but no advantage in hospital-mortality or long-term survival., (Copyright © 2013 S. Karger AG, Basel.)
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- 2013
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14. Etiology of valvular heart disease in the 21st century.
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Boudoulas KD, Borer JS, and Boudoulas H
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- Calcinosis etiology, Cardiomyopathies etiology, Cardiovascular Agents therapeutic use, Disease Susceptibility etiology, Endocarditis etiology, Female, Heart Neoplasms etiology, Heart Valve Diseases drug therapy, Heart Valve Diseases surgery, Heart Valve Prosthesis Implantation, Humans, Iatrogenic Disease, Male, Pedigree, Renal Insufficiency, Chronic etiology, Heart Valve Diseases etiology
- Abstract
A metamorphosis in the etiology of valvular heart disease (VHD) has occurred over the last 6 decades. In this review, the factors contributing to this metamorphosis, the common causes of VHD today, the relationship of valvular calcification to atherosclerosis and the interrelationship of VHD with other systems/organs are presented., (Copyright © 2013 S. Karger AG, Basel.)
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- 2013
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15. Statement on matching language to the type of evidence used in describing outcomes data.
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Borer JS
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- Cardiology, Humans, Language, Editorial Policies, Periodicals as Topic standards
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- 2013
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16. New oral anticoagulants: great promise for therapeutic advance but great knowledge gaps remain to be filled.
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Innasimuthu AL, Kumar S, Akter S, and Borer JS
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- Acute Coronary Syndrome drug therapy, Administration, Oral, Anticoagulants pharmacokinetics, Anticoagulants pharmacology, Atrial Fibrillation drug therapy, Contraindications, Drug Approval, Heart Valve Prosthesis, Humans, Randomized Controlled Trials as Topic, Treatment Outcome, United States, United States Food and Drug Administration, Venous Thromboembolism prevention & control, Anticoagulants administration & dosage
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- 2013
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17. Efficacy of I(f) inhibition with ivabradine in different subpopulations with stable angina pectoris.
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Tendera M, Borer JS, and Tardif JC
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- Age Distribution, Aged, Aged, 80 and over, Angina Pectoris diagnosis, Angina Pectoris epidemiology, Angina Pectoris therapy, Angioplasty, Balloon, Coronary methods, Coronary Artery Bypass methods, Dose-Response Relationship, Drug, Double-Blind Method, Drug Administration Schedule, Electrocardiography, Female, Humans, Incidence, Ivabradine, Male, Middle Aged, Prognosis, Randomized Controlled Trials as Topic, Risk Assessment, Secondary Prevention, Severity of Illness Index, Sex Distribution, Survival Rate, Treatment Outcome, Angina Pectoris drug therapy, Benzazepines administration & dosage, Cyclic Nucleotide-Gated Cation Channels drug effects
- Abstract
Objectives: The antianginal and anti-ischemic efficacy of ivabradine has been demonstrated in large-scale trials. Pooling trial data allowed for subpopulation analyses of ivabradine's antianginal efficacy., Methods: Data on the frequency of angina attacks, short-acting nitrate consumption, and heart rate were pooled from 5 randomized trials in patients with stable angina pectoris receiving 5, 7.5, or 10 mg of ivabradine b.i.d. for 3 or 4 months. The subpopulations were defined according to age, sex, disease characteristics, and comorbidities (severity of angina, history of myocardial infarction, cerebrovascular disease, revascularization status, diabetes, asthma/chronic obstructive pulmonary disease, or peripheral vascular disease)., Results: Efficacy data were available for 2,425 patients (full analysis set), in whom ivabradine reduced the frequency of diary-based angina attacks by 59.4% and nitrate consumption by 53.7%. All subpopulations experienced 51-70% reductions in the frequency of angina attacks, with similar reductions for the other parameters studied. Ivabradine's efficacy was maintained in the presence of different comorbidities. In the safety set, ivabradine reduced heart rate by 14.5%. Ivabradine had a good safety and tolerability profile in all the subpopulations assessed., Conclusions: The antianginal efficacy of ivabradine was consistent across all the subpopulations analyzed, independent of the severity of angina and the presence of a comorbidity., (Copyright 2009 S. Karger AG, Basel.)
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- 2009
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18. Fibronectin gene expression in aortic regurgitation: relative roles of mitogen-activated protein kinases.
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Truter SL, Catanzaro DF, Supino PG, Gupta A, Carter J, Ene AR, Herrold EM, Dumlao TF, Beltran F, and Borer JS
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- Activating Transcription Factor 2 metabolism, Animals, Enzyme Inhibitors pharmacology, Extracellular Matrix physiology, Extracellular Signal-Regulated MAP Kinases antagonists & inhibitors, Extracellular Signal-Regulated MAP Kinases metabolism, Gene Expression Regulation physiology, JNK Mitogen-Activated Protein Kinases antagonists & inhibitors, JNK Mitogen-Activated Protein Kinases metabolism, MAP Kinase Signaling System drug effects, Mitogen-Activated Protein Kinases antagonists & inhibitors, Phosphorylation physiology, RNA, Messenger metabolism, Rabbits, Stress, Mechanical, p38 Mitogen-Activated Protein Kinases antagonists & inhibitors, p38 Mitogen-Activated Protein Kinases metabolism, Aortic Valve Insufficiency metabolism, Aortic Valve Insufficiency physiopathology, Fibronectins genetics, MAP Kinase Signaling System physiology, Mitogen-Activated Protein Kinases metabolism
- Abstract
Objectives: In aortic regurgitation (AR), fibronectin (FN) expression is upregulated. This study sought to determine signal transduction pathways involved in upregulation of FN expression in AR., Methods: Cardiac fibroblasts (CF) from rabbits with surgically induced AR and matched controls (NL) were cultured and assayed for FN expression and kinase activity with and without inhibitors of kinases JNK, p38 mitogen-activated protein kinase (MAPK) and extracellular response kinase (ERK). NL CF also were subjected to cyclic strain mimicking AR for 24 h in culture with and without inhibitors., Results: AR CF exhibited 2.9-fold greater c-Jun phosphorylation (p < 0.01) and 1.5- to 2-fold greater ATF2 phosphorylation (p < 0.05-0.01) than NL. JNK and p38MAPK inhibition reduced c-Jun and ATF2 phosphorylation to NL; ERK inhibition had no effect. FN mRNA expression was similar in pattern to kinase activities. Cyclic strain in NL CF increased c-Jun phosphorylation 2-fold versus unstrained controls (p < 0.005). This was suppressed by inhibition of JNK but not p38MAPK., Conclusion: FN expression in response to the acute mechanical strain resembling AR is upregulated primarily via JNK. However, in chronic AR both JNK and p38MAPK are involved. These signaling pathways represent potential therapeutic targets for normalizing extracellular matrix (ECM) composition and contractile force transmission, believed to be related to ECM composition/organization, in AR., (Copyright 2009 S. Karger AG, Basel.)
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- 2009
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19. Differential expression of matrix metalloproteinases and tissue inhibitors and extracellular matrix remodeling in aortic regurgitant hearts.
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Truter SL, Catanzaro DF, Supino PG, Gupta A, Carter J, Herrold EM, Dumlao TF, and Borer JS
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- Animals, Aortic Valve Insufficiency metabolism, Aortic Valve Insufficiency pathology, Cells, Cultured, Collagen Type I metabolism, Collagen Type III metabolism, Extracellular Matrix Proteins metabolism, Fibrinogen metabolism, Fibrosis, Gene Expression physiology, Matrix Metalloproteinase 14 genetics, Matrix Metalloproteinase 14 metabolism, Matrix Metalloproteinase 2 genetics, Matrix Metalloproteinase 2 metabolism, Matrix Metalloproteinase 9 genetics, Matrix Metalloproteinase 9 metabolism, Myocytes, Cardiac cytology, Rabbits, Signal Transduction physiology, Tissue Inhibitor of Metalloproteinase-1 genetics, Tissue Inhibitor of Metalloproteinase-1 metabolism, Tissue Inhibitor of Metalloproteinase-2 genetics, Tissue Inhibitor of Metalloproteinase-2 metabolism, Tissue Inhibitor of Metalloproteinase-3 genetics, Tissue Inhibitor of Metalloproteinase-3 metabolism, Aortic Valve Insufficiency physiopathology, Matrix Metalloproteinases genetics, Matrix Metalloproteinases metabolism, Myocytes, Cardiac physiology, Tissue Inhibitor of Metalloproteinases genetics, Tissue Inhibitor of Metalloproteinases metabolism
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Objectives: Myocardial fibrosis in experimental aortic regurgitation (AR) features abnormal fibronectin with normal collagen content, but the relevant degradative processes have not been assessed., Methods: To elucidate these degradative processes, mRNA (Northern) and protein levels (Western) of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), as well as MMP activity (zymography), were measured in cardiac fibroblasts (CF) from New Zealand white rabbits with experimental AR paired with normals (NL). Collagen and fibronectin were quantified by immunohistochemical staining., Results: In AR CF versus NL CF, MMP-2 and -14 mRNA and protein were increased (both p < 0.005), while TIMPs 1-3 were slightly decreased (p < 0.05-0.005; TIMP-4 undetectable). Gelatinase activity in AR CF was 1.7 times that in NL CF (p < 0.005); fibronectinase activity was unaffected. The Jun N-terminal kinase (JNK) inhibitor SP600125 suppressed MMP-2 protein (0.4-fold, p < 0.05) and mRNA (0.7-fold, p < 0.005) in AR CF; MMP-2 levels in NL CF were unaffected. AR MMP-9 mRNA, protein and activity were low and indistinguishable from NL. In left ventricular tissue, fibronectin was increased 1.9-fold (AR vs. NL, p < 0.05). Total AR collagen was indistinguishable from NL, but the collagen III to collagen I isoform ratio decreased (0.4-fold, p < 0.05)., Conclusions: Collagen is relatively deficient in AR fibrosis, due at least in part to upregulated MMPs and downregulated TIMPs; fibronectinase is unaltered. JNK-dependent regulation may stimulate both MMP-2 and fibronectin expression in AR, providing a potential therapeutic target., (Copyright (c) 2009 S. Karger AG, Basel.)
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- 2009
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20. Ischemic mitral regurgitation: the 2007 H.J.C. Swan Memorial Prize for Medical Writing.
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Borer JS
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- Awards and Prizes, Humans, Public-Private Sector Partnerships, Journalism, Medical, Mitral Valve Insufficiency diagnosis, Mitral Valve Insufficiency etiology, Mitral Valve Insufficiency physiopathology, Mitral Valve Insufficiency therapy, Myocardial Ischemia complications, Myocardial Ischemia physiopathology
- Published
- 2009
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21. Similarities and differences in design considerations for cell therapy and pharmacologic cardiovascular clinical trials.
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Lewis RM, Gordon DJ, Poole-Wilson PA, Borer JS, and Zannad F
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- Animals, Clinical Trials, Phase I as Topic, Clinical Trials, Phase II as Topic, Ethics, Research, Humans, Patient Selection, Cardiology, Cell- and Tissue-Based Therapy, Clinical Trials as Topic ethics, Research Design
- Abstract
Cell therapies hold the potential for suppression, modification, or cure of disease. Several unique challenges have been recognized as this field has developed. Many of these involve considerations of trial design. This paper summarizes the discussion and suggestions constructed during the 8th Cardiovascular Clinical Trialists Workshop, a meeting involving cardiovascular clinical trialists, biostatisticians, National Institutes of Health scientists, European and United States regulators, and pharmaceutical industry scientists. Investigators must adapt research methods to accommodate the scientific advances associated with cell therapy. Safety and efficacy of cell therapy for cardiovascular indications should be evaluated with the same degree of scientific rigor required of pharmacologic agents, and the same fundamental regulatory requirements and scientific processes apply to both. Clinical trials for these indications should also meet standards similar to those set for drug therapies. Safety should be determined throughout development, dose responsiveness should be established and, while surrogate endpoints are important development tools, the ultimate demonstration of efficacy must rely on clinical benefit. The establishment of a global safety database for cell therapy would significantly advance the field. Efforts to discover innovative therapies must be balanced by a commitment to comprehensively evaluate the safety and efficacy of the new treatments., (Copyright 2007 S. Karger AG, Basel.)
- Published
- 2008
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22. Nitric oxide synthase inhibitor (MTR-105) during open-heart surgery. A pilot double-blind placebo-controlled study of hemodynamic effects and safety.
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Sasson L, Ureche A, Manolache G, Ciubotaru A, Borer JS, and Schachner A
- Subjects
- Adult, Aged, Cardiovascular Diseases surgery, Double-Blind Method, Enzyme Inhibitors pharmacokinetics, Female, Half-Life, Hemodynamics drug effects, Humans, Hypotension drug therapy, Isothiuronium administration & dosage, Isothiuronium pharmacokinetics, Male, Middle Aged, Pilot Projects, Placebos, Vascular Resistance drug effects, Blood Pressure drug effects, Cardiac Surgical Procedures methods, Enzyme Inhibitors administration & dosage, Hypotension prevention & control, Isothiuronium analogs & derivatives, Nitric Oxide Synthase antagonists & inhibitors
- Abstract
Objectives: Hypotension is common immediately following cardiopulmonary bypass. Experimentally, MTR-105 (S-ethylisothiuronium diethylphosphate), a fast-acting synthetic nitric oxide synthase inhibitor, rapidly increases blood pressure. The purpose of the current study was to assess the influence of MTR-105 on hemodynamics early after cardiopulmonary bypass in patients undergoing open-heart surgery., Methods: Thirty-six patients with an ejection fraction >50% undergoing open-heart surgery were randomly assigned to either 50 microg kg(-1) min(-1) MTR-105 (M50, n = 12), 10 microg kg(-1) min(-1) MTR-105 (M10, n = 12) or buffered phosphate solution (placebo control, n = 12). Half suffered from atrial fibrillation and 75% had severe tricuspid regurgitation. Patients received the drug for 6 h after cross-clamp removal. Hemodynamic variables were measured before drug administration until 24 h after operation. Adverse events were recorded from study drug initiation through 30 days after the operation., Results: Compared with control, both MTR-105 doses were associated with an immediate increase in systemic blood pressure (16%) and systemic vascular resistance and a decrease in cardiac index. Half-life time of MTR-105 was calculated to be 4.1 +/- 0.8 h (M10) and 4.45 +/- 0.92 h (M50). Three patients died during hospitalization, unrelated to the study medication., Conclusions: At the doses employed, MTR-105 appears hemodynamically active in increasing both blood pressures., (Copyright 2008 S. Karger AG, Basel.)
- Published
- 2008
- Full Text
- View/download PDF
23. Clinical effect of 'pure' heart rate slowing with a prototype If current inhibitor: placebo-controlled experience with ivabradine.
- Author
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Borer JS
- Subjects
- Clinical Trials as Topic, Heart Conduction System drug effects, Heart Conduction System physiopathology, Heart Rate physiology, Humans, Ion Channels drug effects, Ivabradine, Placebos, Angina Pectoris prevention & control, Benzazepines therapeutic use, Cardiotonic Agents therapeutic use, Heart Rate drug effects
- Abstract
Heart rate slowing is generally accepted as effective for angina prevention but this approach has not been rigorously evaluated as no pure heart rate slowing treatment has been available. With the identification of the I(f) current, the primary modulator of heart rate, and use of this as a target for drug development, the role of isolated heart rate slowing can be elucidated. More than 4,000 patients now have been studied in angina prevention trials with ivabradine, a prototype I(f) current inhibitor devoid of other cardiovascular effects. These studies demonstrate the efficacy of isolated heart rate slowing for angina prevention. Indeed, in one direct comparison with atenolol involving 939 patients, ivabradine not only was non inferior to the Beta-blocker but nominally appeared to be more efficient in angina prevention. Moreover, since ivabradine is devoid of most of the adverse effects of beta-blockers (and of calcium channel blockers), it is a suitable alternative when these established drugs are not adequately tolerated. Additional studies now must assess other potential actions in patients with coronary disease.
- Published
- 2006
- Full Text
- View/download PDF
24. Heart failure in aortic regurgitation: the role of primary fibrosis and its cellular and molecular pathophysiology.
- Author
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Borer JS, Truter SL, Gupta A, Herrold EM, Carter JN, Lee E, and Pitlor L
- Subjects
- Extracellular Matrix physiology, Humans, Aortic Valve Insufficiency physiopathology, Endomyocardial Fibrosis physiopathology, Heart Failure physiopathology, Myocardial Contraction
- Published
- 2004
- Full Text
- View/download PDF
25. The epidemiology of valvular heart diseases: the problem is growing.
- Author
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Supino PG, Borer JS, Yin A, Dillingham E, and McClymont W
- Subjects
- Female, Hospital Mortality trends, Hospitalization statistics & numerical data, Humans, Incidence, Linear Models, Male, New York epidemiology, Prevalence, Heart Valve Diseases epidemiology
- Published
- 2004
- Full Text
- View/download PDF
26. Ventricular arrhythmias in mitral regurgitation: frequency, clinical and prognostic importance, management before and after mitral valve surgery.
- Author
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Hochreiter C, Borer JS, Yin A, Supino PG, Herrold EM, Krieger K, and Isom OW
- Subjects
- Humans, Prevalence, Prognosis, Risk Factors, Tachycardia, Ventricular epidemiology, Tachycardia, Ventricular therapy, Death, Sudden, Cardiac epidemiology, Mitral Valve Insufficiency complications, Tachycardia, Ventricular etiology
- Published
- 2004
- Full Text
- View/download PDF
27. Valve surgery in the asymptomatic patient with aortic regurgitation: current indications and the effect of change rates in objective measures.
- Author
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Borer JS, Supino PG, Hochreiter C, Herrold EM, Yin A, Krieger K, and Isom OW
- Subjects
- Humans, Risk Factors, Ventricular Function, Left, Aortic Valve Insufficiency surgery, Heart Valve Prosthesis
- Published
- 2004
- Full Text
- View/download PDF
28. Mitral regurgitation: natural history in operated and unoperated patients.
- Author
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Hochreiter CA, Borer JS, Herrold EM, Supino PG, Krieger KH, and Isom OW
- Subjects
- Cardiac Surgical Procedures trends, Humans, Survival Analysis, Treatment Outcome, Ventricular Function, Left physiology, Mitral Valve Insufficiency mortality, Mitral Valve Insufficiency physiopathology, Mitral Valve Insufficiency surgery
- Published
- 2002
- Full Text
- View/download PDF
29. The cellular and molecular basis of heart failure in regurgitant valvular diseases: the myocardial extracellular matrix as a building block for future therapy.
- Author
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Borer JS, Truter SL, Herrold EM, Supino PG, Carter JN, and Gupta A
- Subjects
- Aortic Valve Insufficiency complications, Aortic Valve Insufficiency physiopathology, Aortic Valve Insufficiency therapy, Extracellular Matrix pathology, Forecasting, Heart Failure physiopathology, Heart Failure therapy, Heart Valve Diseases physiopathology, Heart Valve Diseases therapy, Humans, Mitral Valve Insufficiency complications, Mitral Valve Insufficiency physiopathology, Mitral Valve Insufficiency therapy, Myocardium cytology, Myocardium pathology, Stroke Volume physiology, Treatment Outcome, Ventricular Dysfunction, Left complications, Ventricular Dysfunction, Left physiopathology, Ventricular Dysfunction, Left therapy, Heart Failure etiology, Heart Valve Diseases complications
- Published
- 2002
- Full Text
- View/download PDF
30. The epidemiology of valvular heart disease: an emerging public health problem.
- Author
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Supino PG, Borer JS, and Yin A
- Subjects
- Aged, Aortic Valve pathology, Female, Heart Valve Diseases etiology, Heart Valve Diseases surgery, Heart Valve Prosthesis, Humans, Longitudinal Studies, Male, Mitral Valve pathology, New York epidemiology, Patient Admission trends, Prevalence, Public Health trends, Pulmonary Valve pathology, Rheumatic Heart Disease complications, Rheumatic Heart Disease epidemiology, Rheumatic Heart Disease surgery, Risk Factors, Sex Factors, Treatment Outcome, Tricuspid Valve pathology, Heart Valve Diseases epidemiology
- Published
- 2002
- Full Text
- View/download PDF
31. Aortic regurgitation: selection of asymptomatic patients for valve surgery.
- Author
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Borer JS, Herrold EM, Hochreiter CA, Supino PG, Yin A, Krieger KH, and Isom OW
- Subjects
- Heart Valve Prosthesis trends, Humans, Patient Selection, Prosthesis Design trends, Risk Factors, Aortic Valve Insufficiency epidemiology, Aortic Valve Insufficiency surgery
- Published
- 2002
- Full Text
- View/download PDF
32. Importance of right ventricular performance measurement in selecting asymptomatic patients with mitral regurgitation for valve surgery.
- Author
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Borer JS, Hochreiter CA, Supino PG, Herrold EM, Krieger KH, and Isom OW
- Subjects
- Humans, Mitral Valve Insufficiency complications, Stroke Volume physiology, United States epidemiology, Ventricular Dysfunction, Left complications, Ventricular Dysfunction, Left physiopathology, Ventricular Dysfunction, Left surgery, Cardiac Surgical Procedures, Heart Ventricles surgery, Mitral Valve Insufficiency physiopathology, Mitral Valve Insufficiency surgery, Patient Selection, Ventricular Function, Right physiology
- Published
- 2002
- Full Text
- View/download PDF
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