Update on the use of trandolapril in the management of cardiovascular disorders

Trandolapril is a well known angiotensin converting enzyme (ACE) inhibitor with many cardiovascular (CV) indications. The objectives of this article are to review the pharmacokinetics and pharmacodynamics properties of trandolapril and to focus on its clinical relevance in cardiovascular medicine. Various populations have been studied in large clinical trials including patients with congestive heart failure (CHF) after an acute myocardial infarction (AMI), diabetics, patients with hypertension (HTN), stable coronary artery disease (CAD) and prevention of proteinuria. Long-term treatment with trandolapril in patients with reduced left ventricular function soon after AMI significantly reduced the risk of overall mortality, mortality from CV causes, sudden death, and the development of severe CHF. Treatment with trandolapril after AMI complicated by left ventricular dysfunction appears to be of considerable importance in patients with diabetes mellitus by saving lives and substantially reducing the risk of progression to severe CHF as well. Moreover, trandolapril reduces progression to proteinuria in high-risk patients. Some of the advantages of trandolapril over other ACE inhibitors are the wide spectrum of patient populations studied, the well established dosage and its proven trough-to-peak effect ratios permitting a safe once-a-day administration

Psychosocial assessment tools for use before transplantation are predictive of post-operative psychosocial and health behavior outcomes: a narrative review of the literature

IntroductionIn end-stage diseases, transplantation may be necessary. The limited number of donors led to the development of several pre-transplant psychosocial assessment tools. We summarized the predictive value of these tools before solid-organ transplantation.MethodsThe PRISMA search strategy and the MEDLINE database were used to review the literature. From 1,050 records, we found thirteen studies using four different scales (Millon Behavioral Health Inventory [MBHI], Psychosocial Assessment of Transplant Candidates [PACT], Stanford Integrated Psychosocial Assessment for Transplantation [SIPAT], and Transplant Evaluation Rating Scale [TERS]).ResultsTERS and MBHI were associated with the highest number of positive studies concerning pre-transplant scores and primary outcomes. Psychosocial scales predict in a systematic way psychosocial and health behavioural outcomes, but generated mixed results for mortality and rejection.DiscussionThis narrative review underlines the need for multidisciplinary evaluation and well-conducted clinical trials to assist transplant teams in utilizing psychosocial evaluation effectively during evaluation of candidates

Cystatin C deficiency in human atherosclerosis and aortic aneurysms

The pathogenesis of atherosclerosis and abdominal aortic aneurysm involves breakdown of the elastic laminae. Elastolytic cysteine proteases, including cathepsins S and K, are overexpressed at sites of arterial elastin damage, but whether endogenous local inhibitors counterbalance these proteases is unknown. We show here that, whereas cystatin C is normally expressed in vascular wall smooth muscle cells (SMCs), this cysteine protease inhibitor is severely reduced in both atherosclerotic and aneurysmal aortic lesions. Furthermore, increased abdominal aortic diameter among 122 patients screened by ultrasonography correlated inversely with serum cystatin C levels. In vitro, cytokine-stimulated vascular SMCs secrete cathepsins, whose elastolytic activity could be blocked when cystatin C secretion was induced by treatment with TGF-β1. The findings highlight a potentially important role for imbalance between cysteine proteases and cystatin C in arterial wall remodeling and establish that cystatin C deficiency occurs in vascular disease

Targeted deletion of matrix metalloproteinase-9 attenuates left ventricular enlargement and collagen accumulation after experimental myocardial infarction

Matrix metalloproteinase-9 (MMP-9) is prominently overexpressed after myocardial infarction (MI). We tested the hypothesis that mice with targeted deletion of MMP9 have less left ventricular (LV) dilation after experimental MI than do sibling wild-type (WT) mice. Animals that survived ligation of the left coronary artery underwent echocardiographic studies after MI; all analyses were performed without knowledge of mouse genotype. By day 8, MMP9 knockout (KO) mice had significantly smaller increases in end-diastolic and end-systolic ventricular dimensions at both midpapillary and apical levels, compared with infarcted WT mice; these differences persisted at 15 days after MI. MMP-9 KO mice had less collagen accumulation in the infarcted area than did WT mice, and they showed enhanced expression of MMP-2, MMP-13, and TIMP-1 and a reduced number of macrophages. We conclude that targeted deletion of the MMP9 gene attenuates LV dilation after experimental MI in mice. The decrease in collagen accumulation and the enhanced expression of other MMPs suggest that MMP-9 plays a prominent role in extracellular matrix remodeling after MI

Baroreflex Activation Therapy for the Treatment of Heart Failure With a Reduced Ejection Fraction

AbstractObjectivesThe objective of this clinical trial was to assess the safety and efficacy of carotid BAT in advanced HF.BackgroundIncreased sympathetic and decreased parasympathetic activity contribute to heart failure (HF) symptoms and disease progression. Baroreflex activation therapy (BAT) results in centrally mediated reduction of sympathetic outflow and increased parasympathetic activity.MethodsPatients with New York Heart Association (NYHA) functional class III HF and ejection fractions ≤35% on chronic stable guideline-directed medical therapy (GDMT) were enrolled at 45 centers in the United States, Canada, and Europe. They were randomly assigned to receive ongoing GDMT alone (control group) or ongoing GDMT plus BAT (treatment group) for 6 months. The primary safety end point was system- and procedure-related major adverse neurological and cardiovascular events. The primary efficacy end points were changes in NYHA functional class, quality-of-life score, and 6-minute hall walk distance.ResultsOne hundred forty-six patients were randomized, 70 to control and 76 to treatment. The major adverse neurological and cardiovascular event–free rate was 97.2% (lower 95% confidence bound 91.4%). Patients assigned to BAT, compared with control group patients, experienced improvements in the distance walked in 6 min (59.6 ± 14 m vs. 1.5 ± 13.2 m; p = 0.004), quality-of-life score (–17.4 ± 2.8 points vs. 2.1 ± 3.1 points; p < 0.001), and NYHA functional class ranking (p = 0.002 for change in distribution). BAT significantly reduced N-terminal pro–brain natriuretic peptide (p = 0.02) and was associated with a trend toward fewer days hospitalized for HF (p = 0.08).ConclusionsBAT is safe and improves functional status, quality of life, exercise capacity, N-terminal pro–brain natriuretic peptide, and possibly the burden of heart failure hospitalizations in patients with GDMT-treated NYHA functional class III HF. (Barostim Neo System in the Treatment of Heart Failure; NCT01471860; Barostim HOPE4HF [Hope for Heart Failure] Study; NCT01720160

Hemodynamic-GUIDEd management of Heart Failure (GUIDE-HF)

In that study, incremental reductions in the PA pressures in the monitored arm were associated with both reduction in the frequency of HFH and improvements in health-related quality of life among patients with both preserved (HFpEF) and reduced ejection fraction (HFrEF).3,4 Additionally, hemodynamic-guided HF management in the subset of HFrEF patients treated with guideline-directed medical therapy (GDMT) was associated with a strong trend toward improved survival compared to traditional clinical management.4,7 Consistent benefit is demonstrated in several retrospective studies from the CHAMPION Trial.10-13 as well as extensive analysis of “real-world� experience.6,14 and in Medicare claims data managed in a commercial setting.5,15 Whether the benefits of PA pressure guided therapy can be extended to a broader pool of patients with milder (NYHA class II) or more severe (NYHA class IV) HF or to those without recent hospitalization for HF but with elevation in natriuretic peptide levels remains unclear. Remotely uploaded PA pressure information from the control group will be blocked from investigator review. [...]other than medication changes resulting from information from RHC procedures, control group subjects will not have pressure-based medication changes over time and should be managed instead according to routine practice as informed by published clinical guidelines. Thresholds for NT-proBNP/BNP corrected for BMI using a 4% reduction per BMI unit over 25 kg/m2 Subjects ≥18 y of age able and willing to provide informed consent Chest circumference of 15) at implant RHC, a history of noncompliance, or any condition that would preclude CardioMEMS PA Sensor implantation Table I Inclusion and exclusion criteria PA pressure goals PA diastolic: 8-20 mm Hg PA mean: 10-25 mm Hg PA systolic: 15-35 mm Hg Optimization phas

The 2010 Canadian Cardiovascular Society guidelines for the diagnosis and management of heart failure update: Heart failure in ethnic minority populations, heart failure and pregnancy, disease management, and quality improvement/assurance programs

Since 2006, the Canadian Cardiovascular Society heart failure (HF) guidelines have published annual focused updates for cardiovascular care providers. The 2010 Canadian Cardiovascular Society HF guidelines update focuses on an increasing issue in the western world - HF in ethnic minorities - and in an uncommon but important setting - the pregnant patient. Additionally, due to increasing attention recently given to the assessment of how care is delivered and measured, two critically important topics - disease management programs in HF and quality assurance - have been included. Both of these topics were written from a clinical perspective. It is hoped that the present update will become a useful tool for health care providers and planners in the ongoing evolution of care for HF patients in Canada. © 2010 Pulsus Group Inc. All rights reserved

Optimization of GDMT for patients with heart failure and reduced ejection fraction: can physiological and biological barriers explain the gaps in adherence to heart failure guidelines?

Heart failure is a growing epidemic with high mortality rates and recurrent hospital admissions that creates a burden on affected individuals, their caregivers and the whole healthcare system. Throughout the years, many randomized trials have established the effectiveness of several pharmacological therapies and electrophysiological devices to reduce hospitalizations and improve quality of life and survival, mostly for patients with heart failure with reduced ejection fraction (HFrEF). These studies led to the publication of national societies’ recommendations to guide clinicians in the management of HFrEF. Yet, many reports have shown significant care gaps in adherence to these recommendations in clinical practice, highlighting suboptimal use and/or dosing of evidence-based therapies. Adherence to guidelines has been shown to be associated with the best prognosis in HFrEF, with patients presenting with intolerances or contraindications having the highest risk of events; however, it remains unclear whether this association is causal or merely a marker of more advanced disease. Furthermore, individual characteristics may limit the possibility of reaching the targeted dosage of specific agents. Herein, we provide a comprehensive overview of clinicians’ adherence to heart failure guidelines in a specialized real-life setting, particularly regarding use and optimization of guideline-derived medical therapies, as well as the implementation of more recent agents such as sacubitril/valsartan and SGLT2 inhibitors. We seek potential explanations for suboptimal treatment and its impact on patient outcomes