Tailored-therapy of ACE-inhibitors in Coronary Artery Disease: Pharmacogenetic Profiling of Treatment Benefit

To optimally treat patients, and to develop ways to guide ACE-inhibitor treatment, it remains essential to identify those patients most likely to benefit from therapy. New research to elucidate such heterogeneity is necessary. If feasible, guided-therapy of ACE-inhibitors will have a large impact on clinical practice by increasing patient's benefit of drug prescriptions and reducing healthcare costs: to get the right drug to the right patient. The quest for the Holy Grail: tailoring drug therapies to individual patients. The purpose of this thesis was to investigate a new approach to guide ACE-inhibitor therapy using patient specific genetic characteristics (19). We studied the feasibility of pharmacogenetic profiling of the treatment benefit of ACE-inhibitor therapy. We focused on the common genetic variation in the candidate genes of the direct pharmacodynamic pathway of ACE-inhibitors: the renin-angiotensin-system and kallikrein-bradykinin system. These studies were conducted within the randomized placebo-controlled EUROPA-trial studying the ACE-inhibitor perindopril versus placebo in ten thousand patients with stable coronary artery disease. The main research questions we examined were as follows: - Is the treatment benefit (reduction of cardiovascular events) of ACE-inhibitor therapy modified by genetic variation between patients? - Is the level of blood pressure and blood pressure reduction by ACE-inhibitor therapy modified by genetic variation between patients? - Can we develop a pharmacogenetic profile to individualize ACE-inhibitor therapy and optimize patients' benefit in stable coronary artery disease

Remote monitoring for better management of LVAD patients: the potential benefits of CardioMEMS

Left ventricular assist devices (LVAD) are frequently used in the treatment of end-stage heart failure (HF), and due to the shortage of heart donors and destination programs, it is likely to keep on growing. Still, LVAD therapy is not without complications and morbidity and rehospitalization rates are high. New ways to improve LVAD care both from the side of the patient and the physician are warranted. Remote monitoring could be a tool to tailor treatment in these patients, as no feedback exists at all about patient functioning on top of the static pump parameters. We aim to provide an overview and evaluation of the novel remote monitoring strategies to optimize LVAD management and elaborate on the opportunities of remote hemodynamic monitoring with CardioMEMS, at home in these patients as the next step to improve care

Remote monitoring of chronic heart failure patients: invasive versus non-invasive tools for optimising patient management

Exacerbations of chronic heart failure (HF) with the necessity for hospitalisation impact hospital resources significantly. Despite all of the achievements in medical management and non-pharmacological therapy that improve the outcome in HF, new strategies are needed to prevent HF-related hospitalisations by keeping stable HF patients out of the hospital and focusing resources on unstable HF patients. Remote monitoring of these patients could provide the physicians with an additional tool to intervene adequately and promptly. Results of telemonitoring to date are inconsistent, especially those of telemonitoring with traditional non-haemodynamic parameters. Recently, the CardioMEMS device (Abbott Inc., Atlanta, GA, USA), an implantable haemodynamic remote monitoring sensor, has shown promising results in preventing HF-related hospitalisations in chronic HF patients hospitalised in the previous year and in New York Heart Association functional class III in the United States. This review provides an overview of the available evidence on remote monitoring in chronic HF patients and future perspectives for the efficacy and cost-effectiveness of these strategies

Remote monitoring of pulmonary artery pressures with cardiomems in patients with chronic heart failure and nyha class III: First experiences in the Netherlands

We report the first patient experiences with the CardioMEMS device in the Erasmus MC Thorax Center in the Netherlands. In line with clinical trial evidence, the device is applicable in patients with chronic heart failure in functional New York Heart Association class III with at least 1 admission for heart failure in the past 12 months. CardioMEMS has been shown to be safe and reliable, and effective in reducing the number of hospitalisations for heart failure by guided therapy based on pulmonary artery pressures

Pulmonary artery pressure telemonitoring by CardioMEMS in a patient pre- and post-left ventricular assist device implantation

We present a case to demonstrate the feasibility of pulmonary artery monitoring with the CardioMEMS sensor for the preoperative optimization of patients with end-stage heart failure undergoing LVAD surgery. Additionally, we demonstrate the feasibility of combining two state-of-the-art techniques by integrating haemodynamic feedback from CardioMEMS and static pump settings of an LVAD. CardioMEMS aids in the remote monitoring of LVAD patients with the potential of identifying complications, pump dysfunction or filling status alterations

Remote monitoring in chronic heart failure patients: Is non-invasive remote monitoring the way to go?

Heart failure (HF) is a major health care issue, and the incidence of HF is only expected to grow further. Due to the frequent hospitalizations, HF places a major burden on the available hospital and healthcare resources. In the future, HF care should not only be organized solely at the clinical ward and outpatient clinics, but remote monitoring strategies are urgently needed to guide, monitor, and treat chronic HF patients remotely from their homes as well. The intuitiveness and relatively low costs of non-invasi

Monitoring pulmonary pressures during long-term continuous-flow left ventricular assist device and fixed pulmonary hypertension: redefining alleged pathophysiological mechanisms?

Pulmonary hypertension (PH) type II (classified by the World Health Organization) is a common complication in chronic left-sided heart failure. In advanced heart failure therapy, fixed PH is an absolute contraindication for heart transplantation after which a left ventricular assist device (LVAD) is the only remaining option. With remote monitoring, we can now continuously evaluate the pulmonary artery pressures during long-term LV unloading by the LVAD. In this case, we demonstrate that fixed PH can be reversed with LVAD implantation, whereby previous thoughts of this concept should be redefined in the era of assist devices

Cardiac monitoring in HER2-positive patients on trastuzumab treatment

Trastuzumab prolongs progression-free and overall survival in patients with human epidermal growth factor receptor 2 (HER2) positive breast cancer. However, trastuzumab treatment is hampered by cardiotoxicity, defined as a left ventricular ejection fraction (LVEF) decline with a reported incidence ranging from 3 to 27% depending on variable factors. Early identification of patients at increased risk of trastuzumab-induced myocardial damage is of great importance to prevent deterioration to irreversible cardiotoxicity. Although current cardiac monitoring with multi gated acquisition (MUGA) scanning and/or conventional 2D-echocardiography (2DE) have a high availability, their reproducibility are modest, and more sensitive and reliable techniques are needed such as 3D-echocardiography (3DE) and speckle tracking echocardiography (STE). But which other diagnostic imaging modalities are available for patients before and during trastuzumab treatment? In addition, what is the optimal frequency and duration of cardiac monitoring? At last, which biomarker monitoring strategies are currently available for the identification of cardiotoxicity in patients treated with trastuzumab