Serial Multiparametric Evaluation of Right Ventricular Function After Left Ventricular Assist Device Implantation

Study Overview
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Brief Summary
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The primary purpose of this study is to investigate the evolution of Right Ventricular (RV) function before and after left ventricular assist device (LVAD) implantation, using novel echocardiographic quantification of RV size and function in combination with comprehensive hemodynamic, laboratory and clinical parameters. The findings of the study will enhance prediction of early and late development of postoperative right-sided heart failure (RHF) and subsequent mortality and morbidity. The secondary purpose of the study is to combine echocardiographic, hemodynamic, laboratory, and clinical data to define optimal management strategies of RHF after LVAD implantation.

Detailed Description
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The study consists of 2 parts: a Pilot study and a Main Study as detailed below. The purpose of the Pilot study is to evaluate the feasibility of RV quantification using two-, three-dimensional and Multiplane echocardiography. About 100 subjects undergoing LVAD implantation in the European Registry for Patients with Mechanical Circulatory Support (EUROMACS) Registry are included in the Pilot study. These 100 patients will undergo routinely scheduled echocardiography before, within 1 week, 3 months and 1 year after LVAD implantation. Echocardiography will be performed using ultrasound machines that are capable of acquisition of two-, three-dimensional and Multiplane Echocardiography of the right ventricle. Echocardiographic analysis will include three-dimensional quantification of the RV size and function as well as RV strain analysis in the Multiplane format as described in the Appendix Echocardiography Procedure Manual. The Echocardiographic analyses of the first 50 patients, included in selected sites, will be used to further specify the protocol for image acquisition and analysis to be used in the Main Study. Furthermore, all sites will first enter 2 patients in the Pilot Study before they can participate in the Main Study. The echocardiographic results of these 2 patients will be assessed by the core lab for quality. The purpose of the Main Study is to assess the evolution of RV function before and after LVAD implantation utilizing the acquisition and analysis protocol developed in the Pilot Study. 500 patients will undergo routinely scheduled echocardiographic imaging before LVAD implantation, and at 1 week, 1 month, 3 months, 6 months and 1 year thereafter. Echocardiography will be performed using the detailed protocol developed in the Pilot Study. All Echocardiographic images will be submitted to an independent Core Laboratory for analysis. The evolution of RV function will be documented with standardised two-, three-dimensional and Multiplane Echocardiography of the right ventricle. The echocardiographic parameters include: RV strain and strain rate, RV Fractional Area Change, RV longitudinal function, RV volumes, RV ejection fraction, tricuspid regurgitation severity, estimated pulmonary artery pressures, pulmonary artery resistance, pulmonary artery compliance, RV stroke work index, right atrial size, and RV - pulmonary coupling. Invasive hemodynamic data will be collected in the perioperative period. These RV parameters will be linked to the occurrence of clinical signs, hemodynamic and laboratory evidence of RHF.

Official Title
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A Prospective, Multicenter, Observational, Investigator Initiated Study, Aiming at Serial Multiparametric Evaluation of Right Ventricular Function to Predict Optimal Management Strategies, of Right Heart Failure After LVAD Implantation

Conditions
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Right Heart Failure

Intervention / Treatment
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* Diagnostic Test: Echocardiography


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects to be included in the study must meet the following inclusion criteria: Consecutive patients accepted for elective LVAD implantation in the context of routine care >17 years of age Written informed consent (IC), either by the patient or by legal representatives Treated with mainstream devices Exclusion Criteria: None

Ages Eligible for Study
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Minimum Age: 17 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| LVAD recipients<br>Consecutive patients accepted for elective LVAD implantation in the context of routine care, will undergo routinely scheduled echocardiography before, within 1 week, 1 month, 3 months and 1 year after LVAD implantation. Echocardiography will be performed using ultrasound machines that are capable of acquisition of two-, three-dimensional and Multiplane Echocardiography of the right ventricle. Invasive hemodynamic data will be collected in the perioperative period. | Diagnostic Test: Echocardiography<br>* Echocardiography<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Moderate or severe RHF | RHF is defined by a triad of: Clinical (right-sided congestion, with or without hypotension, or hypo-perfusion) Imaging evidence (RV dilatation, new > grade 2 tricuspid regurgitation) deterioration right ventricular function score assessed by the echocardiography core laboratory) Hemodynamic evidence (discordant elevated central venous pressure (CVP) or right atrial pressure (RAP) >16 mmHg, despite normal or steady pulmonary capillary wedge pressure (PCWP), or right atrial (RA) to PCWP ratio >0.54). | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severe RHF composite | The occurrence of Severe RHF composite after LVAD implantation | 1 week, 30 days, 90 days, 180 days, 12 months | 
| All-cause death | The occurrence of all-cause death after LVAD implantation | 1 week, 30 days, 90 days, 180 days, 12 months | 
| Cardiovascular death | The occurrence of cardiovascular death after LVAD implantation | 1 week, 30 days, 90 days, 180 days, 12 months | 
| Death or urgent transplantation | The occurrence of death or urgent transplantation after LVAD implantation | 1 week, 30 days, 90 days, 180 days, 12 months | 
| Length of post-operative Intensive Care Unit (ICU) stay | The length of post-operative ICU stay in days after LVAD implantation | 30 days, 90 days, 180 days, 12 months | 
| Length of post-operative hospital stay | The length of post-operative hospital stay in days after LVAD implantation | 30 days, 90 days, 180 days, 12 months | 
| Readmissions for heart failure or RHF | The occurrence of hospital readmissions for heart failure or RHF after LVAD implantation | 30 days, 90 days, 180 days, 12 months | 
| Sepsis | The occurrence of sepsis after LVAD implantation | 1 week, 30 days, 90 days, 180 days, 12 months | 
| LVAD and driveline-related infection | The occurrence of LVAD and driveline-related infection after LVAD implantation | 1 week, 30 days, 90 days, 180 days, 12 months | 
| Early and late bleeding complications | The occurrence of LVAD and driveline-related infection after LVAD implantation | 1 week, 30 days, 90 days, 180 days, 12 months | 
| LVAD pump thrombosis | The occurrence of LVAD and driveline-related infection after LVAD implantation | 1 week, 30 days, 90 days, 180 days, 12 months | 
| Haemolysis | The occurrence of LVAD and driveline-related infection after LVAD implantation | 1 week, 30 days, 90 days, 180 days, 12 months | 
| Arterial thromboembolic events, including stroke | The occurrence of LVAD and driveline-related infection after LVAD implantation | 1 week, 30 days, 90 days, 180 days, 12 months | 
| Venous thromboembolic events, including deep venous thrombosis (DVT) and pulmonary embolism (PE) | The occurrence of LVAD and driveline-related infection after LVAD implantation | 1 week, 30 days, 90 days, 180 days, 12 months | 
| Ventricular arrhythmias, either sustained symptomatic or with appropriate Implantable Cardioverter Defibrillator (ICD) therapy | The occurrence of LVAD and driveline-related infection after LVAD implantation | 1 week, 30 days, 90 days, 180 days, 12 months | 
| Atrial arrhythmias - documented atrial flutter or fibrillation | The occurrence of LVAD and driveline-related infection after LVAD implantation | 1 week, 30 days, 90 days, 180 days, 12 months | 
| Acute Kidney Injury (AKI) according to Kidney Disease Outcomes Quality Initiative (KDIGO) and RIFFLE criteria | The occurrence of LVAD and driveline-related infection after LVAD implantation | 1 week, 30 days, 90 days, 180 days, 12 months | 
| Chronic kidney disease (CKD) according to KDOQI criteria | The occurrence of Chronic kidney disease (CKD) according to KDOQI criteria after LVAD implantation | 1 week, 30 days, 90 days, 180 days, 12 months | 
| Six Minute walk distance in meters | Assessment of Six Minute walk distance in meters before and after LVAD implantation | 90 days and 12 months | 
| Quality of life (QoL) scores | QoL by multiple assessments before and at 90 days, 180 days and at 12 months after LVAD implantation at | 90 days, 180 days and at 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Right Heart Failure, Ventricular Assist Device, ICU Stay, Acute Kidney Injury, Mortality