Assessment of Paravalvular Leak After TAVI by Hemodynamic Measurements and Cardiac MRI

Description

1. INTRODUCTION AND RATIONALE Transcatheter aortic valve implantation (TAVI) has become the standard of care in elderly patients with severe symptomatic aortic valve stenosis and increased surgical risks due to advanced age and multiple comorbidity(2-4). However, in contrast to surgical aortic valve replacement (SAVR), paravalvular leakage after TAVI is fairly common. More than moderate paravalvular leakage is associated with intermediate and long-term morbidity and mortality(5).

Since the introduction of TAVI, implantation- and device technology have improved significantly. Nevertheless, mild paravalvular leakage remains a common finding after implantation of new generation devices. Conflicting evidence exists regarding the impact of mild versus none to trivial paravalvular leakage on mortality and morbidity. Several factors might be of influence on these conflicting results. Patients with left ventricular hypertrophy and no previous aortic regurgitation might experience rapidly rising end-diastolic pressures resulting in heart failure even at small regurgitant volumes as seen with mild paravalvular leakage (6-9). Moreover, paravalvular leakage might have greater impact on survival in patients with impaired left ventricular function as compared to patients with preserved left ventricular ejection fraction(10).

Furthermore, studies have used different definitions of paravalvular leakage, assessed paravalvular leakage at different time intervals and used different prostheses. Since paravalvular leakage might decrease over time in self- expandable TAVI devices, this potentially influenced outcomes(11). The widely used VARC-2 criteria for paravalvular leakage grading comprise echocardiographic measurements only(1). Especially quantitative assessment of paravalvular leakage in the intermediate strata (mild-moderate) using echocardiography (TTE) remains difficult. TAVI under conscious sedation or local anesthesia more or less preclude the use of peri-operative trans esophageal echocardiography (TEE). TTE analysis and grading of paravalvular leakage is limited by patient factors such as pulmonary disease, patient habitus and prior cardio-thoracic surgery. Moreover, TTE has been shown to underestimate paravalvular leakage as compared to cardiac MRI(12-14). However,the presence of clinical relevant paravalvular leakage necessitates post-dilatation; therefore grading of paravalvular leakage preferably should be done intra-operatively.

Hemodynamic parameters have been shown to be of great value in grading paravalvular leakage post implantation(15-18). These objective parameters are easily obtained during TAVI and have been shown to have prognostic relevance. All of these parameters are a function of left ventricular end-diastolic pressure (LVEDP). For instance, diastolic delta (DD), defined as the gradient between diastolic aortic pressure and LVEDP, 18 millimetres of mercury (mmHg) was associated with adverse prognosis(15). Heart rate adjusted diastolic delta (HR-DD) (HR-DD= [DD/heartrate] 80) <25 mmHg/beats per minute (BPM) was associated with mortality at 1 year in a retrospective study(16). Combined with angiography and (transesophageal) echocardiography, it was associated with impaired clinical outcome in balloon-expandable bioprostheses (16, 17). Furthermore, the aortic regurgitation index (ARI), defined as the ratio of the diastolic delta to systolic aortic pressure (Aortic regurgitation index = (DD/Aortic pressure systolic)100) >25 combined with angiographic or echocardiographic assessment of paravalvular leakage had a negative predictive value of 95%-100% for the occurrence of more than mild paravalvular leakage. ARI <25 was associated with 1 year mortality, even after adjustment for paravalvular leakage severity(18-20). However, interpretation of ARI is challenging; bradycardia might lead to an ARI <25 without the presence of relevant paravalvular leakage. Determination of ARI should therefore be performed at a heart rate between 60-80 BPM and preferably over several cycles, especially when measured during atrial fibrillation or extrasystoles.

Both echocardiographic and hemodynamic measures provide an estimation of the amount of paravalvular leak. In contrast to echocardiography, MRI provides accurate quantification of paravalvular leakage volume. In this study the investigators want to assess the contributive value of hemodynamic indices of paravalvular leakage based on paravalvular leakage volume measured by means of cardiac MRI and to assess its association with impaired clinical outcomes during 5 year follow-up.

2. OBJECTIVES 2.1 Primary Objective To assess per-procedural hemodynamic indices of paravalvular leakage and to relate these to paravalvular leakage as quantified by cardiac MRI.

2.2 Secondary Objectives To exploratory assess short- and long-term outcomes in patients with different severity of paravalvular leakage

3. STUDY DESIGN The study is designed as a single center, investigator-initiated, clinical trial.

In case patients want to participate there is no change of standard clinical care. After TAVI, study participants will receive additional cardiac MRI within 1 month. Subsequent 3-month and 1-year out-patient clinical follow-up will be performed. Telephone follow-up will be performed after 2,3,4 and 5 years. The end of the study is defined as the day when the last patient completes her/his last visit planned in the protocol.

4. STUDY POPULATION 4.1 Population (base) Patients with severe symptomatic aortic valve stenosis allocated to TAVI by a dedicated heart team will be screened for potential participation. The definition of severe symptomatic aortic valve stenosis is defined in the inclusion criteria.

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