Calibration of time-densitometry for the quantification of aortic regurgitation

Aortic regurgitation (AR) is common after Transcatheter Aortic Valve
Implantation (TAVI) and is associated with increased mortality in the first
year after the implantation procedure. In the catheter laboratory contrast
aortography (CA) is always performed at the end of each TAVI procedure to
evaluate prosthesis position and evaluate procedural success including
quantifying paraprosthetic regurgitation if present. Yet the grading of AR on
contrast aortography, which was described by Sellers in 1964, is
semi-quantitative, based on visual interpretation and therefore open to
interpretation. Studies that have calculated native valve aortic regurgitant
volumes and fraction based on ventriculography and the indicator dilution
technique demonstrated a wide scatter of regurgitant volumes within each
visually graded category and also substantial overlap between categories. These
studies were done before the widespread use of echocardiography and may have
contributed to the ascension of echocardiography for the evaluation of native
valve AR. Transoesophageal echocardiography (TEE) is now routine practice
during TAVI procedures to ensure optimal valve position and absence of
clinically important valve regurgitation. Transthoracic echocardiography (TTE)
is preferred for routine clinical follow-up of AR in TAVI patients and in
patients with native aortic valve disease.

Yet current guidelines recognize that the quantification of paravalvular AR
after TAVI by echocardiography can be problematic for several reasons: There
may be multiple regurgitant jets, regurgitation jets may follow a circuitous
course around the TAVI prosthesis, dense metal causes acoustic signal
attenuation, the regurgitant jets frequently are too eccentric to be aligned
with the Doppler beam and it is often not possible to locate the vena
contracta. On the other hand carefully performed contrast aortography may in
principle overcome several of the above-mentioned difficulties encountered with
echocardiography, provided that objective measurement rather than subjective
visual scoring of AR were possible.

Computer assisted measurement of radiographic contrast density changes over
time allows objective quantification of myocardial blush grade on coronary
angiograms. Similar principles may be applied to the evaluation of AR.
Recently, a prototype software system was developed (CAAS qRA, Pie Medical
Imaging, Maastricht, The Netherlands) based on time-densitometry to measure AR
based on the area under the contrast time-density curves (RAUC) in the aortic
root and the left ventricle (LV).

In order to understand how to interpret the RAUC and other measurements
obtained from contrast aortography time density curve analysis a comparison
with a golden standard volumetric method, i.e. cardiac Magnetic Resonance
Imaging (CMRI), is needed. CMRI is able to overcome several of the obstacles
discussed above and allows quantification of regurgitant volumes and fraction
with a high level of reproducibility. Yet CMRI carries a financial, logistical
and time cost and, more importantly, is not available on-site in the catheter
laboratory where TAVI is performed. Therefore it is attractive to validate the
measurements obtained from time-densitometry of aortograms with CMRI.

Primary objective:
To validate the quantification of AR by time-densitometry on contrast
aortography with the gold standard of CMRI measurements in order to refine the
interpretation and evaluate the accuracy of the qRA method.

Secondary objective:
To validate the quantification of AR by time-densitometry on contrast
aortography with echocardiographic measures of AR.

A pilot study validating the measurement of AR by time-densitometry analysis
(qRA) on contrast aortography compared to the gold standard of CMRI.

Multicenter study, recruitment of 15 - 20 patients from each of 3 - 4 sites.

A follow-up study on a larger patient population will be initiated only if the
agreement between the investigational method (qRA) is considered to be superior
to echocardiography, i.e. :
(1) The average difference in regurgitant volume and fraction measured by
velocity encoded MRI and qRA on aortography is less than 10%.
and
(2) The average difference in regurgitant volume and fraction between CMRI and
echocardiographic measured AR is higher than (1).

Patients undergo following burden / risk:

Aortography: Extra 30ml of contrast injected. Small extra chance of renal
toxicity or iodine contrast allergy.
CMRI: procedure can cause a claustrophobic reaction or allergic reaction to
gadolinium (MRI contrast).

All subjects will already undergoing invasive evaluation and / or treatment for
coronary artery disease, which is not different from the current standard
cardiological practice and the guidelines of the ACC / AHA / ESC. The only
difference is that a aortography is carried out. The additional risk associated
with the aortography is minimal.
The cardiac MRI (CMRI) is an additional investigation outside the normal
standard diagnostic setting. The additional risk associated with this CMRI is
estimated as minimal.