Einfluss der Hirnmorphologie auf die Inzidenz klinisch inapparenter, cerebraler Embolisationen im Rahmen der kathetergestützten Aortenklappenimplantation

Die Aortenklappenstenose ist einer der häufigsten Herzklappenfehler. Als kausal wirkende, kurative Therapie existiert aktuell nur die Implantation einer Aortenklappenprothese. Dafür eignet sich sowohl der operative Aortenklappenersatz als auch die interventionelle, kathetergestützte Aortenklappenimplantation. Während der Prozedur der interventionellen, kathetergestützten Aortenklappenimplantation kommt es zu mechanischen Belastungen von Aorta und Aortenklappe. Dadurch können cerebrale Embolien verursacht werden, welche sich magnetresonanztomographisch als Diffusionsstörungen darstellen. Ziel der vorliegenden Arbeit ist es, die Beziehung zwischen der Hirnmorphologie und dem Auftreten dieser Diffusionsstörungen zu untersuchen. Die Hirnmorphologie wurde anhand von präinterventionellen MRT erhoben und umfasst die Parameter Hyperintensitäten in der weißen Hirnsubstanz, Hirnvolumen, Hirninfarkte, lakunäre Hirninfarkte und Territorialinfarkte. Die darüber hinaus erhobenen Daten zu Patienteneigenschaften und prozeduralen Eigenschaften stehen in keiner Beziehung zu Diffusionsstörungen. Im Bereich der hirnmorphologischen Paramater zeigen die Hyperintensitäten in der weißen Hirnsubstanz eine signifikante Assoziation zu dem Auftreten von Diffusionsstörungen nach kathetergestützter Aortenklappenimplantation. Trotz der Limitation durch das monozentrische Studienprotokoll mit relativ kleinem Stichprobenumfang zeigen die vorliegenden Daten die Beziehung zwischen Hyperintensitäten in der weißen Hirnsubstanz und dem Auftreten von Diffusionsstörungen nach interventioneller, kathetergestützter Aortenklappenimplantation auf. Weitere Studien sind nötig, um die Rolle der Hirnmorphologie, insbesondere der Hyperintensitäten in der weißen Hirnsubstanz, als Risikofaktor für das Auftreten von Diffusionsstörungen nach interventioneller, kathetergestützter Aortenklappenimplantation näher zu untersuchen

Cerebral white matter lesion burden is associated with the degree of aortic valve calcification and predicts peri-procedural cerebrovascular events in patients undergoing transcatheter aortic valve implantation (TAVI)

ObjectivesTo investigate the impact of aortic valve calcification and brain morphology on acute peri-procedural cerebrovascular events (CVEs) in patients undergoing transcatheter aortic valve implantation (TAVI). BackgroundAortic valve calcification and stenosis can be assessed with echocardiography. Cerebral magnetic resonance imaging (MRI) depicts and quantifies morphological signs of hypoperfusion and vascular embolism, which is of special interest in patients with severe aortic stenosis. Furthermore, subjects who undergo TAVI are prone to suffer of clinically silent peri-procedural CVEs. MethodsA total of 119 patients referred to TAVI were investigated for aortic valve calcification using trans-esophageal echocardiography. Cerebral MRI prior to and immediate after implantation was performed in all patients using a dedicated scan protocol. Prior to TAVI, brain morphology was characterized. Post TAVI, brains were investigated for the onset of acute peri-procedural CVEs using diffusion weighted imaging (DWI). ResultsSeventy-eight patients (65.5%) revealed acute peri-procedural CVEs on MRI after TAVI with a favor of the left hemisphere (57.5%). The degree of valve calcification was associated with peri-procedural CVEs. Patients with a high WML burden had an increased risk for CVEs ((OR) 2.36 (95% CI: 1.09-5.15; P=0.037)), especially when distributed periventricular ((OR: 3.27; 95% CI: 1.47-7.26; P=0.0038)). ConclusionIn patients undergoing TAVI, the degree of aortic valve calcification and periventricular WML burden were correlated with acute peri-procedural CVEs. Future studies are needed to evaluate their independent value for the long-term clinical outcome

Subacute Subclinical Brain Infarctions after Transcatheter Aortic Valve Implantation Negatively Impact Cognitive Function in Long-Term Follow-Up.

To date every post-procedural cerebrovascular embolic event (CVE) is dreaded for its potential to accelerate cognitive decline after transcatheter aortic valve implantation (TAVI). This study differentiates the impact of acute (procedural) and post-acute cerebrovascular embolic events (CVEs) on cognitive performance.Magnetic resonance imaging (MRI) before, early and late after TAVI was performed to quantify embolic burden. Quantification of diffusion- and T1-weighted lesions, as well as white-matter and total brain volumes, as well as cognitive function testing (MMSE) were assessed in 28 patients with a medium follow-up period of 34 months.Procedural diffusion-weighted lesions were observed in 17 patients (61%), but demonstrated locoregional remnants only in a minority of patients in long-term follow-up (6.5%). Acute CVEs did not impact the trajectory of late silent brain infarctions (SBI), white-matter hyperintensities, and cerebral atrophy. Functionally, early CVEs did not affect cognitive function. In contrast, patients with "new" SBIs after TAVI had a trend to cognitive deterioration in long-term follow-up ("new"SBI: MMSE -1.4 / no "new"SBI: MMSE +1.5, p = 0.067). Interestingly, only a fraction of these "new" SBIs evolved from procedural CVEs (22.2%).Aquired SBIs after TAVI, but not DW-CVE per se are associated with functional impairment long-term after TAVI. In the context of subacute thrombosis seen in TAVI prostheses, these findings set the stage for tailored stroke prevention and comprehensive surrogate endpoint definitions in neuroprotective trials

Functional outcome after TAVI.

Cognitive outcome was not influenced by the occurence of new events in diffusion-weighted magnetic resonance imaging (DW-MRI) early after TAVI (FU1, left side). However, patients with “new”, non-procedural SBIs (confirmed in FLAIR-imaging) during long-term follow-up after TAVI have a trend towards cognitive decline as compared to patients without. DW–Diffusion-weighted, FU–Follow-up, FLAIR—Fluid Attenuated Inversion Recovery MMSE–Mini-mental state exam.</p

Trajectories of acute and subacute cerebral lesions after TAVI.

<p>Patients underwent MRI prior (left), early (mid) and late (right) after TAVI. Above: The majority of patients demonstrate cerebral embolic events early after TAVI. No spontaneous lesions were observed prior and late after TAVI. Below: Ten out of 28 patients undergoing TAVI had 14 (old, non-procedural) silent brain infarctions (SBIs) in MRI (left). After long-term follow-up, seven patients without "old" SBIs revealed "new", post-procedural events. Notably, only four out of 18 "new" SBIs had an early procedural correlate in diffusion-weighted imaging (right).</p

Univariate analyses of clinical baseline characteristics dichotomized for the occurence of a new procedural DWI event at follow-up 1.

<p>Univariate analyses of clinical baseline characteristics dichotomized for the occurence of a new procedural DWI event at follow-up 1.</p

Morphological cerebral outcome after TAVI.

<p>The majority of patients (60.7%) had acute lesions in cerebral diffusion-weighted magnetic resonance imaging (DW-MRI) after TAVI. However, there was no association of these acute events (DW-CVEs) and the incidence of SBIs after long-term follow-up. Moreover, DW-CVEs neither aggravated the progression of white matter hyperintensities (> 1.5% / year), nor the progression of cerebral atrophy (> 1% / year). TAVI–Transcatheter aortic valve implantation, DW–diffusion-weighted, CVE–cerebrovascular event, MRI–magnetic resonance imaging, WMH–white matter hyperintensities, TBV–total brain volume, FLAIR—Fluid Attenuated Inversion Recovery.</p

Representative MRIs of patients after TAVI.

<p>Above: Representative MRI data sets of two patients showing raw data (upper row) and overlay images (lower row). Images were acquired early (DWI@FU1 and FLAIR@FU1) and late (FLAIR@FU2) after TAVI. Below: On overlay images, yellow lesions display acute procedural CVEs which vanished without detectable remnants @FU2, purple lesions display acute procedural DW-CVEs with scarring @FU2, red lesions display “new”, non-procedural SBIs @FU2 in a location where previously no DW-CVEs were present, and green lesions display WMHs. DWI@FU1 after TAVI shows procedural CVEs in both patients. FLAIR imaging acquired at FU1 shows mild (left) and severe (right) WMH-load. However, both demonstrated only slight increase throughout the follow-up period of 35 and 41 months, respectively. The left patient developed a parenchymal defect in the left cerebellum (FLAIR@FU2) in the same location of the DW-CVE at FU1, indicating scarring of a procedural CVE. In contrast, the right patient developed an infarct-like lesion in the left frontal lobe in a location where no DW-CVE was previously recognized at FU1 (“new”, non-procedural SBI). Only a fraction of peri-procedural, acute DW-CVEs resulted in detectable infarct-like lesions in follow-up scans (arrow). DWI–Diffusion-weighted imaging, CVE–Cerebrovascular event, WMH–White matter hyperintensities, SBI–Silent brain infarction, FLAIR—Fluid Attenuated Inversion Recovery, FU–Follow-up, TAVI–Transcatheter aortic valve implantation.</p

Univariate analyses of clinical baseline characteristics dichotomized for the occurence of new SBIs at follow-up 2.

<p>Univariate analyses of clinical baseline characteristics dichotomized for the occurence of new SBIs at follow-up 2.</p

Clinical baseline characteristics.

<p>Clinical baseline characteristics.</p