1. ©2010 c.nasel Global Change of Cerebral Hemodynamics in Patients with Chronic Heart Failure Našel C., Stift E., Sykora T., Kirchner T., Filka B., Reiter G., Frank H. Center of Clinical Neurosciences Department of Clinical & Preventive Medicine Danube University Krems Departments of Radiology & Internal Medicine State Clinical Center - Danube District / Tulln

2. ©2010 c.nasel Background: Cardiovascular risk factors were found to be associated with a higher incidence of structural brain lesions Number and extent of white matter lesions are higher in patients with heart failure (HF) than in populations with comparable risk factors Breteler MM, van Swieten JC, Bots ML, et al. Cerebral white matter lesions, vascular risk factors, and cognitive function in a populationbased study: the Rotterdam Study. Neurology 1994;44:1246–52 de Leeuw FE, de Groot JC, Oudkerk M, et al. Hypertension and cerebral white matter lesions in a prospective cohort study. Brain 2002;125:765–72. Almeida JR, Alves TC,Wajngarten M, et al. Late-life depression, heart failure and frontal white matter hyperintensity: a structural magnetic resonance imaging study. Braz J Med Biol Res 2005;38:431–6.......

3. ©2010 c.nasel Background: Cerebral affections with relation to HF: periventricular WM lesions subcortical WM lesions temporo-mesial atrophy lacunar lesions in basal ganglia Cardiac diseases with relation to cerebral affection: idiopathic dilated cardiomyopathy cardiac valve pathologies arrhythmias ( bradycard atrial fibrillation, sick sinus syndrome,... ) dyskinetic disorders of heart wall

4. ©2010 c.nasel Methodical Considerations: One of the strongest predictors for cerebral structural affections associated with chronic HF is left ventricular ejection fraction (LVEF) Vogels RLC et al. Brain magnetic resonance imaging abnormalities in patients with heart failure. Eur J Heart Fail, 2007, 9: 1003-1009 The only available perfusion-MRI based parameter so far, which automatically, quantitatively, reproducibly describes regional bolus delay and global bolus distribution over time within one map is the standardized time-to-peak parameter (stdTTP). Nasel C. et al. Standardized time to peak in ischemic and regular cerebral tissue measured with perfusion MR imaging. AJNR Am J Neuroradiol. 2004; 25:945-50

5. ©2010 c.nasel P-MRI & stdTTP: PerfusionEventImaging - jPerfModule cerebral bolus passage of contrast agent may be seen as the sum of the cardial pulse wave (target related to LVEF) and its transformation by cerebral vessels (constant)...

6. ©2010 c.nasel P-MRI & stdTTP: PerfusionEventImaging - jPerfModule the full automatic analysis of stdTTP-values frequency of an examination reveals that individual stdTTP-values do occur in relation to arterial input and venous wash out...

7. ©2010 c.nasel P-MRI & stdTTP: PerfusionEventImaging - jPerfModule automatic calculation of first pass duration, statistical adjustment of stdTTP-offset and detection of zero point of the first differential gives the arterial rise time (ART)...

8. ©2010 c.nasel P-MRI & stdTTP: PerfusionEventImaging - jPerfModule packing the complete image information into a characteristic number, which estimates the cerebrovascular preload...

9. ©2010 c.nasel P-MRI & stdTTP: PerfusionEventImaging - jPerfModule LVEF US : 44% [WiJo] LVEF US : 63% [GrAl] correlation of cardial restriction and cerebral perfusion signs of prolongated venous pooling (...)

10. ©2010 c.nasel Methods: Multimodal MRI ( 1.5T- Avanto, Siemens Medical Systems, Germany ) - dual echo advanced flair imaging (protoneus) -/+ CE - dynamic susceptibility contrast enhanced MRI (P-MRI) - diffusion wheighted MRI (DWI) with b=1000 s/mm2 - dyn-CE-MR angiography: range: aortic arc – circle of Willis Image postprocessing - calculation of regional cerebral blood flow (rCBF)- and regional mean transit time (rMTT)-maps - calculation of standardised time-to-peak (stdTTP)-maps with stdTTP-based arterial rise time - ROI-based analysis (native MRI), voxel-wise analysis (SPM)

11. ©2010 c.nasel Methods: Analysis - estimation of microvascualar disease (grading 0-4) rang scaled data; Wilcoxon test; - global CBF, MTT and stdTTP rationally scaled data; t-Test - arterial rise time (stdTTP-ART) rationally scaled data; t-Test - voxel-wise analysis t-Tests [vectors: -1,1 & 1,-1] Hypothesis:H0: no difference between reduced and regular LVEF Limitation:small sample size

12. ©2010 c.nasel Subjects: Observation (19 mo) Analysis of 18 matched patients: - indication for routine scans: TIA, vertigo, etc. (no exam. for study reasons ) - NIH-SS score: 0 - no MR-DWI alteration indicating recent / acute ischemia - no stenotic/occlusive cerebrovascular disease - electrocardiography: no myocardial infarction - continous O2-pulse oxymetry: 94- 99% O2-saturation - vascular risk factors equaly distributed in both groups (hypertonia; mild hypercholesterolaemia; no diabetes; no smokers) Group 1 ( n=9; f=3/ m=6; age: 66-85 y ): US-LVEF: 41 ± 16% Group 2 ( n=9; f=4/ m=5; age: 62-86 y ): US-LVEF: 58 ± 2% (Group2 changed, since age is covariate for LVEF and microangipathy)

13. ©2010 c.nasel Results: Group 1 (n=9; f=3/ m=6; age: 66-85 y): US-LVEF: 41 ± 16% Group 2 (n=9; f=4/ m=5; age: 62-86 y): US-LVEF: 58 ± 2% (orig. Grp2. replaced by matched group for covariates) extent of microvascular disease [median] : - grp.1 worse than grp.2: group 1 vs 2 = grade 0 vs 3. perfusion restriction [mean +/- SD: grp.1 vs grp.2] : - global CBF: grp.1 comparable grp.2 = 31.4±14.5vs32.4±6.8ml/100g/min t-test (grp.1<>2; lev.sig.: 0.05); p> 0.05 n.s. - global MTT: grp.1 slightly worse than grp. 2 = 6.3± 2.5vs 4.1±1.1s t-test (grp.1>2; lev.sig.: 0.025); p> 0.05 n.s. stdTTP-based arterial rise time [mean +/- SD: grp.1 vs grp.2] : - stdTTP-ART: grp.1 worse than grp.2 = 9.2 ± 2.2 vs 5.9 ± 0.8 s t-test (grp.1>2; lev.sig.: 0.025); p= 0.021 sig.

14. ©2010 c.nasel P-MRI & stdTTP: PerfusionEventImaging - jPerfModule - reduction of LVEF relates to higher stdTTP-ARTs and MTT -  LVEF and  stdTTP-art.rise time both seem to predicted a higher extent of microangiopathy

15. ©2010 c.nasel Conclusion: - according to earlier studies reduced LVEF was found more frequentlyin patients with larger extent of cerebrovascular disease - LVEF restriction occurs more often in patients with increased cerebral transit time (stdTTP-ART) - stdTTP-ART could potential become useful in identification of patiens with unspecific neurological symptoms due to occult chronic HF larger number of cases needed different cerebrovascular conditions have to be analysed

16. ©2010 c.nasel Global Change of Cerebral Hemodynamics in Patients with Chronic Heart Failure Našel C., Stift E., Sykora T., Kirchner T., Filka B., Reiter G., Frank H. Center of Clinical Neurosciences Department of Clinical & Preventive Medicine Danube University Krems Departments of Radiology & Internal Medicine State Clinical Center - Danube District / Tulln