Commissural misalignment independently predicts leaflet thrombosis after transcatheter aortic valve implantation.

AIMS: Transcatheter aortic valve implantation (TAVI) has become a minimally invasive alternative to surgical aortic valve replacement. Hypo-attenuated leaflet thickening (HALT)-a marker of subclinical leaflet thrombosis commonly detected by cardiac computed tomography (CT) after TAVI-may influence valve durability and function. The purpose of this study was to compare commissural alignment of the native and prosthetic aortic valves in cardiac CT in subjects with and without HALT and thereby identify commissural misalignment as potential predictor for leaflet thrombosis after TAVI. METHODS AND RESULTS: In 170 subjects, 85 with and 85 without HALT in post-TAVI CT, commissural orientation of the prosthesis was determined comparing native and prosthetic aortic valve orientation in cardiac CT by measuring the commissural angle relative to the right coronary ostium in the aortic valve plane. For the prosthetic valve, any deviation ≤ 15° compared to the native valve was classified as "aligned"; 16-30° as "mild", 31-45° as "moderate" and ≥ 45° as "severe" misalignment. Among subjects with HALT, median angular deviation was higher (36°, IQR 31°) than in the control group (29°, IQR 29°, p = 0.042). "Severe" misalignment was more frequent in subjects who developed HALT (n = 31, 37%) compared to the control group (n = 17, 20%, p = 0.013). In logistic regression analysis, more severe deviation (p = 0.015, OR = 1.02 per 1° deviation) and "severe" misalignment (p = 0.018, OR = 2.2) represented independent predictors for the occurrence of HALT after TAVI. CONCLUSION: Subclinical leaflet thrombosis after TAVI is associated with commissural misalignment. Potential clinical advantages of obtaining commissural alignment remain to be systematically assessed.

Highly accelerated, Dixon-based non-contrast MR angiography versus high-pitch CT angiography.

OBJECTIVES: To compare a novel, non-contrast, flow-independent, 3D isotropic magnetic resonance angiography (MRA) sequence that combines respiration compensation, electrocardiogram (ECG)-triggering, undersampling, and Dixon water-fat separation with an ECG-triggered aortic high-pitch computed tomography angiography (CTA) of the aorta. MATERIALS AND METHODS: Twenty-five patients with recent CTA were scheduled for non-contrast MRA on a 3 T MRI. Aortic diameters and cross-sectional areas were measured on MRA and CTA using semiautomatic measurement tools at 11 aortic levels. Image quality was assessed independently by two radiologists on predefined aortic levels, including myocardium, proximal aortic branches, pulmonary veins and arteries, and the inferior (IVC) and superior vena cava (SVC). Image quality was assessed on a 5-point Likert scale. RESULTS: All datasets showed diagnostic image quality. Visual grading was similar for MRA and CTA regarding overall image quality (0.71), systemic arterial image quality (p = 0.07-0.91) and pulmonary artery image quality (p = 0.05). Both readers favored MRA for SVC and IVC, while CTA was preferred for pulmonary veins (all p < 0.05). No significant difference was observed in aortic diameters or cross-sectional areas between native MRA and contrast-enhanced CTA (p = 0.08-0.94). CONCLUSION: The proposed non-contrast MRA enables robust imaging of the aorta, its proximal branches and the pulmonary arteries and great veins with image quality and aortic diameters and cross-sectional areas comparable to that of CTA. Moreover, this technique represents a suitable free-breathing alternative, without the use of contrast agents or ionizing radiation. Therefore, it is especially suitable for patients requiring repetitive imaging.

Computed Tomography-derived Characterization of Pericoronary, Epicardial, and Paracardial Adipose Tissue and Its Association With Myocardial Ischemia as Assessed by Computed Fractional Flow Reserve.

BACKGROUND: Increased pericoronary adipose tissue (PCAT) attenuation derived from coronary computed tomography (CT) angiography (CTA) relates to coronary inflammation and cardiac mortality. We aimed to investigate the association between CT-derived characterization of different cardiac fat compartments and myocardial ischemia as assessed by computed fractional flow reserve (FFRCT). METHODS: In all, 133 patients (median 64 y, 74% male) with coronary artery disease (CAD) underwent CTA including FFRCT measurement followed by invasive FFR assessment (FFRINVASIVE). CT attenuation and volume of PCAT were quantified around the proximal right coronary artery (RCA), left anterior descending artery (LAD), and left circumflex artery (LCX). Epicardial adipose tissue (EAT) and paracardial adipose tissue (PAT; all intrathoracic adipose tissue outside the pericardium) were quantified in noncontrast cardiac CT datasets. RESULTS: Median FFRCT was 0.86 [0.79, 0.91] and median FFRINVASIVE was 0.87 [0.81, 0.93]. Subjects with the presence of myocardial ischemia (n=26) defined by an FFRCT-threshold of ≤0.75 showed significantly higher RCA PCAT attenuation than individuals without myocardial ischemia (n=107) (-75.1±10.8 vs. -81.1±10.6 HU, P=0.011). In multivariable analysis adjusted for age, body mass index, sex and risk factors, increased RCA PCAT attenuation remained a significant predictor of myocardial ischemia. Between individuals with myocardial ischemia compared with individuals without myocardial ischemia, there was no significant difference in the volume and CT attenuation of EAT and PAT or in the PCAT volume of RCA, LAD, and LCX. CONCLUSIONS: Increased RCA PCAT attenuation is associated with the presence of myocardial ischemia as assessed by FFR, while PCAT volume, EAT, and PAT are not.

Influence of reconstruction kernels on the accuracy of CT-derived fractional flow reserve.

OBJECTIVES: We evaluated the influence of image reconstruction kernels on the diagnostic accuracy of CT-derived fractional flow reserve (FFRCT) compared to invasive FFR in patients with coronary artery disease. METHODS: Sixty-nine patients, in whom coronary CT angiography was performed and who were further referred for invasive coronary angiography with FFR measurement via pressure wire, were retrospectively included. CT data sets were acquired using a third-generation dual-source CT system and rendered with medium smooth (Bv40) and sharp (Bv49) reconstruction kernels. FFRCT was calculated on-site using prototype software. Coronary stenoses with invasive FFR ≤ 0.80 were classified as significant. Agreement between FFRCT and invasive FFR was determined for both reconstruction kernels. RESULTS: One hundred analyzed vessels in 69 patients were included. Twenty-five vessels were significantly stenosed according to invasive FFR. Using a sharp reconstruction kernel for FFRCT resulted in a significantly higher correlation with invasive FFR (r = 0.74, p < 0.01 vs. r = 0.58, p < 0.01; p = 0.04) and a higher AUC in ROC curve analysis to correctly identify/exclude significant stenosis (AUC = 0.92 vs. AUC = 0.82 for sharp vs. medium smooth kernel, respectively, p = 0.02). A FFRCT value of ≤ 0.8 using a sharp reconstruction kernel showed a sensitivity of 88% and a specificity of 92% for detecting ischemia-causing lesions, resulting in a diagnostic accuracy of 91%. The medium smooth reconstruction kernel performed worse (sensitivity 60%, specificity 89%, accuracy 82%). CONCLUSION: Compared to invasively measured FFR, FFRCT using a sharp image reconstruction kernel shows higher diagnostic accuracy for detecting lesions causing ischemia, potentially altering decision-making in a clinical setting. KEY POINTS: • Image reconstruction parameters influence the diagnostic accuracy of simulated fractional flow reserve derived from coronary computed tomography angiography. • Using a sharp kernel image reconstruction algorithm delivers higher diagnostic accuracy compared to medium smooth kernel image reconstruction (gold standard invasive fractional flow reserve).

Meta-Analysis of Bioprosthetic Valve Thrombosis After Transcatheter Aortic Valve Implantation.

Bioprosthetic valve thrombosis may complicate transcatheter aortic valve implantation (TAVI). This meta-analysis sought to evaluate the prevalence and clinical impact of subclinical leaflet thrombosis (SLT) and clinical valve thrombosis (CVT) after TAVI. We summarized diagnostic strategies, prevalence of SLT and/or CVT and estimated their impact on the risk of all-cause death and stroke. Twenty studies with 12,128 patients were included. The prevalence of SLT and CVT was 15.1% and 1.2%, respectively. The risk of all-cause death was not significantly different between patients with SLT (relative risk [RR] 0.77; p = 0.22) and CVT (RR 1.29; p = 0.68) compared with patients without. The risk of stroke was higher in patients with CVT (RR 7.51; p <0.001) as compared with patients without, while patients with SLT showed no significant increase in the risk of stroke (RR 1.81; p = 0.17). Reduced left ventricular function was associated with increased prevalence, while oral anticoagulation was associated with reduced prevalence of bioprosthetic valve thrombosis. Bioprosthetic valve thrombosis is frequent after TAVI, but does not increase the risk of death. Clinical valve thrombosis is associated with a significantly increased risk of stroke. Future studies should focus on prevention and treatment of bioprosthetic valve thrombosis.

Quantification of epicardial adipose tissue by cardiac CT: Influence of acquisition parameters and contrast enhancement.

PURPOSE: While computed tomography (CT) is frequently used to quantify epicardial adipose tissue (EAT), the effect of different acquisition parameters on EAT volume has not been systematically reported. We assessed the influence of low-voltage acquisition and contrast enhancement on EAT quantification. METHOD: Two independent cohorts (100 and 127 patients) referred for routine coronary CT were included. One cohort received a low-voltage and a standard voltage non-contrast acquisition (120 and 100 kV), the other cohort underwent non-contrast and contrast-enhanced CT. EAT volume was quantified using a semi-automated analysis software. Whereas the lower EAT threshold was consistently set at -190 Hounsfield Units (HU), different upper thresholds for EAT were analyzed. Bland-Altman analysis was used to analyze the agreement of EAT volume between scans with different acquisition parameters. We referred to a non-enhanced 120 kV acquisition with an upper threshold of -30 HU. RESULTS: Mean EAT volume was 159 ±â€¯76 ml as measured in 120 kV non-contrast data sets with an upper threshold of -30 HU. For 100 kV data sets, an upper threshold of -40 HU showed the best correlation (r = 0.961, p < 0.05). Significant overestimation was found for upper thresholds of -20 and -30 HU and significant underestimation for -50 HU. In non-contrast vs. contrast-enhanced acquisitions, there was a significant underestimation of EAT volume for contrast-enhanced scans (mean difference 31 ml, 95% limits of agreement 27 to -89 ml). CONCLUSIONS: CT-based EAT volume quantification in low-voltage and contrast-enhanced images is feasible. However, adjustment of the upper threshold for detection of fat is mandatory.

Eyeball pressure stimulation induces subtle sympathetic activation in patients with a history of moderate or severe traumatic brain injury.

OBJECTIVE: After traumatic brain injury (TBI), there may be persistent central-autonomic-network (CAN) dysfunction causing cardiovascular-autonomic dysregulation. Eyeball-pressure-stimulation (EPS) normally induces cardiovagal activation. In patients with a history of moderate or severe TBI (post-moderate-severe-TBI), we determined whether EPS unveils cardiovascular-autonomic dysregulation. METHODS: In 51 post-moderate-severe-TBI patients (32.7 ±â€¯10.5 years old, 43.1 ±â€¯33.4 months post-injury), and 30 controls (29.1 ±â€¯9.8 years), we recorded respiration, RR-intervals (RRI), systolic and diastolic blood-pressure (BPsys, BPdia), before and during EPS (120 sec; 30 mmHg), using an ocular-pressure-device (Okulopressor®). We calculated spectral-powers of mainly sympathetic low (LF: 0.04-0.15 Hz) and parasympathetic high (HF: 0.15-0.5 Hz) frequency RRI-fluctuations, sympathetically mediated LF-powers of BPsys, and calculated normalized (nu) LF- and HF-powers of RRI. We compared parameters between groups before and during EPS by repeated-measurement-analysis-of-variance with post-hoc analysis (significance: p < 0.05). RESULTS: At rest, sympathetically mediated LF-BPsys-powers were significantly lower in the patients than the controls. During EPS, only controls significantly increased RRIs and parasympathetically mediated HFnu-RRI-powers, but decreased LF-RRI-powers, LFnu-RRI-powers, and LF-BPsys-powers; in contrast, the patients slightly though significantly increased BPsys upon EPS, without changing any other parameter. CONCLUSIONS: In post-moderate-severe-TBI patients, autonomic BP-modulation was already compromised at rest. During EPS, our patients failed to activate cardiovagal modulation but slightly increased BPsys, indicating persistent CAN dysregulation. SIGNIFICANCE: Our findings unveil persistence of subtle cardiovascular-autonomic dysregulation even years after TBI.

Severity of traumatic brain injury correlates with long-term cardiovascular autonomic dysfunction.

After traumatic brain injury (TBI), central autonomic dysfunction might contribute to long-term increased mortality rates. Central autonomic dysfunction might depend on initial trauma severity. This study was performed to evaluate differences in autonomic modulation at rest and upon standing between patients with a history of mild TBI (post-mild-TBI patients), moderate or severe TBI (post-moderate-severe-TBI patients), and healthy controls. In 20 post-mild-TBI patients (6-78 months after TBI), age-matched 20 post-moderate-severe-TBI patients (6-94 months after TBI) and 20 controls, we monitored respiration, RR intervals (RRI) and systolic blood pressure (BPsys) at supine rest and upon standing. We determined mainly sympathetic low (LF) and parasympathetic high (HF) frequency powers of RRI fluctuations, sympathetically mediated LF-BPsys powers, LF/HF-RRI ratios, normalized (nu) LF-RRI and HF-RRI powers, and compared data between groups, at rest and upon standing (ANOVA with post hoc testing). We correlated autonomic parameters with initial Glasgow Coma Scale (GCS) scores (Spearman test; significance: p < 0.05). Supine BPsys and LFnu-RRI powers were higher while HFnu-RRI powers were lower in post-moderate-severe-TBI patients than post-mild-TBI patients and controls. LFnu-RRI powers were higher and HFnu-RRI powers were lower in post-mild-TBI patients than controls. Upon standing, only post-mild-TBI patients and controls increased LF-BPsys powers and BPsys and decreased HF-RRI powers. GCS scores correlated positively with LFnu-RRI powers, LF/HF-RRI ratios, and inversely with HFnu-RRI powers, at standing position. More than 6 months after TBI, there is autonomic dysfunction at rest and upon standing which is more pronounced after moderate-severe than mild TBI and in part correlates with initial trauma severity.

Valsalva maneuver unveils central baroreflex dysfunction with altered blood pressure control in persons with a history of mild traumatic brain injury.

BACKGROUND: Patients with a history of mild TBI (post-mTBI-patients) have an unexplained increase in long-term mortality which might be related to central autonomic dysregulation (CAD). We investigated whether standardized baroreflex-loading, induced by a Valsalva maneuver (VM), unveils CAD in otherwise healthy post-mTBI-patients. METHODS: In 29 healthy persons (31.3 ± 12.2 years; 9 women) and 25 post-mTBI-patients (35.0 ± 13.2 years, 7 women, 4-98 months post-injury), we monitored respiration (RESP), RR-intervals (RRI) and systolic blood pressure (BP) at rest and during three VMs. At rest, we calculated parameters of total autonomic modulation [RRI-coefficient-of-variation (CV), RRI-standard-deviation (RRI-SD), RRI-total-powers], of sympathetic [RRI-low-frequency-powers (LF), BP-LF-powers] and parasympathetic modulation [square-root-of-mean-squared-differences-of-successive-RRIs (RMSSD), RRI-high-frequency-powers (HF)], the index of sympatho-vagal balance (RRI LF/HF-ratios), and baroreflex sensitivity (BRS). We calculated Valsalva-ratios (VR) and times from lowest to highest RRIs after strain (VR-time) as indices of parasympathetic activation, intervals from highest systolic BP-values after strain-release to the time when systolic BP had fallen by 90 % of the differences between peak-phase-IV-BP and baseline-BP (90 %-BP-normalization-times), and velocities of BP-normalization (90 %-BP-normalization-velocities) as indices of sympathetic withdrawal. We compared patient- and control-parameters before and during VM (Mann-Whitney-U-tests or t-tests; significance: P < 0.05). RESULTS: At rest, RRI-CVs, RRI-SDs, RRI-total-powers, RRI-LF-powers, BP-LF-powers, RRI-RMSSDs, RRI-HF-powers, and BRS were lower in patients than controls. During VMs, 90 %-BP-normalization-times were longer, and 90 %-BP-normalization-velocities were lower in patients than controls (P < 0.05). CONCLUSIONS: Reduced autonomic modulation at rest and delayed BP-decrease after VM-induced baroreflex-loading indicate subtle CAD with altered baroreflex adjustment to challenge. More severe autonomic challenge might trigger more prominent cardiovascular dysregulation and thus contribute to increased mortality risk in post-mTBI-patients.