Understanding the role of the left atrial appendage on the flow in the atrium.

BACKGROUND: The exclusion/occlusion of the left atrial appendage (LAA) is a treatment option for atrial fibrillation (AF) patients who are at high risk of stroke and high risk of bleeding. As the role of the LAA is not well understood or explored, this study aims to assess its role on flow dynamics in the left atrium. METHODS: Computational fluid dynamics (CFD) simulations were carried out for nine AF patients before and after LAA exclusion. The flow parameters investigated included the LA velocities, Time Averaged Wall Shear Stress (TAWSS), Oscillatory Shear Index (OSI), Relative Residence Time (RRT), and Pressure in the LA. RESULTS: This study shows that, on average, a decrease in TAWSS (1.82 ± 1.85 Pa to 1.27 ± 0.96 Pa, p < 0.05) and a slight increase in OSI (0.16 ± 0.10 to 0.17 ± 0.10, p < 0.05), RRT (1.87 ± 1.84 Pa-1 to 2.11 ± 1.78 Pa-1, p < 0.05), and pressure (-19.2 ± 6.8 mmHg to -15.3 ± 8.3 mmHg, p < 0.05) were observed in the LA after the exclusion of the LAA, with a decrease in low-magnitude velocities. CONCLUSION: The exclusion of the LAA seems to be associated with changes in LA flow dynamics. Further studies are needed to elucidate the clinical implications of these changes.

Evaluation of Myocarditis with a Free-breathing 3D Isotropic Whole-Heart Joint T1 and T2 Mapping Sequence.

BACKGROUND: The diagnosis of myocarditis by CMR requires the use of T2 and T1 weighted imaging, ideally incorporating parametric mapping. Current 2D mapping sequences are acquired sequentially and involve multiple breath-holds resulting in prolonged scan times and anisotropic image resolution. We developed an isotropic free-breathing 3D whole-heart sequence which allows simultaneous T1 and T2 mapping and validated it in patients with suspected acute myocarditis. METHODS: Eighteen healthy volunteers and 28 patients with suspected myocarditis underwent conventional 2D T1 and T2 mapping with whole heart coverage and 3D joint T1/T2 mapping on a 1.5T scanner. Acquisition time, image quality, and diagnostic performance were compared. Qualitative analysis was performed using a 4-point Likert scale. Bland-Altman plots were used to assess the quantitative agreement between 2D and 3D sequences. RESULTS: The 3D T1/T2 sequence was acquired in 8mins 26s under free breathing, whereas 2D T1 and T2 sequences were acquired with breath holds in 11mins 44s (p=0.0001). All 2D images were diagnostic. For 3D images, 89% of T1 and 96% of T2 images were diagnostic with no significant difference in the proportion of diagnostic images for the 3D and 2D T1 (p=0.2482) and T2 maps (p=1.0000). Systematic bias in T1 was noted with biases of 102ms, 115ms, and 152ms for basal-apical segments, with a larger bias for higher T1 values. Good agreement between T2 values for 3D and 2D techniques was found (bias of 1.8ms, 3.9ms, and 3.6ms for basal-apical segments). The sensitivity and specificity of the 3D sequence for diagnosing acute myocarditis was 74% (95% confidence interval [CI] 49-91%) and 83% (36-100%) respectively, with an estimated c-statistic (95% CI) of 0.85 (0.79-0.91) and no statistically significant difference between the 2D and 3D sequences for the detection of acute myocarditis for T1 (p=0.2207) or T2 (p=1.0000). CONCLUSION: Free-breathing whole heart 3D joint T1/T2 mapping was comparable to 2D mapping sequences with respect to diagnostic performance, but with the added advantages of free-breathing, and shorter scan times. Further work is required to address the bias noted at high T1 values, but this did not significantly impact on diagnostic accuracy.

Effect of Blood Pressure Levels on Sinus Hemodynamics in Relation to Calcification After Bioprosthetic Aortic Valve Replacement.

Coexisting hypertension and aortic stenosis are common. Some studies showed that elevated blood pressures may be associated with progression of calcific aortic valve disease (CAVD) while others showed no correlation. Flow dynamics in the sinuses of Valsalva are considered key factors in the progression of CAVD. While the relationship between hemodynamics and CAVD is not yet fully understood, it has been demonstrated that they are tightly correlated. This study aims to investigate the effect of changing systolic and diastolic blood pressures (SBP and DBP, respectively) on sinus hemodynamics in relation to potential initiation or progression of CAVD after aortic valve replacement (AVR). Evolut R, SAPIEN 3 and Magna valves were deployed in an aortic root under pulsatile conditions. Using particle image velocimetry, the hemodynamics in the sinus were assessed. The velocity, vorticity, circulation ( Γ ) and shear stress were calculated. This study shows that under elevated SBP and DBP, velocity, vorticity, and shear stress nearby the leaflets increased. Additionally, larger fluctuations of Γ and area under the curve throughout the cardiac cycle were observed. Elevated blood pressures are associated with higher velocity, vorticity, and shear stress near the leaflets which may initiate or accelerate pro-calcific changes in the prosthetic leaflets leading to bioprosthetic valve degeneration.

Association of Bovine Arch Anatomy With Incident Stroke After Transcatheter Aortic Valve Replacement.

BACKGROUND: Acute ischemic stroke complicates 2% to 3% of transcatheter aortic valve replacements (TAVRs). This study aimed to identify the aortic anatomic correlates in patients after TAVR stroke. METHODS AND RESULTS: This is a single-center, retrospective study of patients who underwent TAVR at the Mayo Clinic between 2012 and 2022. The aortic arch morphology was determined via a manual review of the pre-TAVR computed tomography images. An "a priori" approach was used to select the covariates for the following: (1) the logistic regression model assessing the association between a bovine arch and periprocedural stroke (defined as stroke within 7 days after TAVR); and (2) the Cox proportional hazards regression model assessing the association between a bovine arch and long-term stroke after TAVR. A total of 2775 patients were included (59.6% men; 97.8% White race; mean±SD age, 79.3±8.4 years), of whom 495 (17.8%) had a bovine arch morphology. Fifty-seven patients (1.7%) experienced a periprocedural stroke. The incidence of acute stroke was significantly higher among patients with a bovine arch compared with those with a nonbovine arch (3.6% versus 1.7%; P=0.01). After adjustment, a bovine arch was independently associated with increased periprocedural strokes (adjusted odds ratio, 2.16 [95% CI, 1.22-3.83]). At a median follow-up of 2.7 years, the overall incidence of post-TAVR stroke was 6.0% and was significantly higher in patients with a bovine arch even after adjusting for potential confounders (10.5% versus 5.0%; adjusted hazard ratio, 2.11 [95% CI, 1.51-2.93]; P<0.001). CONCLUSIONS: A bovine arch anatomy is associated with a significantly higher risk of periprocedural and long-term stroke after TAVR.

Analysis of Energy and Pressure in the Sinus with Different Blood Pressures after Bioprosthetic Aortic Valve Replacement.

PURPOSE: To investigate the effect of changing systolic and diastolic blood pressures (SBP and DBP, respectively) on sinus flow and valvular and epicardial coronary flow dynamics after TAVR and SAVR. METHODS: SAPIEN 3 and Magna valves were deployed in an idealized aortic root model as part of a pulse duplicating left heart flow loop simulator. Different combinations of SBP and DBP were applied to the test setup and the resulting change in total coronary flow from baseline (120/60 mmHg), effective orifice area (EOA), and left ventricular (LV) workload, with each combination, was assessed. In addition, particle image velocimetry was used to assess the Laplacian of pressure ( ∇ 2 P ) in the sinus, coronary and main flow velocities, the energy dissipation rate (EDR) in the sinus and the LV workload. RESULTS: This study shows that under an elevated SBP, there is an increase in the total coronary flow, EOA, LV workload, peak velocities downstream of the valve, ∇ 2 P , and EDR. With an elevated DBP, there was an increase in the total coronary flow and ∇ 2 P . However, EOA and LV workload decreased with an increase in DBP, and EDR increased with a decrease in DBP. CONCLUSIONS: Blood pressure alters the hemodynamics in the sinus and downstream flow following aortic valve replacement, potentially influencing outcomes in some patients.

Association of transcatheter left atrial appendage occlusion with acute changes in left atrial pressure: An invasive hemodynamic study.

BACKGROUND: The hemodynamic effects of transcatheter left atrial appendage occlusion (LAAO) remain unclear. OBJECTIVE: We sought to assess the effect of LAAO on invasive hemodynamics and their correlation with clinical outcomes. METHODS: We recorded mean left atrial pressure (mLAP) before and after device deployment. We assessed the prevalence and predictors of mLAP increase after deployment, the association between significant mLAP increase after deployment and 45-day peridevice leak (PDL), and the association between mLAP increase and heart failure (HF) hospitalization. A significant mLAP increase was defined as one equal to or greater than the mean percentage increase in mLAP after deployment (≥28%). RESULTS: We included 302 patients (36.4% female; mean age, 75.8 ± 9.5 years). After deployment, mLAP increased in 48% of patients, 38% of whom experienced significant mLAP increase. Independent predictors of mLAP increase were baseline mLAP ≤14 mm Hg, nonparoxysmal atrial fibrillation, and age per 5 years (odds ratios: 3.66 [95% CI, 2.21-6.05], 1.81 [95% CI, 1.08-3.02], and 0.85 [95% CI, 0.73-0.99], respectively). Significant mLAP increase was an independent predictor of 45-day PDL (odds ratio, 2.55; 95% CI, 1.04-6.26). There was no association between mLAP increase and HF hospitalization. CONCLUSION: After deployment, mLAP acutely rises in 48% of patients, although this is not associated with increased HF hospitalizations. PDL is more likely to develop at 45 days in patients with significant increase in mLAP after deployment, although most leaks were small (<5 mm). These findings suggest that mLAP increase after deployment is not associated with major safety concerns. Additional studies are warranted to explore the long-term hemodynamic effects of LAAO.

Flow Dynamic Factors Correlated With Device-Related Thrombosis After Left Atrial Appendage Occlusion.

Background: Device-related thrombosis (DRT) occurs in up to 4% of patients undergoing left atrial appendage occlusion (LAAO) and is associated with substantial morbidity and mortality. However, its pathophysiology, predictors, and optimal management remain unclear. Objectives: This study aims to assess flow dynamic factors correlating to DRT. Methods: A multicenter registry of patients who underwent LAAO and had pre- and post-computed tomography imaging was used. Patient-specific 3-dimensional digital models of the left atrium were created, and finite element simulations were performed to implant an LAAO device into each model in a position that matched the clinical deployment. Computational fluid dynamic simulations were performed to quantify the following flow dynamic parameters: time averaged wall shear stress, oscillatory shear index, and endothelial cell activation potential. Results: A total of 38 patients (19 with DRT and 19 without DRT) were included. Left atrium volumes and mitral valve areas were larger in the DRT cohort compared with controls. Patients with DRT had a significantly lower time averaged wall shear stress (1.76 ± 1.24 Pa vs 2.90 ± 2.70 Pa), a higher oscillatory shear index (0.19 ± 0.11 vs 0.17 ± 0.11), and a higher endothelial cell activation potential (0.23 ± 0.58 Pa-1 vs 0.17 ± 0.30 Pa-1) than the controls (P < 0.001 for all). Thrombus locations identified from in-vivo images correlated well with the flow dynamic parameters tested. Conclusions: Flow dynamic parameters may be able to predict the risk of DRT after LAAO. Further investigation with a larger patient cohort and long-term follow-up is needed to assess the role of computational fluid dynamics in the risk stratification of patients considered for LAAO.

SARS-CoV-2 vaccines and myocarditis.

The development of safe and effective vaccines against severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) was a major turning point in the fight against the Coronavirus 2019 (COVID-19) pandemic. However, pharmacovigilance has revealed a small but significant incidence of cardiac inflammation manifesting clinically as myocarditis or pericarditis, particularly in younger vaccine recipients. The incidence is the highest among men under age 40 within a week of receiving the second dose of the mRNA vaccine. In this review, we summarise the evidence for, and guidelines in relation to, SARS-CoV2 vaccine-related myocarditis.

Conventional aortic root vs valve-sparing root replacement surgery in aortic dilatation syndromes: a comparison of mortality and postoperative complications.

INTRODUCTION: Conventional aortic root and valve-sparing root replacement surgery are two current surgical treatments for aortic dilatation syndromes. This review article aims to review the current literature surrounding these two established techniques. AREAS COVERED: This review article will address the current indications for valve-sparing root replacement surgery, technical considerations in surgical planning and a comparison of clinical outcomes between these two surgical techniques. EXPERT OPINION: Valve-sparing root replacement surgery is a safe and established treatment for aortic syndromes. Valve-sparing surgery procedure avoids the inherent risk of prosthetic valve dysfunction and prosthesis infection by preserving the native aortic valve compared to conventional aortic root surgery. This has been demonstrated in various observational studies and should be considered in clinically and anatomically appropriate patients. Other technical considerations, such as reimplantation versus remodeling technique and aortic cusp repair in select patients, may impact in short-term procedural and long-term clinical success with valve-sparing surgery.

Shockwave Intravascular Lithotripsy for the Treatment of Severe Vascular Calcification.

Vascular calcification is a highly prevalent pathophenotype that is associated with aging, atherosclerotic cardiovascular disease, diabetes mellitus, and chronic kidney disease. When present, it portends a worse clinical outcome and predicts major adverse cardiovascular events. Heavily calcified coronary and peripheral artery lesions are difficult to dilate appropriately with conventional balloons during percutaneous intervention, and the use of several adjunctive strategies of plaque modification has been suggested. Intravascular lithotripsy (IVL) offers a novel option for lesion preparation of severely calcified plaques in coronary and peripheral vessels. It is unique among all technologies in its ability to modify calcium circumferentially and transmurally, thus modifying transmural conduit compliance. In this article, we summarize the currently available evidence on this technology, and we highlight its best clinical application through appropriate patient and lesion selection, with the main objective of optimizing stent delivery and implantation, and subsequent improved short- and long-term outcomes. We believe that the IVL balloon will transform the market, as it is easy to use, with predictable results. However, cost-effectiveness of such advanced technology will need to be considered.

Exome Sequencing Implicates Impaired GABA Signaling and Neuronal Ion Transport in Trigeminal Neuralgia.

Trigeminal neuralgia (TN) is a common, debilitating neuropathic face pain syndrome often resistant to therapy. The familial clustering of TN cases suggests that genetic factors play a role in disease pathogenesis. However, no unbiased, large-scale genomic study of TN has been performed to date. Analysis of 290 whole exome-sequenced TN probands, including 20 multiplex kindreds and 70 parent-offspring trios, revealed enrichment of rare, damaging variants in GABA receptor-binding genes in cases. Mice engineered with a TN-associated de novo mutation (p.Cys188Trp) in the GABAA receptor Cl- channel γ-1 subunit (GABRG1) exhibited trigeminal mechanical allodynia and face pain behavior. Other TN probands harbored rare damaging variants in Na+ and Ca+ channels, including a significant variant burden in the α-1H subunit of the voltage-gated Ca2+ channel Cav3.2 (CACNA1H). These results provide exome-level insight into TN and implicate genetically encoded impairment of GABA signaling and neuronal ion transport in TN pathogenesis.