Tricuspid Valve Leaflets-Lead Interaction: Adjunctive Role of Functional Cardiac Computed Tomography for Clinical Decision Making.

The diagnostic approach toward the management of cardiac implantable electronic device-related tricuspid regurgitation is challenging and undefined. Functional cardiac computed tomography angiography provides a complementary role to echocardiography in the evaluation of lead-leaflet interaction which can help the clinical decision-making process, as presented in this case series.

New Insights and Perspective on Bioprosthetic Valve Fracture From Bench Testing and Computed Tomography Analysis.

Background: Bioprosthetic valve fracture (BVF) during valve-in-valve TAVR (transcatheter aortic valve replacement) is a procedural adjunct designed to optimize the expansion of the transcatheter heart valve and reduce patient-prosthesis mismatch by using a high-pressure balloon to intentionally fracture the surgical heart valve (SHV). Methods: We performed bench testing on 15 bioprosthetic SHV to examine the optimal balloon size and pressure for BVF. We assessed morphological changes and expansion of SHV by computed tomography angiography. Successful BVF was defined as balloon waist disappearance on fluoroscopy and/or sudden pressure drop during balloon inflation. Results: Nine valves met the definition of BVF, 3 of which were confirmed by disruption of the stent frame. We classified surgical valves into 3 subsets: 1) fracturable with metal stent frame (MSF), 2) fracturable with polymer stent frame (PSF) and 3) nonfracturable. In general, valves with MSF were fractured using a balloon size = true internal diameter plus 3-5 mm inflated at high pressure (16-20 ATM) whereas valves with PSF could be fractured with a balloon size = true internal diameter plus 3-5 mm and lower balloon pressure (6-14 ATM). Gains in computed tomography angiography derived inflow area after BVF were 12.3% for MSF and 3.6% for PSF SHV. Conclusions: Gains in CT-determined valve area after BVF depend on the physical properties of the SHV, which in turn influences pressure thresholds and balloon sizing strategy for optimal BVF. Elastic recoil of PSF valves limits the gains in inflow area after BVF.

Deformation in transcatheter heart valves: Clinical implications and considerations.

Transcatheter aortic valve replacement (TAVR) has emerged as a preferred treatment modality for aortic stenosis, marking a significant advancement in cardiac interventions. Transcatheter heart valves (THVs) have also received approval for treating failed bioprosthetic valves and rings across aortic, mitral, tricuspid, and pulmonic positions. Unlike surgically implanted valves, which are sewn into the annulus, THVs are anchored through relative oversizing. Although THVs are designed to function optimally in a fully expanded state, they exhibit a certain degree of tolerance to underexpansion. However, significant deformation beyond this tolerance can adversely affect the valve's hemodynamics and durability, ultimately impacting patient outcomes. Such post-implantation deviations from the valve's intended three-dimensional design are influenced by a variety of physiological and anatomical factors unique to each patient and procedure, leading to underexpansion, eccentric expansion, and vertical deformation. These deformation patterns increase leaflet stress and strain, potentially causing fatigue and damage. This review article delves into the extent of THV deformation, its impact on leaflet function, hypoattenuating leaflet thickening, and structural valve degeneration. It provides an in-depth analysis of deformation specifics in different procedural contexts, including TAVR in native aortic stenosis, aortic and mitral valve-in-valve procedures, and redo-TAVR. Additionally, the review discusses strategies to mitigate THV deformation during the procedure, offering insights into potential solutions to these challenges.

What Powers Trastuzumab's Cardiotoxicity? Decoding Mitochondrial-Related Gene Expression Through Integrative Review and Meta-Analysis in Cardiomyocytes.

Trastuzumab is a monoclonal antibody used in oncotherapy for HER2-positive tumors. However, as an adverse effect, trastuzumab elevates the risk of heart failure, implying the involvement of energy production and mitochondrial processes. Past studies with transcriptome analysis have offered insights on pathways related to trastuzumab safety and toxicity but limited study sizes hinder conclusive findings. Therefore, we meta-analyzed mitochondria-related gene expression data in trastuzumab-treated cardiomyocytes. We searched the transcriptome databases for trastuzumab-treated cardiomyocytes in the ArrayExpress, DDBJ Omics Archive, Gene Expression Omnibus, Google Scholar, PubMed, and Web of Science repositories. A subset of 1270 genes related to mitochondrial functions (biogenesis, organization, mitophagy, and autophagy) was selected from the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology Resource databases to conduct the present meta-analysis using the Metagen package (Study register at PROSPERO: CRD42021270645). Three datasets met the inclusion criteria and 1243 genes were meta-analyzed. We observed 69 upregulated genes after trastuzumab treatment which were related mainly to autophagy (28 genes) and mitochondrial organization (28 genes). We also found 37 downregulated genes which were related mainly to mitochondrial biogenesis (11 genes) and mitochondrial organization (24 genes). The present meta-analysis indicates that trastuzumab therapy causes an unbalance in mitochondrial functions, which could, in part, help explain the development of heart failure and yields a list of potential molecular targets. These findings contribute to our understanding of the molecular mechanisms underlying the cardiotoxic effects of trastuzumab and may have implications for the development of targeted therapies to mitigate such effects.

Validation of 2D flow MRI for helical and vortical flows.

PURPOSE: The main objective of this study was to develop two-dimensional (2D) phase contrast (PC) methods to quantify the helicity and vorticity of blood flow in the aortic root. METHODS: This proof-of-concept study used four-dimensional (4D) flow cardiovascular MR (4D flow CMR) data of five healthy controls, five patients with heart failure with preserved ejection fraction and five patients with aortic stenosis (AS). A PC through-plane generated by 4D flow data was treated as a 2D PC plane and compared with the original 4D flow. Visual assessment of flow vectors was used to assess helicity and vorticity. We quantified flow displacement (FD), systolic flow reversal ratio (sFRR) and rotational angle (RA) using 2D PC. RESULTS: For visual vortex flow presence near the inner curvature of the ascending aortic root on 4D flow CMR, sFRR demonstrated an area under the curve (AUC) of 0.955, p<0.001. A threshold of >8% for sFRR had a sensitivity of 82% and specificity of 100% for visual vortex presence. In addition, the average late systolic FD, a marker of flow eccentricity, also demonstrated an AUC of 0.909, p<0.001 for visual vortex flow. Manual systolic rotational flow angle change (ΔsRA) demonstrated excellent association with semiautomated ΔsRA (r=0.99, 95% CI 0.9907 to 0.999, p<0.001). In reproducibility testing, average systolic FD (FDsavg) showed a minimal bias at 1.28% with a high intraclass correlation coefficient (ICC=0.92). Similarly, sFRR had a minimal bias of 1.14% with an ICC of 0.96. ΔsRA demonstrated an acceptable bias of 5.72°-and an ICC of 0.99. CONCLUSION: 2D PC flow imaging can possibly quantify blood flow helicity (ΔRA) and vorticity (FRR). These imaging biomarkers of flow helicity and vorticity demonstrate high reproducibility for clinical adoption. TRIALS REGISTRATION NUMBER: NCT05114785.

Exertional Angina in a Young Woman Caused by Large Cardiac Paraganglioma.

Coronary ischemia is uncommon in patients in their third decade of life. We present a 21-year-old woman with classic exertional angina secondary to a large cardiac paraganglioma. Cardiac paragangliomas are rare extra-adrenal neuroendocrine tumors that arise from chromaffin cells. Cardiac symptoms can be related to catecholamine excess or anatomical compression.

Preprocedural Computed Tomography Planning for Surgical Aortic Valve Replacement.

BACKGROUND: Selection of transcatheter valve size using preprocedural computed tomography (CT) is standardized and well established. However, valve sizing for surgical aortic valve replacement (SAVR) is currently performed intraoperatively by using sizers, which may result in variation among operators and risk for prosthesis-patient mismatch. This study evaluated the usefulness of CT annulus measurement for SAVR valve sizing. METHODS: This study included patients who underwent SAVR using Inspiris or Magna Ease and received preoperative electrocardiogram-gated CT imaging. Starting from June 2022, study investigators applied a CT sizing algorithm using CT-derived annulus size to guide minimum SAVR label size. The final decision of valve selection was left to the operating surgeon during SAVR. The study compared the appropriateness of valve selection (comparing implanted size with CT-predicted size) and prosthesis-patient mismatch rates without aortic root enlargement between 2 cohorts: 102 cases since June 2022 (CT sizing cohort) and 180 cases from 2020 to 2021 (conventional sizing cohort). RESULTS: Implanted size smaller than CT predicted size and severe prosthesis-patient mismatch were significantly lower by CT sizing than by conventional sizing (12% vs 31% [P = .001] and 0% vs 6% [P = .039], respectively). Interoperator variability was a factor associated with implanted size smaller than CT predicted with conventional sizing, whereas it became nonsignificant with CT sizing. CONCLUSIONS: Applying CT sizing to SAVR led to improved valve size selection, less prosthesis-patient mismatch, and less interoperator variability. CT sizing for SAVR could also be used to predict prosthesis-patient mismatch before SAVR and identify patients who need aortic root enlargement.

Tricuspid valve disease and cardiac implantable electronic devices.

The role of cardiac implantable electronic device (CIED)-related tricuspid regurgitation (TR) is increasingly recognized as an independent clinical entity. Hence, interventional TR treatment options continuously evolve, surgical risk assessment and peri-operative care improve the management of CIED-related TR, and the role of lead extraction is of high interest. Furthermore, novel surgical and interventional tricuspid valve treatment options are increasingly applied to patients suffering from TR associated with or related to CIEDs. This multidisciplinary review article developed with electrophysiologists, interventional cardiologists, imaging specialists, and cardiac surgeons aims to give an overview of the mechanisms of disease, diagnostics, and proposes treatment algorithms of patients suffering from TR associated with CIED lead(s) or leadless pacemakers.

Tricuspid Regurgitation: From Imaging to Clinical Trials to Resolving the Unmet Need for Treatment.

Tricuspid regurgitation (TR) is a highly prevalent and heterogeneous valvular disease, independently associated with excess mortality and high morbidity in all clinical contexts. TR is profoundly undertreated by surgery and is often discovered late in patients presenting with right-sided heart failure. To address the issue of undertreatment and poor clinical outcomes without intervention, numerous structural tricuspid interventional devices have been and are in development, a challenging process due to the unique anatomic and physiological characteristics of the tricuspid valve, and warranting well-designed clinical trials. The path from routine practice TR detection to appropriate TR evaluation, to conduction of clinical trials, to enriched therapeutic possibilities for improving TR access to treatment and outcomes in routine practice is complex. Therefore, this paper summarizes the key points and methods crucial to TR detection, quantitation, categorization, risk-scoring, intervention-monitoring, and outcomes evaluation, particularly of right-sided function, and to clinical trial development and conduct, for both interventional and surgical groups.

Restoration of flow in the aorta: a novel therapeutic target in aortic valve intervention.

Aortic blood flow patterns are closely linked to the morphology and function of the left ventricle, aortic valve and aorta. These flow patterns demonstrate the exceptional adaptability of the cardiovascular system to maintain blood circulation under a broad range of haemodynamic workloads and can be altered in various pathophysiological states. For instance, normal ascending aortic systolic flow is predominantly laminar, whereas abnormal aortic systolic flow is associated with increased eccentricity, vorticity and flow reversal. These flow abnormalities result in reduced aortic conduit function and increased energy loss in the cardiovascular system. Emerging evidence details the association of these flow patterns with loss of aortic compliance, which leads to adverse left ventricular remodelling, poor tissue perfusion, and an increased risk of morbidity and death. In this Perspective article, we review the evidence for the link between aortic flow-related abnormalities and cardiovascular disease and how these changes in aortic flow patterns are emerging as a therapeutic target for aortic valve intervention in first-in-human studies.

Comprehensive Myocardial Assessment by Computed Tomography: Impact on Short-Term Outcomes After Transcatheter Aortic Valve Replacement.

BACKGROUND: Quantification of myocardial changes in severe aortic stenosis (AS) is prognostically important. The potential for comprehensive myocardial assessment pre-transcatheter aortic valve replacement (TAVR) by computed tomography angiography (CTA) is unknown. OBJECTIVES: This study sought to evaluate whether quantification of left ventricular (LV) extracellular volume-a marker of myocardial fibrosis-and global longitudinal strain-a marker of myocardial deformation-at baseline CTA associate with post-TAVR outcomes. METHODS: Consecutive patients with symptomatic severe AS between January 2021 and June 2022 who underwent pre-TAVR CTA were included. Computed tomography extracellular volume (CT-ECV) was derived from septum tracing after generating the 3-dimensional CT-ECV map. Computed tomography global longitudinal strain (CT-GLS) used semi-automated feature tracking analysis. The clinical endpoint was the composite outcome of all-cause mortality and heart failure hospitalization. RESULTS: Among the 300 patients (80.0 ± 9.4 years of age, 45% female, median Society of Thoracic Surgeons Predicted Risk of Mortality score 2.80%), the left ventricular ejection fraction (LVEF) was 58% ± 12%, the median CT-ECV was 28.5% (IQR: 26.2%-32.1%), and the median CT-GLS was -20.1% (IQR: -23.8% to -16.3%). Over a median follow-up of 16 months (IQR: 12-22 months), 38 deaths and 70 composite outcomes occurred. Multivariable Cox proportional hazards model, accounting for clinical and echocardiographic variables, demonstrated that CT-ECV (HR: 1.09 [95% CI: 1.02-1.16]; P = 0.008) and CT-GLS (HR: 1.07 [95% CI: 1.01-1.13]; P = 0.017) associated with the composite outcome. In combination, elevated CT-ECV and CT-GLS (above median for each) showed a stronger association with the outcome (HR: 7.14 [95% CI: 2.63-19.36]; P < 0.001). CONCLUSIONS: Comprehensive myocardial quantification of CT-ECV and CT-GLS associated with post-TAVR outcomes in a contemporary low-risk cohort with mostly preserved LVEF. Whether these imaging biomarkers can be potentially used for the decision making including timing of AS intervention and post-TAVR follow-up will require integration into future clinical trials.

Imaging Methods for Evaluation of Chronic Aortic Regurgitation in Adults: JACC State-of-the-Art Review.

A global multidisciplinary workshop was convened to discuss the multimodality diagnostic evaluation of aortic regurgitation (AR). Specifically, the focus was on assessment tools for AR severity and analyzing evolving data on the optimal timing of aortic valve intervention. The key concepts from this expert panel are summarized as: 1) echocardiography is the primary imaging modality for assessment of AR severity; however, when data is incongruent or incomplete, cardiac magnetic resonance may be helpful; 2) assessment of left ventricular size and function is crucial in determining the timing of intervention; 3) recent evidence suggests current cutpoints for intervention in asymptomatic severe AR patients requires further scrutiny; 4) left ventricular end-systolic volume index has emerged as an additional parameter that has promise in guiding timing of intervention; and 5) the role of additional factors (including global longitudinal strain, regurgitant fraction, and myocardial extracellular volume) is worthy of future investigation.

Bridging the Gaps in Meta-Omic Analysis: Workflows and Reproducibility.

The past few years have seen significant advances in the study of complex microbial communities associated with the evolution of sequencing technologies and increasing adoption of whole genome shotgun sequencing methods over the once more traditional Amplicon-based methods. Although these advances have broadened the horizon of meta-omic analyses in planetary health, human health, and ecology from simple sample composition studies to comprehensive taxonomic and metabolic profiles, there are still significant challenges in processing these data. First, there is a widespread lack of standardization in data processing, including software choices and the ease of installing and running attendant software. This can lead to several inconsistencies, making comparing results across studies and reproducing original results difficult. We argue that these drawbacks are especially evident in metatranscriptomic analysis, with most analyses relying on ad hoc scripts instead of pipelines implemented in workflow managers. Additional challenges rely on integrating meta-omic data, since methods have to consider the biases in the library preparation and sequencing methods and the technical noise that can arise from it. Here, we critically discuss the current limitations in metagenomics and metatranscriptomics methods with a view to catalyze future innovations in the field of Planetary Health, ecology, and allied fields of life sciences. We highlight possible solutions for these constraints to bring about more standardization, with ease of installation, high performance, and reproducibility as guiding principles.

Feasibility of Redo-Transcatheter Aortic Valve Replacement in Sapien Valves Based on In Vivo Computed Tomography Assessment.

BACKGROUND: Our aim was to assess the feasibility of repeat transcatheter aortic valve (TAV) replacement for degenerated Sapien3 (S3) prostheses by simulating subsequent implantation of S3 or Evolut, using in vivo computed tomography-based sizing and the impact on coronary and patient-prosthesis mismatch risks. METHODS: Computed tomography scans from 356 patients with prior S3 TAV replacement implantation were analyzed. The in vivo sizing for second TAV based on averaged area of 3 levels of outflow, mid (narrowest) and inflow, was compared with in vitro recommendations, that is, same size as index S3 for second S3 and 1 size larger for Evolut. Risks of coronary obstruction and patient-prosthesis mismatch were determined by valve-to-aorta distance and estimated effective orifice area, respectively. RESULTS: Overall, the majority of patients (n=328; 92.1%) had underexpanded index S3 with an expansion area of 94% (91%-97%), leading to significant differences in size selection of the second TAV between in vivo and in vitro sizing strategies. Expansion area <89% served as a threshold, resulting in 1 size smaller than the in vitro recommendations were selected in 45 patients (13%) for S3-in-S3 and 13 (4%) for Evolut-in-S3, while the remaining patients followed in vitro recommendations (P<0.01, in vivo versus in vitro sizing). Overall, 57% of total patients for S3-in-S3 simulation and 60% for Evolut-in-S3 were considered low risk for coronary complications. Deep index S3 implantation (odds ratio, 0.76 [interquartile range, 0.67-0.87]; P<0.001) and selecting Evolut as the second TAV (11% risk reduction in intermediate- or high-risk patients) reduced coronary risk. Estimated moderate or severe patient-prosthesis mismatch risk was 21% for S3-in-S3 and 1% for Evolut-in-S3, assuming optimal expansion of the second TAV. CONCLUSIONS: Redo-TAV replacement with S3-in-S3 and Evolut-in-S3 could be feasible with low risk to coronaries in ≈60% of patients, while the remaining 40% will be at intermediate or high risk. The feasibility of redo-TAV replacement is influenced by sizing strategy, type of second TAV, native annular anatomy, and implant depth.

An Elderly Woman With Ventricular Tachycardia.

A woman in her 90s presented to the emergency department with fever, hemoptysis, and syncopal episodes. An electrocardiogram showed monomorphic ventricular tachycardia with a morphology suggesting right ventricular (RV) origin. What would you do next?

Deformation of transcatheter heart valves with mitral valve-in-valve.

BACKGROUND: The use of oversizing in mitral valve-in-valve (MViV) procedures can lead to non-uniform expansion of transcatheter heart valves (THV). This may have implications for THV durability. AIMS: The objective of this study was to assess the extent and predictors of THV deformation in MViV procedures. METHODS: We examined 33 patients who underwent MViV with SAPIEN prostheses. The extent of THV deformation (deformation index, eccentricity, neosinus volume, asymmetric leaflet expansion and vertical deformation) and hypoattenuating leaflet thickening (HALT) were assessed using cardiac computed tomography (CT), performed prospectively at 30 days post-procedure. For descriptive purposes, the THV deformation index was calculated, with values >1.00 representing a more hourglass shape. RESULTS: Non-uniform underexpansion of THV was common after MViV implantation, with a median expansion area of 74.0% (interquartile range 68.1-84.1) at the narrowest level and a THV deformation index of 1.21 (1.13-1.29), but circularity was maintained with eccentricity ranging from 0.24 to 0.28. The degree of oversizing was a key factor associated with greater underexpansion and a higher deformation index (ß=-0.634; p<0.001; ß=0.594; p<0.001, respectively). Overall, the incidence of HALT on the 30-day postprocedural CT was 27.3% (9 of 33). Most patients (32 of 33) were on anticoagulation therapy, but the prothrombin time and international normalised ratio (PT-INR) at the time of the CT scan was <2.5 in 23 of 32 patients. Among patients with a PT-INR of <2.5, HALT was predominantly observed with a high THV deformation index of ≥1.18. CONCLUSIONS: THV deformation, i.e., underexpansion and an hourglass shape, commonly occurs after MViV implantation and is negatively affected by excessive oversizing. Optimising THV expansion during MViV could potentially prevent HALT.

Diagnosis, Classification, and Management Strategies for Mitral Annular Calcification: A Heart Valve Collaboratory Position Statement.

Mitral annular calcium (MAC) with severe mitral valvular dysfunction presents a complex problem, as valve replacement, either surgical or transcatheter, is challenging because of anatomy, technical considerations, concomitant comorbidities, and advanced age. The authors review the clinical and anatomical features of MAC that are favorable (green light), challenging (yellow light), or prohibitive (red light) for surgical or transcatheter mitral valve interventions. Under the auspices of the Heart Valve Collaboratory, an expert working group of cardiac surgeons, interventional cardiologists, and interventional imaging cardiologists was formed to develop recommendations regarding treatment options for patients with MAC as well as a proposed grading and staging system using both anatomical and clinical features.