Impact of Non-Diameter Aortic Indices on Surgical Eligibility: Results from the TITAN: SvS Randomized Controlled Trial.

OBJECTIVES: Traditional criteria for intervention on an asymptomatic ascending aortic aneurysm has been a maximal aortic diameter of ⩾5.5cm. The 2022 ACC/AHA aortic guidelines adopted cross-sectional aortic area/height ratio, aortic size index (ASI) and aortic height index (AHI) as alternate parameters for surgical intervention. The objective of this study was to evaluate the impact of using these newer indices on patient eligibility for surgical intervention in a prospective, multicenter cohort with moderate sized ascending aortic aneurysms between 5.0-5.4 cm. METHODS: Patients enrolled from 2018 to 2023 in the randomization or registry arms of the multicenter trial, TITAN: SvS, were included in the study. Clinical data was captured prospectively in an online database. Imaging data were derived from a core CT lab. RESULTS: Among the 329 included patients, 20% were female. Mean age was 65.0 ± 11.6 years and mean maximal aortic diameter was 50.8 ±3.9 mm. In the one third of all patients (n=109) who met any one of the three criteria (i.e., ASI ⩾ 3.08 cm/m2, AHI ⩾ 3.21 cm/m or cross-sectional aortic area/height ⩾ 10 cm2/m), their mean maximal aortic diameter was 52.5 ±0.52 mm. Alternate criteria were most commonly met in females compared to males: 20% versus 2% for ASI (p<0.001), 39% versus 5% for AHI (p<0.001) and 39% versus 21% for cross-sectional aortic area/height (p=0.002), respectively. CONCLUSIONS: One third of patients in Titan:SvS would meet criteria for surgical intervention based on novel parameters vs. the classic definition of diameter⩾5.5cm. Surgical thresholds for ASI, AHI or cross-sectional aortic area/height ratio are more likely to be met in female patients compared to male patients.

Invasive Management of Hypertrophic Cardiomyopathy With Clinically Important Obstruction: Surgical Myectomy Is Superior, but Only When Accessible.

For patients with hypertrophic cardiomyopathy (HCM), a thickened intraventricular septum and systolic anterior motion of the mitral valve (SAM) can contribute to significant left ventricular outflow tract obstruction (LVOTO), mitral regurgitation, and debilitating symptoms. Current guidelines recommend septal reduction therapy through alcohol septal ablation or surgical septal myectomy for patients whose symptoms persist despite medical therapy. Although alcohol septal ablation is a less invasive treatment option, it is not suitable for patients with septal perforator branch anatomy that is not compatible with the procedure, those with midcavitary obstruction, and patients in whom the mechanism of LVOTO is primarily related to SAM. Septal ablation also has a notably higher rate of atrioventricular block requiring permanent pacemaker insertion, and the need for reintervention has been reported to be 15% or more. In contrast, septal myectomy offers direct visualisation and can address thickened septum and mitral valve (MV) anomalies. It can be used to treat a wider variety of anatomies, with lower rates of reoperation. Aside from the more invasive nature of the procedure, a major limitation of septal myectomy, however, is access, because relatively few surgeons specialise in the procedure. This is important because there is a significant correlation between procedural volumes and outcomes. Patients should be evaluated by a multidisciplinary heart team to ensure that they are aware of all treatment options. In this review, we explore the 2 methods of septal reduction therapy and highlight the need for further training of septal myectomy surgeons to ensure access to optimal septal reduction therapies for Canadian patients with HCM.

CCTA-based CABG SYNTAX Score: a tool to evaluate completeness of coronary segment revascularization after bypass surgery.

To describe the updated coronary computed tomographic angiography (CCTA)-based coronary artery bypass graft (CABG) anatomic SYNTAX Score (aSS) and assess its utility and reproducibility for assessing the completeness of revascularization after CABG. The CCTA-CABG aSS is a visual assessment using CCTA post-CABG which quantifies the failure in effectively grafting stenotic coronary segments, and therefore assesses the completeness of surgical revascularization. It is calculated by subtracting the aSS of successfully anastomosed coronary segments from the aSS of the native coronary tree. The inter-observer reproducibility of the CCTA-CABG aSS was evaluated in 45 consecutive patients with three-vessel disease with or without left main disease who underwent a CCTA 30 days (± 7 days) after CABG. The CCTA-CABG aSS was evaluated in 45 consecutive patients with 117 bypass grafts and 152 anastomoses. The median native coronary aSS was 35.0 [interquartile range (IQR) 27.0-41.0], whilst the median CCTA-CABG aSS was 13.0 (IQR 9.0-20.5). The inter-observer level of agreement for the native coronary aSS and the CCTA-CABG aSS were both substantial with respective Kappas of 0.67 and 0.61. The CCTA-CABG aSS was feasible in all patients who underwent CABG for complex coronary artery disease with substantial inter-observer reproducibility, and therefore can be used to quantify the completeness of revascularization after CABG.

Decreased serotonin transporter activity in the mitral valve contributes to progression of degenerative mitral regurgitation.

Degenerative mitral valve (MV) regurgitation (MR) is a highly prevalent heart disease that requires surgery in severe cases. Here, we show that a decrease in the activity of the serotonin transporter (SERT) accelerates MV remodeling and progression to MR. Through studies of a population of patients with MR, we show that selective serotonin reuptake inhibitor (SSRI) use and SERT promoter polymorphism 5-HTTLPR LL genotype were associated with MV surgery at younger age. Functional characterization of 122 human MV samples, in conjunction with in vivo studies in SERT-/- mice and wild-type mice treated with the SSRI fluoxetine, showed that diminished SERT activity in MV interstitial cells (MVICs) contributed to the pathophysiology of MR through enhanced serotonin receptor (HTR) signaling. SERT activity was decreased in LL MVICs partially because of diminished membrane localization of SERT. In mice, fluoxetine treatment or SERT knockdown resulted in thickened MV leaflets. Similarly, silencing of SERT in normal human MVICs led to up-regulation of transforming growth factor ß1 (TGFß1) and collagen (COL1A1) in the presence of serotonin. In addition, treatment of MVICs with fluoxetine not only directly inhibited SERT activity but also decreased SERT expression and increased HTR2B expression. Fluoxetine treatment and LL genotype were also associated with increased COL1A1 expression in the presence of serotonin in MVICs, and these effects were attenuated by HTR2B inhibition. These results suggest that assessment of both 5-HTTLPR genotype and SERT-inhibiting treatments may be useful tools to risk-stratify patients with MV disease to estimate the likelihood of rapid disease progression.

Extended Myectomy for Hypertrophic Cardiomyopathy: Early Outcomes From a Nascent Centre of Excellence in Canada.

Hypertrophic cardiomyopathy (HCM) is one of the commonest inherited cardiac abnormalities. The disorder is clinically and genetically heterogeneous and is characterized by left ventricular wall thickening that is not explained by abnormal loading conditions. HCM is estimated to affect between 1 in 200 and 1 in 500 people in the general population. In the majority of cases, HCM patients have a relatively benign course; however, if left untreated, this abnormality can lead to sudden cardiac death, especially in young adults and athletes. Therefore, early diagnosis is crucial to help implement the proper management for patients with HCM. In response to the growing need for more HCM centres of excellence in Canada, we developed one such centre at the University of Ottawa Heart Institute from the start of 2018. This centre will help in the early diagnosis and management of HCM patients, especially those with left ventricular outflow tract obstruction who might benefit from myectomy surgery. This paper describes our early experience with surgical myectomy in adult HCM patients between January 2018 and December 2020. We report the results of 27 patients with HCM who underwent myectomy surgery during the study period. All 27 patients survived to discharge, and all were still alive at 6 months postdischarge. Our experience highlights the crucial role that preoperative and perioperative imaging play in the management of this condition, in addition to the vital role of having a committed "heart team" of cardiologists, surgeons, and anesthesiologists.

La cardiomyopathie hypertrophique (CMH) est l'une des plus fréquentes anomalies cardiaques héréditaires. L'anomalie qui est cliniquement et génétiquement hétérogène est caractérisée par l'épaississement de la paroi du ventricule gauche qui n'est pas expliqué par des conditions de charge anormales. On estime que la CMH touche entre une personne sur 200 et une personne sur 500 dans la population générale. Dans la plupart des cas de CMH, l'évolution de la maladie est relativement bénigne. Toutefois, si cette anomalie n'est pas traitée, elle peut mener à la mort subite d'origine cardiaque, particulièrement chez les jeunes adultes et les athlètes. Par conséquent, le diagnostic précoce est crucial à la mise en œuvre d'une prise en charge adéquate des patients atteints de CMH. Pour répondre à la nécessité croissante d'un plus grand nombre de centres d'excellence sur la CMH au Canada, nous avons mis en place l'un de ces centres à l'Institut de cardiologie de l'Université d'Ottawa dès le début de 2018. Ce centre contribuera au diagnostic précoce et à la prise en charge des patients atteints de CMH, particulièrement des patients, dont la CMH est associée à une obstruction de la chambre de chasse du ventricule gauche, qui pourraient bénéficier d'une myectomie. Le présent article décrit nos premières expériences de myectomie chez les patients adultes atteints de CMH entre janvier 2018 et décembre 2020. Nous présentons les résultats de 27 patients atteints de CMH qui ont subi une myectomie durant la période étudiée. Les 27 patients ont survécu jusqu'à la sortie de l'hôpital, et étaient tous encore en vie six mois après. Notre expérience démontre le rôle crucial que joue l'imagerie en phase préopératoire et en phase périopératoire lors de la prise en charge de cette maladie, en plus du rôle essentiel de l'« équipe de cardiologie ¼ dévouée qui est composée de cardiologues, de chirurgiens et d'anesthésistes.

Comprehensive left ventricular outflow tract management beyond septal reduction to relieve obstruction.

The surgical management of patients with hypertrophic obstructive cardiomyopathy can be extremely challenging. Relieving the left ventricular outflow tract obstruction in these patients is often achieved by performing a septal myectomy. However, in many instances, septal reduction alone is not enough to relieve the obstruction. Interventions on the sub-valvular apparatus, including the anomalous chordae tendineae and the abnormal papillary muscles, are often required. In this review, we summarize the embryology and the pathophysiology of the different elements that may contribute to the left ventricular outflow tract obstruction in the setting of hypertrophic obstructive cardiomyopathy. In addition, we highlight the different surgical procedures that a surgeon may adopt to relieve the left ventricular outflow tract obstruction, beyond the septal myectomy.

Severe Mitral Annular Calcification in Two Cases of Hypertrophic Obstructive Cardiomyopathy.

Management of patients with hypertrophic obstructive cardiomyopathy and severe mitral annular calcification can be challenging. Our cases highlight the importance of addressing all elements contributing to left ventricular outflow tract obstruction in cases of hypertrophic obstructive cardiomyopathy: hypertrophic basal interventricular septum, abnormal papillary muscles, and systolic anterior motion of the anterior mitral valve leaflet. Addressing mitral valve repair through aortotomy by performing a septal myectomy, papillary muscle realignment, and resection of aberrant chordae tendineae allows left ventricular outflow tract obstruction and systolic anterior motion to be successfully corrected. The success of these procedures depended on preoperative imaging and intraoperative provocation.

Surgical Techniques for the Treatment of Anomalous Origin of Right Coronary Artery From the Left Sinus: A Comparative Review.

The anomalous aortic origin of the right coronary artery (AAORCA) from the left sinus is a congenital anomaly affecting both the origin and course of the right coronary artery. AAORCA is nowadays easily and increasingly recognized by several cardiac imaging modalities. In most cases, patients remain asymptomatic; however, in some, and especially in young athletes, symptoms start to appear following exertion. A literature review was conducted on the surgical management of AAORCA by searching the Pubmed and Google Scholar databases. The inclusion criteria included manuscripts reporting surgical outcomes of AAORCA for ≥1 of the 3 techniques of interest (unroofing, reimplantation, and coronary artery bypass grafting) and manuscripts written in English and that were published between 2010 and 2020. The surgical management of AAORCA can be done through several techniques, most commonly the unroofing of the intramural segment of the AAORCA, the reimplantation of the native right coronary artery onto the right sinus of the aortic root, and coronary artery bypass grafting with either arterial or venous graft conduits with or without ligation of the proximal right coronary artery. Superiority of one surgical technique has not yet been formally proven because of the rare nature of this condition and the lack of any prospective randomized controlled trial or robust prospective observational studies.

Conduits' Biology Regulates the Outcomes of Coronary Artery Bypass Grafting.

Coronary artery bypass graft (CABG) is the gold standard for coronary surgical revascularization. Retrospective, prospective, and meta-analysis studies looking into long-term outcomes of using different conduits have pointed to the superiority of arterial grafts over veins and have placed the internal mammary artery as the standard conduit of choice for CABG. The superiority of the internal mammary artery over other conduits could be attributable to its intrinsic characteristics; however, little is known regarding the features that render some conduits atherosclerosis-prone and others atherosclerosis-resistant. Here, an overview is provided of the available data on the most commonly used conduits in CABG (internal mammary artery, saphenous vein, radial artery, gastroepiploic artery), highlighting the differences in their cellular biology, mechanical, biochemical, and vasoconstrictive properties. This information should help in furthering our understanding of the clinical outcomes observed for each of these conduits.

Comparative Analysis Following Implementation of Two Types of Y-Composite Multiarterial Revascularization Strategies at a Single Academic Institution.

Background We compared early outcomes, at a single academic institution, of implementing full coronary revascularization in coronary artery bypass grafting using multiarterial Y-composite grafts with multiple sequential anastomoses. Methods and Results Clinical records of 425 consecutive patients who underwent coronary artery bypass grafting using Y-grafting with left internal mammary artery and radial artery (Y-RA group) or right internal mammary artery (Y-RIMA group) from 2015 to 2019, were reviewed. These were compared with the institutional experience of isolated coronary artery bypass grafting cases (in situ on pump/off pump) for the same period of time. When comparing the 4 groups, the Y-RIMA/RA groups revealed a higher number of distal anastomosis than the in situ on- or off-pump groups. When the number of distal arterial anastomosis was analyzed, there was a superiority of using the Y-configuration compared with the in situ approach. Moreover, there were no significant differences among groups for mortality and/or major adverse cardiac and cerebrovascular events in hospital or at 30-day follow-up. A subanalysis comparing the Y-RIMA group with the Y-RA group showed that complementary grafts to the Y-construct were required to accomplish full revascularization more frequently in the Y-RIMA group. Full-arterial revascularization was achieved in 92.2% of the Y-RA group and 72.0% of the Y-RIMA group (P<0.001). In 82.8% of the Y-RA group and 30.8% of the Y-RIMA group, revascularization was completed as an anaortic procedure (P<0.001). Conclusions The 2 types of arterial Y-composite grafting were able to be introduced in the routine practice of our institution showing comparable results to the established institutional practice. This procedure allowed for more arterial distal anastomosis to be performed safely without compromising outcomes.

Glycation and Serum Albumin Infiltration Contribute to the Structural Degeneration of Bioprosthetic Heart Valves.

Valvular heart diseases are associated with significant cardiovascular morbidity and mortality, and often require surgical and/or percutaneous repair or replacement. Valve replacement is limited to mechanical and biological prostheses, the latter of which circumvent the need for lifelong anticoagulation but are subject to structural valve degeneration (SVD) and failure. Although calcification is heavily studied, noncalcific SVD, which represent roughly 30% of BHV failures, is relatively underinvestigated. This original work establishes 2 novel and interacting mechanisms-glycation and serum albumin incorporation-that occur in clinical valves and are sufficient to induce hallmarks of structural degeneration as well as functional deterioration.

Aortic Valve Regurgitation: Pathophysiology and Implications for Surgical Intervention in the Era of TAVR.

Aortic insufficiency (AI) or regurgitation is caused by the malcoaptation of the aortic valve (AV) cusps due to intrinsic abnormalities of the valve itself, a dilatation or geometric distortion of the aortic root, or by some combination thereof. In recent years, there has been an increase in the number of studies suggesting that AI is an active disease process caused by a combination of factors including but not limited to alteration of specific molecular pathways, genetic predisposition, and changes in the mechanotransductive properties of the AV apparatus. As the surgical management of AV disease continues to evolve, increasingly sophisticated surgical and percutaneous techniques for AV repair and replacement, including transcatheter aortic valve replacement (TAVR), have become more commonplace and will likely continue to expand as new devices are introduced. However, these techniques necessitate frequent reappraisal of the biological and mechanobiological mechanisms underlying AV regurgitation to better understand the risk factors for AI development and recurrence following surgical intervention as well as expand our limited knowledge on patient selection for such procedures. The aim of this review is to describe some of the putative mechanisms implicated in the development of AI, dissect some of the cross-talk among known and possible signaling pathways leading to valve remodeling, identify association between these pathways and pharmacological approaches, and discuss the implications for surgical and percutaneous approaches to AV repair in replacement in the TAVR era.

Circulating and tissue matricellular RNA and protein expression in calcific aortic valve disease.

Aortic valve sclerosis is a highly prevalent, poorly characterized asymptomatic manifestation of calcific aortic valve disease and may represent a therapeutic target for disease mitigation. Human aortic valve cusps and blood were obtained from 333 patients undergoing cardiac surgery (n = 236 for severe aortic stenosis, n = 35 for asymptomatic aortic valve sclerosis, n = 62 for no valvular disease), and a multiplex assay was used to evaluate protein expression across the spectrum of calcific aortic valve disease. A subset of six valvular tissue samples (n = 3 for asymptomatic aortic valve sclerosis, n = 3 for severe aortic stenosis) was used to create RNA sequencing profiles, which were subsequently organized into clinically relevant gene modules. RNA sequencing identified 182 protein-encoding, differentially expressed genes in aortic valve sclerosis vs. aortic stenosis; 85% and 89% of expressed genes overlapped in aortic stenosis and aortic valve sclerosis, respectively, which decreased to 55% and 84% when we targeted highly expressed genes. Bioinformatic analyses identified six differentially expressed genes encoding key extracellular matrix regulators: TBHS2, SPARC, COL1A2, COL1A1, SPP1, and CTGF. Differential expression of key circulating biomarkers of extracellular matrix reorganization was observed in control vs. aortic valve sclerosis (osteopontin), control vs. aortic stenosis (osteoprotegerin), and aortic valve sclerosis vs. aortic stenosis groups (MMP-2), which corresponded to valvular mRNA expression. We demonstrate distinct mRNA and protein expression underlying aortic valve sclerosis and aortic stenosis. We anticipate that extracellular matrix regulators can serve as circulating biomarkers of early calcific aortic valve disease and as novel targets for early disease mitigation, pending prospective clinical investigations.

Impact of preoperative fractional flow reserve on arterial bypass graft anastomotic function: the IMPAG trial.

AIMS: Visual estimation is the most commonly used method to evaluate the degree of coronary artery stenosis prior to coronary artery bypass grafting. In interventional cardiology, the use of fractional flow reserve (FFR) to guide revascularization decisions has become routine. We investigated whether the preoperative FFR measurement of coronary lesions is associated with anastomosis function 6 months after surgical revascularization using a multiarterial grafting strategy. METHODS AND RESULTS: In this prospective double-blind study, 67 patients were enrolled from two institutions in Europe and Canada. From these patients, 199 coronary lesions were assessed visually and with FFR at the time of the preoperative angiogram. All patients received coronary revascularization using multiple arterial grafts. A post-operative 6-month angiogram was performed to assess anastomosis functionality using a described angiographic method. The primary outcome was the association between preoperative FFR values and anastomosis function 6 months after surgery. Preoperative FFR was significantly associated with 6-months anastomotic function for all conduits and for all targets (P < 0.001). An FFR value of ≤0.78 was associated with an anastomotic occlusion rate of 3%. CONCLUSION: We found a significant association between the preoperative FFR measurement of the target vessel and the anastomotic functionality at 6 months, with a cut-off of 0.78. Integration of FFR measurement into the preoperative diagnostic workup before multiarterial coronary surgical revascularization leads to improved anastomotic graft function. CLINICAL TRIALS. GOV IDENTIFIER: NCT02527044.