Metastatic melanoma to small bowel: metastasectomy is supported in the era of immunotherapy and checkpoint inhibitors.

BACKGROUND: Metastatic melanoma to the small bowel is an aggressive disease often accompanied by obstruction, abdominal pain, and gastrointestinal bleeding. With advancements in melanoma treatment, the role for metastasectomy continues to evolve. Inclusion of novel immunotherapeutic agents, such as checkpoint inhibitors, into standard treatment regimens presents potential survival benefits for patients receiving metastasectomy. CASE PRESENTATION: We report an institutional experience of 15 patients (12 male, 3 female) between 2014-2022 that underwent small bowel metastasectomy for metastatic melanoma and received perioperative systemic treatment. Median age of patients was 64 years (range: 35-83 years). No patients died within 30 days of their surgery, and the median hospital length of stay was 5 days. Median overall survival in these patients was 30.1 months (range: 2-115 months). Five patients died from disease (67 days, 252 days, 426 days, 572 days, 692 days postoperatively), one patient died of non-disease related causes (1312 days postoperatively), six patients are alive with disease, and three remain disease free. CONCLUSIONS: This case series presents an updated perspective of the utility of metastasectomy for small bowel metastasis in the age of novel immunotherapeutic agents as standard systemic treatment. Small bowel metastasectomy for advanced melanoma performed in conjunction with perioperative systemic therapy is safe and appears to promote long-term survival and enhanced quality of life.

Conditional Survival After Hepatectomy for Colorectal Liver Metastasis: Results from the Colorectal Liver Operative Metastasis International Collaborative (COLOMIC).

INTRODUCTION: Complete resection of colorectal liver metastasis (CLM) improves long-term survival in colorectal cancer. However, there is limited recent data on conditional survival (CS) as postoperative survival milestones are achieved post-hepatectomy. METHODS: A retrospective analysis was performed on the penta-institutional Colorectal Liver Operative Metastasis International Collaborative (COLOMIC), with 906 consecutive CLM hepatectomy cases. CS was calculated using Bayes' theorem and Kaplan-Meier analysis. Additional CS analyses were performed on additional clinicopathologic risk factors, including colon cancer laterality, KRAS mutation status, and extrahepatic disease. RESULTS: The 5-year CS was 40.6%, 45.3%, 52.8%, and 65.3% at 0, 1, 2, and 3 years postoperatively, with significant improvements each year (p < 0.005). CS was not significantly different between right-sided and left-sided colorectal cancers by 3 years postoperatively. Patients with KRAS mutations had worse CS at all timepoints (p < 0.001). Extrahepatic disease was a poor prognostic factor for OS and CS (p < 0.001). However, CS for patients with KRAS mutations or extrahepatic disease improved significantly as 2-year, postoperative survival was achieved (p < 0.05). CONCLUSIONS: Five-year CS after hepatectomy for CLM improved with each passing year of survival postoperatively. Although extrahepatic disease and KRAS mutations are poor prognostic factors for OS, these populations still had improved CS after 2 years postoperatively.

Survival Outcomes of Optimally Treated Colorectal Metastases: The Importance of R0 Status in Surgical Treatment of Hepatic and Peritoneal Surface Disease.

BACKGROUND: Although colorectal hepatic metastases (HM) and peritoneal surface disease (PSD) are distinct biologic diseases, they may have similar long-term survival when optimally treated with surgery. METHODS: This study retrospectively reviewed prospectively managed databases. Patients undergoing R0 or R1 resections were analyzed with descriptive statistics, the Kaplan-Meier method, and Cox regression. Survival was compared over time for the following periods: 1993-2006, 2007-2012, and 2013-2020. RESULTS: The study enrolled 783 HM patients undergoing liver resection and 204 PSD patients undergoing cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC). Compared with PSD patients, HM patients more often had R0 resections (90.3% vs. 32.4%), less often had pre-procedure chemotherapy (52.4% vs. 92.1%), and less often were functionally independent (79.7% vs. 95.6%). The 5-year overall survival for HM was 40.9%, with a median survival period of 45.8 months versus 25.8% and 33.4 months, respectively, for PSD (p < 0.05). When stratified by resection status, R0 HM and R0 PSD did not differ significantly in median survival (49.0 vs. 45.4 months; p = 0.83). The median survival after R1 resection also was similar between HM and PSD (32.6 vs. 26.9 months; p = 0.59). Survival between the two groups again was similar over time when stratified by resection status. The predictors of survival for HM patients were R0 resection, number of lesions, intraoperative transfusion, age, and adjuvant chemotherapy. For the PSD patients, the predictors were peritoneal cancer index (PCI) score, estimated blood loss (EBL), and female gender. CONCLUSION: The study showed that R0 resections are associated with improved outcomes and that median survival is similar between HM and PSD patients when it is achieved. Surveillance and treatment strategies that facilitate R0 resections are needed to improve results, particularly for PSD.

Toward endovascular treatment of type A aortic dissection with smaller landing zones and more patient eligibility.

OBJECTIVE: Type A or ascending aortic dissection is an acute life-threatening condition with high morbidity and mortality. Open surgery remains the standard of care. The development of minimally invasive endografts for type A aortic dissection (TAAD) will require a detailed understanding of the dissection and aortic root anatomy to determine patient eligibility and optimal device specifications. METHODS: Computed tomography images of TAAD cases at our institution from 2012 to 2019 were identified, and three-dimensional reconstructions were performed using OsiriX, version 10.0 (Pixmeo SARL, Bernex, Switzerland). We analyzed key anatomic structures, including centerline length measurements, ascending aorta and aortic root dimensions, and the location and extent of dissection in relationship to the coronary ostia. RESULTS: A total of 53 patients were identified (mean ± standard deviation age, 60.4 ± 17.1 years; 36 men and 17 women), 46 of whom had undergone surgery for TAAD. Four patients had died within 30 days of surgery. In 47 patients (88.7%), the entry tear was distal to the highest coronary ostium. These cases were retrospectively considered for endovascular intervention using a nonbranched, single endograft stent. The proximal landing zone (LZ) was defined as the distance from the highest coronary ostium to the entry tear. Of the 53 patients, 35 (66.0%) had a proximal LZ length of ≥2.0 cm, 38 (71.7%) had a proximal LZ length of ≥1.5 cm, and 42 (79.2%) had a proximal LZ length of ≥1.0 cm. The median proximal and distal LZ diameters of the sinotubular junction (STJ) and distal ascending aorta regions were 3.29 cm (interquartile range [IQR], 2.73-4.10 cm) and 3.49 cm (IQR, 3.09-3.87 cm, respectively), with a median length from the STJ to the innominate takeoff of 8.08 cm (IQR, 6.96-9.40 cm). The median ascending aorta radius of curvature was 6.48 cm (IQR, 5.27-8.00 cm). Of the 53 patients, 25 (47.2%) could be treated with a straight tube graft with a ≤20% diameter mismatch between the proximal and distal LZs. CONCLUSIONS: Almost 80% of the patients with TAAD had had a proximal LZ of ≥1.0 cm. Of these patients, 47.2% had anatomy amenable for endovascular therapy with a nontapered straight tube graft using commercially available devices. To increase patient eligibility for TAAD endovascular intervention, enhanced precision deployment with an adequate seal in shorter LZs will be required. Our results can serve as a guide for endovascular device specifications designed to treat this devastating condition.

Perioperative chemotherapy for resectable colorectal liver metastases: Analysis from the Colorectal Operative Liver Metastases International Collaborative (COLOMIC).

BACKGROUND: Chemotherapy has been increasingly combined with surgery as multimodality treatment for resectable colorectal-liver metastases (CLM). There is paucity of clinical data addressing optimal timing of chemotherapy relative to surgery. We examined outcomes of patients undergoing hepatectomy for resectable CLM. METHODS: Seven hundred and eighteen patients treated with hepatectomy for CLM were analyzed from five hepatobiliary institutions between 2000 and 2018. Overall survival (OS) was measured from time of hepatectomy for patients receiving: surgery alone, neoadjuvant, adjuvant, and neoadjuvant-plus-adjuvant (perioperative) chemotherapy. Kaplan-Meier analysis was performed to detect differences in OS between treatment groups. Single- and multi-variable analysis with Cox proportional hazards were run for OS between groups. RESULTS: One hundred and thirty-seven patients (19.08%) received surgery, 104 (14.48%) received neoadjuvant-only, 214 (29.81%) received adjuvant-only, and 263 (36.63%) received perioperative chemotherapy; with median OS of 48.20, 46.83, 56.27, and 49.93 months, respectively. No differences in median OS were seen between groups on Kaplan-Meier analysis. No significant difference in Charlson-Deyo comorbidity status was seen between groups (p = 0.853), while significant difference was seen in maximum tumor size (p = 0.0023). On multivariate analysis, adjuvant (p = 0.010) and perioperative (p = 0.020) chemotherapy were independently associated with OS compared to surgery alone. DISCUSSION: Despite group differences, chemotherapy after surgery was independently associated with improved OS in CLM.

Outcomes after repeat hepatectomy for colorectal liver metastases from the colorectal liver operative metastasis international collaborative (COLOMIC).

BACKGROUND: Resection of colorectal liver metastasis (CLM) is beneficial when feasible. However, the benefit of second hepatectomy for hepatic recurrence in CLM remains unclear. METHODS: The Colorectal Liver Operative Metastasis International Collaborative retrospectively examined 1004 CLM cases from 2000 to 2018 from a total of 953 patients. Hepatic recurrence after initial hepatectomy was identified in 218 patients. Kaplan-Meier analysis was performed for overall survival (OS) and recurrence-free survival (RFS). Propensity score matching (PSM) was performed to offset selection bias. Cox proportional-hazards regression was performed to identify risk factors associated with OS. RESULTS: A total of 51 patients underwent second hepatectomy. Unadjusted median OS was 60.1 months in repeat-hepatectomy versus 38.3 months in the single-hepatectomy group (p = 0.015). In the PSM population, median OS remained significantly better in the repeat-hepatectomy group (60.1 vs. 33.1 months; p = 0.0023); median RFS was 12.4 months for the repeat-hepatectomy group, versus 9.8 months in the single-hepatectomy group (p = 0.0050). Repeat hepatectomy was associated with lower risk of death (hazard ratio: 0.283; p = 0.000012). Obesity, tobacco use, and high intraoperative blood loss were associated with significant risk of death (p < 0.05). CONCLUSION: In CLM with hepatic recurrence, second hepatectomy was beneficial for OS. With PSM, the OS benefit of performing a second hepatectomy remained significant.

Association of primary tumor laterality with surgical outcomes for colorectal liver metastases: results from the Colorectal Liver Operative Metastasis International Collaborative (COLOMIC).

BACKGROUND: Primary laterality of colorectal cancer is thought to be associated with differences in outcomes. Liver metastasis is the most common site of solitary colorectal cancer spread. However, how primary colorectal cancer laterality affects outcomes in colorectal liver metastasis remains unclear. METHODS: The Colorectal Liver Operative Metastasis International Collaborative (COLOMIC) of operative hepatectomy cases for colorectal liver metastasis was compiled from five participating institutions. This included consecutive cases from 2000 to 2018 at all sites. A total of 884 patients were included in this study. Univariate, multivariate, and Kaplan-Meier analyses were performed. RESULTS: Patients with left-sided versus right-sided cancers had significantly better overall survival: 49.4 vs. 41.8 months (p < 0.05). Patients with KRAS mutations had significantly worse median overall survival compared to KRAS wild-type (43.6 vs 56.1 months; p < 0.001). In left-sided cancers, KRAS mutations were associated with significantly worse median overall survival compared to KRAS wild-type cancers (43.6 vs 56.6 months; p < 0.01). This association was absent in patients with right-sided primary tumors. Multivariate Cox regression analysis revealed different variable sets (non-overlapping) were associated with overall survival, when comparing left-sided and right-sided cancers. CONCLUSION: Understanding how primary tumor laterality and related biological aspects affect long-term outcomes can potentially inform treatment decisions for patients with colorectal liver metastases.

Synchronous Versus Metachronous Colorectal Liver Metastasis Yields Similar Survival in Modern Era.

BACKGROUND: Synchronous colorectal cancer liver metastasis (CRLM) has been viewed as being more aggressive and having shorter survival than metachronous disease. Advances in CRLM management led us to examine differences in treatment characteristics of synchronous versus metachronous CRLM patients along with survival and recurrence. MATERIALS AND METHODS: A retrospective review of hepatic resection for CRLM at a tertiary academic medical center was performed for two periods: a historic cohort from 1992 to 2010 (n = 121), and a modern cohort (n = 179) from 2012 to 2018. Clinical variables were compared between the patient groups, and survival outcomes were characterized. RESULTS: Five-year disease-specific survival for the modern synchronous group compared to the historic synchronous group was 71.7% versus 44.3% (P = 0.02). Modern metachronous versus modern synchronous 5-y disease-specific survival rates were 49.8% versus 71.7% (P = 0.31). Compared to the historic cohort, the modern one had significantly different timing of hepatic resection (P < 0.01) with increased use of liver-first (30.1% versus 7.5%) and simultaneous liver-colon resections (24.1% versus 10.4%), along with greater use of neoadjuvant chemotherapy (96.4% versus 65.6%; P < 0.01). Significantly more patients in the modern synchronous cohort had disease-free or alive-with-disease status at last follow-up, compared to the historic group (P < 0.01), and experienced less disease recurrence (62.7% versus 77.6%; P < 0.05). CONCLUSIONS: Modern synchronous CRLM patients who underwent hepatic resection experienced significantly improved survival compared to a historic cohort. We postulate that increased use of neoadjuvant chemotherapy and liver-first/simultaneous liver-colon resections in the modern synchronous cohort contributed to improved survival.

Ampullary stenosis and choledocholithiasis post Roux-En-Y gastric bypass: challenges of biliary access and intervention.

BACKGROUND: Ampullary stenosis following Roux-en-Y gastric bypass (RYGB) is increasingly encountered. We describe cases of biliary obstruction from ampullary stenosis and choledocholithiasis to illustrate the associated diagnostic and interventional challenges with this condition. METHODS: We reviewed medical records of patients with prior RYGB who underwent a biliary access procedure or surgery for non-malignant disease from January 2012-December 2018. RESULTS: We identified 15 patients (4 male, 11 female; mean age 53.7 years) who had RYGB on average 11.7 years (range 1-32) years before diagnosis of biliary obstruction. Fourteen patients reported abdominal pain, 5 had nausea/emesis, 12 had elevated liver function tests, and 6 had ascending cholangitis. Mean common bile duct (CBD) diameter at presentation was 16.9 mm (range 4.0-25.0 mm). Operations included 3 transduodenal ampullectomies (2 with biliary bypass), 2 CBD explorations with stone extraction, 1 laparoscopic cholecystectomy alone, 1 Whipple procedure, 1 balloon enteroscopy with sphincterotomy, and 7 transgastric endoscopic retrograde cholangiopancreatography. All ampulla pathology was benign in patients who underwent resection. At follow-up (mean 15.4 months; range 0.23-44.5 months), 12/15 (80%) reported symptom resolution or improvement. DISCUSSION: Ampullary stenosis after RYGB presents challenges for diagnostic evaluation and intervention, often requiring multi-disciplinary expertise. The underlying pathology remains to be elucidated.

Range of Pulmonary Autograft Responses to Systemic Pressure Immediately After Ross Procedure.

BACKGROUND: Pulmonary autograft dilatation after Ross operation often necessitates reoperation. To understand autograft remodeling, a biomechanical understanding of human autografts after exposure to systemic pressure is required. We previously developed an ex vivo human pulmonary autograft finite element (FE) model to predict wall stress after exposure to systemic pressure. However, autograft material properties vary significantly among individuals. Our study aim was to quantify range of wall stress changes in a human autograft after Ross operation prior to remodeling based upon normal variation in human autograft mechanical properties. METHODS: A normal human autograft FE model was loaded to pulmonary and systemic arterial pressures. Stress-strain data of normal human autografts (n=24) were incorporated into an Ogden hyper-elastic model to describe autograft mechanical behavior. Autograft wall stresses at pulmonary vs. systemic pressures were examined. Autograft volume-based stress analysis was performed, based on percentage of autograft element volume exceeding 1 standard deviation (SD) above group mean stress at systemic systole. RESULTS: Mean first principal wall stresses (FPS) at systole of systemic versus pulmonary pressures were 129.29±17.47kPa versus 24.42±3.85kPa (p<0.001) at the annulus, 187.53±20.06kPa versus 35.98±2.15kPa at sinuses (p<0.001), and 268.68±23.40kPa versus 50.15±5.90kPa (p<0.001) at sinotubuluar junction (STJ). The percentage of autograft element volume that exceeded one SD above the group mean was 14.3±5.6% for FPS and 12.6±10.1% for second principal stresses. CONCLUSION: We quantified normal human autograft biomechanical responses to systemic pressure based on patient-specific material properties. Regions of peak stresses were observed in autograft sinuses and STJ regions, which corresponded clinically to locations of autograft dilation. Our results provide valuable information on predicting variations in patient-specific ex vivo FE models when population-based material properties are used in settings where patient-specific properties are unknown.

Leaflet Mechanical Properties of Carpentier-Edwards Perimount Magna Pericardial Aortic Bioprostheses.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) has recently been shown to be equivalent to surgical aortic valve replacement (SAVR) in intermediate-risk patients. As TAVR expands towards the traditionally SAVR population, TAVR versus SAVR durability becomes increasingly important. While the durability of TAVR is unknown, valve design - particularly with regards to leaflet stress - impacts on valve durability. Although leaflet stress cannot be measured directly, it can be determined using finite element modeling, with such models requiring the mechanical properties of the leaflets. Balloon-expandable TAVR involves the use of bovine pericardial leaflets treated in the same manner as surgical bioprosthetic leaflets. The study aim was to determine the leaflet mechanical properties of Carpentier-Edwards bioprostheses for future TAVR and SAVR computational models. METHODS: A total of 35 leaflets were excised from 12 Carpentier-Edwards Model 3000TFX Perimount Magna aortic bioprostheses (21 mm, 23 mm, and 25 mm) and subjected to displacement-controlled equibiaxial stretch testing. The stress-strain data acquired were fitted to a Fung constitutive model to describe the material properties in circumferential and radial directions. Leaflet stiffness was calculated at specified physiological stress, corresponding to zero pressure, systemic pressure, and between zero and systemic pressure. RESULTS: The 21-mm bioprostheses had significantly thinner leaflets than the larger bioprostheses. A non-linear stress-strain relationship was observed in all leaflets along the circumferential and radial directions. No significant difference in leaflet stiffness at systemic pressure, or between zero and systemic pressure, was found among the three bioprosthesis sizes. However, the leaflets from the 23 mm bioprosthesis were significantly more compliant than those of the 21 mm and 25 mm bioprostheses at zero pressure in the circumferential direction. No differences were observed in leaflet stiffness in circumferential versus radial directions. CONCLUSIONS: The bovine pericardial leaflets from Carpentier-Edwards Perimount Magna bioprostheses showed no differences in material properties among different valve sizes at systemic pressure. The thinner 21 mm leaflets did not show any corresponding differences in leaflet stiffness, which suggests that the thinner TAV leaflets may have a similar stiffness to their thicker SAV counterparts.

Bicuspid Aortic Valve-Associated Ascending Thoracic Aortic Aneurysm: Patient-Specific Finite Element Analysis.

BACKGROUND: Elective repair of bicuspid aortic valve (BAV)-associated ascending thoracic aortic aneurysm (aTAA) is recommended at lower size limits than tricuspid aortic valve (TAV)-associated aTAA. Rupture/dissection can occur when wall stress exceeds wall strength. Previously, a validated computational method was developed for determining aTAA wall stress, but to date this method has not applied to a patient-specific BAV aTAA. The study aim was to develop a patient-specific BAV aTAA computational model to determine regional wall stress, using the required zero-pressure geometry, wall thickness, material properties, and residual stress. METHODS: A BAV aTAA specimen was excised intact during elective repair, and zero-pressure geometry generated using micro-computed tomography. Residual stress was determined from the aTAA opening angle. aTAA material properties determined using biaxial stretch testing were incorporated into an Ogden hyperelastic model. Finite element analyses (FEAs) were performed in LS-DYNA to determine wall stress distribution and magnitudes at systemic pressure. RESULTS: The left aTAA region had the highest stiffness, followed by the right, and then anterior/posterior walls, suggesting regional variability in mechanical properties. During systole, the mean principal wall stresses were 108.8 kPa (circumferential) and 59.9 kPa (longitudinal), while peak wall stresses were 789.4 kPa (circumferential) and 618.8 kPa (longitudinal). Elevated wall stress pockets were seen in anatomic left aTAA regions. CONCLUSIONS: To the present authors' knowledge, this was the first patient-specific BAV aTAA model based on surgical specimens to be developed. Surgical specimens serve as the 'gold standard' for determining wall stress to validate models based on in-vivo imaging data alone. Regions of maximal wall stress may indicate sites most prone to rupture, and are crucial for evaluating rupture risk based on the wall stress/strength relationship.

Human pulmonary autograft wall stress at systemic pressures prior to remodeling after the Ross procedure.

BACKGROUND AND AIM OF THE STUDY: Remodeling of the pulmonary autograft upon exposure to systemic pressure can lead to progressive dilatation and aneurysmal pathology. Remodeling is driven by changes in autograft wall stress upon exposure to systemic pressure; however, the magnitude of these changes is unknown. Previously, a porcine autograft finite element model was developed to determine wall stress, but the porcine and human material properties differed significantly. Hence, the study aim was to understand human pulmonary autograft biomechanics that lead to remodeling by determining wall stress magnitudes immediately after the Ross procedure using finite element analysis (FEA). METHODS: Human pulmonary root was scanned by high-resolution microcomputed tomography to construct a realistic three-dimensional geometric mesh. Stress-strain data from biaxial stretch testing was incorporated into an Ogden hyperelastic model to describe autograft mechanical properties for an adult Ross patient. Autograft dilatation and wall stress distribution during pulmonic and systemic pressures prior to remodeling were determined using explicit FEA in LS-DYNA. RESULTS: Human pulmonary autograft demonstrated non-linear material properties, being highly compliant in the low-strain region, and stiffening at high strain. The majority of dilatation occurred with < 20 mmHg pressurization. From pulmonary to systemic pressures, the increases in autograft diameter were up to 17%. Likewise, the maximal wall stress increased approximately 14.6-fold compared to diastolic pressures (from 13.0 to 190.1kPa), and six-fold compared to systolic pressures (from 48.6 to 289.6kPa). CONCLUSION: The first finite element model of the human pulmonary autograft was developed and used to demonstrate how autograft material properties prevent significant dilatation upon initial exposure to systemic pressure. Mild dilatation was noted in the sinuses and sinotubular junction. Autograft wall stress was increased greatly when subjected to systemic pressures, and may trigger biomechanical remodeling of the autograft. Sustained exposure to higher wall stresses, coupled with inadequate remodeling, may lead to future autograft dilatation.

Patient-specific finite element analysis of ascending thoracic aortic aneurysm.

BACKGROUND AND AIM OF THE STUDY: Rupture/dissection of ascending thoracic aortic aneurysm (aTAA) is a cardiovascular emergency. Elective surgical repair is primarily based on maximum diameter, but complications have occurred under the size limits for surgical intervention. aTAA wall stress may be a better predictor of patient-specific rupture risk, but cannot be directly measured in vivo. The study aim was to develop an aTAA computational model associated with tricuspid aortic valve (TAV) to determine patient-specific wall stresses. METHODS: A TAV-associated aTAA was excised intact during surgery. Zero-pressure geometry was generated from microcomputed tomography, and an opening angle was used to calculate residual stress. Material properties determined from stress-strain data were incorporated into an Ogden hyperelastic model. Wall stress distribution and magnitudes at systemic pressure were determined using finite element analyses (FEA) in LS-DYNA. RESULTS: Regional material property differences were noted: the left aTAA region had a higher stiffness compared to the right, and anterior/posterior walls. During systole, the mean principal wall stresses were 172.0 kPa (circumferential) and 71.9 kPa (longitudinal), while peak wall stresses were 545.1 kPa (circumferential) and 430.1 kPa (longitudinal). Elevated wall stress pockets were seen in anatomic left and right aTAA regions. CONCLUSION: A validated computational approach was demonstrated to determine aTAA wall stresses in a patient-specific fashion, taking into account the required zero-stress geometry, wall thickness, material properties and residual stress. Regions of maximal wall stress may indicate the sites most prone to rupture. The creation of a patient-specific aTAA model based on a surgical specimen is necessary to serve as the 'gold standard' for comparing models based on in-vivo data alone. Validated data using the surgical specimen are essential for establishing wall stress and rupture-risk relationships.

Minimally invasive treatment of mitral valve disease with severe mitral annular calcification: Meeting paper for Mitral Conclave 2022.

Objective: Mitral valve disease in presence of severe mitral annular calcification (MAC) remains a challenge for surgeons to address. Conventional surgical techniques have potential for heightened morbidity and mortality. The advent of transcatheter heart valve technology and transcatheter mitral valve replacement (TMVR) holds promise to treat mitral valve disease with MAC with excellent clinical outcomes. Methods: We review current treatment strategies for MAC and studies in which TMVR techniques were used. Results: Several studies and a global registry describe outcomes of TMVR for mitral valve disease with MAC. We describe our specific technique on how to perform a minimally invasive transatrial approach for TMVR. Conclusions: TMVR demonstrates strong promise as a safe and effective way to treat mitral valve disease with MAC. We advocate for a minimally invasive transatrial approach when performing TMVR for mitral valve disease with MAC.

Looking towards the future: patient-specific computational modeling to optimize outcomes for transcatheter mitral valve repair.

Severe mitral valve regurgitation (MR) is a heart valve disease that progresses to end-stage congestive heart failure and death if left untreated. Surgical repair or replacement of the mitral valve (MV) remains the gold standard for treatment of severe MR, with repair techniques aiming to restore the native geometry of the MV. However, patients with extensive co-morbidities may be ineligible for surgical intervention. With the emergence of transcatheter MV repair (TMVR) treatment paradigms for MR will evolve. The longer-term outcomes of TMVR and its effectiveness compared to surgical repair remain unknown given the differing patient eligibility for either treatment at this time. Advances in computational modeling will elucidate answers to these questions, employing techniques such as finite element method and fluid structure interactions. Use of clinical imaging will permit patient-specific MV models to be created with high accuracy and replicate MV pathophysiology. It is anticipated that TMVR technology will gradually expand to treat lower-risk patient groups, thus pre-procedural computational modeling will play a crucial role guiding clinicians towards the optimal intervention. Additionally, concerted efforts to create MV models will establish atlases of pathologies and biomechanics profiles which could delineate which patient populations would best benefit from specific surgical vs. TMVR options. In this review, we describe recent literature on MV computational modeling, its relevance to MV repair techniques, and future directions for translational application of computational modeling for treatment of MR.

Left Ventricle Biomechanics of Low-Flow, Low-Gradient Aortic Stenosis: A Patient-Specific Computational Model.

This study aimed to create an imaging-derived patient-specific computational model of low-flow, low-gradient (LFLG) aortic stenosis (AS) to obtain biomechanics data about the left ventricle. LFLG AS is now a commonly recognized sub-type of aortic stenosis. There remains much controversy over its management, and investigation into ventricular biomechanics may elucidate pathophysiology and better identify patients for valve replacement. ECG-gated cardiac computed tomography images from a patient with LFLG AS were obtained to provide patient-specific geometry for the computational model. Surfaces of the left atrium, left ventricle (LV), and outflow track were segmented. A previously validated multi-scale, multi-physics computational human heart model was adapted to the patient-specific geometry, yielding a model consisting of 91,000 solid elements. This model was coupled to a virtual circulatory system and calibrated to clinically measured parameters from echocardiography and cardiac catheterization data. The simulation replicated key physiologic parameters within 10% of their clinically measured values. Global LV systolic myocardial stress was 7.1 ± 1.8 kPa. Mean stress of the basal, middle, and apical segments were 7.7 ± 1.8 kPa, 9.1 ± 3.8 kPa, and 6.4 ± 0.4 kPa, respectively. This is the first patient-specific computational model of LFLG AS based on clinical imaging. Low myocardial stress correlated with low ejection fraction and eccentric LV remodeling. Further studies are needed to understand how alterations in LV biomechanics correlates with clinical outcomes of AS.

Patient-Specific Analysis of Ascending Thoracic Aortic Aneurysm with the Living Heart Human Model.

In ascending thoracic aortic aneurysms (ATAAs), aneurysm kinematics are driven by ventricular traction occurring every heartbeat, increasing the stress level of dilated aortic wall. Aortic elongation due to heart motion and aortic length are emerging as potential indicators of adverse events in ATAAs; however, simulation of ATAA that takes into account the cardiac mechanics is technically challenging. The objective of this study was to adapt the realistic Living Heart Human Model (LHHM) to the anatomy and physiology of a patient with ATAA to assess the role of cardiac motion on aortic wall stress distribution. Patient-specific segmentation and material parameter estimation were done using preoperative computed tomography angiography (CTA) and ex vivo biaxial testing of the harvested tissue collected during surgery. The lumped-parameter model of systemic circulation implemented in the LHHM was refined using clinical and echocardiographic data. The results showed that the longitudinal stress was highest in the major curvature of the aneurysm, with specific aortic quadrants having stress levels change from tensile to compressive in a transmural direction. This study revealed the key role of heart motion that stretches the aortic root and increases ATAA wall tension. The ATAA LHHM is a realistic cardiovascular platform where patient-specific information can be easily integrated to assess the aneurysm biomechanics and potentially support the clinical management of patients with ATAAs.