In Situ Myocardial Regeneration With Tissue Engineered Cardiac Patch Using Spheroid-Based 3-Dimensional Tissue.

BACKGROUND: We have developed a tissue engineered cardiac patch derived from a 3-dimensional (3D) myocardial tissue reinforced with extracellular matrix in an effort to enhance in situ myocardial regeneration. The feasibility of the patch was evaluated in a porcine model by various modalities to assess both the constructive and functional aspects of regeneration. METHODS: A spheroid-based 3D multicellular tissue was created using a 3D net mold system that incorporated cardiomyocytes and embryonic fibroblast cells. The 3D multicellular tissue was incorporated with extracellular matrix sheets and surgically implanted into the right ventricle of a healthy porcine model (n = 4). After 60 days, the implanted patches were evaluated by cardiac magnetic resonance imaging and electroanatomic mapping studies as well as by post-euthanasia analyses, including measurements of mechanical viscoelasticity. RESULTS: Cardiac magnetic resonance imaging revealed improved regional tissue perfusion in the patch area. Electroanatomic mapping exhibited regenerated electrical conductivity in the patch, as evidenced by relatively preserved voltage regions (1.11 ± 0.8 mV) in comparison to the normal right ventricle (4.7 ± 2.8 mV). Histologic and tissue analyses confirmed repopulation of site-specific host cells, including premature cardiomyocytes and active vasculogenesis. These findings were supported by quantitative reverse transcription-polymerase chain reaction. CONCLUSIONS: The tissue engineered cardiac patch effectively facilitated in situ constructive and functional myocardial regeneration, characterized by increased regional tissue perfusion and positive electrical activity in the porcine model.

Impact of prophylactic donor heart tricuspid valve annuloplasty on outcomes in heart transplantation.

BACKGROUND: Tricuspid regurgitation(TR) following heart transplantation could adversely affect clinical outcomes. In an effort to reduce the incidence of TR, prophylactic donor heart tricuspid valve annuloplasty has been performed during heart transplantation in our institution. We assessed early and long-term outcomes. METHODS: Between August 2011 and August 2021, 349 patients who underwent prophylactic tricuspid valve annuloplasty were included. Tricuspid valve annuloplasty was performed using the DeVega annuloplasty technique. The clinical outcomes of the interests included complete atrioventricular block requiring pacemaker implantation, the occurrence of significant TR(defined as moderate or greater), and survival. Long-term survival was compared in patients with and without significant TR using the Kaplan-Meier method. The Cox proportional hazards regression with time-dependent covariate analysis was used to see if significant TR affected the long-term survival. RESULTS: There was one patient(0.3%) who required pacemaker implantation for complete atrioventricular block. No patients developed tricuspid valve stenosis that required intervention. Significant TR developed in 31 patients(8.9%) during the follow-up period. The survival rate of patients who developed significant TR was significantly lower than that of those who did not(log rank < 0.01). Significant TR was associated with the long-term mortality(HR2.92, 95%CI 1.47-5.82, p < 0.01). CONCLUSIONS: Prophylactic donor heart tricuspid valve annuloplasty has the potential to reduce the occurrence of significant TR and can be performed safely. The significant TR that developed in patients with prophylactic annuloplasty negatively affected survival and was an independent predictor of long-term mortality.

Concomitant left atrial appendage closure during left ventricular assist device surgery can reduce ischaemic cerebrovascular accidents.

OBJECTIVES: It remains unknown if the left atrial appendage closure (LAAC) at the time of left ventricular assist device (LVAD) surgery can reduce ischaemic cerebrovascular accidents. METHODS: Consecutive 310 patients who underwent LVAD surgery with HeartMate II or 3 between January 2012 and November 2021 were included in this study. The cohort was divided into 2 groups: patients with LAAC (group A) and without LAAC (group B). We compared the clinical outcomes including the incidence of cerebrovascular accident between 2 groups. RESULTS: Ninety-eight patients were included in group A, and 212 patients in group B. There were no significant differences between 2 groups in age, preoperative CHADS2 score and history of atrial fibrillation. In-hospital mortality did not differ significantly between the 2 groups (group A: 7.1%, group B: 12.3%, P = 0.16). Thirty-seven patients (11.9%) experienced ischaemic cerebrovascular accident (5 patients in group A and 32 patients in group B). The cumulative incidence from ischaemic cerebrovascular accidents in group A (5.3% at 12 months and 5.3% at 36 months) was significantly lower than that in group B (8.2% at 12 months and 16.8% at 36 months; P = 0.017). In a multivariable competing risk analysis, LAAC was associated with reducing ischaemic cerebrovascular accidents (hazard ratio 0.38, 95% confidence interval 0.15-0.97, P = 0.043). CONCLUSIONS: Concomitant LAAC in LVAD surgery can reduce ischaemic cerebrovascular accidents without increasing perioperative mortality and complications.

Systematic review and network meta-analysis of various nadir temperature strategies for hypothermic circulatory arrest for aortic arch surgery.

BACKGROUND: The optimal nadir temperature for hypothermic circulatory arrest during aortic arch surgery remains unclear. We aimed to assess and compare clinical outcomes of all three temperature strategies (deep, moderate, and mild hypothermia) using a network meta-analysis. METHODS: After literature search with MEDLINE and EMBASE through December 2021, studies comparing clinical outcomes with deep (<20°C), moderate (20-28°C), or mild (>28°C) hypothermic circulatory arrest were included. The outcomes of interest were perioperative mortality, stroke, transient ischemia attack (TIA), acute kidney injury (AKI), postoperative bleeding, operative time, and length of hospital stay. RESULTS: Twenty-four comparative studies were identified, including 6018 patients undergoing aortic arch surgery using hypothermic circulatory arrest (deep: 2,978, moderate: 2,525, and mild: 515). Compared to deep hypothermia, mild and moderate hypothermia were associated with lower mortality (mild vs. deep: odds ratio [OR] 0.50; 95% confidence interval (CI) 0.29-0.87, moderate vs. deep: OR 0.68; 95% CI 0.54-0.86). In addition, mild hypothermia was associated with lower stroke (OR 0.50; 95% CI 0.28-0.89), AKI (OR 0.36; 95% CI 0.15-0.88) and postoperative bleeding (OR 0.55; 95% CI 0.31-0.97) compared to deep hypothermia. There was no significant difference between mild and moderate hypothermia in mortality, AKI or bleeding occurrence, while mild hypothermia was associated with shorter operative time and hospital stay. There was no significant difference in TIA rate among three groups. CONCLUSIONS: Mild hypothermia was associated with overall more favorable clinical outcomes with comparable neurological complications compared to deep hypothermia. Furthermore, considering the shorter operative time and hospital stay compared with moderate hypothermia, mild hypothermia may be warranted when appropriate adjunctive cerebral perfusion is employed.

Knowledge gaps in surgical management for aortic dissection.

Aortic dissection (AD) is recognized as a potentially fatal condition and its standard treatment has been surgical intervention for acute type A AD (TAAD) and complicated acute type B AD (TBAD), and medical management for uncomplicated acute type B AD. Due to rapidly evolving device technologies and minimally invasive surgical techniques that have lowered perioperative risk, there are paradigm shifts for the indications and treatment options for both TAAD and TBAD. In this article, we will discuss the current indications and treatment options for TAAD and TBAD by chronicity of the disease, which comprises four categories: acute TAAD, chronic (repaired) TAAD, acute TBAD, and chronic TBAD. We will also discuss the knowledge gaps in the current surgical management strategies and literature evidence. Open surgical intervention remains the reference standard for acute TAAD and chronic TAAD with complications until an endoprosthesis that will suit the complex anatomy of aortic root, ascending aorta, and aortic arch is developed. Thoracic endovascular aortic repair is now the first line for complicated acute and chronic TBADs. However, we need a larger trials to support the safety and durability of the procedures in patients with uncomplicated TBAD. Without additional data, patients are left to choose between existing treatment options, such as open surgical repair and stent-grafting.

Surgical Correction of Spontaneous Outflow Graft Twisting of HeartMate 3 LVAD via a Subcostal Approach.

We present two cases of successful surgical correction of a HeartMate 3 left ventricular assist device (LVAD) outflow graft twisting through a subcostal approach. These twistings were diagnosed with computed tomography or pull-back pressure measurement. Technically, a subcostal approach allowed us to access directly the twisted outflow graft and the device connector in a less invasive fashion as compared with a re-sternotomy. Diagnostic modality and surgical tips that address graft twisting are presented within the discussion of these two case studies. The institutional review board of our institution approved this study and waived the requirement for informed consent.

Management of acute type A aortic dissection in the elderly: an analysis from IRAD.

OBJECTIVES: We sought to examine management and outcomes of (Stanford) type A aortic dissection (TAAAD) in patients aged >70 years. METHODS: All patients with TAAAD enrolled in the International Registry of Acute Aortic Dissection database (1996-2018) were studied (n = 5553). Patients were stratified by age and therapeutic strategy. Outcomes for octogenarians were compared with those for septuagenarians. Variables associated with in-hospital mortality were identified by multivariable logistic regression. RESULTS: In-hospital mortality for all patients (all ages) was 19.7% (1167 deaths), 16.1% after surgical intervention vs 52.1% for medical management (P < 0.001). Of the study population, 1281 patients (21.6%) were aged 71-80 years and 475 (8.0%) were >80 years. Fewer octogenarians underwent surgery versus septuagenarians (68.1% vs 85.9%, P < 0.001). Overall mortality was higher for octogenarians versus septuagenarians (32.0% vs 25.6%, P = 0.008); however, surgical mortality was similar (25.1% vs 21.7%, P = 0.205). Postoperative complications were comparable between surgically managed cohorts, although reoperation for bleeding was more common in septuagenarians (8.1% vs 3.2%, P = 0.033). Kaplan-Meier 5-year survival was significantly superior after surgical repair in all age groups, including septuagenarians (57.0% vs 13.7%, P < 0.001) and octogenarians (35.5% vs 22.6%, P < 0.001). CONCLUSIONS: When compared with septuagenarians, a smaller percentage of octogenarians undergo surgical repair for TAAAD, even though postoperative outcomes are similar. Age alone should not preclude consideration for surgery in appropriately selected patients with TAAAD.

Significant vascular complications in percutaneous axillary intra-aortic balloon pump.

OBJECTIVE: Axillary Intra-aortic balloon pump (IABP) has been increasingly utilized for hemodynamic support in heart failure patients. Vascular complications associated with axillary IABP such as dissection or rupture are relatively rare but not negligible that could negatively affect clinical outcomes. We summarized our experiences. METHODS: This is a retrospective study reviewing of all patients receiving an axillary IABP between June 2016 and November 2020. A total of 199 patients underwent percutaneous axillary IABP placement. 6 patients (6/199, 3.0%) were complicated with arterial/aortic dissection or rupture during the procedures or the course of treatment. We described their clinical presentations and outcomes. RESULTS: Vascular complications included acute type A aortic dissection in 2 patients, descending aortic rupture in 1 patient, abdominal aortic rupture along with type B aortic dissection in 1 patient, and the localized left subclavian artery dissection in 2 patient. 2 type A aortic dissection cases were surgically treated: 1 with emergent left ventricle assist device and ascending aorta replacement, the other with emergent left ventricle assist device. Emergent endovascular treatment was successfully performed in 2 aortic rupture cases. The left subclavian artery dissection cases were managed medically. The postoperative/treatment course was uneventful in all patients. CONCLUSION: Percutaneous axillary IABP therapy can cause significant vascular complications. Early diagnosis and prompt treatment would be the key to improve the clinical outcomesv.

Proximal ascending aorta size is associated with the incidence of de novo aortic insufficiency with left ventricular assist device.

We sought to assess the impact of the aortic root geometry on developing de novo aortic insufficiency (AI) in patients undergoing left ventricular assist device (LVAD). In total, 114 patients underwent LVAD implantation between February 2016 and January 2020 were included in this study (HeartMate3 N = 68, HeartWare N = 46). Significant aortic insufficiency was defined as mild-to-moderate or greater in echocardiography. The cohort was divided into two groups; those who developed significant AI (Group AI: n = 13) and did not (Group non-AI: n = 101). The primary outcomes of interest included late survival and predictors for significant AI. The patients in Group AI were older than Group non-AI (62.6 ± 11.9 vs 51.3 ± 14.0 years, p < 0.01). The diameter of proximal ascending aorta in Group AI was larger than Group non-AI (31.0 ± 5.0 vs 27.4 ± 4.3 mm, p < 0.01). Aortic valve remained closed in 53.8% in Group AI and 36.6% in Group non-AI (p = 0.24). The late survival was not significantly different between the groups (67.1% vs 76.0% at 3 years, log rank = 0.97). The Cox hazard model showed that larger proximal ascending aortic diameter/BSA (HR 1.55, CI 1.19-2.04, p < 0.01) and not-opening aortic valve (HR 4.73, CI 1.43-16.9, p = 0.01) were independent risk factors for significant AI. The cutoff value of proximal ascending aortic diameter/BSA was 15.5 (area under curve: 0.770, sensitivity: 0.69, specificity: 0.79). Dilated proximal ascending aorta at the time of LVAD surgery and not-opening aortic valve during follow-up were associated with the incidence of de novo significant AI.

Conventional sternotomy versus right mini-thoracotomy versus robotic approach for mitral valve replacement/repair: insights from a network meta-analysis.

INTRODUCTION: Minimally invasive cardiac surgery (MICS) through right mini-thoracotomy as well as robotic surgery has emerged for the last decade for mitral valve surgery. However, their risks and benefits are not fully understood yet. Thus, we conducted a network meta-analysis comparing the early- and long-term outcomes of mitral valve surgery via the conventional sternotomy, MICS, and robotic approaches. EVIDENCE ACQUISITION: MEDLINE and EMBASE were searched through November 2020 to identify randomized controlled trials (RCTs) and propensity-score matched (PSM) trials that investigated early- and long-term outcomes after mitral surgery via the conventional sternotomy, MICS, and robotic approaches. A subanalysis focusing on only subjects who initially underwent mitral valve repair was also conducted. EVIDENCE SYNTHESIS: Our systematic literature search identified two RCTs and 19 PSM studies. MICS was related to significant risk reductions of permanent pacemaker implantation, surgical site infection, and transfusion compared to the sternotomy approach. The robotic approach was associated with a significant increase in re-exploration for bleeding compared to sternotomy. The subanalysis showed that MICS was associated with a significant increase requiring mitral valve reoperation compared to the sternotomy approach (hazard ratio 7.33 [95% CI: 1.54-34.97], P=0.012), while no significant difference was observed between the sternotomy and the robotic approach. CONCLUSIONS: Our network meta-analysis demonstrated that MICS was associated with better short-term outcomes compared to the sternotomy approach. Mitral valve reoperation was more frequent with MICS compared with the sternotomy approach after mitral valve repair, while no difference was observed between the sternotomy and robotic approaches.

Sex-Based Aortic Dissection Outcomes From the International Registry of Acute Aortic Dissection.

BACKGROUND: Worse outcomes have been reported for women with type A acute aortic dissection (TAAD). We sought to determine sex-specific operative approaches and outcomes for TAAD in the current era. METHODS: The Interventional Cohort (IVC) of the International Registry of Acute Aortic Dissection (IRAD) database was queried to explore sex differences in presentation, operative approach, and outcomes. Multivariable logistic regression was performed to identify adjusted outcomes in relation to sex. RESULTS: Women constituted approximately one-third (34.3%) of the 2823 patients and were significantly older than men (65.4 vs 58.6 years, P < .001). Women were more likely to present with intramural hematoma, periaortic hematoma, or complete or partial false lumen thrombosis (all P < .05) and more commonly had hypotension or coma (P = .001). Men underwent a greater proportion of Bentall, complete arch, and elephant trunk procedures (all P < .01). In-hospital mortality during the study period was higher in women (16.7% vs 13.8%, P = .039). After adjustment, female sex trended towards higher in-hospital mortality overall (odds ratio, 1.40; P = .053) but not in the last decade of enrollment (odds ratio, 0.93; P = .807). Five-year mortality and reintervention rates were not significantly different between the sexes. CONCLUSIONS: In-hospital mortality remains higher among women with TAAD but demonstrates improvement in the last decade. Significant differences in presentation were noted in women, including older age, distinct imaging findings, and greater evidence of malperfusion. Although no distinctions in 5-year mortality or reintervention were observed, a tailored surgical approach should be considered to reduce sex disparities in early mortality rates for TAAD.

A proposed redosing interval of del Nido cardioplegia solution in adult cardiac surgery: a propensity-matched study.

BACKGROUND: Recently, del Nido cardioplegia solution (DN) has been utilized in adult cardiac surgery. However, adequate interval of maintenance dose(s) is still unclear. The purpose of this study was to assess the safety and efficacy of our DN protocol by comparing with conventional cold whole blood cardioplegia (CWB). METHODS: A total of 1003 consecutive patients (DN group, N = 350 vs. CWB group, N = 653) underwent cardiovascular surgery between July 2013 and September 2018 were included in this study. The DN protocol was to administer 1000 to 1200 ml as an initial dose and to add maintenance dose(s) (500 ml each) every 60 minutes when the estimated cross-clamp time was over 90 minutes. CWB was given every 20 minutes, regardless of cross-clamp time. Propensity matching identified 254 matched pairs for analysis. The preoperative and postoperative data were reviewed. RESULTS: Cross-clamp time was significantly shorter in the DN group compared with the CWB group (107 ± 56 minutes vs. 116 ± 49 minutes, p = 0.0458). A retrograde cannula was used in 124 (48.8%) patients in the DN group and 181 (71.3%) patients in the CWB group (p < 0.0001). There were no significant differences in requiring postoperative cardiac supports (inotropes, mechanical circulatory supports) and major complications. In-hospital mortality was similar between two groups (DN group: 3.2% vs. CWB group: 2.4%, p = 0.5872). CONCLUSIONS: Short-term clinical outcomes in the patients underwent cardiovascular surgery with the DN protocol including the redosing interval strategy were acceptable. Also, DN protocol was associated with shortened cross-clamp time and less usage of the retrograde cannula.

Orthotopic heart transplantation with persistent left superior vena cava draining into coronary sinus: the anterior rerouting technique.

BACKGROUND: We present a surgical technique for a reconstruction of a persistent left superior vena cava draining into the coronary sinus with orthotopic heart transplantation. METHODS: Between January 2013 and July 2019, a total of 224 patients underwent orthotopic heart transplantation in our institution. Among them, three patients (3/224, 1.3%) had a persistent left superior vena cava draining into the coronary sinus. The persistent left superior vena cava and the coronary sinus was isolated and fully mobilized as an en bloc conduit at the time of explanting the heart. After the standard anastomoses using the bicaval technique, the conduit was routed anterior to the great vessels and anastomosed to the right atrial appendage. A smooth venous drainage into the right atrium from the rerouted persistent left superior vena cava was intraoperatively confirmed by transesophageal echocardiography. RESULTS: The postoperative course was uneventful in all patients. There were no major postoperative complication and in-hospital mortality. The routed persistent left superior vena cava-coronary sinus conduits were confirmed to be patent without stenosis/obstruction by an enhanced computed tomography. Cardiac biopsies through the reconstructed persistent left superior vena cava were possible without any difficulty. CONCLUSION: The anterior rerouting technique for a reconstruction of a persistent left superior vena cava draining into the coronary sinus in an orthotopic heart transplantation was feasible and reproducible.

Outcomes of Ambulatory Axillary Intraaortic Balloon Pump as a Bridge to Heart Transplantation.

BACKGROUND: The axillary intraaortic balloon pump (IABP) is frequently used in selected patients for circulatory support as a bridge to heart transplantation. The purpose of this study was to investigate the safety and efficacy of axillary intraaortic balloon pump (IABP) support for heart transplant candidates. METHODS: The study investigators collected data on 133 patients who underwent axillary IABP support as a bridge to transplantation from July 2009 to April 2019. Of these patients, 94 (70.7%) underwent IABP insertion with surgical axillary grafts, and 39 (29.3%) underwent percutaneous IABP insertion. The outcomes of interest included ambulatory data, IABP-related complications, and successful heart transplantation with this type of support. RESULTS: The overall preoperative ejection fraction was 20.3% ± 8.0%. The median duration of axillary IABP support was 21days, with 131patients (98.5%) mobilizing with the device. Hemodynamic variables significantly improved after the axillary IABP support was placed. Overall, 122 patients (91.7%) were successfully bridged to heart transplantation. Six patients (4.5%) required escalation to further mechanical support. Two patients (1.5%) died while awaiting transplantation. Four patients (3.0%) experienced a stroke during axillary IABP support (3 before transplantation and1 after transplantation). Two of the 3 patients with a stroke diagnosis before transplantation recovered and eventually underwent heart transplantation. CONCLUSIONS: With axillary IABP support, most patients were able to ambulate and undergo physical rehabilitation while waiting for heart transplantation. This study demonstrates that axillary IABP results in a high success rate of bridge to transplantation and a low number of complications. Thus, an ambulatory axillary IABP provided efficient and safe support for selected patients as a bridge to heart transplantation.

HeartWare Ventricular Assist Device Cannula Position and Hemocompatibility-Related Adverse Events.

BACKGROUND: HeartWare ventricular assist device (HVAD) cannula position is associated with hemodynamics and heart failure readmissions. However, its impact on hemocompatibility-related adverse events (HRAEs) remains uncertain. METHODS: HVAD patients were followed for 1 year after index hospitalization, when cannula coronal angle was quantified from chest x-ray film. Invasive right heart catheterization and transthoracic echocardiography were performed. One-year occurrences of each HRAE were compared between those with and without a cannula coronal angle of greater than 65 degrees. RESULTS: Among 63 HVAD patients (median age 60 years, 63% male), 10 (16%) had a cannula coronal angle greater than 65 degrees. The wide-angle group had elevated intracardiac pressures and lower pulmonary artery pulsatility index (P < .05). They also had reduced right ventricular function by echocardiography. Freedom from HRAEs tended to be lower in the wide-angle group (24% vs 62%; P = .11). The rate of gastrointestinal bleeding was significantly higher in the greater than 65 degrees group (0.90 events/year vs 0.40 events/year; P = .013). The rates of stroke and pump thrombosis were statistically comparable irrespective of cannula angle (P > .05). CONCLUSIONS: HVAD cannula coronal angle was associated with reduced right ventricular function and HRAEs. Prospective studies evaluating surgical techniques to ensure optimal device positioning and its effects on HRAEs are warranted.

Effect of Concomitant Tricuspid Valve Surgery With Left Ventricular Assist Device Implantation.

BACKGROUND: Tricuspid regurgitation (TR) is common in advanced heart failure (HF) patients. However, the effect of concomitant tricuspid valve repair or replacement (tricuspid valve intervention [TVI]) with left ventricular assist device (LVAD) implantation is controversial. The aim of this study was to investigate the longitudinal trend of TR after LVAD implantation and the effect of TVI on the TR trend and clinical outcomes. METHODS: We retrospectively reviewed patients at our institution who underwent LVAD implantation between April 2014 and August 2018. We evaluated the grade of TR by echocardiography before and after LVAD implantation. Moderate or greater TR was defined as significant. RESULTS: Among 199 consecutive patients, 194 had at least 2 echocardiographic TR assessments before and after LVAD implantation. Of these patients, 108 were included in the TVI-positive (TVI+) group and 86 in the TVI-negative (TVI-) group. In the TVI+ group, the prevalence of significant TR decreased from 52% to about 20% in the first 6 months after implantation (P < .01). Overall survival and HF readmission-free survival were comparable between the TVI+ and TVI- patients. In contrast, patients in both groups who had significant postoperative TR during early follow-up had worse 2-year HF readmission-free survival (36% in patients with significant postoperative TR vs 55% in those without significant postoperative TR; P = .028). CONCLUSIONS: Concomitant TVI with LVAD implantation improved TR in most patients but did not have an impact on clinical outcomes. Significant postoperative TR after LVAD implantation, in patients with and without TVI, was associated with worse HF-free outcomes.