What does complete revascularization mean in 2021? - Definitions, implications, and biases.

PURPOSE OF REVIEW: Coronary revascularization is known to be an excellent treatment for coronary artery disease. However, whether incomplete myocardial revascularization compromises long-term outcomes, as compared to complete revascularization (CR), remains contentious. Herein, we review the concept of and evidence on CR/incomplete revascularization (ICR) and discuss future perspectives. RECENT FINDINGS: When possible, achieving CR in coronary artery bypass grafting is desirable; nonetheless, ICR is also a reasonable option to balance the therapeutic benefits against the risks. SUMMARY: Although angiography-based assessment currently remains the standard of care, fractional flow reserve guidance may reduce the number of lesions requiring revascularization, which may be helpful for an appropriate surgical revascularization strategy. In particular, utilizing this approach may refine hybrid revascularization procedures, especially among high-risk patients.

Functionalization of soft materials for cardiac repair and regeneration.

Coronary artery disease is a leading cause of death in developed nations. As the disease progresses, myocardial infarction can occur leaving areas of dead tissue in the heart. To compensate, the body initiates its own repair/regenerative response in an attempt to restore function to the heart. These efforts serve as inspiration to researchers who attempt to capitalize on the natural regenerative processes to further augment repair. Thus far, researchers are exploiting these repair mechanisms in the functionalization of soft materials using a variety of growth factor-, ligand- and peptide-incorporating approaches. The goal of functionalizing soft materials is to best promote and direct the regenerative responses that are needed to restore the heart. This review summarizes the opportunities for the use of functionalized soft materials for cardiac repair and regeneration, and some of the different strategies being developed.

Muse Cells and Aortic Aneurysm.

The aorta is a well-organized, multilayered structure comprising several cell types, namely, endothelial cells (ECs), vascular smooth muscle cells (VSMCs), and fibroblasts, as well as an extracellular matrix (ECM), which includes elastic and collagen fibers. Aortic aneurysms (AAs) are defined as progressive enlargements of the aorta that carries an incremental risk of rupture as the diameter increases over time. The destruction of the aortic wall tissue is triggered by atherosclerosis, inflammation, and oxidative stress, leading to the activation of matrix metalloproteinases (MMPs), and inflammatory cytokines and chemokines, resulting in the loss of the structural back bone of VSMCs, ECM, and ECs. To date, cell-based therapy has been applied to animal models using several types of cells, such as VSMCs, ECs, and mesenchymal stem cells (MSCs). Although these cells indeed deliver beneficial outcomes for AAs, particularly by paracrine and immunomodulatory effects, the attenuation of aneurysmal dilation with a robust tissue repair is insufficient. Meanwhile, multilineage-differentiating stress-enduring (Muse) cells are known to be endogenous non-tumorigenic pluripotent-like stem cells that are included as several percent of MSCs. Since Muse cells are pluripotent-like, they have the ability to differentiate into cells representative of all three germ layers from a single cell and to self-renew. Moreover, Muse cells are able to home to the site of damage following simple intravenous injection and repair the tissue by replenishing new functional cells through spontaneous differentiation into tissue-compatible cells. Given these unique properties, Muse cells are expected to provide an efficient therapeutic efficacy for AA by simple intravenous injection. In this chapter, we summarize several studies on Muse cell therapy for AA including our recent data, in comparison with other kinds of cell therapies.

Predictors of the need for pacemaker implantation after the Cox maze IV procedure for atrial fibrillation.

PURPOSE: The Cox maze IV (CMIV) procedure is being used increasingly frequently for surgical ablation of atrial fibrillation (AF). This study aimed to identify the risk factors of the need for postoperative pacemaker implantation (PMI) after CMIV. METHODS: Preoperative, intraoperative, and postoperative data were retrospectively collected from 67 consecutive patients who underwent CMIV at our institution; 7 (10.4%) required PMI (as a treatment of brady AF or sick sinus syndrome). RESULTS: Patients who needed PMI tended to have lower preoperative heart rates than those who did not on a 12-lead electrocardiogram (ECG; 68.7 ± 11.6 vs. 79.1 ± 18.5 bpm, p = 0.07) and a 24-h ECG (94,772 ± 9800 vs. 109,854 ± 19,078 beats/day, p = 0.03). A multivariate analysis identified a low amplitude of the fibrillatory wave on preoperative ECG as a risk factor of PMI necessity after CMIV [odds ratio = 14.7; 95% confidence interval (CI) 1.9-324.7; p = 0.007] and internal use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEIs/ARBs) as a negative risk factor (odds ratio = 0.16; 95% CI 0.02-0.99; p = 0.049). CONCLUSIONS: A low amplitude of the fibrillatory wave was identified as a risk factor of PMI necessity, whereas the internal use of ACEIs/ARBs diminished the need for PMI. These factors should be considered before CMIV is performed.

Poly-2-methoxyethylacrylate-coated cardiopulmonary bypass circuit can reduce transfusion of platelet products compared to heparin-coated circuit during aortic arch surgery.

Several coating techniques for extracorporeal circulation have been developed to reduce the systemic inflammatory response during cardiopulmonary bypass (CPB). We compared the clinical effectiveness and biocompatibility of poly-2-methoxyethylacrylate (PMEA)- and heparin-coated CPB circuits in total aortic arch replacement (TAR) with the prolonged use of the bypass technique. Twenty patients who underwent elective TAR were divided randomly into two equal groups: group P (n = 10) to use PMEA-coated circuits and group H (n = 10) to use heparin-coated circuits. Clinical outcomes, hematological variables, and acute phase inflammatory response were analyzed perioperatively. Demographic, CPB, and clinical outcome data were similar for both groups. Hemoglobin and platelet count showed similar time-course curves. However, the amount of platelet products transfused intraoperatively was significantly larger in group H (group P 26.0 ± 7.0 units; group H 33.0 ± 6.7 units, p = 0.04). Total protein, and albumin levels were significantly higher in group P during and after the operation (total protein, p = 0.04; albumin, p = 0.02). The use of PMEA-coated circuit is associated with retainment of perioperative plasma proteins levels and may help to reduce transfusion of platelet products in TAR in comparison with the heparin-coated circuit.

[Issues in Coronary Artery Bypass Grafting for Kawasaki Disease].

Progressive narrowing at the entrance and exit of coronary artery aneurysm can develop at late phase of Kawasaki disease (KD). Evaluation and prediction of progressive coronary lesions remain a challenge in the treatment of post-KD coronary artery disease. We aimed to elucidate long-standing issues imposed on the patients who underwent coronary artry bypass grafting (CABG) for coronary artery lesions associated with KD. Between January, 2000 and December, 2013, CABG for coronary artery lesions associated with KD were performed in 6 patients (male/female: 5/1, mean age 14.5±10.0). There was no operative mortality. Follow-up for the 6 patients has been performed with the average period of 5 years (1~9 years). Cardiac events occurred in 2 patients during follow-up. In 1 patient, left internal thoracic artery (LITA) occluded due to flow competition between the native artery and LITA graft after LITA to LAD bypass grafting. The other patient required a re-do CABG using the free right internal thoracic artery to the circumflex branch because of occlusion at the coronary artery aneurysms after 4 years postoperatively. Meticulous preoperative diagnostic evaluations of coronary artery aneurysm may further improve the long-term outcome after surgical intervention for coronary lesions in conjunction with an aneurysm.

Continuous flow left ventricular assist device implantation concomitant with aortic arch replacement and aortic valve closure in a patient with end-stage heart failure associated with bicuspid aortic valve.

Left ventricular assist device (LVAD) implantation has become an established treatment for patients with end-stage heart failure as a bridge to cardiac transplantation. During LVAD implantation, some patients require concomitant surgeries, including tricuspid valve repair, aortic valve repair or replacement, and patent foramen ovale closure. However, concomitant aortic surgeries are rare in patients requiring LVAD implantation. We successfully performed total arch replacement with an open distal technique, aortic valve closure, and continuous flow LVAD implantation simultaneously.

[Two cases of fulminant myocarditis with mesenteric ischemia].

Fulminant myocarditis (FM) can lead to a refractory cardiogenic shock and multiple organ failure. Mechanical circulatory support (MCS) is not infrequency required to salvage patients in a profound shock. Advanced technology in MCS such as a temporary ventricular assist device can yield improved early outcome. However, incessant mesenteric ischemia remains a challenge to be resolved even with MCS. We here-in report 2 cases of FM associated with mesenteric ischemia that was extremely difficult to diagnose and treat. Therapeutic strategy for FM with mesenteric ischemia is discussed.

[Surgical treatment of coarctation of the aorta concomitant with left main coronary stenosis; report of a case].

A 60-year-old male was referred to our institution for investigation of intractable hypertension. Coarctation of the aorta was detected by computed tomography (CT). Bilateral internal thoracic arteries played an important role as a collateral source to the lower extremity. Coronary angiography showed stenosis at the ostium of left main trunk. Ascending aorta to bilateral external iliac artery bypass grafting and off-pump coronary artery bypass grafting (OPCAB) was done simultaneously, this is because we had to harvest left internal thoracic artery as a conduit for coronary artery bypass grafting(CABG).Postoperative course was uneventful. The patient was discharged 10 days after the operation. We could perform less-invasive surgery despite the simultaneous operations.

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.

Collagen-Based Microcapsules As Therapeutic Materials for Stem Cell Therapies in Infarcted Myocardium.

As cell therapies emerged, it was quickly realized that pro-regenerative cells directly injected into injured tissue struggled within the inflammatory microenvironment. By using microencapsulation, i.e., encapsulating cells within polymeric biomaterials, they are henceforth protected from the harmful extracellular cues, while still being able to receive oxygen and nutrients and release secreted factors. Previous work showed that stem cells encapsulated within a biologically inert material (agarose) were able to significantly improve the function of the infarcted mouse heart. With the aim of using more bioresponsive microcapsules, we sought to develop an enzymatically degradable, type I collagen-based microcapsule for the intramyocardial delivery of bone marrow-derived mesenchymal stromal cells in a murine model of myocardial infarction.

Peptide-Based Functional Biomaterials for Soft-Tissue Repair.

Synthetically derived peptide-based biomaterials are in many instances capable of mimicking the structure and function of their full-length endogenous counterparts. Combine this with the fact that short mimetic peptides are easier to produce when compared to full length proteins, show enhanced processability and ease of modification, and have the ability to be prepared under well-defined and controlled conditions; it becomes obvious why there has been a recent push to develop regenerative biomaterials from these molecules. There is increasing evidence that the incorporation of peptides within regenerative scaffolds can result in the generation of structural recognition motifs that can enhance cell attachment or induce cell signaling pathways, improving cell infiltration or promote a variety of other modulatory biochemical responses. By highlighting the current approaches in the design and application of short mimetic peptides, we hope to demonstrate their potential in soft-tissue healing while at the same time drawing attention to the advances made to date and the problems which need to be overcome to advance these materials to the clinic for applications in heart, skin, and cornea repair.

Electroconductive materials as biomimetic platforms for tissue regeneration.

In many diseases, tissue regeneration is compromised and/or insufficient to restore tissue/organ function. Therefore, novel regenerative therapies are being developed to enhance resident and transplanted cell proliferation and functional differentiation. Numerous biomaterials engineered to include nanocomponents have emerged as promising candidates to fulfil the need of mimicking the properties of the healthy extracellular matrix. This is particularly important for tissues that require electroconductive support to achieve optimal cellular function, such as muscles and neurons. In this review, we summarize and discuss the current state-of-the-art for electroconductive materials in tissue regeneration, with particular emphasis on materials containing nanocomponents.

Injectable human recombinant collagen matrices limit adverse remodeling and improve cardiac function after myocardial infarction.

Despite the success of current therapies for acute myocardial infarction (MI), many patients still develop adverse cardiac remodeling and heart failure. With the growing prevalence of heart failure, a new therapy is needed that can prevent remodeling and support tissue repair. Herein, we report on injectable recombinant human collagen type I (rHCI) and type III (rHCIII) matrices for treating MI. Injecting rHCI or rHCIII matrices in mice during the late proliferative phase post-MI restores the myocardium's mechanical properties and reduces scar size, but only the rHCI matrix maintains remote wall thickness and prevents heart enlargement. rHCI treatment increases cardiomyocyte and capillary numbers in the border zone and the presence of pro-wound healing macrophages in the ischemic area, while reducing the overall recruitment of bone marrow monocytes. Our findings show functional recovery post-MI using rHCI by promoting a healing environment, cardiomyocyte survival, and less pathological remodeling of the myocardium.

Safety and durability of the biodegradable felt in aortic surgery: a propensity score-matched study.

OBJECTIVES: Suture line disruption is a serious complication after aortic surgery. We previously reported in a canine model that basic fibroblast growth factor-incorporated biodegradable polyglycolic acid (PGA) felt prevented tissue derangement at the anastomotic site. This study sought to evaluate the safety and durability of this biodegradable felt. METHODS: Between January 2007 and December 2011, 67 patients who consented to undergo aortic surgery with the basic fibroblast growth factor-incorporated PGA felt were enrolled (Group P). As a control, we retrospectively reviewed the charts of 129 patients who underwent aortic surgery using a polytetrafluoroethylene felt during the same registration period (Group N). On the basis of 18 preoperative covariates, 60 well-matched patient pairs were identified using propensity matching, and their clinical indices were compared. RESULTS: Among the matched pairs, in-hospital mortality and postoperative complication rates did not statistically differ between the groups. During a median follow-up of 4.8 years, the rate of anastomotic aneurysm was 1.7% (1 patient) in both groups. The rates of overall survival and freedom from aortic events did not differ between the groups. In total, 65 anastomoses in Group P and 54 anastomoses in Group N were monitored via computed tomography, and the diameters of the juxta-anastomotic sites in Group N were more likely to be increased than those in Group P {dilatation ratio [(post-discharge diameter - predischarge diameter)/predischarge diameter × 100 (%)]: 4.3% ± 0.6% vs 2.5% ± 0.5%, P = 0.01}. CONCLUSIONS: The basic fibroblast growth factor-incorporated PGA felt was as safe and durable as conventional felt for reinforcement in aortic surgery. The attenuation of juxta-anastomotic aortic dilatation by PGA felt reinforcement may provide more beneficial effects on long-term outcomes.

Selective Cerebral Perfusion with the Open Proximal Technique during Descending Thoracic or Thoracoabdominal Aortic Repair: An Option of Choice to Reduce Neurologic Complications.

PURPOSE: Selective cerebral perfusion with the open proximal technique for thoracoabdominal aortic repair has not been conclusively validated because of its procedural complexity and unreliability. We report the clinical outcomes, particularly the cerebroneurological complications, of an open proximal procedure using selective cerebral perfusion. METHODS: A retrospective chart review identified 30 patients between 2007 and 2015 who underwent aortic repair through left lateral thoracotomy with selective cerebral perfusion, established through endoluminal brachiocephalic and left carotid artery and retrograde left axillary artery. RESULTS: The mean durations of the open proximal procedure and cerebral ischemia (the duration of the open proximal procedure minus the duration of selective cerebral perfusion) were 110.3 ± 40.1 min and 24.8 ± 13.0 min, respectively. There were two cases (7%) of permanent neurologic dysfunction (PND) but no in-hospital deaths. Multivariate analysis identified the duration of cerebral ischemia as an independent risk factor for neurologic complications including temporary neurologic dysfunction (TND; odds ratio (OR): 1.13; p = 0.007), but no correlation was found between selective cerebral perfusion duration and neurologic complications. CONCLUSION: Despite the relatively long duration of the open proximal procedure, selective cerebral perfusion has a potential to protect against cerebral complications during thoracic aortic repair through a left lateral thoracotomy.

Intravenously injected human multilineage-differentiating stress-enduring cells selectively engraft into mouse aortic aneurysms and attenuate dilatation by differentiating into multiple cell types.

OBJECTIVES: Aortic aneurysms result from the degradation of multiple components represented by endothelial cells, vascular smooth muscle cells, and elastic fibers. Cells that can replenish these components are desirable for cell-based therapy. Intravenously injected multilineage-differentiating stress-enduring (Muse) cells, endogenous nontumorigenic pluripotent-like stem cells, reportedly integrate into the damaged site and repair the tissue through spontaneous differentiation into tissue-compatible cells. We evaluated the therapeutic efficacy of Muse cells in a murine aortic aneurysm model. METHODS: Human bone marrow Muse cells, isolated as stage-specific embryonic antigen-3+ from bone marrow mesenchymal stem cells, or non-Muse cells (stage-specific embryonic antigen-3- cells in mesenchymal stem cells), bone marrow mesenchymal stem cells, or vehicle was intravenously injected at day 0, day 7, and 2 weeks (20,000 cells/injection) after inducing aortic aneurysms by periaortic incubation of CaCl2 and elastase in severe combined immunodeficient mice. RESULTS: At 8 weeks, infusion of human Muse cells attenuated aneurysm dilation, and the aneurysmal size in the Muse group corresponded to approximately 62.5%, 55.6%, and 45.6% in the non-Muse, mesenchymal stem cell, and vehicle groups, respectively. Multiphoton laser confocal microscopy revealed that infused Muse cells migrated into aneurysmal tissue from the adventitial side and penetrated toward the luminal side. Histologic analysis demonstrated robust preservation of elastic fibers and spontaneous differentiation into endothelial cells and vascular smooth muscle cells. CONCLUSIONS: After intravenous injection, Muse cells homed and expanded to the aneurysm from the adventitial side. Subsequently, Muse cells differentiated spontaneously into vascular smooth muscle cells and endothelial cells, and elastic fibers were preserved. These Muse cell features together led to substantial attenuation of aneurysmal dilation.

Nanoengineered Electroconductive Collagen-Based Cardiac Patch for Infarcted Myocardium Repair.

We have prepared and tested in vivo a novel nanoengineered hybrid electroconductive cardiac patch for treating the infarcted myocardium. Of the prepared and tested patches, only those containing spherical nanogold were able to increase connexin-43 expression in neonatal rat cardiomyocytes cultured under electrical stimulation. In vivo data indicated that only nano-gold-containing patches were able to recover cardiac function. Histological analysis also revealed that connexin-43 levels and blood vessel density were increased, while the scar size was reduced for animals that received the nanogold patch. Thus, our study indicates that the incorporation of electroconductive properties into a collagen-based cardiac patch can improve its therapeutic potential for treating myocardial infarction.

Predictors of Heparin Resistance Before Cardiovascular Operations in Adults.

BACKGROUND: Heparin resistance (HR) is often encountered during cardiovascular operations that require cardiopulmonary bypass. Clinical risk factors and the mechanism underlying heparin resistance are yet to be determined. The aim of this study was to elucidate the clinically valid preoperative predictors related to HR. METHODS: The study evaluated 489 patients undergoing cardiovascular operations. Of these, 25 patients presented with HR and received antithrombin III for the initiation of cardiopulmonary bypass with an effective activated coagulation time. The remaining 464 patients, who did not receive antithrombin III, served as controls (NHR). Preoperative patient demographic and laboratory data were analyzed to identify risk factors for HR. RESULTS: The preoperative laboratory data showed platelet count, fibrinogen, D-dimer, creatinine, and C-reactive protein were significantly higher in the HR group than in the NHR group. As expected, the antithrombin III level was significantly lower overall in the HR group (86.0% vs 95.5%, p = 0.009); however, 80% of the patients in the HR group showed normal antithrombin III levels preoperatively. Multivariable logistic regression analysis identified chronic aortic dissection, chronic obstructive pulmonary disease, smoking, and elevated fibrinogen levels as independent predictors for HR. CONCLUSIONS: HR was shown to be associated with preoperative high fibrinogen levels, a smoking habit, and a preoperative diagnosis of chronic, but not acute, aortic dissection, with chronic obstructive pulmonary disease as comorbidity. Administration of antithrombin III resolved HR in all of the affected patients, even when their preoperative antithrombin III level was within the normal limit.