Biomaterials for direct cardiac repair-A rapid scoping review 2012-2022.

A plethora of biomaterials for heart repair are being tested worldwide for potential clinical application. These therapeutics aim to enhance the quality of life of patients with heart disease using various methods to improve cardiac function. Despite the myriad of therapeutics tested, only a minority of these studied biomaterials have entered clinical trials. This rapid scoping review aims to analyze literature available from 2012 to 2022 with a focus on clinical trials using biomaterials for direct cardiac repair, i.e., where the intended function of the biomaterial is to enhance the repair of the endocardium, myocardium, epicardium or pericardium. This review included neither biomaterials related to stents and valve repair nor biomaterials serving as vehicles for the delivery of drugs. Surprisingly, the literature search revealed that only 8 different biomaterials mentioned in 23 different studies out of 7038 documents (journal articles, conference abstracts or clinical trial entries) have been tested in clinical trials since 2012. All of these, intended to treat various forms of ischaemic heart disease (heart failure, myocardial infarction), were of natural origin and most used direct injections as their delivery method. This review thus reveals notable gaps between groups of biomaterials tested pre-clinically and clinically. STATEMENT OF SIGNIFICANCE: Rapid scoping review of clinical application of biomaterials for cardiac repair. 7038 documents screened; 23 studies mention 8 different biomaterials only. Biomaterials for repair of endocardium, myocardium, epicardium or pericardium. Only 8 different biomaterials entered clinical trials in the past 10 years. All of the clinically translated biomaterials were of natural origin.

One-month DAPT with ticagrelor and aspirin for patients undergoing coronary artery bypass grafting: rationale and design of the randomised, multicentre, double-blind, placebo-controlled ODIN trial.

The optimal antiplatelet strategy after coronary artery bypass graft (CABG) surgery in patients with chronic coronary syndromes (CCS) is unclear. Adding the P2Y12 inhibitor, ticagrelor, to low-dose aspirin for 1 year is associated with a reduction in graft failure, particularly saphenous vein grafts, at the expense of an increased risk of clinically important bleeding. As the risk of thrombotic graft failure and ischaemic events is highest early after CABG surgery, a better risk-to-benefit profile may be attained with short-term dual antiplatelet therapy followed by single antiplatelet therapy. The One Month Dual Antiplatelet Therapy With Ticagrelor in Coronary Artery Bypass Graft Patients (ODIN) trial is a prospective, randomised, double-blind, placebo-controlled, international, multicentre study of 700 subjects that will evaluate the effect of short-term dual antiplatelet therapy with ticagrelor plus low-dose aspirin after CABG in patients with CCS. Patients will be randomised 1:1 to ticagrelor 90 mg twice daily or matching placebo, in addition to aspirin 75-150 mg once daily for 1 month; after the first month, antiplatelet therapy will be continued with aspirin alone. The primary endpoint is a hierarchical composite of all-cause death, stroke, myocardial infarction, revascularisation and graft failure at 1 year. The key secondary endpoint is a hierarchical composite of all-cause death, stroke, myocardial infarction, Bleeding Academic Research Consortium (BARC) type 3 bleeding, revascularisation and graft failure at 1 year (net clinical benefit). ODIN will report whether the addition of ticagrelor to low-dose aspirin for 1 month after CABG reduces ischaemic events and provides a net clinical benefit in patients with CCS. (ClinicalTrials.gov: NCT05997693).

Multiarterial vs Single-Arterial Coronary Surgery: 10-Year Follow-up of 1 Million Patients.

BACKGROUND: Although many options exist for multivessel coronary revascularization, controversy persists over whether multiarterial grafting (MAG) confers a survival advantage over single-arterial grafting (SAG) with saphenous vein in coronary artery bypass grafting (CABG). This study sought to compare longitudinal survival between patients undergoing MAG and those undergoing SAG. METHODS: All patients undergoing isolated CABG with ≥2 bypass grafts in The Society of Thoracic Surgeons Adult Cardiac Surgery Database (2008-2019) were linked to the National Death Index. Risk adjustment was performed using inverse probability weighting and multivariable modeling. The primary end point was longitudinal survival. Subpopulation analyses were performed and volume thresholds were analyzed to determine optimal benefit. RESULTS: A total of 1,021,632 patients underwent isolated CABG at 1108 programs (100,419 MAG [9.83%]; 920,943 SAG [90.17%]). Median follow-up was 5.30 years (range, 0-12 years). After risk adjustment, all characteristics were well balanced. At 10 years, MAG was associated with improved unadjusted (hazard ratio, 0.59; 95% CI 0.58-0.61) and adjusted (hazard ratio, 0.86; 95% CI, 0.85-0.88) 10-year survival. Center volume of ≥10 MAG cases/year was associated with benefit. MAG was associated with an overall survival advantage over SAG in all subgroups, including stable coronary disease, acute coronary syndrome, and acute infarction. Survival was equivalent to that with SAG for patients age ≥80 years and those with severe heart failure, renal failure, peripheral vascular disease, or obesity. Only patients with a body mass index ≥40 kg/m2 had superior survival with SAG. CONCLUSIONS: Multiarterial CABG is associated with superior long-term survival and should be the surgical multivessel revascularization strategy of choice for patients with a body mass index of less than 40 kg/m2.

Less Invasive and Hybrid Surgical/Interventional Coronary Disease Management: The Future Is Now.

Coronary artery bypass grafting (CABG) has evolved to become the criterion standard in elective revascularisation for coronary artery disease (CAD), particularly in patients with complex or multivessel CAD, left main involvement, diabetes mellitus, or left ventricular dysfunction. Despite the superiority of CABG in patients with the most advanced forms of CAD, a standard CABG operation, through a median sternotomy and with the use of cardiopulmonary bypass, carries well recognised challenges. In this article, we describe newer approaches, such as off-pump CABG, minimally invasive bypass grafting, robotic CABG, and hybrid coronary revascularisation, which we consider as necessary ways to minimise invasion, reduce recovery time, provide the benefits of arterial grafting to more patients, and offer alternatives to mitigate the adverse effects of conventional sternotomy and cardiopulmonary bypass.

The Canadian Cardiovascular Society Classification of Acute Atherothrombotic Myocardial Infarction Based on Stages of Tissue Injury Severity: An Expert Consensus Statement.

Myocardial infarction (MI) remains a leading cause of morbidity and mortality. In atherothrombotic MI (ST-elevation MI and type 1 non-ST-elevation MI), coronary artery occlusion leads to ischemia. Subsequent cardiomyocyte necrosis evolves over time as a wavefront within the territory at risk. The spectrum of ischemia and reperfusion injury is wide: it can be minimal in aborted MI or myocardial necrosis can be large and complicated by microvascular obstruction and reperfusion hemorrhage. Established risk scores and infarct classifications help with patient management but do not consider tissue injury characteristics. This document outlines the Canadian Cardiovascular Society classification of acute MI. It is an expert consensus formed on the basis of decades of data on atherothrombotic MI with reperfusion therapy. Four stages of progressively worsening myocardial tissue injury are identified: (1) aborted MI (no/minimal myocardial necrosis); (2) MI with significant cardiomyocyte necrosis, but without microvascular injury; (3) cardiomyocyte necrosis and microvascular dysfunction leading to microvascular obstruction (ie, "no-reflow"); and (4) cardiomyocyte and microvascular necrosis leading to reperfusion hemorrhage. Each stage reflects progression of tissue pathology of myocardial ischemia and reperfusion injury from the previous stage. Clinical studies have shown worse remodeling and increase in adverse clinical outcomes with progressive injury. Notably, microvascular injury is of particular importance, with the most severe form (hemorrhagic MI) leading to infarct expansion and risk of mechanical complications. This classification has the potential to stratify risk in MI patients and lay the groundwork for development of new, injury stage-specific and tissue pathology-based therapies for MI.

BEaTS-ß: an open-source electromechanical bioreactor for simulating human cardiac disease conditions.

Heart disease remains the leading cause of worldwide mortality. Although the last decades have broadened our understanding of the biology behind the pathologies of heart disease, ex vivo systems capable of mimicking disease progression and abnormal heart function using human cells remain elusive. In this contribution, an open-access electromechanical system (BEaTS-ß) capable of mimicking the environment of cardiac disease is reported. BEaTS-ß was designed using computer-aided modeling to combine tunable electrical stimulation and mechanical deformation of cells cultured on a flexible elastomer. To recapitulate the clinical scenario of a heart attack more closely, in designing BEaTS-ß we considered a device capable to operate under hypoxic conditions. We tested human induced pluripotent stem cell-derived cardiomyocytes, fibroblasts, and coronary artery endothelial cells in our simulated myocardial infarction environment. Our results indicate that, under simulated myocardium infarction, there was a decrease in maturation of cardiomyocytes, and reduced survival of fibroblasts and coronary artery endothelial cells. The open access nature of BEaTS-ß will allow for other investigators to use this platform to investigate cardiac cell biology or drug therapeutic efficacy in vitro under conditions that simulate arrhythmia and/or myocardial infarction.

Designing the coronary artery bypass surgery operation of the future.

PURPOSE OF REVIEW: This article discusses current shortcomings in coronary artery bypass surgery and ways to overcome them. RECENT FINDINGS: Minimally invasive coronary bypass surgery, robotic coronary bypass, and hybrid approaches aim to avoid sternotomy, employ arterial grafts, and minimize the use of cardiopulmonary bypass. Other considerations such as bypass graft validation, the optimization of guideline-directed medical therapy, and the development of coronary surgery specialists are also crucial to further the benefits of coronary artery bypass grafting on future patients. SUMMARY: Coronary artery bypass grafting must become less invasive, be better validated, and be carried out with an even higher emphasis on quality, including graft validation and preoperative/postoperative optimization, if it is to remain the best treatment for advanced, severe coronary artery disease.

Application of Cardiovascular Computed Tomography to the Assessment of Patients With Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy is a common inherited cardiac condition in which regional myocardial thickening and scarring can lead to a range of symptoms including breathlessness, dizziness, chest pain, and collapse with loss of consciousness. It is vital to be able to understand the mechanisms behind these epiphenomena and to be able to distinguish, for example, between syncope because of arrhythmia versus syncope because of mechanical outflow tract obstruction. Therefore, we require a technique that can characterize anatomy, physiology, and myocardial substrate. Traditionally, this role has been the preserve of cardiac magnetic resonance (CMR) imaging. This review makes the case for cardiac computed tomography (CT) as an alternative imaging method. We review the use of functional CT to identify the components of outflow tract obstruction (and obstruction at other levels, which may be simultaneous), and as an aid to interventional and surgical planning. We demonstrate the added value of multiplanar isotropic reformats in this condition, particularly in cases where the diagnosis may be more challenging or where complications (such as early apical aneurysm) may be difficult to recognize with 2-dimensional techniques. In conclusion, our aim is to convince readers that cardiac CT is a highly valuable and versatile tool, which deserves wider usage and greater recognition in those caring for patients with hypertrophic cardiomyopathy.

Optimizing care of patients undergoing cardiac surgery using a digital platform and a multidisciplinary team approach.

OBJECTIVE: Restrictions to care access during the pandemic along with the increasing complexity of patients awaiting cardiac surgery provides unique challenges for care delivery. The University of Ottawa Heart Institute has developed a novel multidisciplinary digital platform, the Prehab Automated Follow-Up (AFU) Program, which delivers patient/caregiver teaching regarding risk factor mitigation, tracks patient symptoms, and screens for optimization using best practice guidelines. This study was conducted to quantify patient outcomes following initiation of the AFU Program. METHODS: Patients awaiting elective cardiac surgery are enrolled and screened via automated telephone conversation, according to best practice guidelines, and a Short Form-12 preoperative assessment. Following this screen, patients are referred for an in-person assessment by an appropriate multidisciplinary team member; namely, a diabetes specialist, physiotherapist, dietitian, smoking cessation counselor, social worker, vocational counselor, and/or psychologist. RESULTS: Since initiation in February 2021, the AFU Program has enrolled more than 1237 patients with 508 multidisciplinary team referrals prompted by the AFU screening platform. Before program initiation, there were no multidisciplinary team referrals for preoperative optimization. Compared with patients treated between February 2020 and February 2021, there was a 2.5% decrease in hospital readmission rate within 30 days of surgery, a 0.6-day shorter hospital stay, and a 2.5% decrease in surgical site infection. CONCLUSIONS: Our cardiac surgery AFU Program reduced adverse health outcomes for patients by identifying and optimizing risk factors that increased quality of patient care. The AFU Program provides patient/caregiver engagement through educational support and multidisciplinary team counseling.

Long-term survival, cardiovascular, and functional outcomes after minimally invasive coronary artery bypass grafting in 566 patients.

OBJECTIVE: Sternotomy has been the gold standard incision for surgical revascularization but may be associated with chronic pain and sternal malunion. Minimally invasive coronary artery bypass grafting allows for complete surgical revascularization through a small thoracotomy in selected patients. There is a paucity of long-term data, particularly functional outcomes, for patients who underwent minimally invasive coronary artery bypass grafting. METHODS: Patients (N = 566) who underwent minimally invasive coronary artery bypass grafting at a single institution over a 17-year period were prospectively followed. The primary outcome was survival. At late follow-up, patients were contacted for a questionnaire on functional outcomes. Multivariable Cox proportional hazard model identified correlates of the primary outcome. RESULTS: Clinical follow-up was complete for 100% of patients (mean 7.0 ± 4.4 years); a follow-up questionnaire was also completed for 83.9% (N = 427) of live patients. Fifty percent of patients (N = 283) had undergone multivessel grafting. At 12 years, survival for the entire cohort was 82.2% ± 2.6%. On late follow-up questionnaire, 12 patients (2.8%) had greater than Canadian Cardiovascular Score Class II angina and 19 patients (4.5%) had greater than New York Heart Association Class II symptoms. More than 98% of patients did not have pain related to the incision site. Cox proportional hazards analysis identified older age, peripheral vascular disease, prior myocardial infarction, left ventricular dysfunction, cancer in the past 5 years, intraoperative transfusion, and hybrid revascularization as correlates of mortality during follow-up. CONCLUSIONS: Minimally invasive coronary artery bypass grafting is a safe and durable alternative to sternotomy coronary artery bypass grafting in selected patients, with excellent short- and long-term outcomes, including for multivessel coronary disease. At long-term follow-up, the proportion of patients with significant symptoms and incisional pain was low.

Expert systematic review on the choice of conduits for coronary artery bypass grafting: endorsed by the European Association for Cardio-Thoracic Surgery (EACTS) and The Society of Thoracic Surgeons (STS).

PREAMBLE: The finalized document was endorsed by the EACTS Council and STS Executive Committee before being simultaneously published in the European Journal of Cardio-thoracic Surgery (EJCTS) and The Annals of Thoracic Surgery (The Annals) and the Journal of Thoracic and Cardiovascular Surgery (JTCVS).

STICH3C: Rationale and Study Protocol.

BACKGROUND: Coronary artery bypass grafting (CABG) is the recommended mode of revascularization in patients with ischemic left ventricular dysfunction (iLVSD) and multivessel disease. However, contemporary percutaneous coronary intervention (PCI) outcomes have improved with the integration of novel technologies and refinement of revascularization strategies, and PCI is often used in clinical practice in this population. There is a lack of evidence from randomized trials comparing contemporary state-of-the-art PCI versus CABG for the treatment of iLVSD and multivessel disease. This was the impetus for the STICH3C trial (Canadian CABG or PCI in Patients With Ischemic Cardiomyopathy), described here. METHODS: The STICH3C trial is a prospective, unblinded, international, multicenter trial with an expected sample size of 754 participants from ≈45 centers. Patients with multivessel/left main coronary artery disease and iLVSD with left ventricular ejection fraction ≤40% considered by the local Heart Team appropriate for and amenable to revascularization by both modes of revascularization will be randomized in a 1:1 ratio to state-of-the-art PCI or CABG. RESULTS: The primary end point is the composite of death from any cause, stroke, spontaneous myocardial infarction, urgent repeat revascularization, or heart failure readmission, summarized as a time-to-event outcome. The key hierarchical end point is time to death and frequency of hospitalizations for heart failure. The key safety outcome is a composite of major adverse events. Disease-specific quality-of-life and health economics measures will be compared between groups. Participants will be followed for a median of 5 years, with a minimum follow-up of 4 years. CONCLUSIONS: STICH3C will directly inform patients, clinicians, and international practice guidelines about the efficacy and safety of CABG versus PCI in patients with iLVSD. The results will provide novel and broad evidence, including clinical events, health status, and economic assessments, to guide care for patients with iLVSD and severe coronary artery disease. REGISTRATION: URL: https://clinicaltrials.gov/; Unique identifier: NCT05427370.

Graft Failure After Coronary Artery Bypass Grafting and Its Association With Patient Characteristics and Clinical Events: A Pooled Individual Patient Data Analysis of Clinical Trials With Imaging Follow-Up.

BACKGROUND: Graft patency is the postulated mechanism for the benefits of coronary artery bypass grafting (CABG). However, systematic graft imaging assessment after CABG is rare, and there is a lack of contemporary data on the factors associated with graft failure and on the association between graft failure and clinical events after CABG. METHODS: We pooled individual patient data from randomized clinical trials with systematic CABG graft imaging to assess the incidence of graft failure and its association with clinical risk factors. The primary outcome was the composite of myocardial infarction or repeat revascularization occurring after CABG and before imaging. A 2-stage meta-analytic approach was used to evaluate the association between graft failure and the primary outcome. We also assessed the association between graft failure and myocardial infarction, repeat revascularization, or all-cause death occurring after imaging. RESULTS: Seven trials were included comprising 4413 patients (mean age, 64.4±9.1 years; 777 [17.6%] women; 3636 [82.4%] men) and 13 163 grafts (8740 saphenous vein grafts and 4423 arterial grafts). The median time to imaging was 1.02 years (interquartile range [IQR], 1.00-1.03). Graft failure occurred in 1487 (33.7%) patients and in 2190 (16.6%) grafts. Age (adjusted odds ratio [aOR], 1.08 [per 10-year increment] [95% CI, 1.01-1.15]; P=0.03), female sex (aOR, 1.27 [95% CI, 1.08-1.50]; P=0.004), and smoking (aOR, 1.20 [95% CI, 1.04-1.38]; P=0.01) were independently associated with graft failure, whereas statins were associated with a protective effect (aOR, 0.74 [95% CI, 0.63-0.88]; P<0.001). Graft failure was associated with an increased risk of myocardial infarction or repeat revascularization occurring between CABG and imaging assessment (8.0% in patients with graft failure versus 1.7% in patients without graft failure; aOR, 3.98 [95% CI, 3.54-4.47]; P<0.001). Graft failure was also associated with an increased risk of myocardial infarction or repeat revascularization occurring after imaging (7.8% versus 2.0%; aOR, 2.59 [95% CI, 1.86-3.62]; P<0.001). All-cause death after imaging occurred more frequently in patients with graft failure compared with patients without graft failure (11.0% versus 2.1%; aOR, 2.79 [95% CI, 2.01-3.89]; P<0.001). CONCLUSIONS: In contemporary practice, graft failure remains common among patients undergoing CABG and is strongly associated with adverse cardiac events.