Remotely Triggered LAD Occlusion Using a Balloon Catheter in Spontaneously Breathing Mice.

Acute myocardial infarction (AMI) is a prevalent and high-mortality cardiovascular condition. Despite advancements in revascularization strategies for AMI, it frequently leads to myocardial ischemia-reperfusion injury (IRI), amplifying cardiac damage. Murine models serve as vital tools for investigating both acute injury and chronic myocardial remodeling in vivo. This study presents a unique closed-chest technique for remotely inducing myocardial IRI in mice, enabling the investigation of the very early phase of occlusion and reperfusion using in-vivo imaging such as MRI or PET. The protocol utilizes a remote occlusion method, allowing precise control over ischemia initiation after chest closure. It reduces surgical trauma, enables spontaneous breathing, and enhances experimental consistency. What sets this technique apart is its potential for simultaneous noninvasive imaging, including ultrasound and magnetic resonance imaging (MRI), during occlusion and reperfusion events. It offers a unique opportunity to analyze tissue responses in almost real-time, providing critical insights into processes during ischemia and reperfusion. Extensive systematic testing of this innovative approach was conducted, measuring cardiac necrosis markers for infarction, assessing the area at risk using contrast-enhanced MRI, and staining infarcts at the scar maturation stage. Through these investigations, emphasis was placed on the value of the proposed tool in advancing research approaches to myocardial ischemia-reperfusion injury and accelerating the development of targeted interventions. Preliminary findings demonstrating the feasibility of combining the proposed innovative experimental protocol with noninvasive imaging techniques are presented herein. These initial results highlight the benefit of utilizing the purpose-built animal cradle to remotely induce myocardial ischemia while simultaneously conducting MRI scans.

Optimization of Absolute Coronary Blood Flow Measurements to Assess Microvascular Function: In Vivo Validation of Hyperemia and Higher Infusion Speeds.

BACKGROUND: Reliable assessment of coronary microvascular function is essential. Techniques to measure absolute coronary blood flow are promising but need validation. The objectives of this study were: first, to validate the potential of saline infusion to generate maximum hyperemia in vivo. Second, to validate absolute coronary blood flow measured with continuous coronary thermodilution at high (40-50 mL/min) infusion speeds and asses its safety. METHODS: Fourteen closed-chest sheep underwent absolute coronary blood flow measurements with increasing saline infusion speeds at different dosages under general anesthesia. An additional 7 open-chest sheep underwent these measurements with epicardial Doppler flow probes. Coronary flows were compared with reactive hyperemia after 45 s of coronary occlusion. RESULTS: Twenty milliliters per minute of saline infusion induced a significantly lower hyperemic coronary flow (140 versus 191 mL/min; P=0.0165), lower coronary flow reserve (1.82 versus 3.21; P≤0.0001), and higher coronary resistance (655 versus 422 woods units; P=0.0053) than coronary occlusion. On the other hand, 30 mL/min of saline infusion resulted in hyperemic coronary flow (196 versus 192 mL/min; P=0.8292), coronary flow reserve (2.77 versus 3.21; P=0.1107), and coronary resistance (415 versus 422 woods units; P=0.9181) that were not different from coronary occlusion. Hyperemic coronary flow was 40.7% with 5 mL/min, 40.8% with 10 mL/min, 73.1% with 20 mL/min, 102.3% with 30 mL/min, 99.0% with 40 mL/min, and 98.0% with 50 mL/min of saline infusion when compared with postocclusive hyperemic flow. There was a significant bias toward flow overestimation (Bland-Altman: bias±SD, -73.09±30.52; 95% limits of agreement, -132.9 to -13.27) with 40 to 50 mL/min of saline. Occasionally, ischemic changes resulted in ventricular fibrillation (9.5% with 50 mL/min) at higher infusion rates. CONCLUSIONS: Continuous saline infusion of 30 mL/min but not 20 mL/min induced maximal hyperemia. Absolute coronary blood flow measured with saline infusion speeds of 40 to 50 mL/min was not accurate and not safe.

An interventional sheep model of severe aortic valve stenosis hemodynamics for the evaluation of alterations in coronary physiology and microvascular function.

We aimed to develop a large animal model of subcoronary aortic stenosis (AS) to study intracoronary and microcirculatory hemodynamics. A total of three surgical techniques inducing AS were evaluated in 12 sheep. Suturing the leaflets together around a dilator (n = 2) did not result in severe AS. Suturing of a pericardial patch with a variable opening just below the aortic valve (n = 5) created an AS which was poorly tolerated if the aortic valve area (AVA) was too small (0.38-1.02 cm2), but was feasible with an AVA of 1.2 cm2. However, standardization of aortic regurgitation (AR) with this technique is difficult. Therefore, we opted for implantation of an undersized AV-bioprosthesis with narrowing sutures on the leaflets (n = 5). Overall, five sheep survived the immediate postoperative period of which three had severe AS (one patch and two bioprostheses). The surviving sheep with severe AS developed left ventricular hypertrophy and signs of increased filling-pressures. Intracoronary assessment of physiological indices in these AS sheep pointed toward the development of functional microvascular dysfunction, with a significant increase in coronary resting flow and hyperemic coronary resistance, resulting in a significantly higher index of microvascular resistance (IMR) and lower myocardial resistance reserve (MRR). Microscopic analysis showed myocardial hypertrophy and signs of fibrosis without evidence of capillary rarefaction. In a large animal model of AS, microvascular changes are characterized by increased resting coronary flow and hyperemic coronary resistance resulting in increased IMR and decreased MRR. These physiological changes can influence the interpretation of regularly used coronary indices.NEW & NOTEWORTHY In an animal model of aortic valve stenosis (AS), coronary physiological changes are characterized by increased resting coronary flow and hyperemic coronary resistance. These changes can impact coronary indices frequently used to assess concomitant coronary artery disease (CAD). At this point, the best way to assess and treat CAD in AS remains unclear. Our data suggest that fractional flow reserve may underestimate CAD, and nonhyperemic pressure ratios may overestimate CAD severity before aortic valve replacement.

Erector spinae plane block for postoperative analgesia in robotically-assisted coronary artery bypass surgery: Results of a randomized placebo-controlled trial.

STUDY OBJECTIVE: To investigate if an erector spinae plane (ESP) block decreases postoperative opioid consumption, pain and postoperative nausea and vomiting in patients undergoing robotically-assisted minimally invasive direct coronary artery bypass surgery (RAMIDCAB). DESIGN: A single-center, double-blind, prospective, randomized, placebo-controlled trial. SETTING: Postoperative period; operating room, post-anesthesia care unit (PACU) and hospital ward in a university hospital. PATIENTS: Sixty-four patients undergoing RAMIDCAB surgery via left-sided mini-thoracotomy and enrolled in the institutional enhanced recovery after cardiac surgery program. INTERVENTIONS: At the end of surgery, patients received an ESP catheter at vertebra T5 under ultrasound guidance and were randomized to the administration of either ropivacaine 0.5% (loading dose of 30 ml and three additional doses of 20 ml each, interspersed with a 6 h interval) or normal saline 0.9% (with an identical administration scheme). In addition, patients received multimodal analgesia including acetaminophen, dexamethasone and patient-controlled analgesia with morphine. Following the final ESP bolus and before catheter removal, the position of the catheter was re-evaluated by ultrasound. Patients, investigators and medical personnel were blinded for the group allocation during the entire trial. MEASUREMENTS: Primary outcome was cumulative morphine consumption during the first 24 h after extubation. Secondary outcomes included location and severity of pain, presence/extent of sensory block, duration of postoperative ventilation and hospital length of stay. Safety outcomes comprised the incidence of adverse events. MAIN RESULTS: Median (IQR) 24-h morphine consumption was not different between the intervention- and control-groups, 67 mg (35-84) versus 71 mg (52-90) (p = 0.25), respectively. Likewise, no differences were detected in secondary and safety endpoints. CONCLUSIONS: Following RAMIDCAB surgery, adding an ESP block to a standard multimodal analgesia regimen did not reduce opioid consumption and pain scores.

Myocardial ischemia-reperfusion injury and the influence of inflammation.

Acute myocardial infarction is caused by a sudden coronary artery occlusion and leads to ischemia in the corresponding myocardial territory which generally results in myocardial necrosis. Without restoration of coronary perfusion, myocardial scar formation will cause adverse remodelling of the myocardium and heart failure. Successful introduction of percutaneous coronary intervention and surgical coronary artery bypass grafting made it possible to achieve early revascularisation/reperfusion, hence limiting the ischemic zone of myocardium. However, reperfusion by itself paradoxically triggers an exacerbated and accelerated injury in the myocardium, called ischemia-reperfusion (I/R) injury. This mechanism is partially driven by inflammation through multiple interacting pathways. In this review we summarize the current insights in mechanisms of I/R injury and the influence of altered inflammation. Multiple pharmacological and interventional therapeutic strategies (ischemic conditioning) have proven to be beneficial during I/R in preclinical models but were notoriously unsuccessful upon clinical translation. In this review we focus on common mechanisms of I/R injury, altered inflammation and potential therapeutic strategies. We hypothesize that a dual approach may be of value because I/R injury patients are predestined with multiple comorbidities and systemic low-grade inflammation, which requires targeted intervention before other strategies can be fully effective.

Robotic-assisted MIDCAB procedure through a minithoracotomy: Step-by-step instructions.

Minimally invasive cardiac surgery has evolved in recent years. Complex minimally invasive surgical techniques can further reduce the morbidity associated with surgical coronary bypass grafting. Robotic-assisted minimally invasive direct coronary artery bypass grafting is an effective and safe procedure in all risk groups. More experience with this procedure over the coming years should lead to the implementation of guidelines and the incorporation in heart-team decisions of schemes for individual patient care. We present a young male patient with familial hypercholesterolemia and chronic total occlusion of the left anterior descending artery (LAD) treated in January 2021 with a robotic-assisted minimally invasive direct coronary artery bypass graft through a minithoracotomy. The procedure was. The patient showed a fast recovery from the uncomplicated procedure and was discharged from the hospital after 3 days. We prepared this case report to facilitate training for this complex technical procedure. Robotic-assisted MIDCAB through a minithoracotomy is a technically demanding but safe minimally invasive alternative to coronary artery bypass grafting in patients with severe coronary lesions not suitable for percutaneous coronary intervention. In a hybrid coronary revascularization strategy, this technique minimizes surgical risk and optimizes long-term outcomes with high patency of surgical grafts.

Arteriovenous Fistulae in Chronic Kidney Disease and the Heart: Physiological, Histological, and Transcriptomic Characterization of a Novel Rat Model.

Background Arteriovenous fistulae (AVFs) are the gold standard for vascular access in those requiring hemodialysis but may put an extra hemodynamic stress on the cardiovascular system. The complex interactions between the heart, kidney, and AVFs remain incompletely understood. Methods and Results We characterized a novel rat model of five-sixths partial nephrectomy (NX) and AVFs. NX induced increases in urea, creatinine, and hippuric acid. The addition of an AVF (AVF+NX) further increased urea and a number of uremic toxins such as trimethylamine N-oxide and led to increases in cardiac index, left and right ventricular volumes, and right ventricular mass. Plasma levels of uremic toxins correlated well with ventricular morphology and function. Heart transcriptomes identified altered expression of 8 genes following NX and 894 genes following AVF+NX, whereas 290 and 1431 genes were altered in the kidney transcriptomes, respectively. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis revealed gene expression changes related to cell division and immune activation in both organs, suppression of ribosomes and transcriptional activity in the heart, and altered renin-angiotensin signaling as well as chronodisruption in the kidney. All except the latter were worsened in AVF+NX compared with NX. Conclusions Inflammation and organ dysfunction in chronic kidney disease are exacerbated following AVF creation. Furthermore, our study provides important information for the discovery of novel biomarkers and therapeutic targets in the management of cardiorenal syndrome.

TRPM4 inhibition by meclofenamate suppresses Ca2+-dependent triggered arrhythmias.

AIMS: Cardiac arrhythmias are a major factor in the occurrence of morbidity and sudden death in patients with cardiovascular disease. Disturbances of Ca2+ homeostasis in the heart contribute to the initiation and maintenance of cardiac arrhythmias. Extrasystolic increases in intracellular Ca2+ lead to delayed afterdepolarizations and triggered activity, which can result in heart rhythm abnormalities. It is being suggested that the Ca2+-activated nonselective cation channel TRPM4 is involved in the aetiology of triggered activity, but the exact contribution and in vivo significance are still unclear. METHODS AND RESULTS: In vitro electrophysiological and calcium imaging technique as well as in vivo intracardiac and telemetric electrocardiogram measurements in physiological and pathophysiological conditions were performed. In two distinct Ca2+-dependent proarrhythmic models, freely moving Trpm4-/- mice displayed a reduced burden of cardiac arrhythmias. Looking further into the specific contribution of TRPM4 to the cellular mechanism of arrhythmias, TRPM4 was found to contribute to a long-lasting Ca2+ overload-induced background current, thereby regulating cell excitability in Ca2+ overload conditions. To expand these results, a compound screening revealed meclofenamate as a potent antagonist of TRPM4. In line with the findings from Trpm4-/- mice, 10 µM meclofenamate inhibited the Ca2+ overload-induced background current in ventricular cardiomyocytes and 15 mg/kg meclofenamate suppressed catecholaminergic polymorphic ventricular tachycardia-associated arrhythmias in a TRPM4-dependent manner. CONCLUSION: The presented data establish that TRPM4 represents a novel target in the prevention and treatment of Ca2+-dependent triggered arrhythmias.

Corrigendum: Robotic Cardiac Surgery in Europe: Status 2020.

[This corrects the article DOI: 10.3389/fcvm.2021.827515.].

Coronary revascularization in patients with HIV.

With combined antiretroviral therapy, people living with HIV (PLWH) survive longer and are now more likely to die from cardiovascular diseases. PLWH presenting with a ST-segment elevation myocardial infarction are likely to have a high thrombus burden and are at high risk for in-hospital and long-term adverse events. An increasing number of PLWH are presenting with stable coronary artery disease related to atherosclerosis. Revascularization in these patients is associated with higher in-hospital and long-term major adverse cardiovascular events, including stent thrombosis and in-stent restenosis. However, data in this expanding population concerning optimal revascularization strategy are still lacking. In particular, data comparing percutaneous versus surgical revascularization in PLWH are needed. In this review we highlight the currently available data related to coronary revascularization in PLWH.

Revascularization strategies in patients with multivessel coronary artery disease: a Bayesian network meta-analysis.

Treatment modalities for multivessel disease have rapidly evolved, yet the preferred strategy remains controversial. This meta-analysis compared outcomes after on-pump (ONCAB), off-pump coronary artery bypass grafting (OPCAB), percutaneous coronary intervention (PCI) or hybrid coronary revascularization. A comprehensive search for observational studies and randomized controlled trials published by August 2020 was performed. A Bayesian network meta-analysis was conducted for early (<30 days) and late (>12 months) outcomes. A total of 119 studies were included (n = 700 458 patients). The main analysis was confined to 31 randomized controlled trials (n = 24 932 patients). PCI was associated with lower early mortality [odds ratio (OR) 0.50, 95% confidence interval (CI) 0.31-0.79] and stroke (OR 0.22, 95% CI 0.06-0.60) rates compared with ONCAB, whereas a reduced risk of early myocardial infarction was observed with OPCAB compared with ONCAB (OR 0.53, 95% CI 0.32-0.83). Late target vessel revascularization and major adverse cardiac and cerebrovascular events were both increased with PCI compared with ONCAB, OPCAB and hybrid coronary revascularization (by 127-203% and 59-64%, respectively), and late major adverse cardiac events were increased in PCI compared with ONCAB and OPCAB (by 64% and 59%). However, PCI was associated with a significantly lower risk of late stroke compared with ONCAB (OR 0.70, 95% CI 0.52-0.89). Sensitivity analyses (i) including observational studies and (ii) limiting to studies with recent cohorts confirmed the findings of the main analysis. Surgical approaches for revascularization remain superior to PCI in patients with multivessel disease. Hybrid coronary revascularization might be viable for some patients, although more evidence from randomized controlled trials is warranted.

Hybrid coronary revascularization versus percutaneous coronary intervention: A systematic review and meta-analysis.

BACKGROUND: Hybrid coronary revascularization (HCR) is an emerging approach for multivessel coronary artery disease (MVD) which combines the excellent long-term outcomes of surgery with the early recovery and reduced short-term complications of percutaneous coronary intervention (PCI). Here, we evaluated the effectiveness of HCR compared to PCI in patients with MVD. METHODS: A systematic database search in PubMed/MEDLINE, Embase, Scopus, and CENTRAL/CCTR was conducted by June 2021. Random-effects meta-analysis was performed, comparing major adverse cardiac and cerebrovascular events (MACCE) at 30 days and at latest follow-up between patients undergoing HCR versus PCI. RESULTS: A total of 27,041 patients (HCR: 939 patients, PCI: 26,102 patients) were included from seven studies published between 2013 and 2021. At latest follow-up, HCR was associated with lower rates of myocardial infarction (OR 0.40, 95% CI 0.20-0.80, p = 0.010) and target vessel revascularization (OR 0.49, 95% CI 0.37-0.64, p < 0.001), while the difference for MACCE did not reach statistical significance (OR 0.46, 95% CI 0.20-1.05, p = 0.061). No differences were observed in terms of 30-day outcomes, nor rates of mortality or stroke at latest follow-up. CONCLUSIONS: HCR might be a valid alternative to multivessel PCI, demonstrating a lower incidence of MI and TVR. Center experience, well-coordinated heart team discussions, and good patient selection likely remain essential to ensure optimal outcomes. Future comparative studies are required to define the optimal target population.

Safe implementation of robotic-assisted minimally invasive direct coronary artery bypass: application of learning curves and cumulative sum analysis.

BACKGROUND: Learning curves are inevitably encountered when first implementing an innovative and complex surgical technique. Nevertheless, a cluster of failures or complications should be detected early, but not deter learning, to ensure safe implementation. Here, we aimed to examine the presence and impact of learning curves on outcome after robotic-assisted minimally invasive direct coronary artery bypass (RA-MIDCAB). METHODS: A retrospective analysis of the first 300 RA-MIDCAB surgeries between July 2015 and December 2020 was performed. Learning curves were obtained via logarithmic regression for surgical time. Cumulative sum (CUSUM) analysis was performed for (I) major complications including MI, stroke, repeat revascularization, and mortality, and (II) other complications, including prolonged ventilation, pneumonia, pleura puncture, lung herniation, pericarditis, pleuritis, arrhythmia, wound complications, and delirium. Expected and unacceptable rates were set at 12% and 20%, respectively, for major complications, and at 40% and 60% for other complications, based on historical data in conventional coronary artery bypass grafting (CABG). RESULTS: Demographic characteristics did not differ between terciles, except for more smokers in the first tercile, and less hypercholesterolemia and more complex procedures in the third tercile. The mean surgical time for all operations was 258±81 minutes, ranging from 127 to 821 minutes. A learning curve was only observed in the first tercile. Subgroup analysis revealed that this learning curve was only observed for procedures consisting of single internal mammary artery (SIMA) with 1 or 2 distal anastomoses but not with bilateral internal mammary arteries (BIMA) or more than 2 distal anastomoses. CUSUM analysis showed that the cumulative rate of major and other complications never crossed the lines for unacceptable rates. Rather, the lower 95% confidence boundary was crossed after 50 cases, indicating improvement in safety. CONCLUSIONS: These results suggest that integration of RA-MIDCAB in the surgical landscape can be safely achieved and complication rates can quickly be reduced below those expected in traditional CABG. Collective experience plays a key role in overcoming the learning curve when more complex procedures and cases are introduced.

Antithrombotic Treatment After Surgical and Transcatheter Heart Valve Repair and Replacement.

New antithrombotic drugs have been developed, new valve types have been designed and minimally invasive transcatheter techniques have emerged, making the choice of antithrombotic therapy after surgical or transcatheter heart valve repair and replacement increasingly complex. Moreover, due to a lack of large randomized controlled trials many recommendations for antithrombotic therapy are based on expert opinion, reflected by divergent recommendations in current guidelines. Therefore, decision-making in clinical practice regarding antithrombotic therapy for prosthetic heart valves is difficult, potentially resulting in sub-optimal patient treatment. This article compares the 2017 ESC/EACTS and 2020 ACC/AHA guidelines on the management of valvular heart disease and summarizes the available evidence. Finally, we established a convenient consensus on antithrombotic therapy after valve interventions based on over 800 annual cases of surgical and transcatheter heart valve repair and replacement and a multidisciplinary team discussion between the department of cardiovascular diseases and cardiac surgery of the University Hospitals Leuven, Belgium.