Intraoperative Evaluation of Transmitral Pressure Gradients after Edge-to-Edge Mitral Valve Repair

Objective: Edge-to-edge repair of the mitral valve (MV) has been described as a viable option used for the surgical management of mitral regurgitation (MR). Based on the significant changes in MV geometry associated with this technique, we hypothesized that edge-to-edge MV repairs are associated with higher intraoperative transmitral pressure gradients (TMPG) compared to conventional methods. Methods: Patient records and intraoperative transesophageal echocardiography (TEE) examinations of 552 consecutive patients undergoing MV repair at a single institution over a three year period were assessed. After separation from cardiopulmonary bypass (CPB), peak and mean TMPG were recorded for each patient and subsequently analyzed. Results: 84 patients (15%) underwent edge-to-edge MV repair. Peak and mean TMPG were significantly higher compared to gradients in patients undergoing conventional repairs: 10.7±0.5 mmHg vs 7.1±0.2 mmHg; P<0.0001 and 4.3±0.2 mmHg vs 2.8±0.1 mmHg; P<0.0001. Only patients with mean TMPG ≥7 mmHg (n = 9) required prompt reoperation for iatrogenic mitral stenosis (MS). No differences in peak and mean TMPG were observed among edge-to-edge repairs performed in isolation, compared to those performed in combination with annuloplasty: 11.0±0.7 mmHg vs 10.3±0.6 mmHg and 4.4±0.3 mmHg vs 4.3±0.3 mmHg. There were no differences in TMPG between various types of annuloplasty techniques used in combination with the edge-to-edge repairs. Conclusions: Edge-to-edge MV repairs are associated with higher intraoperative peak and mean TMPG after separation from CPB compared to conventional repair techniques. Unless gradients are severely elevated, these findings are not necessarily suggestive of iatrogenic MS. Thus, in the immediate postoperative period mildly elevated TMPG can be expected and tolerated after edge-to-edge mitral repairs

Evaluation of Transmitral Pressure Gradients in the Intraoperative Echocardiographic Diagnosis of Mitral Stenosis after Mitral Valve Repair

OBJECTIVE: Acute mitral stenosis (MS) following mitral valve (MV) repair is a rare but severe complication. We hypothesize that intraoperative echocardiography can be utilized to diagnose iatrogenic MS immediately after MV repair. METHODS: The medical records of 552 consecutive patients undergoing MV repair at a single institution were reviewed. Post-cardiopulmonary bypass peak and mean transmitral pressure gradients (TMPG), and pressure half time (PHT) were obtained from intraoperative transesophageal echocardiographic (TEE) examinations in each patient. RESULTS: Nine patients (9/552 = 1.6%) received a reoperation for primary MS, prior to hospital discharge. Interestingly, all of these patients already showed intraoperative post-CPB mean and peak TMPGs that were significantly higher compared to values for those who did not: 10.7±4.8 mmHg vs 2.9±1.6 mmHg; p<0.0001 and 22.9±7.9 mmHg vs 7.6±3.7 mmHg; p<0.0001, respectively. However, PHT varied considerably (87±37 ms; range: 20-439 ms) within the entire population, and only weakly predicted the requirement for reoperation (113±56 vs. 87±37 ms, p = 0.034). Receiver operating characteristic curves showed strong discriminating ability for mean gradients (AUC = 0.993) and peak gradients (area under the curve, AUC = 0.996), but poor performance for PHT (AUC = 0.640). A value of ≥7 mmHg for mean, and ≥17 mmHg for peak TMPG, best separated patients who required reoperation for MS from those who did not. CONCLUSIONS: Intraoperative TEE diagnosis of a peak TMPG ≥17 mmHg or mean TMPG ≥7 mmHg immediately following CPB are suggestive of clinically relevant MS after MV repair

Descending aortic calcification increases renal dysfunction and in-hospital mortality in cardiac surgery patients with intraaortic balloon pump counterpulsation placed perioperatively : a case control study

Introduction: Acute kidney injury (AKI) after cardiac surgery increases length of hospital stay and in-hospital mortality. A significant number of patients undergoing cardiac surgical procedures require perioperative intra-aortic balloon pump (IABP) support. Use of an IABP has been linked to an increased incidence of perioperative renal dysfunction and death. This might be due to dislodgement of atherosclerotic material in the descending thoracic aorta (DTA). Therefore, we retrospectively studied the correlation between DTA atheroma, AKI and in-hospital mortality. Methods: A total of 454 patients were retrospectively matched to one of four groups: -IABP/-DTA atheroma, +IABP/-DTA atheroma, -IABP/+DTA atheroma, +IABP/+DTA atheroma. Patients were then matched according to presence/absence of DTA atheroma, presence/absence of IABP, performed surgical procedure, age, gender and left ventricular ejection fraction (LVEF). DTA atheroma was assessed through standard transesophageal echocardiography (TEE) imaging studies of the descending thoracic aorta. Results: Basic patient characteristics, except for age and gender, did not differ between groups. Perioperative AKI in patients with -DTA atheroma/+IABP was 5.1% versus 1.7% in patients with -DTA atheroma/-IABP. In patients with +DTA atheroma/+IABP the incidence of AKI was 12.6% versus 5.1% in patients with +DTA atheroma/-IABP. In-hospital mortality in patients with +DTA atheroma/-IABP was 3.4% versus 8.4% with +DTA atheroma/+IABP. In patients with +DTA atheroma/+IABP in hospital mortality was 20.2% versus 6.4% with +DTA atheroma/-IABP. Multivariate logistic regression identified DTA atheroma > 1 mm (P = *0.002, odds ratio (OR) = 4.13, confidence interval (CI) = 1.66 to 10.30), as well as IABP support (P = *0.015, OR = 3.04, CI = 1.24 to 7.45) as independent predictors of perioperative AKI and increased in-hospital mortality. DTA atheroma in conjunction with IABP significantly increased the risk of developing acute kidney injury (P = 0.0016) and in-hospital mortality (P = 0.0001) when compared to control subjects without IABP and without DTA atheroma. Conclusions: Perioperative IABP and DTA atheroma are independent predictors of perioperative AKI and in-hospital mortality. Whether adding an IABP in patients with severe DTA calcification increases their risk of developing AKI and mortality postoperatively cannot be clearly answered in this study. Nevertheless, when IABP and DTA are combined, patients are more likely to develop AKI and to die postoperatively in comparison to patients without IABP and DTA atheroma

C-Reactive Protein Gene Variants Are Associated with Postoperative C-reactive Protein Levels After Coronary Artery Bypass Surgery

Background: Elevated baseline C-reactive protein (CRP) levels are associated with increased risk for developing cardiovascular disease. Several CRP gene variants have been associated with altered baseline CRP levels in ambulatory populations. However, the influence of CRP gene variants on CRP levels during inflammatory states, such as surgery, is largely unexplored. We describe the association between candidate CRP gene variants and postoperative plasma CRP levels in patients undergoing primary, elective coronary artery bypass graft (CABG) surgery with cardiopulmonary bypass (CPB). Methods: Using a multicenter candidate gene association study design, we examined the association between seventeen candidate CRP single nucleotide polymorphisms (SNPs) and inferred haplotypes, and altered postoperative CRP levels in 604 patients undergoing CABG surgery with CPB. Perioperative CRP levels were measured immediately prior to surgery, post-CPB and on postoperative days (POD) 1–4. Results: CRP levels were significantly elevated at all postoperative time points when compared with preoperative levels (P < 0.0001). After adjusting for clinical covariates, the minor allele of the synonymous coding SNP, rs1800947 was associated with lower peak postoperative CRP levels ($P = 2.4 × 10^{-4}$) and lower CRP levels across all postoperative time points ($P = 4.8 × 10^{-5}$). rs1800947 remained highly significant after Bonferroni adjustment for multiple comparisons. Conclusion: We identified a CRP gene SNP associated with lower postoperative CRP levels in patients undergoing CABG surgery with CPB. Further investigation is needed to clarify the significance of this association between CRP gene variants and the acute-phase rise in postoperative CRP levels with regard to the risk of adverse postoperative outcomes

Profilin-1 Is Expressed in Human Atherosclerotic Plaques and Induces Atherogenic Effects on Vascular Smooth Muscle Cells

.Here we monitored profilin-1 expression in human atherosclerotic plaques by immunofluorescent staining. The effects of recombinant profilin-1 on atherogenic signaling pathways and cellular responses such as DNA synthesis (BrdU-incorporation) and chemotaxis (modified Boyden-chamber) were evaluated in cultured rat aortic and human coronary vascular smooth muscle cells (VSMCs). Furthermore, the correlation between profilin-1 serum levels and the degree of atherosclerosis was assessed in humans.<0.001 vs. no atherosclerosis or control group).Profilin-1 expression is significantly enhanced in human atherosclerotic plaques compared to the normal vessel wall, and the serum levels of profilin-1 correlate with the degree of atherosclerosis in humans. The atherogenic effects exerted by profilin-1 on VSMCs suggest an auto-/paracrine role within the plaque. These data indicate that profilin-1 might critically contribute to atherogenesis and may represent a novel therapeutic target

Live 3-Dimensional Transesophageal Echocardiography Initial Experience Using the Fully-Sampled Matrix Array Probe

ObjectivesOur study goals were to evaluate the 3-dimensional matrix array transesophageal echocardiographic (3D-MTEE) probe by assessing the image quality of native valves and other intracardiac structures.BackgroundBecause 3-dimensional transesophageal echocardiography with gated rotational acquisition is not used routinely as the result of artifacts, lengthy acquisition, and processing, a 3D-MTEE probe was developed (Philips Medical Systems, Andover, Massachusetts).MethodsIn 211 patients, 3D-MTEE zoom images of the mitral valve (MV), aortic valve, tricuspid valve, interatrial septum, and left atrial appendage were obtained, followed by a left ventricular wide-angled acquisition. Images were reviewed and graded off-line (Xcelera with QLAB software, Philips Medical Systems).ResultsExcellent visualization of the MV (85% to 91% for all scallops of both MV leaflets), interatrial septum (84%), left atrial appendage (86%), and left ventricle (77%) was observed. Native aortic and tricuspid valves were optimally visualized only in 18% and 11% of patients, respectively.ConclusionsThe use of 3D-MTEE imaging, which is feasible in most patients, provides superb imaging of native MVs, which makes this modality an excellent choice for MV surgical planning and guidance of percutaneous interventions. Optimal aortic and tricuspid valve imaging will depend on further technological developments. Fast acquisition and immediate online display will facilitate wider acceptance and routine use in clinical practice

Joint analysis of left ventricular expression and circulating plasma levels of Omentin after myocardial ischemia

BACKGROUND: Omentin-1, also known as Intelectin-1 (ITLN1), is an adipokine with plasma levels associated with diabetes, obesity, and coronary artery disease. Recent studies suggest that ITLN1 can mitigate myocardial ischemic injury but the expression of ITLN1 in the heart itself has not been well characterized. The purpose of this study is to discern the relationship between the expression pattern of ITLN1 RNA in the human heart and the level of circulating ITLN1 protein in plasma from the same patients following myocardial ischemia. METHODS: A large cohort of patients (n = 140) undergoing elective cardiac surgery for aortic valve replacement were enrolled in this study. Plasma and left ventricular biopsy samples were taken at the beginning of cardiopulmonary bypass and after an average of 82 min of ischemic cross clamp time. The localization of ITLN1 in epicardial adipose tissue (EAT) was also further characterized with immunoassays and cell fate transition studies. RESULTS: mRNA expression of ITLN1 decreases in left ventricular tissue after acute ischemia in human patients (mean difference 280.48, p = 0.001) whereas plasma protein levels of ITLN1 increase (mean difference 5.24, p \u3c 0.001). Immunohistochemistry localized ITLN1 to the mesothelium or visceral pericardium of EAT. Epithelial to mesenchymal transition in mesothelial cells leads to a downregulation of ITLN1 expression. CONCLUSIONS: Myocardial injury leads to a decrease in ITLN1 expression in the heart and a corresponding increase in plasma levels. These changes may in part be due to an epithelial to mesenchymal transition of the cells that express ITLN1 following ischemia. Trial Registration Clinicaltrials.gov ID: NCT00985049

The Long Noncoding RNA Landscape of the Ischemic Human Left Ventricle

Background—The discovery of functional classes of long noncoding RNAs (lncRNAs) has expanded our understanding of the variety of RNA species that exist in cells. In the heart, lncRNAs have been implicated in the regulation of development, ischemic and dilated cardiomyopathy, and myocardial infarction. Nevertheless, there is a limited description of expression profiles for these transcripts in human subjects. Methods and Results—We obtained left ventricular tissue from human patients undergoing cardiac surgery and used RNA sequencing to describe a lncRNA profile. We then identified a list of lncRNAs that were differentially expressed between pairs of samples before and after the ischemic insult of cardiopulmonary bypass. The expression of some of these lncRNAs correlates with ischemic time. Coding genes in close proximity to differentially expressed lncRNAs as well as coding genes that have coordinated expression with these lncRNAs are enriched in functional categories related to myocardial infarction including: heart function, metabolism, the stress response, and the immune system. Conclusions—We describe a list of lncRNAs that are differentially expressed after ischemia in the human heart. These genes are predicted to function in pathways consistent with myocardial injury. As a result, lncRNAs may serve as novel diagnostic and therapeutic targets for ischemic heart disease

Effect of concurrent mitral valve surgery for secondary mitral regurgitation upon mortality after aortic valve replacement or coronary artery bypass surgery

ObjectivesIt is uncertain whether concurrent mitral valve repair or replacement for moderate or greater secondary mitral regurgitation at the time of coronary artery bypass graft or aortic valve replacement surgery improves long-term survival.MethodsPatients undergoing coronary artery bypass graft and/or aortic valve replacement surgery with moderate or greater secondary mitral regurgitation were reviewed. The effect of concurrent mitral valve repair or replacement upon long-term mortality was assessed while accounting for patient and operative characteristics and mitral regurgitation severity.ResultsOf 1,515 patients, 938 underwent coronary artery bypass graft or aortic valve replacement surgery alone and 577 underwent concurrent mitral valve repair or replacement. Concurrent mitral valve repair or replacement did not alter the risk of postoperative mortality for patients with moderate mitral regurgitation (hazard ratio = 0.93; 0.75–1.17) or more-than-moderate mitral regurgitation (hazard ratio = 1.09; 0.74–1.60) in multivariable regression. Patients with more-than-moderate mitral regurgitation undergoing coronary artery bypass graft-only surgery had a survival advantage from concurrent mitral valve repair or replacement in the first two postoperative years (P = 0.028) that did not persist beyond that time. Patients who underwent concurrent mitral valve repair or replacement had a higher rate of later mitral valve operation or reoperation over the five subsequent years (1.9% vs. 0.2%; P = 0.0014) than those who did not.ConclusionsThese observations suggest that mitral valve repair or replacement for more-than-moderate mitral regurgitation at the time of coronary artery bypass grafting may be reasonable in a suitably selected coronary artery bypass graft population but not for aortic valve replacement, with or without coronary artery bypass grafting. Our findings are supportive of 2021 European guidelines that severe secondary mitral regurgitation “should” or be “reasonabl[y]” intervened upon at the time of coronary artery bypass grafting but do not support 2020 American guidelines for performing mitral valve repair or replacement concurrent with aortic valve replacement, with or without coronary artery bypass grafting