Defining an Intraoperative Hypotension Threshold in Association with De Novo Renal Replacement Therapy after Cardiac Surgery.

BACKGROUND: Acute kidney injury (AKI) is a frequent and deadly complication after cardiac surgery. In the absence of effective therapies, a focus on risk factor identification and modification has been the mainstay of management. The authors sought to determine the impact of intraoperative hypotension on de novo postoperative renal replacement therapy in patients undergoing cardiac surgery, hypothesizing that prolonged periods of hypotension during and after cardiopulmonary bypass (CPB) were associated with an increased risk of renal replacement therapy. METHODS: Included in this single-center retrospective cohort study were adult patients who underwent cardiac surgery requiring CPB between November 2009 and April 2015. Excluded were patients who were dialysis dependent, underwent thoracic aorta or off-pump procedures, or died before receiving renal replacement therapy. Degrees of hypotension were defined by mean arterial pressure (MAP) as less than 55, 55 to 64, and 65 to 74 mmHg before, during, and after CPB. The primary outcome was de novo renal replacement therapy. RESULTS: Of 6,523 patient records, 336 (5.2%) required new postoperative renal replacement therapy. Each 10-min epoch of MAP less than 55 mmHg post-CPB was associated with an adjusted odds ratio of 1.13 (95% CI, 1.05 to 1.23; P = 0.002), and each 10-min epoch of MAP between 55 and 64 mmHg post-CPB was associated with an adjusted odds ratio of 1.12 (95% CI, 1.06 to 1.18; P = 0.0001) for renal replacement therapy. The authors did not observe an association between hypotension before and during CPB with renal replacement therapy. CONCLUSIONS: MAP less than 65 mmHg for 10 min or more post-CPB is associated with an increased risk of de novo postoperative renal replacement therapy. The association between intraoperative hypotension and AKI was weaker in comparison to factors such as renal insufficiency, heart failure, obesity, anemia, complex or emergent surgery, and new-onset postoperative atrial fibrillation. Nonetheless, post-CPB hypotension is a potentially easier modifiable risk factor that warrants further investigation.

Left ventricular function recovery after revascularization: comparative effects of percutaneous coronary intervention and coronary artery bypass grafting.

PURPOSE OF REVIEW: In 2013, heart failure with recovered ejection fraction (HFrecEF) was introduced as a new heart failure phenotype. This review provides an overview of HFrecEF and the comparative effects of percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) on left ventricular ejection fraction (LVEF) recovery in patients with ischemic cardiomyopathy. RECENT FINDINGS: There has been emerging data indicating that LV functional recovery is possible and HFrecEF is associated with improved survival and better quality of life. CABG may be associated with larger improvement in LVEF when compared with PCI. However, there is significant paucity of studies, which directly compare the impact of PCI and CABG on LVEF recovery in the setting of ischemic cardiomyopathy. SUMMARY: LVEF recovery is emerging as an important outcome with demonstrated survival and quality-of-life benefits. Future randomized clinical trials comparing the impact of contemporary PCI and CABG on LVEF recovery are needed in patients with ischemic cardiomyopathy.

Pivotal contemporary trials of percutaneous coronary intervention vs. coronary artery bypass grafting: a surgical perspective.

Coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) are the two revascularization strategies for patients with coronary artery disease (CAD). While CABG continues to be the gold standard for revascularization, advancements in PCI technology have triggered numerous, often industry-funded investigations to challenge this role. This perspective will provide a summary of previous RCTs comparing CABG vs. PCI. The recently published NOBLE and EXCEL trials will be discussed in depth. Future directions of research pertaining to CABG vs. PCI will be briefly discussed in this document.

Coronary Surgery in Women and the Challenges We Face.

This review was undertaken to understand the dynamics that have shaped our current treatment of women who undergo coronary artery bypass grafting (CABG) and summarize the current literature on surgical revascularization in women. There has been improved access to CABG over the past several decades. Despite this, compared with men, CABG in women involves fewer grafts and less frequent use of arterial grafts, the latter having improved long-term patency compared with saphenous vein grafts. We attempt to determine whether the adverse clinical profile of women, when referred for CABG is responsible for this finding. Female coronary anatomy and pathophysiology are reviewed and an attempt is made to understand how this might affect decisions of selection and outcome measures post CABG. We review the short-term, long-term, and quality of life outcomes in women. These data are taken from large databases, as well as from more recent publications. Randomized controlled trial data and meta-analytic data are used when available. Differential use of and outcomes of surgical strategies, including off-pump CABG and total arterial revascularization, are contrasted with those in men. This review shows that there continues to be widespread differences in surgical approach to coronary artery disease in female vs male patients. We provide evidence suggestive of the existence of issues specific to women that affect selection for surgical procedures and outcomes in women. More work is required to understand the reason for these differences and how to optimize sex-specific outcomes.

The balance between short-term and long-term outcomes of bilateral internal thoracic artery skeletonization in coronary artery bypass surgery: a propensity-matched cohort study.

OBJECTIVES: There is growing interest in the use of bilateral internal thoracic arteries (BITAs) for myocardial revascularization. This study sought to compare the balance between early benefits and long-term outcomes of skeletonized or non-skeletonized conduits and to determine whether differences in outcomes are affected by other patient risk factors. METHODS: BITAs were used in 1504 cases with either SK or NSK conduits. Propensity matching was completed using 22 covariates identifying 441 pairs of patients. The primary outcomes are the sternal wound infection in the short term and the composite outcome of all-cause mortality, myocardial infarction, revascularization and congestive heart failure. Outcomes were assessed using paired analysis techniques and Cox proportional hazards regression models stratified using the matched pairs. RESULTS: Incidences of in-hospital mortality and perioperative myocardial infarction were similar in both groups. There were fewer sternal wound infections in the SK group (5.4 vs 9.1%, P = 0.033). Homogeneity testing of the relative risk estimates confirmed that there was a protective effect of skeletonization in men that was not demonstrated in women (P = 0.020). SK had a protective effect in diabetics not seen in non-diabetics (P = 0.048). The composite outcome of all-cause mortality, myocardial infarction, revascularization and congestive heart failure at a median of 5.6 years was comparable in both groups (hazard ratio 0.81, 95% confidence interval 0.57-1.15). CONCLUSION: Skeletonization results in better perioperative outcomes and comparable cardiac outcomes in patients undergoing BITA with the greatest benefit in men and patients with chronic obstructive pulmonary disease.

Simulation-Based Skill Training for Trainees in Cardiac Surgery: A Systematic Review.

BACKGROUND: Simulation-based training has been an important part of the solution to address the shortfalls in cardiac surgery training. This review was conducted to identify and systematically summarize existing evidence on outcomes and methodological quality of simulation-based skills training for cardiac surgery trainees. METHODS: MEDLINE, Embase, and ERIC (Education Resources Information Center) databases were searched. Studies included peer-reviewed publications with simulation-based skill training in cardiac surgery programs with outcome measures of performance. Data extraction covered the type of skills training, simulator type and fidelity, the level of trainees, assessment tools, assessors, study design and its components, strengths and limitations, and elements required for the Medical Education Research Study Quality Instrument score. The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: Of 16 studies that met the criteria, only four (25%) randomized controlled trials were identified, and the remaining were observational studies. Seven observational studies (43.7%) were single-group pre-post tests. The mean number of trainees was 20.4 (SD, 14.1). Low-fidelity simulators were used in 13 studies (81.2%). Most of the studies (81.3%) were high quality based on a Medical Education Research Study Quality Instrument score of 12 or more. Evidence of assessment tool validation was absent among all studies. No study outcome measures were directed to skills transfer to the operating room or patient outcomes. Overall learning outcomes' effect sizes were consistently high (2.2; SD, 1.6), with junior residents benefitting most (effect size, 2.8; SD, 2.2) CONCLUSIONS: Simulation-based skill training is associated with improved learning outcomes for cardiac surgery trainees with large effect sizes, but more behavior-level outcomes are required to fully assess its value.

Development of a high fidelity pressurized porcine beating heart simulator for cardiac surgery training.

BACKGROUND: Development of a high-fidelity cardiac surgery simulator (CSS) requires integration of a heart model with a mock cardiopulmonary bypass (CPB) circuit that can provide feedback to mimic the pathophysiology of cardiac surgery. However, the cost of commercially available simulators precludes regular use. We describe steps in the construction of a high-fidelity CSS that integrates a pulsatile paracorporeal ventricular-assist device (Pulse-VAD) and a commercially available CPB simulator. METHODS/RESULTS: Eight porcine hearts were initially prepared. The configuration consisted of cannulation of the distal descending aorta and the inferior vena cava to enable pressurization of the heart after connection to the Califia® simulator, as well as Pulse-VAD cannulation (fitted with inflatable balloons) of both ventricles. After each simulation run, the team addressed key issues to derive successive model changes through consensus. Key modifications included: a) pressure maintenance of the cardiac chambers (removal of lungs, Pulse-VAD cannulation sites at the left pulmonary artery and vein, double ligation of arch vessels); b) high-fidelity beating of both ventricles (full Pulse-VAD bladder filling and ensuring balloon neck placement at the valvular plane) and c) reproducible management of porcine anatomy (management of porcine aorta, ligation of left azygous vein and shortened ascending thoracic aortic segment). CONCLUSION: A CSS can be prepared at low cost, with integration into a high-fidelity CPB simulator with a novel beating heart component. This setup can be used in teaching the basics of CPB techniques and complex surgical procedures. Future work is needed to validate this model as a simulation instrument.

Effect of aortic pericardial valve choice on outcomes and left ventricular mass regression in patients with left ventricular hypertrophy.

OBJECTIVES: We sought to assess the effect of 2 contemporary pericardial valves on left ventricular mass regression and clinical outcomes after aortic valve replacement (AVR) in patients with aortic stenosis (AS). METHODS: Patients were followed postoperatively in a dedicated valve clinic. A propensity score was derived for each patient and used to adjust all analyses. Longitudinal analysis was performed using a repeated measures growth curve model. Survival analysis was assessed with a Cox proportional hazards model. RESULTS: Since February 2011, 258 patients with AS and left ventricular hypertrophy underwent AVR with the Trifecta (TR) (St Jude Medical, St Paul, Minn) or Perimount Magna Ease (ME) (Edwards LifeSciences, Irvine, Calif) bioprosthesis. There were longer bypass and crossclamp times and the indexed left ventricular outflow tract was smaller in the TR group. For the TR and ME, respectively, peak (14.4 ± 5.1 mm Hg vs 20.9 ± 7.2 mm Hg; P < .001) and mean (7.3 ± 2.7 mm Hg vs 10.9 ± 4.3 mm Hg; P < .001) gradients were significantly smaller postoperatively in the TR group. There was greater total mass regression (44.3 g/m2; 95% confidence interval [CI], 36.3-52.3 vs 29.5; 95% CI, 20.4-38.5 g/m2; P = .020) and mass regression over time in the TR group compared with the ME group (P = .016). Freedom from readmission, congestive heart failure, and the composite outcome of all-cause mortality, readmission, and congestive heart failure at 2.5 years was significantly improved in the TR group (composite outcome in TR and ME groups, respectively, 90.2; 95% CI, 81.9-94.9 and 78.2; 95% CI, 67.1-86.0; P = .013) CONCLUSIONS: TR use was associated with significantly increased left ventricular mass regression and improved intermediate-term clinical outcome in patients with left ventricular hypertrophy undergoing AVR for AS, compared with use of the ME.

Fibroblast growth factor-2 regulates human cardiac myofibroblast-mediated extracellular matrix remodeling.

BACKGROUND: Tissue fibrosis and chamber remodeling is a hallmark of the failing heart and the final common pathway for heart failure of diverse etiologies. Sustained elevation of pro-fibrotic cytokine transforming growth factor-beta1 (TGFß1) induces cardiac myofibroblast-mediated fibrosis and progressive structural tissue remodeling. OBJECTIVES: We examined the effects of low molecular weight fibroblast growth factor (LMW-FGF-2) on human cardiac myofibroblast-mediated extracellular matrix (ECM) dysregulation and remodeling. METHODS: Human cardiac biopsies were obtained during open-heart surgery and myofibroblasts were isolated, passaged, and seeded within type I collagen matrices. To induce myofibroblast activation and ECM remodeling, myofibroblast-seeded collagen gels were exposed to TGFß1. The extent of ECM contraction, myofibroblast activation, ECM dysregulation, and cell apoptosis was determined in the presence of LMW-FGF-2 and compared to its absence. Using a novel floating nylon-grid supported thin collagen gel culture platform system, myofibroblast activation and local ECM remodeling around isolated single cells was imaged using confocal microscopy and quantified by image analysis. RESULTS: TGFß1 induced significant myofibroblast activation and ECM dysregulation as evidenced by collagen gel contraction, structural ECM remodeling, collagen synthesis, ECM degradation, and altered TIMP expression. LMW-FGF-2 significantly attenuated TGFß1 induced myofibroblast-mediated ECM remodeling. These observations were similar using either ventricular or atrial-derived cardiac myofibroblasts. In addition, for the first time using individual cells, LMW-FGF-2 was observed to attenuate cardiac myofibroblast activation and prevent local cell-mediated ECM perturbations. CONCLUSIONS: LMW-FGF-2 attenuates human cardiac myofibroblast-mediated ECM remodeling and may prevent progressive maladaptive chamber remodeling and tissue fibrosis for patients with diverse structural heart diseases.

Human cardiac fibroblast extracellular matrix remodeling: dual effects of tissue inhibitor of metalloproteinase-2.

OBJECTIVE: Tissue inhibitor of metalloproteinase-2 (TIMP-2) is an endogenous inhibitor of matrix metalloproteinases (MMPs) that attenuates maladaptive cardiac remodeling in ischemic heart failure. We examined the effects of TIMP-2 on human cardiac fibroblast activation and extracellular matrix (ECM) remodeling. METHODS: Human cardiac fibroblasts within a three-dimensional collagen matrix were assessed for phenotype conversion, ECM architecture and key molecular regulators of ECM remodeling after differential exposure to TIMP-2 and Ala+TIMP-2 (a modified TIMP-2 analogue devoid of MMP inhibitory activity). RESULTS: TIMP-2 induced opposite effects on human cardiac fibroblast activation and ECM remodeling depending on concentration. TIMP-2 activated fibroblasts into contractile myofibroblasts that remodeled ECM. At higher concentrations (>10 nM), TIMP-2 inhibited fibroblast activation and prevented ECM remodeling. As compared to profibrotic cytokine transforming growth factor (TGF)-beta1, TIMP-2 activated fibroblasts and remodeled ECM without a net accumulation of matrix elements. TIMP-2 increased total protease activity as compared to TGF-beta1. Ala+TIMP-2 exposure revealed that the actions of TIMP-2 on cardiac fibroblast activation are independent of its effects on MMP inhibition. In the presence of GM6001, a broad-spectrum MMP inhibitor, TIMP-2-mediated ECM contraction was completely abolished, indicating that TIMP-2-mediated fibroblast activation is MMP dependent. CONCLUSION: TIMP-2 functions in a contextual fashion such that the effect on cardiac fibroblasts depends on the tissue microenvironment. These observations highlight potential clinical challenges in using TIMP-2 as a therapeutic strategy to attenuate postinjury cardiac remodeling.

Epicardial infarct repair with basic fibroblast growth factor-enhanced CorMatrix-ECM biomaterial attenuates postischemic cardiac remodeling.

OBJECTIVES: Dysregulation of extracellular matrix (ECM) following myocardial infarction is a key contributor to myocardial fibrosis, chamber dilation, and progression to heart failure. Basic fibroblast growth factor is a potent inhibitor of fibrosis. We propose a novel surgical procedure leveraging a commercially available ECM biomaterial for the treatment of ischemic heart failure. METHODS: Epicardial infarct repair using CorMatrix-ECM biomaterial patch (CorMatrix Cardiovascular Inc, Roswell, Ga) was compared with sham in a rat myocardial infarction model. Key indices of ischemic remodeling, including inflammation, fibrosis, and myocardial performance were evaluated 16 weeks post-treatment. RESULTS: Histology and immunohistochemistry demonstrated comprehensive integration of CorMatrix-ECM biomaterial patch without evidence of immune reaction and an increase in basic fibroblast growth factor expression in treated animals. Functional analysis by serial echocardiography of normal (n = 13), sham (n = 15), nonenhanced CorMatrix-ECM patch (n = 18), and basic fibroblast growth factor-enhanced CorMatrix-ECM patch (n = 10) animals revealed an improvement in ejection fraction in basic fibroblast growth factor-enhanced CorMatrix-ECM patch animals compared with shams (55.3% ± 8.0% vs 35.1% ± 7.6%; P < .001). Prevention of left ventricle remodeling was also confirmed by pressure volume loop analysis, which demonstrated reduced left ventricular end diastolic volumes in basic fibroblast growth factor-enhanced CorMatrix-ECM patch animals (n = 5) compared with shams (n = 6) (208.0 ± 59.3 µL vs 363. 1 ± 108.7 µL; P < .01) and improved left ventricle contractility in nonenhanced CorMatrix-ECM patch (n = 7) and basic fibroblast growth factor-enhanced CorMatrix-ECM patch animals compared with shams (0.709 ± 0.306 and 0.609 ± 0.160 vs 0.437 ± 0.218; P < .05). CONCLUSIONS: Epicardial infarct repair with basic growth factor-enhanced CorMatrix-ECM biomaterial patch attenuates myocardial remodeling and improves cardiac performance after subacute myocardial infarction in a rat coronary ligation model. These observations establish proof-of-concept for this novel surgical approach.