Personalized surgical planning for coronary bypass graft configurations using patient-specific computational modeling to avoid flow competition in arterial grafts.

Objectives: Flow competition between coronary artery bypass grafts (CABG) and native coronary arteries is a significant problem affecting arterial graft patency. The objectives of this study were to compare the predictive hemodynamic flow resulting from various total arterial grafting configurations and to evaluate whether the use of computational fluid dynamics (CFD) models capable of predicting flow can assist surgeons to make better decisions for individual patients by avoiding poorly functioning grafts. Methods: Sixteen cardiac surgeons declared their preferred CABG configuration using bilateral internal mammary and radial arteries for each of 5 patients who had differing degrees of severe triple vessel coronary disease. Surgeons selected both a preferred 'aortic' strategy, with at least one graft arising from the ascending aorta, and a preferred "anaortic" strategy which could be performed as a "no-aortic touch" operation. CT coronary angiograms of the 5 patients were coupled to CFD models using a novel flow solver "COMCAB." Twelve different CABG configurations were compared for each patient of which 4 were "aortic" and 8 were "anaortic." Surgeons then selected their preferred grafting configurations after being shown predictive hemodynamic metrics including functional assessment of stenoses (instantaneous wave-free ratio; fractional flow reserve), transit time flowmetry graft parameters (mean graft flow; pulsatility index) and myocardial perfusion. Results: A total of 87.5% (7/8) of "anaortic" configurations compared to 25% (1/4) of "aortic" configurations led to unsatisfactory grafts in at least 1 of the 5 patients (P = 0.038). The use of the computational models led to a significant decrease in the selection of unsatisfactory grafting configurations when surgeons employed "anaortic" (21.25% (17/80) vs. 1.25% (1/80), P < 0.001) but not "aortic" techniques (5% (4/80) vs. 0% (0/80), P = 0.64). Similarly, there was an increase in the selection of ideal configurations for "anaortic" (6.25% (5/80) vs. 28.75% (23/80), P < 0.001) but not "aortic" techniques (65% (52/80) vs. 61.25% (49/80), P = 0.74). Furthermore, surgeons who planned to use more than one unique "anaortic" configuration across all 5 patients increased (12.5% (2/16) vs. 87.5% (14/16), P<0.001). Conclusions: "COMCAB" is a promising tool to improve personalized surgical planning particularly for CABG configurations involving composite or sequential grafts which are used more frequently in anaortic operations.

Generating robust human valvular interstitial cell cultures: Protocol and considerations.

Research in heart valve biology is a growing field that has yet to elucidate the fundamentals of valve disease. Human valvular interstitial cells (hVICs) are the best option for studying the cellular mechanisms behind valvular pathologies. However, there is a wide range of isolation procedures for these cells published in the literature. To what extent various isolation methods, patient pathologies, and seeding densities influence the behaviour of hVICs remains unclear. Here, we present an optimised method of hVIC isolation from diseased human valves donated at the time of surgery. We show that two rounds of 1000 U/mL collagenase digestion for not >2 h results in a phenotypically stable cell culture with a near complete absence of endothelial cell contamination. We also suggest that cells should be seeded at 10,000 cells/cm2 for experimentation. We found that patient pathology does not affect the success of the isolation procedure, and that instead, successful cultures are predicted by ensuring >500 mg valve tissue as starting material.

Fibroblast growth factor 2 inhibits myofibroblastic activation of valvular interstitial cells.

Heart valve disease is a growing problem worldwide. Though very common in older adults, the mechanisms behind the development of the disease aren't well understood, and at present the only therapeutic option is valve replacement. Valvular interstitial cells (VICs) may hold the answer. These cells can undergo pathological differentiation into contractile myofibroblasts or osteoblasts, leading to thickening and calcification of the valve tissue. Our study aimed to characterise the effect of fibroblast growth factor 2 (FGF-2) on the differentiation potential of VICs. We isolated VICs from diseased human valves and treated these cells with FGF-2 and TGF-ß to elucidate effect of these growth factors on several myofibroblastic outcomes, in particular immunocytochemistry and gene expression. We used TGF-ß as a positive control for myofibroblastic differentiation. We found that FGF-2 promotes a 'quiescent-type' morphology and inhibits the formation of α-smooth muscle actin positive myofibroblasts. FGF-2 reduced the calcification potential of VICs, with a marked reduction in the number of calcific nodules. FGF-2 interrupted the 'canonical' TGF-ß signalling pathway, reducing the nuclear translocation of the SMAD2/3 complex. The panel of genes assayed revealed that FGF-2 promoted a quiescent-type pattern of gene expression, with significant downregulations in typical myofibroblast markers α smooth muscle actin, extracellular matrix proteins, and scleraxis. We did not see evidence of osteoblast differentiation: neither matrix-type calcification nor changes in osteoblast associated gene expression were observed. Our findings show that FGF-2 can reverse the myofibroblastic phenotype of VICs isolated from diseased valves and inhibit the calcification potential of these cells.

Trends in computed tomography aortography and acute aortic syndrome in an emergency department within Aotearoa New Zealand.

OBJECTIVE: Acute aortic syndrome (AAS) comprises a triad of life-threatening aortic conditions that are difficult to diagnose because of their non-specific clinical presentations. Contrast-enhanced computed tomography aortography (CTA) has a high sensitivity and specificity for these conditions. However, under- and over-investigation of patients with suspected AAS using CTA carries significant risk. The aim of the present study was to evaluate the diagnostic imaging practices of CTA use for patients presenting to an ED with suspected AAS. METHODS: All atraumatic thoracic CTAs performed on patients aged ≥15 years old with suspected AAS who presented to Auckland City Hospital between 2009 and 2019 were included. Outcomes of interest were the annual ED and population incidences of AAS, and the rate of CTAs performed. RESULTS: A total of 1646 CTAs were included. There were 135 (8.2%) cases of at least one AAS diagnosis and 220 (13.4%) cases where an alternative diagnosis was made. The population-adjusted number of AAS diagnoses remained relatively stable over the study period, with a mean annual AAS incidence of 19.6 (95% confidence interval 9.9-33.7) per 100 000 patients, and 3.2 (95% confidence interval 1.6-5.4) per 100 000 population. The number of ED presentations increased during the study period, along with the population-adjusted rate of CTAs performed, from approximately 150 per 100 000 patients (2009) to 350 per 100 000 patients (2019). CONCLUSIONS: Thoracic CTA use for investigating suspected AAS in our ED has recently increased. However, the annual incidence of AAS did not increase over the same period, but was higher than reported in overseas institutions.

Models of immunogenicity in preclinical assessment of tissue engineered heart valves.

Tissue engineered heart valves may one day offer an exciting alternative to traditional valve prostheses. Methods of construction vary, from decellularised animal tissue to synthetic hydrogels, but the goal is the same: the creation of a 'living valve' populated with autologous cells that may persist indefinitely upon implantation. Previous failed attempts in humans have highlighted the difficulty in predicting how a novel heart valve will perform in vivo. A significant hurdle in bringing these prostheses to market is understanding the immune reaction in the short and long term. With respect to innate immunity, the chronic remodelling of a tissue engineered implant by macrophages remains poorly understood. Also unclear are the mechanisms behind unknown antigens and their effect on the adaptive immune system. No silver bullet exists, rather researchers must draw upon a number of in vitro and in vivo models to fully elucidate the effect a host will exert on the graft. This review details the methods by which the immunogenicity of tissue engineered heart valves may be investigated and reveals areas that would benefit from more research. STATEMENT OF SIGNIFICANCE: Both academic and private institutions around the world are committed to the creation of a valve prosthesis that will perform safely upon implantation. To date, however, no truly non-immunogenic valves have emerged. This review highlights the importance of preclinical immunogenicity assessment, and summarizes the available techniques used in vitro and in vivo to elucidate the immune response. To the authors knowledge, this is the first review that details the immune testing regimen specific to a TEHV candidate.

Clinical performance of decellularized heart valves versus standard tissue conduits: a systematic review and meta-analysis.

BACKGROUND: Valve replacement surgery is the definitive management strategy for patients with severe valvular disease. However, valvular conduits currently in clinical use are associated with significant limitations. Tissue-engineered (decellularized) heart valves are alternative prostheses that have demonstrated promising early results. The purpose of this systematic review and meta-analysis is to perform robust evaluation of the clinical performance of decellularized heart valves implanted in either outflow tract position, in comparison with standard tissue conduits. METHODS: Systematic searches were conducted in the PubMed, Scopus, and Web of Science databases for articles in which outcomes between decellularized heart valves surgically implanted within either outflow tract position of human subjects and standard tissue conduits were compared. Primary endpoints included postoperative mortality and reoperation rates. Meta-analysis was performed using a random-effects model via the Mantel-Haenszel method. RESULTS: Seventeen articles were identified, of which 16 were included in the meta-analysis. In total, 1418 patients underwent outflow tract reconstructions with decellularized heart valves and 2725 patients received standard tissue conduits. Decellularized heart valves were produced from human pulmonary valves and implanted within the right ventricular outflow tract in all cases. Lower postoperative mortality (4.7% vs. 6.1%; RR 0.94, 95% CI: 0.60-1.47; P = 0.77) and reoperation rates (4.8% vs. 7.4%; RR 0.55, 95% CI: 0.36-0.84; P = 0.0057) were observed in patients with decellularized heart valves, although only reoperation rates were statistically significant. There was no statistically significant heterogeneity between the analyzed articles (I2 = 31%, P = 0.13 and I2 = 33%, P = 0.10 respectively). CONCLUSIONS: Decellularized heart valves implanted within the right ventricular outflow tract have demonstrated significantly lower reoperation rates when compared to standard tissue conduits. However, in order to allow for more accurate conclusions about the clinical performance of decellularized heart valves to be made, there need to be more high-quality studies with greater consistency in the reporting of clinical outcomes.

Low-dose erythropoietin treatment is not associated with clinical benefits in severely anaemic Jehovah's Witnesses: a plea for a change.

BACKGROUND: Jehovah's Witnesses who refuse blood transfusion have high mortality. Erythropoietin (EPO) has been used as an alternative to blood transfusion. The optimal dosing of EPO in anaemic Jehovah's Witnesses is unknown. The aim of our study was to evaluate the clinical benefits of treatment with a low dose (<600 IU/kg/week) of epoietin beta (EPO-ß). MATERIALS AND METHODS: This was an observational study, retrospectively considering a 10-year period during which 3,529 adult Jehovah's Witnesses with a total of 10,786 hospital admissions were identified from databases of four major public hospitals in New Zealand. Patients with severe symptomatic anaemia (haemoglobin <80 g/L) who were unable to tolerate physical activity were included in the study. Patients treated without EPO were assigned to the conventional therapy group and those treated with EPO to the EPO treatment group. RESULTS: Ninety-one Jehovah's Witnesses met the eligibility criteria. Propensity score matching yielded a total of 57 patients. Patients treated with conventional therapy and those treated with EPO had similar durations of severe anaemia (average difference 6.25 days, 95% confidence interval [CI]: -3.77-16.27 days; p=0.221). The mortality rate among Jehovah's Witnesses treated with conventional therapy was 4.68 per year (95% CI: 2.23-9.82), while that in those treated with EPO was 2.77 per year (95% CI: 0.89-8.60). Treatment with EPO was associated with a mortality ratio of 0.59 (95% CI: 0.1-2.6; p=0.236). Both groups of patients had similar in-hospital survival (p=0.703). DISCUSSION: Treatment with low-dose EPO-ß was not associated with either shorter duration of severe anaemia or a reduction in mortality.

Normalized end-systolic volume and pre-load reserve predict ventricular dysfunction following surgery for aortic regurgitation independent of body size.

Pre-operative end-systolic volume (ESV) is predictive of outcome after surgery for severe aortic regurgitation. ESV is influenced by body size and reflects function and afterload, but not pre-load. Left ventricular (LV) chamber size and function were measured in 40 patients (ages 10 to 64 years) by echocardiography before and 7 months after operation and expressed as z-scores in addition to simple indexing. A functional pre-load index, a marker of pre-load reserve, was calculated. Independent risk factors for post-operative LV dysfunction included higher post-operative ESV z-score (odds ratio [OR]: 3.3, p = 0.006) and lower functional pre-load index (OR: 0.3, p = 0.03). ESV per square meter had similar power to the ESV z-score. The ESV uncorrected for body size underestimated risk in smaller patients and overestimated risk in larger patients (p < 0.002). Pre-load reserve is an independent risk factor for LV dysfunction after aortic valve surgery in patients with severe aortic regurgitation. Failure to correct ESV for body size introduces systematic bias to risk assessment.

Are two internal thoracic artery grafts as safe as one? Experience from Green Lane Hospital.

AIM: To compare short-term mortality and major morbidity between patients undergoing elective primary isolated CABG with bilateral internal thoracic artery (BITA) or single internal thoracic artery (SITA) grafts at Green Lane Hospital (Auckland, New Zealand). METHODS: We conducted a retrospective study of short-term outcomes in 5955 patients receiving SITA and 637 patients receiving BITA grafts between 1990 and 2004. Only patients undergoing elective primary isolated coronary artery surgery were included. The primary outcome was a composite end-point (early death, perioperative MI, reoperation for sternal wound complications or significantly prolonged hospital stay). Patients receiving BITA grafts were case-matched with patients receiving SITA grafts for confounding factors and comparison was made between perioperative outcomes in the two groups. RESULTS: After case-matching, no statistically significant difference was found in the incidence of our primary endpoint between patients receiving BITA versus SITA grafts [odds ratio 0.84 (95% CI 0.59, 1.21)]. Furthermore, there was no difference in rates of reoperation for sternal wound complications between the two groups [odds ratio 1.00 (95% CI 0.29, 3.44)]. CONCLUSIONS: Given the potential long-term clinical advantages of BITA grafting, our results support the increased use of BITA grafts in selected patients.

Cerebral ischemic lesions on diffusion-weighted imaging are associated with neurocognitive decline after cardiac surgery.

BACKGROUND AND PURPOSE: Improvements in cardiac surgery mortality and morbidity have focused interest on the neurological injury such as stroke and cognitive decline that may accompany an otherwise successful operation. We aimed to investigate (1) the rate of stroke, new ischemic change on MRI, and cognitive impairment after cardiac valve surgery; and (2) the controversial relationship between perioperative cerebral ischemia and cognitive decline. METHODS: Forty patients (26 men; mean [SD] age 62.1 [13.7] years) undergoing intracardiac surgery (7 also with coronary artery bypass grafting) were studied. Neurological, neuropsychological, and MRI examinations were performed 24 hours before surgery and 5 days (MRI and neurology) and 6 weeks (neuropsychology and neurology) after surgery. Cognitive decline from baseline was determined using the Reliable Change Index. RESULTS: Two of 40 (5%) patients had perioperative strokes and 22 of 35 (63%) tested had cognitive decline in at least one measure (range, 1 to 4). Sixteen of 37 participants (43%) with postoperative imaging had new ischemic lesions (range, 1 to 17 lesions) with appearances consistent with cerebral embolization. Cognitive decline was seen in all patients with, and 35% of those without, postoperative ischemic lesions (P<0.001), and there was an association between the number of abnormal cognitive tests and ischemic burden (P<0.001). CONCLUSIONS: We have provided a reliable estimate of the rate of stroke, postoperative ischemia, and cognitive impairment at 6 weeks after cardiac valve surgery. Cognitive impairment is associated with perioperative ischemia and is more severe with greater ischemic load.

Staphylococcal post-sternotomy mediastinitis: five year audit.

BACKGROUND: The reported rate of post-sternotomy mediastinitis is between 0.8 and 2.3%, with up to 79% of cases caused by staphylococci. Mediastinitis is associated with significant morbidity and mortality. Obesity and diabetes are the only risk factors consistently identified. The aims of the present study were to determine the incidence and risk factors for staphylococci post-sternotomy mediastinitis and to audit its management. METHODS: The clinical records of patients with staphylococcal post-sternotomy mediastinitis between 1 January 1998 and 31 May 2003 were retrospectively reviewed. Information collected included patient demographics, comorbidities, operation type, microbiology findings, surgical and medical management, and outcome. Data collected on cases were compared with data collected in a prospective database of all patients undergoing cardiac surgery. RESULTS: The incidence of staphylococcal post-sternotomy mediastinitis was 1.2% (60 cases in 5176 median sternotomies). Staphylococcus aureus was isolated in 49 (82%) cases and coagulase-negative staphylococci in 11 (18%) cases. Eight (16%) S. aureus isolates were methicillin-resistant. Risk factors associated with mediastinitis were ethnicity, diabetes mellitus, emergency surgery, ejection fraction and length of preoperative hospital stay. In-hospital mortality was 15%. Eighteen per cent of cases were not cured by initial therapy. CONCLUSION: Staphylococcal mediastinitis is a serious complication with significant rates of relapse and mortality. This audit has lead to an evaluation of our clinical pathways to ensure that prevention and management of surgical site infection is optimized.