Do Flow and Pulsatility Index within the Accepted Ranges Predict Long-Term Outcomes after Coronary Artery Bypass Grafting?

BACKGROUND: Transit-time flow measurement (TTFM) is the gold standard for intraoperative detection of graft failure. Several reports show that TTFM and distal coronary bed quality (DCBQ) may also be useful for midterm detection of graft failure. Nonetheless, there are no data regarding their predictive role on long-term outcomes. METHODS: Patients with three-vessel disease who underwent isolated coronary artery bypass grafting (CABG) in 2006 and received at least one graft to the left anterior descending artery (LAD) or to the first obtuse marginal (OM1) or posterior descending artery (PDA) were included. Baseline characteristics, mean graft flow, pulsatility index, and subjective impression of DCBQ for each coronary territory were collected. Long-term cardiovascular (CV) and overall survival, operative mortality, and new percutaneous coronary intervention (PCI) were evaluated. RESULTS: A total of 177 patients underwent isolated CABG. The OM1 was grafted in 131 patients, the LAD in 169 patients, and the PDA in 100 patients. Neither DQCB nor TTFM were predictors for new PCI. Independent predictors for overall survival were age, previous acute myocardial infarction (AMI), and DQCB of OM1 (odds ratio [OR] = 2.97; 95% confidence interval [CI]: 1.15-7.71). Age, previous AMI, and DCBQ of OM1 (OR = 2.5; 95% CI: 1.39-4.81) were independent predictors for CV survival. CONCLUSIONS: TTFM on patients with functioning grafts does not predict long-term survival or performance of new PCI. Subjective evaluation of distal coronary bed, especially of the OM1, has a strong impact on long-term outcomes.

Human mesenchymal stromal cells do not promote recurrence of soft tissue sarcomas in mouse xenografts after radiation and surgery.

BACKGROUND: Mesenchymal stromal cells (MSCs) promote wound healing, including after radiotherapy (RT) and surgery. The use of MSCs in regenerative medicine in the context of malignancy, such as to enhance wound healing post-RT/surgery in patients with soft tissue sarcomas (STSs), requires safety validation. The aim of this study was to determine the effects of human MSCs on STS growth in vitro and local recurrence and metastasis in vivo. METHODS: Human primary STS and HT-1080 fibrosarcoma lines were transduced to express luciferase/eGFP (enhanced green fluorescent protein). Sarcoma cells were co-cultured or co-injected with bone marrow-derived MSCs for growth studies. Xenograft tumor models were established with STS lines in NOD/SCID/γcnull mice. To emulate a clinical scenario, subcutaneous tumors were treated with RT/surgery prior to MSC injection into the tumor bed. Local and distant tumor recurrence was studied using histology and bioluminescence imaging. RESULTS: MSCs did not promote STS proliferation upon co-culture in vitro, which was consistent among MSCs from different donors. Co-injection of MSCs with sarcoma cells in mice exhibited no significant tumor-stimulating effect, compared with control mice injected with sarcoma cells alone. MSC administration after RT/surgery had no effect on local recurrence or metastasis of STS. DISCUSSION: These studies are important for the establishment of a safety profile for MSC administration in patients with STS. Our data suggest that MSCs are safe in STS management after standard of care RT/surgery, which can be further investigated in early-phase clinical trials to also determine the efficacy of MSCs in reducing morbidity and to mitigate wound complications in these patients.

Development and characterization of a new inbred transgenic rat strain expressing DsRed monomeric fluorescent protein.

The inbred rat is a suitable model for studying human disease and because of its larger size is more amenable to complex surgical manipulation than the mouse. While the rodent fulfills many of the criteria for transplantation research, an important requirement is the ability to mark and track donors cells and assess organ viability. However, tracking ability is limited by the availability of transgenic (Tg) rats that express suitable luminescent or fluorescent proteins. Red fluorescent protein cloned from Discosoma coral (DsRed) has several advantages over other fluorescent proteins, including in vivo detection in the whole animal and ex vivo visualization in organs as there is no interference with autofluorescence. We generated and characterized a novel inbred Tg Lewis rat strain expressing DsRed monomeric (DsRed mono) fluorescent protein under the control of a ubiquitously expressed ROSA26 promoter. DsRed mono Tg rats ubiquitously expressed the marker gene as detected by RT-PCR but the protein was expressed at varying levels in different organs. Conventional skin grafting experiments showed acceptance of DsRed monomeric Tg rat skin on wild-type rats for more than 30 days. Cardiac transplantation of DsRed monomeric Tg rat hearts into wild-type recipients further showed graft acceptance and long-term organ viability (>6 months). The DsRed monomeric Tg rat provides marked cells and/or organs that can be followed for long periods without immune rejection and therefore is a suitable model to investigate cell tracking and organ transplantation.

Coronary surgery provides better survival than drug-eluting stent: A pooled meta-analysis of Kaplan- Meier-derived individual patient data.

OBJECTIVES: We explored the current evidence on coronary disease treatment comparing the survival of 2 therapeutic strategies: coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) with drug-eluting stent (DES). METHODS: PubMed, Embase, and Google Scholar were searched for randomized clinical trials comparing CABG versus PCI with DES. The end point was overall mortality. Two statistical approaches were used: the generic inverse variance method, which was used to pool the incident rate ratios, and the pooled meta-analysis of Kaplan-Meier-derived individual patient data. RESULTS: Eight randomized clinical trials comparing 4975 patients undergoing CABG and 4992 patients undergoing PCI were included in our meta-analysis. Generic inverse variance method showed a statistically significant survival benefit of the CABG group (incident rate ratio, 1.21; 95% confidence interval, 1.09-1.35; P < .01). The Kaplan-Meier estimates of survival at 1, 5, and 10 years of the CABG group were 97.1%, 90.3%, and 80.3%, respectively. The Kaplan-Meier estimates of survival at 1, 5, and 10 years of the PCI group were 97.0%, 87.7%, and 76.4%, respectively. The log-rank analysis confirmed a statistically significant benefit in term of overall mortality of the CABG group (hazard ratio, 1.24; 95% confidence interval, 1.11-1.38; P = .0001). CONCLUSIONS: The present meta-analysis suggests that CABG provides a consistent survival benefit over PCI with DES.

The ISCHEMIA trial revisited: setting the record straight on the benefits of coronary bypass surgery and the misinterpretation of a landmark trial.

OBJECTIVES: The ISCHEMIA trial is a landmark study that has been the subject of heated debate within the cardiovascular community. In this analysis of the ISCHEMIA trial, we aim to set the record straight on the benefits of coronary artery bypass grafting (CABG) and the misinterpretation of this landmark trial. We sought to clarify and reorient this misinterpretation. METHODS: We herein analyse the ISCHEMIA trial in detail and describe how its misinterpretation has led to an erroneous guideline recommendation downgrading for prognosis-altering surgical therapy in these at-risk patients. RESULTS: The interim ISCHEMIA trial findings align with previous evidence where CABG reduces the long-term risks of myocardial infarction and mortality in advanced coronary artery disease. The trial outcomes of a significantly lower rate of cardiovascular mortality and a higher rate of non-cardiovascular mortality with the invasive strategy are explained according to landmark evidence. CONCLUSIONS: The ISCHEMIA trial findings are aligned with previous evidence and should not be used to downgrade recommendations in recent guidelines for the indisputable benefits of CABG.

Perspectives in Training and Professional Practice of Cardiac Surgery in Latin America.

INTRODUCTION: There is a lack of information about cardiac surgery training and professional practice in Latin American (LATAM) countries. This study is the first comparative analysis of cardiac surgical training and professional practice across LATAM and provides the fundamentals for future academic projects of the Latin American Association of Cardiac and Endovascular Surgery (LACES). METHODS: International survey-based comparative analysis of the training and professional practice of cardiac surgeons across LATAM. Trainees (residents/fellows) and staf (graduated) surgeons from LATAM countries were included. RESULTS: A total of 289 respondents (staf surgeons N=221 [76.5%]; residents/fellows N=68 [23.5%]) from 18 different countries participated in the survey. Most surgeons (N=92 [45.3%]) reported being unsatisfied with their salaries. Most respondents (N=181 [62.6%]) stated that it was difficult to obtain a leadership position, and 149 (73.8%) stated that it was difficult to find a job after completing training. Only half of the trainee respondents (N=32 [47.1%]) reported that their program had all resident spots occupied. Only 22.1% (N=15) of residents/fellows were satisfied with their training programs. The majority (N=205 [70.9%]) of respondents would choose cardiac surgery as their specialty again. Most surgeons (N=129 [63.9%]) and residents/fellows (N=52 [76.5%]) indicated that the establishment of a LATAM cardiac surgery board examination would be beneficial. CONCLUSION: Modernization and standardization of training, as well as greater access to opportunities, may be required in LATAM to increase professional satisfaction of cardiac surgeons and to reduce disparities in the specialty. Such changes may enhance the regional response to the dynamic challenges in the feld.

Non-Governmental Organizations Delivering Global Cardiac Surgical Care: A Quantitative Impact Assessment.

In low- and middle-income countries (LMICs), 93% of the population lacks safe, timely, and affordable access to cardiac surgical care when needed. As countries slowly build or expand local, independent cardiac centers, non-governmental organizations (NGOs) partially bridge the gap in cardiac surgical care delivery in LMICs. However, little is known about the current scope of cardiac NGOs. Here, we perform an analysis of active NGOs involved with the delivery of cardiac surgical services in LMICs or for patients from LMICs. Cardiac surgery NGOs were identified from medical literature, established NGO databases, and Google Scholar searches. The search was performed between December 2019 and May 2020. NGOs whose websites were not updated or described missions or projects taking place no later than 2015 were considered inactive. Eighty-six NGOs are actively providing cardiac surgery services in LMICs or treating patients from LMICs. Five NGOs performed adult cardiac surgery only, 56 performed pediatric cardiac surgery only, and 25 performed both adult and pediatric cardiac surgery. NGOs originated from 23 different countries and were operational in a total of 111 countries, 96 of them being LMICs. Fifty-three NGOs reported data on annual surgical volume, of which half performed less than 50 operations per year. NGOs effectively address the burden of cardiac surgical disease in LMICs and contribute to local capacity-building. Increased, more detailed, and standardized reporting of the impact and outcomes of NGOs is necessary to better understand annual cardiac surgical volume and to support local centers working towards independent services.

Early anticoagulation after aortic valve replacement with porcine bioprosthesis randomized control trial (ANTIPRO).

OBJECTIVES: Most evidence for anticoagulation (AC) in aortic bioprosthesis is centred on embolic events, bleeding and reintervention risk. The effect of AC on haemodynamics has not been previously assessed. Our hypothesis was that patients with early AC after aortic valve replacement (AVR) with porcine bioprosthesis have better haemodynamics at 1 year of follow-up. METHODS: Prospective, randomized, open-label trial conducted at 2 cardiac surgery centres. All patients undergoing AVR with porcine bioprosthesis were consecutively recruited. The anticoagulated group received warfarin + aspirin and the non-anticoagulated (control) only aspirin. The primary outcome was mean gradient after 1 year of AVR and change in New York Heart Association class. Secondary outcomes were major and minor bleeding, embolic events and prosthetic leak. RESULTS: Of 140 participants in the study, 71 were assigned to the anticoagulated group and 69 to the control group. The mean age of the overall population was 72.4 (SD: 7.1) years. Global EuroSCORE was 7.65 (SD: 5.73). At 1 year, the mean gradient was similar between both groups [18.6 (SD: 1.1 mmHg) and 18.1 (SD: 1.0 mmHg) in the control and anticoagulated groups, respectively, P = 0.701]. No differences in functional class at 3 months or 1 year were found among groups. No differences were found among groups in the secondary outcomes. CONCLUSIONS: The addition of 3 months of oral AC to anti-aggregation treatment was not detected to affect bioprosthetic haemodynamics nor functional class at 1 year after AVR. Likewise, AC does not lead to the higher incidence of complications.

Joint Recommendations From The Latin American Association of Cardiac and Endovascular Surgery (LACES) and The Cardiovascular Anesthesia Committee of The Latin American Confederation of Anesthesia Societies (CLASA) on the Timing for Cardiac Surgery After COVID-19 Infection.

INTRODUCTION: Since the coronavirus disease 2019 (COVID-19) pandemic, cardiac surgeries in patients with previous infection by COVID-19 were suspended or postponed, which led to surgeries performed in patients with an advanced stage of their disease and an increase in the waiting list. There is a heterogeneous attitude in Latin America on the optimal timing to cardiac surgery in patients with previous COVID-19 infection due to scarce data on its outcome. Two Latin American associations joined to establish common suggestions on the optimal timing of surgery in patients with previous COVID-19 infection. METHODS: Data collection was performed using a pre-established form, which included year of publication, objective, type of study (prospective/retrospective, descriptive/analytical), number of patients, year of study, waiting time between infection and surgery, type of surgery, morbidity, mortality, and conclusions regarding the association between mortality and morbidity. Final recommendations were approved by the board of directors of Latin American Association of Cardiac and Endovascular Surgery (LACES) and Latin American Confederation of Anesthesia Societies (CLASA). RESULTS: Of the initial 1,016 articles, 11 comprised the final selection. Only six of them included patients who underwent cardiac surgery. According to the analyzed literature, optimal timing for cardiac surgery needs to consider the following aspects: deferable surgery, symptomatic COVID-19 infection, completeness of COVID-19 vaccination. CONCLUSION: These recommendations derive from the analysis of the scarce literature published at present on outcomes after cardiac surgery in patients with previous COVID-19 infection. These are to be taken as a dynamic recommendation in which Latin American reality was taken into consideration.

Mesenchymal stromal cells mediate a switch to alternatively activated monocytes/macrophages after acute myocardial infarction.

Given the established anti-inflammatory properties of mesenchymal stromal cells (MSCs), we investigated their effect on inflammatory cell infiltration of ischemic cardiac tissue and cardiac function. We employed two types of MSCs, human bone marrow-derived (BM) MSCs and human umbilical cord perivascular cells in an experimental acute myocardial infarction (MI) model with the immune-deficient NOD/SCID gamma null mouse. Cells were infused 48 h after induction of MI and mice assessed 24 h later (72 h after MI) for bone marrow (BM), circulating and cardiac tissue-infiltrating monocytes/macrophages. We showed that in the presence of either MSC type, overall macrophage/monocyte levels were reduced, including pro-inflammatory M1-type macrophages, while the proportion of alternatively activated M2-type macrophages was significantly increased in the circulation and heart but not the BM. Moreover, we found decreased expression of IL-1ß and IL-6, increased IL-10 expression and fewer apoptotic cardiomyocytes without changes in angiogenesis in the infarct area. Fractional shortening was enhanced 2 weeks after cell infusion but was similar to medium controls 16 weeks after MI. In vitro studies showed that BM MSCs increased the frequency of alternatively activated monocytes/macrophages, in part by MSC-mediated secretion of IL-10. Our data suggest a new mechanism for MSC-mediated enhancement of cardiac function, possibly via an IL-10 mediated switch from infiltration of pro-inflammatory to anti-inflammatory macrophages at the infarct site. Additional studies are warranted confirming the role of IL-10 and augmenting the anti-inflammatory effects of MSCs in cardiac regeneration.

Global Longitudinal Strain Predicts Survival and Left Ventricular Function After Mitral Valve Surgery: A Meta-analysis.

The timing for surgical treatment in patients with primary organic severe mitral valve regurgitation and preserved left ventricular ejection fraction (LVEF) systolic is a challenge since it depends upon LV end systolic dimension and LVEF which may be late markers of LV dysfunction. Echocardiography is the most important tool in the diagnosis of mechanisms, etiology, severity, and hemodynamic consequences of mitral regurgitation. The global longitudinal strain (GLS), a new and sensitive method for the detection of LV dysfunction, might be a useful method for the evaluation of preclinical systolic dysfunction. Nevertheless, its role for predicting postoperative outcomes is not well established. A meta-analysis was performed to address the role of GLS in patients with severe mitral regurgitation and preserved LVEF who underwent mitral surgery. We included studies that compared outcomes according to preoperative GLS in regard to survival and postoperative LV function. We included 2358 patients enrolled in 8 studies. Patients with reduced GLS% had worse long term survival after mitral valve surgery (hazard ratio = 1.13, 95% confidence interval [CI]: 1.02-1.26). Patients with preoperatively reduced GLS% had lower LVEF after surgery (mean difference [MD] = -5.06%, 95% CI: -8.97-1.16%) and additionally, patients who presented postoperative LVEF dysfunction had worse preoperative GLS (MD = 4.33, 95% CI: 3.89-4.76). In patients with primary mitral regurgitation, preoperative GLS is a predictor for long term survival and postoperative LVEF. It is a useful parameter to be included when considering early surgery in patients with severe mitral regurgitation and normal LVEF.

Predictive Factors of Mortality in Acute Aortic Dissection and Validity of the EuroSCORE Algorithm in a Small-Sized Cardiac Surgery Institution.

INTRODUCTION: Acute aortic dissection (AAD) is a devastating surgical emergency, with high operative mortality. Several scoring algorithms have been used to establish the expected mortality in these patients. Our objective was to define the predictive factors for mortality in our center and to validate the EuroSCORE and Penn classification system. METHODS: Patients who underwent surgery for AAD from 2006 to 2016 were retrieved from the institution's database. Preoperative, operative and postoperative variables were collected. Observed and expected mortality was calculated by EuroSCORE. Logistic regression analysis and Cox regression analysis were performed to find predictors of operative mortality and survival, respectively. The receiver operating characteristic (ROC) curves were plotted for logistic EuroSCORE, and the area under the ROC curve (AUC) was calculated. RESULTS: 87 patients (27.6% female) underwent surgery for AAD. The mean age was 58.6±9.7 years. Expected and observed operative mortality was 25.8±15.1% and 20.7%, respectively. Penn Aa, Ab and Abc shared similar observed/expected (O/E) mortality ratio. The only independent predictor of operative mortality (OR: 3.63; 95% CI: 1.19-11.09) and survival (HR: 2.6; 95% CI: 1.5-4.8) was female gender. EuroSCORE showed a very poor prediction capacity, with an AUC=0.566. CONCLUSION: Female gender was the only independent predictor of operative mortality and survival in our institution. EuroSCORE is a poor scoring algorithm to predict mortality in AAD, but with consistent results for Penn Aa, Ab and Abc.

The Beneficial Effect of Anticoagulation in Aortic Bioprosthesis is Associated with its Size.

OBJECTIVE: To evaluate the clinical and echocardiographic outcomes in aortic valve replacement (AVR) patients with aortic bioprosthesis under oral anticoagulation (OA). METHODS: Patients who underwent AVR with bioprosthesiswere prospectively enrolled. They were classified based on postoperative use of OA. Clinical and operative variables were collected. Echocardiographic and clinical follow-ups were performed two years after surgery. The primary outcome evaluated was change in transprosthetic gradient. Secondary outcomes analyzed were change in New York Heart Association (NYHA) class, major bleeding episodes, hospitalization, stroke, and transient ischemic attack. RESULTS: We included 103 patients (61 without OA and 42 with OA). Clinical characteristics were similar among groups, except for younger age (76±6.3 vs. 72.4±8.1 years, P=0.016) and higher prevalence of atrial fibrillation (0% vs. 23.8%, P<0.001) in the OA group. Mean (21.4±10 mmHg vs. 16.8±7.7 mmHg, P=0.037) and maximum (33.4±13.7 mmHg vs. 28.4±10.2 mmHg, P=0.05) transprosthetic gradients were higher in patients without OA. Improvement in NYHA class was more frequent in patients with OA (73% vs. 45.3%, P=0.032). Major bleeding, stroke, and hospitalization were similar among groups. OA was the only independent predictor for improvement of NYHA class after multivariate logistic regression analysis (odds ratio [OR]: 5.9, 95% confidence interval [CI]: 1.2-29.4; P=0.028). Stratification by prosthesis size showed that patients with ≤ 21 mm prosthesis benefited from OA. CONCLUSION: Early anticoagulation after AVR with bioprosthesis was associated with significant decrease of transprosthesis gradient and improvement in NYHA class. These associations were seen mainly in patients with ≤ 21 mm prosthesis.

Risk factors for vasoplegia after cardiac surgery: a meta-analysis.

OBJECTIVES: Postoperative vasoplegia (PV) is a common haemodynamic disorder after cardiac surgery and is associated with high operative mortality. Preventive and potent therapeutic measures are critical to improve the outcome. Identification of risk factors for PV may increase awareness and prompt therapeutic action. Our objective was to pool the available evidence on the risk factors for PV in cardiac surgery and to perform a meta-analysis. METHODS: PubMed, Embase, Ovid and Google Scholar databases were searched for studies published between 1965 and 2017. Three investigators independently screened the studies and extracted the data. Pooled estimates were obtained by a random effects model. Preoperative and operative patient data were gathered to determine their association with PV. RESULTS: The search yielded 109 potential studies for inclusion. Of these, 10 articles were analysed and their data extracted. The total number of patients included was 30 035 patients (1524 with vasoplegia and 28 511 without vasoplegia). The only preoperative variable that was significantly associated with PV was renal failure [odds ratio (OR) 1.47; 95% confidence interval (CI) 1.17-1.86]. Patients with isolated coronary artery bypass grafting had a lower risk for PV (OR 0.36; 95% CI 0.22-0.59), whereas previous cardiac surgery (OR 2.03; 95% CI 1.27-3.26) and combined procedures increased its incidence (OR 2.12; 95% CI 1.82-2.47). PV increased with higher use of red blood cells (OR 2.12; 95% CI 1.82-2.47), longer aortic cross-clamp (mean difference 8.15 min; 95% CI 8.79-27.50 min) and cardiopulmonary bypass (mean difference 25.72 min; 95% CI 12.75-38.69 min) duration. CONCLUSIONS: Patients with renal failure, higher use of red blood cell, longer and combined cardiac surgery procedures are at a higher risk for PV. Measures to promptly identify and treat PV in these patients should be considered.