Transcatheter aortic valve implantation versus surgical aortic valve replacement in chronic kidney disease: Meta-analysis of reconstructed time-to-event data.

BACKGROUND: Patients with advanced chronic kidney disease (CKD) are a challenging and understudied population. Specifically, the late outcomes following surgical aortic valve replacement (SAVR) or transcatheter aortic valve implantation (TAVI) in patients with CKD remains uncertain. OBJECTIVES: To compare overall mortality risk in patients with moderate-to-severe CKD following TAVI versus SAVR. METHODS: Study-level meta-analysis of reconstructed time-to-event data from Kaplan-Meier curves of studies published by August 2022. RESULTS: Nine studies met our inclusion criteria. Patients who underwent TAVI had a higher 5-year mortality compared with patients undergoing SAVR in the overall population (HR 1.56, 95% CI 1.44-1.69, P < 0.001) and in populations with similar risk scores (HR 1.15, 95% CI 1.01-1.31, P = 0.035). The landmark analysis revealed a lower risk of 30-day mortality with TAVI (HR 0.62, 95% CI 0.41-0.94, P = 0.023), followed by similar risk until 7.5 months (HR 1, 95% CI 0.78-1.27, P = 0.978). In contrast, the landmark analysis beyond 7.5 months yielded a reversal of the HR in favor of SAVR (TAVI with HR 1.27, 95% CI 1.08-1.49 P = 0.003). CONCLUSIONS: In patients with CKD, TAVI provides an initial survival benefit over SAVR. However, in the long run, a significant survival benefit of SAVR over TAVI was observed. Our findings highlight the need for randomized controlled trials to investigate outcomes in this special population.

Comparison of Multidimensional Frailty Instruments for Estimation of Long-term Patient-Centered Outcomes After Cardiac Surgery.

Importance: Little is known about the performance of available frailty instruments in estimating patient-relevant outcomes after cardiac surgery. Objective: To examine how well the Johns Hopkins Adjusted Clinical Groups (ACG) frailty indicator, the Hospital Frailty Risk Score (HFRS), and the Preoperative Frailty Index (PFI) estimate long-term patient-centered outcomes after cardiac surgery. Design, Setting, and Participants: This retrospective cohort study was conducted in Ontario, Canada, among residents 18 years and older who underwent coronary artery bypass grafting or aortic, mitral or tricuspid valve, or thoracic aorta surgery between October 2008 and March 2017. Long-term care residents, those with discordant surgical encounters, and those receiving dialysis or dependent on a ventilator within 90 days were excluded. Statistical analysis was conducted from July 2021 to January 2022. Main Outcomes and Measures: The primary outcome was patient-defined adverse cardiovascular and noncardiovascular events (PACE), defined as the composite of severe stroke, heart failure, long-term care admission, new-onset dialysis, and ventilator dependence. Secondary outcomes included mortality and individual PACE events. The association between frailty and PACE was examined using cause-specific hazard models with death as a competing risk, and the association between frailty and death was examined using Cox models. Areas under the receiver operating characteristic curve (AUROC) were determined over 10 years of follow-up for each frailty instrument. Results: Of 88 456 patients (22 924 [25.9%] female; mean [SD] age, 66.3 [11.1] years), 14 935 (16.9%) were frail according to ACG criteria, 63 095 (71.3%) according to HFRS, and 76 754 (86.8%) according to PFI. Patients with frailty were more likely to be older, female, and rural residents; to have lower income and multimorbidity; and to undergo urgent surgery. Patients meeting ACG criteria (hazard ratio [HR], 1.66; 95% CI, 1.60-1.71) and those with higher HFRS scores (HR per 1.0-point increment, 1.10; 95% CI, 1.09-1.10) and PFI scores (HR per 0.1-point increment, 1.75; 95% CI, 1.73-1.78) had higher rates of PACE. Similar magnitudes of association were observed for each frailty instrument with death and individual PACE components. The HFRS had the highest AUROC for estimating PACE during the first 2 years and death during the first 4 years, after which the PFI had the highest AUROC. Conclusions and Relevance: These findings could help to tailor the use of frailty instruments by outcome and follow-up duration, thus optimizing preoperative risk stratification, patient-centered decision-making, candidate selection for prehabilitation, and personalized monitoring and health resource planning in patients undergoing cardiac surgery.

Early and late outcomes of surgical aortic valve replacement with sutureless and rapid-deployment valves versus transcatheter aortic valve implantation: Meta-analysis with reconstructed time-to-event data of matched studies.

Sutureless/rapid-deployment (SURD) valves are options different from the stented prostheses included in the pivotal trials comparing surgical aortic valve replacement (AVR) and transcatheter aortic valve implantation (TAVI). We performed a meta-analysis with reconstructed time-to-event data of matched studies published by November 2021 to compare SURD-AVR and TAVI. Primary endpoints were 30-day mortality and overall survival in the follow-up. Secondary endpoints included: 30-day stroke, acute kidney injury (AKI), major bleeding, permanent pacemaker implantation (PPI), paravalvular leak (PVL), prosthesis-patient mismatch (PPM), postoperative aortic valve area (AVA), and mean gradients. Ten studies met our eligibility criteria, including a total of 5134 patients (2567 underwent SURD-AVR and 2567 underwent TAVI). Pooled risk of 30-day mortality did not favor any group (odds ratio [OR]: 0.69; 95% confidence interval [CI]: 0.31-1.53; p = 0.360). Patients undergoing SURD-AVR had lower risk of PVL (OR: 0.09; 95% CI: 0.05-0.17; p < 0.001). No statistically significant differences were observed for 30-day stroke, AKI, major bleeding, PPI, PPM, and postoperative AVA. In the follow-up, we observed a higher risk of mortality (hazard ratio: 1.74; 95% CI: 1.26-2.40; p < 0.001) with TAVI. Patients who underwent SURD-AVR experienced better survival, however, the interpretation of these results warrant caution due to the fact that SURD-AVR patients tended to be younger than TAVI patients. Structural heart surgeons and interventional cardiologists should consider initial risk and life expectancy when referring patients for one approach over the other.

A standardized definition for right ventricular failure in cardiac surgery patients.

Right ventricular failure (RVF) is a significant cause of mortality and morbidity after cardiac surgery. Despite its prognostic importance, RVF remains under investigated and without a universally accepted definition in the perioperative setting. We foresee that the provision of a standardized perioperative definition for RVF based on practical and objective criteria will help to improve quality of care through early detection and facilitate the generalization of RVF research to advance this field. This article provides an overview of RVF aetiology, pathophysiology, current diagnostic modalities, as well as a summary of existing RVF definitions. This is followed by our proposal for a standardized definition of perioperative RVF, one that captures RV structural and functional abnormalities through a multimodal approach based on anatomical, echocardiographic, and haemodynamic criteria that are readily available in the perioperative setting (Central Image).

Aortic Valve Repair Decreases Risks of VRE in AI at 10 Years: A Propensity Score-Matched Analysis.

BACKGROUND: Aortic valve repair (AVr) has emerged as a feasible and effective alternative to AV replacement (AVR) in patients with aortic insufficiency (AI); however, little data exist comparing outcomes. Thus, the objective of this study was to compare early and long-term valve-related complications between AVr and AVR in the treatment of AI. METHODS: This was a single-center, retrospective study of all patients (n = 417) undergoing AVr (n = 264) or AVR (n = 153) for primary AI. Propensity matching using a 1:1 greedy matching algorithm identified 140 patients using 6 covariates (age, sex, left ventricular function, size, presence of aortopathy, and urgency of operation) for comparison. The primary outcome was a composite of all valve-related events (VREs), including endocarditis, myocardial infarction stroke, transient ischemic attack, thromboembolisms, bleeding, and AV reoperation. VREs were defined as per published guidelines. Survival and freedom from VREs were reported using the Kaplan-Meier method. RESULTS: Propensity matching identified 70 well-matched pairs with no major differences in baseline demographics, comorbidities, or AI severity (P = .57). Perioperative outcomes showed no significant differences in VREs (AVR 8 vs AVr 7; P = .78) or mortality (AVR 3 vs AVr 1; P = .62). Event-free survival from the primary outcome at 10 years was significantly better after AVr than after AVR (82% vs 68%; P = .024), with no significant differences in 10-year overall survival between groups (82% vs 72%; P = .29). No significant differences in AI severity (P = .07) or reoperation rate (P = .44) were detected between groups. CONCLUSIONS: This study demonstrated a lower long-term risk of VREs with repair compared with replacement, with low mortality and comparable durability. Further prospective randomized control trials are necessary to formally compare outcomes and determine superiority.

Aortic arch surgery at 32°C: mild hypothermia and unilateral antegrade cerebral perfusion.

OBJECTIVES: With development of antegrade cerebral perfusion, the necessity of deep hypothermic circulatory arrest (CA) in aortic arch surgery has been called into question. To minimize the adverse effects of hypothermia, surgeons now perform these procedures closer to normothermia. This study examined postoperative outcomes of hemiarch replacement patients using unilateral selective antegrade cerebral perfusion and mild hypothermic CA. METHODS: Single-centre retrospective review of 66 patients undergoing hemiarch replacement with mild hypothermic CA (32°C) and unilateral selective antegrade cerebral perfusion between 2011 and 2018. Antegrade cerebral perfusion was delivered using right axillary artery cannulation. Postoperative data included death, neurological dysfunction, acute kidney injury and renal failure requiring new dialysis. Additional intraoperative metabolic data and blood transfusions were obtained. RESULTS: Eighty-six percent of patients underwent elective surgery. Mean age was 67 ± 3 years. Lowest mean core body temperature was 32 ± 2°C. Average CA was 17 ± 5 min. No intraoperative or 30-day mortality occurred. Survival was 97% at 1 year, 91% at 3 years and 88% at 5 years. Permanent and temporary neurological dysfunction occurred in 1 (2%) and 2 (3%) patients, respectively. Only 3 (5%) patients suffered postoperative stage 3 acute kidney injury requiring new dialysis. Intraoperative transfusions occurred in 44% of patients and no major metabolic derangements were observed. CONCLUSIONS: In patients undergoing hemiarch surgery, mild hypothermia (32°C) with unilateral selective antegrade cerebral perfusion via right axillary cannulation is associated with low mortality and morbidity, offering adequate neurological and renal protection. These findings require validation in larger, prospective clinical trials.

Pulmonary Autograft Coronary-Cameral Fistula Leading to LVOT Pseudoaneurysm Post Ross Procedure.

We report the case of a presumed coronary-cameral fistula arising directly below the commissures of the noncoronary cusp (NCC) and left coronary cusp (LCC) of the pulmonary autograft, leading to left ventricular outflow tract pseudoaneurysm and late tamponade post Ross procedure.

Optimal Configuration for Bypass of the Left Anterior Descending Artery During Bilateral Internal Thoracic Artery Grafting.

BACKGROUND: The left internal thoracic artery (LITA) to left anterior descending (LAD) artery bypass remains the reference standard for coronary artery bypass graft surgery. With the advent of bilateral internal thoracic artery (BITA) grafting, optimal bypass configuration to the LAD is unclear. The objective of this study was to compare clinical outcomes between LITA-LAD and right internal thoracic artery (RITA)-LAD configurations in BITA grafting. METHODS: The primary outcome was the need for percutaneous or surgical reintervention of the LAD. Secondary outcomes included all-cause mortality and cardiac mortality. Cox proportional hazard and competing risk models were used with entropy weighting. RESULTS: Among BITA patients, 1527 had LITA-LAD grafts, and 523 RITA-LAD. Before entropy weighting, RITA-LAD patients were older with more diabetes, peripheral vascular disease, and left ventricular dysfunction, more urgent status (P < .05), and more frequently performed off-pump (P < .001). Need for repeat revascularization of the LAD territory at 10 years was 2.8% in the LITA-LAD group and 1.8% in the RITA-LAD group (subhazard ratio = 0.686; 95% confidence interval [CI], 0.296-1.589; P = .38). Adjusted survival at 10 years was 97.2% in the LITA-LAD group and 98.2% in the RITA-LAD group (hazard ratio = 1.056; 95% CI, 0.677-1.647; P = .81). There was no difference in cardiac mortality (subhazard ratio = 1.063; 95% CI, 0.502-2.251; P = .87). CONCLUSIONS: Use of either LITA or RITA for LAD grafting during BITA revascularization has no effect on long-term all-cause or cardiac mortality or need for repeat revascularization of the LAD. Cardiac surgeons should be confident in using a RITA-LAD bypass during BITA grafting.

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.

Can Biomarkers Provide Right Ventricular-Specific Prognostication in the Perioperative Setting?

Since the introduction of biomarkers in the late 1980s, considerable research has been dedicated to their validation and application. As a result, many biomarkers are now commonly used in clinical practice. However, the role of biomarkers in the prediction of right ventricular failure (RVF) and in the prognostication for patients with RVF remains underexplored. Barriers include a lack of awareness of the importance of right ventricular function, especially in the perioperative setting, as well as a lack of reproducible means to assess right ventricular function in this setting. We provide an overview of biomarkers with right ventricular prognostic capabilities that could be further explored in patients expecting cardiac surgery, who are notoriously susceptible to developing RVF. We discuss biomarkers' mechanistic pathways and highlight their potential strengths and weaknesses in use in research and clinical care.

Native Coronary Disease Progression Post Coronary Artery Bypass Grafting.

BACKGROUND: It remains unclear if graft type impacts native disease progression in the target coronary artery post coronary artery bypass grafting (CABG). METHODS: Patients who underwent repeat angiograms at least 6 months post CABG with ≥1 arterial graft were included. Pre/post CABG angiograms were examined by 2 experienced readers. Progression was defined as new stenosis of ≥50% in a previously normal coronary, an increase in previous stenosis of ≥20%, or a new occlusion. Primary outcome was the occurrence of native disease progression in bypassed vessels. Secondary outcomes included complete occlusion, left main (LM) and distal disease progression. Cox-proportional hazard regression models were used for time-to-event outcomes. RESULTS: Study population included 98 patients comprising 263 grafts (143 arterial/120 venous grafts). Median time from surgery to catheterization was 559 days (Interquartile Range 374,910).Ninety-one target vessels showed progression (34.6%) with 75 to complete occlusion (28.5%). Progression was not associated with graft choice (HR 0.74(0.49,1.13) p = 0.163),but was significantly associated with age(p = 0.034),previous PCI(p = 0.002),ACE inhibitor (ACEi) use(p < 0.001),CAD severity (p < 0.001),CCS class III/IV(p = 0.016) and NYHA class III/IV(p < 0.001). Progression to occlusion was significantly associated with SVG (p = 0.019), as well as previous percutaneous coronary intervention (p = 0.007) and ACEi use (p < 0.001). LM disease progression was significantly associated with peripheral vascular disease (HR 5.44(1.92, 15.46), p = 0.001), and not affected by graft type (p = 0.754). CONCLUSIONS: Native CAD progression in non-LM coronaries is multifactorial, while SVG use was only associated with occlusion of non-LM coronaries. The implications of this study warrant consideration for increased arterial grafting in CABG patients, while the negative associations of previous PCI and ACEi use carry important clinical implications, which require further investigation.

COMMENCE trial (Comparing hypOtherMic teMperaturEs duriNg hemiarCh surgEry): a randomized controlled trial of mild vs moderate hypothermia on patient outcomes in aortic hemiarch surgery with anterograde cerebral perfusion.

BACKGROUND: Aortic arch surgery remains the only viable life-saving treatment for aortic arch disease. However, the necessity for cessation of systemic blood flow with hypothermic cardiac arrest carries substantial risk of morbidity and mortality, including poor neurological outcomes and kidney failure. While uncontrolled studies have suggested the safety of operating at warmer temperatures, significant variables remain un-investigated, supporting the need for a randomized clinical trial (RCT) to produce evidence-based guidelines for perfusion strategies in aortic surgery. This study proposes a multi-center RCT in order to compare outcomes of warmer hypothermic strategies during aortic hemiarch surgery on a composite endpoint of neurologic and acute kidney injury (AKI). METHODS/DESIGN: This is a prospective multi-center, single-blind two-arm RCT comparing mild (32 °C) versus moderate (26 °C) hypothermic cardiac arrest in patients (n = 282) undergoing hemiarch surgery with antegrade cerebral perfusion (ACP). The primary endpoint is a composite of neurological injury (incidence of transient ischemic attack and/or stroke) and Kidney Disease Improving Global Outcomes (KDIGO) stage 1 or higher AKI. Secondary outcomes include death, cardiopulmonary bypass time, bleeding, transfusion rates, prolonged mechanical ventilation, myocardial infarction, length of stay, and quality of life measures. Patients will undergo 1:1 block randomization to each treatment arm on day of surgery. Sequence of operation will be at the surgeon's discretion with mandatory guidelines for temperature and ACP administration. Perioperative management will occur as per enrolling center standard of care. Neurocognitive function will be assessed for neurological injury using validated neurological screening tests: NIHSS, MOCA, BI, and MRS throughout patient follow-up. Diagnosis and classification of AKI will be based on rising creatinine values as per the KDIGO criteria. Study duration for each patient will be 60 ± 14 days. DISCUSSION: It is hoped that performing hemiarch surgery using mild hypothermia (32 °C) and selective ACP will result in a 15% absolute risk reduction in the composite outcomes. The potential of this risk reduction will translate into improved patient outcomes, survival, and long-term financial savings to the health care system. In addition, the results of this trial will be used to create the first-ever guidelines for temperature management strategy during aortic surgery. TRIAL REGISTRATION: This trial is registered on ClinicalTrials.gov with the registration number NCT02860364. Registration date August 9th, 2016.

Biomarkers in the Diagnosis, Management, and Prognostication of Perioperative Right Ventricular Failure in Cardiac Surgery-Are We There Yet?

Right ventricular failure (RVF) is a major risk factor for end organ morbidity and mortality following cardiac surgery. Perioperative RVF is difficult to predict and detect, and to date, no convenient, accurate, or reproducible measure of right ventricular (RV) function is available. Few studies have examined the use of biomarkers in RVF, and even fewer have examined their utility in the perioperative setting of patients undergoing cardiac surgery. Of the available classes of biomarkers, this review focuses on biomarkers of (1) inflammation and (2) myocyte injury/stress, due to their superior potential in perioperative RV assessment, including Galectin 3, ST2/sST2, CRP, cTN/hs-cTn, and BNP/NT-proBNP. This review was performed to help highlight the importance of perioperative RV function in patients undergoing cardiac surgery, to review the current modalities of RV assessment, and to provide a review of RV specific biomarkers and their potential utilization in the clinical and perioperative setting in cardiac surgery. Based on current evidence, we suggest the potential utility of ST2, sST2, Gal-3, CRP, hs-cTn, and NT-proBNP in predicting and detecting RVF in cardiac surgery patients, as they encompass the multifaceted nature of perioperative RVF and warrant further investigation to establish their clinical utility.

The Effect of Preoperative Anemia on Patients Undergoing Cardiac Surgery: A Propensity-Matched Analysis.

It is unknown if anemia in the absence of transfusions is an independent risk factor for adverse outcomes in cardiac surgery, and if correction to higher hemoglobin targets impacts these outcomes. This is a retrospective review of 3848 cardiac surgery patients. Propensity matching was completed using 41 covariates. Intraoperative Anemia Analysis matched patients with or without anemia who did not receive intraoperative transfusions (n = 392/group), while Intraoperative Transfusion Analysis matched anemic patients treated conventionally with intraoperative transfusions to end cardiopulmonary bypass hemoglobin greater or less than 95 g/L (n = 261/group). Outcomes of death, renal failure, and 2 composite outcomes were assessed using paired analysis techniques. Study composite 1 consisted of prolonged ventilation, renal failure, myocardial infarction, stroke, or deep sternal wound infection, while composite 2 was the TRICS-III composite. In the Intraoperative Anemia Analysis, anemia was associated with mortality (P = 0.034), stroke (P = 0.021), renal failure (P = 0.015), and a significant increase in the composite measure (control 8.7% vs anemia 16.1%, P = 0.002). These findings were unchanged in patients who did not receive any postoperative transfusions. The Intraoperative Transfusion Analysis showed no difference in mortality or the composite outcome between groups. There was a significant increase in low cardiac output in the lower threshold group (P = 0.001). There were no differences in outcomes between those who did and did not receive postoperative transfusions (P > 0.05). Preoperative anemia in the absence of transfusions is a risk factor for morbidity and mortality after cardiac surgery, and there is no evidence that transfusion to higher end cardiopulmonary bypass hemoglobin levels impacted this risk.

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.

Impact of Gender on Arterial Revascularization Strategies for Coronary Artery Bypass Grafting.

BACKGROUND: There are significant gender differences in arterial revascularization approaches in coronary operations. This study addressed these differences to determine whether discrepancies are related to underlying risk profiles or systematic gender bias. METHODS: Changes in gender-specific rates of revascularization approaches were determined in 19,557 patients undergoing isolated coronary artery bypass grafting (CABG). A propensity-balanced group was generated on a subset of 1,254 CABG patients based on 45 pretreatment covariates to assess rates in matched groups (627 patients per group). RESULTS: In the entire cohort, male gender was associated with increased bilateral internal thoracic artery (BITA) use (odds ratio, 1.667; 95% confidence interval [CI], 1.166 to 2.386; p = 0.005). Multiple-arterial grafting increased yearly in both genders, but the rate of increase in BITA use was greater in men (1.59%/year [95% CI, 1.56 to 1.63] vs 1.37%/year [95% CI, 1.30 to 1.45], p < 0.001) as was the use of 3 arteries (1.16%/year [95% CI, 1.13 to 1.20] vs 0.73%/year [95% CI, 0.67 to 0.80), p < 0.001) and the use of any 2 arteries (2.34%/year (95% CI, 2.32 to 2.35) vs 1.92%/year [95% CI, 1.90 to 1.95], p < 0.001). In the propensity-matched group, there was no difference in BITA use (male: 31.9%, female: 30.1%; p = 0.502), BITA use in low-risk patients (male: 46.4%, female: 38.0%; p = 0.126), or radial artery use (male: 44.5%, female: 44.1%; p = 0.994), but use of 3 arteries was greater in men (10.5% vs 7.3%, p = 0.048). CONCLUSIONS: Women receive less complete multiple arterial coronary revascularization than men. This is likely related to later presentation of coronary artery disease in women with higher comorbidity profiles; however, when matched, bias may still exist limiting the option of grafting with 3 arteries to women.

The Nlrp3 inflammasome promotes myocardial dysfunction in structural cardiomyopathy through interleukin-1ß.

Heart failure is associated with a low-grade and chronic cardiac inflammation that impairs function; however, the mechanisms by which this sterile inflammation occurs in structural heart disease remain poorly defined. Cardiac-specific heterozygous overexpression of the calcineurin transgene (CNTg) in mice results in cardiac hypertrophy, inflammation, apoptosis and ventricular dilatation. We hypothesized that activation of the Nlrp3 inflammasome, an intracellular danger-sensing pathway required for processing the pro-inflammatory cytokine interleukin-1ß (IL-1ß), may contribute to myocardial dysfunction and disease progression. Here we report that Nlrp3 mRNA was increased in CNTg mice compared with wild-type. Consistent with inflammasome activation, CNTg animals had increased conversion of pro-caspase-1 to cleaved and activated forms, as well as markedly increased serum IL-1ß. Blockade of IL-1ß signalling via chronic IL-1 receptor antagonist therapy reduced cardiac inflammation and myocyte pathology in CNTg mice, resulting in improved systolic performance. Furthermore, genetic ablation of Nlrp3 in CNTg mice reduced pro-inflammatory cytokine maturation and cardiac inflammation, as well as improving systolic performance. These findings indicate that activation of the Nlrp3 inflammasome in CNTg mice promotes myocardial inflammation and systolic dysfunction through the production of pro-inflammatory IL-1ß. Blockade of IL-1ß signalling with the IL-1 receptor antagonist reverses these phenotypes and offers a possible therapeutic approach in the management of heart failure.