Effects of RBT-1 on preconditioning response biomarkers in patients undergoing coronary artery bypass graft or heart valve surgery: a multicentre, double-blind, randomised, placebo-controlled phase 2 trial.

Background: RBT-1 is a combination drug of stannic protoporfin (SnPP) and iron sucrose (FeS) that elicits a preconditioning response through activation of antioxidant, anti-inflammatory, and iron-scavenging pathways, as measured by heme oxygenase-1 (HO-1), interleukin-10 (IL-10), and ferritin, respectively. Our primary aim was to determine whether RBT-1 administered before surgery would safely and effectively elicit a preconditioning response in patients undergoing cardiac surgery. Methods: This phase 2, double-blind, randomised, placebo-controlled, parallel-group, adaptive trial, conducted in 19 centres across the USA, Canada, and Australia, enrolled patients scheduled to undergo non-emergent coronary artery bypass graft (CABG) and/or heart valve surgery with cardiopulmonary bypass. Patients were randomised (1:1:1) to receive either a single intravenous infusion of high-dose RBT-1 (90 mg SnPP/240 mg FeS), low-dose RBT-1 (45 mg SnPP/240 mg FeS), or placebo within 24-48 h before surgery. The primary outcome was a preoperative preconditioning response, measured by a composite of plasma HO-1, IL-10, and ferritin. Safety was assessed by adverse events and laboratory parameters. Prespecified adaptive criteria permitted early stopping and enrichment. This trial is registered with ClinicalTrials.gov, NCT04564833. Findings: Between Aug 4, 2021, and Nov 9, 2022, of 135 patients who were enrolled and randomly allocated to a study group (46 high-dose, 45 low-dose, 44 placebo), 132 (98%) were included in the primary analysis (46 high-dose, 42 low-dose, 44 placebo). At interim, the trial proceeded to full enrollment without enrichment. RBT-1 led to a greater preconditioning response than did placebo at high-dose (geometric least squares mean [GLSM] ratio, 3.58; 95% CI, 2.91-4.41; p < 0.0001) and low-dose (GLSM ratio, 2.62; 95% CI, 2.11-3.24; p < 0.0001). RBT-1 was generally well tolerated by patients. The primary drug-related adverse event was dose-dependent photosensitivity, observed in 12 (26%) of 46 patients treated with high-dose RBT-1 and in six (13%) of 45 patients treated with low-dose RBT-1 (safety population). Interpretation: RBT-1 demonstrated a statistically significant cytoprotective preconditioning response and a manageable safety profile. Further research is needed. A phase 3 trial is planned. Funding: Renibus Therapeutics, Inc.

The Effect of Posterior Pericardiotomy on the Incidence of Atrial Fibrillation After Cardiac Surgery-Extended Follow-Up study (PALACS-EF): rationale and design.

Aims: Postoperative atrial fibrillation (POAF) is the most common complication of cardiac surgery and has been associated with increased postoperative morbidity and hospital costs. The Posterior left pericardiotomy for the prevention of AtriaL fibrillation After Cardiac Surgery (PALACS) trial found that posterior pericardiotomy significantly reduced the incidence of POAF (17% vs. 32%, P < 0.001). We present the protocol for The Effect of Posterior Pericardiotomy on the Incidence of Atrial Fibrillation After Cardiac Surgery-Extended Follow-Up study (PALACS-EF): a prospective, extended follow-up of the original PALACS trial. The aim of PALACS-EF is to gain more data regarding the effect of posterior pericardiotomy on postdischarge clinical outcomes. The primary outcome is the time to the first occurrence of the composite of all-cause mortality or hospital cardiovascular readmission. The key secondary outcome is the time to the first occurrence of the composite of all-cause mortality and all-cause hospital readmission. Hospital readmission, myocardial infarction, stroke, transient ischaemic attack, heart failure, systemic embolism, or new arrhythmias with onset since 30-day follow-up will also be recorded. Methods and results: All 420 patients enrolled in the PALACS trial will be included; extended follow-up will be conducted via telephone by blinded research personnel utilizing a standardized script to ensure uniformity and completeness of follow-up. If an event has occurred, documentation will be obtained, and an independent adjudication committee blinded to group assignment will adjudicate outcome events. Results will be reported when a median follow-up of 5 years is achieved. Conclusion: PALACS-EF will provide data to answer the question of whether posterior pericardiotomy improves postdischarge outcomes in patients undergoing cardiac surgery, and it will provide information on the relationship between POAF and adverse postdischarge outcomes including mortality, hospitalization, heart failure, and stroke. Registration: PALACS: NCT02875405, PALACS-EF: NCT05903222.

Hospital characteristics associated with failure to rescue in cardiac surgery.

Objective: The study objective was to examine the association between hospital processes of care and failure to rescue in a diverse, multi-institutional cardiac surgery network. Methods: Failure to rescue was defined as an operative mortality after 1 or more of 4 complications: prolonged ventilation, stroke, renal failure, and unplanned reoperation. Society of Thoracic Surgeons data from 20,950 consecutive patients in the Columbia HeartSource network who underwent 1 of 7 cardiac operations-coronary artery bypass grafting, aortic valve replacement ± coronary artery bypass grafting, mitral valve repair or replacement ± coronary artery bypass grafting-were analyzed to calculate failure to rescue rates. Hospital-specific characteristics were ascertained by survey method. Multivariable mixed-effects logistic models assessed the association of these hospital characteristics with failure to rescue while adjusting for patient-related factors known to be associated with mortality. Results: Failure to rescue rates at affiliate hospitals ranged from 5.45% to 21.74% (median, 12.5%; interquartile range, 6.9%). When controlling for Society of Thoracic Surgeons-predicted risk of mortality with hospital as a random effect, 4 hospital characteristics were found to be associated with lower failure to rescue rates; the presence of cardiac-trained anesthesiologists (odds ratio, 0.41; CI, 0.31-0.55, P < .001), availability of extracorporeal membrane oxygenation mechanical circulatory support (odds ratio, 0.41; CI, 0.31-0.54, P < .001), ratio of intensive care unit beds to intensivists (odds ratio, 0.87; CI, 0.76-0.99, P = .039), and total number of intensive care unit beds (odds ratio, 0.97; CI, 0.96-0.99, P = .002). Conclusions: In a diverse multi-institutional cardiac surgical network, we were able to identify specific hospital processes of care associated with failure to rescue, even when adjusting for patient-related predictors of operative mortality.

Implementing a High-Value Care Discharge Protocol in Patients Undergoing CABG Reduces Readmission.

BACKGROUND: Readmission after coronary artery bypass grafting (CABG) is associated with adverse outcomes and increased cost. We evaluated the impact of a high-value care discharge protocol on readmission, length of stay (LOS), and discharge destination in patients undergoing isolated CABG. METHODS: In 2016, a comprehensive, patient-centered discharge protocol was implemented. A nurse practitioner was the fulcrum of this program, which focused on improving health literacy, disease management, and rigorous follow-up. All patients undergoing isolated CABG between 2012 and 2019 were retrospectively analyzed with regard to 30-day readmission, LOS, and discharge disposition. Differences were analyzed by Mann-Whitney, chi-square, and t tests. Analyses were repeated using propensity matching. RESULTS: A total of 910 consecutive patients undergoing isolated CABG were included in the analyses: 353 preprotocol and 557 postprotocol. Preprotocol patients had a readmission rate of 14.4% (n = 51), compared with 6.8% (n = 38) in the postprotocol patients (P < .001). Median postoperative LOS before implementation was 6 (interquartile range, 5-8) days compared with 5 (interquartile range, 4-6) days postimplementation (P < .001). Postimplementation, a higher proportion of patients were discharged to home compared with a skilled nursing facility (82.7% [n = 461] vs 73.9% [n = 261]; P = .002). After propensity matching, 298 well-balanced patients were included for analysis and these significant reductions in LOS, readmission, and discharge destination persisted. CONCLUSIONS: Implementation of a new discharge protocol was significantly associated with reduced readmission and LOS, along with higher rates of discharge to home in isolated CABG patients. Importantly, the results were sustainable and did not require additional resources, delivering high-value care.

Delayed Treatment of Acute Myocardial Infarction With Ventricular Septal Rupture Due to Patient Fear During the COVID-19 Pandemic.

During the coronavirus disease 2019 (COVID-19) pandmic, more patients are presenting with complications late after acute myocardial infarction. We report the case of a 71-year-old man who delayed seeking medical care for 2 weeks, despite progressive shortness of breath, cough, and tactile fever, for fear of contracting COVID-19 in the hospital. Clinical and echocardiographic evaluation revealed a ventricular septal rupture secondary to acute myocardial infarction. The patient underwent urgent cardiac catheterization, followed by successful saphenous vein grafting to the left anterior descending coronary artery and open surgical repair of the ventricular septal rupture with a bovine pericardial patch. This case highlights a potential long-lasting negative effect that the COVID-19 pandemic will have on the care-seeking behavior and health of patients with acute cardiovascular disease.

A Perspective from New York of COVID 19: Effect and impact on cardiac surgery.

BACKGROUND AND AIM: First reported in December of 2019, the COVID-19 pandemic caused by SARS-CoV-2 has had a profound impact on the implementation of care. Here, we describe our institutional experience with a rapid influx of patients at the epicenter of the pandemic. METHODS: We retrospectively review our experience with the departments of cardiology, cardiothoracic surgery, anesthesia, and critical care medicine and summarize protocols developed in the midst of the pandemic. RESULTS: The rapid influx of patients requiring an intensive level of care required a complete restructuring of units, including the establishment of a new COVID-19 negative unit for the care of patients requiring urgent or emergent non-COVID-19 related care including open-heart surgery. This unique unit allowed for the delivery of safe and effective care in the epicenter of the pandemic. CONCLUSIONS: Here, we demonstrate the response of a large tertiary academic medical center to the COVID-19 pandemic. Specifically, we demonstrate how rapid structural changes can allow for the continued delivery of cardiac surgical care with similar outcomes as those reported before the pandemic.

Staged Endovascular Repair of Aortic Coarctation followed by Double Valve Surgery.

We present a unique case of late diagnosis of coarctation of the aorta in an adult, presenting with congestive heart failure associated with severe aortic and mitral valve insufficiency. To minimize operative risk, staged endovascular repair of the coarctation was initially performed, followed by aortic valve replacement and mitral valve repair. Six months postoperatively, the 41-year-old patient remains completely asymptomatic.

Intraoperative Autologous Blood Donation Leads to Fewer Transfusions in Cardiac Surgery.

BACKGROUND: Blood conservation with antifibrinolytics, topical hemostatics, and strict transfusion triggers are becoming commonplace in cardiac surgery. The aim of this study was to evaluate the effect of a blood conservation protocol centering on standardized intraoperative autologous blood donation (IAD) use in cardiac surgery. METHODS: We reviewed charts of patients who underwent cardiac surgery at our hospital over an 8-year period to analyze transfusion tendencies before and after a new blood conservation policy was implemented. Propensity score matching was used to account for population differences in preoperative and perioperative covariates. RESULTS: Over an 8-year period (January 2009 to December 2017) 1002 patients were studied. Three hundred fifty-two patients before the new blood conservation policy (group 1) were compared with 650 patients after the change (group 2). Fewer group 2 patients required blood transfusions during their hospital stay (78% vs 61%, P < .001), were transfused fewer units (2.8 vs 1.81 units, P < .001), and experienced a shorter length of stay (8.02 vs 7.28 days, P = .012). Propensity score-matched cohorts revealed reductions in any complication (29.5% vs 18.8%, P = .007), fewer postoperative transfusions (70.1% vs 50.9%, P < .001), and a lower transfusion volume (1.82 vs 1.21 units, P = .002) associated with IAD without any associated change in mortality. CONCLUSIONS: IAD use is associated with reduced transfusions in cardiac surgery and may be considered a complementary aspect of blood conservation. Our experience suggests it may be applied with few limitations. A causal relationship between IAD and outcomes should be established with prospective studies.

Ascending aortic aneurysm repair and surgical ablation for atrial fibrillation.

BACKGROUND: Although surgical ablation of atrial fibrillation is commonly performed during concomitant coronary or valve surgery, it is still only performed in a fraction these cases when indicated, and less often in patients undergoing aneurysm surgery. We describe our experience in patients undergoing ascending aneurysm repair and concomitant atrial fibrillation ablation. METHODS: From January 2004 until November 2011, 40 patients underwent ascending aneurysm repair and atrial fibrillation ablation at our institution and were retrospectively analyzed. RESULTS: Average age was 67.6 years (43-85). Root replacement was performed in 23 (57.5 %) and arch replacement with circulatory arrest in 18 (45 %). At an average of 41.8 months, 81 % of patients were in sinus rhythm. Operative survival was 100 %, with 1 and 5 year survival of 97.5 and 93.1 %, respectively. Kaplan-Meier analysis revealed improved overall survival in patients with rhythm success (log-rank test p = 0.037). CONCLUSIONS: Aortic aneurysm repair with concomitant atrial fibrillation ablation is safe and efficacious despite the requirement for an already extensive procedure with rhythm success rates similar to those quoted in the setting of other procedures. Successful restoration of sinus rhythm improves long term survival and should be considered in patients presenting with aortic aneurysm and atrial fibrillation.

Role of cytoskeletal proteins in cerebral cavernous malformation signaling pathways: a proteomic analysis.

Three genetic mutations were found to cause cerebral cavernous malformation (CCM), a vascular anomaly predisposing affected individuals to hemorrhagic stroke. These CCM proteins function together as a protein complex in the cell. Loss of expression of each CCM gene results in loss of in vitro endothelial tube formation. Label-free differential protein expression analysis using multidimensional liquid chromatography/tandem mass spectrometry (2D-LC-MS/MS) was applied to explore the proteomic profile for loss of each CCM gene expression in mouse endothelial stem cells (MEES) compared to mock shRNA and no shRNA control cell-lines. Differentially expressed proteins were identified (p < 0.05). 120 proteins were differentially expressed among the cell-lines. Principal component analysis and cluster analysis show the effects of individual knockdown. In all knockdown cell-lines, altered expression of cytoskeletal proteins is the most common. While all CCM mutations result in similar pathology, different CCM mutations have their own distinct pathogenesis in cell signaling.

Reoperations on the ascending aorta and aortic root in patients with previous cardiac surgery.

BACKGROUND: First time operations on the ascending aorta are performed with low mortality, few complications, and excellent long-term results. Reoperations for aortic pathology in patients with previous cardiac surgery carry significantly more risk. Technical issues during the procedure, as well as age, preoperative New York Heart Association class, and perioperative renal dysfunction, have been shown to contribute heavily to worse outcomes. We analyzed our results with aortic reoperations with the intent of further reducing surgical risk through alterations in surgical technique or patient selection. METHODS: From July 1997 until October 2005, 147 patients having previous cardiac surgery presented with aneurysm or dissection of the ascending aorta or root. Perioperative data were retrospectively analyzed. Morbidity, mortality, and risk factors for these events were calculated. RESULTS: Eight patients expired (5.4%) after their reoperation. Significant (p < 0.05) univariate risk factors for mortality included age greater than 75 years (< 0.001), previous coronary artery bypass grafting (CABG) (< 0.008), cardiopulmonary bypass greater than 240 minutes (< 0.01), need for intraaortic balloon pump support (< 0.001), need for new CABG (< 0.007), postoperative cerebrovascular accident (< 0.032), and tracheostomy (< 0.003). Age 75 years or older (p < 0.025) was the only significant variable for death by multivariate analysis. A majority of patients (n = 87, 60%) required circulatory arrest to complete their procedure. However, neither arch involvement nor type of aortic root procedure was predictive of perioperative mortality. CONCLUSIONS: Surgery on the ascending aorta and root in patients who have had previous cardiac surgery can be performed with low mortality. Advanced age and significant coronary disease may negatively influence surgical results.

Arteriovenous fistula after laser-assisted pacemaker lead extraction.

Acute arteriovenous fistulas have been reported after pacemaker lead extraction. We report a case of an arteriovenous fistula presenting 2 weeks after transvenous laser-assisted lead extraction.

Epicardial beating heart cryoablation using a novel argon-based cryoclamp and linear probe.

OBJECTIVE: Epicardial, beating heart cryoablation for the treatment of atrial fibrillation may be limited by heat from intracardiac blood flow. We therefore evaluated the ability to create cryolesions using an argon-based cryoclamp device, which temporarily occludes blood flow and facilitates transmurality. METHODS: Six mongrel dogs underwent sternotomy. A clamp employing a 10-cm argon-based linear cryoablation device was used epicardially to isolate the pulmonary veins and left atrial appendage. After clamping of lesions, the probe was removed from the cryoclamp device, and the remaining linear lesions, analogous to the Cox maze III, were performed. Pulmonary vein stenosis was evaluated with the use of magnetic resonance imaging. Left atrial function and pulmonary venous flow velocities were assessed with transesophageal echocardiography. Transmurality was confirmed both electrically and histologically. Animals were then put to death at 30 days. RESULTS: All acute and chronic cryoclamp lesions produced conduction block. There was no change in right (RPV) or left pulmonary vein (LPV) diameter on the basis of magnetic resonance imaging at baseline and at planned death (RPV-1, 19.6 +/- 2.9 mm vs 16.9 +/- 2.8 mm, P = .22; RPV-2, 13.2 +/- 2.0 mm vs 11.8 +/- 1.6 mm, P = .22; and LPV, 12.2 +/- 2.4 mm vs 11.2 +/- 1.9 mm, P = .30). Left atrial function and pulmonary venous flow velocities were unchanged. Tissue sections determined transmurality in 93% of cryoclamp lesions and 84% of linear ablations performed with the 10-cm malleable probe. CONCLUSIONS: Epicardial application of this cryoclamp device on the beating heart produced transmural lesions, which persisted 30 days. Linear epicardial cryoablation was not as effective as the cryoclamp device at producing consistent transmural lesions. This novel, versatile device may be useful in treating patients with atrial fibrillation on the beating heart without cardiopulmonary bypass.

No-clamp technique for valve repair or replacement in patients with a porcelain aorta.

BACKGROUND: Patients requiring valvular heart surgery may have circumferential calcification of the ascending aorta. A variety of creative procedures have been described for managing this "porcelain aorta." We describe a technique based on replacement of the ascending aorta and proximal arch under profound hypothermic circulatory arrest, followed by the valve procedure. METHODS: Twenty-five consecutive patients with a porcelain aorta were referred for heart valve surgery. In every case the aorta was replaced under circulatory arrest before the valve procedure. Postoperative morbidity, mortality, and univariate risk factors for death were calculated. Fisher's exact test defined significant perioperative variables with a p value less than 0.05. RESULTS: Of 25 patients, 23 (92%) survived the surgery to hospital discharge. One patient had a stroke (4%) and 2 patients (8%) required reexploration for bleeding. Risk factors for perioperative death by univariate analysis included age more than 78 years (p < 0.009), cardiopulmonary bypass time longer than 200 minutes (p < 0.0001), reexploration for bleeding (p < 0.02), need for intra-aortic balloon pump support (p < 0.001), and postoperative gastrointestinal complications (p < 0.001). CONCLUSIONS: Valve replacement or repair in the patient with a porcelain aorta can be safely accomplished with a technique based on aortic replacement under circulatory arrest. Elderly patients requiring extensive procedures and prolonged periods on bypass have a substantially increased risk for postoperative complications and death.

Surgical treatment of atrial fibrillation using argon-based cryoablation during concomitant cardiac procedures.

BACKGROUND: The development of ablative energy sources has simplified the surgical treatment of atrial fibrillation (AF) during concomitant cardiac procedures. We report our results using argon-based endocardial cryoablation for the treatment of AF in patients undergoing concomitant cardiac procedures. METHODS AND RESULTS: Sixty-three patients with AF who were undergoing concomitant cardiac procedures had the same left atrial endocardial lesion set using a flexible argon-based cryoablative device. Mean age was 65.1+/-1.3 years. Sixty-two percent had permanent AF, whereas 38% had paroxysmal AF. Mean duration of AF was 30.5+/-4.8 months. Mean left atrial diameter was 5.5+/-0.1 cm. Mean ejection fraction was 45+/-1.4%. All endocardial lesions were performed for 1 minute once tissue temperature reached -40 degrees C. Follow-up echocardiograms were obtained to determine freedom from AF. Kaplan-Meier analysis demonstrated an 88.5% freedom from AF rate at 12 months. Ablation time was 16.8+/-0.6 minutes. There were no in-hospital deaths and no strokes. Twelve patients (19%) required postoperative permanent pacemaker placement. CONCLUSIONS: Cryoablation using this flexible argon-based device for the treatment of AF during concomitant cardiac procedures was safe and effective, with 88.5% of patients free from AF at 12 months.

Comparison of open versus bedside percutaneous dilatational tracheostomy in the cardiothoracic surgical patient: outcomes and financial analysis.

BACKGROUND: The clinical and financial outcomes of a change in practice from traditional tracheostomy (open) to bedside percutaneous dilatational tracheostomies (PDT) was evaluated in patients who underwent cardiothoracic surgery. METHODS: During 3 years, 86 tracheostomies were performed in more than 4,000 patients who underwent cardiac surgery, 59 open and 27 PDT. A retrospective analysis was performed comparing clinical and financial outcomes of the two groups. RESULTS: There were no significant differences in demographics, medical histories, operations, or complications between open and PDT except the open group experienced more postoperative arrhythmias (70% [41 of 59] versus 44% [12 of 27], p < 0.05). Total savings associated with 1 year of PDT was $84,000, for a projected discounted savings of $283,000 during the study period. A sensitivity analysis of critical economic variables (number of tracheostomies per year, cost of operating room per minute, cost of intensive care unit bed per day) was included to evaluate the impact on cost savings. The net present value analysis, which discounts future savings by an appropriate interest rate, yielded a range of projected savings of PDT more than 5 years of $73,000 to $541,000 with a best estimate of $304,000 using figures established from our 3-year experience with PDT. Sensitivity analysis of the net present value for each critical variable was $227,000 per day of reduced intensive care unit length of stay, $180,000 per cost of operating room avoidance, $100,000 per intensive care unit bed cost per day, and $11,000 per additional tracheostomy per year. CONCLUSIONS: There were no significant clinical differences between open and PDT in cardiac surgery patients during the 3-year study period; however, PDT offered significant cost savings.