Acute Kidney Injury After Cardiac Surgery.

Acute kidney injury associated with cardiac surgery (CS-AKI) remains a vexing issue. Clinical trials for the prevention of CS-AKI have been disappointing despite enormous initial enthusiasm based on experimental data. The schism in experimental and clinical data has triggered a relook at our understanding of CS-AKI and the experimental and preclinical models. The silver lining in the midst is the standardization of anesthetic and perioperative care proposed by national societies. In this review we discuss the therapeutic targets of major clinical trials.

Longitudinal Examination of Swallowing Safety and Vocal Fold Mobility in Cardiac Surgical Patients.

BACKGROUND: Aspiration and vocal fold mobility impairment (VFMI) are frequently reported in adults after cardiac surgery (CS) and impede recovery. Preoperative and postoperative laryngoscopic evaluations have not been undertaken, masking the incidence and evolution of dysphagia and VFMI in CS patients. We therefore sought to determine frequency of unsafe swallowing and VFMI before and after CS. METHODS: Thirty-five adults undergoing elective CS enrolled. Participants underwent fiberoptic endoscopic evaluations of swallowing and VFMI before and after surgical procedure. Trained raters performed duplicate, blinded ratings with the validated Penetration-Aspiration Scale, and a laryngologist performed blinded ratings of VFMI. Descriptive, Wilcoxon signed rank, and McNemar tests were performed. RESULTS: Preoperative swallowing safety profiles were 60% safe, 34% penetration, and 6% aspiration. Postoperative swallowing safety profiles were 14% safe, 63% penetration, and 23% aspiration. Significant differences in preoperative to postoperative swallowing outcomes were noted for Penetration-Aspiration Scale scores (P < .0001), unsafe swallowing (40% vs 86%; χ2 = 12.8; P = .0003), and aspiration (6% vs 23%; χ2 =6; P = .01). No differences in VFMI were noted preoperatively to postoperatively (partial VFMI, 9% vs 23%; P > .05). CONCLUSIONS: A 4-fold increase in aspiration was observed in CS patients. No cases of vocal fold paralysis were observed across time points. These data highlight the utility of instrumental laryngoscopic evaluations during the acute postoperative phase.

Pericarditis prophylactic therapy after sinus node-sparing hybrid ablation for inappropriate sinus tachycardia/postural orthostatic sinus tachycardia.

Background: Pericarditis is the most common complication following hybrid sinus node-sparing ablation for inappropriate sinus tachycardia (IST)/postural orthostatic tachycardia syndrome (POTS). Objective: The study sought to evaluate the association of prophylaxis therapy on the risk of symptomatic pericarditis following hybrid IST/POTS ablation. Methods: All consecutive patients undergoing to hybrid ablation of symptomatic IST/POTS refractory or intolerant to drugs were retrospectively analyzed. Pharmacological prophylaxis therapy was based on acetylsalicylic acid and colchicine started on the day of the ablation and continued for at least 3 months. The primary endpoint was occurrence of symptomatic pericarditis. The secondary endpoint was occurrence of pericarditis-related complications, including the following: duration of pericarditis >3 months, hospitalization for pericarditis, postpericardiectomy pleuro-pericarditis, and pericardiectomy. Results: A total of 220 patients undergone to hybrid IST/POTS ablation were included and 44 (20%) underwent prophylaxis therapy. Pericarditis occurred in 101 (45.9%) patients, with 97 (96%) in the first 5 days. At survival analysis, prophylaxis was associated with higher rate of freedom from pericarditis (81.9% vs 47.2%, log-rank P < .001). Pericarditis-related complications were low, occurring in 7 (3.2%) patients. There was no difference in pericarditis-related complications between the patients who underwent prophylaxis therapy and patients who did not. At Cox multivariate analysis, predictors of pericarditis were IST (vs POTS) (hazard ratio 0.61, 95% confidence interval0.39-0.99, P = .04) and prophylaxis therapy (hazard ratio 0.27, 95% confidence interval 0.13-0.55, P < .001). Conclusion: In a large cohort of patients undergoing hybrid ablation for IST/POTS, a prophylaxis therapy with acetylsalicylic acid and colchicine was associated with a lower rate of symptomatic pericarditis.

Reconsidering FDA Guidelines: A Single-Center Experience of Prolonged Impella 5.5 Support.

OBJECTIVE: Impella 5.5 (Abiomed, Danvers, MA, USA) is approved by the US Food and Drug Administration (FDA) for mechanical circulatory support for ≤14 days. It is unknown whether prolonged support is associated with worse outcomes. We sought to review our single-center experience with Impella 5.5 and compare outcomes based on support duration. METHODS: We retrospectively reviewed adult patients (≥18 years old) supported with Impella 5.5 at our institution (May 2020 to April 2023). Patients on prolonged support (>14 days) were compared with those supported for ≤14 days. RESULTS: There were 31 patients supported with Impella 5.5 including 14 (45.2%) supported >14 days. Median support duration for those on prolonged support was 43.5 (interquartile range [IQR] 25 to 63.5) days versus 8 (IQR 6, 13) days for those who were not (P < 0.001). Overall, the device-related complication rate was 9.7% and did not differ between groups (P = 0.08). Overall, 30-day postimplant survival was 71% and did not differ by support duration (P = 0.2). In-hospital mortality was 32% and did not differ between cohorts (P > 0.99). Among those surviving to explant (n = 22), long-term strategy included bridge to durable ventricular assist device (18%, n = 4), cardiac transplant (55%, n = 12), and cardiac recovery (27%, n = 6). CONCLUSIONS: High-risk patients with cardiogenic shock may be supported with Impella 5.5 beyond the FDA-approved duration without increased risk of complications or mortality.

Evaluation of the efficacy and safety of amustaline/glutathione pathogen-reduced RBCs in complex cardiac surgery: the Red Cell Pathogen Inactivation (ReCePI) study-protocol for a phase 3, randomized, controlled trial.

BACKGROUND: Red blood cell (RBC) transfusion is a critical supportive therapy in cardiovascular surgery (CVS). Donor selection and testing have reduced the risk of transfusion-transmitted infections; however, risks remain from bacteria, emerging viruses, pathogens for which testing is not performed and from residual donor leukocytes. Amustaline (S-303)/glutathione (GSH) treatment pathogen reduction technology is designed to inactivate a broad spectrum of infectious agents and leukocytes in RBC concentrates. The ReCePI study is a Phase 3 clinical trial designed to evaluate the efficacy and safety of pathogen-reduced RBCs transfused for acute anemia in CVS compared to conventional RBCs, and to assess the clinical significance of treatment-emergent RBC antibodies. METHODS: ReCePI is a prospective, multicenter, randomized, double-blinded, active-controlled, parallel-design, non-inferiority study. Eligible subjects will be randomized up to 7 days before surgery to receive either leukoreduced Test (pathogen reduced) or Control (conventional) RBCs from surgery up to day 7 post-surgery. The primary efficacy endpoint is the proportion of patients transfused with at least one study transfusion with an acute kidney injury (AKI) diagnosis defined as any increased serum creatinine (sCr) level ≥ 0.3 mg/dL (or 26.5 µmol/L) from pre-surgery baseline within 48 ± 4 h of the end of surgery. The primary safety endpoints are the proportion of patients with any treatment-emergent adverse events (TEAEs) related to study RBC transfusion through 28 days, and the proportion of patients with treatment-emergent antibodies with confirmed specificity to pathogen-reduced RBCs through 75 days after the last study transfusion. With ≥ 292 evaluable, transfused patients (> 146 per arm), the study has 80% power to demonstrate non-inferiority, defined as a Test group AKI incidence increase of no more than 50% of the Control group rate, assuming a Control incidence of 30%. DISCUSSION: RBCs are transfused to prevent tissue hypoxia caused by surgery-induced bleeding and anemia. AKI is a sensitive indicator of renal hypoxia and a novel endpoint for assessing RBC efficacy. The ReCePI study is intended to demonstrate the non-inferiority of pathogen-reduced RBCs to conventional RBCs in the support of renal tissue oxygenation due to acute anemia and to characterize the incidence of treatment-related antibodies to RBCs.

A highly penetrant ACTA2 mutation of thoracic aortic disease.

BACKGROUND: The role of ACTA2 mutations in Familial Aortic Disease has been increasingly recognized. We describe a highly penetrant variant (R118Q) in a family with aortic disease. CASE REPORT: A patient presented to us for elective repair of an ascending aortic aneurysm with a family history of his mother expiring after aortic dissection. Genetic testing revealed he was a heterozygous carrier of the ACTA2 missense mutation R118Q. Subsequently, all living family members were tested for this variant and a full medical history was obtained to compile a family tree for the variant and penetrance of an aortic event (defined as lifetime occurrence of aortic surgery / dissection). In total 9 family members were identified and underwent genetic testing with 7/9 showing presence of the ACTA2 R118Q mutation or an aortic event. All patients over the age of 50 (n = 4) had an aortic event. Those events occurred at ages 54, 55, 60, and 62 (mean event at 57.8 ± 3.9 years). Three family members with the variant under the age of 40 have not had an aortic event and most are undergoing regular aortic surveillance via CT scan. CONCLUSIONS: Existing studies of known ACTA2 mutations describe a 76% aortic event rate by 85 years old. The R118Q missense mutation is a less common ACTA2 variant, estimated to be found in about 5% of patients with known mutations. Prior studies have predicted the R118Q mutation to have a slightly decreased risk of aortic events compared to other ACTA2 mutations. In this family, however, we demonstrate 100% penetrance of aortic disease above age 50. In today's era of excellent outcomes in elective aortic surgery, our team aggressively offers elective repair. We advocate for strict aortic surveillance for patients with this variant and would consider elective aortic replacement at 4.5 cm, or at an even smaller diameter in patients with a strong family history of dissection who are identified with this mutation.

Redo procedures after sinus node sparing hybrid ablation for inappropriate sinus tachycardia/postural orthostatic sinus tachycardia.

AIMS: A novel sinus node (SN) sparing hybrid ablation for inappropriate sinus node tachycardia (IST)/postural orthostatic tachycardia syndrome (POTS) has been demonstrated to be an effective and safe therapeutic option in patients with symptomatic drug-resistant IST/POTS. The aim of this study was to evaluate the long-term rate of redo procedures after hybrid IST ablation and procedural strategy, outcomes and safety of redo procedures. METHODS AND RESULTS: All consecutive patients from 2015 to 2023 were prospectively enrolled in the UZ Brussel monocentric IST/POTS registry. They were analysed if the following inclusion criteria were fulfilled: 1) diagnosis of IST or POTS, 2) symptomatic IST/POTS refractory or intolerant to drugs, and 3) hybrid SN sparing ablation performed. The primary endpoint was redo procedure. The primary safety endpoint was pacemaker (PM) implantation. A total of 220 patients undergone to hybrid IST ablation were included, 185 patients (84.1%) were treated for IST and 61 patients (27.7%) for POTS.After a follow-up of 73.3 ± 16.2 months, 34 patients (15.4%) underwent a redo. A total of 23 patients (67.6%) had a redo for IST recurrence and 11 patients (32.4%) for other arrhythmias. Pacemaker implantation was performed in 21 patients (9.5%). Nine patients (4.1%) had no redo procedure and experienced sick sinus syndrome requiring a PM. Twelve patients (5.4%) received a PM as a shared therapeutic choice combined with SN ablation procedure. CONCLUSION: In a large cohort of patients the long-term free survival from redo procedure after hybrid IST ablation was 84.6% with a low PM implantation rate.

Seven-year outcomes following aortic valve replacement with a novel tissue bioprosthesis.

OBJECTIVE: As bioprosthetic aortic valve replacement (AVR) extends to younger cohorts, tissue durability is of paramount importance. We report 7-year outcomes from an AVR bioprosthesis utilizing novel tissue. METHODS: This was an international investigational device exemption trial for novel AVR with annual follow-up and a subset re-consented at 5 years for extended 10-year follow-up. Safety end points and echocardiographic measurements were adjudicated by an independent clinical events committee and by a dedicated core laboratory, respectively. RESULTS: Between January 2013 and March 2016, 689 patients underwent AVR with the study valve. Mean age was 66.9 ± 11.6 years, Society of Thoracic Surgeons risk score was 2.0% ± 1.8%, and 74.3% of patients were New York Heart Association functional class II and III. Five-year follow-up was completed by 512 patients, and 225 re-consented for extended follow-up. Follow-up duration was 5.3 ± 2.2 years (3665.6 patient-years), and 194 and 195 patients completed 6- and 7-year follow-ups, respectively. One-, 5-, and 7-year freedom from all-cause mortality was 97.7%, 89.4%, and 85.4%, respectively. Freedom from structural valve deterioration at 7 years was 99.3%. At 7 years, effective orifice area and mean gradients were 1.82 ± 0.57 cm2 (n = 153), and 9.4 ± 4.5 mm Hg (n = 157), respectively. At 7 years, predominantly none (96.8% [152 out of 157]) or trivial/trace (2.5% [4 out of 157]) paravalvular regurgitation and none (84.7% [133 out of 157]) or trivial/trace (11.5% [18 out of 157]) transvalvular regurgitation were observed. CONCLUSIONS: We report the longest surgical AVR follow-up with novel tissue in an investigational device exemption trial utilizing an independent clinical events committee and an echocardiography core laboratory. This tissue demonstrates excellent outcomes through 7 years and is the benchmark for future surgical and transcatheter prostheses.

Preoperative respiratory strength training is feasible and safe and improves pulmonary physiologic capacity in individuals undergoing cardiovascular surgery.

Objective: To determine the safety, feasibility, and physiologic impact of a preoperative respiratory strength training (RST) program in individuals undergoing elective cardiac surgery (CS). Methods: Twenty-five adults undergoing an elective CS at an academic hospital setting enrolled and completed RST 5 days/week (50 repetitions, 50% training load, ≥3 weeks) at home via telehealth in this open-label prospective cohort study. RST adherence, telehealth attendance, and adverse events were tracked. Pre- and post-RST outcomes of maximum expiratory pressure (MEP), maximum inspiratory pressure (MIP), voluntary cough spirometry, and patient-reported dyspnea were collected. Descriptive analyses and Wilcoxon signed rank-tests were performed. Results: Two participants (9%) did not complete the prescribed RST program. No significant RST-related adverse events occurred. Treatment adherence for all enrolled participants was 90%, and telehealth attendance was 99%. Of the CS patients who completed the prescribed program (n = 23; 91%), treatment adherence and telehealth attendance were excellent (98% and 100%, respectively). Significant increases in primary outcomes were observed: MEP mean change, +15.4 (95% confidence interval [CI], +3.4 to +27.3, P < .007); MIP mean change, +14.9 (95% CI, +9.4 to +20.4, P < .0001). No statistically significant differences in voluntary cough or perceived dyspnea outcomes were observed (P > .05). Conclusions: These preliminary data demonstrate that a preoperative RST program is safe and feasible and can improve short-term respiratory physiologic capacity (MEP and MIP) in CS patients. Future research is warranted to validate the current findings in a larger cohort of CS patients and to determine whether RST improves postoperative extubation outcomes, airway clearance capacity, and aspiration following cardiac surgery.

Hybrid epicardial and endocardial sinus node-sparing ablation therapy for inappropriate sinus tachycardia: Rationale and design of the multicenter HEAL-IST IDE trial.

Background: Inappropriate sinus tachycardia (IST) is defined as resting heart rate >100 beats/min and average 24-hour heart rate >90 beats/min. It is associated with distressing symptoms and significant loss of quality of life. Drugs are not effective in symptom control of IST in up to 30% of patients. Catheter ablation of the sinus node has a high recurrence rate, and the complications are significant. Recently, a novel hybrid sinus node-sparing ablation approach for IST was described. Objective: The objective of the Hybrid Epicardial and Endocardial Sinus Node Sparing Ablation Therapy for Inappropriate Sinus Tachycardia (HEAL-IST) investigational device exemption trial (NCT05280093) is to evaluate safety and effectiveness of the hybrid sinus node-sparing ablation procedure for the treatment of symptomatic, drug-refractory or drug-intolerant IST. Methods: The HEAL-IST trial is a prospective, multicenter, pivotal, single-arm trial. Up to 142 subjects in up to 40 centers will be treated in the trial with a Bayesian adaptive design. Results: Subjects will be assessed for primary safety through 30 days post-hybrid ablation procedure. The primary effectiveness endpoint will be freedom from IST at 12 months. Freedom from IST will be defined as mean heart rate of ≤90 beats/min or at least a 15% reduction in mean heart rate as compared with baseline, in the absence of new or higher dosage of previously failed medications at a 24-month follow-up assessment. Conclusion: The HEAL-IST trial is the first multicenter trial evaluating hybrid IST ablation in patients with symptomatic IST and refractory or intolerant to drugs. The results of this study will help guide decision making regarding the best management in this population.

Intraoperative Hemi-Diaphragm Electrical Stimulation Demonstrates Attenuated Mitochondrial Function without Change in Oxidative Stress in Cardiothoracic Surgery Patients.

Mechanical ventilation during cardiothoracic surgery is life-saving but can lead to ventilator-induced diaphragm dysfunction (VIDD) and prolong ventilator weaning and hospital length of stay. Intraoperative phrenic nerve stimulation may preserve diaphragm force production to offset VIDD; we also investigated changes in mitochondrial function after stimulation. During cardiothoracic surgeries (n = 21), supramaximal, unilateral phrenic nerve stimulation was performed every 30 min for 1 min. Diaphragm biopsies were collected after the last stimulation and analyzed for mitochondrial respiration in permeabilized fibers and protein expression and enzymatic activity of biomarkers of oxidative stress and mitophagy. Patients received, on average, 6.2 ± 1.9 stimulation bouts. Stimulated hemidiaphragms showed lower leak respiration, maximum electron transport system (ETS) capacities, oxidative phosphorylation (OXPHOS), and spare capacity compared with unstimulated sides. There were no significant differences between mitochondrial enzyme activities and oxidative stress and mitophagy protein expression levels. Intraoperative phrenic nerve electrical stimulation led to an acute decrease of mitochondrial respiration in the stimulated hemidiaphragm, without differences in biomarkers of mitophagy or oxidative stress. Future studies warrant investigating optimal stimulation doses and testing post-operative chronic stimulation effects on weaning from the ventilator and rehabilitation outcomes.

Thoracoscopic Left Atrial Appendage Exclusion for Atrial Fibrillation Patients Intolerant to Anticoagulation.

OBJECTIVE: Outcomes associated with isolated epicardial left atrial appendage (LAA) exclusion in atrial fibrillation (AF) patients with a contraindication or intolerance to anticoagulation are not clearly defined, especially in patients with prior stroke. This study evaluated the perioperative safety, medication use, and stroke outcomes for isolated thoracoscopic LAA exclusion for stroke prevention. METHODS: A single-center retrospective study was performed of adults undergoing isolated thoracoscopic LAA exclusion with an epicardial exclusion device without a concomitant surgical procedure. Descriptive statistics were performed. RESULTS: Twenty-five patients met the inclusion criteria. The cohort was 68% male (n = 17) with a mean age of 76.4 ± 6.5 years, a mean preoperative CHA2DS2-VASc score of 4.2 ± 1.4, and a mean preoperative HAS-BLED score of 2.68 ± 1.03. Seventeen patients (68%) had nonparoxysmal AF. There were 11 patients with intolerance of anticoagulation due to intracranial hemorrhage (44%), 6 due to gastrointestinal bleeding (24%), and 4 due to genitourinary bleeding (16%). All procedures were performed thoracoscopically with 100% technical success-the mean LAA stump length was 5.5 ± 2.3 mm on intraoperative transesophageal echocardiography. The median hospital length of stay was 2 (interquartile range [IQR] 1, 6.5) days. The median follow-up time was 430 (IQR 125, 972) days. During follow-up, 1 patient with cerebral angiopathy had temporary neurologic deficits at an outside institution, with brain imaging showing no evidence of ischemic injury. There were no other thromboembolic events over the 38.8 postoperative patient-years examined. All patients were off anticoagulation at last follow-up. CONCLUSIONS: This study shows the perioperative safety, technical success, freedom from anticoagulation, and stroke outcomes of isolated thoracoscopic LAA exclusion in patients with AF at high risk for thromboembolic disease.

Dysphagia after cardiac surgery: Prevalence, risk factors, and associated outcomes.

OBJECTIVES: The study objectives were to determine the prevalence of swallowing impairment in adults after cardiac surgery and examine associated risk factors and health-related outcomes. METHODS: A prospective single-center study was conducted in postoperative adult cardiac surgery patients with no history of dysphagia. A standardized fiberoptic endoscopic evaluation of swallowing was performed within 72 hours of extubation. Blinded raters completed validated outcomes of swallowing safety and efficiency. Demographic, surgical, and postoperative health-related outcomes were collected. Univariate and multivariable regression analyses were performed with odds ratios (OR) and 95% confidence intervals (CIs). RESULTS: In 182 patients examined, imaging confirmed inefficient swallowing (residue) in 52% of patients and unsafe swallowing in 94% (65% penetrators, 29% aspirators). Silent aspiration was observed in 53% of aspirators, and 32% did not clear aspirate material. Independent risk factors for aspiration included New York Heart Association III and IV (OR, 2.9; CI, 1.2-7.0); reoperation (OR, 2.0; CI, 0.7-5.5); transesophageal echocardiogram images greater than 110 (OR, 2.6; CI, 1.1-6.3); intubation greater than 27 hours (OR, 2.1; CI, 0.8-5.3); and endotracheal tube size 8.0 or greater (OR, 3.1; CI, 1.1-8.6). Patients with 3 or 4 identified risk factors had a 16.4 (CI, 3.2-148.4) and 22.4 (CI, 3.7-244.7) increased odds of aspiration, respectively. Compared with nonaspirators, aspirators waited an additional 85 hours to resume oral intake, incurred $49,372 increased costs, and experienced a 43% longer hospital stay (P < .05). Aspiration was associated with pneumonia (OR, 2.6; CI, 1.1-6.5), reintubation (OR, 5.7; CI, 2.1-14.0), and death (OR, 2.8; CI, 1.2-9.0). CONCLUSIONS: Tracheal aspiration was prevalent, covert, and associated with increased morbidity and mortality.

Application of deep hypothermic circulatory arrest in open left chest aortic aneurysm repair.

OBJECTIVES: Deep hypothermic circulatory arrest (DHCA) is often required for patients undergoing repair of descending thoracic aortic aneurysm (DTAA) or thoracoabdominal aortic aneurysm via left thoracotomy when proximal crossclamping is not feasible or when aneurysmal disease extends into the transverse aortic arch. Historical literature suggests higher complications rates due to the technical complexity of this approach; we examined outcomes with this approach at our center. METHODS: Between January 2008 and May 2018, 84 patients with DTAA or Crawford extent I thoracoabdominal aortic aneurysm underwent open repair. DHCA was employed in 46 of 84 (55%) patients, of which 33 (72%) required repair of distal arch and DTAA, and 13 (28%) required repair of the distal arch and extent I thoracoabdominal aortic aneurysm. Patients who underwent DHCA had more chronic dissections than those in the non-DHCA group (70% vs 34%; P ≤ .05). RESULTS: Major adverse outcomes for the DHCA group versus non-DHCA group were as follows: early mortality 3 out of 46 (7%) versus 4 out of 38 (11%) (P = .70), stroke 3 out of 46 (7%) versus 1 out of 38 (3%) (P = .62), permanent spinal cord deficit 2 out of 46 (4%) versus 3 out of 38 (8%) (P = .65), permanent renal failure necessitating dialysis 1 out of 46 (2%) versus 2 out of 38 (5%) (P = .59). Freedom from major adverse outcomes was 38 out of 46 (83%) versus 31 out of 38 (82%) for DHCA versus non-DHCA (P = 1). CONCLUSIONS: DHCA can be employed via left thoracotomy for combined arch and DTAA or extent I thoracoabdominal aortic aneurysm open repair.