Thomas Mark Beaver

BACKGROUND: Despite advances in endocardial catheter ablation (ECA) for persistent atrial fibrillation (PersAF), undertreatment persists, especially in ECA nonresponders and in longstanding PersAF (LSPersAF), with disappointing ablation results. These patients need effective clinical treatment options. METHODS: The DEEP (Dual Epicardial and Endocardial Procedure) was a prospective, multicenter, single-arm, investigational device exemption trial to establish the safety and effectiveness of a combined epicardial/endocardial ablation procedure with left atrial appendage exclusion for PersAF/LSPersAF. Eligibility included age 18 to 75 years; symptomatic PersAF/LSPersAF refractory to ≥1 Class I/III antiarrhythmic drug; and ≤2 previous failed ECAs. Two-stage hybrid ablation included ECA performed at 91 to 121 days after the epicardial first stage (including left atrial appendage exclusion), followed by a 90-day blanking and 90-day antiarrhythmic drug optimization period. Primary effectiveness was defined as freedom from documented atrial fibrillation/atrial flutter/atrial tachycardia episodes >30 seconds through the 12-month follow-up, absent Class I/III antiarrhythmic drugs, except previously failed antiarrhythmic drugs at doses not exceeding those previously failed. Primary safety was defined as a composite of device/procedure-related serious adverse events within 30 days of epicardial ablation and 7 days of ECA. RESULTS: Ninety patients enrolled from February 2015 to December 2020; 83.3% (75/90) were male and mean±SD age was 63.4±7.7 years. AF classification was 83.3% (75/90) PersAF/16.7% (15/90) LSPersAF, and 47.8% (43/90) had prior ECA. The composite serious adverse events rate was 6.7% (6/90 [95% CI, 2.5%–13.9%]; P P =0.0134 versus performance goal) and was 62.4% (53/85 [95% CI, 52.1%–72.7%]) through 2 years. CONCLUSIONS: A collaborative hybrid ablation approach to treating PersAF/LSPersAF is safe and effective. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02393885.

Background: Transfusion has a persistent low risk of transfusion-transmitted infection and transfusion-associated graft- versus -host disease that may be addressed using pathogen reduction. The Red Cell Pathogen Inactivation (ReCePI) trial tested whether amustaline/glutathione pathogen-reduced red cells are noninferior to conventional transfusions for support of acute surgical blood loss. Methods: A phase 3, double-blinded, noninferiority trial randomized cardiac or thoracic–aorta surgery patients with increased risk of red cell transfusion to receive pathogen-reduced or conventional red cells during and for 7 days postsurgery. The primary endpoint was the proportion of patients with acute kidney injury (AKI), which is defined as an increase from baseline of greater than or equal to 0.3 mg/dl serum creatinine within 48 h of surgery. Noninferiority was claimed if the upper bound 95% CI of the treatment difference was less than half (50%) of the observed conventional arm incidence. Adverse events and treatment-emergent red cell antibodies were assessed for 28 and 75 days, respectively. Results: A total of 581 subjects were randomized, and 321 (55%) were transfused with study red cells. Transfused subjects in both arms had similar baseline demographics, medical histories, hemoglobin levels, and surgical procedures. Hemoglobin day 3 nadir levels (8.6 g/dl [7.8 to 9.2] in the pathogen-reduced arm; 8.4 g/dl [7.8 to 9.3] in the conventional arm; P = 0.52) were comparable. Incidence of AKI by 48 h was 46 of 157 (29.3%) in the pathogen-reduced arm and 45 of 161 (28.0%) in the conventional arm (treatment difference, 0.7%; 95% CI, −8.9 to 10.4%; noninferiority margin, 14.0%; P = 0.001 for noninferiority). AKI within 7 days by Kidney Disease Improving Global Outcomes staging criteria was not different (59 of 159 [37.1%] in the pathogen-reduced arm; 55 of 162 [34.0%] in the conventional arm; P = 0.53), but stage III was more common in the pathogen-reduced arm (pathogen-reduced arm, 15 of 159 [9.4%]; conventional arm, 7 of 162 [4.3%]; P = 0.075). Of 159 pathogen-reduced red cell recipients, 5 (3.1%) developed specific, low-titer antibodies without evidence of hemolysis. Conclusions: The incidence of AKI in recipients of pathogen-reduced red cells was noninferior to conventional red cell transfusion. Treatment-emergent antibodies were uncommon and not clinically significant.

Hemodynamically significant pulmonary embolisms (PE) in the pulmonary artery or those crossing a patent foramen ovale (PFO) can become life-threatening emergencies requiring immediate removal. While cases of surgical management for a PE crossing a PFO have been reported, there are no documented cases of a PE extending across both the mitral and aortic valves. A 38-year-old female with a medical history of obesity, depression, and thalassemia minor was transferred from an outside hospital with hemodynamic compromise due to a large PE. Transesophageal echocardiography (TEE) revealed a PE crossing the PFO, extending across the mitral valve, and traversing the aortic valve into the ascending aorta. Cardiopulmonary bypass (CPB) was initiated using standard aortic cannulation distal to the known clot, along with bicaval venous cannulation. The heart was arrested, and the right and left atria were opened in a transeptal fashion. The clot, which extended from the PFO through the mitral and aortic valves, was identified and removed en bloc. A small aortotomy was performed, confirming a clear aorta. An additional clot was found in the right atrium crossing the tricuspid valve and was subsequently removed. Finally, the pulmonary artery was opened, and the bulk of the clot burden was extracted, completing the embolectomy. The patient was successfully weaned from CPB without complications and was extubated within 24 h post-surgery. She underwent inferior vena cava filter placement and was discharged on post-operative day seven. Extensive pulmonary emboli are life-threatening emergencies that require immediate intervention. This study presents an extensive clot burden crossing the PFO, mitral valve, and aortic valve. Prompt surgical intervention is crucial to preventing severe complications such as stroke, myocardial infarction, respiratory failure, death, and long-term sequelae, including pulmonary hypertension and future strokes.

Hemodynamically significant pulmonary embolisms (PE) in the pulmonary artery or those crossing a patent foramen ovale (PFO) can become life-threatening emergencies requiring immediate removal. While cases of surgical management for a PE crossing a PFO have been reported, there are no documented cases of a PE extending across both the mitral and aortic valves. A 38-year-old female with a medical history of obesity, depression, and thalassemia minor was transferred from an outside hospital with hemodynamic compromise due to a large PE. Transesophageal echocardiography (TEE) revealed a PE crossing the PFO, extending across the mitral valve, and traversing the aortic valve into the ascending aorta. Cardiopulmonary bypass (CPB) was initiated using standard aortic cannulation distal to the known clot, along with bicaval venous cannulation. The heart was arrested, and the right and left atria were opened in a transeptal fashion. The clot, which extended from the PFO through the mitral and aortic valves, was identified and removed en bloc. A small aortotomy was performed, confirming a clear aorta. An additional clot was found in the right atrium crossing the tricuspid valve and was subsequently removed. Finally, the pulmonary artery was opened, and the bulk of the clot burden was extracted, completing the embolectomy. The patient was successfully weaned from CPB without complications and was extubated within 24 h post-surgery. She underwent inferior vena cava filter placement and was discharged on post-operative day seven. Extensive pulmonary emboli are life-threatening emergencies that require immediate intervention. This study presents an extensive clot burden crossing the PFO, mitral valve, and aortic valve. Prompt surgical intervention is crucial to preventing severe complications such as stroke, myocardial infarction, respiratory failure, death, and long-term sequelae, including pulmonary hypertension and future strokes.

Thoracic surgery rapidly induces weakness in human diaphragm fibers. The dysfunction is thought to arise from combined effects of the surgical procedures and inactivity. This project tested whether brief bouts of intraoperative hemidiaphragm stimulation would mitigate slow and fast fiber loss of force in the human diaphragm. We reasoned that maintenance of diaphragm activity with brief bouts of intraoperative phrenic stimulation would mitigate diaphragm fiber weakness and myofilament protein derangements caused by thoracic surgery. Nineteen adults (9 females, age 59 ± 12 years) with normal inspiratory strength or spirometry consented to participate. Unilateral phrenic twitch stimulation (twitch duration 1.5 ms, frequency 0.5 Hz, current 2x the motor threshold, max 25 mA) was applied for one minute, every 30 minutes during cardiothoracic surgery. Thirty minutes following the last stimulation bout, biopsies were obtained from the hemidiaphragms for single fiber force mechanics and quantitation of myofilament proteins (abundance and phosphorylation) and compared by a linear mixed model and paired t-test, respectively. Subjects underwent 6 ± 2 hemidiaphragm stimulations at 17 ± 6 mA, during 278 ± 68 minutes of surgery. Longer-duration surgeries were associated with a progressive decline in diaphragm fiber force (p < 0.001). In slow-twitch fibers, phrenic stimulation increased absolute force (+25%, p < 0.0001), cross-sectional area (+16%, p < 0.0001) and specific force (+7%, p < 0.0005). Stimulation did not alter contractile function of fast-twitch fibers, calcium-sensitivity in either fiber type, and abundance and phosphorylation of myofilament proteins. In adults without preoperative weakness or lung dysfunction, unilateral phrenic stimulation mitigated diaphragm slow fiber weakness caused by thoracic surgery, but had no effect on myofilament protein abundance or phosphorylation.