Efficacy of the stand-alone Cox-Maze IV procedure in patients with longstanding persistent atrial fibrillation.

INTRODUCTION: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, and results in significant morbidity and mortality. The Cox-Maze IV procedure (CMP-IV) has been shown to have excellent efficacy in returning patients to sinus rhythm, but there have been few reports of late follow-up in sizable cohorts of patients with longstanding persistent AF, the most difficult type of AF to treat. METHODS AND RESULTS: Between May 2003 and March 2020, 174 consecutive patients underwent a stand-alone CMP-IV for longstanding persistent AF. Rhythm outcome was assessed postoperatively for up to 10 years, primarily via prolonged monitoring (Holter monitor, pacemaker interrogation, or implantable loop recorder). Fine-Gray regression was used to investigate factors associated with atrial tachyarrhythmia (ATA) recurrence, with death as a competing risk. Median duration of preoperative AF was 7.8 years (interquartile range: 4.0-12.0 years), with 71% (124/174) having failed at least one prior catheter-based ablation. There were no 30-day mortalities. Freedom from ATAs was 94% (120/128), 83% (53/64), and 88% (35/40) at 1, 5, and 7 years, respectively. On regression analysis, preoperative AF duration and early postoperative ATAs were associated with late ATAs recurrence. CONCLUSION: Despite the majority of patients having a long-duration of preoperative AF and having failed at least one catheter-based ablation, the stand-alone CMP-IV had excellent late efficacy in patients with longstanding persistent AF, with low morbidity and no mortality. We recommend consideration of stand-alone CMP-IV for patients with longstanding persistent AF who have failed or are poor candidates for catheter ablation.

Preoperative Cognitive Abnormality, Intraoperative Electroencephalogram Suppression, and Postoperative Delirium: A Mediation Analysis.

BACKGROUND: Postoperative delirium is a common complication that hinders recovery after surgery. Intraoperative electroencephalogram suppression has been linked to postoperative delirium, but it is unknown if this relationship is causal or if electroencephalogram suppression is merely a marker of underlying cognitive abnormalities. The hypothesis of this study was that intraoperative electroencephalogram suppression mediates a nonzero portion of the effect between preoperative abnormal cognition and postoperative delirium. METHODS: This is a prespecified secondary analysis of the Electroencephalography Guidance of Anesthesia to Alleviate Geriatric Syndromes (ENGAGES) randomized trial, which enrolled patients age 60 yr or older undergoing surgery with general anesthesia at a single academic medical center between January 2015 and May 2018. Patients were randomized to electroencephalogram-guided anesthesia or usual care. Preoperative abnormal cognition was defined as a composite of previous delirium, Short Blessed Test cognitive score greater than 4 points, or Eight Item Interview to Differentiate Aging and Dementia score greater than 1 point. Duration of intraoperative electroencephalogram suppression was defined as number of minutes with suppression ratio greater than 1%. Postoperative delirium was detected via Confusion Assessment Method or chart review on postoperative days 1 to 5. RESULTS: Among 1,113 patients, 430 patients showed evidence of preoperative abnormal cognition. These patients had an increased incidence of postoperative delirium (151 of 430 [35%] vs.123 of 683 [18%], P < 0.001). Of this 17.2% total effect size (99.5% CI, 9.3 to 25.1%), an absolute 2.4% (99.5% CI, 0.6 to 4.8%) was an indirect effect mediated by electroencephalogram suppression, while an absolute 14.8% (99.5% CI, 7.2 to 22.5%) was a direct effect of preoperative abnormal cognition. Randomization to electroencephalogram-guided anesthesia did not change the mediated effect size (P = 0.078 for moderation). CONCLUSIONS: A small portion of the total effect of preoperative abnormal cognition on postoperative delirium was mediated by electroencephalogram suppression. Study precision was too low to determine if the intervention changed the mediated effect.

Allogeneic Mesenchymal Stem Cells for Treatment of AKI after Cardiac Surgery.

AKI after cardiac surgery remains strongly associated with mortality and lacks effective treatment or prevention. Preclinical studies suggest that cell-based interventions may influence functional recovery. We conducted a phase 2, randomized, double-blind, placebo-controlled trial in 27 centers across North America to determine the safety and efficacy of allogeneic human mesenchymal stem cells (MSCs) in reducing the time to recovery from AKI after cardiac surgery. We randomized 156 adult subjects undergoing cardiac surgery with evidence of early AKI to receive intra-aortic MSCs (AC607; n=67) or placebo (n=68). The primary outcome was the time to recovery of kidney function defined as return of postintervention creatinine level to baseline. The median time to recovery of kidney function was 15 days with AC607 and 12 days with placebo (25th, 75th percentile range, 10-29 versus 6-21, respectively; hazard ratio, 0.81; 95% confidence interval, 0.53 to 1.24; P=0.32). We did not detect a significant difference between groups in 30-day all-cause mortality (16.7% with AC607; 11.8% with placebo) or dialysis (10.6% with AC607; 7.4% with placebo). At follow-up, 12 patients who received AC607 and six patients who received placebo had died. Rates of other adverse events did not differ between groups. In these patients with AKI after cardiac surgery, administration of allogeneic MSCs did not decrease the time to recovery of kidney function. Our results contrast with those in preclinical studies and provide important information regarding the potential effects of MSCs in this setting.

Hemoglobin-associated oxidative stress in the pericardial compartment of postoperative cardiac surgery patients.

Atherosclerosis and valvular heart disease often require treatment with corrective surgery to prevent future myocardial infarction, ischemic heart disease, and heart failure. Mechanisms underlying the development of the associated complications of surgery are multifactorial and have been linked to inflammation and oxidative stress, classically as measured in the blood or plasma of patients. Postoperative pericardial fluid (PO-PCF) has not been investigated in depth with respect to the potential to induce oxidative stress. This is important because cardiac surgery disrupts the integrity of the pericardial membrane surrounding the heart and causes significant alterations in the composition of the pericardial fluid (PCF). This includes contamination with hemolyzed blood and high concentrations of oxidized hemoglobin, which suggests that cardiac surgery results in oxidative stress within the pericardial space. Accordingly, we tested the hypothesis that PO-PCF is highly pro-oxidant and that the potential interaction between inflammatory cell-derived hydrogen peroxide with hemoglobin is associated with oxidative stress. Blood and PCF were collected from 31 patients at the time of surgery and postoperatively from 4 to 48 h after coronary artery bypass grafting, valve replacement, or valve repair (mitral or aortic). PO-PCF contained high concentrations of neutrophils and monocytes, which are capable of generating elevated amounts of superoxide and hydrogen peroxide through the oxidative burst. In addition, PO-PCF primed naive neutrophils resulting in an enhanced oxidative burst upon stimulation. The PO-PCF also contained increased concentrations of cell-free oxidized hemoglobin that was associated with elevated levels of F2α isoprostanes and prostaglandins, consistent with both oxidative stress and activation of cyclooxygenase. Lastly, protein analysis of the PO-PCF revealed evidence of protein thiol oxidation and protein carbonylation. We conclude that PO-PCF is highly pro-oxidant and speculate that it may contribute to the risk of postoperative complications.

Stepwise Multimodality Imaging Assists in Atrial Myxoma Diagnosis and Management.

The case of a 67-year-old man who presented for elective gastroenterology procedures and was in atrial fibrillation is discussed. Transthoracic echocardiography revealed a large atrial mass. Preoperative coronary angiography revealed a heavily vascularized mass. Use of cardiac magnetic resonance identified the cardiac mass as likely an atrial myxoma. (Level of Difficulty: Beginner.).

Feasibility study of intraoperative pericardial fluid biomarkers and length of stay after cardiac surgery.

Objective: Pericardial fluid biomarkers reflect the physiologic state of the myocardium. Previously, we showed a sustained increase in pericardial fluid biomarkers compared with blood in the 48 hours after cardiac surgery. We assess the feasibility of analyzing 9 common cardiac biomarkers from pericardial fluid collected during cardiac surgery and test a preliminary hypothesis of association between the most common biomarkers, troponin and brain natriuretic peptide, and length of stay after surgery. Methods: We prospectively enrolled 30 patients aged 18 years or more undergoing coronary artery or valvular surgery. Patients with ventricular assist devices, atrial fibrillation surgery, thoracic aorta surgery, redo surgery, concomitant noncardiac surgery, and preoperative inotropic support were excluded. Before pericardial excision during surgery, a 1-cm pericardial incision was made to insert an 18-gauge catheter and collect 10 mL of pericardial fluid. Concentrations of 9 established biomarkers of cardiac injury or inflammation including brain natriuretic peptide and troponin were measured. Zero truncated Poisson regression adjusted for Society of Thoracic Surgery Preoperative Risk of Mortality tested for a preliminary association between pericardial fluid biomarkers and length of stay. Results: Pericardial fluid was collected and pericardial fluid biomarkers resulted for all patients. Adjusted for Society of Thoracic Surgery risk, brain natriuretic peptide, and troponin were associated with increased intensive care unit and overall hospital length of stay. Conclusions: In 30 patients, pericardial fluid was obtained and analyzed for cardiac biomarkers. Adjusting for Society of Thoracic Surgery risk, pericardial fluid troponin and brain natriuretic peptide were preliminarily associated with increased length of stay. Further investigation is needed to validate this finding and to investigate the potential clinical utility of pericardial fluid biomarkers.

Performance of an Irrigated Bipolar Radiofrequency Ablation Clamp on Explanted Human Hearts.

BACKGROUND: Bipolar radiofrequency (RF) clamps are commonly used during surgical ablation for atrial fibrillation (AF). This study examined the efficacy of an irrigated bipolar RF clamp to create transmural lesions in an ex vivo human heart model. METHODS: Ten donor hearts, turned down for transplantation, were explanted and arrested with cold cardioplegia. The ablations of the Cox Maze IV procedure were performed using the Cardioblate LP (Medtronic, Inc) irrigated bipolar RF clamp. In the first 5 hearts, each lesion was created with a single application of RF, whereas in the remaining 5 hearts, each lesion was created with a double application of RF without unclamping. Each lesion was cross-sectioned and stained with 2,3,5-triphenyl-tetrazolium chloride to assess ablation depth and transmurality. RESULTS: A total of 100 lesions were analyzed. In the single-ablation group, 222 of 260 sections (85%) and 37 of 50 lesions (74%) were transmural. The efficacy improved significantly in the double-ablation group, in which 348 of 359 sections (97%, P < .001) and 46 of 50 lesions (92%, P = .017) were transmural. Overall, in nontransmural lesions, the epicardial fat thickness was significantly greater (1.69 ± 0.70 mm vs 0.45 ±0.10 mm, P < .001) than the transmural lesions. CONCLUSIONS: A single ablation on human atrial tissue with an irrigated bipolar RF clamp was insufficient to reliably create transmural lesions, but a double ablation significantly increased the lesion and section transmurality. Nontransmural lesions were associated with significantly thicker layers of epicardial fat, which likely decreased tissue energy delivery due to the higher resistance of fat to current flow.

Impact of early pericardial fluid chymase activation after cardiac surgery.

Introduction: Chymase is a highly destructive serine protease rapidly neutralized in the circulation by protease inhibitors. Here we test whether pericardial fluid (PCF) chymase activation and other inflammatory biomarkers determine intensive care unit length of stay, and explore mechanisms of chymase delivery by extracellular vesicles to the heart. Methods: PCF was collected from adult patients (17 on-pump; 13 off-pump) 4 h after cardiac surgery. Extracellular vesicles (EVs) containing chymase were injected into Sprague-Dawley rats to test for their ability to deliver chymase to the heart. Results: The mean intensive care unit (ICU) stay and mean total length of stay was 2.17 ± 3.8 days and 6.41 ± 1.3 days respectively. Chymase activity and 32 inflammatory markers did not differ in on-pump vs. off-pump cardiac surgery. Society of Thoracic Surgeons Predicted Risk of Morbidity and Mortality Score (STS-PROM), 4-hour post-surgery PCF chymase activity and C-X-C motif chemokine ligand 6 (CXCL6) were all independent predictors of ICU and total hospital length of stay by univariate analysis. Mass spectrometry of baseline PCF shows the presence of serine protease inhibitors that neutralize chymase activity. The compartmentalization of chymase within and on the surface of PCF EVs was visualized by immunogold labeling and transmission electron microscopy. A chymase inhibitor prevented EV chymase activity (0.28 fmol/mg/min vs. 14.14 fmol/mg/min). Intravenous injection of PCF EVs obtained 24 h after surgery into Sprague Dawley rats shows diffuse human chymase uptake in the heart with extensive cardiomyocyte damage 4 h after injection. Discussion: Early postoperative PCF chymase activation underscores its potential role in cardiac damage soon after on- or off-pump cardiac surgery. In addition, chymase in extracellular vesicles provides a protected delivery mechanism from neutralization by circulating serine protease inhibitors.

Late results after stand-alone surgical ablation for atrial fibrillation.

OBJECTIVES: Stand-alone surgical ablation of atrial fibrillation is indicated in patients with refractory atrial fibrillation who have failed medical or catheter-based ablation. Few reports of late outcomes after stand-alone surgical ablation exist using comprehensive follow-up with strict definitions of success. This study examined our late outcomes of the stand-alone Cox-Maze IV procedure. METHODS: Between January 2003 and December 2019, 236 patients underwent a stand-alone Cox-Maze IV for refractory atrial fibrillation. Freedom from atrial tachyarrhythmias was assessed by electrocardiography, Holter, or pacemaker interrogation for up to 10 years, with a mean follow-up of 4.8 ± 3.5 years. Rhythm outcomes were compared in multiple subgroups. Factors associated with recurrence were determined using Fine-Gray regression, allowing for death as the competing risk. RESULTS: The majority of patients (176/236, 75%) had nonparoxysmal atrial fibrillation. Median duration of preoperative atrial fibrillation was 6.2 years (interquartile range, 3-11). Fifty-nine percent of patients (140/236) failed 1 or more prior catheter-based ablation. Thirteen patients (6%) experienced a major complication. There was no 30-day mortality. Freedom from atrial tachyarrhythmias was 94% (187/199), 89% (81/91), and 77% (24/31) at 1, 5, and 10 years, respectively. There was no difference in freedom from atrial tachyarrhythmias between patients with paroxysmal atrial fibrillation versus nonparoxysmal atrial fibrillation (P > .05) or those undergoing sternotomy versus a minimally invasive approach (P > .05). Increased left atrial size and number of catheter ablations were associated with late atrial fibrillation recurrence. For patients who experienced any atrial tachyarrhythmia recurrence, the median number of recurrences was 1.5 (1.0-3.0). CONCLUSIONS: The stand-alone Cox-Maze IV had excellent late efficacy at maintaining sinus rhythm in patients with symptomatic, refractory atrial fibrillation, with low morbidity and no mortality. The Cox-Maze IV, in contrast to catheter-based ablation, was equally effective in patients with paroxysmal and nonparoxysmal atrial fibrillation.

Efficacy of a Novel Bipolar Radiofrequency Clamp: An Acute Porcine Model.

OBJECTIVE: Expert consensus guidelines recommend surgical ablation (SA) for patients with symptomatic atrial fibrillation (AF), but less than half of patients with AF undergoing cardiac procedures receive concomitant SA. Complete isolation of the left atrial posterior wall (LAPW) has been shown to be the most critical part of the Cox maze procedure. The purpose of this study was to investigate the performance of a novel radiofrequency (RF) bipolar device, EnCompass™ (AtriCure, Inc., Mason, OH, USA), designed to isolate the LAPW in a single application. METHODS: Five adult pigs underwent SA in a beating heart model. After a single ablation, the heart was arrested, explanted, and stained with triphenyl-tetrazolium-chloride for histological assessment. Each lesion was sectioned, and the ablation depth, muscle, and fat thickness were determined. The lesion width, energy delivery, and ablation times were compared with those from a reference RF clamp (Synergy™, AtriCure). RESULTS: Transmurality was documented in 100% of lesions (5 of 5) and cross sections (160 of 160). Electrical isolation was documented in every instance. There was no evidence of clot, charring, or pulmonary vein stenosis. Compared with the reference clamp, the lesions created by the EnCompass™ clamp were 1.5 times wider on average. The average energy delivered was 5 times higher over a duration that was 4.5 times longer due to the increased volume of tissue ablated. CONCLUSIONS: The EnCompass™ clamp reproducibly created transmural isolation of the LAPW with a single application. This may allow for simplification of the SA strategy and increased adoption of AF treatment during concomitant surgery.

The long-term outcomes and durability of the Cox-Maze IV procedure for atrial fibrillation.

OBJECTIVE: Surgical ablation of atrial fibrillation (AF) is indicated both in patients with AF undergoing concomitant cardiac surgery and in those who have not responded to medical and/or catheter-based ablation therapy. This study examined our long-term outcomes following the Cox-Maze IV procedure (CMP-IV). METHODS: Between May 2003 and March 2018, 853 patients underwent either biatrial CMP-IV (n = 765) or a left-sided CMP-IV (n = 88) lesion set with complete isolation of the posterior left atrium. Freedom from atrial tachyarrhythmia (ATA) was assessed for up to 10 years. Rhythm outcomes were compared in multiple subgroups. Predictors of recurrence were determined using Fine-Gray regression, allowing for death as the competing risk. RESULTS: The majority of patients (513/853, 60%) had nonparoxysmal AF. Twenty-four percent of patients (201/853) had not responded to at least 1 catheter-based ablation. Prolonged monitoring was used in 76% (647/853) of patients during their follow-up. Freedom from ATA was 92% (552/598), 84% (213/253), and 77% (67/87) at 1, 5, and 10 years, respectively. By competing risk analysis, incidence of first ATA recurrence was 11%, 23%, and 35% at 1, 5, and 10 years, respectively. On Fine-Gray regression, age, peripheral vascular disease, nonparoxysmal AF, left atrial size, early postoperative ATAs, and absence of sinus rhythm at discharge were the predictors of first ATA recurrence over 10 years of follow-up. CONCLUSIONS: The CMP-IV had an excellent long-term efficacy at maintaining sinus rhythm. At late follow-up, the results of the CMP-IV remained superior to those reported for catheter ablation and other forms of surgical ablation for AF. Age, left atrial size, and nonparoxysmal AF were the most relevant predictors of late recurrence.

Concomitant surgical ablation for atrial fibrillation is associated with increased risk of acute kidney injury but improved late survival.

BACKGROUND: Acute kidney injury (AKI) after cardiac surgery remains a common complication that has been associated with increased morbidity and mortality. This study implemented Kidney Disease Improving Global Outcomes criteria to evaluate renal outcomes after concomitant surgical ablation for atrial fibrillation. METHODS: Patients with a history of atrial fibrillation who underwent elective cardiac surgery at our institution from 2008 to 2018 were retrospectively reviewed. Those with preoperative renal dysfunction were excluded. Patients were classified as those who underwent concomitant Cox-Maze IV (CMP-IV) (n = 376) or no surgical ablation (n = 498). Nearest neighbor 1:1 propensity matching was conducted on fourteen covariates. AKI was evaluated by mixed effects logistic regression analysis. Long-term survival was evaluated by proportional hazards regression. RESULTS: Propensity matching yielded 308 patients in each group (n = 616). All preoperative variables were similar between groups. The concomitant CMP-IV group had a greater incidence of AKI: 32% (n = 99) versus 16% (n = 49), P < .001. After accounting for bypass time and nonablation operations on mixed effects analysis, concomitant CMP-IV was associated with increased risk of AKI (odds ratio, 1.89; confidence interval, 1.12-3.18; P = .017). While AKI was associated with decreased late survival (P < .001), patients who received a concomitant CMP-IV maintained superior 7-year survival to patients who received no ablation (P < .001). No patients required permanent dialysis. CONCLUSIONS: Concomitant CMP-IV was independently associated with increased risk of AKI in the acute postoperative period. However, the long-term risks of AKI were offset by the significant survival benefit of CMP-IV. Concerns regarding new-onset renal dysfunction should not prohibit recommendation of this procedure in appropriate patients.

Concomitant Cox-Maze IV and Septal Myectomy in Patients With Hypertrophic Obstructive Cardiomyopathy.

BACKGROUND: In patients with hypertrophic obstructive cardiomyopathy, atrial fibrillation is associated with heart failure and increased late mortality. However, the role of surgical ablation in these patients is not well defined. The aim of this study was to evaluate the efficacy of the concomitant Cox-Maze IV procedure in patients undergoing septal myectomy for hypertrophic obstructive cardiomyopathy. METHODS: Between 2005 and 2019, 347 patients who underwent septal myectomy at a single institution (Washington University School of Medicine, Barnes-Jewish Hospital, St Louis, MO) were retrospectively reviewed. For patients with hypertrophic obstructive cardiomyopathy and atrial fibrillation who underwent a concomitant Cox-Maze IV procedure, freedom from atrial tachyarrhythmias (ATAs) on or off antiarrhythmic drugs (AADs) was evaluated annually. Predictors of ATA recurrence were identified using Fine-Gray regression, with death as a competing risk. RESULTS: A total of 42 patients underwent concomitant septal myectomy and Cox-Maze IV procedures. The majority of patients, 69% (29 of 42), had paroxysmal atrial fibrillation with a 2.5-year median duration. Operative mortality was 7% (3 of 42). New York Heart Association functional class was reduced after surgery (P < .01). Rates of freedom from recurrent ATAs at 1- and 5-year intervals were 93% (27 of 29) and 100% (14 of 14), respectively. Rates of freedom from ATAs and AADs were 83% (24 of 29) and 100% (14 of 14) at the same time points, respectively. Increased left atrial diameter predicted first ATA recurrence (P < .01). Cerebrovascular accident risk was lower in patients with atrial fibrillation who underwent concomitant Cox-Maze IV and septal myectomy relative to myectomy only (P = .02). CONCLUSIONS: Late freedom from ATAs on or off AADs was excellent after Cox-Maze IV and septal myectomy. Although there was a higher than expected rate of perioperative complications, the study results suggest that concomitant surgical ablation should be considered in selected patients with hypertrophic obstructive cardiomyopathy and atrial fibrillation.

Surgical ablation for atrial fibrillation is efficacious in patients with giant left atria.

OBJECTIVE: The Cox-Maze IV procedure (CMP-IV) is the most effective treatment for atrial fibrillation. Increased left atrial (LA) size has been identified as a risk factor for failure to restore sinus rhythm. This has biased many surgeons against ablation in patients with giant left atrium (GLA), defined as LA diameter >6.5 cm. In this study we aimed to define the efficacy of the CMP-IV in patients with GLA. METHODS: From April 2004 through March 2020, 786 patients with a documented LA diameter underwent elective CMP-IV, 72 of whom had GLA. Median follow-up duration was 4 years (interquartile range, 1-7 years). Recurrence was defined as any documented atrial tachyarrhythmia (ATA) lasting 30 seconds. ATA recurrence and survival were analyzed across GLA versus non-GLA groups. RESULTS: Median age at surgery was 65 (interquartile range, 56-73) years. Median LA diameter within the GLA group was 7.0 (range, 6.6-10.0) cm. There were no differences in rates of postoperative complications for the 2 groups, including rate of postoperative stroke and pacemaker placement (GLA 14%; non-GLA 12%; P = .682). A trend toward increased 30-day mortality in the GLA group did not reach statistical significance (GLA 6%; non-GLA 2%; P = .051). Freedom from ATAs at 5 years postoperatively was comparable for the 2 groups (GLA 82%; non-GLA 84%). CONCLUSIONS: The CMP-IV had good efficacy in patients with GLA. Our results suggest that LA diameter >6.5 cm should not preclude a patient from undergoing surgical ablation for atrial fibrillation.

Impact of age on atrial fibrillation recurrence following surgical ablation.

OBJECTIVES: The incidence of atrial fibrillation (AF) in patients older than 75 years of age is expected to increase, and its treatment remains challenging. This study evaluated the impact of age on the outcomes of surgical ablation of AF. METHODS: A retrospective review was performed of patients who underwent the Cox-maze IV procedure at a single institution between 2005 and 2017. The patients were divided into a younger (age <75 years, n = 548) and an elderly cohort (age ≥75 years, n = 148). Rhythm outcomes were assessed at 1 year and annually thereafter. Predictors of first atrial tachyarrhythmia (ATA) recurrence were determined using Fine-Gray regression, allowing for death as the competing risk. RESULTS: The mean age of the elderly group was 78.5 ± 2.8 years. The majority of patients (423/696, 61%) had nonparoxysmal AF. The elderly patients had a lower body mass index (P < .001) and greater rates of hypertension (P = .011), previous myocardial infarction (P = .017), heart failure (P < .001), and preoperative pacemaker (P = .008). Postoperatively, the elderly group had a greater rate of overall major complications (23% vs 14%, P = .017) and 30-day mortality (6% vs 2%, P = .026). The percent freedom from ATAs and antiarrhythmic drugs was lower in the elderly patients at 3 (69% vs 82%, P = .030) and 4 years (65% vs 79%, P = .043). By competing risk analysis, the incidence of first ATA recurrence was greater in elderly patients (33% vs 20% at 5 years; Gray test, P = .005). On Fine-Gray regression adjusted for clinically relevant covariates, increasing age was identified as a predictor of ATAs recurrence (subdistribution hazard ratio, 1.03; 95% confidence interval, 1.02-1.05, P < .001). CONCLUSIONS: The efficacy of the Cox-maze IV procedure was worse in elderly patients; however, the majority of patients remained free of ATAs at 5 years. The lower success rate in these greater-risk patients should be considered when deciding to perform surgical ablation.

Impact of Obesity on Atrial Fibrillation Recurrence Following Stand-Alone Cox Maze IV Procedure.

OBJECTIVE: Obesity is a strong and independent factor for the development of atrial fibrillation (AF), and adversely impacts the success of catheter ablation procedures for AF. This study evaluated the impact of body mass index (BMI) on the outcomes following surgical ablation of AF. METHODS: Between 2003 and 2019, 236 patients underwent a stand-alone biatrial Cox maze IV procedure (CMP-IV) for refractory AF. Obesity was defined as BMI ≥30 kg/m2. Patients were divided into two groups: BMI <30 kg/m2 (n = 100) and BMI ≥30 kg/m2 (n = 136). Freedom from atrial tachyarrhythmia (ATA) was determined using electrocardiography, Holter, or pacemaker interrogation at 1 year and annually thereafter. Recurrence was defined as any documented ATA lasting ≥30 s. Predictors of recurrence were determined using multivariable logistic regression. Preoperative and procedural outcomes were compared between groups. RESULTS: Obese patients had a higher rate of diabetes (16% vs 7%, P = 0.044) and larger left atrial diameter (4.9 ± 1.1 cm vs 4.6 ± 1.0 cm, P = 0.021) when compared to non-obese patients. There was no difference in major complication rate between the groups (4% vs 7%, P = 0.389). There was no operative mortality in either group. During 4.1 ± 2.4 years of follow-up, there was no significant difference in freedom from ATA with or without antiarrhythmic drugs in obese patients when compared to the non-obese group (P > 0.05). Absence of sinus rhythm at discharge predicted AF recurrence up to 7 years postoperatively. CONCLUSIONS: As opposed to catheter ablation, obesity did not adversely impact the short and long-term outcomes of stand-alone surgical ablation with CMP-IV, and BMI was not a predictor of AF recurrence. Additionally, there was no significant increase in major complications in obese patients.

Pericardial Mitochondrial DNA Levels Are Associated With Atrial Fibrillation After Cardiac Surgery.

BACKGROUND: Postoperative atrial fibrillation (POAF) is the most common complication after cardiac surgery, and is associated with increased morbidity and mortality. Inflammation has been implicated as an etiology of POAF. Mitochondrial DNA (mtDNA) has been shown to initiate inflammation. This study analyzed inflammatory mechanisms of POAF by evaluating mtDNA, neutrophils, and cytokines/chemokines in the pericardial fluid and blood after cardiac surgery. METHODS: Blood and pericardial fluid from patients who underwent coronary artery bypass or heart valve surgery, or both, were collected intraoperatively and at 4, 12, 24, and 48 hours postoperatively. Real-time polymerase chain reaction was used to quantify mtDNA in the pericardial fluid and blood. A Luminex (Luminex Corp, Austin, TX) assay was used to study cytokine and chemokine levels. Flow cytometry was used to analyze neutrophil infiltration and activation in the pericardial fluid. RESULTS: Samples from 100 patients were available for analysis. Postoperatively, mtDNA and multiple cytokine levels were higher in the pericardial fluid versus blood. Patients who had POAF had significantly higher levels of mtDNA in the pericardial fluid compared with patients who did not (P < .001, area under the curve 0.74). There was no difference in the mtDNA concentration in the blood between the POAF group and non-POAF group (P = .897). Neutrophil concentration increased in the pericardial fluid over time from a baseline of 0.8% to 56% at 48 hours (P < .01). CONCLUSIONS: The pericardial space has a high concentration of inflammatory mediators postoperatively. Mitochondrial DNA in the pericardial fluid was strongly associated with the development of POAF. This finding provides insight into a possible mechanism of inflammation that may contribute to POAF, and may offer novel therapeutic targets.

The Arrhythmic Substrate for Atrial Fibrillation in Patients with Mitral Regurgitation.

OBJECTIVE: Patients with severe mitral regurgitation commonly develop atrial fibrillation. The precise mechanisms of this relationship remain unknown. The objective of this study was to apply noninvasive electrocardiographic imaging of the atria during sinus rhythm to identify changes in atrial electrophysiology that may contribute to development of atrial fibrillation in patients with severe mitral regurgitation referred for mitral valve surgery. METHODS: Twenty subjects (9 atrial fibrillation and mitral regurgitation, 11 mitral regurgitation alone) underwent electrocardiographic imaging. Biatrial electrophysiology was imaged with activation maps in sinus rhythm. The reconstructed unipolar electrograms were analyzed for voltage amplitude, number of deflections and conduction heterogeneity. In subjects with mitral regurgitation, left atrial biopsies were obtained at the time of surgery. Results: Subjects with history of atrial fibrillation demonstrated prolonged left atrial conduction times (110±25 ms vs. mitral regurgitation alone (85±21), p=0.025); right atrial conduction times were unaffected. Variable patterns of conduction slowing were imaged in the left atria of most subjects, but those with prior history of atrial fibrillation had more complex patterns of conduction slowing or unidirectional block. The presence of atrial fibrillation was not associated with the extent of fibrosis in atrial biopsies. CONCLUSIONS: Detailed changes in sinus rhythm atrial electrophysiology can be imaged noninvasively and can be used to assess the impact and evolution of atrial fibrillation on atrial conduction properties in patients with mitral regurgitation. If replicated in larger studies, electrocardiographic imaging may identify patients with mitral regurgitation at risk for atrial fibrillation and could be used to guide treatment strategies.

Bipolar Radiofrequency Ablation on Explanted Human Hearts: How to Ensure Transmural Lesions.

BACKGROUND: Bipolar radiofrequency (RF) clamps have been shown to be capable of reproducibly creating transmural lesions with a single ablation in animal models. Unfortunately in clinical experience the bipolar clamps have not been as effective and often require multiple ablations to create conduction block. This study created a new experimental model using fresh, cardioplegically arrested human hearts turned down for transplant to evaluate the performance of a nonirrigated bipolar RF clamp. METHODS: Nine human hearts turned down for transplant were harvested, and the Cox-Maze IV lesion set was performed with a nonirrigated bipolar RF clamp. In the first 7 hearts a single ablation was performed for each lesion. In the last 2 hearts a set of 2 successive ablations without unclamping were performed. The heart tissue was stained with 2,3,5-triphenyl-tetrazolium chloride. Each ablation lesion was cross-sectioned to assess lesion depth and transmurality. RESULTS: A single ablation with the bipolar RF clamp resulted in 89% (469/529) of the histologic sections and 65% (42/65) of the lesions being transmural. Of the nontransmural sections, 92% occurred in areas with epicardial fat. Performing 2 successive ablations without unclamping resulted in 100% of the cross-sections (201/201) and lesions (25/25) being transmural. CONCLUSIONS: A single ablation failed to create a transmural lesion 35% of the time, and this was associated with the presence of epicardial fat. Two successive ablations without unclamping resulted in 100% lesion transmurality using the bipolar RF clamp.