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.

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.

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.

A 20-year multicenter analysis of dialysis-dependent patients who had aortic or mitral valve replacement: Implications for valve selection.

OBJECTIVE: Valve selection in dialysis-dependent patients can be difficult because long-term survival is diminished and bleeding risks during anticoagulation treatment are greater in patients with renal failure. In this study we analyzed long-term outcomes of dialysis-dependent patients who underwent valve replacement to help guide optimal prosthetic valve type selection. METHODS: Dialysis-dependent patients who underwent aortic and/or mitral valve replacement at 3 institutions over 20 years were examined. The primary outcome was long-term survival. A Cox regression model was used to estimate survival according to 5 ages, presence of diabetes, and/or heart failure symptoms. RESULTS: Four hundred twenty-three available patients were analyzed; 341 patients had biological and 82 had mechanical valves. Overall complication and 30-day mortality rates were similar between the groups. Thirty-day readmission rates for biological and mechanical groups were 15% (50/341) and 28% (23/82; P = .005). Five-year survival was 23% and 33% for the biological and mechanical groups, respectively. After adjusting for age, New York Heart Association (NYHA) class, and diabetes using a multivariable Cox regression model, survival was similar between groups (hazard ratio, 0.93; 95% confidence interval, 0.66-1.29; P = .8). A Cox regression model on the basis of age, diabetes, and heart failure, estimated that patients only 30 or 40 years old, with NYHA class I-II failure without diabetes had a >50% estimated 5-year survival (P < .001). CONCLUSIONS: Dialysis-dependent patients who underwent valve replacement surgery had poor long-term survival. Young patients without diabetes or NYHA III or IV symptoms might survive long enough to justify placement of a mechanical valve; however, a biological valve is suitable for most patients.

Outcomes After the MitraClip Procedure in Patients at Very High Risk for Conventional Mitral Valve Surgery.

OBJECTIVE: Approximately 50% of patients with severe symptomatic mitral regurgitation are deemed too high risk for surgery. The MitraClip procedure is a viable option for this population. Our goal was to assess outcomes and survival of patients who underwent the MitraClip procedure at an institution where mitral valve surgery is routinely performed. METHODS: A retrospective study of patients undergoing the MitraClip procedure was performed. Baseline characteristics, perioperative outcomes, and follow-up echocardiographic and clinical outcomes were examined. Primary end point was survival. Secondary end points included technical failure (residual 3/4+ mitral regurgitation), reoperation, New York Heart Association symptoms, 30-day mortality, and other clinical outcomes. Predictors of mortality were determined using multivariable regression analysis. RESULTS: Fifty consecutive patients underwent the MitraClip procedure during the 4-year period. The average age was 83, the Society of Thoracic Surgeons predicted risk of mortality mean was 9.4%, 88% (44/50) had New York Heart Association III/IV symptoms, 86% (43/50) had 4+ mitral regurgitation, and 72% (36/50) had degenerative mitral disease etiology. Echocardiographic data (median [interquartile range] follow-up = 43 [26-392]) showed that 86% (43/50) of patients had 2+ or less mitral regurgitation. Sixty percent (24/40) had New York Heart Association I/II symptoms at last follow-up. Predictors of mortality were higher Society of Thoracic Surgeons predicted risk of mortality (P = 0.042, hazard ratio = 1.098) and previous cardiac surgery (P = 0.013, hazard ratio = 3.848). Survival at 1 and 2 years was 75% and 63%, respectively. CONCLUSIONS: Many patients with mitral valve regurgitation who are high risk for open surgery can be treated with the MitraClip procedure. In our study, most patients (86%) had a technically successful operation and postoperative outcomes including survival were acceptable.

The hemodynamic and atrial electrophysiologic consequences of chronic left atrial volume overload in a controllable canine model.

OBJECTIVE: The purpose of this study was to determine the effects of chronic left atrial volume overload on atrial anatomy, hemodynamics, and electrophysiology using a titratable left ventriculoatrial shunt in a canine model. METHODS: Canines (n = 16) underwent implantation of a shunt between the left ventricle and the left atrium. Sham animals (n = 8) underwent a median sternotomy without a shunt. Atrial activation times and effective refractory periods were determined using 250-bipolar epicardial electrodes. Biatrial pressures, systemic pressures, left atrial and left ventricle diameters and volumes, atrial fibrillation inducibility, and durations were recorded at the initial and at 6-month terminal study. RESULTS: Baseline shunt fraction was 46% ± 8%. The left atrial pressure increased from 9.7 ± 3.5 mm Hg to 13.8 ± 4 mm Hg (P < .001). At the terminal study, the left atrial diameter increased from a baseline of 2.9 ± 0.05 cm to 4.1 ± 0.6 cm (P < .001) and left ventricular ejection fraction decreased from 64% ± 1.5% to 54% ± 2.7% (P < .001). Induced atrial fibrillation duration (median, range) was 95 seconds (0-7200) compared with 0 seconds (0-40) in the sham group (P = .02). The total activation time was longer in the shunt group compared with the sham group (72 ± 11 ms vs 62 ± 3 ms, P = .003). The right atrial and not left atrial effective refractory periods were shorter in the shunt compared with the sham group (right atrial effective refractory period: 156 ± 11 ms vs 141 ± 11 ms, P = .005; left atrial effective refractory period: 142 ± 23 ms vs 133 ± 11 ms, P = .35). CONCLUSIONS: This canine model of mitral regurgitation reproduced the mechanical and electrical remodeling seen in clinical mitral regurgitation. Left atrial size increased, with a corresponding decrease in left ventricle systolic function, and an increased atrial activation times, lower effective refractory periods, and increased atrial fibrillation inducibility. This model provides a means to understand the remodeling by which mitral regurgitation causes atrial fibrillation.