An experimental model of chronic severe mitral regurgitation.

Objective: To develop a minimally invasive, reproducible model of chronic severe mitral regurgitation (MR) that replicates the clinical phenotype of left atrial (LA) and left ventricular dilation and susceptibility to atrial fibrillation. Methods: Under transesophageal echocardiographic guidance, chordae tendinae were avulsed using endovascular forceps until the ratio of regurgitant jet area to LA area was ≥70%. Animals survived for an average of 8.6 ± 1.6 months (standard deviation) and imaged with monthly transthoracic echocardiography (TTE). Animals underwent baseline and preterminal magnetic resonance imaging. Terminal studies included TTE, transesophageal echocardiography, and rapid atrial pacing to test inducibility of atrial tachyarrhythmias. Results: Eight dogs underwent creation of severe MR and interval monitoring. Two were excluded-one died from acute heart failure, and the other had resolution of MR. Six dogs underwent the full experimental protocol; only one required medical management of clinical heart failure. MR remained severe over time, with a mean terminal regurgitant jet area to LA area of 71 ± 14% (standard deviation) and regurgitant fraction of 52 ± 11%. Mean LA volume increased over 130% (TTE: 163 ± 147%, P = .039; magnetic resonance imaging: 132 ± 54%, P = .011). Mean left ventricular end-diastolic volume increased by 38 ± 21% (P = .008). Inducible atrial tachyarrhythmias were seen in 4 of 6 animals at terminal surgery, and none at baseline. Conclusions: Within the 6 dogs that successfully completed the full experimental protocol, this model replicated the clinical phenotype of severe MR, which led to marked structural and electrophysiologic cardiac remodeling. This model allowed for precise measurements at repeated time points and will facilitate future studies to elucidate the mechanisms of atrial and ventricular remodeling secondary to MR and the pathophysiology of valvular atrial fibrillation.

Impact of aortic valve effective height following valve-sparing root replacement on postoperative insufficiency and reoperation.

BACKGROUND: This study evaluated the impact of anatomic aortic root parameters during valve-sparing root replacement on the probability of postoperative aortic insufficiency and freedom from aortic valve reoperation. METHODS: From 1995 to 2020, 177 patients underwent valve-sparing root replacement (163 reimplantations, 14 remodeling). Preoperative and postoperative echocardiograms were analyzed to measure annulus and sinus diameters, effective height of leaflet coaptation, and degree of aortic insufficiency. Logistic regression was used to evaluate predictors of 2+ or greater late postoperative aortic insufficiency. Fine-Gray regression determined predictors for aortic valve reintervention. RESULTS: The study population included 122 (69%) men with a mean age of 43 ± 15 years. A total of 119 patients (67%) had an identified connective tissue disorder. The cumulative incidence of aortic valve reoperation was estimated as 7% at 5 years and 12% at 10 years. The probability of 2+ or greater late postoperative aortic insufficiency was inversely related to effective height during valve-sparing root replacement (P = .018). As postoperative effective height fell below 11 mm, the probability of 2+ or greater aortic insufficiency exceeded 10%. On multivariable logistic regression, effective height (odds ratio, 0.53; 0.33-0.86; P = .010), preoperative annulus diameter (odds ratio, 1.44; 1.13-1.82; P = .003), and degree of preoperative aortic insufficiency (odds ratio, 2.57; 1.45-4.52; P = .001) were associated with increased incidence of 2+ or greater late postoperative aortic insufficiency. On multivariable Fine-Gray regression, risk factors for aortic valve reintervention included preoperative annulus diameter (subdistribution hazard ratio, 1.28 [1.03-1.59], P = .027), history of 3+ or greater aortic insufficiency (subdistribution hazard ratio, 4.28; 1.60-11.44; P = .004), and 2+ or greater early postoperative aortic insufficiency (subdistribution hazard ratio, 5.22; 2.29-11.90; P < .001). CONCLUSIONS: Measures to increase effective height during valve-sparing root replacement may decrease the risk of more than mild postoperative aortic insufficiency after repair and the need for aortic valve reoperation.

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.

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 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.

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.

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.