A, Low-power photomicrograph exhibiting prominent fatty infiltration of the atrial wall extending from the epicardial surface (top) to the endocardial surface (bottom). B, Marked myocyte vacuolization with delicate interstitial fibrosis. C, Marked myocyte hypertrophy exhibiting both enlarged and hyperchromatic nuclei and scattered binucleate forms. D, Epicardial lymphocytic inflammation. 

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... slides were prepared routinely using 4-mmthick sections, stained with hematoxylin and eosin. The following histologic features were subjectively graded (none, mild, moderate, marked): myocyte vacuolization, myocardial fatty infiltration, and lymphocytic infiltration (Fig. 1). Mural thrombus was recorded as present or absent. In addition, myocyte hypertrophy was assessed as mild, moderate, or marked based on the number of erythrocytes that could be positioned across the widest myocyte diameter (4 erythrocytes representing mild hypertrophy, 5 moderate hypertrophy, and 6 or more marked hypertrophy). ...

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... fibrillation (AF) is the most commonly encountered sustained cardiac arrhythmia in clinical prac- tice, with an estimated prevalence of 1% to 2% in North America and Europe. 1–3 Its prevalence significantly in- creases with age, affecting 9% of adults over the age of 80 years, and is expected to more than double by the year 2050 as the population ages. 1,3 AF is associated with appreciable morbidity and mortality, which typically re- sult from thromboembolic events, the most serious of which is ischemic stroke. 4 Traditionally, several risk factors for AF have been identified. These include advanced age, male sex, white race, diabetes mellitus, hypertension, and various forms of cardiovascular disease. 1,5 More recently, several addi- tional risk factors have emerged, including left atrial en- largement, obesity, and obstructive sleep apnea. 6–8 The management of AF for most patients is nonsurgical and includes risk factor reduction, antith- rombotic medications, and rate and rhythm management. 9 However, a subset of patients is refractory to pharmacological therapy and benefits from either cathe- ter-based or surgical ablative procedures. 10 The Cox- maze procedure was introduced in 1987 as a surgical means of isolating macroreentrant circuits, whether in an atrium or a pulmonary vein, thought to be responsible for AF. This procedure also involves the removal of 1 or both atrial appendages, which markedly reduces the risk of thromboembolic events. 10–12 Histopathologic changes in atrial appendages removed during the Cox-maze operation have been reported but have not been studied in detail in a large cohort. 13–15 The observed microscopic features may provide insight into the causes of AF among individuals without an isolated and identifiable origin within an atrium or pulmonary vein and also provide information as to the likelihood of recurrence of AF. Previous small series, which examined the morphologic changes in atrial appendages removed during the Cox-maze procedure, have either focused on only 1 appendage or have not differentiated between the 2 appendages. 13–15 In the current study, several histologic features are examined qualitatively in atrial appendages removed during the Cox-maze procedure at a large tertiary care institution. These in turn are correlated with several clinical features, including recurrence of AF after surgery. It represents the largest and most detailed study of its kind to date. All patients who had undergone resection of 1 or both atrial appendages during the Cox-maze procedure at Mayo Clinic in Rochester, MN, between January 1, 2004, and December 31, 2005, were identified from the institu- tional surgical pathology archives. The study group included 86 consecutive patients, resulting in the removal of 143 atrial appendages (removal of both in 57 patients, the right alone in 17, and the left alone in 12). Two autopsy-based control groups were utilized to control for histopathologic features related to underlying heart disease, rather from the AF alone. Control group 1 included 26 age-matched individuals without AF or structural heart disease, from whom 51 atrial appendages were examined (both in 25, and right alone in 1). Control group 2 included 20 individuals with heart disease but without AF, from whom 38 atrial appendages were examined (both in 18, and left alone in 2). Among the 20 patients, 12 had underlying ischemic heart disease (IHD), 3 had cardiac amyloidosis, 2 had native valve endocarditis, and 1 each had hypertensive heart disease, pulmonary heart disease, and hypertrophic cardiomyopathy. Patient age (at the time of surgery), sex, and type and duration of preoperative AF were recorded [paroxysmal AF was defined as recurrent (>2) AF episodes, self-terminating within 7 d; persistent AF as AF lasting >7 d, or <7 d with pharmacologic electrical car- dioversion; and long-term persistent AF as AF con- tinuous for >1 y]. Clinical features recorded at the time of surgery include congestive heart failure, embolization, systemic hypertension, and nonischemic dilated cardiomyopathy. Details of the Cox-maze procedure, including ana- tomic site(s) ablated and ablation method(s) utilized, were noted. Recurrence of or freedom from AF was documented in 57 patients for whom long-term follow-up (>6 mo postoperatively) information was available. Glass slides were prepared routinely using 4- m m- thick sections, stained with hematoxylin and eosin. The following histologic features were subjectively graded (none, mild, moderate, marked): myocyte vacuolization, myocardial fatty infiltration, and lymphocytic infiltration (Fig. 1). Mural thrombus was recorded as present or absent. In addition, myocyte hypertrophy was assessed as mild, moderate, or marked based on the number of erythrocytes that could be positioned across the widest myocyte diameter (4 erythrocytes representing mild hypertrophy, 5 moderate hypertrophy, and 6 or more marked hypertrophy). Endocardial fibroelastosis (EFE) and myocardial interstitial fibrosis were evaluated with hematoxylin and eosin and Verhoeff-Van Gieson stains. EFE was subjectively graded as mild, moderate, or marked on the basis of the degree of endocardial thick- ening. Myocardial interstitial fibrosis was subjectively graded as absent, mild (perivascular only), moderate (pericellular), or marked (pericellular and replacement type) (Fig. 2). Finally, amyloid deposition was evaluated with sulfated alcian blue and Congo red stains (sections for Congo red–stained slides were cut at 10 m m). The Pearson w test and the Student t test were used for 2-sample comparisons of proportions. Statistical significance was set at P < 0.05. Of the 86 study patients, 47 (55%) were men, and the mean age at surgery was 61 years (range, 22 to 83 y). For the 2 control groups, the sex distribution was similar to that of the study group, but the mean age for group 2 was approximately 1 decade older than for the study group or for group 1 (Table 1). Preoperative AF was paroxysmal in 37 patients and persistent or long-term persistent in 49 patients. The average duration of preoperative AF was 52 months (range, 1 to 480 mo) in the 84 patients for whom data were available. AF was attributed to mitral valve disease in 51 (59%) of the 86 study patients (46 with moderate to severe mitral regurgitation, 3 with moderate to severe mitral stenosis, and 2 with combined regurgitation and stenosis). Other underlying conditions included severe tricuspid regurgitation in 6 patients, secundum-type atrial septal defect in 5, severe aortic regurgitation in 4, hypertrophic cardiomyopathy in 4, IHD in 4, hypertensive heart disease in 2, and, in 1 case each, atrioventricular septal defect, left atrial myxoma, and chronic pulmonary hypertension. Seven patients had no apparent underlying predisposition to AF. Systemic hypertension coexisted in 46 (53%) of the 86 patients (Table 1). Peripheral embolization (all cere- brovascular) had occurred in 10 (12%) patients preoperatively. Congestive heart failure was diagnosed in 14 (16%) patients, and another 6 (7%) had nonischemic dilated cardiomyopathy. Seventy-nine patients underwent biatrial ablation; of these, the traditional “cut-and-sew” (CS) surgical technique was utilized in 58, and alternative energy sources were utilized in 21 (17 radiofrequency ablations, and 4 cryoablations). Of the 58 patients who underwent the CS Cox-maze procedure, alternative energy sources were also utilized in 21 patients (16 with combined radiofrequency and cryoablation and 5 with radiofrequency ablation alone). Seven patients underwent unilateral ablation, including 2 of the right atrium using traditional CS Cox- maze; 2 of the left atrium using combined radiofrequency and cryoablation; 2 of the right atrium using cryoablation alone; and 1 of a pulmonary vein using radiofrequency ablation. The average age, sex, type and duration of preoperative AF, and frequency of AF recurrence after surgery were similar among patients who underwent cut-and-sew Cox-maze procedures and those in whom alternative energy sources were used (Table 2). For this statistical analysis, only the 79 patients who underwent biatrial Cox-maze procedures were considered, because the number of patients who underwent unilateral procedures was insufficient to draw meaningful statistical conclusions. Of the 143 atrial appendages removed from the 86 study patients, there were 74 right atrial appendages (RAA) and 69 left atrial appendages (LAA). The RAA ranged in greatest dimension from 1.4 to 5.0 cm (mean, 2.8 cm) and the LAA from 2.9 to 7.1 cm (mean, 4.6 cm). The difference in mean greatest dimension between RAA and LAA was statistically significant ( P < 0.0001). Moderate or marked myocyte hypertrophy and any degree of myocardial interstitial fibrosis occurred more frequently in the RAA than in the LAA ( P = 0.0173 and 0.0029, respectively). Conversely, myocardial fatty infiltration, EFE, and mural thrombus were identified more often in the LAA than in the RAA ( P = 0.0329, 0.039, and 0.0204, respectively). Myocyte vacuolization, inflammation (epicardial, myocardial, and endocardial), amyloid deposition, and myocyte iron accumulation were seen with similar frequency in both appendages (Table 3). Lymphocytes were the predominant (and usually only) inflammatory cell type present. Other inflammatory cell types included plasma cells (seen in the epicardium of 2 RAA), eosinophils (transmural in 1 LAA, epicardial in 1 LAA), and neutrophils (in the epicardium of 1 LAA). Multinucleate cells and granulomas were not identified. Amyloid deposition ...