Gregory W. Fink

Left versus right atrial difference in dominant frequency, K+ channel transcripts, and fibrosis in patients developing atrial fibrillation after cardiac surgery

BACKGROUND The development of atrial fibrillation (AF) after cardiac surgery is associated with adverse outcomes; however, the mechanism(s) that trigger and maintain AF in these patients are unknown. OBJECTIVE The purpose of this study was to test our hypothesis that postoperative AF is maintained by high-frequency sources in the left atrium (LA) resulting from ion channel and structural features that differ from the right atrium (RA). METHODS Forty-four patients with no previous history of AF who underwent cardiac surgery consented to LA and RA biopsies. Histologic sections evaluated fatty infiltration, fibrosis, and iron deposition; quantitative reverse transcription-polymerase chain reaction (RT-PCR) assessed ion channel expression. In a subset of 27 patients, LA and RA unipolar recording leads were also placed. In patients who developed AF, the dominant frequency (DF) for each lead was calculated using fast Fourier transform. RESULTS DFs during AF were LA 6.26 +/- 0.8 Hz, RA 4.56 +/- 0.7 Hz (P <.01). RT-PCR revealed LA-to-RA differences in mRNA abundance for Kir2.3 (1.8:1) and Kir3.4 (2.3:1). While LA fibrosis was greater in patients developing AF compared with those remaining in normal sinus rhythm (10.8% +/- 11% vs. 3.8% +/- 3.5%; P = .03), the amount of LA fibrosis inversely correlated with the LA DF. CONCLUSIONS This is the first demonstration of LA-to-RA frequency differences during postoperative AF, which are associated with LA-to-RA differences in mRNA levels for potassium channel proteins and LA fibrosis. These results strongly suggest that sources of AF after cardiac surgery are located in the LA and are stabilized by LA fibrosis.

Atrial myxomas: Pathologic types, tumor location, and presenting symptoms

Abstract  Background: Atrial myxoma is the most common cardiac neoplasm. Although not widely reported, two anatomic types have been observed: solid and papillary. We examined whether differences in gross or microscopic appearance and location correlated with symptomatology, specifically congestive heart failure (CHF), neurologic symptoms, and embolic events. Methods: We performed a retrospective review of atrial myxomas removed from 1972 to 2002, recording the clinical presentation, diagnostic modality, tumor location, gross, and microscopic features for each patient. Twenty‐six patients (16 females and 10 males) had atrial myxomas excised. Two patients (one female and one male) were excluded due to unavailable pathologic slides. Results: In 24 patients there were 15 solid and 9 papillary tumors. CHF was more prevalent in solid myxomas, while neurologic symptoms and embolic events were more common in papillary tumors. Tumor location further correlated with presenting symptoms. Ninety‐two percent of patients presenting with CHF had tumors attached to the atrial septum. Extraseptal myxomas more frequently presented with neurologic (80% vs. 29%) and embolic features (50% vs. 25%). All patients exhibiting clefted tumor surface had a history of embolization. A higher percentage of solid myxomas (93%) showed hemorrhage within the tumor than with papillary (56%). Conclusions: CHF was more common with solid myxomas, and neurologic and embolization events were more common in the papillary type. Septal tumor location showed strong association with CHF, while extraseptal location correlated with neurologic events. We speculate that the various gross and microscopic patterns reflect secondary changes within these neoplasms over the course of their natural history.

Elevated Pre-Operative Serum Peptides for Collagen I and III Synthesis Result in Post-Surgical Atrial Fibrillation

OBJECTIVES This study sought to determine if serum markers for collagen I and III synthesis, the carboxyl terminal peptide from pro-collagen I (PICP) and the amino terminal peptide from pro-collagen III (PIIINP), correlate with left atrial (LA) fibrosis and post-operative atrial fibrillation (AF). BACKGROUND AF after cardiac surgery is associated with adverse outcomes. We recently demonstrated that LA fibrosis is associated with post-operative AF in patients with no previous history of AF. METHODS Fifty-four patients having cardiac surgery without a history of AF consented to left and right atrial biopsies and a pre-operative peripheral blood draw. Picrosirius red staining quantified the percentage of fibrosis, and reverse transcriptase polymerase chain reaction assessed atrial tissue messenger ribonucleic acid transcripts involved in the fibrosis pathway. PICP and PIIINP levels were measured using an enzyme immunosorbent assay. RESULTS Eighteen patients developed AF, whereas 36 remained in normal sinus rhythm. LA fibrosis was higher in patients who developed AF versus normal sinus rhythm (6.13 ± 2.9% vs. 2.03 ± 1.9%, p = 0.03). LA messenger ribonucleic acid transcripts for collagen I, III, transforming growth factor, and angiotensin were 1.5- to 2.0-fold higher in AF patients. Serum PICP and PIIINP levels were highest in AF versus normal sinus rhythm (PICP: 451.7 ± 200 ng/ml vs. 293.3 ± 114 ng/ml, p = 0.006; PIIINP: 379 ± 286 pg/ml vs. 191.6 ± 162 pg/ml, p = 0.01). Furthermore, there was a linear correlation between LA fibrosis and serum PICP levels (R(2) = 0.2; p = 0.01), and of the markers, only PICP was independently associated with AF. CONCLUSIONS This demonstrates that serum PICP and PIIINP levels correlate with the presence of LA fibrosis and may act as predictors for post-operative AF even in the absence of previous history of AF.

New approach to the surgical management of pulmonary arteriovenous malformations after cavopulmonary anastomosis

The development of pulmonary arteriovenous malformations after cavopulmonary bypass in patients with congenital heart disease is well documented. We report successful management of pulmonary arteriovenous malformations after cavopulmonary bypass in a patient with an interrupted inferior vena cava (IVC) and multiple hepatic veins utilizing an extracardiac conduit from the hepatic veins to the hemiazygous continuation of the interrupted IVC. This technique, performed without circulatory arrest or an atriotomy, may limit morbidity associated with intracardiac procedures in patients with single ventricle morphology. Furthermore, this case suggests an alternative technique for completion Fontan in patients with an interrupted IVC and multiple hepatic venous drainage.

Surgical management of leiomyosarcoma of the mediastinum

Leiomyosarcoma of the mediastinum is sufficiently rare; therefore therapeutic approaches are not well defined. Current therapy primarily rests with the thoracic surgeon. We report a single case of a large leiomyosarcoma of the mediastinum invading the heart and right lung. Our diagnostic and therapeutic approach to this patient is presented and the pertinent literature is reviewed. We conclude that little advancement has been made with regard to adjuvant therapies for leiomyosarcoma of the mediastinum, and the only opportunity for cure remains with full surgical extirpation.

Novel Treatment of an 11-cm Saphenous Vein Graft Aneurysm

Saphenous vein graft pseudoaneurysms are rare and potentially fatal complications after coronary artery bypass graft surgery. Here we present an 11-cm saphenous vein graft pseudoaneurysm from a 20-year-old vein graft to the obtuse marginal artery. The pseudoaneurysm was directly located beneath the sternum and adjacent to two patent grafts. Therefore, we used a novel approach to access the aorta through a right thoracotomy, and using a pericardial patch, we closed the ostia to the pseudoaneurysm. Postoperatively there was no longer flow into the aneurysm, and at 1-year follow-up the patient is doing well.

Chemically Modified Tetracycline Improves Contractility in Porcine Coronary Ischemia/Reperfusion Injury

Abstract  Background: Reperfusion of ischemic myocardium has been implicated in extension of infarct size and deleterious clinical outcomes. Anti‐inflammatory agents reduce this reperfusion injury. Chemically modified tetracycline‐3 (CMT‐3) (Collagenex Pharmaceuticals, Newtown, PA, USA) lacks antimicrobial properties yet retains anti‐inflammatory activity. We examined infarct size and myocardial function in a porcine coronary artery occlusion/reperfusion model in CMT‐3‐treated and control animals. Methods: Yorkshire pigs (n = 8) underwent median sternotomy, pretreatment with heparin (300 U/kg and 67 U/kg/hr IV) and lidocaine (1 mg/kg IV) and were divided into two groups. Group one (n = 4) had the left anterior descending artery (LAD) occluded for 1 hour, after which it was reperfused for 2 hours. Group two (n = 4) had an identical protocol to group one except CMT‐3 (2 mg/kg IV) was administered prior to occlusion of the LAD. Results: Animals receiving CMT‐3 had significantly decreased infarct size in relation to the ventricular area‐at‐risk (AAR) (28 ± 9% vs. 64 ± 8%; p < 0.05). Myocardial contractile function was superior in the CMT‐3 treatment, indicated by a higher cardiac index (2.9 ± 0.3 vs. 2.0 ± 0.3 L/min/m2; p < 0.05) and stroke volume index (22 ± 2 vs. 17 ± 1 L/m2/beat; p < 0.05). Conclusions: CMT‐3 decreased infarct size in relation to the AAR resulting in relative preservation of contractility, suggesting CMT‐3 may improve outcomes during myocardial ischemia reperfusion.

Discrete Subaortic Stenosis in a Patient with a History of Repaired AV Canal Defect

(Echocardiography 2011;28:E196‐E197)