Saqib Masroor

Histopathological substrate for chronic atrial fibrillation in humans

BACKGROUNDnThere is a lack of understanding of the substrate for microreentrant circuits and triggered activity of the pulmonary vein (PV) muscle sleeves and atria in patients with atrial fibrillation (AF).nnnOBJECTIVEnThis study sought to examine the histological substrate of patients with chronic AF.nnnMETHODSnWe stained 23 biopsies taken from the PV-left atrium (LA) junction and right atrial appendage from 5 chronic AF patients and 3 sinus rhythm (SR) patients undergoing mitral valve surgery using periodic acid-Schiff (PAS) test, and antibodies to hyperpolarization-activated cyclic nucleotide-gated potassium channel 4 (HCN4), CD117/c-kit, myoglobin, tyrosine hydroxylase (TH), growth-associated protein 43, cholineacetyltransferase, and synaptophysin, as well as trichrome.nnnRESULTSnAs opposed to being clustered together in the subendocardial layer in SR patients, PAS-positive cells were separated from each other by inflammatory infiltrate and collagen fibers in AF patients. These cells stained positively for HCN4 and myoglobin, indicating they were cardiomyocytes that might have a potential pacemaking function, but different from CD117/c-kit-positive interstitial Cajal-like cells (ICLC). In AF patients, the intercellular space was occupied by a lymphomononuclear infiltrate (100% vs 33% in SR patients, P = .002), and a greater amount of interstitial fibrosis (37% +/- 5.6% vs 7.4% +/- 2.8%, P = .009). Nerve densities did not differ between AF and SR patients. However, the density of sympathetic nerve twigs in AF patients was significantly greater as compared to the others nerves (P = .03).nnnCONCLUSIONnHCN4-/PAS-positive cardiomyocytes and CD117/c-kit-positive ICLC scattered among abundant inflammatory infiltrate, fibrous tissue, and sympathetic nerve structures in the atria and at the PV-LA junctions might be a substrate for the maintenance of chronic AF.

Endocardial hypothermia and pulmonary vein isolation with epicardial cryoablation in a porcine beating-heart model.

OBJECTIVEnThe objective of this study was to investigate whether epicardial cryoablation could achieve sufficient endocardial hypothermia to create transmural lesions leading to acute and sustained pulmonary vein isolation in a normothermic beating-heart model.nnnMETHODSnThirty-five- to 45-kg pigs underwent median sternotomy. Epicardial cryoablation was performed on the right ventricle after insertion of thermocouples. Endocardial temperatures from thermocouples were recorded continuously and correlated with the thickness of the myocardium. Thirteen animals underwent pulmonary vein isolation as a box lesion by using 5-minute epicardial cryoablation. Endocardial temperatures were measured in 5 of these animals. Ten animals survived for 7 or 30 days. Electrical isolation was tested at the time of surgical intervention and again at death. Hearts were removed en bloc and submitted for gross and microscopic examination.nnnRESULTSnEndocardial temperature varied inversely with tissue thickness, ranging from -60 degrees C in 5-mm-thick tissue to staying unchanged in tissue more than 10 mm thick. During pulmonary vein isolation, median endocardial temperatures were between -1 degrees C and -22 degrees C. Acute electrical isolation was achieved in all 13 animals. All except one of the animals maintained electrical isolation long-term. Histologic analysis revealed transmurality in 89% of sections, although none of the box lesions were completely transmural.nnnCONCLUSIONnEpicardial cryoablation can produce long-term pulmonary vein isolation in a beating heart. Dose-response studies demonstrate consistent endocardial hypothermia in tissues up to 7 mm thick. To our knowledge, this is the first report documenting endocardial hypothermia during epicardial cryoablation. This technology holds promise for performing the complete maze procedure on a beating heart.

Initial Experience With Minimally Invasive Surgical Exclusion of the Left Atrial Appendage With an Epicardial Clip

Objective Atrial fibrillation (AF) is the primary cardiac abnormality associated with ischemic stroke. Atrial fibrillation affects 2.7 million people with a stroke rate of 3.5% per year. Most of the emboli in patients with nonvalvular AF originate in the left atrial appendage (LAA). Surgical exclusion of the LAA decreases the yearly risk of stroke to 0.7% when combined with a Maze procedure. Traditional oversewing the LAA from inside the left atrium is associated with a significant number of recanalizations of LAA. An alternate technique is epicardial clipping, which has been approved through sternotomy for permanent exclusion of LAA. We present our initial experience of epicardial clipping of the LAA using a minimally invasive approach. Methods Between May 2012 and December 2015, a total of 24 consecutive patients underwent minimally invasive, echo-guided epicardial clipping. Indications for the procedure were persistent (n = 12) or paroxysmal (n = 12) AF in patients who could not tolerate full anticoagulation because of a combination of gastrointestinal bleeding (n = 7), hemorrhagic stroke (n = 5), ischemic stroke (n = 5), intramuscular bleeding (n = 3), falls (n = 2), urinary tract bleeding (n = 2), subdural hematoma (n = 1), traumatic aortic intramural hematoma (n = 1), and lifestyle and career practices inconsistent with anticoagulation (n = 1). The clipping was performed through three 5-mm ports in the left seventh intercostal space (n = 22) or a 5-cm incision in the fifth intercostal space (n = 2). Echocardiography was performed to exclude the presence of LAA thrombus and to confirm exclusion of LAA before final deployment of the clip. Results The mean age was 73.6 years. The mean CHA2DS2VASC score was 4.7 and the mean HAS-BLED score was 3.8. The mean postoperative length of stay was 6.4 days. One patient died of stroke-related complications 10 days after successful clipping, and two patients required thoracentesis to drain recurrent pleural effusions. All patients had successful exclusion of LAA defined as residual sac of less than 1 cm. Conclusions Isolated epicardial left atrial clipping is a safe treatment option in high-risk patients with AF. Long-term success in preventing stroke is still to be determined, but short-term results are very encouraging.