Melissa M. Anastacio

Surgical Experience With Cardiac Papillary Fibroelastoma Over a 15-Year Period

BACKGROUND Papillary fibroelastomas are rare, benign cardiac tumors. They are predominantly asymptomatic. However, they can lead to serious complications, namely thromboembolic events. Symptomatic lesions can be managed primarily with surgical excision and valvular preservation. Controversy exists as to the management of asymptomatic lesions. METHODS All patients diagnosed with cardiac papillary fibroelastoma between 1996 and 2012 at a single institution were queried for clinical and pathologic characteristics. RESULTS Twenty-three patients with 29 lesions were identified. Most lesions were solitary, less than 1.0 cm in diameter, and occurred in patients greater than 60 years of age. The most common presentation was thromboembolic complication. All were managed successfully with surgical excision. One patient developed a recurrence or metachronous lesion within 3 months of initial surgical intervention. CONCLUSIONS Papillary fibroelastomas are rare, benign, predominantly asymptomatic cardiac tumors that can cause potentially serious complications. The natural history and etiology of papillary fibroelastomas are largely unknown. Controversy exists over the management of asymptomatic lesions. However, there is consensus that symptomatic lesions should undergo surgical excision with valvular preservation when possible. A unique case of a possible papillary fibroelastoma recurrence is also described.

Relationship Between Mitochondrial Matrix Volume and Cellular Volume in Response to Stress and the Role of ATP-Sensitive Potassium Channel

Background— Cardiac myocytes demonstrate significant swelling and associated reduced contractility in response to stress that is prevented by the ATP-sensitive potassium channel opener, diazoxide (DZX) via an unknown mechanism. One proposed mechanism of cardioprotection is mitochondrial matrix swelling. To establish the relationship between mitochondrial and cellular volume during stress, this study examined the effect of DZX on mitochondrial volume. Methods and Results— Isolated mouse mitochondria were exposed to the following solutions: Tyrode, isolation buffer, cardioplegia (CPG)±DZX±ATP-sensitive potassium channel inhibitor, 5-hydroxydecanoate, and metabolic inhibition (MI)±DZX±5-hydroxydecanoate. Mitochondrial volume was measured. DZX resulted in significant mitochondrial swelling (P<0.0001 versus Tyrode). MI and CPG resulted in significant mitochondrial swelling compared with baseline volume. The addition of DZX did not alter the response of mitochondrial volume to CPG (P=0.912) but increased swelling in response to MI (P=0.036). The addition of 5-hydroxydecanoate to MI+DZX or CPG+DZX significantly reduced mitochondrial swelling (P<0.003 MI+DZX versus MI+DZX+5HD; P<0.001 CPG+DZX versus CPG+DZX+5HD). Conclusions— Both cellular and mitochondrial volume increased during exposure to MI and CPG. DZX did not alter mitochondrial volume during CPG; however, it was associated with an increase in mitochondrial volume during MI. 5-Hydroxydecanoate reduced mitochondrial volume during exposure to both stresses with DZX, supporting a role for a mitochondrial ATP-sensitive potassium channel in the mechanism of cardioprotection by DZX.

Laser Extraction of Pacemaker Lead Traversing a Patent Foramen Ovale and the Mitral Valve

Left ventricular lead misplacement is an infrequent complication of pacemaker or defibrillator lead insertion. It most commonly occurs through defects in the interatrial septum. Although patients may remain asymptomatic, the most common clinical complication is a thromboembolic event. Percutaneous technology has been described to safely remove misplaced leads. We present a case of a patient with a pacemaker lead in the left ventricle through a patent foramen ovale that was successfully extracted using excimer laser technology.

Cardioprotective mechanism of diazoxide involves the inhibition of succinate dehydrogenase

BACKGROUND The adenosine triphosphate-sensitive potassium (KATP) channel opener, diazoxide, preserves myocyte volume homeostasis and contractility during stress via an unknown mechanism. Pharmacologic overlap has been suggested between succinate dehydrogenase (SDH) activity and KATP channel modulators. Diazoxide may be cardioprotective due to the inhibition of SDH which may form a portion of the mitochondrial KATP channel. To determine the role of inhibition of SDH in diazoxides cardioprotection, this study utilized glutathione to prevent the inhibition of SDH. METHODS SDH activity was measured in isolated mitochondria exposed to succinate (control), malonate (inhibitor of succinate dehydrogenase), diazoxide, and varying concentrations of glutathione alone or in combination with diazoxide. Enzyme activity was measured by spectrophotometric analysis. To evaluate myocyte volume and contractility, cardiac myocytes were superfused with Tyrodes physiologic solution (Tyrodes) (20 minutes), followed by test solution (20 minutes), including Tyrodes, hyperkalemic cardioplegia (stress), cardioplegia + diazoxide, cardioplegia + diazoxide + glutathione, or glutathione alone; followed by Tyrodes (20 minutes). Myocyte volume and contractility were recorded using image grabbing software. RESULTS Both malonate and diazoxide inhibited succinate dehydrogenase. Glutathione prevented the inhibition of succinate dehydrogenase by diazoxide in a dose-dependent manner. The addition of diazoxide prevented the detrimental myocyte swelling due to cardioplegia alone and this benefit was lost with the addition of glutathione. However, glutathione elicited an independent cardioprotective effect on myocyte contractility. CONCLUSIONS The ability of diazoxide to provide beneficial myocyte homeostasis during stress involves the inhibition of succinate dehydrogenase, which may also involve the opening of a purported mitochondrial adenosine triphosphate sensitive potassium channel.

Iatrogenic left internal thoracic artery to left subclavian vein fistula after excimer laser pacemaker lead extraction

From the Division of Cardiothoracic Surgery, Department of Surgery, the Division of CardiovascularMedicine, Department ofMedicine, and theMallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, Mo. Disclosures: Authors have nothing to disclose with regard to commercial support. Received for publication Dec 15, 2011; accepted for publication Jan 4, 2012; available ahead of print Feb 3, 2011. Address for reprints: Jennifer S. Lawton,MD,Washington University School ofMedicine, 660 S Euclid Ave, Campus Box 8234, St Louis, MO 63110 (E-mail: lawtonj@wustl.edu). J Thorac Cardiovasc Surg 2012;143:e35-7 0022-5223/

Cardioprotective Benefits of Adenosine Triphosphate-Sensitive Potassium Channel Opener Diazoxide Are Lost with Administration after the Onset of Stress in Mouse and Human Myocytes

36.00 Copyright 2012 by The American Association for Thoracic Surgery doi:10.1016/j.jtcvs.2012.01.014

Left Main Disease Progression Following Left Branch Vessel Percutaneous Intervention in Patients Who Are Referred for Coronary Artery Bypass Grafting

BACKGROUND Adenosine triphosphate-sensitive (KATP) potassium channel opener diazoxide (DZX) maintains myocyte volume and contractility during stress via an unknown mechanism when administered at the onset of stress. This study was performed to investigate the cardioprotective potential of DZX when added after the onset of the stresses of hyperkalemic cardioplegia, metabolic inhibition, and hypo-osmotic stress. STUDY DESIGN Isolated mouse ventricular and human atrial myocytes were exposed to control Tyrodes solution (TYR) for 10 to 20 minutes, test solution for 30 minutes (hypothermic hyperkalemic cardioplegia [CPG], CPG + 100uM diazoxide [CPG+DZX], metabolic inhibition [MI], MI+DZX, mild hypo-osmotic stress [0.9T], or 0.9T + DZX), with DZX added after 10 or 20 minutes of stress, followed by 20 minutes of re-exposure to TYR (±DZX). Myocyte volume (human + mouse) and contractility (mouse) were compared. RESULTS Mouse and human myocytes demonstrated significant swelling during exposure to CPG, MI, and hypo-osmotic stress that was not prevented by DZX when administered either at 10 or 20 minutes after the onset of stress. Contractility after the stress of CPG in mouse myocytes significantly declined when DZX was administered 20 minutes after the onset of stress (p < 0.05 vs TYR). Contractility after hypo-osmotic stress in mouse myocytes was not altered by the addition of DZX. CONCLUSIONS To maintain myocyte volume homeostasis and contractility during stress (hyperkalemic cardioplegia, metabolic inhibition, and hypo-osmotic stress), KATP channel opener diazoxide requires administration at the onset of stress in this isolated myocyte model. These data have potential implications for any future clinical application of diazoxide.

Congenital fistula from the left main coronary artery to the left atrium presenting with an acute myocardial infarction

We studied patients presenting for coronary artery bypass grafting (CABG) with significant left main coronary artery disease (LMD) despite previously documented minimal or no LMD at percutaneous coronary intervention (PCI) for left‐sided branch coronary artery disease.

Inhibition of Succinate Dehydrogenase by Diazoxide Is Independent of the ATP-Sensitive Potassium Channel Subunit Sulfonylurea Type 1 Receptor

FIGURE 1. A representative slice of the chest computed tomographic scan shows an aneurysmal left main coronary artery and thrombus in the proximal left anterior descending coronary artery. CLINICAL SUMMARY A 23-year-old man with a history of Asperger syndrome had been born with LMCA to left atrial fistula and had undergone 2 coil embolizations at the ages of 5 and 7 years. At the age of 17 years, he had a myocardial infarction, which was attributed to embolism to a marginal branch of the left circumflex coronary artery. Cardiac catheterization at the time showed residual flow through the portion of the CAF between the left main ostium and the coils. The patient returned in March 2012 with chest pain and was found to have a myocardial infarction. Computed tomographic scan demonstrated persistence of the fistula to the coils, as well as thrombus within the fistula and all 3 branches of the LMCA (Figure 1). After transfer to our institution, the patient had recurrent chest pain with electrocardiographic changes. Urgent cardiac catheterization demonstrated a fistula originating within millimeters of the left main ostium and the previously placed coils (Figure 2, A and B). Proximal thrombus was identified in the left anterior descending coronary artery, the ramus, and the left circumflex coronary artery. The patient was urgently taken to the operating room. Under cardioplegic arrest, the LMCAwas extremely friable and tore easily, even with gentle dissection. The LMCA just before its branching and the inferior path of the fistula were therefore both ligated. The previously placed coils were visualized superiorly near Waterston’s groove. A bovine pericardial patch was sewn inside the aorta, where the left main ostium had been and only friable tissue remained. Coronary artery bypass grafting was performed with the left