Left main disease progression following left branch vessel percutaneous intervention in patients who are referred for coronary artery bypass grafting.

BACKGROUND AND AIM OF THE STUDY: 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. METHODS: Patients undergoing CABG for LMD with previous PCI were separated into fast or slow stenosis progression using percent change in LMD from first PCI to CABG divided by time (progression velocity). Outcomes and Kaplan-Meier survival were compared between the two groups. RESULTS: Between September 1997 and June 2010, 4837 patients underwent CABG with 1235 of them having previous PCI of which 118 had LMD and previous left-sided branch PCI. Using median progression velocity fast and slow progression groups were identified (0.53 ± 0.18 and 4.5 ± 4.8%/month, p < 0.001). Mean follow-up was 4.9 ± 3.6 years and 6.9 ± 3.9 years, respectively. Fast progression patients were younger (p = 0.042), with higher baseline LMD at PCI (16.4% vs. 9% stenosis, p = 0.025), and a mean of 2.5 years to LMD compared to 10.6 years for the slow group (p < 0.001). There was no difference between the groups in number or type of PCI and number or type of vessel intervened. Kaplan-Meier survival was similar at one, three, and five years. CONCLUSIONS: Fast LMD progression patients were younger and made up 4.7% (59/1235) of patients undergoing CABG with a history of PCI. Rapid progression was not related to number, type of PCI, or branch vessel intervened.

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.

Cardioprotective benefits of adenosine triphosphate-sensitive potassium channel opener diazoxide are lost with administration after the onset of stress in mouse and human myocytes.

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 Tyrode's 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.

Safety and efficacy of implementing a multidisciplinary heart team approach for revascularization in patients with complex coronary artery disease: an observational cohort pilot study.

IMPORTANCE: Since the advent of transcatheter aortic valve replacement, the multidisciplinary heart team (MHT) approach has rapidly become the standard of care for patients undergoing the procedure. However, little is known about the potential effect of MHT on patients with coronary artery disease (CAD). OBJECTIVE: To determine the safety and efficacy of implementing the MHT approach for patients with complex CAD. DESIGN, SETTING, AND PARTICIPANTS: Observational cohort pilot study of 180 patients with CAD involving more than 1 vessel in a single major academic tertiary/quaternary medical center. From May 1, 2012, through May 31, 2013, MHT meetings were convened to discuss evidence-based management of CAD. All cases were reviewed by a team of interventional cardiologists and cardiac surgeons within 72 hours of angiography. All clinical data were reviewed by the team to adjudicate optimal treatment strategies. Final recommendations were based on a consensus decision. Outcome measures were tracked for all patients to determine the safety and efficacy profile of this pilot program. EXPOSURES: Multidisciplinary heart team meeting. MAIN OUTCOMES AND MEASURES: Thirty-day periprocedural mortality and rate of major adverse cardiac events. RESULTS: Most of the patients underwent percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG); a small percentage of patients underwent a hybrid procedure or medical management. Incidence of 30-day periprocedural mortality was low across all groups of patients (PCI group, 5 of 64 [8%]; CABG group, 1 of 87 [1%]). The rate of major adverse cardiac events during a median follow-up of 12.1 months ranged from 12 of 87 patients (14%) in the CABG group to 15 of 64 (23%) in the PCI group. CONCLUSIONS AND RELEVANCE: Outcomes of patients with complex CAD undergoing the optimal treatment strategy recommended by the MHT were similar to those of published national standards. Implementation of the MHT approach for patients with complex CAD is safe and efficacious.

Video-assisted minimally invasive mitral valve surgery: transitioning from sternotomy to mini-thoracotomy.

Minimally invasive right thoracotomy approaches to complex mitral valve surgery have emerged as safe and effective alternatives to traditional median sternotomy. Early experiences were associated with concerns over repair failures, neurological events and longer cardiopulmonary bypass times. However, several technique refinements over the last decade have led to a resurgence of minimally invasive thoracotomy/thoracoscopic mitral surgery with improved short-term outcomes and equivalent long-term durability to sternotomy. We describe one such approach that utilizes video assistance along with direct vision to facilitate reproducible mitral surgery.

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 diazoxide's 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 Tyrode's physiologic solution (Tyrode's) (20 minutes), followed by test solution (20 minutes), including Tyrode's, hyperkalemic cardioplegia (stress), cardioplegia + diazoxide, cardioplegia + diazoxide + glutathione, or glutathione alone; followed by Tyrode's (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.

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

BACKGROUND: Diazoxide maintains myocyte volume and contractility during stress via an unknown mechanism. The mechanism of action may involve an undefined (genotype unknown) mitochondrial ATP-sensitive potassium channel and is dependent on the ATP-sensitive potassium channel subunit sulfonylurea type 1 receptor (SUR1). The ATP-sensitive potassium channel openers have been shown to inhibit succinate dehydrogenase (SDH) and a gene for a portion of SDH has been found in the SUR intron. Diazoxide may be cardioprotective via inhibition of SDH, which can form part of an ATP-sensitive potassium channel or share its genetic material. This study investigated the role of inhibition of SDH by diazoxide and its relationship to the SUR1 subunit. STUDY DESIGN: Mitochondria were isolated from wild-type and SUR1 knockout mice. Succinate dehydrogenase activity was measured by spectrophotometric analysis of 2,6-dichloroindophenol reduction for 20 minutes as the relative change in absorbance over time. Mitochondria were treated with succinate (20 mM), succinate + 1% dimethylsulfoxide, succinate + malonate (8 mM) (competitive inhibitor of SDH), or succinate + diazoxide (100 µM). RESULTS: Both malonate and diazoxide inhibit SDH activity in mitochondria of wild-type mice and in mice lacking the SUR1 subunit (p < 0.05 vs control). CONCLUSIONS: The ability of DZX to inhibit SDH persists even after deletion of the SUR1 gene. Therefore, the enzyme complex SDH is not dependent on the SUR1 gene. The inhibition of SDH by DZX can play a role in the cardioprotection afforded by DZX; however, this role is independent of the ATP-sensitive potassium channel subunit SUR1.

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.

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.

Prevention of surgical site infections.

In the current era of pay-for-performance standards, the incidence of surgical site infections is increasingly becoming an institutional marker of quality assurance. Surgical site infections lead to increased morbidity and mortality in the surgical population and contribute to an already rising healthcare cost. As a result, the surgical community goes to great lengths to prevent this costly and occasionally lethal complication. Many practices are evidence based, however, many are not. In this article, the most commonly used preventive strategies in practice today and the evidence behind each are reviewed. In addition, an overview of the epidemiology, pathophysiology and microbiology of surgical site infections will be provided.

Cognitive function in patients with chronic granulomatous disease: a preliminary report.

Chronic granulomatous disease is an inherited immunodeficiency in which phagocytes fail to generate superoxide and its metabolites, resulting in severe recurrent infections and frequent hospitalizations. Chronic illness and frequent hospitalizations can affect growth and development as well as social and educational opportunities. Since no data have been reported on cognitive functioning in patients with this illness, the authors sought to examine cognitive function in a group of patients with chronic granulomatous disease. A retrospective chart review of 26 patients seen and followed at the National Institutes of Health who had received cognitive testing at the request of parent or staff was performed. Demographic information including medical, psychiatric, and developmental histories was gathered. Six patients (23%) were found to have an IQ of 70 or below, indicative of cognitive deficits, and all of those patients had defects in the membrane-linked cytochrome b558. The prevalence of cognitive deficits in this selected population of chronic granulomatous disease patients was high. The determination of the true distribution of cognitive functioning in the general chronic granulomatous disease population is important, since cognitive deficits have implications for educational planning and potential therapies such as transplantation and gene therapy in children.