[Show abstract][Hide abstract] ABSTRACT: : Perioperative pulmonary hypertension can originate from an established disease or acutely develop within the surgical setting. Patients with increased pulmonary vascular resistance are consequently at greater risk for complications. Despite the various specific therapies available, the ideal therapeutic approach in this patient population is not currently clear. This article describes the basic principles of perioperative pulmonary hypertension and reviews the different classes of agents used to promote pulmonary vasodilation in the surgical setting.
Journal of cardiovascular pharmacology 04/2014; 63(4):375-84. · 2.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Atrial Fibrillation (AF), the most common sustained arrhythmia, has a strong genetic component, but the mechanism by which common genetic variants lead to increased AF susceptibility is unknown. Genome-wide association studies (GWAS) have identified that the single nucleotide polymorphisms (SNPs) most strongly associated with AF are located on chromosome 4q25 in an intergenic region distal to the PITX2 gene. Our objective was to determine whether the AF-associated SNPs on chromosome 4q25 were associated with PITX2c expression in adult human left atrial appendages. Analysis of a lone AF GWAS identified four independent AF risk SNPs at chromosome 4q25. Human adult left atrial appendage tissue was obtained from 239 subjects of European Ancestry and used for SNP analysis of genomic DNA and determination of PITX2c RNA expression levels by quantitative PCR. Subjects were divided into three groups based on their history of AF and pre-operative rhythm. AF rhythm subjects had higher PITX2c expression than those with history of AF but in sinus rhythm. PITX2c expression was not associated with the AF risk SNPs in human adult left atrial appendages in all subjects combined or in each of the three subgroups. However, we identified seven SNPs modestly associated with PITX2c expression located in the introns of the ENPEP gene, ∼54 kb proximal to PITX2. PITX2c expression in human adult left atrial appendages is not associated with the chromosome 4q25 AF risk SNPs; thus, the mechanism by which these SNPs are associated with AF remains enigmatic.
PLoS ONE 01/2014; 9(1):e86245. · 3.73 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Patients with TOF following complete repair and PS after surgical valvotomy often develop significant pulmonic regurgitation (PR), eventually requiring valve replacement (PVR). Though criteria exist for the timing of PVR in TOF, it remains less clear when to intervene in valvotomy patients and whether TOF recommendations can be applied. Our aim was to compare the structural and functional sequelae of valvotomy for pulmonic stenosis (PS) with complete repair for tetralogy of Fallot (TOF). We compared the clinical characteristics, electrocardiograms, echocardiograms, cardiac MRI and invasive hemodynamics of 109 adults (34 PS and 75 TOF) newly referred to a congenital heart disease center for evaluation of PR between 2005 and 2012. Both cohorts were similar in terms of baseline demographics and presenting NYHA function class. Valvotomy patients had a slightly greater degree of PR by echo, though it was similar by cardiac MRI. ECG QRS width was greater in TOF (114±27 vs. 150±28 ms, p<0.001). MRI right ventricular ejection fraction (49±8 vs. 41±11%, p=0.001) and left ventricular ejection fraction (59±7 vs. 52±10%, p=0.002) were lower in TOF. Pacemaker or defibrillator implantation was significantly higher in TOF (3% vs. 23%, p=0.011). In conclusion, patients post-valvotomy and complete repair present with similar degrees of PR and symptom severity. Biventricular systolic function and ECG QRS width appear less affected, suggesting morphologic changes in TOF and its repair that extend beyond the effects of PR. These findings suggest the need for developing disease-specific guidelines for patients with PR post-valvotomy.
[Show abstract][Hide abstract] ABSTRACT: -The genetic mechanisms of atrial fibrillation (AF) remain incompletely understood. Previous differential expression studies in AF were limited by small sample size and provided limited understanding of global gene networks, prompting the need for larger-scale, network-based analyses.
-Left atrial tissues from Cleveland Clinic cardiac surgery patients were assayed using Illumina Human HT-12 mRNA microarrays. The dataset included three groups based on cardiovascular co-morbidities: mitral valve (MV) disease without coronary artery disease (CAD) (n=64); CAD without MV disease (n=57); and lone AF (LAF) (n=35). Weighted gene co-expression network analysis was conducted in the MV group to detect modules of correlated genes. Module preservation was assessed in the other two groups. Module eigengenes were regressed on AF severity or atrial rhythm at surgery. Modules whose eigengenes correlated with either AF phenotype were analyzed for gene content. 14 modules were detected in the MV group; all were preserved in the other two groups. One module (124 genes) was associated with AF severity and atrial rhythm across all groups. Its top hub gene, RCAN1, is implicated in calcineurin-dependent signaling and cardiac hypertrophy. Another module (679 genes) was associated with atrial rhythm in the MV and CAD groups. It was enriched with cell signaling genes and contained cardiovascular developmental genes including TBX5.
-Our network-based approach found two modules strongly associated with AF. Further analysis of these modules may yield insight into AF pathogenesis by providing novel targets for functional studies.
[Show abstract][Hide abstract] ABSTRACT: Purpose
Despite thorough radiologic evaluation prior to lung transplantation (LTx), explanted lungs occasionally harbor non-small cell lung cancer (NSCLC). However, the incidence and outcomes for this phenomenon are unknown. We describe our center’s experience with unexpected explant NSCLC and its impact on post-transplant survival.
Methods and Materials
From April 2007 to April 2012, 522 patients underwent LTx at the Cleveland Clinic. Review of medical records was performed which included surgical pathology of the explanted lung(s), pathologic cancer staging and postoperative course. Specific attention was given to cancer progression and recurrence. Overall survival was determined using Kaplan-Meier method.
Thirteen patients (2.5% incidence) were noted to have explant NSCLC. Listing diagnosis was UIP in 9 (69%) and COPD in 4 (31%) with 8 undergoing double LTx and 5 undergoing single LTx. Mean age at transplantation was 63 ± 6 years. Time from the last chest CT scan to transplantation was 103 ± 83 days. All malignancies were primary NSCLC with adenocarcinoma in 9 (69%) and squamous cell carcinoma in 4 (31%). 8 patients were Stage I, 4 Stage II and 1 Stage IV. 7 (53%) patients underwent post-transplant cancer treatment. Progression of disease occurred in 8 (62%) patients at a mean follow-up of 9.9 ± 6.5 months, with overall survival 14% at 2 years. [figure 1]
Despite heightened screening, incidence of unsuspected NSCLC is surprisingly high. Moreover, despite the complete resection afforded by native pneumonectomy and adjuvant therapy, overall survival is poor due to rapid malignant progression. A unique pre-transplant surveillance screening program needs to be devised for this high risk population
The Journal of Heart and Lung Transplantation 04/2013; 32(4):214. · 5.11 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background Heparin is routinely administered to brain-dead donors before cardiac arrest, although it is not universally allowed for donation after cardiac death (DCD) donors due to concerns that death may be hastened. The lack of heparin may lead to thrombosis and compromised graft function. We evaluated the impact of timing of heparin administration and thrombi formation in a DCD pig model.Methods Eight domestic adult pigs were administered systemic heparin (30,000 IU): four prior to cardiac arrest through intravenous injection (prearrest heparin) and four after cardiac arrest via injection into the right atrium followed by open cardiac massage (postarrest heparin). Pigs were euthanized with potassium chloride and a minimum of 5 minutes of cardiac silence allowed before organ procurement. Lungs were flushed with antegrade and retrograde Perfadex, and pulmonary preservation solution effluent was evaluated for gross thrombi. Organs were fixed in formalin, sagittally sectioned, and evaluated by a pulmonary pathologist blinded to treatment.Results Antegrade and retrograde flushes demonstrated no significant thrombi. Gross pathologic evaluation revealed no occlusive central thrombi. Scant peripheral thrombi were detected in both treatment groups. No microscopic thrombi were noted in either treatment group.Conclusions Delayed heparin administration after cardiac death does not affect thrombus formation in an animal model of lung procurement after cardiac death. Concern about clinically significant thrombosis occurring when heparin is not given before cardiac arrest appears unfounded. These findings suggest that DCD lungs can be used regardless of antemortem heparin administration.
The Thoracic and Cardiovascular Surgeon 12/2012; · 0.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Extracorporeal membrane oxygenation (ECMO) is rarely used as a bridge to lung transplantation (BTT) because of its associated morbidity and mortality. However, recent advancements in perfusion technology and critical care have revived interest in this application of ECMO. We retrospectively reviewed our utilization of ECMO as BTT and evaluated our early and midterm results. Nineteen patients were placed on ECMO with the intent to transplant of which 14 (74%) were successfully transplanted. Early and midterm survival of transplanted patients was 75% (1 year) and 63% (3 years), respectively, with the most favorable results observed in interstitial lung disease patients supported in the venovenous configuration. Extracorporeal membrane oxygenation-bridged transplant survival rates were equivalent to nonbridged recipients, but early morbidity and mortality are high and the failure to bridge to transplant is significant. Overall, successfully bridged patients can derive a tangible benefit, albeit with considerable consumption of resources.
ASAIO journal (American Society for Artificial Internal Organs: 1992) 08/2012; 58(5):526-9. · 1.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Open, hybrid, and endovascular procedures are used for grown-up patients with aortic coarctation and complications after repair, an expanding population. We sought to characterize patients and procedures, assess early and late outcomes, and describe indications to guide treatment of these complex patients.
Between May 1999 and January 2011, 110 patients underwent open (n=40), hybrid (n=11), or endovascular (n=59) repair of coarctation (n=43), recurrent aortic coarctation (n=42), or postrepair aneurysm (n=25). Mean age was 38±14 years. Sixty-eight had previous repairs (median 27 years earlier; range, 1 to 50). Twenty-two had prior cardiovascular operations other than coarctation and 50% had bicuspid valve. Fifty-nine concomitant procedures were performed in 45 patients (40%). Data were from the prospective database, chart review, and Social Security Death Index.
Technical success was achieved in 100%, with no hospital deaths, no strokes, and no paraplegia. Complications were uncommon and included respiratory failure (n=2, 1.8%), and temporary renal failure (n=2, 1.8%). Twenty-two patients required reinterventions, but half of those were planned. There was no difference in occurrence of unplanned reintervention between approaches (endovascular 12%, hybrid 18%, open 12.5%). Length of stay was 4.8±4.8 days. Transcoarct gradient fell from 37.6±18 mm Hg preoperatively to 7.0±6.9 mm Hg in coarctation patients. Postrepair aneurysm patients had no late ruptures, and maximum diameter shrunk from 5.9±1.3 cm preoperatively to 4.8±1.3 cm. Estimated survival at 1, 5, and 8 years was 95%, 95%, and 90%, respectively.
Coarctation, recurrent coarctation, and postrepair aneurysm/pseudoaneurysm in adolescent and adult patients can be safely and effectively managed with open, hybrid, or endovascular techniques. Optimal results are achievable in this complex population of patients with a multimodality approach tailored to surgical indication and anatomy. All survivors of coarctation repair require lifelong surveillance.
The Annals of thoracic surgery 06/2012; 94(3):751-6; discussion 757-8. · 3.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Acute pulmonary embolism (PE) compromises oxygenation and is typically considered a contraindication to lung donation for transplantation. We report the use of ex vivo lung perfusion (EVLP) to evaluate and possibly improve a pair of donor lungs with PE and poor oxygen exchange to a condition that might have been suitable for subsequent transplantation. A pair of donor lungs was procured for research after being declined for clinical use and placed on the EVLP circuit for 7 hours. Functional monitoring of the lungs revealed an increase in the partial pressure of oxygen to fraction of inspired oxygen ratio (P/F ratio) from 268 in situ to 458 after EVLP. While on the circuit, pulmonary vascular resistance decreased as dynamic compliance of the lungs increased, suggesting they might have been acceptable for transplantation.
ASAIO journal (American Society for Artificial Internal Organs: 1992) 05/2012; 58(4):432-4. · 1.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Pulmonary vein stenosis can complicate ablation procedures for atrial fibrillation and often presents with severe respiratory symptoms. Described in this case report is a 21-year-old male who underwent a bilateral surgical augmentation of the pulmonary veins for severe occlusive pulmonary vein stenosis. The occluded left lower and right upper lobe veins were surgically modified to regain flow to the left atrium. Follow-up computed tomogram imaging showed patency of the veins intervened upon and an exercise test demonstrated an oxygen saturation of 98% at peak stress.This case report marks the first-ever surgical intervention for acquired pulmonary vein stenosis.
Journal of Cardiovascular Electrophysiology 03/2012; 23(6):656-8. · 3.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: There is a limited experience using pediatric organs for adult lung transplantation (LTx), with size matching the major concern. We reviewed our experience transplanting pediatric donor lungs into adult recipients with endpoints of post-LTx complications and overall patient survival.
From 2/1990 to 12/2007, 609 adults underwent primary LTx at our institution. Thirty-eight (6.2%) patients underwent LTx with organs from pediatric donors (≤16 years). Of these, median donor age was 13 years (range: 7 to 16) and median recipient age 55 (range: 24 to 66). Endpoints analyzed included size matching accuracy, airway and pleural complications, time to extubation, intensive care unit (ICU) and hospital lengths of stay, as well as survival.
Gross undersizing of the donor lung was present in 2/38 (5.3%) and of the donor bronchus in 11/38 (29%). Five patients (13%) experienced a major postoperative airway complication. Thoracentesis prior to discharge was necessary in 4/38 (11%) patients and chest tube reinsertion in 10/38 (26%) for pleural effusion. Median time to extubation was 2 days. ICU and hospital lengths of stay were 6 and 16 days, respectively. Kaplan-Meier survival at 30 days, 1 year, 3 years, and 5 years post-transplant was 89%, 74%, 63%, and 55%.
Despite sizing concerns, transplantation of pediatric lungs into adult recipients is feasible. Size mismatch may predispose to higher rates of airway and pleural complications. Hospital course and overall survival appear comparable to adult-to-adult LTx, and concerns over size matching should not preclude pediatric organ use for adult candidates.
The Thoracic and Cardiovascular Surgeon 01/2012; 60(4):275-9. · 0.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The risk of death and complications of infective endocarditis (IE) treated medically has to be balanced against those from surgery in constructing a therapeutic approach. Recent literature has drawn conflicting conclusions on the benefit of surgery for IE. We reviewed patients treated surgically for IE at the Cleveland Clinic from 2003 to 2007 to examine their outcomes.
A retrospective review of consecutive patients who underwent surgery for native and prosthetic valve endocarditis between January 1, 2003, and December 31, 2007, was conducted. Surgical outcomes were reviewed to include survival and postoperative complications. Survival was evaluated at end of hospital stay, 30 days, 1 year, and at last follow-up.
Four hundred twenty-eight patients underwent surgery for IE during the study period: 248 (58%) had native valve endocarditis and 180 (42%) had prosthetic valve endocarditis. Overall 90% of patients survived to hospital discharge. When compared with patients with native valve infection, patients with prosthetic infection had significantly higher 30-day mortality (13% versus 5.6%; p<0.01), but long-term survival was not significantly different (35% versus 29%; p=0.19). Patients with IE caused by Staphylococcus aureus had significantly higher hospital mortality (15% versus 8.4%; p<0.05), 6-month mortality (23% versus 15%; p=0.05), and 1-year mortality (28% versus 18%; p=0.02) compared with non-S aureus IE.
Surgical treatment of IE was associated with 90% hospital survival. Outcomes within the 30 days were better for native valve than for prosthetic valve endocarditis. Long-term outcomes were similar. Finally, S aureus was associated with significantly higher mortality compared with other pathogens.
The Annals of thoracic surgery 12/2011; 93(2):489-93. · 3.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Immunosuppressed patients are at an increased risk for severe disease from influenza A (H1N1). We report a case of a patient who died of septic complications from H1N1 acquired at the time of single lung transplant.
The Thoracic and Cardiovascular Surgeon 03/2011; 59(2):126-7. · 0.93 Impact Factor