ABSTRACT
We report the technique needed to effectively repair a left main coronary artery shredding after rotational atherectomy and destruction of the left main coronary artery. The patient had been deemed inoperable at another center because of diffuse distal coronary disease. The complication led to cardiac tamponade and hemodynamic collapse, necessitating cardiopulmonary resuscitation and salvage surgery. This is perhaps the first case in the literature to show a successful repair of such a complex and significant left main, left anterior descending, and left circumflex coronary artery rupture in a patient in extremis.
Subject(s)
Atherectomy, Coronary , Coronary Artery Disease , Humans , Coronary Vessels/diagnostic imaging , Coronary Vessels/surgery , Coronary Artery Disease/surgery , Atherectomy, Coronary/methods , Coronary AngiographyABSTRACT
BACKGROUND: We hypothesized that gene expression profiles of mitral valve (MV) leaflets from patients with Barlow's disease (BD) are distinct from those with fibroelastic deficiency (FED). METHODS: MVs were obtained from patients with BD (7 men, 3 women; 61.4 ± 12.7 years old) or FED (6 men, 5 women; 54.5 ± 6.0 years old) undergoing operations for severe mitral regurgitation (MR). Normal MVs were obtained from 6 donor hearts unmatched for transplant (3 men, 3 women; 58.3 ± 7.5 years old), and gene expression was assessed using cDNA microarrays. Select transcripts were validated by quantitative reverse-transcription polymerase chain reaction, followed by an assessment of protein levels by immunostaining. RESULTS: The global gene expression profile for BD was clearly distinct from normal and FED groups. A total of 4,684 genes were significantly differential (fold-difference >1.5, p < 0.05) among the three groups, 1,363 of which were commonly altered in BD and FED compared with healthy individuals (eg TGFß2 [transforming growth factor ß2] and TGFß3 were equally upregulated in BD and FED). Most interesting were 329 BD-specific genes, including ADAMTS5 (a disintegrin-like and metalloprotease domain with thrombospondin-type 5), which was uniquely downregulated in BD based on microarrays and quantitative reverse-transcription polymerase chain reaction. Consistent with this finding, the ADAMTS5 substrate versican was increased in BD and conversely lower in FED. CONCLUSIONS: MV leaflets in BD and FED exhibit distinct gene expression patterns, suggesting different pathophysiologic mechanisms are involved in leaflet remodeling. Moreover, downregulation of ADAMTS5 in BD, along with the accumulation of its substrate versican in the valvular extracellular matrix, might contribute to leaflet thickening and enlargement.
Subject(s)
ADAMTS5 Protein/genetics , Mitral Valve Insufficiency/genetics , Mitral Valve Prolapse/genetics , Versicans/metabolism , ADAMTS5 Protein/metabolism , Adult , Aged , Case-Control Studies , Female , Humans , Male , Microarray Analysis , Middle Aged , Mitral Valve Insufficiency/metabolism , Mitral Valve Insufficiency/pathology , Mitral Valve Prolapse/metabolism , Mitral Valve Prolapse/pathology , Proteolysis , Reverse Transcriptase Polymerase Chain Reaction , TranscriptomeSubject(s)
Coronary Artery Bypass, Off-Pump , Coronary Artery Bypass , Aorta , Network Meta-AnalysisABSTRACT
BACKGROUND: With increasing prevalence of injected drug use in the United States, a growing number of intravenous drug users (IVDUs) are at risk for infective endocarditis (IE) that may require surgical intervention; however, few data exist about clinical outcomes of these individuals. METHODS: We evaluated consecutive adult patients undergoing surgery for active IE between 2002 and 2014 pooled from 2 prospective institutional databases. Death and valve-related events, including reinfection or heart valve reoperation, thromboembolism, and anticoagulation-related hemorrhage were evaluated. RESULTS: Of the 436 patients identified, 78 (17.9%) were current IVDUs. The proportion of IVDUs increased from 14.8% in 2002 to 2004 to 26.1% in 2012 to 2014. IVDUs were younger (aged 35.9 ± 9.9 years vs 59.3 ± 14.1 years) and had fewer cardiovascular risk factors than non-IVDUs. During follow-up (median, 29.4 months; quartile 1-3, 4.7-72.6 months), adverse events among all patients included death in 92, reinfection in 42, valve-reoperation in 35, thromboembolism in 17, and hemorrhage in 16. Operative mortality was lower among IVDUs (odds ratio, 0.25; 95% confidence interval [CI], 0.06-0.71), but overall mortality was not significantly different (hazard ratio [HR], 0.78; 95% CI, 0.44-1.37). When baseline profiles were adjusted by propensity score, IVDUs had higher risk of valve-related complications (HR, 3.82; 95% CI, 1.95-7.49; P < .001) principally attributable to higher rates of reinfection (HR, 6.20; 95% CI, 2.56-15.00; P < .001). CONCLUSIONS: The proportion of IVDUs among surgically treated IE patients is increasing. Although IVDUs have lower operative risk, long-term outcomes are compromised by reinfection.
Subject(s)
Endocarditis/surgery , Substance Abuse, Intravenous/complications , Adult , Endocarditis/mortality , Female , Humans , Male , Middle Aged , Postoperative Complications , Propensity Score , Prospective Studies , Recurrence , Risk Factors , Treatment OutcomeABSTRACT
BACKGROUND: Surgical dogma suggests that homografts should be used preferentially, compared with conventional xenograft or mechanical prostheses, in the setting of infective endocarditis (IE), because they have greater resistance to infection. However, comparative data that support this notion are limited. METHODS: From the prospective databases of 2 tertiary academic centers, we identified 304 consecutive adult patients (age ≥17 years) who underwent surgery for active IE involving the aortic valve (AV), in the period 2002 to 2014. Short- and long-term outcomes were evaluated using propensity scores and inverse-probability weighting to adjust for selection bias. RESULTS: Homografts, and xenograft and mechanical prostheses, were used in 86 (28.3%), 139 (45.7%), and 79 (26.0%) patients, respectively. Homografts were more often used in the setting of prosthetic valve endocarditis (58.1% vs 28.8%, P = .002) and methicillin-resistant Staphylococcus (25.6% vs 12.1%, P = .002), compared with conventional prostheses. Early mortality occurred in 17 (19.8%) in the homograft group, and 20 (9.2%) in the conventional group (P = .019). During follow-up (median: 29.4 months; interquartile-range: 4.7-72.6 months), 60 (19.7%) patients died, and 23 (7.7%) experienced reinfection, with no significant differences in survival (P = .23) or freedom from reinfection rates (P = .65) according to the types of prostheses implanted. After adjustments for baseline characteristics, using propensity-score analyses, use of a homograft did not significantly affect early death (odds ratio 1.61; 95% confidence interval [CI], 0.73-3.40, P = .23), overall death (hazard ratio 1.10; 95% CI, 0.62-1.94, P = .75), or reinfection (hazard ratio 1.04; 95% CI, 0.49-2.18, P = .93). CONCLUSIONS: No significant benefit to use of homografts was demonstrable with regard to resistance to reinfection in the setting of IE. The choice among prosthetic options should be based on technical and patient-specific factors. Lack of availability of homografts should not impede appropriate surgical intervention.
Subject(s)
Allografts , Aortic Valve/surgery , Bioprosthesis , Endocarditis/surgery , Heterografts , Prosthesis Failure , Academic Medical Centers , Adult , Aged , Aortic Valve/pathology , Databases, Factual , Endocarditis/diagnostic imaging , Endocarditis/microbiology , Endocarditis/mortality , Female , Graft Rejection , Graft Survival , Heart Valve Prosthesis , Heart Valve Prosthesis Implantation/adverse effects , Heart Valve Prosthesis Implantation/methods , Humans , Male , Middle Aged , Multivariate Analysis , Postoperative Complications/epidemiology , Postoperative Complications/physiopathology , Prognosis , Proportional Hazards Models , Prosthesis-Related Infections/diagnosis , Prosthesis-Related Infections/epidemiology , Retrospective Studies , Risk Assessment , Survival Analysis , Treatment Outcome , Ultrasonography , United StatesABSTRACT
IMPORTANCE: Statins affect several mechanisms underlying acute kidney injury (AKI). OBJECTIVE: To test the hypothesis that short-term high-dose perioperative atorvastatin would reduce AKI following cardiac surgery. DESIGN, SETTING, AND PARTICIPANTS: Double-blinded, placebo-controlled, randomized clinical trial of adult cardiac surgery patients conducted from November 2009 to October 2014 at Vanderbilt University Medical Center. INTERVENTIONS: Patients naive to statin treatment (n = 199) were randomly assigned 80 mg of atorvastatin the day before surgery, 40 mg of atorvastatin the morning of surgery, and 40 mg of atorvastatin daily following surgery (n = 102) or matching placebo (n = 97). Patients already taking a statin prior to study enrollment (n = 416) continued taking the preenrollment statin until the day of surgery, were randomly assigned 80 mg of atorvastatin the morning of surgery and 40 mg of atorvastatin the morning after (n = 206) or matching placebo (n = 210), and resumed taking the previously prescribed statin on postoperative day 2. MAIN OUTCOMES AND MEASURES: Acute kidney injury defined as an increase of 0.3 mg/dL in serum creatinine concentration within 48 hours of surgery (Acute Kidney Injury Network criteria). RESULTS: The data and safety monitoring board recommended stopping the group naive to statin treatment due to increased AKI among these participants with chronic kidney disease (estimated glomerular filtration rate <60 mL/min/1.73 m2) receiving atorvastatin. The board later recommended stopping for futility after 615 participants (median age, 67 years; 188 [30.6%] were women; 202 [32.8%] had diabetes) completed the study. Among all participants (n = 615), AKI occurred in 64 of 308 (20.8%) in the atorvastatin group vs 60 of 307 (19.5%) in the placebo group (relative risk [RR], 1.06 [95% CI, 0.78 to 1.46]; P = .75). Among patients naive to statin treatment (n = 199), AKI occurred in 22 of 102 (21.6%) in the atorvastatin group vs 13 of 97 (13.4%) in the placebo group (RR, 1.61 [0.86 to 3.01]; P = .15) and serum creatinine concentration increased by a median of 0.11 mg/dL (10th-90th percentile, -0.11 to 0.56 mg/dL) in the atorvastatin group vs by a median of 0.05 mg/dL (10th-90th percentile, -0.12 to 0.33 mg/dL) in the placebo group (mean difference, 0.08 mg/dL [95% CI, 0.01 to 0.15 mg/dL]; P = .007). Among patients already taking a statin (n = 416), AKI occurred in 42 of 206 (20.4%) in the atorvastatin group vs 47 of 210 (22.4%) in the placebo group (RR, 0.91 [0.63 to 1.32]; P = .63). CONCLUSIONS AND RELEVANCE: Among patients undergoing cardiac surgery, high-dose perioperative atorvastatin treatment compared with placebo did not reduce the risk of AKI overall, among patients naive to treatment with statins, or in patients already taking a statin. These results do not support the initiation of statin therapy to prevent AKI following cardiac surgery. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00791648.
Subject(s)
Acute Kidney Injury/prevention & control , Atorvastatin/administration & dosage , Cardiac Surgical Procedures/adverse effects , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Acute Kidney Injury/blood , Acute Kidney Injury/etiology , Aged , Aged, 80 and over , Aspartate Aminotransferases/blood , Atorvastatin/adverse effects , Creatinine/blood , Double-Blind Method , Drug Administration Schedule , Female , Glomerular Filtration Rate , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Male , Medication Adherence/statistics & numerical data , Middle Aged , Postoperative Complications , Renal Insufficiency, Chronic/complicationsABSTRACT
OBJECTIVE: We hypothesized that increased postgraduate surgical experience correlates with improved operative efficiency and long-term survival in standard cardiac surgery procedures. METHODS: Utilizing a prospectively collected retrospective database, we identified patients who underwent isolated coronary artery bypass grafting (CABG) (n = 3726), aortic valve replacement (AVR) (n = 1626), mitral valve repair (n = 731), mitral valve replacement (MVR) (n = 324), and MVR + AVR (n = 184) from January 2002 through June 2012. After adjusting for patient risk and surgeon variability, we evaluated the influence of surgeon experience on cardiopulmonary bypass and crossclamp times, and long-term survival. RESULTS: Mean surgeon experience after fellowship graduation was 16.0 ± 11.7 years (range, 1.0-35.2 years). After adjusting for patient risk and surgeon-level fixed effects, learning curve analyses demonstrated improvements in cardiopulmonary bypass and crossclamp times with increased surgeon experience. There was marginal improvement in the predictability (R(2) value) of cardiopulmonary bypass and crossclamp time for CABG with the addition of surgeon experience; however, all other procedures had marked increases in the R(2) following addition of surgeon experience. Cox proportional hazard models revealed that increased surgeon experience was associated with improved long-term survival in AVR (hazard ratio [HR], 0.85; P < .0001), mitral valve repair (HR, 0.73; P < .0001), and MVR + AVR (HR, 0.95; P = .006) but not in CABG (HR, 0.80; P = .15), and a trend toward significance in MVR (HR, 0.87; P = .09). CONCLUSIONS: In cardiac surgery, not including CABG, surgeon experience is an important determinant of operative efficiency and of long-term survival.
Subject(s)
Clinical Competence , Coronary Artery Bypass/education , Education, Medical, Graduate/methods , Heart Valve Prosthesis Implantation/education , Learning Curve , Aged , Aged, 80 and over , Cardiopulmonary Bypass/education , Coronary Artery Bypass/adverse effects , Coronary Artery Bypass/mortality , Databases, Factual , Efficiency , Female , Heart Valve Prosthesis Implantation/adverse effects , Heart Valve Prosthesis Implantation/mortality , Humans , Linear Models , Logistic Models , Male , Middle Aged , Multivariate Analysis , Proportional Hazards Models , Quality Indicators, Health Care , Retrospective Studies , Risk Factors , Time Factors , Treatment OutcomeABSTRACT
Modern treatment of coronary artery disease (CAD) requires a patient-centered approach. With several technological advances, the options for treatment must be carefully weighed and novel approaches tested for safety and efficacy. In this chapter, we outline some of the new approaches available to cardiac surgeons for the treatment of CAD, including off pump coronary artery bypass grafting, minimally invasive as well as hybrid and robotic coronary revascularization. We discuss current evidence and controversies, and highlight the future directions and challenges in the field of surgical coronary revascularization.
Subject(s)
Coronary Artery Bypass/methods , Coronary Artery Disease/therapy , Percutaneous Coronary Intervention/methods , Robotic Surgical Procedures/methods , Combined Modality Therapy , Coronary Artery Bypass/adverse effects , Coronary Artery Disease/diagnosis , Coronary Artery Disease/surgery , Humans , Patient Selection , Percutaneous Coronary Intervention/adverse effects , Risk Assessment , Risk Factors , Robotic Surgical Procedures/adverse effects , Treatment OutcomeABSTRACT
BACKGROUND: Pulmonary embolectomy is often indicated for central pulmonary embolism (PE) with hemodynamic instability, but remains controversial for hemodynamically stable patients with signs of right ventricular dysfunction. Because thrombolytic therapy is often contraindicated postoperatively, we reviewed risk factors and outcomes of pulmonary embolectomy for stable and unstable central PE, particularly in the early postoperative period. METHODS: Between October 1999 and September 2013, 115 patients underwent pulmonary embolectomy for central, hemodynamically unstable PE (49 of 115, 43%) or hemodynamically stable PE (56 of 115, 49%). Ten operations for alternate indications (right atrial mass, endocarditis) were excluded for comparison analysis, leaving 105 patients. RESULTS: Mean age was 59 ± 13 years; 46 of 105 patients (44%) had recent surgery (within 5 weeks): orthopedic (12 of 46, 25%), neurosurgery (11 of 46, 24%), or general surgery (10 of 46, 22%). Preoperative demographics did not differ between groups, except for the frequency of cardiopulmonary resuscitation among unstable patients (11 of 49, 22%) versus stable patients (0 of 56, 0%; p < 0.001). Operative mortality for the combined groups was 6.6% (7 of 105): unstable 10.2% (5 of 49) versus stable 3.6% (2 of 56; p = 0.247). Of 11 patients requiring preoperative cardiopulmonary resuscitation, 4 died. Six-month, 1-year, and 3-year survival rates were, respectively, 75%, 68.4%, and 65.8% for unstable PE, and 92.6%, 86.7%, and 80.4% for stable PE (p = 0.018). CONCLUSIONS: This large series of pulmonary embolectomies demonstrates excellent early and late survival rates for patients with stable PE and unstable PE. These findings confirm pulmonary embolectomy as a beneficial therapeutic option for central PE, especially during the postoperative period when thrombolytic therapy is often contraindicated.
Subject(s)
Embolectomy , Pulmonary Embolism/surgery , Aged , Contraindications , Embolectomy/adverse effects , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Postoperative Complications/epidemiology , Pulmonary Embolism/diagnostic imaging , Pulmonary Embolism/drug therapy , Pulmonary Embolism/mortality , Pulmonary Embolism/physiopathology , Retrospective Studies , Risk Factors , Thrombolytic Therapy , Tomography, X-Ray Computed , Treatment OutcomeABSTRACT
OBJECTIVES: Aortic valve replacement (AVR) in patients with severely atherosclerotic aortas (porcelain aorta) presents a significant technical challenge. Two strategies are deep hypothermic circulatory arrest (DHCA) during conventional surgery and transcatheter aortic valve replacement (TAVR). The aim of this study was to examine the outcomes in patients who underwent DHCA for AVR with a porcelain aorta to identify whether older patients are more suitable for TAVR. METHODS: Between October 2004 and December 2012, 122 patients underwent AVR using DHCA for atherosclerotic aorta. Patients with concomitant valve surgery were excluded. Overall, 63.9% (78/122) were of age <80 (non-octogenarian group, NOG) and 36.1% (44/122) were >80 (octogenarian group, OG). Of the total cohort, 62.3% (76/122) had concomitant coronary artery bypass graft surgery. RESULTS: The mean age for the whole cohort was 75.7 ± 8.5 years; 70.2 ± 8.1 years for the NOG and 83.4 ± 2.6 years for the OG (P = 0.001). The OG had a higher rate of preoperative renal failure (20.5%, 9/44 vs 7.7%, 6/78, P = 0.048) and trends towards a greater history of cerebrovascular disease (9.1%, 4/44 vs 1.3%, 1/78, P = 0.056), but fewer reoperations (6.8%, 3/44 vs 19.2%, 15/78, P = 0.069). Cardiopulmonary bypass time, aortic cross-clamp time and circulatory arrest time were similar between the two groups. Postoperative complication rates were similar except for permanent stroke (OG 18.2%, 8/44 vs NOG 6.4%, 5/78, P = 0.065). The overall operative mortality rate was 8.2% (10/122); however, the OG had significantly higher operative mortality compared with the NOG (15.9%, 7/44 vs 3.8%, 3/78, P = 0.035). One- and 5-year survival rates were 88.9 and 79.3% for the NOG versus 75.0 and 65.9% for the OG (P = 0.027), respectively. CONCLUSIONS: Postoperative neurological events and operative mortality were, respectively, 3- and 4-fold higher in octogenarians undergoing AVR using DHCA. Such patients may represent suitable candidates for TAVR if favourable outcomes are demonstrated in patients with atherosclerotic aortas. Surgical AVR remains the standard treatment option with excellent outcomes for patients <80 years old with unclampable aortas.
Subject(s)
Aortic Diseases/complications , Atherosclerosis/complications , Circulatory Arrest, Deep Hypothermia Induced/adverse effects , Heart Valve Diseases/surgery , Heart Valve Prosthesis Implantation/adverse effects , Vascular Calcification/complications , Age Factors , Aged , Aged, 80 and over , Aortic Diseases/diagnosis , Aortic Diseases/mortality , Atherosclerosis/diagnosis , Atherosclerosis/mortality , Boston , Circulatory Arrest, Deep Hypothermia Induced/mortality , Female , Heart Valve Diseases/complications , Heart Valve Diseases/diagnosis , Heart Valve Diseases/mortality , Heart Valve Prosthesis Implantation/mortality , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Postoperative Complications/mortality , Retrospective Studies , Risk Factors , Severity of Illness Index , Time Factors , Treatment Outcome , Vascular Calcification/diagnosis , Vascular Calcification/mortalityABSTRACT
BACKGROUND: Increasing evidence indicates that proteotoxicity plays a pathophysiologic role in experimental and human cardiomyopathy. In organ-specific amyloidoses, soluble protein oligomers are the primary cytotoxic species in the process of protein aggregation. While isolated atrial amyloidosis can develop with aging, the presence of preamyloid oligomers (PAOs) in atrial tissue has not been previously investigated. METHODS AND RESULTS: Atrial samples were collected during elective cardiac surgery in patients without a history of atrial arrhythmias, congestive heart failure, cardiomyopathy, or amyloidosis. Immunohistochemistry was performed for PAOs using a conformation-specific antibody, as well as for candidate proteins identified previously in isolated atrial amyloidosis. Using a myocardium-specific marker, the fraction of myocardium colocalizing with PAOs (PAO burden) was quantified (green/red ratio). Atrial samples were obtained from 92 patients, with a mean age of 61.7±13.8 years. Most patients (62%) were male, 23% had diabetes, 72% had hypertension, and 42% had coronary artery disease. A majority (n=62) underwent aortic valve replacement, with fewer undergoing coronary artery bypass grafting (n=34) or mitral valve replacement/repair (n=24). Immunostaining detected intracellular PAOs in a majority of atrial samples, with a heterogeneous distribution throughout the myocardium. Mean green/red ratio value for the samples was 0.11±0.1 (range 0.03 to 0.77), with a value ≥0.05 in 74 patients. Atrial natriuretic peptide colocalized with PAOs in myocardium, whereas transthyretin was located in the interstitium. Adjusting for multiple covariates, PAO burden was independently associated with the presence of hypertension. CONCLUSION: PAOs are frequently detected in human atrium, where their presence is associated with clinical hypertension.
Subject(s)
Amyloid beta-Protein Precursor/analysis , Atrial Function , Heart Atria/chemistry , Hypertension/metabolism , Aged , Atrial Natriuretic Factor/analysis , Female , Fibrosis , Heart Atria/pathology , Heart Atria/physiopathology , Humans , Hypertension/pathology , Hypertension/physiopathology , Immunohistochemistry , Male , Middle Aged , Prealbumin/analysis , Protein Aggregates , Randomized Controlled Trials as TopicABSTRACT
Modern treatment of cardiovascular disease requires a patient-centered approach. With several technological advances, the options for treatment must be carefully weighed and novel approaches tested for safety and efficacy. In this article, we outline some of the new approaches available to cardiothoracic surgeons for the treatment of cardiovascular diseases, including off-pump coronary artery bypass grafting, transcatheter valve replacement, and hybrid and robotic technology. We discuss current evidence and controversies and highlight the challenges that we face in training surgeons in an environment of ever-evolving surgical techniques.
Subject(s)
Cardiovascular Diseases/surgery , Thoracic Surgical Procedures/trends , Coronary Artery Bypass, Off-Pump/methods , Coronary Artery Bypass, Off-Pump/trends , Education, Medical, Graduate/methods , Heart Valve Prosthesis Implantation/methods , Heart Valve Prosthesis Implantation/trends , Humans , Robotic Surgical Procedures/methods , Robotic Surgical Procedures/trends , Thoracic Surgical Procedures/education , Thoracic Surgical Procedures/methodsSubject(s)
American Heart Association , Angina, Stable/diagnosis , Angina, Stable/therapy , Cardiology/standards , Myocardial Ischemia/diagnosis , Myocardial Ischemia/therapy , Cardiac Catheterization/standards , Coronary Angiography/standards , Humans , Percutaneous Coronary Intervention/standards , United StatesABSTRACT
Valve endocarditis is associated with high morbidity and mortality and requires a thorough evaluation including early surgical consultation to identify patients who may benefit from surgery. We review 5 recent articles that highlight the current debates related to best treatment strategies for valve endocarditis. Recent publications have focused on neurologic risk assessment, timing of surgery, and prognostic factors associated with native and prosthetic valve endocarditis. The initial patient assessment and management is best performed by a multidisciplinary team. Future investigations should focus on identifying surgical candidates early and the outcomes affected by replacement valve choice in both native and prosthetic valve endocarditis.
Subject(s)
Aortic Valve , Disease Management , Echocardiography/methods , Embolism/prevention & control , Endocarditis, Bacterial/surgery , Endocarditis/mortality , Endocarditis/surgery , Endocarditis/therapy , Heart Valve Diseases/therapy , Heart Valve Prosthesis/microbiology , Practice Guidelines as Topic , Prosthesis-Related Infections/surgery , Staphylococcal Infections/therapy , Tricuspid Valve/surgery , Female , Humans , MaleABSTRACT
Abnormalities in atrial myocardium increase the likelihood of arrhythmias, including atrial fibrillation (AF). The deposition of misfolded protein, or amyloidosis, plays an important role in the pathophysiology of many diseases, including human cardiomyopathies. We have shown that genes implicated in amyloidosis are activated in a cellular model of AF, with the development of preamyloid oligomers (PAOs). PAOs are intermediates in the formation of amyloid fibrils, and they are now recognized to be the cytotoxic species during amyloidosis. To investigate the presence of PAOs in human atrium, we developed a microscopic imaging-based protocol to enable robust and reproducible quantitative analysis of PAO burden in atrial samples harvested at the time of elective cardiac surgery. Using PAO- and myocardial-specific antibodies, we found that PAO distribution was typically heterogeneous within a myocardial sample. Rigorous imaging and analysis protocols were developed to quantify the relative area of myocardium containing PAOs, termed the Green/Red ratio (G/R), for a given sample. Using these methods, reproducible G/R values were obtained when different sections of a sample were independently processed, imaged, and analyzed by different investigators. This robust technique will enable studies to investigate the role of this novel structural abnormality in the pathophysiology of and arrhythmia generation in human atrial tissue.