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Biomedical subjects

Patrick M McCarthy

Publications and source records attributed to Patrick M McCarthy.

At least 19 recordsLinked to original sources

Reduction of surgical mortality and morbidity in diabetic patients undergoing cardiac surgery with a combined intravenous and subcutaneous insulin glucose management strategy.

OBJECTIVE: To determine if glucose management in postcardiothoracic surgery patients with a combined intravenous (IV) and subcutaneous (SC) insulin regimen reduces mortality and morbidity in patients with diabetes and stress-induced hyperglycemia. RESEARCH DESIGN AND METHODS: Retrospective review of 614 consecutive patients who underwent cardiothoracic (CT) surgery in 2005 was performed to evaluate the incidence and treatment of postoperative hyperglycemia and operative morbidity and mortality. Hyperglycemic patients (glucose >6.05 mmol/l) were treated with IV insulin in the intensive care unit (ICU) followed by SC insulin (outside ICU). Subgroup analysis was performed on 159 coronary artery bypass grafting (CABG)-only patients. RESULTS: Among all CT surgeries, patients with a preoperative diagnosis of diabetes had higher rates of postoperative mortality (7.3 vs. 3.3%; P = 0.03) and pulmonary complications (19.5 vs. 11.6%; P = 0.02) but had similar rates of infections and cardiac, renal, and neurological complications on univariate analysis. However, on multivariate analysis, a preoperative diagnosis of diabetes was not a significant factor in postoperative mortality or pulmonary complications. In CABG-only patients, no significant differences were seen in outcomes between diabetic and nondiabetic patients. Independent of diabetic status, glucose > or =11 mmol/l on ICU admission was predictive of higher rates of mortality and renal, pulmonary, and cardiac postoperative complications. CONCLUSIONS: A combination of IV insulin (in the ICU) and SC insulin (outside the ICU), a less costly and less nursing-intensive therapy than 3 days of IV insulin postoperatively, results in a reduction of the increased surgical morbidity and mortality in diabetic patients after CT surgery.

Aged↗

Monocyte chemotactic protein-3 is a myocardial mesenchymal stem cell homing factor.

MSCs have received attention for their therapeutic potential in a number of disease states, including bone formation, diabetes, stem cell engraftment after marrow transplantation, graft-versus-host disease, and heart failure. Despite this diverse interest, the molecular signals regulating MSC trafficking to sites of injury are unclear. MSCs are known to transiently home to the freshly infarcted myocardium. To identify MSC homing factors, we determined chemokine expression pattern as a function of time after myocardial infarction (MI). We merged these profiles with chemokine receptors expressed on MSCs but not cardiac fibroblasts, which do not home after MI. This analysis identified monocyte chemotactic protein-3 (MCP-3) as a potential MSC homing factor. Overexpression of MCP-3 1 month after MI restored MSC homing to the heart. After serial infusions of MSCs, cardiac function improved in MCP-3-expressing hearts (88.7%, p < .001) but not in control hearts (8.6%, p = .47). MSC engraftment was not associated with differentiation into cardiac myocytes. Rather, MSC engraftment appeared to result in recruitment of myofibroblasts and remodeling of the collagen matrix. These data indicate that MCP-3 is an MSC homing factor; local overexpression of MCP-3 recruits MSCs to sites of injured tissue and improves cardiac remodeling independent of cardiac myocyte regeneration.

Animals↗

The impact of left ventricular reconstruction on survival in patients with ischemic cardiomyopathy.

OBJECTIVE: Left ventricular reconstruction (LVR) is performed to improve the morphologic structure and function of the heart in patients with heart failure. This procedure has been performed at the Cleveland Clinic Foundation since 1997. We assessed mortality, functional status, and predictors of outcome in these patients. METHODS: Data were extracted from multiple prospectively acquired datasets on demographic, clinical, and operative details of 220 consecutive patients who underwent LVR between July 1997 and July 2003, where the indication for surgery was heart failure (of whom 66% had New York Heart Association (NYHA) functional class III or IV symptoms). Mortality, functional status, and postoperative complications were ascertained by reference to the clinical record, social security death index, and by phone contact. Mean preoperative left ventricular ejection fraction (LVEF) was 21.5+/-7.3% and mean left ventricular end-diastolic diameter was 6.4+/-1.0 cm. The mean age was 61.4+/-9.0 years and 80% were male. The majority (86%) of patients underwent concomitant coronary artery bypass grafting and 49% underwent mitral valve surgery. RESULTS: Thirty-day mortality was 1% and survival at 1, 3, and 5 years was 92%, 90%, and 80%, respectively. Of the survivors for whom data on NYHA functional class were available, 85% were in NYHA functional class I or II. Mortality was predicted by reduced preoperative ejection fraction <20% (unadjusted hazard ratio 1.53, p = 0.02), body mass index < or = 24 kg/m2 (unadjusted hazard ratio 1.69, p = 0.01), QRS duration > or = 130 ms (unadjusted hazard ratio 1.66, p = 0.01) and the requirement for renal replacement therapy postoperatively (unadjusted hazard ratio 3.85, p < 0.01). Mean LVEF improved to 24.7+/-8.86% (p < 0.01) and left ventricular volumes were also significantly reduced. CONCLUSIONS: In selected patients with heart failure, LVR, in conjunction with revascularization and valve surgery, is associated with excellent survival, improved symptoms, and improved LVEF and left ventricular dimensions.

Aged↗

Determinants of recurrent or residual functional tricuspid regurgitation after tricuspid annuloplasty.

BACKGROUND: The durability of tricuspid valve (TV) repair by annuloplasty is limited. Identification of mechanisms of recurrent or residual tricuspid regurgitation (TR) after annuloplasty is necessary to improve results of TV repair. The purpose of this study was to investigate echocardiographic determinants of mid-term outcome after TV annuloplasty. METHODS AND RESULTS: This study consisted of 39 patients with functional TR who had echocardiography preoperatively, early postoperatively (5+/-2 days), and >1 year (20+/-6 months) after TV annuloplasty. Detailed echocardiographic measurements were performed, including TR severity, TV annular dimension, TV leaflet displacement, left ventricular (LV) function, and right ventricular (RV) function and pressures. Preoperative leaflet tethering height and area predicted early and mid-term outcome of annuloplasty. Early postoperative LV ejection fraction and TR severity influenced degree of TR >1 year after surgery. In addition, increased RV pressure was related to worse TR during late follow-up. CONCLUSIONS: Although TV tethering is an important determinant of recurrent or residual TR, LV and RV function and pressures impact repair durability. These factors identify patients at risk for repair failure; such individuals require development of additional surgical strategies to improve results of tricuspid valve repair and close surveillance after surgery.

Aged↗

Mitral valve repair with Carpentier-McCarthy-Adams IMR ETlogix annuloplasty ring for ischemic mitral regurgitation: early echocardiographic results from a multi-center study.

BACKGROUND: Ischemic mitral regurgitation (IMR) is associated with asymmetric changes in annular and ventricular geometry. Surgical repair with standard symmetric annuloplasty rings results in a high incidence of residual or recurrent mitral regurgitation (MR). The Carpentier-McCarthy-Adams (CMA) IMR ETlogix annuloplasty ring is the first remodeling ring specifically designed to treat asymmetric leaflet tethering and annular dilatation. We used quantitative 2-dimensional echo to examine early results of mitral valve (MV) repair with the CMA IMR ETlogix annuloplasty ring in patients with IMR. METHODS AND RESULTS: Fifty-nine patients (aged 68+/-12 years) with grade > or = 2+ IMR (graded on a scale of 0 to 4+) underwent MV repair with the CMA IMR ETlogix annuloplasty ring. We assessed the mitral annular diameter (MAD), tethering area (TA), and tenting height (TH) of the MV in 4-chamber, 2-chamber, and long axis views at mid-systole before and 3 to 10 days after surgery. After surgery, 57 of 59 (97%) patients had grade 0 or 1+ MR, whereas 2 patients had 2+ MR. MV repair with the CMA IMR ETlogix ring significantly reduced MAD, TA, and TH (P<0.001, for all 3 echo views), particularly in the long axis and 4-chamber views. CONCLUSIONS: Surgical repair of IMR with the novel asymmetric CMA IMR ETlogix annuloplasty ring provided excellent early results with effective reduction of MR, MAD, and leaflet tethering. This novel etiology-specific strategy may result in improved outcomes in IMR patients.

Aged↗

Echocardiographic predictors of successful versus unsuccessful mitral valve repair in ischemic mitral regurgitation.

Mitral valve (MV) annuloplasty is the standard surgical technique for the management of ischemic mitral regurgitation (MR). However, < or = 1/3 of patients develop recurrent MR after annuloplasty. Therefore, we sought to identify the preoperative echocardiographic parameters that predict annuloplasty failure in patients with ischemic MR. Intraoperative transesophageal echocardiograms from 365 patients who underwent MV repair for ischemic MR were reviewed. Of the 365 patients, 297 (81%) had satisfactory outcomes with < 2+ MR, and 68 (19%) had recurrent MR (> or = 2+) during a mean follow-up of 269 days. The mitral annular parameters, including mitral annular diameter, tethering height, and tethering area of the mitral leaflets, were determined in 3 different echocardiographic views. On multiple logistic stepwise regression analysis, a higher mitral annular diameter, higher tethering area, and higher MR severity were identified as independent predictors for failure of MV repair (p < 0.0001). In conclusion, these results demonstrated that preoperative echocardiographic findings can be used to identify patients with ischemic MR at increased risk of repair failure. These echocardiographic measurements should be used to guide the cardiologist and cardiac surgeon in the choice of MV repair versus replacement in patients with ischemic MR.

Adult↗

Human degenerative valve disease is associated with up-regulation of low-density lipoprotein receptor-related protein 5 receptor-mediated bone formation.

OBJECTIVES: The goal of this research was to define the cellular mechanisms involved in myxomatous mitral valve disease and calcific aortic valve disease and to redefine the term degenerative valve disease in terms of an active cellular biology. BACKGROUND: "Degenerative" valvular heart disease is the primary cause of regurgitant and stenotic valvular lesion in the U.S. However, the signaling pathways are not known. We hypothesize that valve degeneration occurs due to an osteoblastic differentiation process mediated by the low-density lipoprotein receptor-related protein 5 (Lrp5) signaling pathway to cause valve thickening. METHODS: We examined human diseased valves: myxomatous mitral valves (n = 23), calcified tricuspid aortic valves (n = 27), calcified bicuspid aortic valves (n = 23), and control tissue from mitral and aortic valves (n = 40). The valves were examined by reverse transcriptase-polymerase chain reaction, Western blot, and immunohistochemistry for signaling markers important in osteoblast differentiation: Sox9 and Cbfa1 (transcription factors for osteoblast differentiation); Lrp5 and Wnt3 (osteoblast differentiation signaling marker), osteopontin and osteocalcin (osteoblast endochrondral bone matrix proteins), and proliferating cell nuclear antigen (a marker of cell proliferation). Cartilage development and bone formation was measured by Alcian blue stain and Alizarin red stain. Computed Scano MicroCT-40 (Bassersdorf, Switzerland) analysis measured calcium burden. RESULTS: Low-density lipoprotein receptor-related protein 5, osteocalcin, and other osteochrondrogenic differentiation markers were increased in the calcified aortic valves by protein and gene expression (p > 0.001). Sox9, Lrp5 receptor, and osteocalcin were increased in myxomatous mitral valves by protein and gene expression (p > 0.001). MicroCT was positive in the calcified aortic valves and negative in the myxomatous mitral valves. CONCLUSIONS: The mechanism of valvular heart disease involves an endochondral bone process that is expressed as cartilage in the mitral valves and bone in the aortic valves. Up-regulation of the Lrp5 pathway may play a role in the mechanism for valvular heart disease.

Aged↗

Altered expression of disintegrin metalloproteinases and their inhibitor in human dilated cardiomyopathy.

BACKGROUND: Disintegrin metalloproteinases (ADAMs) may contribute to structural cardiac remodeling by altering cell-surface matrix receptors (integrins) and activating potent biomolecules. We compared expression of ADAMs, their endogenous inhibitor tissue inhibitor of metalloproteinases (TIMP)-3, and integrins in human heart tissue with varied patterns of structural remodeling. METHODS AND RESULTS: Myocardium was obtained from patients with dilated cardiomyopathy (n=20), hypertrophic obstructive cardiomyopathy (n=5), and nonfailing donor hearts (n=7). Paired samples (n=10) were obtained before left ventricular assist device insertion and at transplantation. The expressions of ADAM10, ADAM12, ADAM15, and ADAM17, TIMP-3, and integrin receptors beta1D and beta3 were determined by quantitative immunoblotting. Integrin shedding was assessed by the ratio of integrin cleavage products to intact protein abundance. Confocal microscopy was performed. Dilated cardiomyopathy was characterized by increased ADAM10 and ADAM15 expression and reduced TIMP-3 expression. The integrin beta1D cleavage ratio was elevated, indicating receptor shedding. ADAM10 and ADAM15 expressions correlated with the cleavage ratio. ADAM10 colocalized with integrin beta1D by confocal microscopy. ADAM10 expression correlated with clinical indices of chamber dilatation and systolic dysfunction. Hemodynamic unloading reduced ADAM10 and ADAM12 expressions and increased integrin beta1D expression. ADAM12 and integrin beta1D expressions were increased in HOCM. ADAM17 was increased in both dilated cardiomyopathy and hypertrophic obstructive cardiomyopathy. CONCLUSIONS: Disintegrin metalloproteinases are differentially expressed in human myocardium, reflecting the underlying pattern of structural remodeling. ADAM10 and ADAM15 may contribute to cardiac dilatation by reducing cell-matrix interactions via integrin shedding. Targeting disintegrin metalloproteinases, perhaps by restoring deficient TIMP-3 levels with gene or cell-based therapies, may prevent progressive chamber dilatation in human dilated cardiomyopathy.

ADAM Proteins↗

Myocardial viability testing and the effect of early intervention in patients with advanced left ventricular systolic dysfunction.

BACKGROUND: The clinical value of revascularization and other procedures in patients with severe systolic heart failure is unclear. It has been suggested that assessing ischemia and viability by positron emission tomography (PET) with fluorodeoxyglucose (FDG) imaging may identify patients for whom revascularization may lead to improved survival. We performed a propensity analysis to determine whether there might be a survival advantage from revascularization. METHODS AND RESULTS: We analyzed the survival of 765 consecutive patients (age 64+/-11 years, 80% men) with advanced left ventricular systolic dysfunction (ejection fraction < or =35%) and without significant valvular heart disease who underwent PET/FDG study at the Cleveland Clinic between 1997 and 2002. Early intervention was defined as any cardiac intervention (surgical or percutaneous) within the first 6 months of the PET/FDG study. In the entire cohort, 230 patients (30%) underwent early intervention (188 [25%] had open heart surgery, most commonly coronary artery bypass grafting, and 42 [5%] had percutaneous revascularization); 535 (70%) were treated medically. Using 39 demographic, clinical and PET/FDG variables, we were able to propensity-match 153 of the 230 patients with 153 patients who did not undergo early intervention. Among the propensity-matched group, there were 84 deaths during a median of 3 years follow-up. Early intervention was associated with a markedly lower risk of death (3-year mortality rate of 15% versus 35%, propensity adjusted hazard ratio 0.52, 95% CI 0.33 to 0.81, P=0.0004). CONCLUSIONS: Among systolic heart failure patients referred for PET/FDG, early intervention may be associated with improved survival irrespective of the degree of viability.

Aged↗

Surgery for paroxysmal atrial fibrillation in the setting of mitral valve disease: a role for pulmonary vein isolation?

BACKGROUND: It is unknown whether pulmonary vein isolation or a complete Cox-Maze procedure is needed to ablate paroxysmal atrial fibrillation in patients with mitral valve disease. Our objective was to assess the impact of different surgical treatments for this arrhythmia in patients undergoing mitral valve surgery. METHODS: From July 1993 to January 2004, 152 patients underwent combined surgical treatment of paroxysmal atrial fibrillation and mitral valve disease. Ablation procedures included pulmonary vein isolation alone (n = 31, 20%), pulmonary vein isolation with left atrial connecting lesions (n = 80, 53%), and Cox-Maze (n = 41, 27%). The latter had longer durations of atrial fibrillation than the former (p < 0.0001). Rhythm documented on 1,225 postoperative electrocardiograms was used to estimate prevalence of, and risk factors for, atrial fibrillation across time. Ablation failure was defined as occurrence of atrial fibrillation any time beyond 6 months after operation. RESULTS: Prevalence of postoperative atrial fibrillation peaked at 22% at 2 weeks and declined to 9% at 1 year. Risk factors included older age (p = 0.09), larger left atrium (p = 0.05), and rheumatic (p = 0.003) and degenerative etiologies (p = 0.03). Freedom from ablation failure was 84% at one year. Ablation procedure did not affect prevalence of atrial fibrillation or incidence of ablation failure. CONCLUSIONS: Pulmonary vein isolation alone may be adequate treatment for patients with paroxysmal atrial fibrillation undergoing mitral valve surgery, particularly when it is of short duration. A randomized trial is necessary to examine this strategy, especially in patients with longer duration of paroxysmal atrial fibrillation.

Aged↗

Surgery for permanent atrial fibrillation: impact of patient factors and lesion set.

BACKGROUND: Whether a complete Cox-maze procedure is needed to ablate permanent atrial fibrillation in patients undergoing concomitant cardiac surgery is unknown. Our objective was to assess the effectiveness of different lesion sets in such patients. METHODS: From November 1991 to January 2004, 575 patients underwent surgical treatment of permanent atrial fibrillation (duration > 6 months); mitral valve disease was the primary indication for surgery in 74%. Procedures included pulmonary vein isolation alone (n = 68, 12%), pulmonary vein isolation with left atrial connecting lesions (n = 265, 46%), and Cox-maze (n = 242, 42%). Rhythm documented on 5,120 postoperative electrocardiograms was used to estimate time-related prevalence of, and risk factors for, atrial fibrillation. RESULTS: Prevalence of postoperative atrial fibrillation peaked at 46% two weeks after operation, declining to 24% at one year. Patient-related risk factors for increased prevalence included older age (p < 0.0001), larger left atrium (p < 0.0001), and longer duration of preoperative atrial fibrillation (p = 0.0008). The Cox-maze procedure and lesion sets resembling it created with alternative energy sources had a similarly low prevalence of late postoperative atrial fibrillation; in contrast, pulmonary vein isolation and lesion sets that did not include a lesion to the mitral anulus were less effective. CONCLUSIONS: This study suggests that in cardiac surgical patients with permanent atrial fibrillation the left atrial lesion set should include wide pulmonary vein isolation, at least one connection between right and left pulmonary veins, and a connection to the mitral anulus. Availability of alternative energy sources to create lesions sets has virtually eliminated the need for the cut-and-sew Cox-maze procedure.

Adult↗

Duration of inotropic support after left ventricular assist device implantation: risk factors and impact on outcome.

OBJECTIVES: Because duration of inotropic support after left ventricular assist device implantation has been recognized as a surrogate for right ventricular dysfunction, we sought to (1) identify its preimplantation risk factors, particularly its association with preimplantation right ventricular dysfunction, and (2) assess its impact on clinical outcomes. METHODS: Between 1991 and 2002, left ventricular assist devices were implanted in 207 patients, exclusive of those receiving preoperative mechanical circulatory support, which precluded measuring right ventricular stroke work. Duration of inotropic support was analyzed as a continuous variable, truncated by death or transplantation, and in turn as a risk factor for these 2 events. RESULTS: Inotropic support decreased from 100% on the day of implantation to 57%, 33%, and 22% by days 7, 14, and 21. Its duration was strongly associated with lower preimplantation right ventricular stroke work index, older age, and nonischemic cardiomyopathy and was associated (P < .04) with higher mortality before transplantation but not with transition to transplantation. We identified no preimplantation risk factors for right ventricular assist device use because of its relatively infrequent use in this population (18 patients, only 4 of whom survived to transplantation). CONCLUSION: Duration of inotropic support after left ventricular assist device insertion is strongly correlated with low preimplantation right ventricular stroke work index. In turn, it was associated with reduced survival to transplantation. Thus, right ventricular stroke work measured before implantation might be useful in decision making for biventricular support, destination therapy, or total artificial heart.

Cardiomyopathies↗

Reverse ventricular remodeling: mechanical options.

PURPOSE OF REVIEW: The aim of this review is to update the cardiovascular clinician on the current status of surgical therapies aimed at achieving reverse ventricular remodeling. RECENT FINDINGS: Relevant research focusing on mechanical options for reverse ventricular remodeling will be referenced and summarized. SUMMARY: Heart failure is a tremendous burden on society in terms of both lives lost and healthcare costs. Knowledge of both medical and surgical therapies aimed at improving ventricular efficiency and reversing ventricular remodeling should be in the armamentarium of clinicians treating heart failure patients.

Heart Failure↗

Determinants of ischemic mitral regurgitation in patients with chronic anterior wall myocardial infarction: a real time three-dimensional echocardiography study.

OBJECTIVE: We sought to elucidate the geometric determinants of ischemic mitral regurgitation (IMR) in patients with chronic anterior myocardial infarction (MI). MATERIALS AND METHODS: In 16 patients with anterior MI only (Group A) and 18 patients with both anterior and inferoposterior MI (Group B), three parallel equidistant anteroposterior (AP) planes (medial, central, lateral) perpendicular to the mitral valvular commissure-commissure plane were generated. The systolic tenting area of the mitral valve (MVTa) and the angles between the annular plane and leaflets (anterior, Aalpha; posterior, Palpha) on the AP planes were measured. The left ventricular end-systolic and end-diastolic volumes, and end-diastolic and end-systolic mitral annular area (MAAs) were obtained. RESULT: The regurgitant orifice area (ROA) was significantly smaller in Group A than Group B (0.08 +/- 0.09 vs 0.20 +/- 0.18 cm(2), P < 0.05). In the total of 34 patients, the medial MVTa (P < 0.001), MAAs (P < 0.05) and the spherical index (P < 0.05) were three independent determinants of ROA while the left ventricular volumes were not. MAAs was the only independent determinant of ROA in Group A, while the medial MVTa was in Group B. Palpha (P < 0.05) and MVTa (P = 0.06) tended to be larger in the medial than the lateral side in Group B, while no differences were found in Group A. CONCLUSION: The geometry of the mitral valve apparatus was more important than the left ventricular volumes in determining the severity of IMR in patients with anterior MI. The posteromedial side tenting could play a critical role in causing significant IMR when the inferoposterior MI coexists with anterior MI.

Aged↗

Effects of surgical ventricular restoration on left ventricular function: dynamic MR imaging.

PURPOSE: To retrospectively evaluate with dynamic magnetic resonance (MR) imaging the changes in global and regional left ventricular (LV) function after surgical ventricular restoration (SVR) performed in chronic ischemic heart disease patients with large nonaneurysmal or aneurysmal postmyocardial infarction zones. MATERIALS AND METHODS: The study was performed with institutional review board approval, and a waiver of individual informed consent was obtained. The study was HIPAA compliant. Patients (83 men, 22 women; mean age, 61 years +/- 9 [standard deviation]) were evaluated with MR imaging before and after SVR as follows: pre-SVR examination (n = 105; 25 days +/- 39 before SVR; median, 7 days; range, 1-189 days), early post-SVR examination (n = 95, 7 days +/- 3 after SVR), and late post-SVR (n = 35, 313 days +/- 158 after SVR). Cine MR imaging allowed calculation of ejection fraction and rate-corrected velocity of circumferential fiber shortening (Vcf(C)) for global LV functional evaluation, whereas tagged MR imaging (spatial modulation of magnetization with harmonic phase analysis) permitted assessment of regional circumferential strain (E(C)) with coronary distribution. Vcf(C) and E(C) were computed at both LV base- and mid-LV short-axis levels remote from the site of anteroapical SVR. RESULTS: Prior to SVR, LV dilatation and diminished global and regional LV function were observed. At early post-SVR examination, Vcf(C) had improved significantly but E(C) showed a worsening trend overall, although only E(C )of the right coronary artery at the mid-LV level worsened significantly. At late post-SVR examination, Vcf(C) values were improved when compared with pre-SVR values, although E(C) showed no statistically significant improvement. When compared with that at early post-SVR examination, however, E(C) showed significant improvement in two segments: left anterior descending artery and right coronary artery at mid-LV level. CONCLUSION: Although volume-based indexes of global LV function improve significantly after SVR, regional LV function did not improve significantly; there was evidence of continued LV remodeling after SVR.

Cardiac Surgical Procedures↗

The Cox maze procedure in mitral valve disease: predictors of recurrent atrial fibrillation.

OBJECTIVES: The Cox maze procedure is the gold standard for ablation of atrial fibrillation in patients undergoing mitral valve surgery, and new approaches to atrial fibrillation ablation must be compared with it. Therefore, we sought to determine the time-related prevalence of atrial fibrillation and its risk factors after combined Cox maze and mitral valve surgery. METHODS: From November 1991 through January 2004, 263 patients (mean left atrial diameter, 5.8 +/- 1.2 cm) underwent combined mitral valve surgery (repair in 71%) and a cut-and-sew Cox maze procedure for atrial fibrillation (permanent, 74%; persistent, 7%; paroxysmal, 16%). Rhythm documented on 2367 postoperative electrocardiograms was used to estimate the prevalence of atrial fibrillation across time. RESULTS: Hospital mortality was 1.9%. Postoperative atrial fibrillation prevalence peaked at 36% at 2 weeks, decreasing to 21% at 5 years. Risk factors for higher postoperative atrial fibrillation prevalence varied with time and included longer duration of preoperative atrial fibrillation (P = .003), larger left atrial diameter (P = .01), older age (P = .0002), and higher left ventricular mass index (P = .02). CONCLUSIONS: In some patients undergoing mitral valve surgery and a Cox maze procedure, atrial fibrillation recurs over time, mandating close, long-term follow-up of heart rhythm. Earlier operation and left atrial size reduction should be considered to improve results in selected patients.

Atrial Fibrillation↗

Calcified rheumatic valve neoangiogenesis is associated with vascular endothelial growth factor expression and osteoblast-like bone formation.

BACKGROUND: Rheumatic heart disease is the most common cause of valvular disease in developing countries. Despite the high prevalence of this disease, the cellular mechanisms are not well known. We hypothesized that rheumatic valve calcification is associated with an osteoblast bone formation and neoangiogenesis. METHODS AND RESULTS: To test this hypothesis, we examined human rheumatic valves replaced at surgery (n=23), normal human valves (n=20) removed at cardiac transplantation, and degenerative mitral valve leaflets removed during surgical valve repair (n=15). Microcomputed tomography was used to assess mineralization fronts to reconstruct the extents of mineralization. Immunohistochemistry was used to localize osteopontin protein, alpha-actin, osteocalcin, vascular endothelial growth factor, von Willebrand factor, and CD68 (human macrophage). Microcomputed tomography demonstrated complex calcification developing within the heavily calcified rheumatic valves, not in the degenerative mitral valves and control valves. Immunohistochemistry localized osteopontin and osteocalcin to areas of smooth muscle cells within microvessels and proliferating myofibroblasts. Vascular endothelial growth factor was present in areas of inflammation and colocalized with the CD68 stain primarily in the calcified rheumatic valves. Alizarin red, osteopontin, and osteocalcin protein expression was upregulated in the calcified rheumatic valves and was present at low levels in the degenerative mitral valves. CONCLUSIONS: These findings support the concept that rheumatic valve calcification is not a random passive process but a regulated, inflammatory cellular process associated with the expression of osteoblast markers and neoangiogenesis.

Adult↗