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Biomedical subjects

Patrick M McCarthy

Publications and source records attributed to Patrick M McCarthy.

At least 91 records · Page 5Linked to original sources
PubMed2003

Mitral valve repair with aortic valve replacement is superior to double valve replacement.

OBJECTIVES: Double valve replacement has been advocated for patients with combined aortic and mitral valve disease. This study investigated the alternative that, when feasible, mitral valve repair with aortic valve replacement is superior. PATIENTS AND METHODS: From 1975 to 1998, 813 patients underwent aortic valve replacement with either mitral valve replacement (n = 518) or mitral valve repair (n = 295). Mitral valve disease was rheumatic in 71% and degenerative in 20%. Mitral valve replacement was more common in patients with severe mitral stenosis (P =.0009), atrial fibrillation (P =.0006), and in patients receiving a mechanical aortic prosthesis (P =.0002). These differences were used for propensity-matched multivariable comparisons. Follow-up extended reliably to 16 years, mean 6.9 +/- 5.9 years. RESULTS: Hospital mortality rate was 5.4% for mitral valve repair and 7.0% for replacement (P =.4). Survivals at 5, 10, and 15 years were 79%, 63%, and 46%, respectively, after mitral valve repair versus 72%, 52%, and 34%, respectively, after replacement (P =.01). Late survival was increased by mitral valve repair rather than replacement (P =.03) in all subsets of patients, including those with severe mitral valve stenosis. After repair of nonrheumatic mitral valves, 5-, 10-, and 15-year freedom from valve replacement was 91%, 88%, and 86%, respectively; in contrast, after repair of rheumatic valves, it was 97%, 89%, and 75% at these intervals. CONCLUSIONS: In patients with double valve disease, aortic valve replacement and mitral valve repair (1) are feasible in many, (2) improve late survival rates, and (3) are the preferred strategy when mitral valve repair is possible.

Adult↗
PubMed2003

Persistent abnormal left ventricular systolic torsion in dilated cardiomyopathy after partial left ventriculectomy.

OBJECTIVE: Rotation of the left ventricular apex relative to the base, or left ventricular torsion, is related to myocardial contractility and structure and is a sensitive indicator of cardiac dysfunction. We have quantified left ventricular systolic rotation and torsion in patients with dilated cardiomyopathy before and after partial left ventriculectomy in an attempt to characterize the effects of this surgical procedure on ventricular ejection mechanics. METHODS: Magnetic resonance imaging with tissue tagging was performed before partial left ventriculectomy in 24 patients, 9 of whom underwent repeat imaging 3 months after surgery. Left ventricular rotation was quantified in each patient at three short-axis levels: apex, midventricle, and base. Torsion was defined as the difference between basal and apical rotation at any time. Results were subdivided for regional analysis at each level and related to cardiac function (ejection fraction, cardiac index, and velocity of circumferential fiber shortening). RESULTS: Before surgery, left ventricular rotation was regionally heterogeneous and abnormal in magnitude and pattern, and increased end-systolic torsion was associated with better cardiac function. After surgery, clinical indices of cardiac function showed improvement; however, rotation magnitude was unchanged at the apex and reduced at the base and midventricle, particularly in the anterior wall and septum. CONCLUSIONS: The pattern and magnitude of ventricular rotation were impaired by dilated cardiomyopathy. Left ventricular rotation and torsion were further diminished after partial left ventriculectomy, indicating that improvement in clinical indices of cardiac function was not reflective of an improvement in this measure of myocardial mechanics.

Adolescent↗
PubMed2003

An evaluation of the use of new Doppler methods for detecting longitudinal function abnormalities in a pacing-induced heart failure model.

BACKGROUND: Doppler tissue echocardiography and color M-mode Doppler flow propagation velocity have proven useful in evaluating cross-sections of patients with left ventricular (LV) dysfunction, but experience with serial changes is limited. PURPOSE AND METHODS: We tested their use by evaluating the temporal changes of LV function in a pacing-induced congestive heart failure model. Rapid ventricular pacing was initiated and maintained in 20 dogs for 4 weeks. Echocardiography was performed at baseline and weekly during brief pacing cessation. RESULTS: With rapid pacing, LV volume significantly increased and ejection fraction (57%-28%), stroke volume (37-18 mL), and mitral annulus systolic velocity (16.1-6.6 cm/s) by Doppler tissue echocardiography significantly decreased, with ejection fraction and mitral annulus systolic velocity closely correlated (r = 0.706, P <.0001). In contrast to the mitral inflow velocities, mitral annulus early diastolic velocity decreased steadily (12.3-7.3 cm/s) resulting in a dramatic decrease in mitral annulus early/late (1.22-0.57) diastolic velocity with no tendency toward pseudonormalization. The color M-mode Doppler flow propagation velocity also showed significant steady decrease (57-24 cm/s) throughout the pacing period. Multiple regression analysis chose mitral annulus systolic velocity (r = 0.895, P <.0001) and propagation velocity (r = 0.782, P <.0001) for the most important factor predicting LV systolic and diastolic function, respectively. CONCLUSIONS: Doppler tissue echocardiography and color M-mode Doppler flow could evaluate the serial deterioration in LV dysfunction throughout the pacing period. These were more useful in quantifying progressive LV dysfunction than conventional ehocardiographic techniques, and were probably relatively independent of preload. These techniques could be suitable for longitudinal evaluation in addition to the cross-sectional study.

Animals↗
PubMed2003

Quilty lesions are associated with increased expression of vitronectin receptor (alphavbeta3) and subsequent development of coronary vasculopathy.

BACKGROUND: Quilty lesions are common after heart transplantation; however, their relationship to vasculopathy has not been described. We tested the hypothesis that Quilty lesions are associated with increased expression of vitronectin receptor (alphavbeta3) and the subsequent development of coronary vasculopathy. METHODS: A total of 140 heart transplant recipients underwent coronary intravascular ultrasound at baseline and at 1 year after transplantation, and we measured the change in coronary maximal intimal thickness. Endomyocardial biopsy specimens taken within 8 weeks after transplantation showed Quilty lesions in 54 of 140 (39%) patients (Quilty group). We compared these results with the remaining 86 of 140 patients (61%) who had no evidence of Quilty lesions during the same period (control group). We evaluated 10 endomyocardial biopsy specimens from each group for alphavbeta3, using immunohistochemistry staining and immunoblotting. RESULTS: Quilty lesions stained positive for alphavbeta3, and Western blot analysis showed a 1.3-fold (p = 0.004) increase in expression of alphavbeta3. Compared with control, the Quilty group tended to have a greater incidence of post-transplant ischemic injury complicated by fibrosis (54% vs 38%, p = 0.08) and a greater reported incidence of "previous biopsy site" during the first 4 weeks after transplantation (48% vs 32%, p = 0.06). At 1 year, the Quilty group had a significant increase in the change in coronary maximal intimal thickness seen with intravascular ultrasound (0.54 +/- 0.34 vs 0.42 +/- 0.28 mm, p = 0.038). CONCLUSIONS: This is the first report to describe the association of Quilty lesions with coronary vasculopathy and its association with increased alphavbeta3 expression.

Adult↗
PubMed2003

A simplified method for identification of human cardiac myosin heavy-chain isoforms.

Cardiac myosin is a central participant in the cross-bridge cycling that mediates myocyte contraction and consists of multiple subunits that mediate both hydrolysis of ATP and mechanical production of contractile force Two isoforms of myosin heavy chain (MHC- alpha and MHC- beta ) are known to exist in mammalian cardiac tissue, and it is within this myosin subunit that ATPase activity resides. These isoforms differ by less than 0.2% in total molecular mass and amino acid sequence, but, strikingly, influence the rate and efficiency of energy utilization for generation of contractile force. Changes in the MHC- alpha /MHC- beta ratio has been classically viewed as an adaptation of a failing myocyte in both animal models and humans; however, their measurement has traditionally required specialized preparations and materials for sufficient resolution. Here we describe a greatly simplified method for routine assessments of myosin isoform composition in human cardiac tissues. The primary advantages of our approach include higher throughput and reduced supply costs with no apparent loss of statistical power, reproducibility or achieved results. Use of this more convenient method may provide enhanced access to an otherwise specialized technique and could provide additional opportunity for investigation of cardiac myocyte adaptive changes.

Cardiac Myosins↗
PubMed2003

Evolving strategies for surgical management of patients with severe left ventricular dysfunction.

As a result of an increasing population with advanced congestive heart failure and the lack of growth in cardiac transplantation, surgical treatments for heart failure have been re-examined. These therapies represent the evolution of well-known operations such as coronary bypass surgery and valve surgeries, and the more novel left ventricular reconstruction and operations aimed at inhibiting left ventricular remodeling. When performed by surgeons with experience in this evolving speciality within cardiovascular surgery, surgery for advanced heart failure is a treatment of choice for many patients.

Journal Article↗
PubMed2003

Contemporary surgical treatment for atrial fibrillation.

Traditional surgical treatment of AF is the Cox-Maze III procedure. The Cox-Maze III procedure cures AF in >90% of patients and virtually eliminates the risk of stroke. Recent understanding of the importance of the pulmonary veins and left atrium in the pathogenesis of AF has resulted in the development of new surgical approaches. New operations to ablate AF use alternate energy sources (radiofrequency, microwave, cryothermy) and simplified left atrial lesion sets. These operations cure AF in 70-80% of patients. This article describes contemporary and emerging surgical approaches to AF, synthesizes results of these operations, and proposes a strategy for choice of operation based on patient presentation.

Atrial Appendage↗
PubMed2003

Evidence of specialized conduction cells in human pulmonary veins of patients with atrial fibrillation.

UNLABELLED: Specialized Conducting Cells in Human PV. INTRODUCTION: Depolarizations similar to those from the sinus node have been documented from the pulmonary veins after isolation procedures. We assessed the hypothesis that sinus node-like tissue is present in the pulmonary veins of humans. METHODS AND RESULTS: Pulmonary vein tissue was obtained from five autopsies (four individuals with a history of atrial fibrillation and one without a history of atrial arrhythmias) and five transplant heart donors. Autopsy veins were fixed in formaldehyde and processed for light microscopy to identify areas having possible conductive-like tissue. Areas requiring additional study were extracted from paraffin blocks and reprocessed for electron microscopy. Donor specimens were fixed in formaldehyde for histologic sections and glutaraldehyde for electron microscopy. Myocardial cells with pale cytoplasm were identified by light microscopy in 4 of the 5 autopsy subjects. Electron microscopy confirmed the presence of P cells, transitional cells, and Purkinje cells in the pulmonary veins of these cases. CONCLUSION: Our report is the first to show the presence of P cells, transitional cells, and Purkinje cells in human pulmonary veins. Whether these cells are relevant in the genesis of atrial fibrillation requires further study.

Adolescent↗
PubMed2003

Determinants of the development of mitral regurgitation in pacing-induced heart failure.

The pacing-induced heart failure model provides an opportunity to assess the structural and functional determinants of mitral regurgitation (MR) in dilated cardiomyopathy. This study aimed to evaluate MR to better understand the multitude of factors contributing to its development. Heart failure was induced by rapid ventricular pacing (230 beats/min) in 40 mongrel dogs. Left ventricular (LV) size and MR were evaluated echocardiographically. LV contractility was analyzed using a conductance catheter. MR increased to mild in 12 animals (regurgitant orifice area, 0.06+/-0.05 cm(2)), moderate in 15 (0.14+/-0.07 cm(2)), and severe in 13 (0.34+/-0.16 cm(2)). The grade of MR had an inverse relationships with E(max) (the slope of the end-systolic pressure-volume relationship, p<0.01) and dE/dt (the slope of the maximum rate of change of pressure-end-diastolic volume [V(ED)] relationship, p<0.01) and positive relationships with V(ED) and end-diastolic cross-sectional areas and lengths (p<0.05) by univariate analysis. The dE/dt had an independently significant (p<0.01) relationship by multivariable logistic regression. Many factors influence the development of MR and because of its similarity to the clinical situation, this model can be used to investigate MR and heart failure, as well as new surgical therapies.

Animals↗
PubMed2003

Curative surgery for atrial fibrillation: current status and minimally invasive approaches.

Atrial fibrillation (AF) is the most common disorder of heart rhythm. Affecting 2.2 million Americans and millions more worldwide, AF is a dangerous and costly epidemic. AF is associated with an increased risk of stroke, premature death and billions of dollars in healthcare expenditures. Traditional treatments of AF, which include medications aimed at rate or rhythm control have been disappointing, leaving most patients in AF and failing to eliminate the risk of stroke. In contrast, advances in surgical and catheter-based therapies offer the chance to cure AF. With more than a decade of experience, surgical treatment of AF is the most effective means of curing this arrhythmia. The classic Maze procedure eliminates AF in more than 90% of patients. A complex but safe operation, the Maze procedure is applied by relatively few surgeons. Recently, however, there has been a resurgence of interest in surgical treatment of AF. Advances in the understanding of the pathogenesis of AF and development of new ablation technologies enable surgeons to perform pulmonary vein ablation and create linear left atrial lesions rapidly and safely. Such procedures, which are generally applied to patients with AF and valvular heart disease, add 15 minutes to operative time and cure AF in approximately 80% of patients. New ablation technologies have been adapted to enable thoracoscopic and minimally invasive surgical AF ablation in patients with isolated AF, extending the possibility of cure to large numbers of patients.

Atrial Fibrillation↗
PubMed2003

Cardiac transplantation at the Cleveland Clinic.

The cardiac transplant program at the Cleveland Clinic began in 1984 and has performed nearly 1,100 heart transplants. One-year actual graft and patient survival was 88% among 185 adult recipients transplanted between 1997-1999. In the past 20 years, we have seen a significant evolution of recipient selection criteria, donor suitability, immunosuppressive therapies, and posttransplant patient surveillance. Many of the changes in our program are a result of the bleak forecast, that even in a utopian situation, there would be an inadequate supply of donors. Since the potential growth in transplantable organs appears to be finite, every mechanism possible should be utilized to decrease the demand for this scarce resource. It is of utmost importance that all medical and surgical options have been exhausted prior to listing a patient for transplantation. More than 90% of our transplants are performed in patients who are UNOS Status 1A or 1B. Every patient on the waiting list must be reviewed periodically, to ensure that transplantation is still the most viable option. Finally, to reduce the risk of rejection and preserve graft survival, we must continue the search for novel immunosuppressants.

Heart Transplantation↗
PubMed2002

Predictors of severe right ventricular failure after implantable left ventricular assist device insertion: analysis of 245 patients.

BACKGROUND: Insertion of an implantable left ventricular assist device (LVAD) complicated by early right ventricular (RV) failure has a poor prognosis and is largely unpredictable. Prediction of RV failure after LVAD placement would lead to more precise patient selection and optimal device selection. METHODS AND RESULTS: We reviewed data from 245 patients (mean age, 54+/-11 years; 85% male) with 189 HeartMate (77%) and 56 Novacor (23%) LVADs. Ischemic cardiomyopathy predominated (65%), and 29% had dilated cardiomyopathy. Overall, RV assist device (RVAD) support was required after LVAD insertion for 23 patients (9%). We compared clinical and hemodynamic parameters before LVAD insertion between RVAD (n=23) and No-RVAD patients (n=222) to determine preoperative risk factors for severe RV failure. By univariate analysis, female gender, small body surface area, nonischemic etiology, preoperative mechanical ventilation, circulatory support before LVAD insertion, low mean and diastolic pulmonary artery pressures (PAPs), low RV stroke work (RVSW), and low RVSW index (RVSWI) were significantly associated with RVAD use. Elevated PAP and pulmonary vascular resistance were not risk factors. Risk factors by multivariable logistic regression were preoperative circulatory support (odds ratio [OR], 5.3), female gender (OR, 4.5), and nonischemic etiology (OR, 3.3). CONCLUSIONS: The need for circulatory support, female gender, and nonischemic etiology were the most significant predictors for RVAD use after LVAD insertion. Regarding hemodynamics, low PAP and low RVSWI, reflecting low RV contractility, were important parameters. This information may lead to better patient selection for isolated LVAD implantation.

Adolescent↗
PubMed2002

Increased tissue factor expression predicts development of cardiac allograft vasculopathy.

BACKGROUND: Cardiac allograft vasculopathy (CAV) limits the long-term success of cardiac transplantation. The incidence of CAV is increased in patients with elevated plasma levels of oxidized lipids or fibrin deposition within right heart biopsy (RHB) specimens. The present study investigated whether tissue factor (TF), the expression of which is regulated by oxidized lipids, is upregulated in patients with CAV. METHODS AND RESULTS: A TF score was developed to quantify TF expression in RHB specimens from 63 consecutive patients undergoing routine annual posttransplantation RHB and coronary angiography. In patients >2 years (3.0+/-0.8 years) posttransplantation (n=35), a high TF score was observed with greater frequency (75% versus 26%, P<0.004) in patients with CAV than those without CAV. In patients <2 years (0.87+/-0.48 years) posttransplantation (n=28) without evidence of CAV, the TF score was determined and patients were followed up prospectively. A high TF score had a positive predictive value of 78.6% for the development of CAV, and a low TF score had a negative predictive value of 100%. CONCLUSIONS: These data demonstrate that early TF expression predicts subsequent development of CAV. Increased TF expression could link the elevated levels of oxidized LDL and fibrin deposition known to precede CAV. These findings suggest that TF may play a role in the pathophysiology of CAV and could offer a potential prognostic tool and a novel target for the prevention of CAV, possibly with antioxidants or inhibitors of the TF pathway.

Adult↗
PubMed2002

The gene expression fingerprint of human heart failure.

Multiple pathways are responsible for transducing mechanical and hormonal stimuli into changes in gene expression during heart failure. In this study our goals were (i) to develop a sound statistical method to establish a comprehensive cutoff point for identification of differentially expressed genes, (ii) to identify a gene expression fingerprint for heart failure, (iii) to attempt to distinguish different etiologies of heart failure by their gene expression fingerprint, and (iv) to identify gene clusters that show coordinated up- or down-regulation in human heart failure. We used oligonucleotide microarrays to profile seven nonfailing (NF) and eight failing (F) human hearts with a diagnosis of end-stage dilated cardiomyopathy. Biological and experimental variability of the hybridization data were analyzed, and then a statistical analysis procedure was developed, including Student's t test after log-transformation and Wilcoxon Mann-Whitney test. A comprehensive cutoff point composed of fold change, average difference, and absolute call was then established and validated by TaqMan PCR. Of 6,606 genes on the GeneChip, 103 genes in 10 functional groups were differentially expressed between F and NF hearts. A dendrogram identified a gene expression fingerprint of F and NF hearts and also distinguished two F hearts with distinct etiologies (familial and alcoholic cardiomyopathy, respectively) with different expression patterns. K means clustering also revealed two potentially novel pathways associated with up-regulation of atrial natriuretic factor and brain natriuretic peptide and with increased expression of extracellular matrix proteins. Gene expression fingerprints may be useful indicators of heart failure etiologies.

Adult↗
PubMed2002

Survival after aortic valve replacement for severe aortic stenosis with low transvalvular gradients and severe left ventricular dysfunction.

OBJECTIVE: We sought to assess whether aortic valve replacement (AVR) among patients with severe aortic stenosis (AS), severe left ventricular (LV) dysfunction and a low transvalvular gradient (TVG) is associated with improved survival. BACKGROUND: The optimal management of patients with severe AS with severe LV dysfunction and a low TVG remains controversial. METHODS: Between 1990 and 1998, we evaluated 68 patients who underwent AVR at our institution (AVR group) and 89 patients who did not undergo AVR (control group), with an aortic valve area < or = 0.75 cm(2), LV ejection fraction < or = 35% and mean gradient < or = 30 mm Hg. Using propensity analysis, survival was compared between a cohort of 39 patients in the AVR group and 56 patients in the control group. RESULTS: Despite well-matched baseline characteristics among propensity-matched patients, the one- and four-year survival rates were markedly improved in patients in the AVR group (82% and 78%), as compared with patients in the control group (41% and 15%; p < 0.0001). By multivariable analysis, the main predictor of improved survival was AVR (adjusted risk ratio 0.19, 95% confidence interval 0.09 to 0.39; p < 0.0001). The only other predictors of mortality were age and the serum creatinine level. CONCLUSIONS: Among select patients with severe AS, severe LV dysfunction and a low TVG, AVR was associated with significantly improved survival.

Adult↗