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P M McCarthy

Publications and source records attributed to P M McCarthy.

At least 19 recordsLinked to original sources
PubMed2005

Early and late rejection and HLA sensitization at the time of heart transplantation in patients bridged with left ventricular assist devices.

Over the years, the frequency of heart transplant candidates with HLA sensitization has increased as a result of the number of patients bridged to transplant using left ventricular assist devices (LVAD). Here we have examined 119 patients who were bridged to transplant with LVAD for a relationship between HLA antibodies and early (30 days) and late (2 years or more) rejection, as evidenced by endomyocardial biopsies. Both cytotoxic panel-reactive antibody reactions against a panel of T lymphocytes (T-PRA) and the percentage of transplants that occurred across a positive class I flow cross-match were examined. Biopsies were scored using ISHLT criteria. At 30 days, patients who had a biopsy grade of 0 had a mean T-PRA at transplant of 2.2%, while the mean PRAs of the other biopsy grades were significantly higher (P < .001). A similar pattern was seen with the highest biopsy results at 2 years or later (P < .001). None of the patients who had a grade 0 biopsy at 30 days posttransplant had a positive flow cytometry class I cross-match (P = .02), although the same pattern did not occur later due to a small number of patients (n = 3) who had negative biopsies. Thus, when biopsy results were examined early or late posttransplant, patients with negative biopsy results tended to have less HLA sensitization. While the methods of HLA sensitization involve humoral responses, more aggressive immunosuppression might be warranted to attempt to reduce cellular rejection posttransplant if HLA class I antibodies are present at the time of transplant.

Flow Cytometry↗
PubMed2004

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 health care 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 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.

Aged↗
PubMed2002

Preload-adjusted maximal power: a novel index of left ventricular contractility in atrial fibrillation.

BACKGROUND: Left ventricular contractility in atrial fibrillation is known to change in a beat to beat fashion, but there is no gold standard for contractility indices in atrial fibrillation, especially those measured non-invasively. OBJECTIVE: To determine whether the non-invasive index of contractility "preload-adjusted PWR(max)" (maximal ventricular power divided by the square of end diastolic volume) can accurately measure left ventricular contractility in a beat to beat fashion in atrial fibrillation. METHODS: Atrial fibrillation was induced experimentally using 60 Hz stimulation of the atrium and maintained in 12 sheep; four received diltiazem, four digoxin, and four no drugs (control). Aortic flow, left ventricular volume, and left ventricular pressure were monitored simultaneously. Preload-adjusted PWR(max), the slope of the end systolic pressure-volume relation (E(max)), and the maximum rate of change of left ventricular pressure (dP/dt(max)) were calculated in a beat to beat fashion. RESULTS: Preload-adjusted PWR(max) correlated linearly with load independent E(max) (p < 0.0001) and curvilinearly with load dependent dP/dt(max) (p < 0.0001), which suggested the load independence of preload-adjusted PWR(max). After five minutes of diltiazem administration, preload-adjusted PWR(max), dP/dt(max), and E(max) fell significantly (p < 0.0001) to 62%, 64%, and 61% of baseline, respectively. Changes were not significant after five minutes of digoxin (103%, 98%, and 102%) or in controls (97%, 96%, and 95%). CONCLUSIONS: Preload-adjusted PWR(max) correlates linearly with E(max) and is a useful measure of contractility even in atrial fibrillation. Non-invasive application of this method, in combination with echocardiography and tonometry, may yield important information for optimising the treatment of patients with atrial fibrillation.

Animals↗
PubMed2001

Relationship between early diastolic intraventricular pressure gradients, an index of elastic recoil, and improvements in systolic and diastolic function.

BACKGROUND: Early diastolic intraventricular pressure gradients (IVPGs) have been proposed to relate to left ventricular (LV) elastic recoil and early ventricular "suction." Animal studies have demonstrated relationships between IVPGs and systolic and diastolic indices during acute ischemia. However, data on the effects of improvements in LV function in humans and the relationship to IVPGs are lacking. METHODS AND RESULTS: Eight patients undergoing CABG and/or infarct exclusion surgery had a triple-sensor high-fidelity catheter placed across the mitral valve intraoperatively for simultaneous recording of left atrial (LA), basal LV, and apical LV pressures. Hemodynamic data obtained before bypass were compared with those with similar LA pressures and heart rates obtained after bypass. From each LV waveform, the time constant of LV relaxation (tau), +dP/dt(max), and -dP/dt(max) were determined. Transesophageal echocardiography was used to determined end-diastolic (EDV) and end-systolic (ESV) volumes and ejection fractions (EF). At similar LA pressures and heart rates, IVPG increased after bypass (before bypass 1.64+/-0.79 mm Hg; after bypass 2.67+/-1.25 mm Hg; P<0.01). Significant improvements were observed in ESV, as well as in apical and basal +dP/dt(max), -dP/dt(max), and tau (each P<0.05). Overall, IVPGs correlated inversely with both ESV (IVPG=-0.027[ESV]+3.46, r=-0.64) and EDV (IVPG=-0.027[EDV]+4.30, r=-0.70). Improvements in IVPGs correlated with improvements in apical tau (Deltatau =5.93[DeltaIVPG]+4.76, r=0.91) and basal tau (Deltatau =2.41[DeltaIVPG]+5.13, r=-0.67). Relative changes in IVPGs correlated with changes in ESV (DeltaESV=-0.97[%DeltaIVPG]+23.34, r=-0.79), EDV (DeltaEDV=-1.16[%DeltaIVPG]+34.92, r=-0.84), and EF (DeltaEF=0.38[%DeltaIVPG]-8.39, r=0.85). CONCLUSIONS: Improvements in LV function also increase IVPGs. These changes in IVPGs, suggestive of increases in LV suction and elastic recoil, correlate directly with improvements in LV relaxation and ESV.

Blood Pressure↗
PubMed2001

Ascorbate attenuates atrial pacing-induced peroxynitrite formation and electrical remodeling and decreases the incidence of postoperative atrial fibrillation.

Atrial fibrillation (AF), the most common chronic arrhythmia, increases the risk of stroke and is an independent predictor of mortality. Available pharmacological treatments have limited efficacy. Once initiated, AF tends to self-perpetuate, owing in part to electrophysiological remodeling in the atria; however, the fundamental mechanisms underlying this process are still unclear. We have recently demonstrated that chronic human AF is associated with increased atrial oxidative stress and peroxynitrite formation; we have now tested the hypothesis that these events participate in both pacing-induced atrial electrophysiological remodeling and in the occurrence of AF following cardiac surgery. In chronically instrumented dogs, we found that rapid (400 min(-1)) atrial pacing was associated with attenuation of the atrial effective refractory period (ERP). Treatment with ascorbate, an antioxidant and peroxynitrite decomposition catalyst, did not directly modify the ERP, but attenuated the pacing-induced atrial ERP shortening following 24 to 48 hours of pacing. Biochemical studies revealed that pacing was associated with decreased tissue ascorbate levels and increased protein nitration (a biomarker of peroxynitrite formation). Oral ascorbate supplementation attenuated both of these changes. To evaluate the clinical significance of these observations, supplemental ascorbate was given to 43 patients before, and for 5 days following, cardiac bypass graft surgery. Patients receiving ascorbate had a 16.3% incidence of postoperative AF, compared with 34.9% in control subjects. In combination, these studies suggest that oxidative stress underlies early atrial electrophysiological remodeling and offer novel insight into the etiology and potential treatment of an enigmatic and difficult to control arrhythmia. The full text of this article is available at http://www.circresaha.org.

Aged↗
PubMed2001

Mechanical unloading restores beta-adrenergic responsiveness and reverses receptor downregulation in the failing human heart.

BACKGROUND: Mechanical unloading of the failing human heart with a left ventricular assist device (LVAD) results in clinically documented reversal of chamber dilation and improvement of cardiac function. We tested the hypothesis that LVAD support normalizes the ability of cardiac muscle to respond to sympathetic nervous system stimulation by reversing the downregulation of beta-adrenergic receptors. METHODS AND RESULTS: Human LV tissue was obtained from nonfailing hearts of unmatched organ donors and failing hearts at the time of transplantation, with or without LVAD. Baseline contractile parameters and inotropic response to a beta-adrenergic agonist were measured in isolated trabecular muscles. beta-Adrenergic receptor density was quantified by radioligand binding. Results showed a significant increase in the response to beta-adrenergic stimulation after LVAD (developed tension increased by 0.76+/-0.09 g/mm(2) in nonfailing, 0.38+/-0.07 in failing, and 0.68+/-0.10 in failing+LVAD; P<0.01), accompanied by an increased density of beta-adrenergic receptors (58.7+/-9.6 fmol/mg protein in nonfailing, 26.2+/-3.8 in failing, and 63.0+/-8.3 in failing+LVAD; P<0.05). These changes were unrelated to the duration of support. CONCLUSIONS: Data demonstrate that mechanically supporting the failing human heart with an LVAD can reverse the downregulation of beta-adrenergic receptors and restore the ability of cardiac muscle to respond to inotropic stimulation by the sympathetic nervous system. This indicates that functional impairment of cardiac muscle in human heart failure is reversible.

Adult↗
PubMed2001

Impaired myofibrillar energetics and oxidative injury during human atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is associated with severe contractile dysfunction and structural and electrophysiological remodeling. Mechanisms responsible for impaired contractility are undefined, and current therapies do not address this dysfunction. We have found that myofibrillar creatine kinase (MM-CK), an important controller of myocyte contractility, is highly sensitive to oxidative injury, and we hypothesized that increased oxidative stress and energetic impairment during AF could contribute to contractile dysfunction. Methods and Results-- Right atrial appendages were obtained from AF patients undergoing the Maze procedure and from control patients who were in normal sinus rhythm and undergoing cardiac surgery. MM-CK activity was reduced in AF patients compared with controls (25.4+/-3.4 versus 18.2+/-3.8 micromol/mg of myofibrillar protein per minute; control versus AF; P<0.05). No reduction in total CK activity or myosin ATPase activity was detected. This selective reduction in MM-CK activity was associated with increased relative expression of the beta-myosin isoform (25+/-6 versus 63+/-5%beta, CTRL versus AF; P<0.05). Western blotting of AF myofibrillar isolates demonstrated no changes in protein composition but showed increased prevalence of protein oxidation as detected by Western blotting for 3-nitrotyrosine (peroxynitrite biomarker) and protein carbonyls (hydroxyl radical biomarker; P<0.05). Patterns of these oxidative markers were distinct, which suggests discrete chemical events and differential protein vulnerabilities in vivo. MM-CK inhibition was statistically correlated to extent of nitration (P<0.01) but not to carbonyl presence. CONCLUSIONS: The present results provide novel evidence of oxidative damage in human AF that altered myofibrillar energetics may contribute to atrial contractile dysfunction and that protein nitration may be an important participant in this condition.

Aged↗
PubMed2001

High prevalence of coronary atherosclerosis in asymptomatic teenagers and young adults: evidence from intravascular ultrasound.

BACKGROUND: Most of our knowledge about atherosclerosis at young ages is derived from necropsy studies, which have inherent limitations. Detailed, in vivo data on atherosclerosis in young individuals are limited. Intravascular ultrasonography provides a unique opportunity for in vivo characterization of early atherosclerosis in a clinically relevant context. METHODS AND RESULTS: Intravascular ultrasound was performed in 262 heart transplant recipients 30.9+/-13.2 days after transplantation to investigate coronary arteries in young asymptomatic subjects. The donor population consisted of 146 men and 116 women (mean age of 33.4+/-13.2 years). Extensive imaging of all possible (including distal) coronary segments was performed. Sites with the greatest and least intimal thickness in each CASS segment were measured in multiple coronary arteries. Sites with intimal thickness >/=0.5 mm were defined as atherosclerotic. A total of 2014 sites within 1477 segments in 574 coronary arteries (2.2 arteries per person) were analyzed. An atherosclerotic lesion was present in 136 patients, or 51.9%. The prevalence of atherosclerosis varied from 17% in individuals <20 years old to 85% in subjects >/=50 years old. In subjects with atherosclerosis, intimal thickness and area stenosis averaged 1.08+/-0.48 mm and 32.7+/-15.9%, respectively. For all age groups, the average intimal thickness was greater in men than women, although the prevalence of atherosclerosis was similar (52% in men and 51.7% in women). CONCLUSIONS: This study demonstrates that coronary atherosclerosis begins at a young age and that lesions are present in 1 of 6 teenagers. These findings suggest the need for intensive efforts at coronary disease prevention in young adults.

Adolescent↗
PubMed2001

Regional heterogeneity of function in nonischemic dilated cardiomyopathy.

OBJECTIVE: To quantify regional three-dimensional (3D) motion and myocardial strain using magnetic resonance (MR) tissue tagging in patients with non-ischemic dilated cardiomyopathy (DCM). METHODS: MR grid tagged images were obtained in multiple short- and long-axis planes in thirteen DCM patients. Regional 3D displacements and strains were calculated with the aid of a finite element model. Five of the patients were also imaged after LV volume reduction by partial left ventriculectomy (PLV), combined with mitral and tricuspid valve repair. RESULTS: DCM patients showed consistent, marked regional heterogeneity. Systolic lengthening occurred in the septum in both circumferential (%S(C) -5+/-7%) and longitudinal (%S(L) -2+/-5%) shortening components (negative values indicating lengthening). In contrast, the lateral wall showed relatively normal systolic shortening (%S(C) 12+/-6% and %S(L) 6+/-5%, P<0.001 lateral vs. septal walls). A geometric estimate of regional stress was correlated with shortening on a regional basis, but could not account for the differences in shortening between regions. In the five patients imaged post-PLV, septal function recovered (%S(C) 9+/-5%,%S(L) 6+/-5%, P<0.02 pre vs. post) with normalization of wall stress, whereas lateral wall shortening was reduced (%S(C) 7+/-6%,%S(L) 3+/-3%, P<0.02 pre vs. post) around the site of surgical resection. CONCLUSIONS: A consistent pattern of regional heterogeneity of myocardial strain was seen in all patients. Reduced function may be related to increased wall stress, since recovery of septal function is possible after PLV. However, simple geometric stress determinants are not sufficient to explain the functional heterogeneity observed.

Adult↗
PubMed2001

Left ventricular assist device bridge to recovery: a review of the current status.

The use of the left ventricular assist device as a bridge to recovery represents a new phenomenon. This article focuses on bridge-to-recovery in the settings of myocarditis and dilated cardiomyopathy with a review of the hemodynamic, neurohormonal, physiologic, cellular, and molecular changes of recovery during left ventricular assist device support. Despite numerous markers of success, there is a disconnect from the limited clinical successes that are reviewed. The current status and future options to increase the chances of success are highlighted.

Adult↗
PubMed2001

Nosocomial bloodstream infections in patients with implantable left ventricular assist devices.

BACKGROUND: Implantable left ventricular assist devices (LVAD) are used as a bridge to transplantation but are associated with a high risk of infection including nosocomial bloodstream infections (BSI). METHODS: We retrospectively reviewed the medical records of all patients with implantable LVAD at the Cleveland Clinic with 72 hours or longer of LVAD support from January 1992 through June 2000, to determine the attack rate, incidence, and impact of nosocomial BSI in patients with LVAD. A nosocomial BSI was defined using Centers for Disease Control and Prevention definition. An LVAD-related BSI was defined as one where the same pathogen is cultured from the device and the blood with no other obvious source. Two hundred fourteen patients were included in the study (17,831 LVAD-days). RESULTS: One hundred forty BSI were identified in 104 patients for an attack rate of 49% and incidence of 7.9 BSI per 1000 LVAD-days. Thirty-eight percent of the BSI were LVAD associated. The most common pathogens causing BSI were coagulase-negative staphylococci (n = 33), Staphylococcus aureus, and Candida spp. (19 each), and Pseudomonas aeruginosa (16 each). A Cox proportional hazard model found BSI in patients with LVAD to be significantly associated with death (hazard ratio = 4.02, p < 0.001). Fungemia had the highest hazard ratio (10.9), followed by gram-negative bacteremia (5.1), and gram-positive bacteremia (2.2). CONCLUSIONS: Patients with implantable LVAD have a high incidence of BSI, which are associated with a significantly increased mortality. Strategies for prevention of infection in LVAD recipients should focus on the drive line exit site until technical advances can achieve a totally implantable device.

Bacteremia↗
PubMed2001

Safety and efficacy of intraarterial thrombolysis for perioperative stroke after cardiac operation.

BACKGROUND: Acute ischemic stroke after cardiac operations is a devastating complication with limited therapeutic options. As clinical trials of thrombolysis for acute ischemic stroke exclude patients with recent major surgery, the safety of intraarterial thrombolysis in this setting is unknown. METHODS: Thirteen patients with acute ischemic stroke within 12 days of cardiac operation underwent intraarterial thrombolysis within 6 hours of stroke symptom onset. The National Institutes of Health Stroke Scale was used to assess neurologic recovery. RESULTS: The mean age was 69 years (standard deviation +/-5 years) and 62% were men. Cardiac procedures included valve operations in 6 patients, coronary artery bypass grafting in 4, valve and coronary artery bypass grafting in 2, and left ventricular assist device in 1 patient. Atrial fibrillation occurred in 5 patients (38%). The mean time from operation to stroke was 4.3 days (standard deviation +/- 3 days). Thrombolysis was initiated within 3.6 hours (standard deviation +/-1.6 hours) of stroke symptom onset. Recanalization was complete in 1 patient, partial in 5, and 7 patients had low flow. Neurologic improvement occurred in 5 patients (38%). One patient needed a chest tube for hemothorax, 2 others were transfused for low hemoglobin. No operative intervention for bleeding was necessary. CONCLUSIONS: In select patients with acute ischemic stroke after recent cardiac operation, intraarterial thrombolysis appears to be reasonably safe and may lead to neurologic recovery.

Aged↗
PubMed2001

A simple method of left ventricular reconstruction without patch for ischemic cardiomyopathy.

Interest in reconstructive surgery for ischemic cardiomyopathy has increased. We prospectively studied patients undergoing left ventricular reconstruction for ischemic cardiomyopathy. This report describes our technique for no-patch repair of left anterior descending aneurysms or akinetic areas. Patients are selected for surgery with discreet left anterior descending scar, usually detected by preoperative magnetic resonance imaging scan and three-dimensional echocardiography, with compensated heart failure or other indications for surgery such as severe coronary artery disease or mitral regurgitation.

Cardiomyopathies↗
PubMed2001

Surgical treatments for heart failure.

The surgical options for CHF are a part of a larger paradigm shift in management. Viable and effective surgical options other than cardiac transplant and ventricular assist devices clearly exist and are applicable to a large portion of patients with CHF. These surgical therapies are of acceptable risk before decompensated CHF develops. The rapidly evolving therapies for altering LV remodeling, which underlies CHF progression, are an exciting area that may be joined in the future by molecular advances in myoblast transfer and gene therapy. These therapies are the basis of the discipline of CHF surgery within cardiovascular surgery.

Cardiomyopathy, Dilated↗
PubMed2001

Hypogammaglobulinemia following cardiac transplantation: a link between rejection and infection.

BACKGROUND: Hypogammaglobulinemia (HGG) has been reported after solid organ transplantation and is noted to confer an increased risk of opportunistic infections. OBJECTIVES: In this study, we sought to assess the relationship between severe HGG to infection and acute cellular rejection following heart transplantation. METHODS: Between February 1997 and January 1999, we retrospectively analyzed the clinical outcome of 111 consecutive heart transplant recipients who had immunoglobulin G (IgG) level monitoring at 3 and 6 months post-transplant and when clinically indicated. RESULTS: Eighty-one percent of patients were males, mean age 54 +/- 13 years, and the mean follow-up period was 13.8 +/- 5.7 months. Patients had normal IgG levels prior to transplant (mean 1137 +/- 353 mg/dl). Ten percent (11 of 111) of patients developed severe HGG (IgG < 350 mg/dl) post-transplant. The average time to the lowest IgG level was 196 +/- 125 days. Patients with severe HGG were at increased risk of opportunistic infections compared to patients with IgG > 350 mg/dl (55% [6 of 11] vs. 5% [5 of 100], odds ratio = 22.8, p < 0.001). Compared to patients with no rejection, patients who experienced three or more episodes of rejection had lower mean IgG (580 +/- 309 vs. 751 +/- 325, p = 0.05), and increased incidence of severe HGG (33% [7 of 21] vs. 2.8% [1 of 35], p = 0.001). The incidence of rejection episodes per patient at 1 year was higher in patients with severe HGG compared to patients with IgG >350 (2.82 +/- 1.66 vs. 1.36 +/- 1.45 episodes/patient, p = 0.02). The use of parenteral steroid pulse therapy was associated with an increased risk of severe HGG (odds ratio = 15.28, p < 0.001). CONCLUSIONS: Severe HGG after cardiac transplantation may develop as a consequence of intensification of immunosuppressive therapy for rejection and hence, confers an increased risk of opportunistic infections. IgG level may be a useful marker for identifying patients at high risk.

Agammaglobulinemia↗