Biomedical subjects

Francis D Pagani

Publications and source records attributed to Francis D Pagani.

At least 19 recordsLinked to original sources

PubMed2006

Improved mechanical reliability of the HeartMate XVE left ventricular assist system.

BACKGROUND: The HeartMate XVE left ventricular assist device is a valuable treatment option for patients with end-stage heart failure. During the past several years, the XVE has undergone a series of design enhancements to improve reliability. We compared the reliability of the two most recent design iterations of the XVE pump (stitch modification to the inflow valve assembly and new inflow valve housing redesign) to the earlier VE version. METHODS: A retrospective evaluation of device reliability was performed for 268 devices implanted in 245 patients (VE: n = 167 devices, 147 patients, implant dates October 16, 1998, to December 19, 2003; XVE: n = 101 devices, 98 patients, implant dates August 1, 2002, to April 14, 2004). RESULTS: Median duration of device support for the VE and XVE was 159 days (range, 0 to 1,206 days) and 229 days (range, 0 to 693 days), respectively (p = 0.495). Significantly fewer major device malfunctions occurred within the XVE group as compared with the VE group (6 versus 36, respectively; p = 0.0003). The number of major device malfunctions per patient-year of support for inflow valve dysfunction, bearing wear, and other failures for the VE and XVE were 0.2 versus 0.04 (p = 0.006), 0.16 versus 0.01 (p = 0.005), and 0.06 versus 0.04 (p = 1.000), respectively. The freedom from major device malfunction at 1 year was 76% +/- 6% for the VE and 97% +/- 2% for the XVE device (p < 0.001). The freedom from death as a result of major device malfunction at 1 year was 97% +/- 2% for the VE and 98% +/- 2% for the XVE (p = 0.698). CONCLUSIONS: Design enhancements to the HeartMate XVE have significantly reduced the incidence of major device malfunctions compared with the earlier VE model because of a reduction in failure modes from bearing wear and inlet valve dysfunction. Further follow-up is necessary to establish the long-term durability of the most recent XVE pump version.

Adolescent↗

PubMed2005

Safety and feasibility of autologous myoblast transplantation in patients with ischemic cardiomyopathy: four-year follow-up.

BACKGROUND: Successful autologous skeletal myoblast transplantation into infarcted myocardium in a variety of animal models has demonstrated improvement in cardiac function. We evaluated the safety and feasibility of transplanting autologous myoblasts into infarcted myocardium of patients undergoing concurrent coronary artery bypass grafting (CABG) or left ventricular assist device (LVAD) implantation. In addition, we sought to gain preliminary information on graft survival and any associated changes in cardiac function. METHODS AND RESULTS: Thirty patients with a history of ischemic cardiomyopathy participated in a phase I, nonrandomized, multicenter pilot study of autologous skeletal myoblast transplantation concurrent with CABG or LVAD implantation. Twenty-four patients with a history of previous myocardial infarction and a left ventricular ejection fraction <40% were enrolled in the CABG arm. In a second arm, 6 patients underwent LVAD implantation as a bridge to heart transplantation, and patients donated their explanted native hearts for testing at the time of heart transplantation. Myoblasts were successfully transplanted in all patients without any acute injection-related complications or significant long-term, unexpected adverse events. Follow-up positron emission tomography scans showed new areas of glucose uptake within the infarct scar in CABG patients. Echocardiography measured an average change in left ventricular ejection fraction from 28% to 35% at 1 year and of 36% at 2 years. Histological evaluation in 4 of 6 patients who underwent heart transplantation documented survival and engraftment of the skeletal myoblasts within the infarcted myocardium. CONCLUSIONS: These results demonstrate the survival, feasibility, and safety of autologous myoblast transplantation and suggest that this modality offers a potential therapeutic treatment for end-stage heart disease.

Adult↗

PubMed2005

Impact of mitral valve annuloplasty on mortality risk in patients with mitral regurgitation and left ventricular systolic dysfunction.

OBJECTIVES: This study was designed to assess effects of mitral valve annuloplasty (MVA) on mortality in patients with mitral regurgitation (MR) and left ventricular (LV) systolic dysfunction. BACKGROUND: Mitral valve annuloplasty improves hemodynamics and symptoms in these patients, but effects on long-term mortality are not well established. METHODS: We retrospectively analyzed consecutive patients with significant MR and LV systolic dysfunction on echocardiography between 1995 and 2002. Cox regression analysis, including MVA as a time-dependent covariate and propensity scoring to adjust for differing probabilities of undergoing MVA, was used to identify predictors of death, LV assist device implantation, or United Network for Organ Sharing-1 heart transplantation. RESULTS: Of 682 patients identified, 419 were deemed surgical candidates; 126 underwent MVA. Propensity score derivation identified age, ejection fraction, and LV dimension to be associated with undergoing MVA. End points were reached in 120 (41%) non-MVA and 62 (49%) MVA patients. Increased risk of end point was associated with coronary artery disease (hazard ratio [HR] 1.80, 95% confidence interval [CI] 1.30 to 2.49), blood urea nitrogen (HR 1.01, 95% CI 1.005 to 1.02), cancer (HR 2.77, 95% CI 1.45 to 5.30), and digoxin (HR 1.66, 95% CI 1.15 to 2.39). Reduced risk was associated with angiotensin-converting enzyme inhibitors (HR 0.65, 95% CI 0.44 to 0.95), beta-blockers (HR 0.59, 95% CI 0.42 to 0.83), mean arterial pressure (HR 0.98, 95% CI 0.97 to 0.99), and serum sodium (HR 0.93, 95% CI 0.90 to 0.96). Mitral valve annuloplasty did not predict clinical outcome. CONCLUSIONS: In this analysis, there is no clearly demonstrable mortality benefit conferred by MVA for significant MR with severe LV dysfunction. A prospective randomized control trial is warranted for further study of mortality with MVA in this population.

Aged↗

PubMed2005

Anterior leaflet repair with patch augmentation for mitral regurgitation.

BACKGROUND: Anterior leaflet repair continues to pose significant operative challenges, particularly in patients with retracted or "short" anterior leaflets, due to rheumatic or radiation induced mitral valve disease. This often results in abandonment of repair in favor of mitral valve replacement, requiring anticoagulation and altering left ventricular (LV) function and geometry. This study examines our experience of anterior leaflet repair with patch augmentation. METHODS: Forty-two patients underwent mitral valve repair for a shortened anterior leaflet from 1994 to 2003. Twenty-two patients with a mean age of 53 +/- 6 years had radiation valvulitis (XR) whereas 20 patients, age 28 +/- 7 years had rheumatic heart disease (RHD). Those patients with XR had a mean New York Heart Association (NYHA) class of 3.2 +/- 0.4 and an angina score of 2.1 +/- 0.6 compared with a NYHA class 3.8 +/- 0.2 and no angina in RHD patients. All patients presented with severe MR. Anterior leaflet augmentation with a gluteraldehyde-treated, autologous pericardial patch and complete annuloplasty ring was used in all patients. Additionally, extensive subvalvar debridement was performed in RHD patients. Twelve XR patients underwent concomitant CABG with a mean of 2.4 +/- 0.8 grafts/patient. Additional surgical procedures included tricuspid valve repair, anterior septal defect, and aortic valve replacement. Mean follow-up was 39 +/- 10 months for XR patients and 12 +/- 25 months for RHD patients. RESULTS: There were two late deaths in XR patients from underlying malignancies and no deaths in RHD patients. Two RHD patients required reoperation for recurrent mitral regurgitation at 3 and 20 months. All patients demonstrated clinical improvements (NYHA I-II) following repair. No mitral stenosis was induced. CONCLUSIONS: Despite anterior leaflet shortening from XR or rheumatic alterations, opportunity still exists for gratifying mitral valve repair. By utilizing anterior leaflet patch augmentation, concomitantly with ring annuloplasty, anticoagulation is avoided, LV geometry is preserved, and follow-up reveals excellent functional improvement.

Adult↗

PubMed2005

Effect of oral vitamin E and C therapy on calcineurin inhibitor levels in heart transplant recipients.

BACKGROUND: A recent prospective trial demonstrated that oral vitamins C and E retard the early progression of transplant-associated coronary arteriosclerosis; as a result, a number of centers have added these agents to their maintenance regimens. This study reviewed the impact of vitamin E and C supplementation on calcineurin inhibitor trough concentrations. METHODS: A retrospective chart review of the first 29 heart transplant patients prescribed anti-oxidant agents was performed. Twenty-two patients taking cyclosporin A (CsA) and 7 patients taking tacrolimus were prescribed vitamin C (500 mg twice a day) and vitamin E (400 IU twice a day). Serum chemistries and drug levels were measured before and after vitamin therapy was initiated. RESULTS: The baseline CsA trough concentration (mean +/- SD) was 137 +/- 39 ng/ml and it declined to 99 +/- 54 ng/ml (p = 0.007) after anti-oxidant therapy was initiated. The average percentage decrease in the CsA trough concentration was 30%. No significant changes were seen in the patients taking tacrolimus. CONCLUSIONS: These data demonstrate that supplementation with the anti-oxidant agents vitamin C and vitamin E decreases CsA concentrations but does not appear to effect tacrolimus concentrations. Although more detailed pharmacokinetic analysis is necessary to clarify the exact mechanism of this interaction, physicians who take care of transplant recipients should be aware that more frequent CsA concentration monitoring is warranted after initiating these anti-oxidant agents.

Adult↗

PubMed2005

Feasibility and safety of autologous myoblast transplantation in patients with ischemic cardiomyopathy.

Successful autologous skeletal myoblast transplantation into infarcted myocardium in a variety of animal models has demonstrated improvement in cardiac function. We evaluated the safety and feasibility of transplanting autologous myoblasts into infarcted myocardium of patients undergoing concurrent coronary artery bypass grafting (CABG) or left ventricular assist device implantation (LVAD). In addition, we sought to gain preliminary information on graft survival and any potential improvement of cardiac function. Eighteen patients with a history of ischemic cardiomyopathy participated in a phase I, nonrandomized, multicenter pilot study of autologous skeletal myoblast transplantation concurrent with CABG or LVAD implantation. Twelve patients with a history of previous myocardial infarction (MI) and a left ventricular ejection of less than 30% were enrolled in the CABG arm. In a second arm, six patients underwent LVAD implantation as a bridge to heart transplantation and were required to donate their heart for testing at the time of heart transplant. Myoblasts were successfully transplanted in all patients without any acute injection-related complications or significant long-term unexpected adverse events. Follow-up PET scans showed new areas of viability within the infarct scar in CABG patients. Echocardiography measured an average improvement in left ventricular ejection fraction (LVEF) from 25% to 34%. Histological evaluation in four out of five patients who underwent heart transplantation documented survival and engraftment of the skeletal myoblasts within the infarcted myocardium. These interim results demonstrate survival, feasibility, and safety of autologous myoblast transplantation and suggest that this modality may offer a potential therapeutic treatment for end-stage heart disease.

Adult↗

PubMed2004

Atrial reduction plasty Cox maze procedure: extended indications for atrial fibrillation surgery.

BACKGROUND: The Cox maze procedure yields good results for atrial fibrillation (AF). However, patients with predictors of failure-chronic long-standing AF, low amplitude fibrillatory waves, and large left atriums-are generally thought not to benefit from a maze procedure. We report an aggressive approach for these patients, utilizing biatrial reduction plasty concomitantly with the Cox maze procedure for AF. METHODS: A complete Cox maze procedure utilizing supplemental RF ablation was performed in 36 patients. All underwent resection of both atrial appendages and biatrial reduction plasty encompassing resection of the left atrial posterior wall from left to right pulmonary veins and from inferior pulmonary veins to the mitral annulus, as well as removal of the right atrial lateral wall. Mitral or tricuspid valve repair, or both, was performed on 32 patients. RESULTS: These patients had a mean AF duration of 45 +/- 89 months. Their preoperative left atria measured 66 +/- 16 mm, with mean AF waves of 0.74 +/- 0.3 mm. Mean preoperative New York Heart Association class was 2.7 +/- 0.7 and left ventricular ejection fraction was 48 +/- 9. Cross clamp and bypass times were 91 +/- 35 minutes and 124 +/- 33 minutes, respectively. The average posterior left atrial tissue resected was 5.4 x 2.1 cm, and mean resected atrial weight was 10.3 +/- 2 g. There were no deaths and length of stay was 5.5 +/- 2 days. At a follow-up time of 19 +/- 16 months, 32 of the 36 patients were in normal sinus rhythm and New York Heart Association class I. CONCLUSIONS: Aggressive biatrial reduction plasty Cox maze procedure was effective in 89% of these "low success" AF patients. This simple procedure can extend utilization of the Cox maze procedure to more patients with chronic AF.

Aged↗

PubMed2004

Invited commentary.

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Heart Transplantation↗

PubMed2004

Infection in permanent circulatory support: experience from the REMATCH trial.

BACKGROUND: This analysis of the REMATCH Trial focuses on infection, which was an important source of morbidity and mortality. We use the information to suggest ways to decrease the incidence and effects of device-related infection. METHODS: Patients were randomized prospectively to receive left ventricular assist devices (LVADs) or optimal medical management (OMM) for end-stage heart failure. Infection variables included sepsis adjudicated as the cause of death; sepsis reported as a serious adverse event; percutaneous site or pocket infection; and pump housing, inflow- or outflow-tract infection. We compared the incidence and prevalence of events between groups and generated time-related descriptions. RESULTS: Survival with LVAD (n=68 patients) was superior to OMM survival (n=61 patients) with a 47% decrease in risk of death (p <0.001), but the aggregate adverse event rate was greater for patients with LVADs (risk ratio, 2.29; 95% confidence interval, 1.85-2.84). Freedom from sepsis in patients with LVADs was 58% at 1 year and 48% at 2 years after implantation with superior survival in non-septic patients (60% vs 39% at 1 year and 38% vs 8% at 2 years in non-septic vs septic patients with LVADs, p <0.06). Percutaneous site or pocket infection did not affect survival (p=0.86). The hazard for onset of sepsis peaked within the first 3 weeks after implantation. CONCLUSIONS: Survival is improved with permanent LVAD implantation compared with OMM therapy. However, infection causes substantial morbidity and mortality. Decreasing infections will increase survival and decrease morbidity in permanent LVAD recipients and will improve the risk-benefit ratio for permanent LVAD therapy.

Antibiotic Prophylaxis↗

PubMed2003

Autologous skeletal myoblasts transplanted to ischemia-damaged myocardium in humans. Histological analysis of cell survival and differentiation.

OBJECTIVES: We report histological analysis of hearts from patients with end-stage heart disease who were transplanted with autologous skeletal myoblasts concurrent with left ventricular assist device (LVAD) implantation. BACKGROUND: Autologous skeletal myoblast transplantation is under investigation as a means to repair infarcted myocardium. To date, there is only indirect evidence to suggest survival of skeletal muscle in humans. METHODS: Five patients (all male; median age 60 years) with ischemic cardiomyopathy, refractory heart failure, and listed for heart transplantation underwent muscle biopsy from the quadriceps muscle. The muscle specimen was shipped to a cell isolation facility where myoblasts were isolated and grown. Patients received a transplant of 300 million cells concomitant with LVAD implantation. Four patients underwent LVAD explant after 68, 91, 141, and 191 days of LVAD support (three transplant, one LVAD death), respectively. One patient remains alive on LVAD support awaiting heart transplantation. RESULTS: Skeletal muscle cell survival and differentiation into mature myofibers were directly demonstrated in scarred myocardium from three of the four explanted hearts using an antibody against skeletal muscle-specific myosin heavy chain. An increase in small vessel formation was observed in one of three patients at the site of surviving myotubes, but not in adjacent tissue devoid of engrafted cells. CONCLUSIONS: These findings represent demonstration of autologous myoblast cell survival in human heart. The implanted skeletal myoblasts formed viable grafts in heavily scarred human myocardial tissue. These results establish the feasibility of myoblast transplants for myocardial repair in humans.

Aged↗

PubMed2003

Myocardial proinflammatory cytokine expression and left ventricular remodeling in patients with chronic mitral regurgitation.

BACKGROUND: In an animal model, stretch was shown to induce myocardial tumor necrosis factor-alpha (TNF-alpha) expression. The purposes of this study were to determine whether the left ventricular (LV) volume overload that occurs in patients with chronic mitral regurgitation (MR) can induce myocardial and systemic TNF-alpha expression and whether there is a relationship between TNF-alpha expression and LV remodeling. METHODS AND RESULTS: Plasma TNF-alpha and its receptors were measured before mitral valve (MV) repair surgery in 26 MR patients and 23+/-12 months after MV repair surgery in 9 MR patients. Myocardial mRNA copies of TNF-alpha were determined in 11 MR and 10 donor hearts using quantitative RT-PCR. Compared with 15 control subjects, pre-MV repair plasma TNF-alpha (3.59+/-1.81 versus 2.03+/-1.02 pg/mL, P<0.005) and its receptor levels were elevated in MR patients. Myocardial TNF-alpha mRNA copies (corrected for beta-actin mRNA expression) in MR patients and donor hearts were 38.96+/-42.74x10(6) and 0.88+/-0.75x10(6), respectively (P=0.01). After MV surgery, there was a decrease in the plasma levels of TNF-alpha (2.79+/-1.14 versus 3.51+/-1.34 pg/mL, P=0.02) and its receptors. There was a correlation between myocardial TNF-alpha expression and preoperative LV end-diastolic and end-systolic volumes. Moreover, there was an inverse correlation between myocardial TNF-alpha expression and regression in LV end-diastolic (r=-0.76, P=0.007) and end-systolic (r=-0.73, P=0.01) volumes after MV surgery. CONCLUSIONS: TNF-alpha is expressed in the myocardium and plasma of MR patients. Correction of the LV volume overload with MV surgery results in reversal of TNF-alpha expression. There is a relationship between TNF-alpha expression and parameters of LV remodeling, suggesting that TNF-alpha may play a role in the pathogenesis of the LV remodeling that occurs in MR.

Adult↗

PubMed2003

Patient selection for left ventricular assist device therapy.

Patient selection for left ventricular assist device (LVAD) therapy is the most important process in obtaining a successful outcome. Evaluation requires assessing the appropriateness for device implantation based on need and risk of LVAD implant to the patient. Appropriate patients can be selected without the need for invasive hemodynamic measurements and selection can be based on symptoms, appropriateness of medical therapy, and on the need for inotropic therapy. Assessing the risk of LVAD therapy to the patient requires evaluating the degree of organ dysfunction and technical factors. Patients should be offered the option of LVAD therapy if they meet criteria for need, possess the potential for organ recovery, and have appropriate operative risk.

Heart Failure↗

PubMed2003

Surgical management of patients in the REMATCH trial.

The donor shortage makes cardiac transplantation a less than ideal treatment for end-stage heart failure. The utility of the left ventricular assist device (LVAD) as a permanent form of circulatory support has recently been established in the REMATCH (Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure) trial. In this report, we describe the surgical management of LVAD patients in REMATCH and their short-term outcomes. Between 1998 and 2001, 129 patients with end-stage heart failure, who were excluded from consideration for transplantation, were enrolled in the REMATCH clinical trial. Patients were randomized to two treatment arms: optimal medical management or HeartMate vented electric LVAD implantation. The primary end point of the study was death from any cause. Secondary end points included the incidence of serious adverse events, the duration of hospitalization, quality of life, and functional status. Sixty-eight patients received an LVAD, 55 (81%) of whom survived for longer than 1 month. The median intensive care unit and hospital lengths of stay (LOS) for those that survived at least 1 month were 15 and 34 days, respectively. Sixty-seven (99%) patients had a serious adverse event. The rates of perioperative bleeding, late bleeding, right heart failure, and sepsis were 0.42, 0.53, 0.15, and 0.53 events/patient-year, respectively. Factors predictive of a longer LOS for the implant hospitalization included sepsis, age, and late bleeding (p < 0.0001). The patients' New York Heart Association functional class improved significantly at 1 month compared with base line (p < 0.001). Functional class improved in LVAD-supported patients despite a high adverse event rate. Most adverse events occurred within 30 days of device implantation. Sepsis, age, and late bleeding were the major determinants of LOS.

Heart Failure↗

PubMed2003

Successful treatment of vancomycin resistant Enterococcus faecium mediastinitis associated with left ventricular assist devices.

We present 2 cases of vancomycin-resistant Enterococcus faecium mediastinitis associated with left ventricular assist devices in the setting of heart transplantation. Despite complicated operative courses and deep infection secondary to antimicrobial resistant organisms, both patients were successfully treated and have remained infection free in the long term.

Adult↗

PubMed2003

Extracorporeal mechanical circulatory assist.

There are currently several safe and effective options to provide temporary MCS for patients presenting with cardiogenic shock or refractory heart failure. Newer device designs are currently being developed that will increase the options available to patients. Due to the technological advancements, it will be difficult to predict what devices will ultimately prove to be the most efficacious. It is likely that a variety of devices will be necessary, depending on clinical circumstances and patient characteristics.

Equipment Design↗

PubMed2003

Roseomonas infection associated with a left ventricular assist device.

Roseomonas species have been increasingly noted as causes of human infection. We present what we believe is the first case of left ventricular assist device (LVAD) infection secondary to Roseomonas. The clinical characteristics of Roseomonas infection and the pertinent features of LVAD infection are reviewed.

Ampicillin↗

PubMed2002

Nosocomial infections in left ventricular assist device recipients.

Infection remains a serious complication of left ventricular assist device (LVAD) implantation. We performed a cohort study to assess infections among patients who underwent LVAD implantation from October 1996 through May 1999. Thirty-six LVADs were implanted in 35 patients; the mean duration (+/- standard deviation) of LVAD use was 73+/-60 days (total for all patients, 2565 days). Sixteen patients developed surgical site infections (SSIs; rate, 6.2 infections per 1000 LVAD days); 9 were deep-tissue or organ/space infections and 7 were superficial. Other infections included 7 cases of pneumonia (rate, 2.7 cases per 1000 LVAD days), 6 venous infections (rate, 2.3 per 1000 LVAD days), 2 bloodstream infections (rate, cases 0.8 per 1000 LVAD days), 3 urinary tract infections, and 2 skin and soft-tissue infections. Deep SSIs were associated with the requirement for postoperative hemodialysis (P=.02). Overall use of antibiotics was extensive, and a trend toward infection with antibiotic-resistant organisms was noted. Infections were a frequent complication of LVAD implantation. Further studies of interventions for preventing infection in LVAD recipients are warranted.

Adolescent↗

PubMed2002

Left ventricular assist device therapy improves utilization of donor hearts.

OBJECTIVES: We sought to determine the survival experiences of patients bridged to heart transplantation with either intravenous (IV) inotropes or an implantable left ventricular assist device (LVAD). BACKGROUND: Because of the operative risks of LVAD implantation and the reported lower mortality associated with inotropic therapy, bridging to heart transplantation with inotropes is thought to be the preferred treatment option. METHODS: Between April 1, 1996, and May 10, 2001, a total of 104 patients were bridged to heart transplantation with either IV inotropes (n = 38) or an implantable LVAD (n = 66; HeartMate). Survival was compared (Kaplan-Meier method) for three periods: survival to transplantation, post-transplantation survival and overall survival (i.e., survival from the onset of bridging to follow-up). RESULTS: Survival to transplantation was 81 +/- 5% at three months for the LVAD group and 64 +/- 11% for the inotrope group (p = NS). Post-transplantation survival was 95 +/- 4% at three years for the LVAD group (two deaths) and 65 +/- 10% at three years for the inotrope group (nine deaths; p = 0.007). Overall survival was 77 +/- 6% at three years for the LVAD group and 44 +/- 9% at three years for the inotrope group (p = 0.01). CONCLUSIONS: Overall survival for patients who were bridged to heart transplantation with an implantable LVAD was superior to that of patients who were bridged with inotropes. Bridging to transplantation with an implantable LVAD improves utilization of donor hearts.

Adolescent↗