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1.
Am J Transplant ; 17(12): 3020-3032, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28643428

ABSTRACT

According to the Centers for Disease Control, heart failure (HF) remains a pervasive condition with high morbidity and mortality, affecting 5.8 million people in the United States and 23 million worldwide. For patients with refractory end-stage HF, heart transplantation is the "gold standard" for definitive treatment. However, the demand for heart transplantation has consistently exceeded the availability of donor hearts, with approximately 2331 orthotopic heart transplantations performed in the United States in 2015 despite an estimated 100 000 to 250 000 patients with New York Heart Association class IIIB or IV symptoms that are refractory to medical treatment, making such patients potential transplant candidates. As such, the need for mechanical circulatory support (MCS) to treat patients with end-stage HF has become paramount. In this review, we focus on the history, advancements, and current use of durable MCS device therapy in the treatment of advanced heart failure.


Subject(s)
Extracorporeal Circulation , Heart Failure/surgery , Heart Transplantation , Heart-Assist Devices , Humans
2.
Am J Transplant ; 13(5): 1203-16, 2013 May.
Article in English | MEDLINE | ID: mdl-23433101

ABSTRACT

In an open-label, 24-month trial, 721 de novo heart transplant recipients were randomized to everolimus 1.5 mg or 3.0 mg with reduced-dose cyclosporine, or mycophenolate mofetil (MMF) 3 g/day with standard-dose cyclosporine (plus corticosteroids ± induction). Primary efficacy endpoint was the 12-month composite incidence of biopsy-proven acute rejection, acute rejection associated with hemodynamic compromise, graft loss/retransplant, death or loss to follow-up. Everolimus 1.5 mg was noninferior to MMF for this endpoint at month 12 (35.1% vs. 33.6%; difference 1.5% [97.5% CI: -7.5%, 10.6%]) and month 24. Mortality to month 3 was higher with everolimus 1.5 mg versus MMF in patients receiving rabbit antithymocyte globulin (rATG) induction, mainly due to infection, but 24-month mortality was similar (everolimus 1.5 mg 10.6% [30/282], MMF 9.2% [25/271]). Everolimus 3.0 mg was terminated prematurely due to higher mortality. The mean (SD) 12-month increase in maximal intimal thickness was 0.03 (0.05) mm with everolimus 1.5 mg versus 0.07 (0.11) mm with MMF (p < 0.001). Everolimus 1.5 mg was inferior to MMF for renal function but comparable in patients achieving predefined reduced cyclosporine trough concentrations. Nonfatal serious adverse events were more frequent with everolimus 1.5 mg versus MMF. Everolimus 1.5 mg with reduced-dose cyclosporine offers similar efficacy to MMF with standard-dose cyclosporine and reduces intimal proliferation at 12 months in de novo heart transplant recipients.


Subject(s)
Graft Rejection/drug therapy , Heart Transplantation , Mycophenolic Acid/analogs & derivatives , Sirolimus/analogs & derivatives , Acute Disease , Anti-Inflammatory Agents, Non-Steroidal , Antineoplastic Agents , Asia/epidemiology , Australia/epidemiology , Biopsy , Dose-Response Relationship, Drug , Europe/epidemiology , Everolimus , Female , Follow-Up Studies , Graft Rejection/diagnosis , Graft Rejection/epidemiology , Humans , Immunosuppressive Agents/administration & dosage , Incidence , Male , Middle Aged , Mycophenolic Acid/administration & dosage , Myocardium/pathology , North America/epidemiology , Prospective Studies , Sirolimus/administration & dosage , South America/epidemiology , Treatment Outcome , Ultrasonography, Interventional
4.
Am J Transplant ; 6(6): 1377-86, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16686761

ABSTRACT

The most advantageous combination of immunosuppressive agents for cardiac transplant recipients has not yet been established. Between November 2001 and June 2003, 343 de novo cardiac transplant recipients were randomized to receive steroids and either tacrolimus (TAC) + sirolimus (SRL), TAC + mycophenolate mofetil (MMF) or cyclosporine (CYA) + MMF. Antilymphocyte induction therapy was allowed for up to 5 days. The primary endpoint of >/=3A rejection or hemodynamic compromise rejection requiring treatment showed no significant difference at 6 months (TAC/MMF 22.4%, TAC/SRL 24.3%, CYA/MMF 31.6%, p = 0.271) and 1 year (p = 0.056), but it was significantly lower in the TAC/MMF group when compared only to the CYA/MMF group at 1 year (23.4% vs. 36.8%; p = 0.029). Differences in the incidence of any treated rejection were significant (TAC/SRL = 35%, TAC/MMF = 42%, CYA/MMF = 59%; p < 0.001), as were median levels of serum creatinine (TAC/SRL = 1.5 mg/dL, TAC/MMF = 1.3 mg/dL, CYA/MMF = 1.5 mg/dL; p = 0.032) and triglycerides (TAC/SRL = 162 mg/dL, TAC/MMF = 126 mg/dL, CYA/MMF = 154 mg/dL; p = 0.028). The TAC/SRL group encountered fewer viral infections but more fungal infections and impaired wound healing. These secondary endpoints suggest that the TAC/MMF combination appears to offer more advantages than TAC/SRL or CYA/MMF in cardiac transplant patients, including fewer >/=3A rejections or hemodynamic compromise rejections and an improved side-effect profile.


Subject(s)
Cyclosporine/therapeutic use , Graft Rejection/prevention & control , Heart Transplantation/immunology , Mycophenolic Acid/analogs & derivatives , Sirolimus/therapeutic use , Adult , Antiviral Agents/therapeutic use , Cytomegalovirus Infections/prevention & control , Drug Therapy, Combination , Female , Graft Rejection/epidemiology , Heart-Lung Transplantation/immunology , Humans , Hypolipidemic Agents/therapeutic use , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Mycophenolic Acid/therapeutic use , Neoplasms/epidemiology , Patient Selection , Postoperative Complications/classification , Postoperative Complications/epidemiology , Treatment Outcome , United States
6.
Am J Transplant ; 6(1): 150-60, 2006 Jan.
Article in English | MEDLINE | ID: mdl-16433769

ABSTRACT

Rejection diagnosis by endomyocardial biopsy (EMB) is invasive, expensive and variable. We investigated gene expression profiling of peripheral blood mononuclear cells (PBMC) to discriminate ISHLT grade 0 rejection (quiescence) from moderate/severe rejection (ISHLT > or = 3A). Patients were followed prospectively with blood sampling at post-transplant visits. Biopsies were graded by ISHLT criteria locally and by three independent pathologists blinded to clinical data. Known alloimmune pathways and leukocyte microarrays identified 252 candidate genes for which real-time PCR assays were developed. An 11 gene real-time PCR test was derived from a training set (n = 145 samples, 107 patients) using linear discriminant analysis (LDA), converted into a score (0-40), and validated prospectively in an independent set (n = 63 samples, 63 patients). The test distinguished biopsy-defined moderate/severe rejection from quiescence (p = 0.0018) in the validation set, and had agreement of 84% (95% CI 66% C94%) with grade ISHLT > or = 3A rejection. Patients >1 year post-transplant with scores below 30 (approximately 68% of the study population) are very unlikely to have grade > or = 3A rejection (NPV = 99.6%). Gene expression testing can detect absence of moderate/severe rejection, thus avoiding biopsy in certain clinical settings. Additional clinical experience is needed to establish the role of molecular testing for clinical event prediction and immunosuppression management.


Subject(s)
Gene Expression Profiling , Graft Rejection/diagnosis , Heart Transplantation , Adolescent , Adult , Aged , Female , Graft Rejection/genetics , Graft Rejection/pathology , Heart Transplantation/immunology , Humans , Immunosuppression Therapy , Leukocytes, Mononuclear/chemistry , Male , Middle Aged , RNA, Messenger/analysis
7.
Am Heart J ; 142(3): 461-5, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11526359

ABSTRACT

BACKGROUND: Photopheresis was evaluated as a means of preventing restenosis on the basis of immune modulation. METHODS: This was a prospective, randomized, controlled clinical trial analyzing clinical restenosis at 6 months after percutaneous transluminal coronary angioplasty (PTCA). Seventy-eight patients with single-vessel angioplasty were randomly assigned to a control group of 41 patients and a treatment group of 37 patients. At 6 months, there were 72 evaluable patients: 39 control patients and 33 treated. Twenty-nine control patients received balloon PTCA only and 10 patients received stents. Twenty treated patients received PTCA only and 13 patients received stents. Baseline clinical characteristics of both groups were similar. The treatment group received photopheresis for a total of 5 treatments. Primary end points were death from any cause, myocardial infarction, ischemia, and repeat revascularization procedures. RESULTS: By intention-to-treat analysis, clinical restenosis occurred in 27% of control patients versus 8% of treated patients (P =.040, relative risk = 0.30). CONCLUSIONS: Photopheresis therapy in patients undergoing balloon PTCA with and without stent deployment has been shown to be effective in reducing restenosis. The use of photopheresis in such patients merits further investigation.


Subject(s)
Angioplasty, Balloon, Coronary , Coronary Disease/surgery , Photopheresis , Adolescent , Adult , Aged , Aged, 80 and over , Coronary Disease/pathology , Female , Humans , Male , Middle Aged , Myocardial Infarction , Myocardial Ischemia , Recurrence , Stents
8.
J Heart Lung Transplant ; 20(4): 449-56, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11295583

ABSTRACT

BACKGROUND: Although the left ventricular assist device (LVAD) has been increasingly used as a bridge to transplant, its effect on post-transplant outcome is uncertain. We, therefore, designed this study using the Cardiac Transplant Research Database to compare patients supported on an LVAD before transplant with those treated with intravenous inotropic medical therapy. METHODS AND RESULTS: Of the 5,880 patients transplanted between 1990 and 1997, a total of 502 received support from LVADs and 2,514 received intravenous inotropic medical therapy at the time of transplant. Kaplan-Meier analysis showed no significant difference in post-transplant survival between the LVAD and medical-therapy groups (p = 0.09). Results of a multivariate Cox regression analysis were consistent with that of the Kaplan-Meier analysis and did not identify LVAD as a significant risk factor for mortality. The percentage of patients who received LVADs as a function of total transplants increased from 2% in 1990 to 16% in 1997. Furthermore, although the number of extracorporeal LVADs remained relatively constant, the number of intracorporeal LVADs increased over time. Multivariate parametric analysis found that the risk factors for post-transplant death in the LVAD group were extracorporeal LVAD use (p = 0.0004), elevated serum creatinine (p = 0.05), older donor age (p = 0.03), increased donor ischemic time (p < 0.0001), and earlier year of transplant (p = 0.03). CONCLUSIONS: Given a limited donor supply, the intracorporeal LVAD helps the sickest patients survive to transplant and provides post-transplant outcome similar to that of patients supported on inotropic medical therapy. Therefore, patients supported on LVADs before transplant may receive the greatest marginal benefit when compared with other transplant candidates.


Subject(s)
Cardiotonic Agents/therapeutic use , Heart Transplantation , Heart-Assist Devices/adverse effects , Cardiotonic Agents/administration & dosage , Female , Heart Transplantation/adverse effects , Heart Transplantation/mortality , Humans , Injections, Intravenous , Logistic Models , Male , Middle Aged , Multivariate Analysis , Prospective Studies , Statistics, Nonparametric , Survival Analysis , Treatment Outcome
10.
Transplantation ; 71(1): 70-8, 2001 Jan 15.
Article in English | MEDLINE | ID: mdl-11211198

ABSTRACT

BACKGROUND: The widespread use of cyclosporine has improved the survival of cardiac transplant patients as a result of reduced morbidity and mortality from rejection and infection. The original oil-based form of cyclosporine demonstrated unpredictable absorption resulting in an increased frequency of acute and chronic rejection in patients with poor bioavailability. The primary end. points of the present, prospective, randomized multicenter, double-blind trial were to compare the efficacy of the micro-emulsion form of cycolsporine (CsA-NL) with the oil-based formulation as determined by cardiac allograft and recipient survival and the incidence and severity of the acute rejection episodes and to determine the safety and tolerability of CsA-NL compared with Sandimmune CsA-(SM) in the study population. The 6-month analysis of the study showed reduced number of CsA-NL patients requiring antilymphocyte antibody therapy for rejection, fewer International Society of Heart and Lung Transplantation grade > or =3A rejections in female patients and fewer infections. Our report represents the final analysis of the results 24 months after transplantation. METHODS: A total of 380 patients undergoing de novo cardiac transplants at 24 centers in the United States, Canada, and Europe were enrolled in this double-blind, randomized trial evaluating the efficacy and safety of CsA-NL versus CsA-SM. Acute allograft rejection was diagnosed by endomyocardial biopsy and graded according to the International Society of Heart and Lung Transplantation nomenclature. Kaplan-Meier analysis and Fisher's exact test were used for comparisons between groups. RESULTS: After 24 months, allograft and recipient survival were identical in both groups. There were fewer CsA-NL patients (6.9%) requiring antilymphocyte antibody therapy for rejection than in the CsA-SM-treated patient group (17.7%, P=0.002). There were fewer discontinuations of study drug for treatment failures in the CsA-NL groups (7; 3.7%) compared with the CsA-SM group (18; 9.4%, P=0.037). The average corticosteroid dose was lower in the CsA-NL group (0.37 mg/kg/day) compared with the CsA-SM group (0.48 mg/kg/day, P=0.034) over the 24-month study period. Overall, there was no difference in blood pressure or creatinine between the two study groups. CONCLUSIONS: The final results of this multi-center, randomized study of two forms of cyclosporine confirmed that there were fewer episodes of rejection requiring antilymphocyte antibodies and fewer study discontinuations for treatment failures in CsA-NL-treated patients compared to those treated with CsA-SM. The use of CsA-NL did not predispose these patients to a higher risk of adverse events.


Subject(s)
Cyclosporine/administration & dosage , Cyclosporine/pharmacokinetics , Heart Transplantation/immunology , Adolescent , Adult , Aged , Chemistry, Pharmaceutical , Emulsions/administration & dosage , Humans , Maximum Tolerated Dose , Middle Aged , Oils/administration & dosage , Therapeutic Equivalency , Time Factors
11.
Transplantation ; 70(3): 505-13, 2000 Aug 15.
Article in English | MEDLINE | ID: mdl-10949195

ABSTRACT

BACKGROUND: Adhesion of leukocytes to vascular endothelium is an early step in cardiac allograft rejection leading to migration of lymphocytes into parenchymal tissues. Cell adhesion molecule (CAM) protein expression appears to increase as a result of rejection. The relationship of CAM gene expression to rejection is less well defined. The goal of this study was to define cell adhesion molecule gene expression in relation to the presence of acute cellular rejection in endomyocardial biopsies from cardiac transplant recipients. METHODS: To quantitatively assess intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin gene expression, we developed a competitive PCR system using nonhomologous DNA fragments (MIMICs) with complementary sequences to CAM gene-specific primers as internal standards. MIMIC fragments with known concentrations were mixed in serial dilutions with constant amounts of cDNA from the biopsy specimens and amplified with common primers under the same polymerase chain reaction conditions. The relative CAM cDNA concentrations were determined by comparing the density of MIMIC to target cDNA bands on agarose gel. ICAM-1, VCAM-1, and E-selectin mRNA concentrations were analyzed from 38 cardiac transplant biopsies divided into 3 groups according to ISHLT rejection grade: group 1-grade 0 (n=13); group 2-grade 1A or 1B (n=13); group 3-grade 3A (n=12). Glyceraldehyde-3-phosphate dehydrogenase (a constitutive gene) was quantified in the same way as CAMs to normalize the relative levels of CAMs. RESULTS: The results expressed as mean (1x10(-3) pM) (+/-SEM) in groups 1, 2, and 3, respectively, were: ICAM-1; 5+/-1; 57+/-4*; 64+/-13*, VCAM-1; 0.8+/-0.1; 6+/-1**; 9+/-1*, E-selectin; 0.4+/-0.2; 0.8+/-0.2; 0.4+/-0.1 (*P<0.001 versus group 1; **P<0.01 versus group 1). CONCLUSIONS: ICAM-1 and VCAM-1 gene expression was increased during rejection in endomyocardial biopsy specimens. Competitive polymerase chain reaction can be used to quantitatively assess gene expression in biopsy specimens from patients.


Subject(s)
Cell Adhesion Molecules/genetics , Heart Transplantation/immunology , Acute Disease , Base Sequence , DNA Primers/genetics , E-Selectin/genetics , Endocardium/immunology , Endocardium/metabolism , Gene Expression , Graft Rejection/etiology , Heart Transplantation/adverse effects , Humans , Intercellular Adhesion Molecule-1/genetics , Myocardium/immunology , Myocardium/metabolism , Polymerase Chain Reaction/methods , RNA, Messenger/genetics , RNA, Messenger/metabolism , Vascular Cell Adhesion Molecule-1/genetics
12.
Chest ; 116(6): 1550-7, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10593775

ABSTRACT

STUDY OBJECTIVES: Both oxygen therapy and nasal continuous positive airway pressure (CPAP) therapy have independently been shown to be effective in the treatment of Cheyne-Stokes respiration (CSR) in patients with congestive heart failure (CHF). The purpose of this study was to compare the short-term effects of oxygen therapy and nasal CPAP therapy on CSR in a group of stable patients with severe CHF. DESIGN: Prospective, randomized, controlled trial. SETTING: University hospital. PATIENTS: Twenty-five stable patients (mean [+/- SD] age, 56 +/- 9) with CHF and a mean left ventricular ejection fraction (LVEF) of 17 +/- 0.8%. INTERVENTIONS AND MEASUREMENTS: All patients had a right heart catheterization prior to the study and an echocardiogram performed to measure LVEF. In addition, all patients had an initial sleep study to identify the presence of CSR. Sleep studies included continuous recordings of breathing pattern, pulse oximetry, and EEG. Those patients identified as having CSR were randomized to a night on oxygen therapy (2 L/min by nasal cannula) and another night on nasal CPAP therapy (9 +/- 0.3 cm H(2)O). RESULTS: Fourteen of the 25 patients (56%) studied had CSR (apnea hypopnea index [AHI], 36 +/- 7 events per hour) during their initial sleep study. Nine of the 14 patients with CSR completed the study. When compared with baseline measurements, both oxygen therapy and nasal CPAP therapy significantly decreased the AHI (from 44 +/- 9 to 18 +/- 5 and 15 +/- 8 events per hour, respectively; p < 0.05), with no significant difference between the two modalities. The mean oxygen saturation increased significantly and to a similar extent with oxygen therapy and nasal CPAP therapy (from 93 +/- 0.7% to 96 +/- 0.8% and 95 +/- 0. 7%, respectively; p < 0.05), as did the lowest oxygen saturation during the night (from 80 +/- 2% to 85 +/- 3% and 88 +/- 2%, respectively; p < 0.05). In addition, the mean percent time the oxygen saturation was < 90% also improved with both interventions (from a baseline of 17 +/- 5 to 6 +/- 3% with oxygen therapy and 5 +/- 2% with nasal CPAP therapy; p < 0.05). When compared with baseline measurements, the apnea-hypopnea length, cycle length, circulation time, and heart rate did not significantly change with either oxygen therapy or nasal CPAP therapy. Total sleep time and sleep efficiency decreased only with nasal CPAP therapy (from 324 +/- 20 to 257 +/- 14 min, and from 82 +/- 3 to 72 +/- 2%, respectively; p < 0.05). The arousal index, when compared with baseline, remained unchanged with both oxygen therapy and nasal CPAP therapy. CONCLUSION: CSR occurs frequently in stable patients with severe CHF. In addition, oxygen therapy and nasal CPAP therapy are equally effective in decreasing the AHI in those CHF patients with CSR.


Subject(s)
Cheyne-Stokes Respiration , Heart Failure/physiopathology , Oxygen Inhalation Therapy , Positive-Pressure Respiration , Sleep/physiology , Aged , Female , Humans , Male , Middle Aged , Prospective Studies , Ventricular Function, Left
13.
Transplantation ; 68(5): 663-71, 1999 Sep 15.
Article in English | MEDLINE | ID: mdl-10507486

ABSTRACT

BACKGROUND: The introduction of cyclosporine has resulted in significant improvement in the survival of cardiac allograft recipients due to decreased mortality from infection and rejection. The original oil-based cyclosporine formulation exhibits variable and unpredictable bioavailability that correlates with an increased incidence of acute and chronic rejection in those patients in whom this is most pronounced. The primary objectives of this prospective, multicenter, randomized, double-blind study in cardiac transplant patients were: to compare the efficacy of cyclosporine microemulsion (CsA-NL) with oil-based cyclosporine (CsA-SM) as measured by cardiac allograft and recipient survival and the incidence and severity of acute rejection episodes; and to assess the safety and tolerability of CsA-NL compared with CsA-SM in this population. This report represents the analysis of results 6 months after transplantation. METHODS: A total of 380 patients undergoing their first cardiac transplant at 24 centers in the United States, Canada, and Europe were enrolled in this double-blind, randomized trial examining the safety and efficacy of CsA-NL versus CsA-SM. Rejection was diagnosed using endomyocardial biopsy and were graded according to standardized criteria of the International Society of Heart and Lung Transplantation (ISHLT). Clinical parameters were monitored during the study. Survival and freedom from were used for analysis as was Fisher's exact test for comparisons between groups. RESULTS: At 6 months after transplantation, allograft and patient survival were the same for both groups. The frequency of ISHLT grade 3A or greater episodes in the two groups was identical. Fewer CsA-NL patients (5.9%) required antilymphocyte antibody (ATG or OKT-3) therapy for rejection compared with the CsA-SM-treated patients (14.1%, P=0.01). Females with ISHLT rejection grade > or = 3A treated with CsA-NL had a 46% lower incidence of rejection compared with the CsA-SM-treated group (31.3% vs. 57.6%, P=0.032). Fewer infections were seen in the CsA-NL. With the exception of baseline and 1 week posttransplant creatinines which were higher in the CsA-NL group, the overall creatinine was not significantly different between the two groups. CONCLUSIONS: This multicenter, randomized study of cardiac transplant recipients documented less severe rejection (in particular those requiring antibody therapy) and a lower incidence of infection in CsA-NL-treated patients. Results from the female subgroup analysis suggest that the improved bioavailability of CsA-NL might reduce the frequency of rejection episodes in female patients. The use of CsA-NL was not associated with an increased risk of adverse events.


Subject(s)
Cyclosporine/administration & dosage , Heart Transplantation , Immunosuppressive Agents/administration & dosage , Adolescent , Adult , Aged , Cyclosporine/adverse effects , Cyclosporine/therapeutic use , Double-Blind Method , Emulsions , Female , Graft Rejection/physiopathology , Humans , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Oils , Postoperative Complications , Safety , Time Factors , Treatment Outcome
14.
Am J Cardiol ; 84(8): 894-9, 1999 Oct 15.
Article in English | MEDLINE | ID: mdl-10532506

ABSTRACT

Milrinone is a phosphodiesterase inhibitor that has been shown to improve hemodynamic parameters in patients with class III to IV heart failure when administered intravenously for < or =48 hours. This study examines the tolerability of long-term intravenous milrinone therapy and assesses its utility in allowing upward titration of oral vasodilator agents. A retrospective review of hospital records identified 63 patients who underwent hemodynamic monitoring and received intravenous milrinone for >24 hours in a critical care setting. Hemodynamics and medications were recorded before and after 24 hours of milrinone therapy. Additional medications, as well as any adverse events, were recorded throughout milrinone therapy. The mean dose of milrinone was 0.43 +/- 0.10 microg/kg/min, with a mean duration of 12 +/- 15 days (range 1 to 70). Therapy was continued for >48 hours in 89% of patients. After 24 hours of milrinone therapy, patients exhibited significant improvements in pulmonary artery pressures, pulmonary capillary wedge pressures, and cardiac index. When compared with baseline, significantly more patients received angiotensin-converting enzyme (ACE) inhibitors after 24 hours of milrinone and at the end of milrinone therapy (67% vs 86%, p <0.01). Likewise, significantly more patients also received oral hydralazine and/or nitrates at the end of milrinone therapy (38% vs 65%, p <0.01) when compared with baseline. The mean doses of most oral medications at the 3 time periods were similar. The ACE inhibitor dose was significantly higher at the end of milrinone therapy when compared with baseline, and hydralazine dose was significantly higher at the end of therapy when compared with 24 hours. Few adverse effects were noted, with only 10% of patients experiencing symptomatic ventricular tachycardia and 2 patients with significant hypotension requiring discontinuation of the drug. The adverse events were similar in the group of patients who received milrinone for > or =7 days compared with the entire cohort. Milrinone was well tolerated over the long term in a controlled inpatient setting, and allowed uptitration of oral vasodilator therapy.


Subject(s)
Angiotensin-Converting Enzyme Inhibitors/administration & dosage , Heart Failure/drug therapy , Hemodynamics/drug effects , Milrinone/administration & dosage , Phosphodiesterase Inhibitors/administration & dosage , Administration, Oral , Chi-Square Distribution , Drug Administration Schedule , Female , Heart Failure/physiopathology , Humans , Infusions, Intravenous , Male , Middle Aged , Retrospective Studies , Statistics, Nonparametric , Treatment Outcome
15.
Curr Opin Cardiol ; 14(2): 151-4, 1999 Mar.
Article in English | MEDLINE | ID: mdl-10191974

ABSTRACT

Cardiac transplantation has become the therapy of choice for the treatment of end-stage congestive heart failure. One of the major problems after cardiac transplantation is acute cellular rejection. The diagnosis of rejection is crucial to the management of transplant patients because rejection must be successfully diagnosed and reversed. Endomyocardial biopsy is the major method for detecting cardiac transplant rejection; however, this approach is invasive and is associated with morbidity and mortality. One noninvasive approach for detecting rejection is to monitor changes in the intramyocardial electrograms using pacemakers. Changes in the ventricular evoked response amplitude (VERA) obtained during ventricular pacing have been correlated with the presence of acute cellular rejection in both single center studies in Europe and a multicenter trial in five transplant centers in the United States. Given the high negative predictive value for the VERA, this approach may provide a screen to determine if individual patients require more invasive procedures such as endomyocardial biopsy and may aid in reducing the number of biopsies needed.


Subject(s)
Electrophysiology/methods , Graft Rejection/diagnosis , Heart Transplantation , Graft Rejection/physiopathology , Humans , Pacemaker, Artificial , Predictive Value of Tests , Reproducibility of Results
16.
N Engl J Med ; 339(24): 1744-51, 1998 Dec 10.
Article in English | MEDLINE | ID: mdl-9845709

ABSTRACT

BACKGROUND: Photopheresis is an immunoregulatory technique in which lymphocytes are reinfused after exposure to a photoactive compound (methoxsalen) and ultraviolet A light. We performed a preliminary study to assess the safety and efficacy of photopheresis in the prevention of acute rejection of cardiac allografts. METHODS: A total of 60 consecutive eligible recipients of primary cardiac transplants were randomly assigned to standard triple-drug immunosuppressive therapy (cyclosporine, azathioprine, and prednisone) alone or in conjunction with photopheresis. The photopheresis group received a total of 24 photopheresis treatments, each pair of treatments given on two consecutive days, during the first six months after transplantation. The regimen for maintenance immunosuppression, the definition and treatment of rejection episodes, the use of prophylactic antibiotics, and the schedule for cardiac biopsies were standardized among all 12 study centers. All the cardiac-biopsy samples were graded in a blinded manner at a central pathology laboratory. Plasma from the subgroup of 34 patients (57 percent) who were enrolled at the nine U.S. centers was analyzed by polymerase-chain-reaction amplification for cytomegalovirus DNA. RESULTS: After six months of follow-up, the mean (+/-SD) number of episodes of acute rejection per patient was 1.44+/-1.0 in the standard-therapy group, as compared with 0.91+/-1.0 in the photopheresis group (P=0.04). Significantly more patients in the photopheresis group had one rejection episode or none (27 of 33) than in the standard-therapy group (14 of 27), and significantly fewer patients in the photopheresis group had two or more rejection episodes (6 of 33) than in the standard-therapy group (13 of 27, P=0.02). There was no significant difference in the time to a first episode of rejection, the incidence of rejection associated with hemodynamic compromise, or survival at 6 and 12 months. Although there were no significant differences in the rates or types of infection, cytomegalovirus DNA was detected significantly less frequently in the photopheresis group than in the standard-therapy group (P=0.04). CONCLUSIONS: In this pilot study, the addition of photopheresis to triple-drug immunosuppressive therapy significantly decreased the risk of cardiac rejection without increasing the incidence of infection.


Subject(s)
Graft Rejection/prevention & control , Heart Transplantation , Immunosuppressive Agents/therapeutic use , Photopheresis , Combined Modality Therapy , Cytomegalovirus Infections/diagnosis , Cytomegalovirus Infections/epidemiology , Female , Humans , Immunosuppression Therapy/methods , Incidence , Infections/epidemiology , Male , Middle Aged , Survival Analysis
18.
Ann Thorac Surg ; 65(1): 88-94, 1998 Jan.
Article in English | MEDLINE | ID: mdl-9456101

ABSTRACT

BACKGROUND: The effect of donor and recipient gender on the outcome of heart transplantation (HT) remains uncertain. METHODS: One hundred seventy-four patients who underwent HT were divided into four groups according to donor and recipient gender. Group A consisted of 81 men who received male donor hearts, group B of 18 women who received female donor hearts, group C of 21 women who received male donor hearts, and group D of 54 men who received female donor hearts. All patients were treated by the same group of surgeons according to standard HT protocols. Comparisons were made between groups with regard to short- and long-term outcomes. RESULTS: Donor gender and recipient gender did not affect outcomes significantly. Overall, donor-recipient gender mismatching significantly increased the number of rejection episodes and reduced creatinine clearance, survival, and censored survival in the first year after HT (p < 0.05). More specifically, among female recipients, donor-recipient gender mismatching significantly increased the number of rejection episodes and decreased creatinine clearance in the first year after HT (p < 0.05); among male recipients, donor-recipient gender mismatching significantly reduced 1-year survival and censored survival to date after HT (p < 0.05). CONCLUSIONS: Donor-recipient gender matching plays a significant role in determining HT outcomes.


Subject(s)
Heart Transplantation , Adult , Creatinine/metabolism , Female , Graft Rejection , Hemodynamics , Humans , Male , Middle Aged , Sex Factors , Tissue Donors , Treatment Outcome
19.
J Heart Lung Transplant ; 16(8): 813-21, 1997 Aug.
Article in English | MEDLINE | ID: mdl-9286773

ABSTRACT

BACKGROUND: The natural history of patients experiencing hemodynamic compromise with rejection has been incompletely characterized. This multiinstitutional study examined the outcome of such episodes, particularly with regard to the extent of cellular infiltrate on the index endomyocardial biopsy. METHODS: From January 1, 1990, through June 30, 1994, 3367 patients in the Cardiac Transplant Research Database experienced 4137 episodes of rejection. Severe hemodynamic compromise occurred in approximately 5% of the rejection episodes, and this proportion remained relatively constant over time. RESULTS: Recipient risk factors for rejection with severe hemodynamic compromise included black race, female recipient sex, and diabetes. The 3-month actuarial survival rate was 60% after rejection with severe hemodynamic compromise versus 95% after rejection with no or mild compromise. Low initial biopsy score conferred a higher early survival, but a lower survival at 2 years after rejection with severe hemodynamic compromise. Among patients who survive an initial rejection episode with severe hemodynamic compromise, survival at 2 years after an episode was 46% among those who had a low initial biopsy score versus 84% with a high biopsy score. CONCLUSIONS: Rejection with hemodynamic compromise, although rare, represents a major complication of heart transplantation with a poor long-term outcome. Survivors of hemodynamically compromising rejection episodes associated with low biopsy scores in the International Society for Heart and Lung Transplantation grading system have a significantly worse long-term outcome than survivors of episodes associated with high scores. These findings suggest that immunologic mechanisms other than lymphocytic infiltration of the cardiac allograft are important and distinct causes of allograft dysfunction.


Subject(s)
Endomyocardial Fibrosis/pathology , Graft Rejection/pathology , Heart Failure/pathology , Heart Transplantation/pathology , Hemodynamics/physiology , Actuarial Analysis , Adult , Biopsy , Black People , Cause of Death , Endocardium/pathology , Endomyocardial Fibrosis/mortality , Female , Graft Rejection/mortality , Heart Failure/mortality , Heart Transplantation/mortality , Humans , Male , Middle Aged , Myocardium/pathology , Risk Factors , Survival Rate
20.
Ann Thorac Surg ; 64(1): 142-7, 1997 Jul.
Article in English | MEDLINE | ID: mdl-9236350

ABSTRACT

BACKGROUND: Left ventricular assist devices (LVADs) are being used as bridges to heart transplantation (HT). Infection of the LVAD in this patient population represents a serious complication, as simple LVAD removal or delaying HT may result in death. To improve outcomes in this group of patients, we performed HT in the presence of LVAD infection. METHODS: Eighteen patients underwent LVAD implantation followed by HT. Ten underwent HT in the absence of LVAD infection (group 1); and 8, in the presence of LVAD infection (group 2). All patients were treated similarly except for modification of immunosuppression in group 2 patients. RESULTS: Infectious and noninfectious complications were equivalent between the two groups. There was no difference between groups in regard to intraoperative deaths (one versus none), long-term survival (8/10 versus 7/8), wound complications (three versus none), and mean length of hospital stay after HT (21 versus 26 days). CONCLUSIONS: Patients with LVAD infection are too seriously ill to allow LVAD removal or delay of HT. Transplantation in the face of infection is an effective treatment option.


Subject(s)
Heart Diseases/surgery , Heart Transplantation , Heart-Assist Devices , Prosthesis-Related Infections/surgery , Heart Diseases/complications , Humans , Immunosuppression Therapy , Immunosuppressive Agents/therapeutic use , Prosthesis-Related Infections/complications , Retrospective Studies , Survival Analysis
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