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Purpose: To review the risk factors, clinical presentation, diagnosis, and treatment of nonvalvular infections of the cardiovascular system.Data Sources: A MEDLINE search of English-language articles from 1966 to 1993 relating to myocardial abscesses, mural endocarditis, infective endarteritis and mycotic aneurysms, infection of pacemakers and implantable defibrillators, prosthetic vascular graft infections, and infected atrial myxomas; manual review of article bibliographies.Study Selection and Data Extraction: Case series and single reports, prospective and retrospective clinical studies, autopsy studies, and reviews were selected if they contained sufficient information about the prevalence, clinical manifestations, microbiologic features, management, and outcome of nonvalvular cardiovascular infections.Results: Nonvalvular infections of the cardiovascular system most commonly occur on previously damaged endocardium or vascular intima and are usually associated with intravascular devices such as graft material or pacemakers. Rarely, they can involve primary cardiac tumors such as myxomas. Most patients affected are beyond the fifth decade of life. Risk factors include cardiovascular disease, diabetes mellitus, and malignancy. The sexes are affected equally. The clinical presentations of nonvalvular endovascular infections are subtle and diagnoses are difficult to make, often requiring not only a high index of suspicion but also the use of sophisticated radiologic techniques. Hence, for many of these infections, the diagnosis is made late in the course of the infection, and survival rates are poor. Complications include peripheral embolization, cardiac rupture, vascular aneurysm rupture, and pericarditis. Therapy frequently involves surgical intervention in addition to the use of antibiotics.Conclusions: Although uncommon, nonvalvular infections of the cardiovascular system will increase in frequency as the use of implantable devices and prosthetic materials increases in the elderly. Studies are needed to determine the most appropriate diagnostic methods, treatment regimens, and methods for prevention of these infections. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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.

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.

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.

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.

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.