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Biomedical subjects

Mario C Deng

Publications and source records attributed to Mario C Deng.

At least 19 recordsLinked to original sources
PubMed2006

Prostaglandin E1 testing in heart failure-associated pulmonary hypertension enables transplantation: the PROPHET study.

BACKGROUND: Elevated pulmonary vascular resistance (PVR) is relevant to prognosis of congestive heart failure and heart transplantation. Proof of reversibility by pharmacologic testing in potential transplantation candidates is important because it indicates a reduced probability of right ventricular failure or death in the early post-transplant period. This study aimed to clarify the possible extent of acute reversibility of elevated PVR in a large, consecutive cohort of heart transplant candidates. METHODS: This study included 208 consecutive patients (age 52 +/- 10 years, 89% men and 11% women, ejection fraction 21 +/- 9%, Vo2max 12.6 +/- 4.2 ml/kg/min) being evaluated for heart transplantation in 7 transplant centers in Germany and Switzerland. Testing was performed with increasing intravenous doses of prostaglandin E1 (PGE1; average maximum dose 173 +/- 115 ng/kg/min for at least 10 minutes) in 92 patients exhibiting a baseline PVR of > 2.5 Wood units (WU) and/or a transpulmonary gradient (TPG) of > 12 mm Hg. RESULTS: PGE1 testing lowered PVR from 4.1 +/- 2.0 to 2.1 +/- 1.1 WU (p < 0.01), increased cardiac output from 3.8 +/- 1.0 to 5.0 +/- 1.5 liters/min (p < 0.01), and decreased TPG from 14 +/- 4 to 10 +/- 3 mm Hg (p < 0.01), mean pulmonary artery pressure (PAM) from 39 +/- 9 to 29 +/- 9 mm Hg (p < 0.01) and mean pulmonary capillary wedge pressure (PCWP) from 24 +/- 7 to 19 +/- 9 mm Hg (p < 0.01). Mean aortic pressure (MAP) decreased to 85% and systemic vascular resistance (SVR) to 65% of baseline values (p < 0.01). Symptomatic systemic hypotension was not observed. For the whole population the percentage of patients with PVR > 2.5 WU was reduced from 44.2% to 10.5% with PGE1. PVR decreased in each patient; only 2 patients (1%) remained ineligible for listing because of a final PVR of > 4.0 WU. TPG, ejection fraction and male gender were independent predictors of reversibility of PVR. CONCLUSIONS: Elevated PVR in heart transplant candidates is highly reversible and can be normalized during acute pharmacologic testing with PGE1.

Adult↗
PubMed2006

The role of Staphylococcus aureus adhesins in the pathogenesis of ventricular assist device-related infections.

Ventricular assist devices (VADs) are an important form of therapy for end-stage congestive heart failure. However, infection of the VAD, which is often caused by Staphylococcus aureus, poses a major threat to survival. Using a novel in vitro binding assay with VAD membranes and a heterologous lactococcal system of expression, we identify 3 S. aureus proteins--clumping factor A (ClfA) and fibronectin binding proteins A and B (FnBPA and FnBPB) as the main factors involved in adherence to VAD polyurethane membranes. Adherence is greatly diminished by long implantation times, reflecting a change in topological features of the VAD membrane, and is primarily mediated by the FnBPA domains in the staphylococcal proteins. We also compare the adherence of S. aureus mutant strains and show that other staphylococcal components appear to be involved in adherence to VAD membranes. Finally, we demonstrate that ClfA, FnBPA, and FnBPB mediate bacterial infection of implanted murine intra-aortic polyurethane patches.

Adhesins, Bacterial↗
PubMed2006

Relationship between renal function and left ventricular assist device use.

BACKGROUND: Poor renal function may affect outcomes after left ventricular assist device (LVAD) placement. Conversely, LVADs may optimize circulation and improve renal function. METHODS: To assess the relationship between renal function and LVAD use, changes in creatinine clearances (CrCl, in mL/min) were assessed retrospectively in 220 patients who underwent LVAD placement. These patients were also divided into four groups based on CrCl quartiles (< 47, 48-68, 69-95, and > 95) and compared for outcomes post-LVAD placement. RESULTS: Eighty-four patients died on LVAD support. Survival on LVAD was worse for patients with the worst baseline CrCl (42%, 52%, 63%, and 79% for 6 month and 26%, 34%, 47%, and 66% for 12 month survival for quartiles 1-4; both p < 0.01 for trend). Adjusting for other covariates, patients in the lowest CrCl quartile were at a higher risk of dying postimplant (odds ratio 1.95, 95% confidence interval 1.14-3.63). Paired sample analysis showed the following changes in CrCl: preoperative to week 1, 77.0 +/- 46.6 to 92.1 +/- 51.1 (p < 0.01; n = 202), week 1 to 2, 89.4 +/- 49.2 to 95.2 +/- 52.4 (p = 0.01, n = 171), week 2 to 3, 107.5 +/- 58.1 to 113.7 +/- 66.1 (p = 0.16, n = 74), and week 3 to 4, 111.1 +/- 56.6 to 110.5 +/- 56.8 (p = 0.87, n = 60). For the 60 patients with baseline CrCl less than 50, CrCl increased from 36.7 +/- 9.2 to 60.1 +/- 35.5 (p < 0.01; n = 55 pairs) from preimplant to week 1. In 37 of these patients (62%) on intraaortic balloon pump support preimplant, CrCl increased from 38.4 +/- 8.2 to 67.9 +/- 40.3 mL/minute (p < 0.01) during week 1 postimplant. Recovery of renal function to CrCl greater than 50 was associated with a trend towards better 30-day survival (84% vs 66%, p = 0.09). CONCLUSIONS: Baseline poor renal function is associated with worse outcomes after LVAD implantation. However, renal function improves substantially and rapidly in post-LVAD survivors and is associated with improved outcomes. These data underscore the importance of careful patient selection for LVAD therapy.

Adult↗
PubMed2005

Nodular endocardial infiltrates (Quilty lesions) cause significant variability in diagnosis of ISHLT Grade 2 and 3A rejection in cardiac allograft recipients.

BACKGROUND: Endomyocardial biopsy is used to guide therapy after heart transplantation. An accurate and reliable diagnosis of rejection is critical for proper patient management. METHODS: A sub-set of 827 biopsies from 273 patients were identified from 8 centers participating in the Cardiac Allograft Gene Expression Observational Study. These included all biopsies graded by local center pathologists as International Society for Heart and Lung Transplantation (ISHLT) Grade 1B or higher and also randomly chosen Grade 0 and 1A biopsies. Each of these cases was reviewed in a blinded manner by 3 study pathologists in the absence of clinical data. The study pathologists were assigned an ISHLT grade and noted nodular endocardial infiltrates (Quilty lesions). RESULTS: The study pathologists were significantly more likely than local pathologists to diagnose ISHLT Grade 0, 1A and 3B rejection and significantly less likely to diagnose ISHLT Grade 1B, 2 and 3A rejection. Concordance between local and study pathologists was lowest for Grade 2 (17% agreement). Quilty lesions were noted in 3.3% of local Grade 0 cases and in 31% and 37% of local Grade 2 and 3A cases, respectively. Quilty lesions were recognized by study pathologists in 35% of local Grade 2 cases "downgraded" to Grade 0 or 1, but in only 10% of local Grade 2 cases confirmed by study pathologists. CONCLUSIONS: The greatest variability between pathologists in application of the ISHLT grading system is in Grade 2 biopsies, and Quilty lesions are a major contributing factor to the lack of concordance. Accurate application of the ISHLT grading system requires improved recognition and understanding of Quilty lesions.

Adolescent↗
PubMed2005

The economic implications of noninvasive molecular testing for cardiac allograft rejection.

Endomyocardial biopsy is the mainstay for monitoring cardiac allograft rejection. A noninvasive strategy--peripheral blood gene expression profiling of circulating leukocytes--is an alternative with proven benefits, but unclear economic implications. Financial data were obtained from five cardiac transplant centers. An economic evaluation was conducted to compare the costs of outpatient biopsy with those of a noninvasive approach to monitoring cardiac allograft rejection. Hospital outpatient biopsy costs averaged 3297 US dollars, excluding reimbursement for professional fees. Costs to Medicare and private payers averaged 3581 US dollars and 4140 US dollars, respectively. A noninvasive monitoring test can reduce biopsy utilization. The savings to health care payers in the United States can be conservatively estimated at approximately 12.0 million US dollars annually. Molecular testing using gene expression profiling of peripheral circulating leukocytes is a new technology that offers physicians a noninvasive, less expensive alternative to endomyocardial biopsy for monitoring allograft rejection in cardiac transplant patients.

Biopsy↗
PubMed2004

Left ventricular pressure and volume unloading during pulsatile versus nonpulsatile left ventricular assist device support.

BACKGROUND: Nonpulsatile axial or centrifugal pumps are the latest generation of left ventricular assist devices (LVAD). Whether left ventricular (LV) unloading and outcome in these devices is similar to pulsatile LVADs during long-term support has not been investigated. We compared LV unloading and mortality between different types of LVAD support (pulsatile versus nonpulsatile). METHODS: In 31 patients undergoing long-term LVAD implantation (nonpulsatile = 10, pulsatile = 21) preoperative and postoperative echocardiographic and hemodynamic assessment with right heart catheterization had been obtained. RESULTS: All patients had similar echocardiographic, hemodynamic, and clinical heart failure characteristics at baseline. The degree of LV pressure unloading was the same in both device types, caused by similar reduction of mean pulmonary pressure (18.6 +/- 5.1 versus 18.3 +/- 7.5 mm Hg) and pulmonary capillary wedge pressure (8.9 +/- 4.4 versus 8.0 +/- 7.0 mm Hg). Left ventricular volume unloading was pronounced with a pulsatile device owing to a statistically significant higher pump output (5.1 +/- 1.0 L/min) in comparison with nonpulsatile LVADs (3.6 +/- 0.9 L/min, p < 0.001). Echocardiographic-determined end-systolic indicators confirm this augmentation in pulsatile LVADs. Etiology or the time interval of hemodynamic reassessment had no impact in left ventricular pressure unloading, but LV volume unloading decreased between day 60 and 120 in patients with nonpulsatile LVADs. The preoperative and postoperative transplant mortality was comparable in both groups. CONCLUSIONS: Left ventricular pressure unloading is similar in patients with nonpulsatile as compared with pulsatile implantable long-term assist devices. Left ventricular volume unloading is pronounced in pulsatile LVADs.

Adolescent↗
PubMed2004

Orthotopic heart transplantation: highlights and limitations.

A little more than three decades after the successful introduction of cardiac transplantation, this revolutionary concept of advanced heart failure treatment has gained tremendous momentum and is considered the gold standard therapy in selected patients. More specific modalities of immunosuppression continue to decrease the impact of acute and chronic rejection and immunosuppression-related side effects. The success of cardiac transplantation has led to a widespread initiation of transplant programs and a run on cardiac transplantation waiting lists. The increasing gap between waiting lists and donor organ supply has stimulated research to identify those patients who benefit most from cardiac transplantation, as well as research to develop alternative therapies for advanced heart failure. Furthermore, it serves as a stimulus to address paradigmatic issues that are fundamental to modern medicine and society.

Female↗
PubMed2004

Vasoactive peptides during long-term follow-up of patients after cardiac transplantation.

BACKGROUND: Vasoactive peptides are accepted indicators of the degree of heart failure and its progression or improvement following medical therapy. Normalization of cardiac hemodynamics by cardiac transplantation (HTx) may lead to normalization of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) plasma levels shortly after the procedure. METHODS: Long-term follow-up was done for 14 consecutive patients, 12 men and 2 women, 49 years of age (range 24 to 64 years). ANP and BNP were measured by radioimmunoassay (RIA) in central venous plasma samples (before breakfast, at steady state) at the following intervals after HTx: 7 to 30 (1), 31 to 60 (2), 61 to 90 (3), 120 to 180 (4) and 210 to 365 (5) days. RESULTS: During follow-up, ANP decreased significantly within 2 months after HTx and continued of this level, whereas BNP decreased continuously without reaching normal values. The mean ratio of ANP:BNP increased from 3.23 to 8.01 during follow-up. Whereas right atrial pressure (RAP), right ventricular pressure (RVP), right ventricular end-diastolic pressure (RVEDP) and pulmonary capillary wedge pressure (PCWP) did not change during follow-up, cardiac output (CO) improved slightly, but significantly from 5.21 liters/min to 5.9 liters/min (p = 0.035). CONCLUSIONS: Normalization of left ventricular function after orthotopic HTx does not induce an early diminution of ANP and BNP plasma levels to normal concentrations. Although elevated ANP concentrations showed only minimal changes within 1 year, BNP decreased significantly as early as 2 months after HTx, without reaching normal values during the year of follow-up. Also, the ratio of ANP and BNP increased significantly from 3.23 to 8.01. These results demonstrate the contribution of other factors beyond cardiac function that determine the levels of these peptides.

Atrial Natriuretic Factor↗
PubMed2004

Under-utilization of mechanical circulatory support in Canada: why and what can be done?

In October of 2002, a workshop was held as part of the Canadian Cardiovascular Congress in Edmonton, Canada, entitled "Under-Utilization of Mechanical Circulatory Support in Canada. Why and What Can Be Done?" The workshop examined various issues related to the use of mechanical circulatory support devices in the Canadian context. Representatives from all Canadian centers with active mechanical circulatory support programs were invited to participate and participants included surgeons and cardiologists, as well as other affiliated health professionals. Opinions were solicited from the workshop participants and a series of recommendations were formulated.

Assisted Circulation↗
PubMed2004

Surrogate markers for late cardiac allograft survival.

While no definite well-validated surrogate marker for late cardiac allograft outcome is available, the early detection of cardiac allograft vasculopathy represents the 'key' candidate as an effective surrogate. Intravascular ultrasound detected intimal thickening has been noted to possess prognostic capability despite the presence of a normal coronary angiogram. Several prospective investigations have pointed to accurate thresholds of intimal thickening that are prognostically relevant and predict not only future angiographic disease but also hard allograft related endpoints including ischemic cardiac events, allograft failure, and death. Because of the resolution of intravascular ultrasound, this technique accords reproducibility and the ability to standardize the degree of intimal thickening over time. Other candidates that may serve as surrogates once appropriately evaluated include measures of allograft pump function, intragraft histology, and peripheral markers including but not limited to structural proteins (cardiac specific troponins), inflammatory markers (CRP), fibrogenic markers (TGF-beta, fibroblast growth factor), and immune markers (anti-HLA Ab and indirect alloantibodies).

Biomarkers↗