Open heart surgery in patients with end-stage renal failure: fifteen-year experience.

OBJECTIVE: Risk factors and results of cardiac surgery with cardiopulmonary bypass (CPB) in hemodialysis-dependent renal failure patients at our center were evaluated. METHODS: Out of 16,425 patients undergoing open heart surgery with CPB at our center between January 1991 and April 2006, 91 (0.6%) experienced hemodialysis-dependent end-stage renal failure. Preoperative, operative, and postoperative findings of two groups of patients were evaluated: those with normal renal function (control group) and those with chronic renal failure undergoing regular hemodialysis (HDRF group). Survival analyses of the hemodialysis group of patients were performed. RESULTS: In the hemodialysis group, 54 (59.3%) patients underwent coronary artery surgery, 31 (34.1%) patients had valve surgery, four (4.4%) patients had aortic surgery, and two others (2.2%) experienced concomitant coronary and peripheral artery surgery. CPB and aortic cross-clamping (ACC) times were longer in the HDRF group (p=0.000 and 0.002, respectively). There was no significant difference between the two groups with regard to either reoperations, infections, pulmonary and gastrointestinal system complications, or cerebrovascular event parameters (p=0.167, 0.341, 1.000, 1.000, and 1.000, respectively). There was no difference between groups in the postoperative development of low cardiac output (p=0.398). The early mortality rate was 7.7% (seven patients) in the HDRF group and 4.8% (780 patients) in the controls (p=0.211). The actuarial survival rates in HDRF survivors at one, two, three, four, five, and ten years were overall 86%, 80%, 68.1%, 45.4%, 20%, and 6.8%, respectively. CONCLUSIONS: Open heart surgery in hemodialysis patients is associated with a higher incidence of risks, but can be performed with acceptable operative complications and mortality with an effective hemodialysis program.

Placement of a left ventricular assist device in a patient with dextrocardia.

Dextrocardia most commonly presents in the setting of situs inversus, but it may occur as an isolated anomaly with normal position of the abdominal organs. Herein we present a 54-year-old man with ischemic cardiomyopathy and dextrocardia with normal position of the abdominal organs who presented with an exacerbation of congestive heart failure requiring inotropic support as well as mechanical ventilation. An implantable, wearable left ventricular assist device was placed in this patient to allow for ambulation and eventual discharge home. The patient survived 4 months before he developed pneumonia and expired.

Role of mast cells and their mediators in failing myocardium under mechanical ventricular support.

BACKGROUND: Mast cells have been implicated in tissue remodeling and fibroblast stimulation. We explored the effect of mechanical support by left ventricular assist device (LVAD) in failing myocardium and looked into grade and distribution of interstitial fibrosis, mast cell density, mast cell phenotypes and basic fibroblast growth factor (bFGF) expression pre- and post-LVAD. METHODS: Myocardial tissue was obtained from 20 patients with end-stage cardiomyopathy at the time of LVAD implantation and LVAD removal and from 7 donor hearts not used for transplantation. Tissue sections were stained for mast cells using tryptase as a marker and the myocardial fibrosis was measured. Double staining for tryptase and chymase was performed for detection of chymase-positive mast cells. Fluorescent microscopy showed the relationship of mast cells to bFGF, and bFGF expression was quantified by Western blot. RESULTS: There was a significant increase in mast cells in heart failure vs normal myocardium. A secondary increase in mast cells occurred after long-term (>40 days) support compared with matched pre-LVAD samples (mean +/- SEM; 57.4 +/- 8.6 cells/10 fields vs 45.1 +/- 7.6 SEM cells/10 fields, p < 0.01). The secondary increase in mast cells was associated specifically with an increase in chymase-negative mast cells (p < 0.01). These findings are statistically significant with concurrent decreased expression of bFGF and decreased fibrosis in the same patient tissues (p < 0.01). CONCLUSIONS: We suggest that, under long-term support, there is a change in phenotypic expression in mast cells, which can alter fibroblast functions. The decreased myocardial bFGF levels might be the result of these phenotypically altered mast cells.

What price support? Ventricular assist device induced systemic response.

Use of ventricular support systems has been associated with myriad systemic complications. Engendered by the blood-biomaterial interface of a unique host/device relationship, these complications include diverse humoral dyscrasias that frequently culminate in episodes of bleeding, hemolysis and thrombogenicity, heightened susceptibility to inflammation and infection, and transient immunal compromise. Recent endeavor in biocompatibility research has served to illustrate the critical role played by cellular, humoral, and neurohormonal components in regulating cytokine expression and has provided insight into the complexities involved in such biomechanical juxtapositions. The following is intended as a review of current literature attempting to address the many aspects of this host/device interaction and their consequences for the supported patient.

End-stage heart failure with multiple intracardiac thrombi: a rescue strategy.

The use of ventricular assist devices as a bridge to transplantation has become a widely used option for patients with end-stage heart failure. In contrast to total artificial hearts, ventricular assist devices support the failing heart by bypassing one or both ventricles. In certain cases (myocardial tumors, graft failure, transplant rejection, endocarditis, intracardiac thrombus formation), however, it may be advantageous to excise the heart and replace it with an artificial device. Total artificial hearts are intracorporeal devices designed for this purpose. Unfortunately, some patients are too small or are, for other reasons, ineligible for a total artificial heart. We describe the case of a 55-year-old woman who had ischemic cardiomyopathy and thrombus formation in all 4 cardiac chambers. To reduce the risk of thromboembolic events, we elected to replace her heart completely with 2 extracorporeal ventricular assist devices. The heart was excised via a median stemotomy approach, and the outflow cannulae (from device to patient) were connected to both atrial remnants. The 2 inflow cannulae (from patient to device) were anastomosed end-to-end to the aorta and the pulmonary artery, respectively. After attaining a flow of more than 5 L, the 2 extracorporeal assist devices effectively and efficiently performed the work of the native heart. Thus re-established, organ perfusion was improved by this mechanically driven circulation, as signified by an initial decrease in creatinine and blood urea nitrogen levels. The patient, however, did not recover from postoperative neurological dysfunction and died of respiratory insufficiency and multiple-organ failure on the 26th postoperative day.

Organ-specific regulation of pro-inflammatory molecules in heart, lung, and kidney following brain death.

BACKGROUND: Nonspecific inflammatory events following brain death may increase the intensity of the immunological host response. The present study investigated the course of pro-inflammatory molecules in heart, lung, kidney, and plasma after brain death induction. MATERIALS AND METHODS: Brain death was induced in five pigs by inflation of an intracranial Foley catheter and five pigs were sham-operated as controls. Each experiment was terminated 6 h after brain death/sham operation and the organs were harvested. We measured the mRNA and protein levels for TNF-alpha, IL-1beta, and IL-6 in heart, lung, kidney, and plasma. Additionally, the mRNA expression for IL-6R, ICAM-1, MCP-1, and TGF-beta was determined in each organ. RESULTS: After 6 h, the plasma cytokine levels were higher in the brain-dead animals than in the sham-operated. In heart, lung, and kidney there was an increase in IL-6 and IL-1beta following brain death, while TNF-alpha was up-regulated in lung only (P < 0.05). MCP-1 and TGF-beta were significantly higher in heart and lung and IL-6R increased in heart after brain death (P < 0.05). CONCLUSIONS: Brain death was associated with non-uniform cytokine expression patterns in the investigated organs. These expression patterns may cause variable pro-inflammatory priming resulting in different degrees of damage and explain the organ-specific variation in outcomes after transplantations.

Plasma neurohormone levels correlate with left ventricular functional and morphological improvement in LVAD patients.

OBJECTIVE: Brain natriuretic peptide (BNP) and endothelin-1 (ET-1) have been shown to be markers of left ventricular (LV) function. To determine the feasibility of using serial assays of these neurohormones in the assessment of cardiac status in the left ventricular assist device (LVAD) setting, we examined the relationship between LV function, myocardial morphology, and plasma levels of these hormones in LVAD recipients. METHODS: Plasma BNP and ET-1 levels were serially assayed in 19 end-stage congestive heart failure (CHF) patients before and after LVAD implantation with various devices (i.e., MicroMed DeBakeyVAD/DVAD, Novacor/NVAD, TCI Heartmate/TCI, Thoratec/TVAD). Echocardiography performed correspondingly at the time points of the hormonal assays and immunohistochemical collagen staining of left ventricular tissue samples, derived from six non-failing hearts as well as from LVAD patients at the time of device insertion and removal, were then contrasted. Patients were grouped according to device used and etiology of heart disease (ischemic or dilated cardiomyopathy, ICM/DCM). RESULTS: LVAD therapy significantly improved LV ejection fraction (EF%: 21 +/- 3.8% to 28.11 +/- 3.57%), cardiac output (CO: 3.49 +/- 1.3 to 7.3 +/- 0.2 l/m), and left ventricular end-diastolic diameter (LVEDD: 6.68 +/- 0.92 versus 4.79 +/- 1.54 cm, P < 0.0001) in all patients. Absolute BNP and ET-1 plasma levels remained significantly lower in all patients after LVAD implantation (both P < 0.001). The NVAD group exhibited the most BNP reduction and EF% increase (P < 0.0004 and P < 0.038, respectively). Average collagen levels were reduced in all patients (P < 0.0005). Among the devices, the NVAD group demonstrated the most evident change (P < 0.0036), while there was comparable reduction in the DCM and ICM groups (both P < 0.03). In general, postoperative BNP and ET-1 trends exhibited a notable parallelism with both manifesting bi-phasic tendencies and an inverse proportionality to corresponding EF% measurements. CONCLUSIONS: Device selection appears to influence the cardiac morphological and neurohormonal expressive tendencies exhibited by recipients. Plasma BNP and ET-1 levels correlate with both LV function and myocardial morphological improvement. Alterations in the levels of these hormones during LVAD support may be real-time indicators of prevailing myocardial autocrine/paracrine activity and as such may be of potential use in future algorithms of cardiac assessment and therapeutic decision-making with regard to transplant urgency and/or possible device explantation.

Interaction between isolated human myocardial mast cells and cultured fibroblasts.

INTRODUCTION: Previously, we reported an increase in interstitial collagen and total mast-cell numbers in heart failure versus normal myocardium. A secondary increase, primarily in chymase-negative mast cells, occurred following LVAD support compared to matched pre-LVAD tissue samples and was associated with a decrease in interstitial collagen and bFGF. To further elucidate the changes in interstitial collagen, we investigated the direct interaction between mast cells, isolated from failing myocardium with or without previous LVAD support, and human fibroblasts in a coculture model. Additionally, the expression of HSP-47, the pro-collagen-specific chaperone protein, was determined in the particular myocardium. MATERIALS AND METHODS: Myocardial tissue was obtained from 10 patients with end-stage dilated cardiomyopathy (DCM) at the time of transplantation. Five patients were transplanted following LVAD support, five patients without previous LVAD support. Mast cells were isolated according to a standard protocol, including collagenase digestion and cell separation. The isolated mast cells were co-cultured with human fibroblasts for 12 h, with or without stimulation of degranulation, and protein synthesis was measured by [(3)H]-proline incorporation. HSP-47 immunostaining was performed in the different myocardial samples and the positive cells were quantified. RESULTS: Stimulated mast cells isolated from DCM tissue (without previous LVAD support) caused a 92% increase in [(3)H]-proline incorporation and consequently in protein production in fibroblasts compared to mast-cell free culture (P < 0.01), while conversely stimulated mast cells isolated from LVAD supported myocardium decreased the [(3)H]-proline incorporation by 63% (P < 0.01) below baseline. Nonstimulated mast cells did not significantly alter the protein production over baseline. There was also a significant increase in the number of HSP-47-positive cells in DCM myocardium compared to normal (P < 0.01) and there was a shift toward normal after LVAD support (P < 0.01). CONCLUSION: We demonstrate that fibroblast protein production in vitro is significantly altered by mast cells and that the direction of change is dependent on whether myocardium was supported by LVAD. We suggest that under long-term LVAD support there is a phenotypic alteration in myocardial mast cells, which leads to a change in concentration and/or composition of mediators, capable of re-remodeling the myocardial matrix.