Larry O. Thompson

Degree of cardiac fibrosis and hypertrophy at time of implantation predicts myocardial improvement during left ventricular assist device support

BACKGROUND There have been increasing reports of cardiac improvement in heart failure patients supported by left ventricular assist devices (LVADs i.e.), including a number of patients who have tolerated removal of the device without the benefit of cardiac transplant. In the current study, we retrospectively investigated echocardiographic and histologic changes in patients supported by LVADs (n = 18). The goal of our study was to determine if the degree of cardiac fibrosis and myocyte size in pre-implant biopsies could predict myocardial improvement as assessed by improvements in ejection fraction (EF) during LVAD support. METHODS We determined total collagen content in myocardial biopsy specimens by a semi-quantitative analysis of positive Picro-Sirius Red-stained areas and myocyte size measurements by computerized edge detection software. RESULTS During LVAD support, 9 of the 18 patients (Group A) were distinguished by significant improvement in ejection fraction (pre <20% vs unloaded 34 +/- 5%). In addition, Group A patients had significantly less fibrosis and smaller myocytes than their Group B counterparts, whose EF did not improve. There was an inverse correlation between pre-implant biopsy collagen levels and myocyte size with increases in EF during LVAD unloading. CONCLUSIONS We found that the patients who demonstrated the greatest improvements in EF during support had less fibrosis and smaller myocytes at the time of device implantation. We propose that tissue profiling a patients pre-implant biopsy for fibrosis and myocyte size may allow stratification in Stage IV heart failure and may predict myocardial improvement during LVAD support.

Revascularization and ventricular restoration in patients with ischemic heart failure: the STICH trial

Purpose of review As techniques for the management of patients with ischemic heart failure have evolved, controversy has arisen with respect to the roles of revascularization and ventricular restoration procedures. This review addresses current thinking on the management of these patients and describes a prospective randomized trial that will have an impact on future treatment selection. Recent findings Although the basis for improved survival with coronary artery bypass grafting lies in the viability of ischemic myocardium, nuclear medicine studies and stress echocardiography have failed to adequately select for tissues that are capable of recovery. Recent studies have suggested an additional benefit to combining ventricular restoration with bypass surgery. However, the role for these techniques has not been definitively established. Summary The currently enrolling Surgical Treatment for Ischemic Heart Failure (STICH) trial promises to address these issues and thereby improve the management of patients with this disease.

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.

Betreuung von Patienten an linksventrikulären Unterstützungssystemen mittels Koordinator: Erfahrungen des Methodist DeBakey Heart Centers

ZusammenfassungHintergrundLinksventrikuläre mechanische Supportsysteme, left ventricular assist devices oder kurz LVAD, erlauben, Patientien mit terminalen Herzversagen bis zur Transplantation zu unterstützen. Dies hat positiven Einfluss zum einen auf die Überlebensrate als auch auf mögliche peri-operative Komplikationen. Wir berichten über unsere Erfahrungen mit einem LVAD-Koordinator, insbesondere hinsichtlich Patientengenesung und Inzidenz an Komplikationen.MethodikIn der Zeit vom Juni 2000 und Januar 2002 erhielten 28 Patienten mit terminaler therapierefrakterer Herzinsuffizienz ein linksventrikuläres Assist Device, 14 Patienten in der Zeit vor Einsatz eines LVAD-Koordinators und weitere 14 Patienten unter der Betreuung eines LVAD-Koordinators. Die untersuchten Kriterien waren dabei Auftreten von Infektionen, lebensbedrohlichen Thromboembolien, Blutungsereignissen und Kostenaufwand, definiert als reine Krankenhauskosten ohne Personal- und Materialkosten.ErgebnisseIn der Prä-Koordinator-Gruppe wurden 2 Patienten mit Ihrem LVAD nach Hause entlassen, 7 Patienten (50%) entwickelten eine therapiepflichtige Infektion, 5 Patienten (35%) hatten lebensbedrohliche thrombembolische Komplikationen. 6 Patienten aus dieser Gruppe wurden transplantiert und 8 Patienten verstarben an dem Unterstützungssystem, woraus sich eine Überlebensrate von 42% errechnet. In der von einem LVAD-Koordinator betreuten Patientengruppe wurden 7 Patienten mit ihrem LVAD nach Hause entlassen, 4 Patienten entwickelten Infektionen und 1 Patient cerebrale Thrombembolien mit irreversiblen neurologischen Schäden. 10 Patienten wurden transplantiert, 3 Patienten verstarben am Assist Device und 1 Patient war bei Studienende noch am Assist Device. Die Überlebensrate in dieser Gruppe war 78%.ZusammenfassungDer Einsatz eines LVAD-Koordinators für die Betreuung von an linksventrikulären Assist Devices befindlichen Patienten trug in unserem Patienten-Kollektiv zu einer höheren Überlebensrate, niedrigeren Komplikationsrate und auch niedrigeren Krankenhauskosten bei.SummaryBackgroundUse of left ventricular assist devices (LVAD) for support of endstage heart failure patients as a bridge to cardiac transplantation creates opportunities both for improved patient survival rate and for lower peri-operative complications. We investigated the effect on patient outcomes and incidence of complication of assigning an LVAD coordinator for heightened clinical monitoring and patient management in this population.MethodsBetween June 2000 and January 2002, 28 patients with terminal heart failure underwent LVAD implantation, 14 patients prior to LVAD-coordinator employment and 14 patients under supervision of the LVAD coordinator. Patients’ records were retrospectively analyzed for incidence of infection, life-threatening thromboembolic and bleeding events, and hospital charges.ResultsIn the pre-coordinator group, two patients were discharged home while on LVAD support. Seven patients (50%) developed infections requiring antibiotic treatment; five patients (35%) had severe life-threatening thromboembolic events. Six patients were transplanted and eight patients died while on LVAD support, giving an overall survival of 42% in this group. In the post-coordinator group, seven patients were discharged home while on LVAD support. Four patients developed infections, one patient had a severe life-threatening thromboembolic event. Ten patients were successfully transplanted, one patient is currently supported on the device, and 3 patients died, for an overall survival of 78% in this group.ConclusionThe use of a fulltime professional coordinator has had a beneficial impact on patient outcomes. Patient survival was improved, device-related complications were reduced and eligible patients could be discharged safely from the hospital.

Hirntodinduzierte aktivierung proinflammatorischer reaktionen in potentiellen spenderorganen

ZusammenfassungHintergrundEine Serie unspezifischer inflammatorischer Ereignisse, ausgelöst durch explosiven Hirntod, scheint in potentiellen Spenderorganen eine Reihe von funktionellen und immunologischen Veränderungen zu verursachen. Ziel dieser Studie ist es, den Verlauf pro-inflammatorischer Zytokine in Herz, Lunge und Niere hirntoter Tiere aufzuzeigen.MethodikBei 4 Hausschweinen wurde Hirntod durch akuten Druckanstieg über einen intrakraniell eingebrachten Foley- Katheter herbeigeführt. Weitere 4 Schweine wurden scheinoperiert und dienten somit als Kontrolltiere. Jedes Experiment wurde 6 Stunden nach Hirntodinduktion beendet und die Organe wurden entnommen. Wir bestimmten die mRNA-Expression für TNF-α, IL-1β und IL-6 mittels rt-PCR in Herz, Lunge und Niere. Die Ergebnisse werden als Relation der Dichtewerte der Zytokine zum Housekeeping-Gen β-actin in der Gelelektrophorese beschrieben.ErgebnisseDie 6h-Werte für IL-1β- und IL-6-mRNA waren in allen untersuchten Organen von hirntoten Tieren signifikant höher als in den von scheinoperierten. TNF-α mRNA-Expression war in Lungegewebe hirntoter Tiere ebenfalls signifikant höher, wohingegen in Herz- und Nierengewebe die Werte für TNF-α mRNA in der Hirntod-Gruppe eher niedriger waren als in der Kontrollgruppe (statistisch nicht signifikant).SchlussfolgerungExplosiver Hirntod führt zu Zytokininduktion in den peripheren Organen. Aufgrund unserer Ergebnisse schlussfolgern wir, dass es sich hierbei um eine organ-spezifische Regulation handelt.SummaryBackgroundOrgan dysfunction after explosive brain death has been well documented. In addition, a series of nonspecific inflammatory events may increase the intensity of the immunological host response. The aim of the present study was to monitor the course of proinflammatory cytokines in heart, lung and kidney after brain death induction.MethodsBrain death (BD) was induced in 4 pigs by inflation of an intracranial Foley catheter and separately 4 pigs were sham-operated. Each experiment was terminated 6 hours after brain death/sham operation and the organs were harvested. We determined the mRNA-expression for TNF-α, IL-1β and IL-6 in the heart, lung and kidney using rt-PCR techniques. The results are presented as absorbance intensity (Mean±SEM). β-actin was used for standardization.ResultsAfter 6 hours, IL-1β and IL-6 mRNA expression increased significantly in all investigated organs in the brain dead animals compared to sham-operated. TNF-α transcripts increased significantly only in lung, while in heart and kidney TNF-α mRNA tended even to lower values in brain dead animals.ConclusionBrain death was associated with an increase in mRNA concentration of IL-1β and IL-6 in lung, heart and kidney, while TNF-α mRNA expression was only up-regulated in lung. We suggest that brain death initiates a cascade of organ-specific inflammatory events that may play a crucial role in early graft dysfunction and rejection via a priming effect on the transplanted organ.

Effect of mechanical ventricular unloading on mast cells in failing myocardium

age-matched nondiabetic patients. Results: Age and gender were similar for diabetic and nondiabetics (54.6 /10.5 with 82% male versus 55.4 /10.6 with 81% male). Using Kaplan Meier analysis, there was no difference in 1, 3, 5, or 10-year survival between diabetics and nondiabetics (Log rank p 0.1682, figure), or between type 1 and type 2 diabetics (p 0.44). Diabetic males had a survival advantage over females (p 0.018). Donor CMV status (p 0.085), LVAD (p 0.975), male/female mismatch (p 0.743), obesity (p 0.202), and pretransplant creatinine of 1.5 or greater (p 0.726) did not significantly impact survival. The incidence of infection within three years was 47.8% for diabetics and 32.9% for nondiabetics (p 0.006). The overall incidence of rejection and coronary artery disease within five years was 80.1% and 26.7% for diabetics as compared to 63.6% and 27.5% for nondiabetics (p 0.374, p 0.924). Conclusion: These results demonstrate similar short and long-term survival for diabetics as compared to nondiabetics undergoing cardiac transplantation. Furthermore, the incidence of post-transplant rejection and coronary artery disease were similar. This supports proceeding with transplantation in carefully selected diabetic patients.