H. Müller

Intramyocardial Electrogram Variability in the Monitoring of Graft Rejection After Heart Transplantation

The ventricular evoked response is a well‐standardized electrophysiological signal that can be used for noninvasive, long‐term cardiac transplant monitoring. Rejection‐sensitive and infection‐specific parameters extracted from intramyocardial electrograms correlate with clinical results. The influences of pacing rate, transition from intrinsic to paced rhythm and positional changes on the diagnostic parameters were studied. Increasing the pacing rate shortened the ventricular evoked response and directly influenced the infection specific parameter. The rejection‐sensitive parameter remained stable at pacing rates between 100 and 120 beats/min. Measurements made immediately after the patient assumed a supine position and after switching to paced rhythm showed a decrease in the rejection‐sensitive parameter. A change in position from supine to upright did not influence the rejection‐sensitive parameter, but higher values were measured after returning to the supine position. In conclusion, noninvasive recordings of the ventricular evoked response for monitoring of cardiac allograft should be done at the same time of day, at the same pacing rate, and with the patient resting for at least 5 minutes before measurements are made.

Definitions of cytomegalovirus disease after heart transplantation: Antigenemia as a marker for antiviral therapy

In this prospective study, cytomegalovirus (CMV) antigenemia was defined as the marker for initiation and episodes of antigenemia as the indicator for the duration of antiviral therapy (CMV hyperimmune globulin and ganciclovir). The CMV antigenemia assay and CMV-specific IgM and IgG antibody tests were used to monitor CMV infection in 22 heart transplant recipients who, between October 1992 and July 1994, were followed up for 6 months. A total of 178 out of 627 antigenemia assays tested positive. The highest number of positive cells was greater after primary infection than after either reactivation (43.3 vs 0.3; P<0.01) or reinfection (43.3 vs 9.3; P=NS). Sixty episodes of antigenemia were observed. More episodes of antigenemia were seen after primary infection than after either reactivation (4.6 vs 0.2; P<0.01) or reinfection (4.6 vs 2.2; P=NS). The detection of antigenemia indicated the initiation of antiviral therapy within 24 h after the blood sample was harvested. Therapy was stopped immediately after a subsequent negative result became available. Our experience indicates that antigenemia directed antiviral therapy prevents CMV disease after primary and secondary infection in heart transplant recipients.

Intramyocardial electrograms for non-invasive rejection monitoring: initial experience with an infection-specific parameter.

Abstract Non‐invasive rejection monitoring based on the analysis of paced intramyocardial electrograms enables repeated or even daily graft surveillance. The rejection‐sensitive parameter is calculated from the maximum slope of the descending part of the t wave. Biopsy‐proven rejection grade 2 or higher (ISHLT classification) can safely be detected. Nevertheless, infection influences the rejection‐sensitive parameter in the same manner as does rejection (99% negative predictive value for rejection grade 2 or higher, 17 % positive predictive value). We defined the infection‐specific parameter as the time on the O line between the pacemaker stimulus and the crossover with the maximum slope of the descending part of the t wave. Patients were classified prospectively according to infection status: patients without infection and those with clinically apparent infection. Patients with clinically apparent infections had a significantly longer infection‐specific parameter. A simultaneous decrease of the rejection‐sensitive parameter and an increase in the infection‐specific parameter was observed during clinical infection; a decrease in the rejection‐sensitive parameter and no changes in the infection‐specific parameter were observed during rejection. This preliminary analysis revealed that discrimination of rejection and infection might be possible by the analysis of intramyocardial electrograms.

Prostaglandins in Heart Transplantation

Heart transplant recipients with secondary pulmonary hypertension (PH) are prone to acute right ventricular (RV) graft failure after orthotopic heart transplantation (oHTX). A suitable donor heart of a healthy individual is not adapted to elevated RV afterload caused by PH. In contrast, the majority of potential heart transplant recipients suffer from chronic left ventricular (LV) failure. LV insufficiency requires elevated filling pressures to maintain cardiac output (CO), (LV backwards failure) and causes systemic hypotension (LV forward failure) which induces systemic and pulmonary vasoconstriction. This increases systemic (SVR) and pulmonary vascular resistance (PVR), induces RV hypertrophy and secondary PH. After oHTX, the unadapted transplanted RV is exposed to the recipients PVR, RV afterload mismatch results in acute RV failure when the patient is weaned from cardiopulmonary bypass. RV volume overload, dilatation and structural damage are followed by RV failure and death. The preoperative estimation of PVR and of the reactivity of the pulmonary vascular bed to pulmonary vasodilators permits the selection of patients with reversible PH that are still suitable for oHTX. Many attempts failed to define a clear borderline beyond which oHTX is not feasible. In fact, RV failure after oHTX is caused by both, the elevated RV afterload of the recipient and by insufficient RV performance. Reduction of RV afterload by pulmonary vasodilator therapy reduces the risk of RV failure resulting from RV forward failure. The risk of inadequate myocardial function remains.

Management of complications after varicoportal anastomosis in liver transplantation

ZusammenfassungDie Pfortaderthrombose galt lange Zeit als relative Kontraindikation zur Lebertransplantation. Die intraoperative Diagnose machte aufwendige und risikoreiche chirurgische Maßnahmen nötig, welche mit einer erhöhten Mortalität und Morbidität verbunden waren. Wir präsentieren einen Fallbericht mit intraoperativ diagnostizierter Pfortaderthrombose bei Lebertransplantation und einen risikoärmeren Lösungsansatz in dem eine varikoportale Anastomose durchgeführt wurde. Postoperative Komplikationen waren Ascites und eingeschränkte Nierenfunktion. Der Aszites konnte konservativ therapiert werden und war nach einem Monat rückläufig. Die Nierenfunktion verbesserte sich, eine Dialyse war nicht indiziert. Nach einem halben Jahr hatte der Patient eine normale Leber- und Nierenfunktion.SummaryThe presence of portal vein thrombosis is a potential limitation for liver transplantation. An intraoperative diagnosis is linked to extensive surgical treatment and massive postoperative complications and mortality. We present a surgical less risky method for the treatment of intraoperatively diagnosed portal and mesenteric vein thrombosis that served as salvage therapy for a patient who underwent liver transplantation in our centre. Postoperative complications were ascites and renal failure. Persistent ascites required repeated paracentesis during the first month after liver transplantation but medical treatment sufficed thereafter. Moderate renal failure as defined by the K/DOQI-guidelines improved gradually and dialysis was never indicated. Six months after transplantation, the patient had normal liver function and adequate renal function.

Right ventricular pathophysiology and function monitoring during heart transplantation

Summary After orthotopic heart transplantation, right ventricular failure resulting from right ventricular afterload mismatch remains a significant complication. Heart transplant recipients suffer from chronic left ventricular failure which requires elevated filling pressures to maintain cardiac output. Systemic hypotension induces systemic and pulmonary vasoconstriction. This induces right ventricular hypertrophy and secondary pulmonary hypertension. After oHTX, the unadapted transplanted RV is exposed to the recipients PVR, and RV afterload mismatch results in acute RV failure. The preoperative estimation of PVR and of the reactivity of the pulmonary vascular bed to pulmonary vasodilators permits the selection of patients with reversible PH who are still suitable for oHTX. Reduction of RV afterload by pulmonary vasodilator therapy reduces the risk of RV failure. Right ventricular function monitoring after orthotopic heart transplantation is done using invasive hemodynamic monitoring, computer tomography (fast evolution CT), echocardiography, troponin T and CHARM (computerized heart allograft recipient monitoring).Zusammenfassung Nach Herztransplantation ist rechtsventrikuläres Versagen wegen „Afterload Mismatch” eine häufige Komplikation. Patienten auf der Warteliste für eine Herztransplantation leiden an chronischer linksventrikulärer Insuffizienz und halten das Herzzeitvolumen durch Erhöhung des Füllungsdruckes aufrecht. Hypotension erzeugt jedoch periphere und pulmonale Vasokonstriktion, die Folgen sind rechtsventrikuläre Hypertrophie und sekundärer pulmonaler Hypertonus. Nach der Transplantation ist der nicht adaptierte rechte Ventrikel des Spenderherzens dem erhöhten pulmonalen Widerstand des Empfängers ausgesetzt, gefolgt von Rechtsherzinsuffizienz. Die präoperative Abschätzung des pulmonalen Gefäßwiderstandes und die Reaktion auf pulmonale Vasodilatatoren erlaubt eine ungefähre Abschätzung des Risikos und die Auswahl von Patienten mit reversiblem pulmonalen Hypertonus. Die Senkung des rechtsventrikulären Afterloads nach der Transplantation reduziert das Risiko des rechtsventrikulären Versagens. Das Monitoring der rechtventrikulären Funktion besteht aus invasiver Druckmessung, Computertomographie (fast evolution CT), Echocardiographie, Troponin T and CHARM (Computerized heart allograft recipient monitoring).

Practical Aspects of Prostaglandin E1 before and after Solid Organ Transplantation

Prostaglandins and analogues for therapeutic use gained importance in the early eighties, when a substantial number of clinical studies about their therapeutical effects was published6, 12, 17, 22. Out of the huge family of prostanoids, prostaglandins E1 (PG E1) and I2 and their synthetical analogues are the most important substances in clinical practice in the field of solid organ transplantation. Organ procurement and organ preservation4, 5, 9, 15, 19 as well as treatment of primary graft failure8, 10 have been described as possible indications for PG E1. Vasodilating effects of prostaglandins are mediated by increasing cAMP levels in vascular smooth muscle cells. This mediation by cAMP is shared with beta-agonists and phosphodiesterase-inhibitors, but not with nitrates and nitric oxide3, 14, 21. Treatment of elevated pulmonary vascular resistance (PVR), which is frequently needed after heart transplantation (HTX), and in the pretransplant evaluation as well as bridging to transplan-tation1, 7, 20 has been the indication for PG E1 in our patient cohort.