Berthold Petutschnigg

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.

Donor heart quality control. Analysis of echocardiographic (EC) findings and patient outcome

Abstract  In a retrospective analysis, 149 echocardiographic (EC) evaluations were compared with conventional clinical parameters for donor heart selection. Of these cases, 12 % were found with severe impairment of ventricular wall motion or with morphological abnormalities. Nearly half of the echocar‐diographically diagnosed pathologi cal findings in donor hearts were not detected by conventional standards for heart screening. Analysis of EC‐screened donor heart outcome showed a primary graft nonfunction rate of 3.1 %. We suggest EC as an additional screening instrument for further dynamic and morphological information about donor heart condition. Potential donors can be saved for transplantation and severe complications can be avoided by de tecting occult cardiac dysfunction. Early detection of cardiac dysfunction may have an impact on donor therapy and can avoid unnecessary and expensive transportation of the surgical team to the harvest site.

Evoked epimyocardial electrogram for rejection diagnosis after heart transplantation

An endomyocardial electrogram (ECG) was reported to be a sensitive and practicable method for rejection monitoring after heart transplantation. Long-term follow up was limited, however, by variations of signals. The repolarization part of ECG signals vary with changes of heart rate. Both can be avoided by using pacemaker-induced signals. For stimulation and sensing of the ventricular-evoked response, a new type of electrode with fractal surface structure was used. Twenty patients undergoing heart transplantation were evaluated. Amplitudes of the depolarization and repolarization part of the ventricular-evoked response signals were analyzed and related to the degree of acute rejection according to histological findings from endomyocardial biopsy. Signals were transferred by Internet and analyzed automatically. In the case of focal moderate rejection (grade 2, International Society for Heart Transplantation grading) and higher degrees of rejection, a significant amplitude decrease was found. This sensitive non-invasive method for rejection monitoring with a high level of reliability provides the possibility of reducing the number of endomyocardial biopsies.

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.

Transplantevalution und Therapie mit Prostaglandin E1 bei Patienten mit erhöhtem Lungengefäßwiderstand

ZusammenfassungGrundlagenErhöhter Lungengefäßwiderstand stellt einen bedeutenden Risikofaktor für das frühe Rechtsherzversagen nach orthotoper Herztransplantation dar.Methoden11 Patienten (männlich, Durchschnittsalter 49,2 Jahre [21 bis 62 Jahre]) mit chronischer Linksherzinsuffizienz wurden zur Senkung ihres Lungengefäßwiderstandes mit i.v. verabreichtem Prostaglandin E1 (mittlere Erhaltungsdosis 35 ng/kg/min [25 bis 60 ng/kg/min]), Dopamin und Furosemid über 6 bis 8 Tage behandelt. Die Applikation wurde über eine Perfusionspumpe gesteuert. Alle hämodynamischen Messungen wurden mit einem Swan-Ganz-Thermodilutionskatheter durchgeführt. Die statistischen Daten wurden unter Anwendung des Wilcoxon-Signed-Ranks-Tests errechnet.ErgebnisseNoch 10 Tage nach Beendigung der i.v. Therapie war eine signifikante Abnahme des Lungengefäßwiderstandes nachweisbar (im Mittel 224 dyn s cm−5 im Vergleich zu 440 dyn s cm−5 vor der Therapie, p<0,005). Eine orthotope Herztransplantation erschien nun bei allen Patienten durchführbar.SchlußfolgerungenDer Effekt von Prostaglandin E1 auf den Lungengefäßwiderstand kann als diagnostischer Parameter für die Transplantevaluation bei Patienten mit chronischer Linksherzschwäche verwendet werden. Die nach einwöchiger Therapie mit Prostaglandin E1, Dopamin und Furosemid über mindestens 10 Tage anhaltende hämodynamische Verbesserung im kleinen Kreislauf legt die Möglichkeit einer internistischen Therapie bei sekundär erhöhtem Lungengefäßwiderstand nahe.SummaryBackgroundElevated pulmonary vascular resistance is an important risk factor for early right ventricular failure after orthotopic heart transplantation.MethodsIn order to decrease their pulmonary vascular resistance 11 patients (male, mean age 49.2 years [21 to 62 years]) with chronic left-heart failure were treated i.v. with prostaglandin E1 (mean dosage 35 ng/kg/min [25 to 60 ng/kg/min]) in combination with dopamine and furosemide for 6 to 8 days. Drugs were administered by the use of a motor syringe-pump. All hemodynamic data were determined by right heart catheterization using a Swan-Ganz catheter and thermodilution-technique. For the calculation of the statistics the Wilcoxon signed ranks test was used.Results10 days after the discontinuation of this therapy patients still showed a significantly decreased pulmonary vascular resistance (224 dyn s cm−5 in average compared to 440 dyn s cm−5 in average before therapy, p<0.005). Patients were considered eligible for an orthotopic heart transplantation.ConclusionsProstaglandin E1 can be used in the pretransplantation evaluation of left heart failure patients. The persistence of the hemodynamic improvement after an one-week treatment with prostaglandin E1, dopamine and furosemide for at least 10 days suggests that an internal therapy in heart failure patients with elevated pulmonary vascular resistance is possible.

Preoperative prostaglandin E1 treatment to prevent right ventricular failure after orthotopic heart transplantation

Elevated pulmonary vascular resistance (PVR) and pulmonary hypertension (PH) are high risk factors for early graft failure in orthotopic heart transplantation (oHTx). The need for an oversized donor in patients with elevated PVR aggravates the shortage of suitable donor organs. To decrease the elevated PVR to values suitable for orthotopic heart transplantation prostaglandin E1 (PGE1) was administered in 11 patients (11 male, mean age 49.2 years, mean dosage 35 ng/kg per min over 6-8 days). Ten days after the discontinuation of the PGE1 therapy, recatheterization was done. All haemodynamic data were determined by right heart catheterization using a Swan Ganz catheter and thermodilution technique before, and 10 days after, PGE1 treatment. The Wilcoxon signed ranks test was used for statistics. PVR significantly decreased in all patients (5.5 to 2.8 Wood units, P < 0.005). All patients were considered to be suitable for oHTX and put on the waiting list. At the time of writing, in eight of these patients (eight male, mean age 49.6 years; four ischemic, four dilatative CMP) oHTX had been successfully performed. No right ventricular failure occurred in the postoperative phase. These results sugest that long-term moderation of elevated PVR by PGE1 therapy weeks or months before transplantation enables oHTX in patients with elevated PVR.

Erstversorgung des Bauchtraumas

Erfahrene Notarzte evaluieren den Patienten »vom Scheitel bis zur Sohle«. Kopfschmerzen (im Rahmen eines Schadel-Hirn-Traumas), Atemnot (im Rahmen eines Thoraxtraumas), Frakturschmerz (im Rahmen einer Fraktur) sind fur den Verunfallten so dominant, dass ein Abdominaltrauma sehr haufig erst bei genauerer Untersuchung – auch fur den Patienten – als mogliche Verletzung erkannt wird. In diesem Beitrag wird das isolierte Bauchtrauma berucksichtigt, Kombinationsverletzungen oder der polytraumatisierte Patient sind nicht Thema dieser Zusammenfassung.

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).