Wilfried Rödiger

Combination therapy with carvedilol and amiodarone in patients with severe heart failure

Carvedilol and at least in some studies, amiodarone have been shown to improve symptoms and prognosis of patients with heart failure. There are no reports on the outcome of combined treatment with both drugs on top of angiotensin‐converting enzyme inhibitors (ACEI), diuretics and digitalis.

Experience with coronary sinus lead implantations for cardiac resynchronization therapy in 244 patients

ZusammenfassungEinleitungDie kardiale Resynchronisationstherapie (CRT) stellt ein neues Verfahren zur Behandlung der Herzinsuffizienz dar. Da die Implantation eines CRT-Systems komplexer als eine normale Schrittmacherimplantation ist, sind Daten zu perioperativer Sicherheit und Komplikationen von besonderer Bedeutung.MethodikVon Januar 1999 bis Juni 2005 wurde in unserem Zentrum bei 244 Patienten (Pat.; mittleres Alter 64±12 Jahre, 82% männlich) die Implantation eines CRT-Systems versucht. Bei 44% lag eine koronare Herzkrankheit und bei 29% Vorhofflimmern vor. Bei 71 Pat. wurde ein vorbestehender Schrittmacher aufgerüstet.ErgebnisseBei 239 Pat. (97%) gelang eine CRT-Implantation (285 Interventionen). 27% der Systeme verfügten über eine Defibrillationsmöglichkeit. 2 Patienten benötigten epikardiale Elektroden. Insgesamt 130 CS-Elektroden wurden posterolateral implantiert, 97 anterolateral und 28 anterior. 88% der Eingriffe erfolgten mit der „over-the-wire“-Technik. Es kam zu keinen perioperativen Todesfällen, jedoch zu 37 Komplikationen (12,5%): CS-Dissektion (n=9), CS-Perforation (n=1), Kammerflimmern (n=4), Asystolie (n=5), Lungenödem (n=1), Pneumothorax (n=2), CS-Elektrodenrevision wegen Dislokation (n=7) oder Zwerchfellzucken (n=12) und Explantation wegen Infektion (n=2). Bei 88% der Patienten besserte sich die NYHA-Klasse, jedoch nur bei 55% mit anteriorer Elektrodenlage.ZusammenfassungPerioperative Komplikationen traten bei ca. 10–15% aller CRT-Implantationen auf, jedoch ohne Todesfall oder bleibende Morbidität. Die meisten Patienten profitierten von dem Eingriff. Während der Implantation müssen externe Defibrillation und Stimulation verfügbar sein. Eine anteriore CS-Elektrodenposition sollte vermieden werden.SummaryIntroductionCardiac resynchronization therapy (CRT) using coronary sinus (CS) leads is a new method for the therapy of congestive heart failure (CHF). Because the intervention is more complex than regular pacemaker implantations, information on the feasibility and side effects of this method are of interest.MethodsFrom 1999 to June 2005, CRT implantations were attempted in 244 patients (pts; mean age 64±12 years, range 14–90 years), 82% were male, 44% had coronary artery disease, 29% were in atrial fibrillation, 71 had preexisting pacemakers.ResultsIn 97% of the pts the intervention was successful (27% of the systems with defibrillation capabilities). In 285 interventions, 255 CS leads were positioned according to CS vein anatomy in 130 posterolateral, 97 anterolateral and 28 anterior side branches (16 patients received 2 CS leads). Over-the-wire leads were used in 88%, 71% were additionally preshaped. We observed no mortality but 37 complications (12.5%): CS dissection in 9, CS perforation in 1, ventricular fibrillation in 4, asystole in 5, pulmonary edema in 1, pneumothorax in 2, need for early CS lead revision in 19 (dislodgement n=7, phrenic nerve stimulation n=12) and infection with explantation in 2 cases. An improvement in NYHA functional class was found in 88% of pts (only 55% if anterior lead position).ConclusionPerioperative complications during CS lead implantation occur in 10–15% of cases. Most patients responded well to CRT. Patients should be informed about the possible need for a reoperation. During implantation, immediate defibrillation and stimulation capabilities must be available. Anterior lead positions should be avoided.

Sudden death and tailored medical therapy in elective candidates for heart transplantation

BACKGROUND Due to the shortage of donor organs there is a long waiting time for heart transplantation. As a consequence, a high mortality rate on the waiting list diminishes the potential benefit of the procedure. Tailored medical therapy optimized according to the individual patients demands was introduced to select responding HTx candidates for continued management without transplantation. The development of modes of death over time (heart failure, sudden arrhythmic) in this population is unknown. METHODS In 434 elective candidates for heart transplantation, submitted to our institution in the years 1984-1997 (50% coronary artery disease, mean age 51.6 +/- 12 years, 86% males) medical therapy was adjusted according to the results of repeated right heart catherizations. Adjuncts to conventional therapy with ACE inhibitors, digitalis and diuretics were amiodarone, beta-blockers, spironolactone, oral anticogulants, molsidomine or nitrates. Only patients not responding to these measures were processed to HTx. Clinical events (death, mode of death, HTx, resuscitation) were noted and analyzed by the Kaplan-Meier method and related to patients characteristics by multivariance analysis. RESULTS During the mean follow-up of 2.36 +/- 2.4 years only 113 patients (25%) received a donor heart. One hundred-sixteen patients (26%) died without transplantation. Eighty-three (72%) of the deaths were sudden, 24 (20%) due to progression of heart failure and 9 (8%) due to other reasons. A shift from heart failure to sudden death was observed. Including 8 successful resuscitations due to documented VT/VF, there is a 20% risk of having a major arrhythmic event during the first two years of observation. Long-term (>1 year) medical responders had better hemodynamics at entry. Patients who died suddenly had similar clinical and hemodynamic data at entry than patients who needed an early transplant, but were in a comparable NYHA stage before death than long-term medical responders (2.15 +/- 0.8 vs 1.82 +/- 0.6, NS). Patients dying suddenly had significant more ventricular premature beats (1.6 +/- 2.9%/24 hours vs 1.06 +/- 2.8%/24 hours, p < .01) and complex ventricular arrhythmias (7.3 +/- 2.7/24 hours vs 1.98 +/- 5.6/24 hours, p < .01) than long-term responders. Seventy-five percent of all sudden death occurred during the first 2 observation years. CONCLUSIONS The rate of heart failure death in elective candidates for heart transplantation under optimized medical therapy is low when patients are followed closely and transplant can be done rapidly after deterioration is recognized. Sudden death represents the highest risk for most patients. This event occurred predominantly in stable patients under tailored medical therapy without indication for HTx at that time. Our results strongly demand strategies for risk stratification and the investigation of prophylactic measures in this population.

Rate-responsive pacing in patients with heart failure: long-term results of a randomized study

AIMS Chronotropic incompetence (CI) in patients with congestive heart failure (CHF) develops frequently under beta-blocker and amiodarone therapy. It can be corrected by pacing. We performed a randomized study to test whether pacing is beneficial in CHF patients with CI. METHODS AND RESULTS Congestive heart failure patients under combined beta-blocker and amiodarone therapy (n = 77) were randomly assigned to inhibited pacing (INH; basal rate 40 bpm/hysteresis 30 bpm; n = 38) or to DDDR pacing with optimized atrioventricular delay (OPT; stimulation rate 65-120 bpm, n = 39). Groups showed similar baseline values in NYHA class, heart rate, and ejection fraction (EF) and were followed up to 10 years. The resting and mean 24 h heart rate after 1 year decreased by -2.6/-5 bpm in INH, but increased by +3.6/+6.0 bpm in the OPT group (P < 0.001). The QRS interval after 1 year increased by 12 +/- 23 ms in the INH group, but +32 +/- 36 ms in the OPT group (P < 0.01). Patients with INH developed a greater left ventricular EF (LVEF) when compared with OPT patients (+10.6 +/- 8 vs. +2 +/- 10%, respectively; P = 0.04). Changes in LVEF were negatively correlated with heart rate, but not with QRS width changes. Prognosis and the event rate were better in the INH group. CONCLUSION In the long-term follow-up, single-site ventricular pacing in patients with CHF and low LVEF is associated with significant clinical events and a poor prognosis.

Tumor marker determination after orthotopic heart transplantation

BACKGROUND Because the risk of developing malignant tumors after heart transplantation is approximately 100-fold higher, methods for rapid diagnosis must be developed to allow early and aggressive treatment in these patients. Although tumor markers have been used frequently for surveying already detected cancer, we studied their value in screening for tumors in heart transplant patients. METHODS The levels of the tumor markers CEA, CA19-9, CA125, CA72-4, TPA, TPS, and CYFRA 21-1 were determined prospectively in 3-month intervals in 91 heart transplant patients between 1993 and 1998. RESULTS In eight patients a definite diagnosis of cancer was made during the marker survey (mean observation time 2.85 +/- 1.3 years), including bronchogenic carcinoma in six, renal carcinoma in one, and colon cancer in one. All patients with bronchogenic carcinoma were smokers. The markers had a sensitivity below 60% to detect cancer. Given a 2-fold cutoff level (10 ng/mL), the CEA was the only marker with sufficient specificity (93.8%, only one false-positive result). Two patients were symptom-free even though they had elevated CEA levels. In one of those patients, disseminated intractable cancer was diagnosed at first evaluation, whereas no tumor was found in the other case at first evaluation. Subsequently, by means of fluorodeoxyglucose positron emission tomography, a hypermetabolic region was found in the right upper mediastinum. Control computed tomographic scan 4 weeks after the first investigation showed disseminated intractable disease also in this patient. Another heart transplant patient with colon cancer showed a normalization of the CEA after hemicolectomy and an increase in the CEA when liver dissemination developed. There was a relationship between cardiac death and CA125 and TPS in some heart transplant patients. CONCLUSIONS We conclude that the CEA is the only tumor marker with adequate sensitivity and specificity to detect subclinical malignancies in the follow-up of heart transplant patients. However, because of several limitations (limited diagnostic and therapeutic possibilities and enormous costs), we cannot recommend screening by tumor markers on a regular basis. Because of the elevated risk of cancer in patients who had organ transplantation, further prophylactic measures, especially smoking cessation programs, must be developed. Once a malignancy is diagnosed, tumor markers can help target clinical decisions. Additionally, nonspecific increases in CA125 and TPS levels might be related to nonmalignant circulatory disturbances and cardiac death.

Aortic valve replacement with homografts. An overview

ZusammenfassungDie Implantation (eigentlich Transplantation) frischer oder kryokonservierter menschlicher Herzklappen (Homografts) in Aortenposition gehört seit über 30 Jahren zum herzchirurgischen Repertoire. Homografts sind attraktive Alternativen zu mechanischen oder xenobiologischen Klappen, da eine Antikoagulation vermieden und eine nahezu normale Anatomie hergestellt werden kann. Behandelnde Ärzte sollten über die verfügbaren Implantate, die Operationsmethoden und die zu erwartenden Ergebnisse informiert sein, um Patienten mit Klappenvitien entsprechend beraten zu können und individuelle Komplikationsmöglichkeiten in der Nachsorge früh zu erfassen.Dargelegt wird eine Literaturübersicht zum Thema Homograftklappen. Es erfolgt eine Schilderung des Verfahrens der Graftgewinnung, der Herstellung und der Konservierung. Die Einsatzgebiete von Homografts werden erläutert und die Operationstechniken (subkoronar, Miniroot, Wurzelersatz) sowie die Ross-Operation diskutiert. Erwähnung findet auch der Einsatz von Homograftklappen bei frühkindlichen Herzfehlern. Komplikationen und wichtige Aspekte der Nachsorge werden kommentiert.Homografts eignen sich zum Aorten- und Pulmonalklappenersatz bei speziellen Indikationen (jugendlicher Patient, Kontraindikation zur Antikoagulation, Endokarditis). Angaben zu Langzeitergebnissen schwanken je nach Zentrum, eingesetzter Operationsmethode und Klappentyp. Pulmonale Homografts in Aortenposition sind im Gegensatz zu aortalen Homografts negativ zu beurteilen. Der Stellenwert von Homografts und der Ross-Operation im Vergleich zu ungestützten Xenografts sollte durch weitere möglichst multizentrische Langzeitstudien überprüft werden. Im Bereich der Kinderherzchirurgie haben sich Homografts bewährt, vor allem zur Rekonstruktion der rechtsventrikulären Ausflussbahn. Homograftimplantate in Mitralposition gehören noch nicht zur klinischen Routine und zeigen bislang enttäuschende Resultate. Die wesentliche Limitation im Einsatz von Homografts ist ihre geringe Verfügbarkeit; deshalb können Homografts nur begrenzt für die oben erwähnten speziellen Indikationen zur Verfügung gestellt werden.AbstractThe implantation of fresh or cryopreserved human heart valves (homografts) in aortic position is a tool in cardiac surgery since 30 years. Homografts are attractive alternatives to the implantation of mechanical or xenobiological prostheses, because anticoagulation can be avoided and a near normal anatomy can be restored. Physicians should know about the several kinds of grafts and operative techniques to adequately take care of the patients in follow-up.This overview on the literature covers methods of harvesting, preparation and conservation of homografts according to standard protocols of the European Homograft Bank in Brussels. Their use in the therapy of human valvular disease is discussed with special emphasis to operative techniques (subcoronary, root) and the Ross procedure and in pediatric surgery. Complications and aspects of postoperative care are discussed including immunologic phenomena.Homografts are useful tools for aortic valve replacement, especially in juveniles, in the presence of contraindications for anticoagulation and in endocarditis. Whereas aortic homografts have excellent long-term results, pulmonic homografts show a significant rate of malformation. Further studies should be performed to clarify the role of the Ross operation or stentless xenografts compared to homografts in aortic position. In pediatric cardiac surgery homografts are of value especially for the reconstruction of the right ventricular outflow tract. Homografts in mitral position show dissapointing results up to now. The major limitation in the use of homografts is the mismatch of availability and request, therefore homografts can only be used for the above mentioned special indications.The implantation of fresh or cryopreserved human heart valves (homografts) in aortic position is a tool in cardiac surgery since 30 years. Homografts are attractive alternatives to the implantation of mechanical or xenobiological prostheses, because anticoagulation can be avoided and a near normal anatomy can be restored. Physicians should know about the several kinds of grafts and operative techniques to adequately take care of the patients in follow-up. This overview on the literature covers methods of harvesting, preparation and conservation of homografts according to standard protocols of the European Homograft Bank in Brussels. Their use in the therapy of human valvular disease is discussed with special emphasis to operative techniques (subcoronary, root) and the Ross procedure and in pediatric surgery. Complications and aspects of postoperative care are discussed including immunologic phenomena. Homografts are useful tools for aortic valve replacement, especially in juveniles, in the presence of contraindications for anticoagulation and in endocarditis. Whereas aortic homografts have excellent long-term results, pulmonic homografts show a significant rate of malfunction. Further studies should be performed to clarify the role of the Ross operation or stentless xenografts compared to homografts in aortic position. In pediatric cardiac surgery homografts are of value especially for the reconstruction of the right ventricular outflow tract. Homografts in mitral position show disappointing results up to now. The major limitation in the use of homografts is the mismatch of availability and request, therefore homografts can only be used for the above mentioned special indications.

Intensified medical therapy in heart transplant candidates

Abstract Background: Because of donor shortage, heart transplantation (HTx) as therapy for end-stage heart failure is limited by a mortality rate of 25% on waiting lists, and lists are steadily increasing. Aim: To analyse whether an intensive medical therapeutic regimen for heart failure (based on the results of frequent haemodynamic studies) can delay or even prevent the need for HTx. Methods: Data analysis of 517 patients who were referred to our institution for HTx from 1984 to 1996 is presented. Characteristics and management of 359 non-emergency, New York Heart Association (NYHA) III or IV heart transplant candidates, without contraindications (and with sufficient compliance) are described. All candidates receiving conventional therapy with ACE inhibitors, digitalis and diuretics at entry were evaluated. Drug therapy was intensified as follows: a further reduction of preload; a further reduction of afterload; individualised diuresis; and amiodarone therapy. Results: Under this regimen, clinical and haemodynamic parameters improved in many patients. Only 95 patients (26%) were primary non-responders to intensified medical therapy and had to be listed for HTx early (during the first year of follow-up). Actuarial survival rates of the early listed versus the early responding HTx candidates, at 1 and 5 years, were 68.3%/87% and 41%/59%, respectively (p=0.02). An additional benefit of co-therapy with amiodarone and calcium antagonists was found. The most important mode of cardiac death was sudden (32% at 5 years), whereas mortality due to pump failure was much lower (13% at 5 years). Only 38 patients (16%):had to be listed for HTx in further follow-up. Conclusions: Intensive medical therapy in heart transplant candidates may be an alternative to immediate HTx, especially in times of donor shortage or in countries without a transplantation program. Responders to therapy showed a similar or even better prognosis than HTx patients. This conservative approach may allow available donor hearts to be saved for those patients most needing a transplant.

Symptome bei Patienten nach Schrittmacher-Implantation Was zeigen Patienten ausgelöste Elektrogramme?

ZusammenfassungUnsere Studie zeigt in den von Patienten ausgelösten Elektrogrammen meist einen unauffälligen stimulierten oder spontanen Rhythmus ohne den Hinweis auf eine Arrhythmie. In diesen Fällen muß man davon ausgehen, daß die Symptome nicht in Zusammenhang mit einer Rhythmusstörung sondern anderen Ursachen stehen.

Incidence and risk factors of sudden death after orthotopic heart transplantation

ZusammenfassungStudienziel: Es sollten die Häufigkeit und die zugrundeliegenden Risikofaktoren plötzlicher Todesfälle nach orthotoper Herztransplantation (HTx) untersucht werden. Hintergrund: Einige Berichte beschrieben eine hohe Rate plötzlicher Todesfälle bei herztransplantierten Patienten. Dies führt zu einer deutlichen Limitierung im Langzeiterfolg des aufwendigen Verfahrens. Zur Inzidenzrate, zugrundeliegenden Risikofaktoren und sich daraus ableitenden präventiven Maßnahmen gibt es bislang keine eindeutige Datenlage. Methode: Retrospektive Analyse von 120 Herztransplantatempfängen eines einzelnen Zentrums der Jahre 1984–1999 (Überlebende der unmittelbar postoperativen Phase, Gesamt-HTx n=142). Klinische Ereignisse (Tod, Todesart, Re-HTx, Wiederbelebung) wurden vermerkt, die Wahrscheinlichkeit des Auftretens mit der Kaplan-Meier-Methode berechnet und mittels Multivarianzanalyse zu den Patientencharakteristika in Beziehung gesetzt. Der plötzliche Tod innerhalb oder außerhalb des Hospitals wurde definiert als Tod innerhalb einer Stunde nach Symptomeintritt, oder als unbeobachteter, nicht erwarteter Tod. Klinische und postmortale Befunde (Autopsie verfügbar bei 12/18 plötzlich verstorbenen Patienten) wurden ebenfalls zur Todesart in Beziehung gesetzt. Ergebnisse: Während der mittleren Beobachtungszeit von 4,6±3,5 Jahren verstarben 45 Patienten (38%). Als Todesart fand sich ein nicht-plötzlicher Tod bei 27 stationären Patienten. 18 Todesfälle traten plötzlich auf, 14 davon außerhalb des Spitals. Zusätzlich traten drei Herzstillstände mit erfolgreicher Reanimation auf, wobei einer dieser Patienten 3 Monate später plötzlich verstarb. Dies ergab eine Gesamtzahl von 21 Herzstillständen bei 20 HTx-Patienten. Das aktuarische Risiko eines Herzstillstandes betrug 20% nach 6 und 40% nach 12 Jahren. Basierend auf den Autopsieresultaten konnte als Ätiologie der Ereignisse eine Transplantatvaskulopathie bei 15 Patienten und eine Abstoßung (International Society for Heart and Lung Transplantation Grad >>;3A) bei 5 Patienten angenommen werden. Bei einem Patienten konnte die Todesursache nicht eindeutig klassifiziert werden. Alle 3 erfolgreich reanimierten Patienten zeigten beim Ereignis dokumentierte bradykarde Rhythmusstörungen (2× totaler AV-Block, 1× Sinusarrest). Bei ihnen wurden Herzschrittmacher implantiert. Einer dieser Patienten verstarb plötzlich 3 Monate später. Unter den plötzlich verstorbenen HTx-Patienten fanden sich signifikant mehr Raucher, eine erniedrigte Auswurffraktion und eine schlechtere Hämodynamik. Die QRS-Breite und das PR-Intervall waren bei den plötzlich verstorbenen Patienten mit Transplantatvaskulopathie signifikant verbreitert. In drei Einzelfällen konnte ein Abfall der Herzfrequenzvariabilität, das Auftreten einer anhaltenden ventrikulären Tachykardie beziehungsweise eine ST-Streckensenkung beobachtet werden. Schlußfolgerung: Nach Herztransplantation kommt es im Langzeitverlauf zu einer deutlichen Rate plötzlicher Todesfälle. Da die Gesamtzahl herztransplantierter Patienten immer mehr ansteigt wird der plötzliche Tod in dieser Population zu einem signifikanten Problem. In unserer Untersuchung konnten 75% der Herzstillstände einer Transplantatvaskulopathie und der Rest Abstoßungen zugeordnet werden. Zumindest einige Ereignisse werden durch bradykarde Störungen verursacht. Es müssen diagnostische Strategien entwickelt werden, um HTx-Patienten mit hohem Risiko zu erfassen.SummaryObjectives: To clarify the incidence of sudden arrythmic death and associated risk factors in patients after orthotopic heart transplantation (HTx). Background: Some reports indicate a significant rate of sudden death in heart transplant recipients limiting long-term success of the operation. Incidence, underlying risk factors, etiologies, and methods for prediction or prevention of sudden death are poorly defined. Methods: Retrospective analysis of our cohort of 120 cardiac allograft recipients surviving the perioperative phase out of a total of 142HTx patients of the years 1984–1999. Clinical events (death, mode of death, Re-HTx, resuscitation) were noted and analyzed by the Kaplan-Meier method and related to the patients‘ characteristics by multivariate analysis. Sudden death in or out of hospital was defined as death within one hour of symptoms or unwittnessed death. Clinical and postmortem findings (autopsies are available in 12/18 sudden death patients) were correlated to the mode of death. Results: During a mean follow-up interval of 4.6±3.5 years, 45 patients died (38%). The mode of death was non-sudden in 27 inpatients. 18 deaths were sudden, 14 of these out of hospital. In addition there were three cardiac arrests with successful resuscitations, one of those patients died three month later suddenly, giving a number of a total of 21 cardiac arrests in 20HTx patients. The actuarial risk of cardiac arrest was 20% after 6 and 40% after 12 years. Based on postmortem analysis the etiologies of the events were attributed to transplant vasculopathy in 15 patients, rejection in 5 patients (International Society for Heart and Lung Transplantation grade >3A), and to unknown reasons in one. All three patients successfully resuscitated from cardiac arrest had documented bradycardic events (2×total AV block, 1×sinus arrest). Pacemakers were implanted in these patients. One of those died suddenly 2 months later. Significantly more HTx patients dying suddenly are smokers, had a lower left ventricular ejection fraction, and worse hemodynamics. QRS width and PR interval were significantly broadened in patients with transplant vasculopathy and cardiac arrest. In three cases, a decrease in heart rate variability, the occurence of sustained VT, and ST segment depressions prior to the cardiac arrest could be demonstrated. Conclusions: Sudden death occurs at a substantial rate after HTx. As HTx patient numbers are rising constantly, sudden cardiac death in this population will represent a significant problem. In our patients about 75% of the arrests can be attributed to graft-vasculopathy and one quarter to acute rejection. Diagnostic strategies have to be developed to detect patients at risk. Interestingly, some events may be caused from bradyarrhythmic rhythm disturbances.