Chirurgische Optionen bei fortgeschrittener Herzinsuffizienz und interdisziplinäres Management 25 Jahre HTX MUW / AKH Michael Grimm Herzchirurgie Medizinische Universität Wien

Herzinsuffizienz Prognose vs. Malignom 4 3 5 2 1 0.2 0.4 0.6 0.8 1.0 Überlebensrate Jahre ♀ ♂ Ovar Herzinsuffizienz Lunge Darm Prostata Brust Blase Fig 1. Five-year survival following a first admission to any Scottish hospital in 1991 for heart failure, myocardial infarction and the four most common sites of cancer specific to men and women More ‘malignant’ than cancer? Five-year survival following a first admission for heart failure Simon Stewart a, b, Kate MacIntyre b, David J. Hole c, Simon Capewell b and John J.V. McMurray   Abstract Background: The prognostic impact of heart failure relative to that of ‘high-profile’ disease states such as cancer, within the whole population, is unknown. Methods: All patients with a first admission to any Scottish hospital in 1991 for heart failure, myocardial infarction or the four most common types of cancer specific to men and women were identified. Five-year survival rates and associated loss of expected life-years were then compared. Results: In 1991, 16.224 men had an initial hospitalisation for heart failure (n=3.241), myocardial infarction (n=6932) or cancer of the lung, large bowel, prostate or bladder (n=6051). Similarly, 14.842 women were admitted for heart failure (n=3606), myocardial infarction (n=4916), or cancer of the breast, lung, large bowel or ovary (n=6320). With the exception of lung cancer, heart failure was associated with the poorest 5-year survival rate (approximately 25% for both sexes). On an adjusted basis, heart failure was associated with worse long-term survival than bowel cancer in men (adjusted odds ratio, 0.89; 95% CI, 0.82–0.97; P<0.01) and breast cancer in women (odds ratio, 0.59; 95% CI, 0.55–0.64; P<0.001). The overall population rate of expected life-years lost due to heart failure in men was 6.7 years/1000 and for women 5.1 years/1000. Conclusion: With the notable exception of lung cancer, heart failure is as ‘malignant’ as many common types of cancer and is associated with a comparable number of expected life-years lost. Stewart S. Eur J Heart Fail 2001;3:315-22

evidence-based medicine medical treatment of CHF evolving surgical treatment of CHF Class I referral for HTX in eligible patients revascularization of ischemic myocardium Class II correction of IMR Class III partial left ventriculectomy The surgical management of patients with end-stage heart failure has evolved in a less structured fashion. Heart transplantation remains the ultimate treatment for heart failure, but the persistent shortage of donor hearts continues to limit the annual growth of this approach. Thus, heart transplantation is not an available option for most patients with heart failure and continues to be performed only at large, highly specialized medical centers (See "Indications and contraindications for cardiac transplantation"). Surgical approaches to end-stage heart failure are rapidly evolving. Although large randomized trials are unusual in this field, important steps have been made over the past 10 to 15 years, as outlined and discussed below. The role of any of these approaches remains to be proven (show table 1) [1 Hunt ACC/AHA Guidelines Circulation 2001

Transplantation des Herzens Herz-Ersatz Transplantation des Herzens exzellente Langzeit – Palliation limitierte Anzahl an Spendern Qualität vor Quantität Assist Device Überbrückung zur Transplantation Überbrückung zur Erholung Langzeit Implantation

Interdisziplinäre Ambulanz für chirurgische Therapie der Herzinsuffizienz Kardiologie, Intensivmedizin, Radiologie, Chirurgie Indikation Triage präoperative Konditionierung perioperatives Management postoperative Strategie

Bypasschirurgie – reduzierte LV-Funktion EF < 40% 100 < 2002 (n=350) ≥ 2002 (n=210) 80 60 log-rank<.001 Überleben (%) 40 20 1 2 3 4 5 6 7 Jahre ÖGK 06

Resektion - Herzwand-Aneurysma Dor Operation > 2002 (n=56) ÖGK 06

Sekundäre Mitralinsuffizienz MI durch Papillarmuskel infarzierter, nicht-rupturierter PM rupturierter PM funktionelle MI simple Ringdilatation (sek. LV-Vergrößerung) lokales LV-remodeling (restriktives hinteres Segel) Kombination IMR is a ventricular disease, not a valvular disease.” Steven Bolling heterogeneous Cohort Even though different descriptive terms were used, an important message is that we distinguish between “functional IMR,” infarcted but not ruptured papillary muscle, and ruptured papillary muscle. The vast majority is represented by patients with functional IMR, which can be due to one of the following reasons: (1) simple annular dilatation (secondary to left ventricular [LV] enlargement), which causes incomplete mitral leaflet coaptation associated with Carpentier type I (normal) leaflet motion; (2) local LV remodeling with papillary muscle displacement producing apical tethering or tenting of the leaflets (with Carpentier type III-b restricted systolic leaflet motion); or (3) both mechanisms.

Überleben n.s. Methods.From January 1976 to January 1996, 223 patients with ischemic mitral insufficiency underwent mitral valve reconstruction (n = 152) or prosthetic mitral valve replacement (n = 71). Coronary artery bypass grafting was performed in 89% of cases of mitral reconstruction and 80% of cases of prosthetic replacement. In the group undergoing reconstruction, 77% had valvuloplasty with a ring annuloplasty and 23% had valvuloplasty with suture annuloplasty. In the group undergoing prosthetic replacement, 82% of patients received bioprostheses and 18% received mechanical prostheses. Conclusion. Initial mortalities were similar among patients undergoing prosthetic replacement and valve reconstruction. Poor outcome was primarily related to preexisting comorbidities. Patients undergoing valve reconstruction had fewer valve-related complications. Valve reconstruction resulted in excellent durability and freedom from complications. These findings suggest that mitral valve reconstruction should be considered for appropriate patients with ischemic mitral insufficiency. Suffice it to say, the patients who underwent mitral repair at New York University were not as sick as those who required MVR (as was also the case in the Gillinov report2); medium-term survival was suboptimal but roughly equivalent between the two types of procedures. Certain subsets of patients were identified who appeared to do better if they could undergo repair. This lack of pronounced difference in survival between the repair and the MVR groups is similar to the conclusions just reported by Calafiore Grossi JTCVS 2001

komplikations – freies Überleben 0.03 OBJECTIVE: This study reviews the 223 consecutive mitral valve operations for ischemic mitral insufficiency performed at New York University Medical Center between January 1976 and January 1996. The results for mitral valve reconstruction are compared with those for prosthetic mitral valve replacement. METHODS: From January 1976 to January 1996, 223 patients with ischemic mitral insufficiency underwent mitral valve reconstruction (n = 152) or prosthetic mitral valve replacement (n = 71). Coronary artery bypass grafting was performed in 89% of cases of mitral reconstruction and 80% of cases of prosthetic replacement. In the group undergoing reconstruction, 77% had valvuloplasty with a ring annuloplasty and 23% had valvuloplasty with suture annuloplasty. In the group undergoing prosthetic replacement, 82% of patients received bioprostheses and 18% received mechanical prostheses. RESULTS: Follow-up was 93% complete (median 14.6 mo, range 0-219 mo). Thirty-day mortality was 10% for mitral reconstruction and 20% for prosthetic replacement. The short-term mortality was higher among patients in New York Heart Association functional class IV than among those in classes I to III (odds ratio 5.75, confidence interval 1.25-26.5) and was reduced among patients with angina relative to those without angina (odds ratio 0.26, confidence interval 0.05-1.2). The 30-day death or complication rate was similarly elevated among patients in functional class IV (odds ratio 5.53; confidence interval 1.23-25.04). Patients with mitral valve reconstruction had lower short-term complication or death rates than did patients with prosthetic valve replacement (odds ratio 0.43, confidence interval 0.20-0.90). Eighty-two percent of patients with mitral valve reconstruction had no insufficiency or only trace insufficiency during the long-term follow-up period. Five-year complication-free survivals were 64% (confidence interval 54%-74%) for patients undergoing mitral valve reconstruction and 47% (confidence interval 33%-60%) for patients undergoing prosthetic valve replacement. Results of a series of statistical analyses suggest that outcome was linked primarily to preoperative New York Heart Association functional class. CONCLUSIONS: Initial mortalities were similar among patients undergoing prosthetic replacement and valve reconstruction. Poor outcome was primarily related to preexisting comorbidities. Patients undergoing valve reconstruction had fewer valve-related complications. Valve reconstruction resulted in excellent durability and freedom from complications. These findings suggest that mitral valve reconstruction should be considered for appropriate patients with ischemic mitral insufficiency. Grossi JTCVS 2001

Replacement / Repair low risk high risk benefit from repair (no complex MI, normal lateral wall-motion) benefit from repair high risk (complex jet, abnormal lateral wall-motion) replacement rather than repair Gillinov JTCVS 2001

Mitralklappen - Rekonstruktion sekundäre, nicht-ischämische Mitralinsuffizienz 100 Assist Device Transplant (LVEDD > 70 mm) 80 60 Überleben (%) 40 20 > 2002 (n=46) 1 2 3 4 Jahre ÖGK 06

Zukunft - Myokardregeneration alternative Verfahren Zelltherapie alternative Verfahren Gentherapie

Zelltherapie genetisch modifizierte Myoblasten - Ratte besseres Überleben von peripheren Muskelzellen nach intrakardialer Transplantation mittels in-vitro Transfektion mit CSF-1 verbessert über Myokardregeneration die Funktion Cardiovasc Res 08

alternative Verfahren epikardiale Schockwellentherapie - Ratte + p<.05 vs. control + SWT control JTCVS 2009

alternative Verfahren epikardiale Schockwellentherapie - Ratte ___ SWT ___ control LAD Ligatur SWT * † † † * † * * * * * * p<.05 vs. Ausgangswert † p<.05 vs. SWT JTCVS 2009

alternative Verfahren epikardiale Schockwellentherapie - Schwein EF% –– Kontrolle — SWT * 20 30 40 50 60 70 80 Infarkt 4 Wo nach Infarkt SWT 8 Wo nach Infarkt Abschluss * p<0.05 vs. Kontrolle JTCVS in press

Umsetzung from bench to bedside

Gentherapie placental growth factor (PlGF) - Ratte * patent application MUW 08

Chirurgie der Herzinsuffizienz unverzichtbarer Bestandteil im interdisziplinären Management des Patienten mit progressiver Herzinsuffizienz Transplantation Assist Device konventionelle Chirurgie translationale Forschung