Sudden death and tailored medical therapy in elective candidates for hearttransplantation

Background: Due to the shortage of donor organs there is a long waiting tim e for heart transplantation. As a consequence, a high mortality rate on the waiting list diminishes the potential benefit of the procedure. Tailored m edical therapy optimized according to the individual patients demands was i ntroduced to select responding HTx candidates for continued management with out transplantation. The development of modes of death over time (heart fai lure, 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 convention al therapy with ACE inhibitors, digitalis and diuretics were amiodarone, be ta-blockers, spironolactone, oral anticogulants, molsidomine or nitrates. O nly patients not responding to these measures were processed to HTx. Clinic al events (death, mode of death, HTx, resuscitation) were noted and analyze d by the Kaplan-Meier method and related to patients characteristics by mul tivariance 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 witho ut 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 shif t from heart failure to sudden death was observed. Including 8 successful r esuscitations due to documented VT/VF, there is a 20% risk of having a majo r arrhythmic event during the first two years of observation. Long-term (>1 year) medical responders had better hemodynamics at entry. Patients who di ed suddenly had similar clinical and hemodynamic data at entry than patient s who needed an early transplant, but were in a comparable NYHA stage befor e 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 ven tricular arrhythmias (7.3 +/- 2.7/24 hours vs 1.98 +/- 5.6/24 hours, p < .0 1) than long-term responders. Seventy-five percent of all sudden death occu rred during the first 2 observation years. Conclusions: The rate of heart failure death in elective candidates for hea rt 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. Th is event occurred predominantly in stable patients under tailored medical t herapy without indication for HTx at that time. Our results strongly demand strategies for risk stratification and the investigation of prophylactic m easures in this population.