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

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.

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.

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.

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.