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Severe renal dysfunction complicating cardiogenic shock is not a contraindication to mechanical support as a bridge to cardiac transplantation
each of the study subjects. Further study is necessary to determine if skeletal myoblast transplantation will provide clinical benefit to patients with ischemic cardiomyopathy. Perspective: This study represents the first proof of successful engraftment and differentiation of skeletal myoblasts into the scarred myocardium of human patients with ischemic cardiomyopathy. It remains to be shown if skeletal myoblast transplantation can lead to improved ventricular function. Future studies must also demonstrate the safety of these injections in patients without LVAD support. TK
practice in heart transplantation: initiation of statin therapy as soon as possible after transplantation in the absence of contraindications or documented intolerance, regardless of serum cholesterol levels. KA
Severe Renal Dysfunction Complicating Cardiogenic Shock Is Not A Contraindication to Mechanical Support as a Bridge to Cardiac Transplantation Knot UN, Mishra M, Yamani MH, et al. J Am Coll Cardiol 2003; 41:381–5. Study Question: Does severe renal dysfunction complicating cardiogenic shock impair survival in recipients of a left ventricular assist device (VAD) as a bridge to cardiac transplantation. Methods and Results: Data were examined for 215 consecutive patients who received a VAD from 1992 to 2000 and selected patients who had a serum creatinine ⱖ3.0 mg/dL at the time of VAD placement. Demographic, laboratory and clinical outcome data were collected. Eighteen patients met the inclusion criteria. Mean serum creatinine at the time of VAD placement was 4.0⫾0.7 mg/dL (range 3.0 –5.2 mg/ dL). Seven patients required temporary renal support with continuous venovenous hemodialysis (CVVHD). Eleven patients underwent cardiac transplantation. At 6 months post-transplantation, mean serum creatinine was 2.0⫾0.6 mg/dL (range 1.3–3.5 mg/dL). None of the transplanted patients required subsequent renal support. Seven patients died with a VAD before transplantation. Three died early (⬍1 month) after VAD placement, and all three required CVVHD until death. Four patients survived for ⬎1 month after VAD placement; all four had resolution of renal dysfunction with mean serum creatinine of 1.9⫾1.2 mg/dL (range 0.8 –3.6 mg/dL) without the need for renal support. Overall 30-day and 6-month survival after VAD placement, survival to transplantation and survival 1-year post-transplantation were similar to patients without severe renal dysfunction. Conclusions: Contemporary use of VAD leads to resolution of severe renal dysfunction in most cardiogenic shock patients and comparable long-term outcomes to patients without renal dysfunction. Perspective: Although this study had very limited statistical power to identify differences in outcome, the results are consistent with recent experience in larger VAD/transplant centers. When acute renal failure occurs as a complication of cardiogenic shock, substantial recovery of renal dysfunction and good survival may be achieved when cardiac output and renal blood flow are restored by VAD support, although short-term CVVHD is often required. Even so, the key to maximizing post-VAD survival is its initiation at the earliest sign of end organ dysfunction. KA
Simvastatin Initiated Early After Heart Transplantation: 8-Year Prospective Experience Wenke K, Meiser B, Thiery J, et al. Circulation 2003;107:93–7. Study Question: Since clinical trials have shown statins to reduce cholesterol levels, mortality and the development of transplant vasculopathy in heart transplant recipients, this study asked whether these effects and safety persisted over an 8-year period post transplant. Methods and Results: In 1991, a prospective, randomized unmasked study was initiated to compare the efficacy of simvastatin, started on the fourth postoperative day (n⫽35), with that of dietary therapy alone (n⫽37). Because of significantly improved survival and a lower incidence of transplant vasculopathy, most patients in both groups received statins as open-label prescriptions after 4 years. After 8 years, the Kaplan-Meier survival rate was 88.6% in the simvastatin group vs. 59.5% in the control group (p⬍0.006 by log rank; hazard ratio, 0.24; 95% CI, 0.08 – 0.71). Deaths in the simvastatin and control groups were due to transplant vasculopathy (1 vs. 4; p⬍0.2), severe transplant rejection (1 vs. 5; p⬍0.1), malignancies (0 vs. 3; p⬍0.1) and other causes (2 vs. 3; p⬍0.7). The incidence of transplant vasculopathy confirmed by angiography was 24.4% in the simvastatin group vs. 54.7% in the control group (p⬍0.02 by log rank). There was no difference in organ function between the two groups. No severe adverse effects of the therapy were observed up to the end of the 8-year observation period. Conclusions: Simvastatin therapy initiated early after heart transplantation leads to significantly better 8-year survival rates and a significantly lower incidence of transplant vasculopathy without impairment of organ function or severe adverse effects. Perspective: This is the longest reported follow-up of patients maintained on statin therapy following heart transplantation. The remarkable 88.6% 8-year survival in the simvastatin group represents 100% conditional survival from the fifth through the eighth year posttransplant and is quite likely a chance event. Nevertheless, this study confirms the advisability of what has become standard clinical
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practice in heart transplantation: initiation of statin therapy as soon as possible after transplantation in the absence of contraindications or documented intolerance, regardless of serum cholesterol levels. KA
Severe Renal Dysfunction Complicating Cardiogenic Shock Is Not A Contraindication to Mechanical Support as a Bridge to Cardiac Transplantation Knot UN, Mishra M, Yamani MH, et al. J Am Coll Cardiol 2003; 41:381–5. Study Question: Does severe renal dysfunction complicating cardiogenic shock impair survival in recipients of a left ventricular assist device (VAD) as a bridge to cardiac transplantation. Methods and Results: Data were examined for 215 consecutive patients who received a VAD from 1992 to 2000 and selected patients who had a serum creatinine ⱖ3.0 mg/dL at the time of VAD placement. Demographic, laboratory and clinical outcome data were collected. Eighteen patients met the inclusion criteria. Mean serum creatinine at the time of VAD placement was 4.0⫾0.7 mg/dL (range 3.0 –5.2 mg/ dL). Seven patients required temporary renal support with continuous venovenous hemodialysis (CVVHD). Eleven patients underwent cardiac transplantation. At 6 months post-transplantation, mean serum creatinine was 2.0⫾0.6 mg/dL (range 1.3–3.5 mg/dL). None of the transplanted patients required subsequent renal support. Seven patients died with a VAD before transplantation. Three died early (⬍1 month) after VAD placement, and all three required CVVHD until death. Four patients survived for ⬎1 month after VAD placement; all four had resolution of renal dysfunction with mean serum creatinine of 1.9⫾1.2 mg/dL (range 0.8 –3.6 mg/dL) without the need for renal support. Overall 30-day and 6-month survival after VAD placement, survival to transplantation and survival 1-year post-transplantation were similar to patients without severe renal dysfunction. Conclusions: Contemporary use of VAD leads to resolution of severe renal dysfunction in most cardiogenic shock patients and comparable long-term outcomes to patients without renal dysfunction. Perspective: Although this study had very limited statistical power to identify differences in outcome, the results are consistent with recent experience in larger VAD/transplant centers. When acute renal failure occurs as a complication of cardiogenic shock, substantial recovery of renal dysfunction and good survival may be achieved when cardiac output and renal blood flow are restored by VAD support, although short-term CVVHD is often required. Even so, the key to maximizing post-VAD survival is its initiation at the earliest sign of end organ dysfunction. KA
Simvastatin Initiated Early After Heart Transplantation: 8-Year Prospective Experience Wenke K, Meiser B, Thiery J, et al. Circulation 2003;107:93–7. Study Question: Since clinical trials have shown statins to reduce cholesterol levels, mortality and the development of transplant vasculopathy in heart transplant recipients, this study asked whether these effects and safety persisted over an 8-year period post transplant. Methods and Results: In 1991, a prospective, randomized unmasked study was initiated to compare the efficacy of simvastatin, started on the fourth postoperative day (n⫽35), with that of dietary therapy alone (n⫽37). Because of significantly improved survival and a lower incidence of transplant vasculopathy, most patients in both groups received statins as open-label prescriptions after 4 years. After 8 years, the Kaplan-Meier survival rate was 88.6% in the simvastatin group vs. 59.5% in the control group (p⬍0.006 by log rank; hazard ratio, 0.24; 95% CI, 0.08 – 0.71). Deaths in the simvastatin and control groups were due to transplant vasculopathy (1 vs. 4; p⬍0.2), severe transplant rejection (1 vs. 5; p⬍0.1), malignancies (0 vs. 3; p⬍0.1) and other causes (2 vs. 3; p⬍0.7). The incidence of transplant vasculopathy confirmed by angiography was 24.4% in the simvastatin group vs. 54.7% in the control group (p⬍0.02 by log rank). There was no difference in organ function between the two groups. No severe adverse effects of the therapy were observed up to the end of the 8-year observation period. Conclusions: Simvastatin therapy initiated early after heart transplantation leads to significantly better 8-year survival rates and a significantly lower incidence of transplant vasculopathy without impairment of organ function or severe adverse effects. Perspective: This is the longest reported follow-up of patients maintained on statin therapy following heart transplantation. The remarkable 88.6% 8-year survival in the simvastatin group represents 100% conditional survival from the fifth through the eighth year posttransplant and is quite likely a chance event. Nevertheless, this study confirms the advisability of what has become standard clinical
ACC CURRENT JOURNAL REVIEW May/Jun 2003
53