Focused Issue of This Month Treatment of Medically Intractable EndStage Heart Failure Jin Ho Choi, MD Department of Emergency Medicine, Sungkyunkwan University School of Medicine Email : jinho.choi@samsung.com Eun Seok Jun, MD Department of Cardiology, Sungkyunkwan University School of Medicine Email : esjeon@skku.edu J Korean Med Assoc 2008; 51(4): 306-316 Abstract Heart failure is the final pathway for myriad diseases that affect the heart. Patients with refractory symptoms of heart failure despite ultimate medical therapy have very poor prognosis. In these patients, replacement of failing heart with permanent organ transplantation or ventricular assist device, which is temporarily or permanently implanted, is often lifesaving and can improve long term prognosis. Cardiac transplantation is the established standard for the treatment of endstage cardiac disease refractory to medical therapy. The clinical success of transplantation has been streadily improving with the refinement of recipient selection, better donor management, and better immunosuppressive agents. Recent substantial evolution of mechanical circulatory assist devices improved dramatically the outcome of not only patients in decompensated heart failure but also a large proportion of acute heart failure patients in cardiogenic shock. With this evolution, implantable sophisticated devices are being used as destination therapy as a substitute for transplantation and are expected to diminish the intrinsic shortage of donor compared to the epidemic of heart failure. Keywords : Endstage heart failure; Heart transplantation; Mechanical assist device 306
Treatment of Medically Intractable End Stage Heart Failure Table 1. Anticipated survival according to severity of advanced heart failure (adapted from Consensus Conference Report, J Am Coll Cardiol 2001; 37: 340). Disease entity Severity of Heart Failure Expected > 50% Mortality Cardiogenic shock Chronic heart failure with exacerbation into critical low output state Inhospital Acute myocardial infarction Postcardiotomy shock Chronic heart failure Dependent on intravenous inotropic therapy 3 ~6 months Class IV symptoms on oral therapy 12~24 months Refractory symptoms at rest or minimal exertion Less than 12 months Risk factors such as decreasing sodium, Less than 12 months increasing creatinine and/or blood urea nitrogen Stabilization as class III More than 24 months Heart failure Refractory ventricular arrhythmias Variable, not estimated Chronic severe posttransplant graft dysfunction with allograft vasculopathy Less than 12 months 307
Jun ES Choi JH Table 2. Indications and Contraindications for heart transplantation (adapted from Edwards NM ed, Cardiac Transplantation. The Columbia University Medical Center/New YorkPresbyterian Hospital Manual. Totowa, New Jersey: Humana Press, 2004). Indications VO 2 max < 10~14mg/kg/min NYHA class IV History of recurrent hospitalization for congestive heart failure Recurrent symptomatic ventricular arrhythmia Refractory ischemia without feasibility of revascularization and left ventricular Ejection fraction < 20~25% Contraindications Age > 65 year Active infection Active ulcer disease Severe diabetes mellitus with endorgan damage Severe peripheral vascular or cerebrovascular disease Coexisting neoplasm Morbid obesity Creatinine clearance < 40~50ml/min, effective renal plasma flow < 200ml/min Biliribin > 2.5mg/dl, transaminases > 2 normal Severe pulmonary dysfunction with FVC and FEV1 < 40% of predicted Especially with intrinsic lung disease Pulmonary artery systolic pressure > 60mmHg, Mean transpulmonary gradient > 15mmHg Pulmonary vascular resistance > 5 Wood units Active pulmonary thromboembolism Active diverticulitis 308
Treatment of Medically Intractable End Stage Heart Failure Table 3. Immunosuppressive agents after heart transplantation Classification Drugs Mechanism Steroid Prednisolone, Methylprednisolone Nonspecific anti inflammatory agent Inhibition of IL2 gene transcription Calcineurin inhibitor Cyclosporine Binds FKBP, inhibit IL 2 gene transcription Tacrolimus (Prograf) Azathioprine Inhibit purine metabolism Antiproliferative agents Mycophenolate mofetil (MMF, Cellcept) Inhibit purine metabolism Sirolimus, Everolimus Block IL2R downstream Polyclonal anti T cell Ab Anti T cell ATGAM, RATG, ATS Monoclonal anti T cell Ab Anti T cell Antibodies Anti CD3: OKT3 Anti IL2R: Daclizumab (Zenapax), Basiliximab (Simulect) Monoclonal anti B cell Ab Anti B cell Anti CD20: Rituximab (Rituxan, MabThera) 309
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Treatment of Medically Intractable End Stage Heart Failure Figure 1. Survival rates of heart failure (Adapted from Levy, N Engl J Med 2002; 347: 1397-1402). 311
Jun ES Choi JH Oxygenator Femoral artery Centrifugal pump Femoral vein 7Fr 16Fr 20Fr Figure 2. Diagram of percutaneous cardiopulmonary support system (PCPS; EBS Capiox, Terumo, Japan). 312
Treatment of Medically Intractable End Stage Heart Failure Outflow conduit Outflow conduit Inflow conduit Inflow conduit Rt. sided pump Lt. sided pump A Pneumatic drive line B External battery pack Skin entry site Aorta Left ventricle To aorta Outlet stator and diffuser Motor Pump housing From left ventricle System controller Continuous flow LVAD Percutaneous lead Percutaneous lead Rotor Blood flow Inlet stator and blood flow straightener C Figure 3. Diagrams of ventricular assist device (A: Impella (Abiomed, USA), B: BiVAD, C: implantable continuous flow pump)(adapted from Miller, New Engl J Med 2007: 357; 9: 885-896). 313
Jun ES Choi JH Figure 4. Scheme for selection of patients with acute cardiac disease or congestive heart failure for implantation of left ventricular assist devices (adapted from Rose, et al. N Engl J Med 2001; 345: 1435-1443). 314
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