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cardiac transplantation; heart transplant

Indications: 1) refractory cardiogenic shock 2) *dependence on intravenous inotropic support 3) VO2max < 10-14 mL/kg/min (severely limited functional capacity)* 4) *severe ischemia (limiting functional capacity) despite optimal medical therapy not amenable to reperfusion (CABG, PCI) 5) *recurrent significant ventricular arrhythmia refractory to therapy [2] 6) insufficient indication alone a) *low LV ejection fraction b) *history of NYHA HF class 3 or 4 [2] 7) other criteria considered (may be center-dependent) a) *< 60 years of age; < 70 years of age [13] b) *strong psychosocial support system c) *free of extra-cardiac organ dysfunction that would complicate recovery d) *exhausted all other therapeutic options * despite optimal medical therapy Contraindications: (may be center-dependent) 1) diabetes with end-organ damage, nephropathy, retinopathy 2) major chronic disabling illness 3) severe pulmonary hypertension 4) severe peripheral vascular disease 5) active infection 6) significant chronic & likely functional impairment of other vital organs (renal failure, cirrhosis, COPD ...) 7) active substance abuse (including smoking) 8) obesity 9) current mental or psychosocial instability 10) active or recent malignancy [2] Clinical manifestations: - due to absence of normal vagal tone, resting heart rate is typically 90-110/min [2] Laboratory: - cardiac transplantation 20 mRNA expression analysis (CPT) - routine within 1st 6 months to assess asymptomatic rejection [2] - endomyocardial biopsy is alternative [2] Complications: 1) acute cellular rejection a) most recipients experience 2-3 rejections during the 1st 6 months b) rejection after 12-24 months is uncommon unless immunosuppression has been decreased c) patients > 55 years of age experience less rejection d) manifests as left ventricula dysfinction resulting in acute heart failure - atrial flutter & atrial fibrillation common e) rejection severity is graded by histopathologic changes on endomyocardial biopsy 1] lymphocytic infiltration 2] myocyte necrosis 2) acute humoral rejection a) interstitial edema with deposition of immunoglobulin & complement b) rarely observed > 6 weeks after transplantation c) presents with severe left ventricular dysfunction 3) infection secondary to immunosuppression a) effects of immunosuppression are maximal 6-12 weeks after transplantaion b) most frequent cause of death in the 1st year following transplantation c) bacterial infections are common in the 1st month d) viral & opportunistic infections occur later e) pneumonitis is the most common early & late infection f) 30% of patients experience at least 1 major infection after transplantation g) cytomegalovirus within the 1st year [2] 1] most important infectious cause of morbidity 2] generally occurs 6-12 weeks following transplantation 4) infection from donor organ (hepatitis C) [14] - HCV seropositive donor confers survival disadvantage [3] 5) cardiac allograft vasculopathy - post-transplant coronary artery disease (CAD) is the primary cause of death >1 year after transplant - occurs in > 32-50% of patients within 5 years [2,7] - most common cause of heart failure - uncommon to present as chest pain (transplanted heart lacks innervation) - represents diffuse intimal hyperplasia rather than focal coronary artery stenosis - revascularization generally not beneficial 6) cyclosporine-induced hypertension 7) obesity & hyperlipidemia 8) increased risk of malignancy a) skin cancer b) B-cell lymphoma associated with Epstein-Barr virus- induced B-cell proliferation c) lung cancer [4] d) substantial radiation exposure (children) [8] - increased risk of cancer later in life, especially - breast cancer - thyroid cancer Management: 1) transplant rejection a) endomyocardial biopsy is used to assess rejection [2] - absence of or non-specific signs/symptoms of mild to moderate rejection - low grade fever, exertional dyspnea, malaise, abdominal pain, mild hypotension & tachycardia - weekly for 1st pre-operative month - biweekly for next 2 months - then reduce to 2-4 times/year b) clinical manifestations of severe rejection - hypotension - 3rd heart sound - atrial & ventricular arrhythmias c) immunosuppressive therapy: - cyclosporine - glucocorticoids - azathioprine - severe rejection - antithymocyte globulin (ATG) - monoclonal antibody OKT3 (Muromonab-CD3) d) plasmapheresis for acute humoral rejection 2) treatment of cyclosporine-induced hypertension a) Ca+2 channel blockers are 1st line agents b) addition of 2nd agent often required - diuretic - beta blocker - ACE inhibitor 3) treatment of hyperlipidemia - HMG CoA reductase inhibitor 4) assessment of coronary artery disease (CAD) - angina pectoris does not occur because of lack of innervation - CAD may present as dyspnea on exertion [2] - routine ECG to assess silent ischemia/infarction - thallium-201/MIBI scintigraphy generally unreliable - dobutamine echocardiography generally unreliable - coronary angiography is generally method of choice - intracoronary vascular ultrasonography may be better than angiography - retransplantation is only treatment for multivessel disease 5) lymphoma often regresses following reduction in immunosuppression 6) survival: - 90% at 1 year - 65-70% at 5 years

Related

post cardiac transplant coronary artery disease

Specific

heart/lung transplantation

General

organ transplantation

References

  1. Manual of Medical Therapeutics, 28th ed, Ewald & McKenzie (eds), Little, Brown & Co, Boston, 1995, pg 125
  2. Medical Knowledge Self Assessment Program (MKSAP) 11, 15, 16, 17, 18, 19 American College of Physicians, Philadelphia 1998, 2009, 2012, 2015, 2018, 2022.
  3. Gasink LB et al, Hepatitis C virus seropositivity in organ donors and survival in heart transplant recipients. JAMA 2006, 296:1843 PMID: 17047214 - Qamar AA and Rubin RH Poorer outcomes for recipients of heart allografts from HCV-positive donors: Opening the silos. JAMA 2006, 296:1900 PMID: 17047220
  4. Engels EA et al. Spectrum of cancer risk among US solid organ transplant recipients. JAMA 2011 Nov 2; 306:1891. PMID: 22045767
  5. Page RL 2nd, Miller GG, Lindenfeld J. Drug therapy in the heart transplant recipient: part IV: drug-drug interactions. Circulation. 2005 Jan 18;111(2):230-9. PMID: 15657387
  6. Mancini D, Lietz K. Selection of cardiac transplantation candidates in 2010. Circulation. 2010 Jul 13;122(2):173-83 PMID: 20625142
  7. Schmauss D, Weis M. Cardiac allograft vasculopathy: recent developments. Circulation. 2008 Apr 22;117(16):2131-41 PMID: 18427143
  8. Johnson JN et al Cumulative Radiation Exposure and Cancer Risk Estimation in Children with Heart Disease. Circulation. June 9, 2014 PMID: 24914037 http://circ.ahajournals.org/content/early/2014/05/08/CIRCULATIONAHA.113.005425.abstract - Andreassi MG and Picano E Reduction of Radiation to Children: Our Responsibility to Change. Circulation. June 9, 2014 PMID: 24914036 http://circ.ahajournals.org/content/early/2014/05/08/CIRCULATIONAHA.114.010699.abstract
  9. Garbade J, Barten MJ, Bittner HB, Mohr FW. Heart transplantation and left ventricular assist device therapy: two comparable options in end-stage heart failure? Clin Cardiol. 2013 Jul;36(7):378-82 PMID: 23595910
  10. Toyoda Y, Guy TS, Kashem A. Present status and future perspectives of heart transplantation. Circ J. 2013;77(5):1097-110. Epub 2013 Apr 3. PMID: 23614963
  11. Mehra MR, Kobashigawa J, Starling R et al Listing criteria for heart transplantation: International Society for Heart and Lung Transplantation guidelines for the care of cardiac transplant J Heart Lung Transplant. 2006 Sep;25(9):1024-42. PMID: 16962464
  12. Birati EY, Rame JE. Post-heart transplant complications. Crit Care Clin. 2014 Jul;30(3):629-37. Review. PMID: 24996612
  13. Geriatric Review Syllabus, 10th edition (GRS10) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2019
  14. Montgomery RA Perspective. Getting Comfortable with Risk. N Engl J Med 2019; 381:1606-1607. Oct 24. PMID: 31644844 https://www.nejm.org/doi/full/10.1056/NEJMp1906872
  15. National Heart, Lung, and Blood Institute (NHLBI) Heart Transplant https://www.nhlbi.nih.gov/health-topics/heart-transplant