What are the indications, contraindications, evaluation criteria, and peri‑operative management for heart transplantation in a patient with end‑stage heart failure?

Heart Transplantation in End-Stage Heart Failure

Referral for cardiac transplantation is a Class I recommendation (Level of Evidence B) for all potentially eligible patients with refractory end-stage heart failure who remain severely symptomatic despite optimal medical and device therapy. 1

Primary Indications for Heart Transplantation

Heart transplantation significantly increases survival, exercise capacity, quality of life, and return to work compared with conventional treatment in properly selected patients. 1

Patients should be referred when they meet these criteria:

• Severe symptoms at rest or minimal exertion despite >2 months of optimal medical and device therapy 1, 2
• LVEF <25% with peak VO₂ <12 mL/kg/min on cardiopulmonary exercise testing 1, 2
• ≥3 heart failure hospitalizations in the previous 12 months without obvious precipitating cause 1, 2
• Dependence on continuous intravenous inotropic therapy to maintain adequate organ perfusion 1, 2
• Progressive end-organ dysfunction with worsening renal and/or hepatic function due to reduced perfusion 1, 2
• Severe hemodynamic compromise: pulmonary capillary wedge pressure ≥20 mmHg AND systolic blood pressure ≤80-90 mmHg OR cardiac index ≤2 L/min/m² 1, 2

The 2016 ESC guidelines emphasize that before considering a patient to have refractory heart failure, physicians must confirm diagnostic accuracy, identify contributing conditions, and ensure all conventional medical strategies have been optimally employed. 1

Absolute Contraindications to Heart Transplantation

The following are absolute contraindications per the 2016 ESC guidelines 1:

• Active infection (though HIV, hepatitis, Chagas disease, and tuberculosis can be considered with strict management protocols) 1
• Severe peripheral arterial or cerebrovascular disease 1
• Pharmacologically irreversible pulmonary hypertension (LVAD should be considered first with subsequent re-evaluation) 1
• Irreversible renal dysfunction (e.g., creatinine clearance <30 mL/min) 1
• Systemic disease with multi-organ involvement 1
• Other serious co-morbidity with poor prognosis 1
• Pre-transplant BMI >35 kg/m² (weight loss is recommended to achieve BMI <35 kg/m²) 1
• Current alcohol or drug abuse 1
• Uncertain social supports 1

Critical nuance: Some contraindications are transient and treatable. For patients with cancer requiring heart transplantation, close collaboration with oncology specialists should occur to stratify risk of tumor recurrence. 1

Pre-Transplant Evaluation Criteria

Patients must demonstrate:

• Motivation, adequate information, and emotional stability 1
• Capability of complying with intensive postoperative treatment 1
• End-stage heart failure with severe symptoms, poor prognosis, and no remaining alternative treatment options 1

The evaluation process requires multidisciplinary collaboration to determine if: (1) the patient's cardiac status is limited enough despite optimal medical therapy to benefit from transplantation; (2) the patient lacks comorbidities that would preclude transplantation; and (3) the patient demonstrates compliance and possesses adequate social support. 3

Perioperative Management Principles

Pre-Transplant Stabilization

Meticulous identification and control of fluid retention is a Class I recommendation (Level of Evidence B) in patients with refractory end-stage heart failure. 1

Referral to a heart failure program with expertise in managing refractory heart failure is a Class I recommendation (Level of Evidence A) before transplantation. 1

Anesthetic Considerations

The American College of Cardiology and American Heart Association provide specific guidance for patients with left ventricular failure undergoing surgery 4:

• Maintain sinus rhythm and control ventricular rate to optimize left ventricular filling 4
• Titrate intravascular volume carefully to ensure adequate forward cardiac output without excessive rise in left atrial pressure 4
• Use invasive hemodynamic monitoring and intraoperative transesophageal echocardiography to guide management 4
• Preferred vasopressors: phenylephrine or norepinephrine (not agents that reduce preload) 4
• Avoid tachycardia as it shortens diastolic filling time, resulting in inadequate left ventricular filling and decreased cardiac output 4
• Treat systemic hypertension with arterial dilators rather than preload-reducing agents like nitroglycerin 4

Post-Transplant Challenges

The main long-term challenges include consequences of immunosuppressive therapy: antibody-mediated rejection, infection, hypertension, renal failure, malignancy, and coronary artery vasculopathy. 1

Bridging Strategies: LVAD as Bridge to Transplant

An LVAD should be considered (Class IIa recommendation, Level of Evidence C) in patients with end-stage HFrEF despite optimal medical and device therapy who are eligible for heart transplantation to improve symptoms, reduce risk of heart failure hospitalization, and reduce risk of premature death. 1

Key timing consideration: Earlier LVAD implantation at INTERMACS Levels 4-5 shows superior outcomes (1-year survival 78.7-93.0%) compared to waiting until more severe deterioration at Levels 1-2 (1-year survival 52.6-63.1%). 2

Critical pitfall: Waiting too long to refer patients for LVAD evaluation is a common mistake. Earlier implantation in less severely ill patients shows better outcomes than delaying until cardiogenic shock. 2

LVAD Evaluation Requirements

Evaluation of right ventricular function is crucial since postoperative RV failure greatly increases perioperative mortality and reduces survival to and after transplantation. 1, 2

• If severe biventricular failure or high risk for persistent RV failure exists, consider BiVAD (only for transplant-eligible patients, not destination therapy) 1, 2
• For patients with chronic biventricular failure, implantation of a BiVAD may be necessary, though outcomes are inferior to LVAD therapy 1

Alternative to Transplantation: Destination Therapy

An LVAD should be considered (Class IIa recommendation, Level of Evidence B) as destination therapy in highly selected patients with refractory end-stage heart failure who are not eligible for heart transplantation and have an estimated 1-year mortality over 50% with medical therapy to reduce risk of premature death. 1

End-of-Life Considerations

When severe symptoms persist despite all recommended therapies:

• Options for end-of-life care should be discussed with the patient and family (Class I recommendation, Level of Evidence C) 1
• Patients with implantable defibrillators should receive information about the option to inactivate the defibrillator (Class I recommendation, Level of Evidence C) 1

Common Pitfalls to Avoid

Do not use these therapies in refractory end-stage heart failure:

• Partial left ventriculectomy is not recommended in patients with nonischemic cardiomyopathy (Class III recommendation) 1
• Routine intermittent infusions of vasoactive and positive inotropic agents are not recommended (Class III recommendation, Level of Evidence A) 1

Continuous intravenous infusion of a positive inotropic agent may be considered only for palliation of symptoms (Class IIb recommendation, Level of Evidence C), not as definitive therapy. 1