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Therapeutic options for end stage heart failure (HF) was the main topic of a lively and stimulating FOCUS session held at the European Society of Cardiology (ESC) 2007 Congress. Michael Böhm (Homburg, Germany) and Marco Metra (Brescia, Italy) were chairing and Piotr Ponikowski (Wroclaw, Poland), Paul Mohacsi (Berne, Switzerland) and Mary Ryder (Dublin, Ireland) were the speakers.
Michael Bohm introduced the topic of end-stage HF. Piotr Ponikowski further highlighted the differences between advanced chronic HF (ACHF) and end-stage HF.
Improvement of cardiovascular treatment and implantation of automatic implantable cardioverter defibrillators are increasing the number of patients progressing to ACHF and end-stage HF. The characteristics of the patients with ACHF have been recently outlined in a position statement by the Study Group on ACHF of the Heart Failure Association of ESC. They include the following criteria: 1) severe symptoms of HF (NYHA class III or IV); 2) history of episodes of fluid retention and/or of reduced cardiac output at rest (peripheral hypoperfusion); 3) objective evidence of severe cardiac dysfunction, shown by at least either a low LVEF ( < 30%) and/or a LV end-systolic volume >60 mL/m2, a pseudonormal or restrictive mitral inflow pattern, high LV filling pressures, high BNP or NT-ProBNP plasma levels; 4) severe impairment of functional capacity shown by either inability to exercise or 6MWT distance <300 meters or peak VO2 < 12 to 14 ml/kg/min; 4) history of > 1 HF hospitalisation in the past 6 months; 5) optimal medical treatment including diuretics, inhibitors of the renin-angiotensin-aldosterone system, and beta-blockers, unless poorly tolerated or contraindicated, and CRT, when indicated.(1)
End-stage HF represents a “more advanced” stage of ACHF. Patients’ limitation and, above all, patients’ prognosis are extremely severe. Importantly, while ACHF is still a reversible condition, this is not the case for end-stage HF. All possible therapies have already been used and heart transplantation or, as shown below, left ventricular assist device (LVAD) are the only possible options.
Some clinical features have an essential role in patients with ACHF and end-stage HF. Congestion and, namely, its persistence after discharge, are particularly important. Patients with persistent clinical signs of congestion, such as jugular vein congestion, oedema, weight gain, need of larger doses of diuretics, have a poor prognosis. Inotrope-dependence, defined as clinical deterioration after inotrope infusion withdrawal, indicates a further increase in risk with a median survival of 4-6 months.
Myocardial injury and impaired left ventricular function have an essential role in the pathophysiology of end-stage HF. These patients often have marked neurohormonal activation, with heightened sympathetic activity and reduced vagal drive, insulin resistance and inflammatory activation. All these changes contribute to the progression of myocardial injury up to a stage when adequate tissue and organ perfusion can not be longer provided. Peripheral changes with impaired skeletal muscle perfusion, abnormal skeletal muscle metabolism and reduced muscle mass contribute to patients’ symptoms.
Paul Mohacsi has thoroughly shown the medical treatment and devices for treatment of end-stage HF. Medical treatment should first include all evidence based therapies for patients with chronic HF. Thus, ACE inhibitors, angiotensin receptor blockers, aldosterone antagonists and beta-blockers should be administered to these patients and titrated to target doses, when possible. Unfortunately, patients with ACHF and end-stage HF frequently can not tolerate these therapies. Other more experimental approaches like triiodthyronin, levosimendan and iron and erythropoietin (in anaemic patients), should be considered.
Cardiac resynchronisation therapy has been associated with an improvement in symptoms, well being, exercise capacity (6MWTD and peak VO2) as well as with reduced hospitalisations and mortality, compared to control, in patients with moderate to severe HF, LV systolic dysfunction and prolonged QRS duration. This device is clearly indicated, whenever possible.
Heart transplantation and LVADs are the “last option” for the increasing number of patients in whom all the previous tools have failed or have been insufficient. New devices, like left atrium to aorta by-pass by Tandem heart, can yield increased cardiac output to the levels necessary to achieve adequate peripheral perfusion and avoid organ damage. Moreover, reduction in cardiac work may allow recovery of myocardial function in selected cases.
The indications to LVADs include end- stage HF, acute HF caused by either acute myocarditis, acute myocardial infarction (after revascularisation procedures have been tried but have been ineffective), end-stage cardiomyopathy, postoperative low cardiac output, postoperative graft failure in transplanted patients. Patients with an indication to LVAD are generally transplant candidates with severe hemodynamic impairment, shown by a cardiac index < 2 L//min/m2, systolic blood pressure < 80 mmHg, pulmonary wedge pressure > 20 mmHg, on optimal medical treatment. Right ventricular function, myocardial ischemia, valvular disease, intracardiac shunts, arrhythmias, must also be excluded as causes of HF. Important extracardiac diseases are also criteria of exclusion.
The main complications of LVADs include bleeding and reoperation (approximately 30% of patients), right ventricular failure (≈ 10%), thromboembolism (up to 20%), infections (25%), rare complications are device dysfunction and haemolysis. Age, co-morbidities and pulmonary vascular resistance are the main prognostic factors for patients with LVADs.
Palliative care is the last option for patients with end-stage HF. This topic has been elegantly covered by Mary Ryder. Palliative care has been defined by the World Health Organisation in 2007 as “… an approach that improves the quality of life of patients and their families facing the problem associated with life-threatening illness, through the prevention and relief of suffering by means of early identification and impeccable assessment and treatment of pain and other problems, physical, psychosocial and spiritual’. Patients with end-stage HF may realise they have a dim prognosis and are going to die soon. Feelings like fear may become extremely important.
Recent studies have shown that pain, fatigue, breathlessness, anxiety, depression are the most frequent symptoms of the patients with terminal illnesses. Differently from patients with cancer, patients with end-stage HF generally have important co-morbidities that further worsen quality of life and that may dominate patients’ clinical problems. Social world is severely shrunken, health and social services, patients and family education are generally lacking. Again, differently from cancer, which is generally characterised by progressive worsening till death, HF is often characterised by multiple episodes of worsening followed by relapses. This causes a rather unpredictable clinical course with further difficulties, if not lack of chances, to program end of life care.
The number of patients who progress to ACHF and end-stage HF is going to increase in the next years. These patients have marked neurohormonal and inflammatory activation. However, severe cardiac dysfunction with lung and peripheral congestion and tissue hypoperfusion are the hallmarks of this condition. Optimal medical treatment and, when indicated, CRT have failed to improve patient’s condition and/or are not tolerated. LVADs and heart transplantation are indicated, when possible. Palliative care helps the patient affording his/her final days. However, it is not sufficiently implemented in many European countries.
(1) Metra M, Ponikowski P, Dickstein K, McMurray JJ, Gavazzi A, Bergh CH, Fraser AG, Jaarsma T, Pitsis A, Mohacsi P, Bohm M, Anker S, Dargie H, Brutsaert D, Komajda M; Heart Failure Association of the European Society of Cardiology. Advanced chronic heart failure: A position statement from the Study Group on Advanced Heart Failure of the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail. 2007;9:684-94.
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Options for end stage heart failure - Focus session
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