**3.2. General indications**

Currently, the European Society of Cardiology guidelines for treatment of end stage heart failure include the use of left ventricular assist devices as a Class IB recommendation in patient's refractory to medical therapy while waiting for a heart transplant. In addition, the American Heart Association has also issued a guidance document describing the use of mechanical circulatory support in the setting of bridge to transplant as a Class IB recommendation [12]. There is data to suggest that patients bridged to heart transplant with LVAD have higher posttransplant mortality compared to those without LVADs. However, much of this data stems from old risk calculations based on outcomes after implantation of pulsatile flow LVADs. As identified above, complication rates improved markedly as these devices have largely given way to continuous flow VADs with a more acceptable side-effect profile.

The current indications for heart transplantation include hemodynamically compromised patients with New York Heart Association class III-IV, as well as patients with stage D heart failure who are in refractory cardiogenic shock and dependent on intravenous inotropic support to maintain adequate organ perfusion. Further indications include severe angina that limits routine activity and is not amenable to revascularization, and recurrent symptomatic ventricular arrhythmias refractory to all other therapeutic modalities. Once listed, the current United Network for Organ Sharing (UNOS) organ-allocation system gives its highest transplant priority status (Status 1A) to those hospitalized patients who dependent on either inotropic medical therapy, or mechanical circulatory support such as LVAD support. UNOS designates an intermediate priority status (Status 1B) to those patients who are receiving inotropic or mechanical support at home. Patients who have infectious, bleeding, or thromboembolic complications while on VAD support may be advanced to 1A status until the time of transplantation; there is an additional discretionary option where patients with LVAD support may be advanced to Status 1A based on the decision of their transplant team and lasting for 1 month before downgrade back to 1B. Most other patients are given standard priority on the waitlist (Status 2).

In order to assist with optimal patient selection for placement of an LVAD, the INTERMACS registry has developed seven clinical profiles to identify patients. (1) Level 1 includes patients who are in critical cardiogenic shock requiring mechanical support. (2) Level 2 includes patients who are declining despite inotropic support. (3) Level 3 includes patients who are stable on inotropic support. (4) Level 4 includes patients with resting symptoms. (5) Level 5 includes patients who are intolerant to exertion. (6) Level 6 includes patients who are able to engage in limited exertion. (7) Level 7 includes patients who have advanced NYHA III heart failure. In the early years of LVAD implementation, the first two profiles (Level 1 and 2) comprised 60–80% of the LVAD candidates who were considered to be candidates for bridge to transplant. More recently, a shift has occurred in response to improved patient selection and risk stratification such that that the majority of patients implanted are now INTERMACS 3 and 4 profiles. Currently, 80% of patients who are being implanted with LVAD fall within INTERMACS Levels 2–4 [13].

A number of additional risk stratification and preoperative predictive factors have been developed to help select LVAD candidates and predict in-hospital mortality. For example, a multivariable risk score has been generated from preoperative factors of destination-therapy patients, and this highlights risk factors such as low albumin, low platelet count, abnormal liver function test or evidence of right ventricular dysfunction [14]. More recently, a risk score for LVAD patients was developed which showed that age and center experience were determinants of long-term survival [15]. While conventionally, LVAD placement is increasingly likely with increasing severity of INTERMACS profile, the ROADMAP clinical trial has shown that early implantation in lower INTERMACS profiles (4–7) outcomes are as favorable as earlier trials with improvements in quality of life [16]. Survival patterns from the UNOS database suggest that with the current LVAD technology, patients supported with LVAD support as a bridge to therapy demonstrate an improved survival while listed for heart transplantation, and the use of LVADs as a bridging strategy could potentially improve patient survival while waiting for transplantation, in turn allowing for better allocation of donor hearts [17]. Similarly, a 2016 study utilizing the United Network of Organ Sharing (UNOS) database showed those patients who underwent LVAD implantation prior to being listed for heart transplantation had improved survival compared to those who were medically managed; this survival benefit extended to those who were implanted with a LVAD while awaiting heart transplantation [18].

In general, the implementation of the VAD has led to a number of significant effects upon heart transplantation and the donor population. (1) There are now a significant number of patients with end stage heart failure who would otherwise have died while awaiting emergency transplantation, who are now surviving to have heart transplants performed under non-emergent circumstances. This has a profound effect on the pool of available donors as well as the acuity of transplant. (2) Cardiogenic shock with multi-organ dysfunction, previously an indication for emergency transplantation, is increasingly becoming a contraindication to transplantation due to the relatively poor likelihood of successful transplantation. With the option for temporization and recover without risking the high perioperative mortality and loss of scarce allografts associated with transplantation, the procedure is now being supplanted by mechanical support and then transplantation when the patients are recovered and shock is reversed. (3) The overpopulation of waitlists by patients with LVADs with acuity Status 1A who receive priority over ambulatory patients will make heart transplantation increasingly unlikely as a therapy for the treatment of ambulatory heart failure. (4) The LVAD as a bridge to transplant has allowed end stage heart failure to be treated in certain patients as an ambulatory disease in an outpatient fashion, rather than a disease requiring continued ICU management [6].
