**2. Assessing prognosis of the patient with HF**

In spite of the recent treatment advances, HF mortality is expected to be around 10% per year in large randomized studies [3], with a median survival of approximately 2 years in unselected cohorts [4]. Because mortality during the first year post-HTx ranges between 12 and 20% and the median of survival of the heart transplant is 12 years [5], it is important to carry out an adequate prognostic stratification in order to select those patients who will obtain the maximum benefit from HTx. Along these lines, we will review the most important clinical features and risk factors that should direct clinicians to undergo an early and comprehensive evaluation, and confirm if the patient is an appropriate candidate for the available advanced therapies, before a more severe deterioration is present and treatment options become compromised.

#### **2.1. Clinical parameters**

optimization by selection and up-titration of appropriate drugs (e.g., beta-blockers and inhibitors of the renin-angiotensin-aldosterone axis), device implantation (resynchronization therapy, implanted cardioverter defibrillator), and surgical intervention if appropriate (e.g., valve replacement in case of valve disease) becomes mandatory. Only in cases where conventional HF treatment is not well tolerated and/or the patient presents an unfavorable course we will raise the option of HTx. At this point, it is useful to recognize the clinical and hemodynamic parameters that identify patients in an advanced-HF (AHF) situation (**Table 1**), which represents 5% of the total number of patients in HF [2]. In the case of patients in cardiogenic shock (CS), the priority is to get the patient out of the shock situation and correct multi-organ failure, for which we will usually need inotropic and vasoactive treatment, intra-aortic balloon counterpulsation and, in some cases, ventricular mechanical assistance devices (VAD). Once the patient is stable, we will have to attempt to wean the VAD, if we consider that myocardial

The long waiting times and the increasing number of unstable patients have favored the development of mechanical circulatory support (MCS) therapies as bridge to transplant (BTT) and bridge to candidacy or decision (BTC/BTD). This was initially achieved by the use of shortterm ventricular assist devices (STVADs), but in the last decades long-term ventricular assist

**1.**Severe symptoms of heart failure with dyspnea and/or fatigue at rest or on minimal exertion (NYHA functional

2. Episodes of fluid retention (pulmonary and/or systemic congestion, peripheral edema) and/or of reduced cardiac

**c.** High left ventricular filling pressures (mean PCWP >16 mmHg, and/or mean RAP >12 mmHg by pulmonary

3. Objective evidence of severe cardiac dysfunction, shown by at least 1 of the following

**b.** Pseudonormal or restrictive mitral inflow pattern on Doppler echocardiography

**d.** High natriuretic peptide levels, in the absence of non-cardiac causes

**b.** 6-minute walk test ≤300 m or less in females and/or patients aged ≥75 years

6. Presence of all the previous features despite "attempts to optimize" therapy including diuretics, reninangiotensin-aldosterone system inhibitors, and beta-blockers, unless these are poorly tolerated or contraindicated,

**Table 1.** Definition of advanced heart failure according to ESC (Adapted from Metra et al. [2]).

NYHA: New York Heart Association; PCWP: pulmonary capillary wedge pressure; RAP: right atrial pressure.

4. Severe impairment of functional capacity shown by 1 of the following:

recovery is an option, or HTx otherwise.

class III or IV)

12 Heart Transplantation

output at rest (peripheral hypoperfusion)

artery catheterization)

**a.** Inability to exercise

**a.** Low left ventricular ejection fraction (<30%)

**c.** Peak oxygen consumption <12 to 14 mL/kg/min

and cardiac resynchronization when indicated

5. History of ≥1 heart failure hospitalization in the past 6 months

Multiple clinical parameters are associated with higher mortality in HF patients. During the last years, there has been a considerable effort by clinicians to define the common characteristics of AHF, and these can be seen in **Table 1**. For instance, progressive treatment intolerance, persistent clinical signs of HF, echocardiographic and hemodynamic signs of low output, multiorgan involvement and repeated hospitalizations, severely compromise patients' prognosis [6].

#### **2.2. Etiology of heart failure**

Ischemic cardiomyopathy has traditionally been associated with higher mortality, especially when severe left ventricular dysfunction and three-vessel or main stem left coronary artery disease unsuitable for revascularization is present [7]. Congenital heart diseases are also associated with greater mortality because of the higher degree of pulmonary arterial hypertension and possible previous cardiac surgeries [5]. Therefore, we recommend referring these patients to specific transplant centers with congenital heart disease expertise.

hypereosinophilic syndrome, use of anthracyclines), infiltrative disease (e.g., amyloidosis or sarcoidosis), and storage cardiomyopathy (Anderson-Fabry disease, Danon disease, hemochromatosis) with amyloidosis being the most common etiology. Nonetheless, genetic restrictive cardiomyopathy is also a diagnostic possibility that should be taken into account, especially when family involvement is present. In this regard, DES mutations are characterized by severe diastolic dysfunction and atrio-ventricular block, with progressive systolic

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In regards to amyloidosis, it is important to distinguish between the different types of amyloid deposit because of the different prognosis and treatment strategies. In immunoglobulin light chain amyloidosis (AL or primary amyloidosis) the evolution of HF is very fast, and although HTx is feasible, significant involvement of other organs should be ruled out. Nonetheless, HTx outcomes are significantly worse, even with bone marrow transplant, and survival rates reach 82% and 65% at 1 and 5 years, respectively [15, 16]. In cases of hereditary transthyretin amyloidosis, HF does not progress as rapidly as in light chain amyloidosis, and it is recommended to perform HTx followed by liver transplant at a second time point to prevent further myocardial compromise, although the advent of new drugs to treat transthyretin amyloid and the different mutations involved may change this strategy. In any case, it is also essential

Among the different types of cardiomyopathies, serious multi-organ involvement, particularly neuromuscular involvement that could compromise the respiratory capacity should always be ruled out. Thus, the decision to go to HTx must be taken after a comprehensive multidisciplinary evaluation that should involve at least, a HF specialist, a pneumologist and

Clinical assessment of functional capacity is a subjective measure of the patient's ability to perform daily activities that can easily be obtained, and correlates with the severity of the disease. It is measured by the New York Heart Association (NYHA) scale, which stratifies four groups (functional class) from less to more limitations in physical activity. Candidates for HTx are most of the time in functional class IV despite optimal medical treatment (stage D of the American Heart Association classification), although they can alternate with some periods

In spite of its usefulness, this scale is a subjective measure that an change depending on the patient and physician's interpretation, and should be complemented by the use of more objective tests. The cardiopulmonary exercise test (CPET) measures peak oxygen uptake (VO2), which is the most accurate measure of exercise capacity and cardiopulmonary performance [18]. According to the latest guidelines, a peak VO2 ≤ 14 mL/kg/min or peak VO2 ≤ 12 mL/kg/ min in the presence of β-blockers at maximal exertion should be used to include patients in HTx list, although this should not be the unique parameter. In cases of a sub-maximal cardiopulmonary exercise test, defined as the ratio of carbon dioxide output/oxygen uptake (also called respiratory exchange ratio [RER]) < 1, the use of ventilation to carbon dioxide slope

dysfunction and early-onset end-stage HF, and frequent neuromuscular disease.

to exclude severe amyloid involvement of other organs [17].

(VE/VCO2) > 35 is also useful because of its prognostic value [19].

a neurologist.

**2.3. Functional capacity**

of partial recovery to functional class III.

Cardiomyopathies are disorders in which the heart muscle is structurally and functionally abnormal in the absence of other causes such as coronary artery disease, arterial hypertension, valvular heart disease, congenital heart disease or any other condition that may cause abnormal loading conditions. In idiopathic dilated cardiomyopathies, the presence of a higher degree of fibrosis demonstrated by delayed gadolinium enhancement in cardiac magnetic resonance (MRI) is associated with worse prognosis and sudden death [8]. T1 and T2 mapping are MRIbased techniques that are able to measure the extracellular volume in the heart, which have also been shown to correlate with prognosis in patients with HF and cardiomyopathies [9].

Moreover, a non-negligible number of patients are affected by familial dilated cardiomyopathy (DCM), which can sometimes be easily identified with a simple family pedigree [10]. On this subject, with the advent of next generation sequencing gene techniques, we are now able to identify multiple mutations associated with DCM in more than 50 genes [11]. The most frequent ones are titin (TTN), lamin (LMNA) and desmin (DES). Pathogenic mutations in LMNA [12] and DES [13] as well as filamin C (FLNC) [14] genes are specifically related with frequent arrhythmias and subsequent worse prognosis. Therefore, genetic testing should also be taken into account when stratifying patients, especially because they usually affect young individuals, with less evident HF symptoms in spite of the severe myocardial disease.

The indication for HTx in patients with hypertrophic cardiomyopathy (HCM) is unusual and should be reserved for patients with persistent marked symptoms, after all therapeutic possibilities have been applied, including septal reduction techniques. It is more frequent to perform HTx in patients with HCM with progressive severe left ventricular dysfunction and/or a restrictive pattern.

Arrhythmogenic cardiomyopathy is produced by the alteration of cardiac desmosomes, which predisposes to an abnormal response to mechanical stress. Genetically, it is transmitted predominantly in an autosomal dominant manner with a variable clinical expression and an incomplete penetrance that is dependent of age. It is a frequent cause of sudden death and ventricular arrhythmias, especially in young adults and athletes, because it is linked to severe ventricular arrhythmias, especially when it affects the left ventricle. Furthermore, in spite of the use of implantable cardiac defibrillators (ICD), severe cardiac events including sudden cardiac death and mortality might appear over time, because of progressive biventricular dysfunction and untreatable arrhythmias. Hence, HTx should always be taken into account during follow-up [13, 14].

Restrictive cardiomyopathy (RCM) is the least common and it comprises a group of diseases of the myocardium, characterized by a rigid myocardium that produces diastolic dysfunction that leads to a restrictive physiology, with a normal or reduced systolic and diastolic ventricular volumes and non-thickened or minimally thickened ventricular walls. The majority of the restrictive cardiomyopathies can be secondary to a toxic process (e.g., radiotherapy, hypereosinophilic syndrome, use of anthracyclines), infiltrative disease (e.g., amyloidosis or sarcoidosis), and storage cardiomyopathy (Anderson-Fabry disease, Danon disease, hemochromatosis) with amyloidosis being the most common etiology. Nonetheless, genetic restrictive cardiomyopathy is also a diagnostic possibility that should be taken into account, especially when family involvement is present. In this regard, DES mutations are characterized by severe diastolic dysfunction and atrio-ventricular block, with progressive systolic dysfunction and early-onset end-stage HF, and frequent neuromuscular disease.

In regards to amyloidosis, it is important to distinguish between the different types of amyloid deposit because of the different prognosis and treatment strategies. In immunoglobulin light chain amyloidosis (AL or primary amyloidosis) the evolution of HF is very fast, and although HTx is feasible, significant involvement of other organs should be ruled out. Nonetheless, HTx outcomes are significantly worse, even with bone marrow transplant, and survival rates reach 82% and 65% at 1 and 5 years, respectively [15, 16]. In cases of hereditary transthyretin amyloidosis, HF does not progress as rapidly as in light chain amyloidosis, and it is recommended to perform HTx followed by liver transplant at a second time point to prevent further myocardial compromise, although the advent of new drugs to treat transthyretin amyloid and the different mutations involved may change this strategy. In any case, it is also essential to exclude severe amyloid involvement of other organs [17].

Among the different types of cardiomyopathies, serious multi-organ involvement, particularly neuromuscular involvement that could compromise the respiratory capacity should always be ruled out. Thus, the decision to go to HTx must be taken after a comprehensive multidisciplinary evaluation that should involve at least, a HF specialist, a pneumologist and a neurologist.

#### **2.3. Functional capacity**

disease unsuitable for revascularization is present [7]. Congenital heart diseases are also associated with greater mortality because of the higher degree of pulmonary arterial hypertension and possible previous cardiac surgeries [5]. Therefore, we recommend referring these patients

Cardiomyopathies are disorders in which the heart muscle is structurally and functionally abnormal in the absence of other causes such as coronary artery disease, arterial hypertension, valvular heart disease, congenital heart disease or any other condition that may cause abnormal loading conditions. In idiopathic dilated cardiomyopathies, the presence of a higher degree of fibrosis demonstrated by delayed gadolinium enhancement in cardiac magnetic resonance (MRI) is associated with worse prognosis and sudden death [8]. T1 and T2 mapping are MRIbased techniques that are able to measure the extracellular volume in the heart, which have also

been shown to correlate with prognosis in patients with HF and cardiomyopathies [9].

als, with less evident HF symptoms in spite of the severe myocardial disease.

a restrictive pattern.

14 Heart Transplantation

during follow-up [13, 14].

Moreover, a non-negligible number of patients are affected by familial dilated cardiomyopathy (DCM), which can sometimes be easily identified with a simple family pedigree [10]. On this subject, with the advent of next generation sequencing gene techniques, we are now able to identify multiple mutations associated with DCM in more than 50 genes [11]. The most frequent ones are titin (TTN), lamin (LMNA) and desmin (DES). Pathogenic mutations in LMNA [12] and DES [13] as well as filamin C (FLNC) [14] genes are specifically related with frequent arrhythmias and subsequent worse prognosis. Therefore, genetic testing should also be taken into account when stratifying patients, especially because they usually affect young individu-

The indication for HTx in patients with hypertrophic cardiomyopathy (HCM) is unusual and should be reserved for patients with persistent marked symptoms, after all therapeutic possibilities have been applied, including septal reduction techniques. It is more frequent to perform HTx in patients with HCM with progressive severe left ventricular dysfunction and/or

Arrhythmogenic cardiomyopathy is produced by the alteration of cardiac desmosomes, which predisposes to an abnormal response to mechanical stress. Genetically, it is transmitted predominantly in an autosomal dominant manner with a variable clinical expression and an incomplete penetrance that is dependent of age. It is a frequent cause of sudden death and ventricular arrhythmias, especially in young adults and athletes, because it is linked to severe ventricular arrhythmias, especially when it affects the left ventricle. Furthermore, in spite of the use of implantable cardiac defibrillators (ICD), severe cardiac events including sudden cardiac death and mortality might appear over time, because of progressive biventricular dysfunction and untreatable arrhythmias. Hence, HTx should always be taken into account

Restrictive cardiomyopathy (RCM) is the least common and it comprises a group of diseases of the myocardium, characterized by a rigid myocardium that produces diastolic dysfunction that leads to a restrictive physiology, with a normal or reduced systolic and diastolic ventricular volumes and non-thickened or minimally thickened ventricular walls. The majority of the restrictive cardiomyopathies can be secondary to a toxic process (e.g., radiotherapy,

to specific transplant centers with congenital heart disease expertise.

Clinical assessment of functional capacity is a subjective measure of the patient's ability to perform daily activities that can easily be obtained, and correlates with the severity of the disease. It is measured by the New York Heart Association (NYHA) scale, which stratifies four groups (functional class) from less to more limitations in physical activity. Candidates for HTx are most of the time in functional class IV despite optimal medical treatment (stage D of the American Heart Association classification), although they can alternate with some periods of partial recovery to functional class III.

In spite of its usefulness, this scale is a subjective measure that an change depending on the patient and physician's interpretation, and should be complemented by the use of more objective tests. The cardiopulmonary exercise test (CPET) measures peak oxygen uptake (VO2), which is the most accurate measure of exercise capacity and cardiopulmonary performance [18]. According to the latest guidelines, a peak VO2 ≤ 14 mL/kg/min or peak VO2 ≤ 12 mL/kg/ min in the presence of β-blockers at maximal exertion should be used to include patients in HTx list, although this should not be the unique parameter. In cases of a sub-maximal cardiopulmonary exercise test, defined as the ratio of carbon dioxide output/oxygen uptake (also called respiratory exchange ratio [RER]) < 1, the use of ventilation to carbon dioxide slope (VE/VCO2) > 35 is also useful because of its prognostic value [19].

Also, the 6-minute walking test (6'WT) measures the distance that the patient is able to walk in 6 minutes and is useful when a cardiopulmonary test is not available. A walking distance of less than 300 m is associated with an annual mortality above 50% [20], and is one of the criteria of AHF.

• Direct parameters: 1-right atrial pressure, 2-sistolic pulmonary arterial pressure (SPAP), 3-mean pulmonary arterial pressure (MPAP), 4-pulmonary capillary wedge pressure

• Indirect parameters: 1-transpulmonary gradient (TPG): Defined as the difference between mean pulmonary arterial pressure and capillary wedge pressure (TPG = MPAP-PCWP), 2-pulmonary vascular resistance (PVR) defined as TPG/CO is usually expressed in Wood

Reversible PHT is defined as a drop in SPAP ˂ 50 mmHg, TPG ˂ 12 mmHg and PVR ˂ 3 Woods units after optimization of cardiac index and loading conditions (indicated mainly by central venous pressure, systemic vascular resistance and systemic arterial pressure) by the use of intravenous diuretics, inotropes and vasodilators, if necessary. A combination of inotropes with direct vasodilators (e.g., dobutamine and nitroprusside) and selective vasodilators (e.g., sildenafil, nitric oxide) is also commonly used. It is important to mention that if after the pulmonary vasodilation test the PVR drops <3 UW but the systolic blood pressure

In any case, but especially when irreversible or fixed PHT is present, it is important to rule out concomitant pulmonary disease, obstructive sleep apnea syndrome or chronic pulmonary

**INTERMACS level Description 1 year survival with** 

Hemodynamic instability with increasing inotropic and vasopressor support, and critical hypoperfusion of

Dependent on inotropic support but continues with signs of clinical deterioration (worsening renal failure, nutritional depletion, and inability to restore volume

Stable with low/intermediate doses of inotropes, but necessary due to arterial hypotension, progressive renal

Patient at home on oral therapy but with high doses of diuretics and frequent symptoms of congestion at rest

Comfortable at rest and without symptoms during daily living activities, but who becomes symptomatic

Patient in NYHA class III with no recent episode of

with any meaningful physical exertion

Comfortable at rest but unable to engage in any activity 93 ± 3.9%

**LTVAD**

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52.6 ± 5.6%

63.1 ± 3.1%

78.4 ± 2.5%

78.7 ± 3%

units, 3-cardiac index expressed as the result of CO/body surface area.

falls to less than 85 mmHg, there is still a high risk of PGF after HTx [29, 30].

target organs.

balance).

failure, worsening symptoms

or with regular activity

acute decompensation

**Table 2.** INTERMACS patient profile (Source Ponikowsky et al. [27]).

(PCWP), and 4-cardiac output (CO).

1. Cardiogenic Shock ("crash and

2. Progressive decline despite inotropic support ("sliding fast" on

3. Stable but inotrope-dependent ("dependent stability")

4. Resting symptoms on oral therapy ("frequent flyer")

6. Exertion limited ("walking

7. Advanced NYHA class III

NYHA: New York Heart Association.

5. Exertion intolerant ("housebound")

wounded")

("placeholder")

burn")

inotropes)

#### **2.4. Risk scores**

Currently, there are several risk scores available that might help in patient stratification, and give support in decision making. In ambulatory patients, there are two risk scores that complement the prognostic information obtained from CPET:


The Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) is a database created in 2006, with information of more than 15,000 patients who received an MCS [25]. The INTERMACS classification was created from this registry and helps to stratify patients in an AHF situation, see **Table 2**. In this regard, patients in a higher INTERMACS profile (1 or 2) seem to have worse post-HTx outcomes than those in better pre-operative condition (INTERMACS 3-4) [26].

#### **2.5. Hemodynamic parameters**

Pulmonary hypertension (PHT) is defined by a mean pulmonary arterial pressure greater than 25 mmHg, and usually develops in response to a passive backward transmission of elevated filling pressures from the left ventricle. Nonetheless, irreversible PHT might eventually develop in response to chronic elevated pressures that cause vascular remodeling, and is closely related to primary graft failure (PGF) due to right ventricular failure (RVF), which carries an elevated mortality after HTx [28]. Therefore right heart catheterization is recommended before HTx and should be done periodically, every 3–6 months [19], especially if reversible PHT has been previously confirmed.

The main direct (measured directly during procedure) and indirect (calculated from direct parameters) parameters evaluated during right heart catheterization are:


Reversible PHT is defined as a drop in SPAP ˂ 50 mmHg, TPG ˂ 12 mmHg and PVR ˂ 3 Woods units after optimization of cardiac index and loading conditions (indicated mainly by central venous pressure, systemic vascular resistance and systemic arterial pressure) by the use of intravenous diuretics, inotropes and vasodilators, if necessary. A combination of inotropes with direct vasodilators (e.g., dobutamine and nitroprusside) and selective vasodilators (e.g., sildenafil, nitric oxide) is also commonly used. It is important to mention that if after the pulmonary vasodilation test the PVR drops <3 UW but the systolic blood pressure falls to less than 85 mmHg, there is still a high risk of PGF after HTx [29, 30].

In any case, but especially when irreversible or fixed PHT is present, it is important to rule out concomitant pulmonary disease, obstructive sleep apnea syndrome or chronic pulmonary


NYHA: New York Heart Association.

Also, the 6-minute walking test (6'WT) measures the distance that the patient is able to walk in 6 minutes and is useful when a cardiopulmonary test is not available. A walking distance of less than 300 m is associated with an annual mortality above 50% [20], and is one of the

Currently, there are several risk scores available that might help in patient stratification, and give support in decision making. In ambulatory patients, there are two risk scores that com-

**1.** The Seattle Heart Failure Model (SHFM) has 21 variables; it is derived from a study of 1125 patients with NYHA class IIIB or IV, during the Prospective Randomized Amlodipine Survival Evaluation (PRAISE) [21]. It was used in the REMATCH trial cohort for predicting 1-year mortality in the medical and LTVAD groups with good accuracy [22]. The model was also prospectively validated in five additional cohorts consisting of 9942 HF patients and 17,307 person-years of follow-up [23]. When an estimated 1-year survival of less than

**2.** The Heart Failure Survival Score (HFSS) is calculated with the following variables: VO2 max, ejection fraction of the left ventricle, sodium, mean arterial pressure, ischemic etiology, resting heart rate, QRS > 120 ms. Patients in the medium and high risk category should be considered for advanced-HF therapies such as HTx listing or VAD implanta-

The Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) is a database created in 2006, with information of more than 15,000 patients who received an MCS [25]. The INTERMACS classification was created from this registry and helps to stratify patients in an AHF situation, see **Table 2**. In this regard, patients in a higher INTERMACS profile (1 or 2) seem to have worse post-HTx outcomes than those in better pre-operative condition

Pulmonary hypertension (PHT) is defined by a mean pulmonary arterial pressure greater than 25 mmHg, and usually develops in response to a passive backward transmission of elevated filling pressures from the left ventricle. Nonetheless, irreversible PHT might eventually develop in response to chronic elevated pressures that cause vascular remodeling, and is closely related to primary graft failure (PGF) due to right ventricular failure (RVF), which carries an elevated mortality after HTx [28]. Therefore right heart catheterization is recommended before HTx and should be done periodically, every 3–6 months [19], especially if

The main direct (measured directly during procedure) and indirect (calculated from direct

parameters) parameters evaluated during right heart catheterization are:

plement the prognostic information obtained from CPET:

80% is obtained, patients should be considered for HTx [19].

criteria of AHF.

16 Heart Transplantation

**2.4. Risk scores**

tion [24].

(INTERMACS 3-4) [26].

**2.5. Hemodynamic parameters**

reversible PHT has been previously confirmed.

**Table 2.** INTERMACS patient profile (Source Ponikowsky et al. [27]).

thromboembolism. If there is no responsible pulmonary disease, there are several studies that have shown that the chronic use of bosentan or sildenafil might reduce PHT and acheive reversibility of PHT after 3–4 months of this therapy [31]. If despite an appropriate vasodilator treatment there is no reversibility of the PHT, LTVAD therapy should be considered, together with selective vasodilator treatment (usually sildenafil) [32].

pressure after some months with LTVAD [24]. In a similar fashion, renal dysfunction due to cardiorenal syndrome can improve enough to consider HTx. In this group, we can also

Regarding LTVAD as DT, one of the limitations of this strategy is the increase in adverse events associated with long-term use of LTVAD. The ROADMAP study took a sample of 200 patients in INTERMACS 4–7 and divided them into two groups: optimal medical management (OMM) or OMM plus LTVAD. The final result showed an improvement in functional capacity in the second group but with a significant increase in adverse events, especially hemorrhagic complications [36]. Although current indications for DT consider a more advanced profile of patients (criteria derived from the REMATCH and HeartMate II DT trials [37]), the results of the ROADMAP study give us and idea of the advantages and disadvantages of the use of LTVAD as DT, further supporting the fact that HTx remains the ideal therapy in this population.

Regardless of the selected strategy, the most important fact is to ensure a correct selection of candidates for LTVAD implantation. One of the tools used to predict outcomes of these patients using mechanical support is the HeartMate II Risk Score, which is derived from an analysis of the HeartMate II registry. Briefly, it is based on five variables (age, serum albumin, creatinine, INR, and center volume of LVAD) used to create an equation that predicts mortality at 90 days [38]. Moreover, because LTVADs only support the left ventricle, one of the critical points to take into consideration is the potential right ventricular failure (RVF) after MCS is initiated. Nowadays, there are no comprehensively evaluated tools to predict RVF, but some hemodynamic and echocardiographic parameters might be useful. Concerning hemodynamic evaluation, a right ventricular stroke work index less than 250 mmHg·mLm2

right atrial pressure > 15 mmHg and central venous pressure/PCWP >0.63 are considered important risk factors of RVF [40]. Echocardiographic parameters include tricuspid annular motion (TAPSE) < 7.5 mm [41], right ventricular to left ventricular end diastolic diameter ratio > 0.72 [42], severe tricuspid regurgitation, right ventricular short/long axis ratio > 0.6 [43] and right ventricular free wall strain [44]. A biventricular approach using continuous blood flow pumps has recently been reported with limited success considering the significant num-

Finally, it is very important to ensure optimal patient's self-care training by specialized nurses, and appropriate follow-up is indispensable for the success of a LTVAD program. Daily care of the device, especially considering the correct management of the driveline wound is of paramount importance to avoid infection. Moreover, the correct management of concomitant cardiovascular risk factors such as hypertension or diabetes, and other comorbidities is also a

The decision of including a patient in the HTx waiting list is not easy and should be taken together by a medical and surgical team, in a case-by-case comprehensive evaluation. Only

ber of adverse events during follow-up [45].

relevant issue in these patients that should be pursued.

**4. Inclusion in heart transplant waiting list**

), in which the

19

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[39],

include patients with recently diagnosed cancer or obesity (BMI > 35 kg/m2

implantation of a LTVAD could give them time to re-evaluate candidacy.
