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Current Management and Treatment

  • Alessandro Altinier
  • Alessia Paldino
  • Marta Gigli
  • Aniello Pappalardo
  • Gianfranco Sinagra
Open Access
Chapter

Abstract

The prevalence of heart failure (HF) is escalating rapidly, consuming significant healthcare resources, inflicts significant morbidity and mortality, and greatly impacts quality of life. Dilated cardiomyopathy (DCM) is a frequent cause of HF and is characterized by a progressive course. Nowadays pharmacological and non-pharmacological therapies have dramatically changed DCM’s natural history. Familial screening program represents the first step in order to identify preclinic manifestation of DCM: first-degree relatives carrying a disease-causing mutation or without a clear genetic background must perform a periodic clinical and instrumental evaluation. Patients with a clinical diagnosis of HF and LV dysfunction should receive recommended therapies: beta-blockers (BB), ACE inhibitors (ACEi) or angiotensin receptor blockers (ARB), aldosterone antagonists, and more recently angiotensin receptor-neprilysin inhibitor (ARNI) and ivabradine are established therapies for chronic HF. In case of persistent systolic dysfunction and/or severe intraventricular conduction delay, an ICD and/or CRT are indicated. Finally, heart transplantation and mechanical circulatory support (MCS) are options that can be used in critically ill HF who can’t be stabilized by medical therapy alone.

Keywords

Dilated cardiomyopathy Familial screening program Medical treatment Angiotensin receptor-neprilysin inhibitor Mechanical circulatory support 

Abbreviations and Acronyms

ACEi

Angiotensin-converting enzyme inhibitor

AF

Atrial fibrillation

AHA/ACC

American Heart Association/American College of Cardiology

ARB

Angiotensin II type I receptor blockers

ARNI

Angiotensin receptor-neprilysin inhibitor

CRT-D

Cardiac resynchronization therapy-defibrillator

CRT-P

Cardiac resynchronization therapy-pacemaker

DCM

Dilated cardiomyopathy

ESC

European Society of Cardiology

FMR

Functional mitral regurgitation

HF

Heart failure

HT

Heart transplantation

ICD

Implantable cardioverter-defibrillator

LBBB

Left bundle branch block

LV

Left ventricular

LVAD

Implantable left ventricular assist device

LVEF

Left ventricular ejection fraction

MCS

Mechanical circulatory support

MRA

Mineralocorticoid receptor antagonists

MRI

Magnetic resonance imaging

NIDCM

Nonischemic dilated cardiomyopathy

RV

Right ventricular

SCD

Sudden cardiac death

VT

Ventricular tachycardia

Dilated cardiomyopathy (DCM) is a frequent cause of heart failure (HF) and is characterized by dilation and impaired contraction of one or both ventricles. Patients affected by DCM have impaired systolic function and may or may not develop overt HF and atrial and/or ventricular arrhythmias. Sudden cardiac death (SCD) can occur at any stage of the disease. Important breakthroughs have redefined opportunities to change the natural history of the disease with familial and sport activity screening programs and a broad range of medical therapies, devices, and care strategies, including readmission reduction programs and ambulatory outpatient disease management for those with more advanced disease (Table 13.1, Fig. 13.1).
Table 13.1

Screening programs and pharmacological and non-pharmacological treatments of HF in DCM patients: levels of recommendations from ESC guidelines

 

When?

Recommendation

Screening

Familial screening program

– First-degree relatives, if a specific gene mutation is identified in the proband

Recommended (from age 10 to 12 years)

– Family history of SCD in a first-degree relative

Can be useful

Sport activity screening

– For all young competitive athletes by history, physical examination, and ECG

Recommended by ESC

– For all young competitive athletes with history and physical examination

Recommended by AHA/ACC

Pharmacological treatment

ACEi

– Patients with asymptomatic LV systolic dysfunction, in order to prevent or delay the onset of HF

Recommended (I B)

– Patients with symptomatic LV systolic dysfunction, in order to reduce HF, hospitalization, and death

Recommended (I A)

ARB

– Patients with symptomatic LV systolic dysfunction, in order to reduce HF hospitalization and death, unable to tolerate an ACE-I

Recommended (I B)

Beta-blocker

– Patients with symptomatic LV systolic dysfunction, in order to reduce HF, hospitalization, and death

Recommended (I A)

MRA

– Patients with LV systolic dysfunction still symptomatic with an optimized dosage of ACEi and beta-blocker, in order to reduce HF hospitalization and death

Recommended (I A)

Sacubitril/Valsartan

– Patients with LV systolic dysfunction (EF ≤ 35%) still symptomatic (NYHA II–III) with an optimized dosage of ACEi (or ARB), beta-blocker, and MRA in order to reduce HF hospitalization and death

Recommended (I B)

Ivabradine

– Patients with LV systolic dysfunction (EF ≤ 35%) still symptomatic, in sinus rhythm and a resting heart rate ≥70 bpm, with an optimized dosage of ACEi(or ARB), beta-blocker, and MRA in order to reduce HF hospitalization and cardiovascular death

Recommended (IIa B)

Diuretics

– To reduce symptoms and signs of congestion

Recommended (I B)

Hydralazine and isosorbide dinitrate

– Black patients with symptomatic LV systolic dysfunction in case of intolerance or contraindication to ACEi or ARB, in order to reduce mortality

Recommended (IIb B)

– Patients with LV systolic dysfunction (EF ≤ 35%) and still symptomatic (NYHA III–IV) with an optimized dosage of ACEi and beta-blocker, in order to reduce HF hospitalization and death

Recommended (IIa B)

Non-pharmacological treatment

ICD

– Patients with LV systolic dysfunction (EF ≤ 35%) and symptomatic (NYHA II–III) despite 3 months of OMT, in order to reduce SCD and all-cause mortality

Recommended (I B)

CRT

– Patients with LV systolic dysfunction (EF ≤ 35%), in sinus rhythm and symptomatic despite OMT, in order to reduce morbidity and mortality

 
 

 • QRS duration ≥150 ms and LBBB QRS

Recommended (I A)

 

 • QRS duration 130–149 ms and LBBB QRS

Recommended (I B)

 

 • QRS duration ≥150 and non-LBBB QRS

Recommended (IIa B)

 

 • QRS duration 130–149 ms

Recommended (IIb B)

IABP or VA-ECMO

– Refractory acute HF or cardiogenic shock, with a short-term MCS, depending on patient age, comorbidities, and neurological function

Recommended (IIb C)

MitraClip

– HF patients with moderate to severe secondary FMR, inoperable or at high surgical risk, in order to improve symptoms and quality of life

Recommended (IIb C)

LVAD

– Patients with LV systolic dysfunction (LVEF ≤ 35%), end-stage HF despite OMT/device and eligible for HT, in order to improve symptoms and reduce the HF hospitalization and premature death (bridge to transplant)

Recommended (IIa C)

– Patients with LV systolic dysfunction (LVEF ≤ 35%), end-stage HF despite OMT/device and not eligible for HT, in order to improve symptoms and reduce the HF hospitalization and premature death

Recommended (IIa B)

HT

– Patients with LV systolic dysfunction (LVEF ≤ 35%), end-stage HF despite OMT in the absence of contraindications, in order to increase survival, exercise capacity, and quality of life

Recommended

SCD sudden cardiac death, ESC European Society of Cardiology, AHA American Heart Association, ACC American College of Cardiology, LV left ventricle, HF heart failure, ACEi angiotensin-converting enzyme inhibitor, ARB angiotensin II type I receptor blockers, MRA mineralocorticoid/aldosterone receptor antagonists, EF ejection fraction, ICD implantable cardioverter-defibrillator, CRT cardiac resynchronization therapy, FMR functional mitral regurgitation, IABP intra-aortic balloon pump, VA-ECMO venoarterial extracorporeal membrane oxygenation, LVAD implantable left ventricular assist device, HT heart transplantation

Fig. 13.1

Management and escalation therapy for HF in DCM. ACEi angiotensin-converting enzyme inhibitor, ARB angiotensin II type I receptor blockers, MRA mineralocorticoid/aldosterone receptor antagonists, ICD implantable cardioverter defibrillator, CRT cardiac resynchronization therapy, VA-ECMO venoarterial extracorporeal membrane oxygenation, LVAD implantable left ventricular assist device, BiVAD biventricular assist device

13.1 Familial Screening Program

Contrary to what was believed in the past, in the broad spectrum of DCM, 20–50% forms are now known to be familial [1]. Autosomal dominant inheritance is the most frequent pattern of transmission, with less than 50% chance of inheriting the disease for each pregnancy because of incomplete penetrance [2].

These elements represent the rationale to perform a complete family screening in order to identify preclinic manifestations of DCM among relatives, taking into account that DCM has a progressive course [3] and family members can remain asymptomatic for a long period [4, 5, 6, 7]. Familial screening program, recommended to proband’s first-degree relatives, allows an early identification and treatment of the disease, reducing morbidity and mortality and preventing the high costs of advanced HF management [8].

Family history of at least three generations is recommended in order to recognize the potential heritability of the disease [9]. The pedigree analysis should investigate family occurrence of HF of unknown etiology before the age of 60, SCD, and pacemaker implantation early in life [4]. Furthermore, family history of skeletal myopathies (as Duchenne or Becker disease) or presence of sensorineural hearing loss (congenital or occurred after the second decade of life) can suggest the diagnosis of a syndromic disease involving also the heart.

When the disease is recognized in at least two close relatives, a final diagnosis of familial DCM can be made [3, 4, 10].

In addition to family history, periodic screening, consisting of physical examination and instrumental evaluation (ECG and echocardiogram), can mark the transition to the phenotypic expression of the disease, even when the relative is yet asymptomatic [4, 6]. An early detection of this transition represents the rationale for familial screening proposed by European and American guidelines [11, 12].

According to guidelines, genetic testing is recommended for first-degree relatives when a specific mutation is identified in the proband [4, 11, 13], starting from the age of 10–12, although earlier testing can be considered in laminopathies [11].

In genotype-positive relatives, annual clinical follow-up is recommended in order to recognized an early expression of the disease [11]. Conversely, clinical follow-up is not required in the case of negative genetic testing, which excludes future development of the disease and the risk of its transmission to the offspring [11].

In case of proband’s death, postmortem molecular analyses can be useful to detect the disease-causing mutation in addition to an accurate histological and morphological evaluation of the heart in order to clarify the disease phenotype [14].

Genetic testing, however, is not always conclusive: identification of uncertain significant genetic variants or the absence of any identified mutation in the proband on extensive gene screening represents an example of diagnostic ineffectiveness. In these settings, genetic testing is not recommended for close relatives [15].

Repeated cardiac evaluation should be performed at regular intervals: every 1–3 years until the age of 10, 1–2 years between 10 and 20 years, and then every 2–5 years until the age of 50–60, when the penetrance of DCM is usually complete [11].

When a relative is diagnosed as a new case of DCM, even if asymptomatic, the clinical work-up described for the proband starts, including additional tests, such as cardiopulmonary exercise and/or cardiac magnetic resonance imaging (MRI) [11].

13.2 Sport Activity Screening Program

SCD has been associated to competitive sport activity in the adolescents and young adult athletes [16, 17], with an increased risk compared with nonathletic counterparts [18]. Specific cardiomyopathies have been recognized as leading causes of sport-related cardiac arrest such as hypertrophic cardiomyopathy in the USA and arrhythmogenic right ventricular cardiomyopathy in Italy [18, 19].

DCM has been also taken into account as a possible cause of SCD: in international records 1–8% of fatalities of cardiovascular origin have been related to DCM [18, 19, 20]. In this context, clinical evaluation of athletes has the important goal of identifying the disease when asymptomatic and protecting them from SCD by sport competition restriction and specific treatment.

American Heart Association/American College of Cardiology (AHA/ACC) and European Society of Cardiology (ESC) recommendations agree that cardiovascular screening for young athletes is justifiable and compelling on ethical, legal, and medical grounds [21, 22], but the two societies propose different screening programs.

The AHA/ACC focuses screening only on physical examination and medical history with consequent cost restriction and reduction of false-positive ECG [22]. On the other hand, ESC and International Olympic Committee recommend also to perform a resting 12-lead ECG [21, 23], in order to detect abnormalities connected to preclinical pathological cardiovascular conditions that cannot be identified by the only clinical approach [21, 23, 24].

The most frequent ECG abnormal findings always requiring further assessment to exclude the presence of a cardiomyopathy are the following:
  • T-wave inversion in lateral, infero-lateral, or extended to anterior leads

  • ST-segment depression

  • Pathologic Q waves

  • Complete left bundle branch block (LBBB)

  • Multiple premature ventricular beats

When pathological findings emerge, the initial evaluation requires additional tests [18, 21], as recommended by the ESC section of Sports Cardiology, based itself on the Italian protocol [21]: echocardiography, stress testing, Holter ECG monitoring, and eventually cardiac MRI in selected cases [24, 25].

In some cases, differential diagnosis between DCM and athlete’s heart may be challenging. Indeed, athlete’s heart is a clinical phenotype derived from cardiac remodeling induced by sport activity, mostly in endurance sports, and is characterized by enlarging left ventricle with borderline or mildly reduced left ventricular ejection fraction (LVEF) (i.e., between 45 and 55%) [26]. There are many hints helping to distinguish DCM from athlete’s heart [25]:
  • Positive family history of SCD, cardiac arrest, or cardiac disease

  • ECG abnormalities

  • Ventricular arrhythmias at 24-h Holter ECG monitoring or stress testing

  • LVEF below 45% and regional wall motion abnormalities

  • Right ventricular dysfunction associated with LV dysfunction

  • Late gadolinium enhancement (LGE) at cardiac MRI

In doubt or borderline cases, demonstrating a significant increase in LVEF during exercise echocardiography or LVEF and diameter normalization at cardiac MRI after an adequate period of detraining may support the diagnosis of athlete’s heart [27]. Sport screening benefits go beyond the detection of DCM in the single athlete: when the disease is recognized, a cardiological evaluation can be extended to the first-degree relatives in order to identify other potential affected family members [18].

Athletes recognized to be affected by DCM should not participate in competitive sports because of an increased risk of SCD during exercise [21]. Finally, there are no sufficient evidences supporting that sport activity increases the risk of DCM development or SCD in genotype-positive/phenotype-negative athletes [25].

13.3 Medical Treatment

DCM is a common cause of HF and treatment reflects the management of chronic HF. DCM patients, indeed, can be divided into two different classes on the base of the presence of clinical symptoms:
  • Asymptomatic left ventricular systolic dysfunction: in patients with depressed LV systolic function in the absence of symptoms, onset of HF should be delayed or prevented primarily by controlling hypertension [28] and, when the LVEF is ≤40%, by initiating angiotensin-converting enzyme inhibitor (ACEi) therapy [29] prior to beta-blocker therapy, since the evidences supporting ACEi therapy are stronger [30].

  • Symptomatic HF with reduced ejection fraction: patients of this category should all be treated. The goals of therapy are to reduce mortality and morbidity; improve symptoms, quality of life, and functional status and decrease hospitalization rate [31].

Pharmacologic and device therapy should be primarily accompanied by the management of contributing factors of HF and by lifestyle modification. For instance, hypertension and ischemic heart disease can impair cardiac function and exacerbate HF clinical symptoms; therefore, they should be considered and treated in DCM patients [12]. The main lifestyle recommendations are sodium and fluid restriction, abstinence from alcohol intake, and adequate body weight loss [31].

For patients with symptomatic HF, a new therapeutic algorithm has been proposed by the current European guidelines [31]. Neurohormonal antagonists, ACEi or angiotensin II type I receptor blockers (ARB) in case of ACEi intolerance, are recommended from the beginning in association with beta-blocker. The addition of mineralocorticoid receptor antagonists (MRA) should be considered in patients still symptomatic with an optimized dosage of ACEi and beta-blocker. ACEi [29, 32, 33], ARB [34, 35], beta-blocker [36, 37, 38], and MRA [39, 40] have demonstrated, in several clinical trials, to reduce risk of HF hospitalization and death in patient with HF and reduced EF.

More recently, two new molecules have been included to the recommended pharmacological therapy: an angiotensin receptor-neprilysin inhibitor (ARNI) and the hyperpolarization channel blocker ivabradine [31]. In particular, Sacubitril/Valsartan, tested in PARADIGM trial, is recommended for patients on optimal medical therapy, tolerating ACEi or ARB, but still in II–III NYHA class [31, 41]. Ivabradine is indicated for patients in sinus rhythm that continue to have a resting heart rate over 70 bpm even on beta-blocker therapy based on SHIFT trial [31, 42]. Both these two drugs have shown to improve survival and reduce hospitalization in patients with HF [41, 42].

Diuretic therapy is intended to reduce symptoms and signs of congestion, but no clinical trial could demonstrate any effect on morbidity and mortality [31].

Finally, in case of intolerance or contraindication to ACEi or ARB, combination of hydralazine and isosorbide dinitrate (not approved in Italy) in symptomatic patients with HF and reduced LVEF has demonstrated to reduce mortality [43]. The same association, combined with conventional HF therapy, in NYHA class III–IV black patients, can reduce mortality and HF hospitalizations [44].

Cardioactive pharmacological drugs should be adjusted and up-titrated every 2 weeks to the maximally tolerated doses that should be achieved within 3–6 months from initial diagnosis of HF [45]. During follow-up, frequent reassessment of the clinical status, biohumoral parameters, and ventricular function should be performed in order to achieve therapeutic decision about possible defibrillator or biventricular pacing implantation [31].

13.4 Ventricular and Supraventricular Arrhythmias

Ventricular and supraventricular arrhythmias often coexist with DCM and HF. The treatment of atrial fibrillation (AF) can substantially alter long-term outcomes in patients with heart failure, but the subject of what is the most effective management strategy is debated. Rhythm control with antiarrhythmic drugs is not superior to rate control in patients with coexisting HF and AF [46]. Catheter ablation is a well-established option for symptomatic atrial fibrillation that is resistant to drug therapy in patients with otherwise normal cardiac function, and various studies have shown that ablation is associated with positive outcomes in patients with heart failure [47]. A recent study showed that catheter ablation for AF in patients with HF was associated with a significantly lower rate of a composite end point of death from any cause or hospitalization for worsening heart failure than was medical therapy [48].

Finally, a common feature of DCM regardless of the underlying cause is a propensity to ventricular arrhythmias, being expression of disease’s end stage or an intrinsic characteristic of the disease, often connected to particular genotype (i.e., laminopathies). Therapy for ventricular arrhythmias is also needed for recurrent arrhythmias that cause symptoms, most commonly recurrent ICD shocks. Amiodarone is the preferred major antiarrhythmic agent, particularly when ventricular function is severely depressed. In patients with compensated heart failure, sotalol is an option. For patients with recurrent sustained monomorphic ventricular tachycardia (VT), catheter ablation is a therapeutic option to consider, but experience is limited in comparison with that for VTs that occur in patients with coronary artery disease. Success rates depend on VT substrate location, which can be endocardial, intramural, or epicardial. Endocardial VTs can be generally ablated, whereas an epicardial approach is necessary in one-third of cases, but it is associated with higher complication rates. However, sustained monomorphic VT that triggers frequent ICD shocks or electrical storms can be controlled with ablation and adjunctive antiarrhythmic medications in the majority of cases. Experienced centers performing catheter ablation in patients with nonischemic cardiomyopathy have reported that complete absence of inducible VT can be achieved in 38–67% of patients [49].

13.5 Implantable Cardioverter-Defibrillator

Prophylactic implantation of an ICD is a class I recommendation for patients with nonischemic dilated cardiomyopathy (NIDCM), symptomatic HF with NYHA class II–III, and an LVEF ≤ 35% [31]. However, the evidence for a benefit is stronger for patients with ischemic heart disease than it is for patients with other HF etiologies. Among patients with NIDCM, these indications are based on two randomized trials, the DEFINITE and SCD-HeFT trial, performed in the 2000s, which showed a trend toward a reduction of mortality in the ICD arm [50, 51, 52]. Accordingly, the current recommendation is based on analysis of subgroup of NIDCM patients of minor trials or on meta-analysis of smaller studies with NIDCM patients [51].

The recent DANISH trial [53] casts a shadow on this strong recommendation: 1156 patients with severe nonischemic LV systolic impairment were randomly assigned to receive an ICD on top of medical therapy or medical therapy alone and followed for a median of 5.6 years. In both ICD and control arms, 58% of the patients received cardiac resynchronization therapy (CRT). Although ICD was associated with a risk of SCD that was half that associated with conventional therapy, mortality from any cause was similar in the ICD and control groups (HR 0.87; 95% CI 0.68–1.12), as well as in patients with CRT-defibrillator (CRT-D) and CRT-pacemaker (CRT-P) (p = 0.59), leaving unclear whether patients eligible for CRT should routinely receive an ICD. These results, probably due to lower rates of events in NIDCM than ischemic patients and the comprehensive medical therapy plus CRT of study population, urge the search for other predictors of sudden death over LVEF, in order to identify the patient who can best benefit from ICD, potentially reducing device-related adverse events in those who will not experience appropriate ICD interventions. Other noninvasive markers of arrhythmic risk may help to improve the appropriateness of ICD implantation: fibrosis identification by late gadolinium enhancement in cardiac MRI seems the most promising risk predictor [54].

13.6 Cardiac Resynchronization Therapy

Approximately 30% of patients with HF and LV systolic function impairment have a wide QRS complex on the surface electrocardiogram [55], and cumulative mortality increases proportionally with QRS duration [56]. Left bundle branch block (LBBB), associated itself with increased mortality, determines ventricular dyssynchrony as the final result of transmural functional line of block located between the LV septum and the lateral wall with a prolonged activation time [57]. Use of biventricular pacing had been proposed in pharmacological refractory HF patients with intraventricular conduction delay to optimize cardiac performance, through epicardial and then transvenous electrodes. Since then, many trials have demonstrated that CRT, in appropriately selected patients, reduces mortality and morbidity [58] and improves systolic function, symptoms, and quality of life [59, 60].

The effect of CRT, compared to optimized medical therapy, was evaluated by two trials. The COMPANION study demonstrated for the first time a better outcome in patients implanted with CRT plus a defibrillator with advanced HF and a QRS interval > 120 ms than those under pharmacological therapy alone [61]: in the subgroup analyses, hazard ratios for death from any cause of CRT-D as compared with pharmacologic therapy were 0.50 (95% CI, 0.29–0.88) in NIDCM. In the CARE-HF study, CRT reduced all-cause mortality, and the survival benefit with CRT-D over an implantable ICD was consistent in a subgroup analysis of patients with ischemic and nonischemic DCM [62].

Patients enrolled in CRT trials had severe LV systolic dysfunction: most patients had a LVEF < 35%, but other, as MADIT-CRT [59] or RAFT [63], considered LVEF < 30%. Only few patients with an LVEF of 35–40% have been randomized.

As a result, CRT is indicated, according to ESC guidelines [31], as class I recommendation for patients in sinus rhythm, with LBBB, a QRS longer than 130 ms, and LVEF of 35% or less. Evidences are weaker for non-LBBB intraventricular conduction delay and QRS < 150 ms. CRT is contraindicated when QRS is not prolonged: a recent study demonstrated that in patients with systolic HF and a QRS duration < 130 ms, CRT may increase mortality and has no effect on the rate of death or hospitalization for HF [64].

Reverse remodeling is one of the most important mechanisms of action of CRT, but not all patients respond successfully: patients with nonischemic etiology have greater improvement in LV function and decrease in NYHA class after CRT [65]. Data from MADIT-CRT were used to identify factors associated with positive response: female sex, nonischemic etiology, QRS ≥ 150 ms, LBBB, prior HF hospitalization, baseline LVEDV < 125 mL/m2, and LAVI (left atrial volume index) < 40 mL/m2 were associated with favorable reverse modeling after CRT implantation [66].

Choice between CRT-P and CRT-D may be hard in selected patients, since most of them with LVEF ≤ 35% have an indication for a concomitant ICD. There are no prospective data proving a benefit of CRT-D over CRT-P, and the only randomized trial to compare CRT-P and CRT-D failed to demonstrate a difference in morbidity or mortality between these strategies [61]. Observational and retrospective studies show that older patients (age ≥ 75 years), particularly if without dilated LV and with nonischemic etiology, and pacemaker-dependent patients are less likely to benefit from CRT-D compared with CRT-P [67, 68].

13.7 Advanced Heart Failure, Mechanical Circulatory Support, Functional Mitral Regurgitation Correction, Heart Transplantation, and Palliative Care

Use of optimal medical therapy, cardiac resynchronization, and implantable defibrillators has changed HF prognosis dramatically. However, 0.5–5% of patients respond poorly to recommended therapy and can develop severe chronic advanced HF with a wide scenario going from refractory deterioration up to cardiogenic shock [69].

Mechanical circulatory support (MCS) devices can be used in critically ill HF patients who can’t be stabilized by medical therapy alone. Their goals are to unload the failing ventricle and maintain an adequate end-organ perfusion. Acute and chronic settings require different types of MCS, with short- or mid-/long-term action.

Short-term MCS (few days to weeks) are the systems of choice in patients with acute HF or cardiogenic shock: they include intra-aortic balloon pump and venoarterial extracorporeal membrane oxygenation. They permit to stabilize hemodynamics and gain time for recovery or reevaluation for the possibility of either a more durable MCS or heart transplant.

In a more chronic setting, functional mitral regurgitation (FMR) is a common finding in patients with DCM and left ventricular impairment and is associated with a poor prognosis [70]. In recent years percutaneous correction of mitral regurgitation with the MitraClip system has been established as an alternative treatment option for surgically high-risk patients with degenerative and FMR [71]. Worldwide experience reports high procedural success rates and favorable clinical outcomes in patients with systolic HF and FMR [71, 72]. Patient selection is a crucial issue to obtain the best benefit for patients. A recent report showed that anteroposterior diameter of the mitral annulus and LV end-diastolic volume were significantly associated with device failure during follow-up, and the assessment of these two parameters might be particularly useful for the selection of the optimal candidates to percutaneous treatment of FMR [73].

Heart transplantation (HT) is a well-recognized treatment that significantly increases quality of life and survival for eligible patients with advanced HF, severe symptoms, poor prognosis, and no remaining alternative choices [74]. Unfortunately suitable donor availability is extremely limited. In these cases, implantable left ventricular assist device (LVAD) technology has improved considerably in the last years. This MCS, historically used only for short periods as bridge-to-transplantation, nowadays is being used increasingly also as a permanent treatment or “destination therapy” [75]. In this scenario, right ventricular (RV) assessment is crucial considering RV failure to occur in up to 50% of cases following LVAD implantation and resulting in high perioperative mortality and morbidity rates [76, 77, 78]. An important contribution to evaluation for candidacy to LVAD was the introduction of the INTERMACS classification, which categorizes patients for the purpose of risk assessment prior to LVAD implant or HT [79], ranging from 1 (cardiogenic shock) to 7 (advanced NYHA III), and describes patient’s clinical status in terms of hemodynamic stability, inotrope dependence, and functional capacity. Since outcomes in INTERMACS 3 (stable on inotropes) are better than in class I–II, this class has been advocated as the optimal group for implantation. However, the choice remains tough for clinicians, since patients can experience adverse events and complications in up to 60% of cases by 6 months postimplantation, including bleeding, thromboembolic events, infections, and right ventricle failure [80].

Advanced ages, multiple comorbidities, and poorly controlled symptoms characterize the HF terminal stage. In this setting, symptoms management and emotional support of the patients and their family are the principal components of palliative care in advanced HF, in order to improve quality of life [31]. Currently, no consensus has been reached in international guidelines about the right time to start palliative care because of the absence of end-of-life objective criteria. However, the decisions should be always taken by physicians according to the patient and the family.

References

  1. 1.
    Hershberger RE, Cowan J, Morales A, Siegfried JD. Progress with genetic cardiomyopathies: screening, counseling, and testing in dilated, hypertrophic, and arrhythmogenic right ventricular dysplasia/cardiomyopathy. Circ Heart Fail. 2009;2(3):253–61.  https://doi.org/10.1161/CIRCHEARTFAILURE.108.817346.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Mestroni L, Brun F, Spezzacatene A, Sinagra G, Taylor MR. Genetic causes of dilated cardiomyopathy. Prog Pediatr Cardiol. 2014;37(1–2):13–8.CrossRefGoogle Scholar
  3. 3.
    Sisakian H. Cardiomyopathies: evolution of pathogenesis concepts and potential for new therapies. World J Cardiol. 2014;6(6):478.  https://doi.org/10.4330/wjc.v6.i6.478.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Burkett EL, Hershberger RE. Clinical and genetic issues in familial dilated cardiomyopathy. J Am Coll Cardiol. 2005;45(7):969–81.CrossRefGoogle Scholar
  5. 5.
    Mahon NG, Murphy RT, MacRae CA, Caforio ALP, Elliott PM, McKenna WJ. Echocardiographic evaluation in asymptomatic relatives of patients with dilated cardiomyopathy reveals preclinical disease. Ann Intern Med. 2005;143(2):108–15.CrossRefGoogle Scholar
  6. 6.
    Crispell KA, Hanson EL, Coates K, Toy W, Hershberger RE. Periodic rescreening is indicated for family members at risk of developing familial dilated cardiomyopathy. J Am Coll Cardiol. 2002;39(9):1503–7.CrossRefGoogle Scholar
  7. 7.
    Hershberger RE, Lindenfeld J, Mestroni L, Seidman CE, Taylor MRG, Towbin JA, et al. Genetic evaluation of cardiomyopathy—a Heart Failure Society of America practice guideline. J Card Fail. 2009;15(2):83–97.  https://doi.org/10.1016/j.cardfail.2009.01.006.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Hershberger RE, Morales A. Dilated cardiomyopathy overview. GeneReviews®. Seattle: University of Washington; 1993.Google Scholar
  9. 9.
    Ackerman MJ, Priori SG, Willems S, Berul C, Brugada R, Calkins H, et al. HRS/EHRA expert consensus statement on the state of genetic testing for the channelopathies and cardiomyopathies: this document was developed as a partnership between the Heart Rhythm Society (HRS) and the European Heart Rhythm Association (EHRA). Heart Rhythm. 2011;8(8):1308–39.  https://doi.org/10.1016/j.hrthm.2011.05.020.CrossRefPubMedGoogle Scholar
  10. 10.
    Hershberger RE, Siegfried JD. Update 2011: clinical and genetic issues in familial dilated cardiomyopathy. J Am Coll Cardiol. 2011;57(16):1641–9.  https://doi.org/10.1016/j.jacc.2011.01.015.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Charron P, Arad M, Arbustini E, Basso C, Bilinska Z, Elliott P, et al. Genetic counselling and testing in cardiomyopathies: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J. 2010;31(22):2715–28.  https://doi.org/10.1093/eurheartj/ehq271.CrossRefPubMedGoogle Scholar
  12. 12.
    Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE, Drazner MH, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. J Am Coll Cardiol. 2013;62(16):e147–239.  https://doi.org/10.1016/j.jacc.2013.05.019.CrossRefPubMedGoogle Scholar
  13. 13.
    van Spaendonck-Zwarts KY, van den Berg MP, van Tintelen JP. DNA analysis in inherited cardiomyopathies: current status and clinical relevance. Pacing Clin Electrophysiol. 2008;31(Suppl 1):S46–9.  https://doi.org/10.1111/j.1540-8159.2008.00956.x.CrossRefPubMedGoogle Scholar
  14. 14.
    Basso C, Burke M, Fornes P, Gallagher PJ, de Gouveia RH, Sheppard M, et al. Guidelines for autopsy investigation of sudden cardiac death. Virchows Arch. 2008;452(1):11–8.CrossRefGoogle Scholar
  15. 15.
    Wolf MJ, Noeth D, Rammohan C, Shah SH. Complexities of genetic testing in familial dilated cardiomyopathy. Circ Cardiovasc Genet. 2016;9(1):95–9.  https://doi.org/10.1161/CIRCGENETICS.115.001157.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Corrado D, Thiene G, Nava A, Rossi L, Pennelli N. Sudden death in young competitive athletes: clinicopathologic correlations in 22 cases. Am J Med. 1990;89(5):588–96.CrossRefGoogle Scholar
  17. 17.
    Maron BJ, Shirani J, Poliac LC, Mathenge R, Roberts WC, Mueller FO. Sudden death in young competitive athletes. JAMA. 1996;276(3):199.CrossRefGoogle Scholar
  18. 18.
    Corrado D, Basso C, Rizzoli G, Schiavon M, Thiene G. Does sports activity enhance the risk of sudden death in adolescents and young adults? J Am Coll Cardiol. 2003;42(11):1959–63.CrossRefGoogle Scholar
  19. 19.
    Maron BJ, Doerer JJ, Haas TS, Tierney DM, Mueller FO. Sudden deaths in young competitive athletes: analysis of 1866 deaths in the United States, 1980–2006. Circulation. 2009;119(8):1085–92.  https://doi.org/10.1161/CIRCULATIONAHA.108.804617.CrossRefPubMedGoogle Scholar
  20. 20.
    Harmon KG, Drezner JA, Maleszewski JJ, Lopez-Anderson M, Owens D, Prutkin JM, et al. Pathogeneses of sudden cardiac death in National Collegiate Athletic Association Athletes. Circ Arrhythm Electrophysiol. 2014;7(2):198–204.  https://doi.org/10.1161/CIRCEP.113.001376.CrossRefPubMedGoogle Scholar
  21. 21.
    Corrado D, Pelliccia A, Bjørnstad HH, Vanhees L, Biffi A, Borjesson M, et al. Cardiovascular pre-participation screening of young competitive athletes for prevention of sudden death: proposal for a common European protocol. Consensus statement of the study Group of Sport Cardiology of the Working Group of Cardiac Rehabilitation and Exercise Physiology and the Working Group of Myocardial and Pericardial Diseases of the European Society of Cardiology. Eur Heart J. 2005;26(5):516–24.CrossRefGoogle Scholar
  22. 22.
    Maron BJ, Thompson PD, Ackerman MJ, Balady G, Berger S, Cohen D, et al. Recommendations and considerations related to preparticipation screening for cardiovascular abnormalities in competitive athletes: 2007 update: a scientific statement from the American Heart Association Council on Nutrition, Physical Activity, and Metabolism: endorsed by the American College of Cardiology Foundation. Circulation. 2007;115(12):1643–455.CrossRefGoogle Scholar
  23. 23.
    Pelliccia A, Fagard R, Bjørnstad HH, Anastassakis A, Arbustini E, Assanelli D, et al. Recommendations for competitive sports participation in athletes with cardiovascular disease: a consensus document from the Study Group of Sports Cardiology of the Working Group of Cardiac Rehabilitation and Exercise Physiology and the Working Group of Myocardial and Pericardial Diseases of the European Society of Cardiology. Eur Heart J. 2005;26(14):1422–45.CrossRefGoogle Scholar
  24. 24.
    Corrado D, Schmied C, Basso C, Borjesson M, Schiavon M, Pelliccia A, et al. Risk of sports: do we need a pre-participation screening for competitive and leisure athletes? Eur Heart J. 2011;32(8):934–44.  https://doi.org/10.1093/eurheartj/ehq482.CrossRefPubMedGoogle Scholar
  25. 25.
    Zorzi A, Pelliccia A, Corrado D. Inherited cardiomyopathies and sports participation. Neth Heart J. 2018;26(3):154–65.  https://doi.org/10.1007/s12471-018-1079-3.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Baggish AL, Wood MJ. Athlete’s heart and cardiovascular care of the athlete: scientific and clinical update. Circulation. 2011;123(23):2723–35.  https://doi.org/10.1161/CIRCULATIONAHA.110.981571.CrossRefPubMedGoogle Scholar
  27. 27.
    Galderisi M, Cardim N, D’Andrea A, Bruder O, Cosyns B, Davin L, et al. The multi-modality cardiac imaging approach to the athlete’s heart: an expert consensus of the European Association of Cardiovascular Imaging. Eur Hear J Cardiovasc Imaging. 2015;16(4):353–353r.CrossRefGoogle Scholar
  28. 28.
    Wright JT Jr, Williamson JD, Whelton PK, Snyder JK, Sink KM, Rocco MV, et al. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2017;377(25):2506.CrossRefGoogle Scholar
  29. 29.
    Yusuf S, Pitt B, Davis CE, Hood WB, Cohn JN. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med. 1991;325(5):293–302.CrossRefGoogle Scholar
  30. 30.
    Exner DV, Dries DL, Waclawiw MA, Shelton B, Domanski MJ. Beta-adrenergic blocking agent use and mortality in patients with asymptomatic and symptomatic left ventricular systolic dysfunction: a post hoc analysis of the studies of left ventricular dysfunction. J Am Coll Cardiol. 1999;33(4):916–23.CrossRefGoogle Scholar
  31. 31.
    Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, et al. 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016;37(27):2129–200.  https://doi.org/10.1093/eurheartj/ehw128.CrossRefGoogle Scholar
  32. 32.
    CONSENSUS Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure. N Engl J Med. 1987;316(23):1429–35.CrossRefGoogle Scholar
  33. 33.
    Wollert KC, Studer R, von Bülow B, Drexler H, Horowitz JD, Massie BM, et al. Survival after myocardial infarction in the rat. Role of tissue angiotensin-converting enzyme inhibition. Circulation. 1994;90(5):2457–67.CrossRefGoogle Scholar
  34. 34.
    Young JB, Dunlap ME, Pfeffer MA, Probstfield JL, Cohen-Solal A, Dietz R, et al. Mortality and morbidity reduction with candesartan in patients with chronic heart failure and left ventricular systolic dysfunction: results of the CHARM low-left ventricular ejection fraction trials. Circulation. 2004;110(17):2618–26.CrossRefGoogle Scholar
  35. 35.
    Cohn JN, Tognoni G. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med. 2001;345(23):1667–75.CrossRefGoogle Scholar
  36. 36.
    CIBIS-II Investigators and Committees. The cardiac insufficiency bisoprolol study II (CIBIS-II): a randomised trial. Lancet. 1999;353(9146):9–13.Google Scholar
  37. 37.
    Packer M, Fowler MB, Roecker EB, Coats AJS, Katus HA, Krum H, et al. Effect of carvedilol on the morbidity of patients with severe chronic heart failure: results of the carvedilol prospective randomized cumulative survival (COPERNICUS) study. Circulation. 2002;106(17):2194–9.CrossRefGoogle Scholar
  38. 38.
    Hjalmarson A, Goldstein S, Fagerberg B, Wedel H, Waagstein F, Kjekshus J, et al. Effects of controlled-release metoprolol on total mortality, hospitalizations, and well-being in patients with heart failure: the metoprolol CR/XL randomized intervention trial in congestive heart failure (MERIT-HF). MERIT-HF Study Group. JAMA. 2000;283(10):1295–302.CrossRefGoogle Scholar
  39. 39.
    Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med. 1999;341(10):709–17.CrossRefGoogle Scholar
  40. 40.
    Zannad F, McMurray JJV, Krum H, van Veldhuisen DJ, Swedberg K, Shi H, et al. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med. 2011;364(1):11–21.  https://doi.org/10.1056/NEJMoa1009492.CrossRefPubMedGoogle Scholar
  41. 41.
    McMurray JJV, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, et al. Angiotensin–neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371(11):993–1004.  https://doi.org/10.1056/NEJMoa1409077.CrossRefGoogle Scholar
  42. 42.
    Swedberg K, Komajda M, Böhm M, Borer JS, Ford I, Dubost-Brama A, et al. Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study. Lancet. 2010;376(9744):875–85.  https://doi.org/10.1016/S0140-6736(10)61198-1.CrossRefPubMedGoogle Scholar
  43. 43.
    Cohn JN, Archibald DG, Ziesche S, Franciosa JA, Harston WE, Tristani FE, et al. Effect of vasodilator therapy on mortality in chronic congestive heart failure. N Engl J Med. 1986;314(24):1547–52.CrossRefGoogle Scholar
  44. 44.
    Taylor AL, Ziesche S, Yancy C, Carson P, D’Agostino R, Ferdinand K, et al. Combination of isosorbide dinitrate and hydralazine in blacks with heart failure. N Engl J Med. 2004;351(20):2049–57.CrossRefGoogle Scholar
  45. 45.
    Yancy CW, Januzzi JL, Allen LA, Butler J, Davis LL, Fonarow GC, et al. 2017 ACC expert consensus decision pathway for optimization of heart failure treatment: answers to 10 pivotal issues about heart failure with reduced ejection fraction. J Am Coll Cardiol. 2018;71(2):201–30.  https://doi.org/10.1016/j.jacc.2017.11.025.CrossRefPubMedGoogle Scholar
  46. 46.
    Roy D, Talajic M, Nattel S, Wyse DG, Dorian P, Lee KL, et al. Rhythm control versus rate control for atrial fibrillation and heart failure. N Engl J Med. 2008;358(25):2667–77.  https://doi.org/10.1056/NEJMoa0708789.CrossRefPubMedGoogle Scholar
  47. 47.
    Khan MN, Jaïs P, Cummings J, Di Biase L, Sanders P, Martin DO, et al. Pulmonary-vein isolation for atrial fibrillation in patients with heart failure. N Engl J Med. 2008;359(17):1778–85.  https://doi.org/10.1056/NEJMoa0708234.CrossRefPubMedGoogle Scholar
  48. 48.
    Marrouche NF, Brachmann J, Andresen D, Siebels J, Boersma L, Jordaens L, et al. Catheter ablation for atrial fibrillation with heart failure. N Engl J Med. 2018;378(5):417–27.  https://doi.org/10.1056/NEJMoa1707855.CrossRefPubMedGoogle Scholar
  49. 49.
    Dinov B, Fiedler L, Schönbauer R, Bollmann A, Rolf S, Piorkowski C, et al. Outcomes in catheter ablation of ventricular tachycardia in dilated nonischemic cardiomyopathy compared with ischemic cardiomyopathy: results from the prospective heart Centre of Leipzig VT (HELP-VT) study. Circulation. 2014;129(7):728–36.  https://doi.org/10.1161/CIRCULATIONAHA.113.003063.CrossRefPubMedGoogle Scholar
  50. 50.
    Priori SG, Blomström-Lundqvist C, Mazzanti A, Blom N, Borggrefe M, Camm J, et al. 2015 ESC guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: the task force for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death of the European Society of Cardiology (ESC). Eur Heart J. 2015;36(41):2793–867.  https://doi.org/10.1093/eurheartj/ehv316.CrossRefPubMedGoogle Scholar
  51. 51.
    Kadish A, Dyer A, Daubert JP, Quigg R, Estes NAM, Anderson KP, et al. Prophylactic defibrillator implantation in patients with nonischemic dilated cardiomyopathy. N Engl J Med. 2004;350:2151–8.CrossRefGoogle Scholar
  52. 52.
    Bardy GH, Lee KL, Mark DB, Poole JE, Packer DL, Boineau R, et al. Amiodarone or an implantable cardioverter–defibrillator for congestive heart failure. N Engl J Med. 2005;352(21):225–37.CrossRefGoogle Scholar
  53. 53.
    Kober L, Thune JJ, Nielsen JC, Haarbo J, Videbaek L, Korup E, et al. Defibrillator implantation in patients with nonischemic systolic heart failure. N Engl J Med. 2016;375(13):1221–30.  https://doi.org/10.1056/NEJMoa1608029.CrossRefGoogle Scholar
  54. 54.
    Di Marco A, Anguera I, Schmitt M, Klem I, Neilan T, White JA, et al. Late gadolinium enhancement and the risk for ventricular arrhythmias or sudden death in dilated cardiomyopathy: systematic review and meta-analysis. JACC Heart Fail. 2017;5(1):28–38.  https://doi.org/10.1016/j.jchf.2016.09.017.CrossRefPubMedGoogle Scholar
  55. 55.
    Khan NK, Goode KM, Cleland JGF, Rigby AS, Freemantle N, Eastaugh J, et al. Prevalence of ECG abnormalities in an international survey of patients with suspected or confirmed heart failure at death or discharge. Eur J Heart Fail. 2007;9(5):491–501.CrossRefGoogle Scholar
  56. 56.
    Iuliano S, Fisher SG, Karasik PE, Fletcher RD, Singh SN. Department of Veterans Affairs Survival Trial of antiarrhythmic therapy in congestive heart failure. QRS duration and mortality in patients with congestive heart failure. Am Heart J. 2002;143(6):1085–91.CrossRefGoogle Scholar
  57. 57.
    Auricchio A, Fantoni C, Regoli F, Carbucicchio C, Goette A, Geller C, et al. Characterization of left ventricular activation in patients with heart failure and left bundle-branch block. Circulation. 2004;109(9):1133–9.CrossRefGoogle Scholar
  58. 58.
    Cleland JG, Abraham WT, Linde C, Gold MR, Young JB, Claude Daubert J, et al. An individual patient meta-analysis of five randomized trials assessing the effects of cardiac resynchronization therapy on morbidity and mortality in patients with symptomatic heart failure. Eur Heart J. 2013;34(46):3547–56.  https://doi.org/10.1093/eurheartj/eht290.CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Moss AJ, Hall WJ, Cannom DS, Klein H, Brown MW, Daubert JP, et al. Cardiac-resynchronization therapy for the prevention of heart-failure events. N Engl J Med. 2009;361(14):1329–38.  https://doi.org/10.1056/NEJMoa0906431.CrossRefPubMedGoogle Scholar
  60. 60.
    Cleland JGF, Calvert MJ, Verboven Y, Freemantle N. Effects of cardiac resynchronization therapy on long-term quality of life: an analysis from the CArdiac Resynchronisation-Heart Failure (CARE-HF) study. Am Heart J. 2009;157(3):457–66.  https://doi.org/10.1016/j.ahj.2008.11.006.CrossRefPubMedGoogle Scholar
  61. 61.
    Bristow MR, Saxon LA, Boehmer J, Krueger S, Kass DA, De Marco T, et al. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med. 2004;350(21):2140–50.CrossRefGoogle Scholar
  62. 62.
    Cleland JGF, Daubert J-C, Erdmann E, Freemantle N, Gras D, Kappenberger L, et al. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med. 2005;352(15):1539–49.CrossRefGoogle Scholar
  63. 63.
    Tang ASL, Wells GA, Talajic M, Arnold MO, Sheldon R, Connolly S, et al. Cardiac-resynchronization therapy for mild-to-moderate heart failure. N Engl J Med. 2010;363(25):2385–95.  https://doi.org/10.1056/NEJMoa1009540.CrossRefPubMedGoogle Scholar
  64. 64.
    Ruschitzka F, Abraham WT, Singh JP, Bax JJ, Borer JS, Brugada J, et al. Cardiac-resynchronization therapy in heart failure with a narrow QRS complex. N Engl J Med. 2013;369(15):1395–405.  https://doi.org/10.1056/NEJMoa1306687.CrossRefPubMedGoogle Scholar
  65. 65.
    Gasparini M, Mantica M, Galimberti P, Genovese L, Pini D, Faletra F, et al. Is the outcome of cardiac resynchronization therapy related to the underlying etiology? Pacing Clin Electrophysiol. 2003;26(1 Pt 2):175–80.CrossRefGoogle Scholar
  66. 66.
    Goldenberg I, Moss AJ, Hall WJ, Foster E, Goldberger JJ, Santucci P, et al. Predictors of response to cardiac resynchronization therapy in the multicenter automatic defibrillator implantation trial with cardiac resynchronization therapy (MADIT-CRT). Circulation. 2011;124(14):1527–36.  https://doi.org/10.1161/CIRCULATIONAHA.110.014324.CrossRefPubMedGoogle Scholar
  67. 67.
    Morani G, Gasparini M, Zanon F, Casali E, Spotti A, Reggiani A, et al. Cardiac resynchronization therapy-defibrillator improves long-term survival compared with cardiac resynchronization therapy-pacemaker in patients with a class IA indication for cardiac resynchronization therapy: data from the Contak Italian Registry. Europace. 2013;15(9):1273–9.  https://doi.org/10.1093/europace/eut032.CrossRefPubMedGoogle Scholar
  68. 68.
    Looi K-L, Gajendragadkar PR, Khan FZ, Elsik M, Begley DA, Fynn SP, et al. Cardiac resynchronisation therapy: pacemaker versus internal cardioverter-defibrillator in patients with impaired left ventricular function. Heart. 2014;100(10):794–9.  https://doi.org/10.1136/heartjnl-2014-305537.CrossRefPubMedGoogle Scholar
  69. 69.
    Lloyd-Jones D, Adams RJ, Brown TM, Carnethon M, Dai S, De Simone G, et al. Executive summary: heart disease and stroke statistics—2010 update: a report from the American Heart Association. Circulation. 2010;121(7):948–54.  https://doi.org/10.1161/CIRCULATIONAHA.109.192666.CrossRefPubMedGoogle Scholar
  70. 70.
    Stolfo D, Merlo M, Pinamonti B, Poli S, Gigli M, Barbati G, et al. Early improvement of functional mitral regurgitation in patients with idiopathic dilated cardiomyopathy. Am J Cardiol. 2015;115(8):1137–43.  https://doi.org/10.1016/j.amjcard.2015.01.549.CrossRefGoogle Scholar
  71. 71.
    Franzen O, van der Heyden J, Baldus S, Schlüter M, Schillinger W, Butter C, et al. MitraClip® therapy in patients with end-stage systolic heart failure. Eur J Heart Fail. 2011;13(5):569–76.  https://doi.org/10.1093/eurjhf/hfr029.CrossRefPubMedGoogle Scholar
  72. 72.
    Auricchio A, Schillinger W, Meyer S, Maisano F, Hoffmann R, Ussia GP, et al. Correction of mitral regurgitation in nonresponders to cardiac resynchronization therapy by MitraClip improves symptoms and promotes reverse remodeling. J Am Coll Cardiol. 2011;58(21):2183–9.  https://doi.org/10.1016/j.jacc.2011.06.061.CrossRefPubMedGoogle Scholar
  73. 73.
    Berardini A, Biagini E, Saia F, Stolfo D, Previtali M, Grigioni F, et al. Percutaneous mitral valve repair: the last chance for symptoms improvement in advanced refractory chronic heart failure? Int J Cardiol. 2017;228:191–7.  https://doi.org/10.1016/j.ijcard.2016.11.241.CrossRefPubMedGoogle Scholar
  74. 74.
    Mehra MR, Canter CE, Hannan MM, Semigran MJ, Uber PA, Baran DA, et al. The 2016 International Society for Heart Lung Transplantation listing criteria for heart transplantation: a 10-year update. J Heart Lung Transplant. 2016;35(1):1–23.  https://doi.org/10.1016/j.healun.2015.10.023.CrossRefPubMedGoogle Scholar
  75. 75.
    Rose EA, Gelijns AC, Moskowitz AJ, Heitjan DF, Stevenson LW, Dembitsky W, et al. Long-term use of a left ventricular assist device for end-stage heart failure. N Engl J Med. 2001;345(20):1435–43.CrossRefGoogle Scholar
  76. 76.
    Lietz K, Long JW, Kfoury AG, Slaughter MS, Silver MA, Milano CA, et al. Outcomes of left ventricular assist device implantation as destination therapy in the post-REMATCH era: implications for patient selection. Circulation. 2007;116(5):497–505.CrossRefGoogle Scholar
  77. 77.
    Matthews JC, Koelling TM, Pagani FD, Aaronson KD. The right ventricular failure risk score. J Am Coll Cardiol. 2008;51(22):2163–72.  https://doi.org/10.1016/j.jacc.2008.03.009.CrossRefPubMedPubMedCentralGoogle Scholar
  78. 78.
    Ochiai Y, McCarthy PM, Smedira NG, Banbury MK, Navia JL, Feng J, et al. Predictors of severe right ventricular failure after implantable left ventricular assist device insertion: analysis of 245 patients. Circulation. 2002;106(12 Suppl 1):I198–202.PubMedGoogle Scholar
  79. 79.
    Stevenson LW, Pagani FD, Young JB, Jessup M, Miller L, Kormos RL, et al. INTERMACS profiles of advanced heart failure: the current picture. J Heart Lung Transplant. 2009;28(6):535–41.  https://doi.org/10.1016/j.healun.2009.02.015.CrossRefPubMedGoogle Scholar
  80. 80.
    Kilic A, Acker MA, Atluri P. Dealing with surgical left ventricular assist device complications. J Thorac Dis. 2015;7(12):2158–64.  https://doi.org/10.3978/j.issn.2072-1439.2015.10.64.CrossRefPubMedPubMedCentralGoogle Scholar

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Authors and Affiliations

  • Alessandro Altinier
    • 1
  • Alessia Paldino
    • 1
  • Marta Gigli
    • 1
  • Aniello Pappalardo
    • 1
  • Gianfranco Sinagra
    • 2
  1. 1.Cardiovascular DepartmentAzienda Sanitaria Universitaria Integrata, University of Trieste (ASUITS)TriesteItaly
  2. 2.Cardiovascular DepartmentAzienda Sanitaria Universitaria IntegrataTriesteItaly

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