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Heart failure remains one of the most prevalent diseases worldwide and in recent decades, left ventricular assist devices (LVADs) have become an important treatment option. With increasing device experience, there is particular interest in the use of LVADs as a bridge to recovery that allows the patient's heart to undergo reverse remodeling, whereby the device can be explanted and the heart can function at an improved state. There are many considerations that play a role in this process, including the ability of the device to unload the heart, the innate physiology of the heart to recover and the use of concomitant therapies. This review provides an overview of the most current literature as it pertains to these processes and gives a view into the future directions of LVADs as a tool for achieving myocardial recovery. [ABSTRACT FROM AUTHOR]

Ventricular assist-device ( VAD) implantation is a life-saving therapy which will later become either a bridge-to-transplantation or definitive therapy if heart transplantation ( HTx) is not possible. VAD-supported failing hearts often recover at the molecular and cellular level, but translation of these changes into functionally stable cardiac recovery allowing long-term HTx/ VAD-free outcomes after VAD removal is relatively rare, related to the aetiology, severity, and duration of myocardial damage. The reason for the discrepancy between high recovery rates on cellular and molecular levels and the low rate of cardiac recovery allowing VAD explantation is unknown. For selected patients VAD explantation is feasible. HTx/ VAD-free outcomes for >15 years are possible even if recovery remains incomplete and the underlying cause for VAD implantation was idiopathic dilated cardiomyopathy. Echocardiography and right heart catheterization are necessary to assess clinically relevant cardiac recovery. Certain echo parameters appeared highly predictive for post-weaning cardiac function and reliable for weaning decisions. The elective therapeutic use of VADs for heart failure ( HF) reversal in its earlier stages is a future goal possibly achievable by development of tools to predict HF reversibility already before VAD implantation and increase the number of weaning candidates by improvement of adjunctive therapies to optimize unloading-promoted recovery. The present article summarizes the knowledge about unloading-promoted myocardial recovery and reviews the available data on its clinical relevance, its post-explant stability, and its assessment for decision-making in favour of or against VAD explantation. The review also aims to provide a theoretical and practical basis for clinicians intending to be engaged in this field. [ABSTRACT FROM AUTHOR]

Introduction Cardiovascular disease is a major cause of death worldwide. Different medical and surgical therapeutic options are well established, but a significant number of patients are not amenable to standard therapeutic options. Cell-based therapies after clinical application have shown different results in recent years. Here, we are giving a comprehensive overview on major available clinical data regarding cell therapy. Background Cell-based therapies and tissue engineering provide new promising platforms to develop upcoming therapeutic options. Initial clinical trials were able to generate promising results. A variety of different stem cell types have been used for the clinical application. Different adult cardiac stem cells and progenitor cells, including mesenchymal, CD34+ and CD133+ autologous human bone marrow-derived stem cells ( BMCs), human myoblasts, and peripheral blood-derived stem and progenitor cells ( PBSCs) have been used for the therapy for end-stage heart failure. Future experiments will show the importance of novel cell populations and clarify the mechanism causing cell therapy-mediated observed effects. Conclusion Several clinical trials have reported on sole therapy, as well as combined application of autologous adult stem cells with conventional revascularization. The reported promising findings encourage further research in the field of the translational research. [ABSTRACT FROM AUTHOR]

OBJECTIVES Fulminant myocarditis with cardiogenic shock is fatal without mechanical circulatory support. Once haemodynamic stability has been established with a ventricular assist device (VAD), the decision to wait for myocardial recovery as opposed to listing for an orthotopic heart transplant (OHT) can be difficult. We have undertaken this study to establish the criteria for determining the need for heart transplantation following VAD implant for fulminant myocarditis. METHODS A total of 442 VADs were implanted between 1993 and 2011. Twenty-four VADs were implanted for fulminant myocarditis with refractory cardiogenic shock. We retrospectively analysed the variables and the pathology for this cohort. Patients who had a full recovery of myocardial function and subsequent VAD explant (Explant) were compared with those bridged to OHT. There was one acute death. RESULTS There was no difference in the past medical history between the groups. Explant patients had a more acute onset of heart failure with a median of 7 days between the onset of symptoms and VAD implant, when compared with 22 days for OHT (P = 0.01). A rapid recovery in myocardial function was seen in the Explant group, with recovery of myocardial function (ejection fraction = 53 ± 24%) in 14 ± 7 days. Myocardial function was sustained for 5 years following the VAD explant. The female gender favoured myocardial recovery and VAD explantability. Two patients had giant cell myocarditis, neither of whom had a recovery of function, and they were bridged to heart transplant with a VAD. CONCLUSIONS Fulminant myocarditis is a fatal condition without mechanical support. The rapid onset of symptoms is associated with a complete recovery of myocardial function and VAD explant. The absence of rapid recovery of myocardial function should prompt listing for a heart transplant. [ABSTRACT FROM AUTHOR]

Myocardial recovery occurs in approximately 5% of left ventricular assist device recipients. In selected patients, it is possible to electively perform left ventricular assist device explantation after accurate myocardial function recovery assessment. Several surgical approaches and techniques have been reported in the literature that focus on left ventricular assist device removal and preservation of left ventricular geometry. We provide a detailed step-by-step tutorial for continuous-flow left ventricular assist device explantation facilitated by the use of a manufactured titanium apical recovery plug., (© The Author 2022. Published by MMCTS on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Medical and device therapies that reduce heart failure morbidity and mortality also lead to decreased left ventricular volume and mass and a more normal elliptical shape of the ventricle. These are due to changes in myocyte size, structure, and organization that have been referred to collectively as reverse remodeling. Moreover, there are subsets of patients whose hearts have undergone reverse remodeling either spontaneously or after medical or device therapies and whose clinical course is associated with freedom from future heart failure events. This phenomenon has been referred to as myocardial recovery. Despite the frequent interchangeable use of the terms “myocardial recovery” and “reverse remodeling” to describe the reversal of various aspects of the heart failure phenotype after medical and device therapy, the literature suggests that there are important differences between these 2 phenomena and that myocardial recovery and reverse remodeling are not synonymous. In this review, we discuss the biology of cardiac remodeling, cardiac reverse remodeling, and myocardial recovery with the intent to provide a conceptual framework for understanding myocardial recovery. [ABSTRACT FROM AUTHOR]

Peripartum cardiomyopathy is diagnosed in women who develop systolic heart failure in the last month of pregnancy or within 5 months of delivery. This diagnosis should not be made in women with pre-existing cardiac disease or another cause of cardiac dysfunction. To prevent delay in diagnosis and treatment, a high index of suspicion is required given the overlapping symptoms of late pregnancy and heart failure. Traditional heart failure medical therapies are indicated, although drugs must be carefully reviewed for safety during pregnancy and lactation. Long-term prognosis is largely determined by the degree of ventricular recovery. Patients with acute or persistent hemodynamic compromise despite medical therapy should be considered for mechanical circulatory support and evaluated promptly for cardiac transplantation. A multidisciplinary team is required to care for patients with peripartum cardiomyopathy through parturition and beyond. All peripartum cardiomyopathy patients should be counseled that repeat pregnancy can negatively impact cardiac function and lead to recurrent heart failure or even death. Patients with persistent ventricular dysfunction should be strongly advised against another pregnancy. [ABSTRACT FROM AUTHOR]

Abstract: Background: Clinical and experimental studies have traditionally focused on understanding the mechanisms for why a heart fails. We hypothesize that the pathways involved with myocardial recovery are not simply the reverse of those that cause heart failure. However, determining when and how a decompensated heart can recover remains unknown. Methods: Male C57BL/6 mice underwent minimally invasive aortic banding for 3, 4, or 6 wk with or without subsequent band removal for 1 wk (debanding). Physiologic and genomic characterization was performed with intracardiac pressure-volume recordings, rt-PCR, and microarray analysis. Results: Heart weight/body weight ratios and PV loops demonstrated a transition from compensated left ventricular hypertrophy to decompensated heart failure between 3 and 4 wk. Pressure-relief afforded by debanding allowed functional recovery and normalization of LVH after both 3 and 4, but not 6 wk of banding. Whole genome microarrays demonstrated 397 genes differentially expressed in recovered hearts, 250 genes differentially expressed in the nonrecoverable (6 wk) hearts, and only 10 genes shared by both processes. In particular, altered expression patterns of apoptotic and metalloproteinase genes correlated with the heart’s ability to functionally recover. Conclusions: This clinically-relevant model (1) allows us to temporally and mechanistically characterize the failing heart, (2) demonstrates a unique genomic signature that may predict when a failing heart can recover following pressure relief, and (3) will prove useful as a template for testing therapeutic strategies aimed at recovery of the failing heart. [Copyright &y& Elsevier]

Background: Response to catecholamines is blunted in terminal heart failure due to β-receptor downregulation and uncoupling from adenylyl cyclase (AC). Improved myocardial responsiveness to catecholamines after ventricular assist device (VAD) support is associated with upregulation of β1-adrenergic receptors (β1-ARs). Little is known about the regulation of AC and β2-AR coupling after VAD; moreover β2-AR stimulation during VAD was claimed to induce myocardial recovery. Methods: We analyzed in VAD-supported human myocardium the regulation of AC activity upon β1-AR and selective β2-AR stimulation in 8 non-failing hearts (NF) and 17 paired samples of VAD patients. AC messenger RNA was measured by TaqMan. AC was stimulated via β2-AR using clenbuterol (β2-AR agonist) and bisoprolol (β1-AR blocker). Organ bath experiments were done with trabeculae from both ventricles. Samples were stratified according to chronic or acute heart failure history. Results: Isoprenaline-induced AC activity was downregulated (p < 0.001) pre-VAD and increased significantly (p < 0.05) after unloading (mean ± standard deviation pmole/mg/min) in NF (47.9 ± 14.9), pre-VAD (24.35 ± 13.3), and post-VAD (50.04 ± 50.25). Forskolin stimulation revealed significant (p < 0.05) upregulation of AC activity during VAD, especially in acutely failing hearts (NF, 192.1 ± 68.7; pre-VAD, 191.1 ± 60.4; post-VAD, 281.5 ± 133). However, forskolin stimulation relative to isoprenaline-induced inotropy remained reduced before and after VAD compared with NF. The selective stimulation of β2-AR did not reveal influence of VAD support on β2-AR–AC coupling. Stimulation of ventricular trabeculae by > 100 μmole/liter clenbuterol revealed negative inotropic responses. Conclusions: VAD does not influence β2-AR coupling to AC stimulation. Elevated response to catecholamines after VAD support is influenced by β1-AR upregulation and modulation of AC activity. Restoration of β-adrenergic responsiveness was restricted to acutely failing hearts. [Copyright &y& Elsevier]

Background--Detection of cardiac recovery that allows long-term cardiac stability after ventricular assist device (VAD) explantation is a major goal. After normalization of ventricular diameters during unloading, the pre-explant left ventricular ejection fraction (LVEF) allows the detection of patients with the potential to remain stable after VAD explantation. However, some patients with LVEF >45% before VAD explantation show early recurrence of heart failure (HF). We aimed to find out if unstable improvement can be recognized before VAD explantation. Methods and Results--Among 96 patients weaned from VADs since 1995, a relatively homogenous group of 53 patients with nonischemic chronic cardiomyopathy (CCM) was selected for the study. The pre-explant stability of major parameters of LV function, size, and geometry that were measured by echocardiography during serial "off-pump" trials was tested for relationship with cardiac stability after VAD explantation. LVEF, systolic peak wall motion velocity (Sm), end-diastolic diameter (LVEDD), end-diastolic relative wall thickness (RWTED) and end-diastolic short/long-axis ratio (S/LED) were selected for evaluation. In postweaning unstable patients, the selected parameters showed relevant instability already before VAD explantation during the time period between best cardiac improvement and VAD explantation and also during the final off-pump trial just before VAD explantation. For all parameters, there were significant differences (P<0.05) in pre-explant changes between patients with and without postweaning cardiac stability. Using the optimal cutoff values obtained from receiver-operating characteristic analysis, we found for our selected parameters predictive values for postexplant cardiac stability of ≥1 year, ≥13 years, and ≥15 years, ranging between 94% and 100%, 92%, and 100%, and 78% and 100%, respectively. Using for all parameter changes the cutoff value of 10%, we found similar predictive values for cardiac stability of ≥1 year, ≥13 years, and ≥15 years, ranging between 93% and 97%, 90% and 96%, and 83% and 92%, respectively. Conclusions--Our results strongly suggest the possibility to improve the prediction of postexplant transplant/VAD-free outcome in CCM patients with cardiac improvement during VAD support by analyzing the pre-explant stability of several LV off-pump echocardiographic parameters during serial off-pump trials. [ABSTRACT FROM AUTHOR]

Medical and device therapies that reduce heart failure morbidity and mortality also lead to decreased left ventricular volume and mass, and a more normal elliptical shape of the ventricle. These are due to changes in myocyte size, structure, and organization that have been referred to collectively as 'reverse remodeling.' Moreover, there are subsets of patients whose hearts have undergone reverse remodeling following mechanical circulatory support with a ventricular assist device (VAD), who are able to be weaned from their VADs, which has been referred to as 'myocardial recovery.' Although the term myocardial recovery has been used to describe the reversal of various aspects of the heart failure phenotype following medical and device therapy, there is no consensus with regard to what constitutes myocardial recovery; moreover, the methodology for identifying myocardial recovery in patients is unclear. These topics will be discussed in the current review. [ABSTRACT FROM AUTHOR]

Abstract: Background: Recovery of ventricular function during left ventricular assist device (LVAD) support allowing device explantation occurs infrequently. We explored the hypothesis that certain patient profiles are more likely to exhibit LV recovery during LVAD support. Methods and Results: A retrospective analysis of data from the HeartMate II bridge to transplant (BTT) and destination therapy (DT) trials was conducted, including 490 BTT, 600 DT, and 18 compassionate-use patients. Of the 1,108 patients, 20 (1.8%; 10 BTT, 10 DT) were explanted owing to LV recovery. The median age was 33 years, and 12 patients (60%) were <40 years of age. History of heart failure was <1 year for 11 patients (61%), and the primary etiology was nonischemic (90%). Of the patients with nonischemic etiologies and <1-year history of heart failure, 13% were explanted. Three patients required LVAD reimplantation; of the remaining 17, 16 remain alive. At follow-up (median 510 days), the mean ejection fraction was 42% (20%–67%) and the mean left ventricular end-diastolic diameter was 55 ± 8 mm. At the 2-year follow-up (n = 13), patients were New York Heart Association functional class I or II and overall survival rate was 85 ± 11%. Conclusions: The results of this study suggest that LV recovery is most likely to occur in young patients (<40 years) with nonischemic cardiomyopathy of <1 year duration. Two-year postexplant survival was excellent. [Copyright &y& Elsevier]

Abstract: Background: Whether myocardial recovery occurs more frequently in peripartum cardiomyopathy (PPCM) than in recent onset cardiomyopathies in men and nonperipartum women has not been prospectively evaluated. This was examined through an analysis of outcomes in the Intervention in Myocarditis and Acute Cardiomyopathy 2 (IMAC2) registry. Methods and Results: IMAC2 enrolled 373 subjects with recent onset nonischemic dilated cardiomyopathy. Left ventricular ejection fraction (LVEF) was assessed at entry and 6 months, and subjects followed for up to 4 years. Myocardial recovery was compared between men (group 1), nonperipartum women (group 2) and subjects with PPCM (group 3). The cohort included 230 subjects in group 1, 104 in group 2, and 39 in group 3. The mean LVEF at baseline in groups 1, 2, and 3 was 0.23 ± 0.08, 0.24 ± 0.08, and 0.27 ± 0.07 (P = .04), and at 6 months was 0.39 ± 0.12, 0.42 ± 0.11, and 0.45 ± 0.14 (P = .007). Subjects in group 3 had a much greater likelihood of achieving an LVEF >0.50 at 6 months than groups 1 or 2 (19 %, 34%, and 48% respectively, P = .002). Conclusions: Prospective evaluation confirms myocardial recovery is greatest in women with PPCM, poorest in men, and intermediate in nonperipartum women. On contemporary therapy, nearly half of women with PPCM normalize cardiac function by 6 months. [Copyright &y& Elsevier]

Background: Off-pump implantation of left ventricular assist device (LVAD) axial or centrifugal flow pumps in patients with low ejection fraction (EF) is of major clinical relevance. In addition, all pre-clinical, long-term implantations performed so far have been carried out in healthy animals, but this does not reflect the eventual clinical setting. In this study we established a new technique using a miniaturized axial flow pump in sheep with chronically ischemic myocardium. Methods: Sheep (n = 15) underwent intracoronary sphere injection to create chronic ischemic heart failure. Reduced EF was assessed using transesophageal echocardiography. All animals underwent implantation of a new miniaturized axial flow pump via an extraperitoneal, subcostal surgical approach. Results: Our technique allows easy exposure of the diaphragmatic surface of the heart and the descending aorta. Ten animals (range 65 to 78 kg) underwent off-pump implantation 30 (range 25 to 33) days after intracoronary sphere injection. All animals had significantly reduced EF (25 ± 4.8%) and were receiving high doses of inotropic agents to maintain cardiac function. Nine animals survived the surgical procedure. The average 12-hour blood loss was 435 ml. Cardiac index improved significantly in all animals. The procedure time was not extended by any adverse events (60 to 145 minutes). Conclusions: The extraperitoneal, subcostal surgical approach is less invasive than a median sternotomy and allows centrifugal or axial to be implanted quickly and without cardiopulmonary bypass (CPB). Avoiding CPB and an extensive mediastinal dissection can help to decrease significantly the number of complications in patients with end-stage organ failure. [Copyright &y& Elsevier]

Aims Unloading-promoted reversal of heart failure (HF) allows long-term transplant-free outcome after ventricular assist device (VAD) removal. However, because few patients with chronic cardiomyopathy (CCM) were weaned from VADs (the majority only recently), the reliability of criteria used for weaning decisions to predict long-term post-weaning success is barely known. After 15 years of weaning experience, we assessed this issue. Methods and results In 47 patients with CCM as the underlying cause for HF, who were part of a total of 90 patients weaned from bridge-to-transplant-designed VADs since 1995, we analysed data on cardiac morphology and function collected before VAD implantation, echocardiographic parameters recorded during ‘off-pump’ trials, duration of HF before implantation, and stability of recovery before and early after VAD removal. Post-weaning 5 year freedom from HF recurrence reached 66%. Only five patients (10.6%) died due to HF recurrence or weaning-related complications. Pre-explantation off-pump left ventricular ejection fraction (LVEF) of ≥50 and ≥45% revealed predictive values for cardiac stability lasting ≥5 years after VAD removal of 91.7 and 79.1%, respectively. With each unit of LVEF reduction, the risk of HF recurrence became 1.5 times higher. The predictive value of LVEF ≥45% also became >90% if additional parameters like pre-explantation LV size and geometry, stability of unloading-induced cardiac improvement before VAD removal, and HF duration before VAD implantation were also considered. Definite cut-off values for certain parameters (including tissue-Doppler-derived LV wall motion velocity) allowed formulation of weaning criteria with high predictability for post-weaning stability, also in patients with incomplete cardiac recovery. Conclusions Ventricular assist device removal in CCM patients is feasible and can be successful even after incomplete cardiac recovery. Parameters of pre-explantation cardiac function, LV size and geometry, their stability during final off-pump trials, and HF duration allow detection of patients with the potential to remain stable for >5 post-weaning years. [ABSTRACT FROM PUBLISHER]

Heart failure is considering one of the most prevalent diseases in recent years. Despite advances in the treatment with new drugs and devices such as implantable defibrillator and cardiac resynchronization therapy, the progression in heart failure leads to deterioration in the quality of life, frequent hospitalizations and high mortality rates. Advanced stage of this disease remains heart transplantation for treatment choice, although is not the adequate therapy for all the patients. Many of them require support with inotropic drugs, which lead to a progressive deterioration and limited survival, because waiting times are prolonged or transplantation is not performed. Therefore, progress in circulatory support devices allow to consider these as the treatment while awaiting transplantation and an alternative when the transplant is not considered an option. It is our objective to review the progress and the usefulness of circulatory support devices in patients with advanced heart failure, in which the last option is heart transplantation. [ABSTRACT FROM AUTHOR]

Recent advances in the field of left ventricular device support have led to an increased use of left ventricular assist devices (LVADs) in patients with end stage heart disease. The primary imaging modality to monitor patients with LVADs has been echocardiography. The purpose of this review is to highlight the clinical role of echo and other noninvasive imaging modalities in the assessment of cardiac structure and function in patients with pulsatile and continuous flow LVADs. In addition, we discuss the role of imaging with emphasis on echo to detect LVAD dysfunction and device related complications. [ABSTRACT FROM AUTHOR]

Background: Myocardial β-adrenergic receptor (β-AR) signaling is severely impaired in chronic heart failure (HF). This study was conducted to determine if left ventricular (LV) β-AR signaling could be restored after continuous-flow LV assist device (LVAD) support. Methods: Twelve patients received LVADs as a bridge to transplant. Paired LV biopsy specimens were obtained at the time of LVAD implant (HF group) and transplant (LVAD group). The mean duration of LVAD support was 152 ± 34 days. Myocardial β-AR signaling was assessed by measuring adenylyl cyclase (AC) activity, total β-AR density (Bmax), and G protein-coupled receptor kinase-2 (GRK2) expression and activity. LV specimens from 8 non-failing hearts (NF) were used as controls. Results: Basal and isoproterenol-stimulated AC activity was significantly lower in HF vs NF, indicative of β-AR uncoupling. Continuous-flow LVAD support restored basal and isoproterenol-stimulated AC activity to levels similar to NF. Bmax was decreased in HF vs NF and increased to nearly normal in the LVAD group. GRK2 expression was increased 2.6-fold in HF vs NF and was similar to NF after LVAD support. GRK2 activity was 3.2-fold greater in HF vs NF and decreased to NF levels in the LVAD group. Conclusions: Myocardial β-AR signaling can be restored to nearly normal after continuous-flow LVAD support. This is similar to previous data for volume-displacement pulsatile LVADs. Decreased GRK2 activity is an important mechanism and indicates that normalization of the neurohormonal milieu associated with HF is similar between continuous-flow and pulsatile LVADs. This may have important implications for myocardial recovery. [Copyright &y& Elsevier]

The maximum ventricular elastance is a reliable index for assessing the cardiac function from changes in its pressure-volume relationship. The advantage of this index is that it can represent the contractility of either unassisted hearts or native hearts assisted with rotary blood pumps. However, there are situations in which changes in the ventricular load required for the conventional estimation method might be risky. For example, in a bridge-to-recovery the cardiac function should also be continuously observed after the implantation of a rotary blood pump. In this article, we present the results of the estimation of the maximum elastance with in vivo data using the parameter optimization method, which is a single-beat estimation method. The estimated values for the normal cardiac function (6.8 ± 0.6, 4.5 ± 0.9, 4.2 ± 1.8 mm Hg/mL) were significantly different from those for the low cardiac function (3.2 ± 1.5, 1.9 ± 1.0, 1.9 ± 1.2 mm Hg/mL) from the data of the three animals that were analyzed. Besides, the maximum elastance values were independent of the pump rotational speed. These results indicate that this index might be useful for the detection of the myocardial recovery. [ABSTRACT FROM AUTHOR]

We report a possible new therapeutic strategy, using extracorporeal cardiopulmonary support (ECLS), for severe refractory cardiogenic shock (SRCS) in a patient with Tako-tsubo cardiomyopathy (TC). TC is a syndrome characterized by left ventricular wall motion abnormalities, without coronary artery disease, mimicking the diagnosis of acute coronary syndrome. This ventricular dysfunction can be reversible; however, it can progress into refractory cardiogenic shock with limited therapeutic options available. For the first time in a Tako-tsubo patient with refractory cardiogenic shock, we used ECLS treatment in order to rest the heart, sustain circulation and end-organ perfusion, and promote potential ventricular recovery. ECLS might be the selected treatment for SRCS in patients with TC, and seems to be an effective and useful ultimate therapeutic strategy for preventing death. [ABSTRACT FROM AUTHOR]

Mechanical circulatory support is an important adjunct to the management of patients with advanced heart failure. Technological advances in this area have improved overall survival and decreased the incidence of complications. In addition, they have expanded the population suitable for this therapy. The challenge for clinicians is to translate the clinical evidence into the selection of the most appropriate device that will benefit an individual patient. This paper will review ventricular assist devices currently available and their clinical indications. [ABSTRACT FROM AUTHOR]

We report the use of extra-corporeal cardiopulmonary support (ECLS), in a case of complicating refractory severe cardiogenic shock, in a patient with Tako-tsubo cardiomyopathy (TC). Tako-tsubo cardiomyopathy syndrome is characterized by left ventricular (LV) wall motion abnormalities, usually without coronary artery disease, mimicking the diagnosis of acute coronary syndrome. This ventricular dysfunction is typically reversible in the acute phase, though it can progress into refractory cardiogenic shock with limited therapeutic options available. Here, we report for the first time in a Tako-tsubo patient with refractory cardiogenic shock, the use of ECLS treatment in order to unload the heart, sustain circulation and end-organ perfusion, and promote potential ventricular recovery. Extra-corporeal life support allowed inotropic drug weaning while maintaining end-organ function and supported the patient until myocardial recovery. The patient recovered completely, and a normal LV ejection fraction was documented by 2D echocardiography on day 7. From our experience, ECLS can be an appropriate treatment for severe refractory cardiogenic shock in patients with TC. Extra-corporeal life support was an effective ultimate solution. [ABSTRACT FROM PUBLISHER]

The purpose was to study dobutamine magnetic resonance cine imaging (DOB-MRI) and delayed myocardial contrast enhancement (DE) early after reperfused acute myocardial infarction (AMI) for the predicion of segmental myocardial recovery and to find the optimal dose of dobutamine. Fifty patients (56±12 years, 42 males) with reperfused AMI underwent DOB-MRI and DE studies 3.5 (1–19) days after reperfusion. In DOB-MRI systolic wall thickening (SWT) was measured in 18 segments at rest and during dobutamine at 5, 10 and 20 μg*kg−1*min−1. Dysfunctional segments were identified and the extent of DE was measured for each segment. Segmental recovery was examined after 8 (5–15) months. Two hundred-forty-eight segments were dysfunctional with presence of DE in 193. DOB-MRI showed the best prediction of recovery at 10 μg*kg−1*min−1 of dobutamine with sensitivity of 67%, specificity of 63% and accuracy of 66% using a cut-off value for SWT of 2.0 mm. DE revealed a sensitivity of 68%, specificity of 65% and accuracy of 67% using a cut-off value of 46%. Combined analysis of DOB-MRI and DE did not improve diagnostic performance. Early prediction of segmental myocardial recovery after AMI is possible with DOB-MRI and DE. No improvement is achieved by dobutamine >10 μg*kg−1*min−1 or a combination of DOB-MRI and DE. [ABSTRACT FROM AUTHOR]

Some patients in need of hemodynamic support do not respond to intra-aortic balloon pump (IABP) therapy. Hemodynamic stability can then be obtained by a more potent cardiac assist device, like the Impella catheter pump. Whether additional IABP support additional to Impella support can provide more optimal hemodynamic myocardial conditions is examined in this study. Seven sheep were implemented with IABP and Impella. An acute myocardial infarction was induced. Hemodynamic performance was assessed during baseline, during Impella support and IABP support individually, and during the combined Impella plus IABP support. The Impella support provided a reduction of afterload with 30% and an increase of coronary artery flow with 47%. The IABP increased coronary artery flow (13%), carotid artery flow (16%), and aortic ascending blood pressure (6%); a similar (but stronger) effect was provided when using the IABP support additional to Impella support and, respectively, increases of 33, 21, and 19% were established. The oxygen demand–supply ratio decreased by 25% due to the extra use of the IABP. A combination of IABP and Impella provides the most optimal hemodynamic myocardial conditions compared to either stand-alone support. [ABSTRACT FROM AUTHOR]

The role of ventricular-assist devices in the management of end-stage heart failure is growing. Initially developed as a ‘bridge to transplantation’, they are now implanted permanently in patients who need cardiac replacement but are not candidates for cardiac transplantation (‘destination therapy’). Furthermore, observations from expert centers indicate that a significant proportion of patients under long-term mechanical assistance can be weaned from mechanical circulatory support after significant functional recovery of their native heart (‘bridge to recovery’). This review discusses the emerging roles of mechanical circulatory support and their direct implications in clinical practice. Evolution of devices, important aspects of candidate selection, challenging issues in the management of ventricular-assist device patients (infection, device malfunction, anticoagulation-thromboembolic complications, psychosocial issues and cost) and ongoing research targeting sustained myocardial recovery are discussed. [ABSTRACT FROM AUTHOR]

Much has been learned since the 1980s regarding the epidemiology, etiology, and outcomes of children with dilated cardiomyopathy (DCM). However, relatively little is understood about myocardial recovery in pediatric DCM: (1) when does pediatric DCM recover; (2) what are the predictors of recovery; (3) what are the clinical features of recovery; and (4) what are clinical and research gaps? A purpose of the Fifth International Conference on Childhood Cardiomyopathy was to update researchers and clinicians with interests in pediatric cardiomyopathy and heart failure on recent findings in myocardial recovery in DCM. This review is a summary of literature with details on cardiac recovery, not simply survival, in children with DCM. More children with DCM are surviving without heart transplant in the current era of heart failure management, but the rate of recovery in these survivors is not widely known. Recovery of cardiac function ranges from 11-52% across multiple single and multi- center studies. Robust predictors for myocardial recovery in pediatric DCM are lacking. Future studies need to identify non-invasive markers of recovery to guide both prognostication at the time of diagnosis and to evaluate pharmaceuticals or device therapies that promote recovery. Studies of myocardial recovery in children need to include quality of life measures, long-term outcomes, and risk factors for heart failure recurrence or sudden death. • Like non-idiopathic dilated cardiomyopathy, idiopathic dilated cardiomyopathy can recover • Myocardial recovery frequently occurs early but can occur late in the disease course • Serial changes are more important predictors of improvement than presenting features • Research gaps include clinical and biomarker predictors of myocardial recovery • The impact on quality of life of various treatment approaches to cardiomyopathy needs further study [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text. Background: Variable definitions and an incomplete understanding of the gradient of reverse cardiac remodeling following continuous flow left ventricular assist device (LVAD) implantation has limited the field of myocardial plasticity. We evaluated the continuum of LV remodeling by serial echocardiographic imaging to define 3 stages of reverse cardiac remodeling following LVAD. Methods: The study enrolled consecutive LVAD patients across 4 study sites. A blinded echocardiographer evaluated the degree of structural (LV internal dimension at end-diastole [LVIDd]) and functional (LV ejection fraction [LVEF]) change after LVAD. Patients experiencing an improvement in LVEF ≥40% and LVIDd ≤6.0 cm were termed responders, absolute change in LVEF of ≥5% and LVEF <40% were termed partial responders, and the remaining patients with no significant improvement in LVEF were termed nonresponders. Results: Among 358 LVAD patients, 34 (10%) were responders, 112 (31%) partial responders, and the remaining 212 (59%) were nonresponders. The use of guideline-directed medical therapy for heart failure was higher in partial responders and responders. Structural changes (LVIDd) followed a different pattern with significant improvements even in patients who had minimal LVEF improvement. With mechanical unloading, the median reduction in LVIDd was −0.6 cm (interquartile range [IQR], −1.1 to −0.1 cm; nonresponders), −1.1 cm (IQR, −1.8 to −0.4 cm; partial responders), and −1.9 cm (IQR, −2.9 to −1.1 cm; responders). Similarly, the median change in LVEF was −2% (IQR, −6% to 1%), 9% (IQR, 6%–14%), and 27% (IQR, 23%–33%), respectively. Conclusions: Reverse cardiac remodeling associated with durable LVAD support is not an all-or-none phenomenon and manifests in a continuous spectrum. Defining 3 stages across this continuum can inform clinical management, facilitate the field of myocardial plasticity, and improve the design of future investigations. [ABSTRACT FROM AUTHOR]

Temporary mechanical circulatory support (TMCS) provides short-term support to patients with or at risk of refractory cardiogenic shock. Although indications, contraindications, and complications of TMCS may guide device selection, optimal strategies for device weaning and explant remain poorly defined. Under the revised adult heart allocation policy implemented by the United Nations for Organ Sharing in October 2018, rejustification of heart transplant listing status includes demonstrating TMCS dependency with attempted device wean trials. However, standardized device-specific weaning and explant protocols have not been proposed or evaluated. This review highlights when to use percutaneous TMCS in cardiogenic shock, with a focus on weaning and explant considerations. Terminology for important concepts that guide device escalation, de-escalation, and explantation have been defined. Clinical, hemodynamic, metabolic, and imaging features have been defined, which can guide a tailored approach to TMCS weaning and explant based on the approach used at the Cleveland Clinic. A narrative review of published studies that have reported TMCS weaning protocols and survey results of member centers from CS-MCS working group centers is also provided. Future research is needed to better understand optimal timing and implementation of standardized protocols to achieve successful TMCS weaning and explant., Competing Interests: Funding Support and Author Disclosures Dr Soltesz has been a speaker for Abiomed; and has provided training for Abbott. Dr Tong has been a consultant and a speaker for Abbott and Abiomed. Dr Hernandez-Montfort has been a consultant for Abiomed and LivaNova. Dr Estep has been a consultant for Abbott and Getinge; and has been a medical advisor for Medtronic Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Data on ventricular unloading-promoted myocardial recovery and post-weaning outcome in children is scarce. We analyzed the weaning outcome in children with heart failure (HF) supported with ventricular assist device (VAD)., Methods: A multi-institutional data on VAD implanted in 193 children and adolescents with HF between April 1990 and November 2015 was reviewed. Among them, 25 children (mean age 3.4±3.0, range, 0.058-16.3 years, 15 females) were weaned from VAD. Etiology of HF were myocarditis (n=11), dilated cardiomyopathy (DCMP) (n=7), ischemic HF (n=3), arrhythmogenic CMP (n=1), post-correction of congenital heart disease (CHD) (n=1) and acute graft failure (n=1). Mean duration of HF before VAD implantation was 59.4±3 days., Results: Age, duration of HF, DCMP, cardiac arrest and duration of VAD are essential clinical characteristics to delineate who may have the potential to myocardial recovery. Echocardiographic parameters pre-implantation, during the final off-pump trial and during the post-explantation follow-ups revealed that LVEF, LVEDD and relative wall thickness (RWT) showed significant differences (P<0.001) among patients stratified by outcome to assess recovery. Presently, 21 (84.0%) of the weaned patients are alive with their native hearts 1.3-19.1 years after VAD explantation. An additional weaned patient had HF recurrence 3 months post-weaning and was transplanted., Conclusions: Post-weaning myocardial recovery and cardiac stability of children with HF from several etiologies supported with a VAD appears sustainable and durable. Young patients with short HF duration are more likely to recover. Absence of cardiac arrest, cardiac size, geometry and function may prospectively identify patients who may be likely to have myocardial recovery., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure forms (available at http://dx.doi.org/10.21037/cdt-20-278). The series “Heart Failure in the Young and Old: Insights into Various Therapies” was commissioned by the editorial office without any funding or sponsorship. RH served as the unpaid Guest Editor of the series and serves as an unpaid editorial board member of Cardiovascular Diagnosis and Therapy from July 2019 to Jun 2021. The authors have no other conflicts of interest to declare., (2021 Cardiovascular Diagnosis and Therapy. All rights reserved.)

The first and successful implantation of a ventricular assist device in 1990 has allowed an 8-year-old child with an end-stage heart failure to undergo a heart transplantation. This milestone paved the way to consider support with ventricular assist in the armamentarium of heart failure management in infants, children and adolescents. Several systems have evolved and faded owing to unacceptable complications. Indications and contraindications to implantation have been established. Anticoagulation management is still on its way to impeccability. Despite the challenges, issues and concerns revolving around ventricular assist devices, the system definitely supports pediatric patients with end-stage heart failure until heart transplantation and could allow recovery of the myocardium., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure forms (available at http://dx.doi.org/10.21037/cdt-20-282). The series “Heart Failure in the Young and Old: Insights into Various Therapies” was commissioned by the editorial office without any funding or sponsorship. RH served as the unpaid Guest Editor of the series and serves as an unpaid editorial board member of Cardiovascular Diagnosis and Therapy from July 2019 to Jun 2021. The authors have no other conflicts of interest to declare., (2021 Cardiovascular Diagnosis and Therapy. All rights reserved.)

Although complete myocardial recovery after ventricular assist device (VAD) implantation is rather seldom, systematic search for recovery is worthwhile because for recovered patients weaning from VADs is feasible and can provide survival benefits with long-term freedom from heart failure (HF) recurrence, even if a chronic cardiomyopathy was the primary cause for the drug-refractory HF necessitating left ventricular (LVAD) or biventricular support (as bridge-to-transplantation or definitive therapy) and even if recovery remains incomplete. LVAD patients explanted for myoacardial recovery compared to those transplanted from LVAD support showed similar survival rates and a significant proportion of explanted patients can achieve cardiac and physical functional capacities that are within the normal range of healthy controls. In apparently sufficiently recovered patients, a major challenge remains still the pre-explant prediction of the weaning success which is meanwhile reliably possible for experienced clinicians. In weaning candidates, the combined use of certain echocardiography and right heart catheterization parameters recorded before VAD explantation can predict post-weaning cardiac stability with good accuracy. However, in the absence of standardization or binding recommendations, the protocols for assessment of native cardiac improvement and also the weaning criteria differ widely among centers. Currently there are still only few larger studies on myocardial recovery assessment after VAD implantation. Therefore, the weaning practice relies mostly on small case series, local practice patterns, and case reports, and the existing knowledge, as well as the partially differing recommendations which are based mainly on expert opinions, need to be periodically systematised. Addressing these shortcomings, our review aims to summarize the evidence and expert opinion on the evaluation of cardiac recovery during mechanical ventricular support by paying special attention to the reliability of the methods and parameters used for assessment of myocardial recovery and the challenges met in both evaluation of recovery and weaning decision making., Competing Interests: Conflicts of Interest: The authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/cdt-20-288). The series “Heart Failure in the Young and Old: Insights into Various Therapies” was commissioned by the editorial office without any funding or sponsorship. RH served as the unpaid Guest Editor of the series, and serves as an unpaid editorial board member of Cardiovascular Diagnosis and Therapy from Jul 2019 to Jun 2021. The authors have no other conflicts of interest to declare., (2021 Cardiovascular Diagnosis and Therapy. All rights reserved.)

Objectives: Left ventricular assist device (LVAD) implantation for end-stage heart failure patients has been on the rise, providing a reliable long-term option. For some LVAD patients, longer term LV unloading leads to recovery; hence, the need for evaluating potential myocardial recovery and weaning eligibility has emerged., Methods: All patients who underwent contemporary LVAD explantation at our institution between 2009 and 2020 were included in the study. Patients in New York Heart Association I, left ventricular ejection fraction >40%, a cardiac index >2.4 l/min and a peak oxygen intake >50% predicted underwent a 4-phase weaning assessment. A minimally invasive approach using a titanium plug was the surgery of choice in the most recent explants. Kaplan-Meier curves were used to estimate the survival at 1 and 5 years., Results: Twenty-six patients (17 HeartMate II, 9 HeartWare) underwent LVAD explantation after a median 317 days of support [IQ (212-518)], range 131-1437. Mean age at explant was 35.8 ± 12.7 years and 85% were males. Idiopathic dilated cardiomyopathy was the underlying diagnosis in 70% of cases. Thirteen (48%) patients were on short-term mechanical circulatory support and 60% required intensive care unit admission prior to the LVAD implantation. At 1 year, Kaplan-Meier estimated survival was 88%, whereas at 6 years, it was 77%. The average left ventricular ejection fraction at 1 year post-explant was 44.25% ± 8.44., Conclusions: The use of a standardized weaning protocol (echocardiographic and invasive) and a minimally invasive LVAD explant technique minimizes periprocedural complications and leads to good long-term device-free survival rates., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

A minimally invasive approach to left ventricular assist device (LVAD) insertion may benefit patients at the time of implant, but whether the approach to LVAD insertion influences the outcome of subsequent cardiovascular reoperations is unknown. Here we present the case of a 50-year-old male who underwent LVAD insertion through a minimally invasive approach and subsequently had left ventricular recovery. LVAD explant was performed without the use of any blood products or inotropic support. This case demonstrates that a minimally invasive approach to LVAD insertion may also facilitate subsequent device explant.

Background: Baseline predictors of myocardial recovery after cardiac resynchronization therapy (CRT) in left bundle branch block (LBBB)-associated idiopathic nonischemic cardiomyopathy (NICM) are unknown.Methods: A retrospective study included subjects with idiopathic NICM, left ventricular ejection fraction (LVEF) ≤35%, and LBBB. Myocardial recovery was defined as post-CRT LVEF ≥50%. Logistic regression analyses described associations between baseline characteristics and myocardial recovery. Cox regression analyses estimated the hazard ratio (HR) between myocardial recovery status and adverse clinical events.Results: In 105 subjects (mean age 61 years, 44% male, mean initial LVEF 22.6% ± 6.6%, 81% New York Heart Association class III, and 98% CRT-defibrillators), myocardial recovery after CRT was observed in 56 (54%) subjects. Hypertension, heart rate, and serum blood urea nitrogen (BUN) had negative associations with myocardial recovery in univariable analyses. These associations persisted in multivariable analysis: hypertension (odds ratio (OR), 0.40; 95% confidence interval (CI), 0.17-0.95; p = 0.04), heart rate (OR per 10 bpm, 0.69; 95% CI, 0.48-0.997; p = 0.048), and serum BUN (OR per 1 mg/dl, 0.94; 95% CI, 0.88-0.99; p = 0.04). Subjects with post-CRT LVEF ≥50%, when compared to <50%, had lower risk for adverse clinical events (heart failure hospitalization, appropriate implantable cardioverter-defibrillator shock, appropriate anti-tachycardia pacing therapy, ventricular assist device implantation, heart transplantation, and death) over a median follow-up of 75.9 months (HR, 0.38; 95% CI, 0.16-0.88; p = 0.02).Conclusion: In LBBB-associated idiopathic NICM, myocardial recovery after CRT was associated with absence of hypertension, lower heart rate, and lower serum BUN. Those with myocardial recovery had fewer adverse clinical events. [ABSTRACT FROM AUTHOR]