This article updates the Heart Failure Association of the European Society of Cardiology (ESC) 2007 classification of advanced heart failure and describes new diagnostic and treatment options for ...these patients. Recognizing the patient with advanced heart failure is critical to facilitate timely referral to advanced heart failure centres. Unplanned visits for heart failure decompensation, malignant arrhythmias, co‐morbidities, and the 2016 ESC guidelines criteria for the diagnosis of heart failure with preserved ejection fraction are included in this updated definition. Standard treatment is, by definition, insufficient in these patients. Inotropic therapy may be used as a bridge strategy, but it is only a palliative measure when used on its own, because of the lack of outcomes data. Major progress has occurred with short‐term mechanical circulatory support devices for immediate management of cardiogenic shock and long‐term mechanical circulatory support for either a bridge to transplantation or as destination therapy. Heart transplantation remains the treatment of choice for patients without contraindications. Some patients will not be candidates for advanced heart failure therapies. For these patients, who are often elderly with multiple co‐morbidities, management of advanced heart failure to reduce symptoms and improve quality of life should be emphasized. Robust evidence from prospective studies is lacking for most therapies for advanced heart failure. There is an urgent need to develop evidence‐based treatment algorithms to prolong life when possible and in accordance with patient preferences, increase life quality, and reduce the burden of hospitalization in this vulnerable patient population.
Desmosomal and phospholamban (PLN) mutations are associated with arrhythmogenic cardiomyopathy. Ultimately, most cardiomyopathic hearts develop significant cardiac fibrosis.
To compare the fibrosis ...patterns of desmosomal and p. Arg14del PLN-associated cardiomyopathies with the pattern in hearts with other hereditary cardiomyopathies.
A midventricular transversal slice was obtained from hearts of 30 patients with a cardiomyopathy with a known underlying mutation and from 8 controls. Fibrosis and fatty changes were quantitatively analyzed using digital microscopy.
Hearts from patients with desmosomal mutations (n = 6) showed fibrosis and fibrofatty replacement in the left ventricular (LV) outer myocardium, mainly in the posterolateral wall, and in the right ventricle. A similar phenotype, but with significantly more severe fibrotic changes in the LV, was found in the PLN mutation group (n = 8). Cardiomyopathies associated with lamin A/C (n = 5), sarcomeric (n = 8), and desmin (n = 3) mutations all showed a different pattern from that of the desmosomal and PLN mutation carriers. The posterolateral LV wall appeared to be the most discriminative area with fibrosis and fatty changes predominantly at the outer compact myocardium in 13 of 14 hearts with desmosomal and PLN mutations (93%), in 0 of 13 hearts with lamin A/C and sarcomeric mutations (0%), and in 1 of 3 desminopathic hearts (33%) (P < .001).
Desmosomal- and PLN-associated cardiomyopathies have a fibrosis pattern distinct from the patterns in other hereditary cardiomyopathies. The posterolateral LV wall appeared to be the most discriminative region between mutation groups. These results may provide a roadmap for cardiac imaging interpretation and may help in further unraveling disease mechanisms.
Cardiac allograft vasculopathy (CAV) is a multifactorial pathology limiting the survival of cardiac transplants. The etiology of CAV is unclear, but antibody-mediated and cellular-mediated responses ...have been implicated. We, and others, have observed ectopic lymphoid structures (ELS) surrounding epicardial coronary arteries with CAV. The potential contribution of these ELS to CAV has not been elucidated.
Epicardial coronary arteries were collected from 59 transplant patients at 2 centers and studied for ELS presence and composition using immunohistochemistry. The intima and ELS were isolated, and the expression of the genes involved in tertiary lymphoid organ (TLO) formation was measured by quantitative polymerase chain reaction.
ELS presence was related to survival after transplantation (p = 0.013) and histologic composition of CAV (p < 0.001). ELS contain B and T lymphocytes, macrophages, and antibody-producing (immunoglobulin Ig M and/or IgG) plasma cells. A sub-population of B lymphocytes appeared to be cluster of differentiation (CD)20(+)CD27(+) memory B lymphocytes. The messenger RNA expression of TLO markers (lymphotoxin-β, and chemokine C-C motif ligand 19 and 21) was significantly higher in ELS than in the neointimal lesions. The ELS observed in this study exhibited some TLO markers but did not exhibit the distinct areas rich in B and T lymphocytes that are normally found in classic TLOs.
The cellular composition of the ELS differs from the cellular infiltrate in CAV intimal lesions. The presence of memory B lymphocytes and plasma producing IgM and IgG cells suggests that ELS are related to local antibody production, potentially contributing to antibody-mediated CAV. ELS associated with coronary vessels containing CAV show features of underdeveloped TLOs; classic TLOs may not develop due to patient immunosuppression.
Long-term mechanical circulatory support (LT-MCS) is an important treatment modality for patients with severe heart failure. Different devices are available, and many-sometimes ...contradictory-observations regarding patient selection, surgical techniques, perioperative management and follow-up have been published. With the growing expertise in this field, the European Association for Cardio-Thoracic Surgery (EACTS) recognized a need for a structured multidisciplinary consensus about the approach to patients with LT-MCS. However, the evidence published so far is insufficient to allow for generation of meaningful guidelines complying with EACTS requirements. Instead, the EACTS presents an expert opinion in the LT-MCS field. This expert opinion addresses patient evaluation and preoperative optimization as well as management of cardiac and non-cardiac comorbidities. Further, extensive operative implantation techniques are summarized and evaluated by leading experts, depending on both patient characteristics and device selection. The faculty recognized that postoperative management is multidisciplinary and includes aspects of intensive care unit stay, rehabilitation, ambulatory care, myocardial recovery and end-of-life care and mirrored this fact in this paper. Additionally, the opinions of experts on diagnosis and management of adverse events including bleeding, cerebrovascular accidents and device malfunction are presented. In this expert consensus, the evidence for the complete management from patient selection to end-of-life care is carefully reviewed with the aim of guiding clinicians in optimizing management of patients considered for or supported by an LT-MCS device.
This clinical consensus statement reviews the use of inotropic support in patients with advanced heart failure. The current guidelines only support use of inotropes in the setting of acute ...decompensated heart failure with evidence of organ malperfusion or shock. However, inotropic support may be reasonable in other patients with advanced heart failure without acute severe decompensation. The clinical evidence supporting use of inotropes in these situations is reviewed. Particularly, patients with persistent congestion, systemic hypoperfusion, or advanced heart failure with need for palliation, and specific situations relevant to implantation of left ventricular assist devices or heart transplantation are discussed. Traditional and novel drugs with inotropic effects are discussed and use of guideline‐directed therapy during inotropic support is reviewed. Finally, home inotropic therapy is described, and palliative care and end‐of‐life aspects are reviewed in relation to management of ongoing inotropic support (including guidance for maintenance and weaning of chronic inotropic therapy support).
Background
Late right heart failure (LRHF) is a common complication during long‐term left ventricular assist device (LVAD) support. We aimed to identify risk factors for LRHF after LVAD implantation.
...Methods
Patients undergoing primary LVAD implantation between 2006 and 2019 and surviving the perioperative period were included for this study (n = 261). Univariate Cox proportional hazards analysis was used to assess the association of clinical covariates and LRHF, stratified for device type. Variables with p < 0.10 entered the multivariable model. In a subset of patients with complete echocardiography or right catheterization data, this multivariable model was extended. Postoperative cardiopulmonary exercise test data were compared in patients with and without LRHF.
Results
Nineteen percentage of patients suffered from LRHF after a median of 12 months, of which 67% required hospitalization. A history of atrial fibrillation (AF) (HR: 2.06 1.08–3.93, p = 0.029), a higher preoperative body mass index (BMI) (HR: 1.07 1.01–1.13, p = 0.023), and intensive care unit (ICU) duration (HR: 1.03 1.00–1.06, p = 0.025) were independent predictors of LHRF in the multivariable model. A significant relation between the severity of tricuspid regurgitation (TR) and LRHF (HR: 1.91 1.13–3.21, p = 0.016) was found in patients with echocardiographic data. Patients with LRHF demonstrated a lower maximal workload and peak VO2 at 6 months postoperatively.
Conclusion
A history of AF, BMI, and longer ICU stay may help identify patients at high risk for LRHF. Severity of TR was significantly related to LRHF in a subset of patients
The aim, methods, and results of this study, where risk factors for late right heart failure in long‐term mechanical circulatory support were analyzed
Patients on continuous flow left ventricular assist devices (cf‐LVADs) are able to return to an active lifestyle and perform all sorts of physical activities. This study aims to evaluate exercise ...hemodynamics in patients with a HeartMate II cf‐LVAD (HM II). Thirty (30) patients underwent a bicycle exercise test. Along with exercise capacity, systemic cardiovascular responses and pump performance were evaluated at 6 and 12 months after HM II implantation. From rest to maximum exercise, heart rate increased from 87 ± 14 to 140 ± 32 beats/minute (bpm) (P < 0.01), while systolic arterial blood pressure increased from 93 ± 12 to 116 ± 21 mm Hg (P < 0.01). Total cardiac output (TCO) increased from 4.1 ± 1.1 to 8.5 ± 2.8 L/min (P < 0.01) while pump flow increased less, from 5.1 ± 0.7 to 6.4 ± 0.6 L/min (P < 0.01). Systemic vascular resistance (SVR) decreased from 1776 ± 750 to 1013 ± 383 dynes.s/cm5 (P < 0.001) and showed the strongest correlation with TCO (r = −0.72; P < 0.01). Exercise capacity was affected by older age, while blood pressure increased significantly in men compared with women. Exercise capacity remained consistent at 6 and 12 months after HM II implantation, 51% ± 13% and 52% ± 13% of predicted VO2max for normal subjects corrected for age and gender. In conclusion, pump flow of the HM II may contribute partially to TCO during exercise, while SVR was the strongest determinant of TCO.
Background
The interleukin‐33 (IL‐33)/suppressor of tumorigenicity 2 (ST2) pathway is suggested to play an important role in fibrosis, remodelling and the progression of heart failure (HF). Increased ...soluble (sST2) levels are associated with adverse outcome in the average HF population. Less is known about sST2 levels in end‐stage HF. Therefore, we studied sST2 levels in end‐stage HF and the effect of unloading by left ventricular assist device (LVAD) support on sST2 levels.
Method and results
Serial plasma measurements of sST2 were performed pre‐implantation and 1, 3 and 6 months after (LVAD) implantation in 38 patients. sST2 levels were elevated in end‐stage HF just prior to LVAD implantation (74.2 ng/mL IQR 54.7‐116.9; normal <35 ng/mL) and decreased substantially during LVAD support, to 29.5 ng/mL IQR 24.7‐46.6(P < .001). Patients with INTERMACS profile I had significantly higher sST2 levels compared to patients in profile II and profile III. A moderate correlation was found between sST2 and C‐reactive protein (r = .580, P < .010).
Conclusion
Levels of sST2 are elevated in end‐stage HF patients with variability that suggests multiple inputs to a pro‐inflammatory and pro‐fibrotic pathway. Cardiogenic shock and increased C‐reactive protein levels are associated with higher sST2 levels. LVAD support results in a significant drop in sST2 levels with normalization within 3 months postimplantation. This suggests that LVAD support leads to lessening of fibrosis and inflammation, which might eventually be used to target medical policy: explantation of the LVAD versus permanent use or cardiac transplantation.
Aims
Growth differentiation factor‐15 (GDF‐15) is a stress‐responsive cytokine and is emerging as a biomarker of cardiac remodelling. Left ventricular assist devices (LVADs) provide unloading of the ...left ventricle, resulting in partial reverse remodelling. Our aim was to study GDF‐15 in patients with a non‐ischaemic dilated cardiomyopathy (DCM) during LVAD support.
Methods and results
We analysed circulating GDF‐15 in 30 patients before and 1, 3, and 6 months after LVAD implantation and before heart transplantation or explantation. In addition, mRNA and protein expression of GDF‐15 were evaluated in myocardial tissue obtained prior to and after LVAD support. Circulating GDF‐15 was significantly higher before LVAD implantation as compared with healthy controls (P < 0.001). After 1 month of mechanical support, GDF‐15 levels were significantly decreased compared with pre‐implantation levels (P < 0.001) and remained stable thereafter. Circulating GDF‐15 was significantly correlated with kidney function and the severity of myocardial fibrosis. Interestingly, GDF‐15 mRNA and protein expression in the myocardium were hardly detectable.
Conclusions
High circulating levels of GDF‐15 in patients with end‐stage non‐ischaemic DCM correlate with myocardial fibrosis and kidney function and decline strongly after 1 month of mechanical unloading, remaining stable thereafter. However, cardiac mRNA and protein expression of GDF‐15 are very low, suggesting that the heart is not an important source of GDF‐15 production in these patients.
Continuous-flow left ventricular assist devices (CF-LVADs) are increasingly used in the management of patients with end-stage heart failure; however, CF-LVAD support can be hampered by the occurrence ...of ventricular arrhythmias (VAs) (1-5). In a multivariate Cox regression model, only pre-LVAD VA remained as an independent predictor of late post-LVAD VA (adjusted hazard ratio HR: 2.13; 95% confidence interval CI: 1.06 to 4.27; p = 0.03) (Figure 1B).
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