Prevention and Rehabilitation After Heart Transplantation: A Clinical Consensus Statement of the European Association of Preventive Cardiology, Heart Failure Association of the ESC, and the European Cardio Thoracic Transplant Association, a Section of ESOT.

Little is known either about either physical activity patterns, or other lifestyle-related prevention measures in heart transplantation (HTx) recipients. The history of HTx started more than 50 years ago but there are still no guidelines or position papers highlighting the features of prevention and rehabilitation after HTx. The aims of this scientific statement are (i) to explain the importance of prevention and rehabilitation after HTx, and (ii) to promote the factors (modifiable/non-modifiable) that should be addressed after HTx to improve patients' physical capacity, quality of life and survival. All HTx team members have their role to play in the care of these patients and multidisciplinary prevention and rehabilitation programmes designed for transplant recipients. HTx recipients are clearly not healthy disease-free subjects yet they also significantly differ from heart failure patients or those who are supported with mechanical circulatory support. Therefore, prevention and rehabilitation after HTx both need to be specifically tailored to this patient population and be multidisciplinary in nature. Prevention and rehabilitation programmes should be initiated early after HTx and continued during the entire post-transplant journey. This clinical consensus statement focuses on the importance and the characteristics of prevention and rehabilitation designed for HTx recipients.

Prevention and rehabilitation after heart transplantation: A clinical consensus statement of the European Association of Preventive Cardiology, Heart Failure Association of the ESC, and the European Cardio Thoracic Transplant Association, a section of ESOT.

Little is known either about either physical activity patterns, or other lifestyle-related prevention measures in heart transplantation (HTx) recipients. The history of HTx started more than 50 years ago but there are still no guidelines or position papers highlighting the features of prevention and rehabilitation after HTx. The aims of this scientific statement are (i) to explain the importance of prevention and rehabilitation after HTx, and (ii) to promote the factors (modifiable/non-modifiable) that should be addressed after HTx to improve patients' physical capacity, quality of life and survival. All HTx team members have their role to play in the care of these patients and multidisciplinary prevention and rehabilitation programmes designed for transplant recipients. HTx recipients are clearly not healthy disease-free subjects yet they also significantly differ from heart failure patients or those who are supported with mechanical circulatory support. Therefore, prevention and rehabilitation after HTx both need to be specifically tailored to this patient population and be multidisciplinary in nature. Prevention and rehabilitation programmes should be initiated early after HTx and continued during the entire post-transplant journey. This clinical consensus.

Prevention and rehabilitation after heart transplantation: A clinical consensus statement of the European Association of Preventive Cardiology, Heart Failure Association of the ESC, and the European Cardio Thoracic Transplant Association, a section of ESOT.

Little is known either about either physical activity patterns, or other lifestyle-related prevention measures in heart transplantation (HTx) recipients. The history of HTx started more than 50 years ago but there are still no guidelines or position papers highlighting the features of prevention and rehabilitation after HTx. The aims of this scientific statement are (i) to explain the importance of prevention and rehabilitation after HTx, and (ii) to promote the factors (modifiable/non-modifiable) that should be addressed after HTx to improve patients' physical capacity, quality of life and survival. All HTx team members have their role to play in the care of these patients and multidisciplinary prevention and rehabilitation programmes designed for transplant recipients. HTx recipients are clearly not healthy disease-free subjects yet they also significantly differ from heart failure patients or those who are supported with mechanical circulatory support. Therefore, prevention and rehabilitation after HTx both need to be specifically tailored to this patient population and be multidisciplinary in nature. Prevention and rehabilitation programmes should be initiated early after HTx and continued during the entire post-transplant journey. This clinical consensus statement focuses on the importance and the characteristics of prevention and rehabilitation designed for HTx recipients.

Assessing and managing frailty in advanced heart failure: An International Society for Heart and Lung Transplantation consensus statement.

Frailty is increasingly recognized as a salient condition in patients with heart failure (HF) as previous studies have determined that frailty is highly prevalent and prognostically significant, particularly in those with advanced HF. Definitions of frailty have included a variety of domains, including physical performance, sarcopenia, disability, comorbidity, and cognitive and psychological impairments, many of which are common in advanced HF. Multiple groups have recently recommended incorporating frailty assessments into clinical practice and research studies, indicating the need to standardize the definition and measurement of frailty in advanced HF. Therefore, the purpose of this consensus statement is to provide an integrated perspective on the definition of frailty in advanced HF and to generate a consensus on how to assess and manage frailty. We convened a group of HF clinicians and researchers who have expertise in frailty and related geriatric conditions in HF, and we focused on the patient with advanced HF. Herein, we provide an overview of frailty and how it has been applied in advanced HF (including potential mechanisms), present a definition of frailty, generate suggested assessments of frailty, provide guidance to differentiate frailty and related terms, and describe the assessment and management in advanced HF, including with surgical and nonsurgical interventions. We conclude by outlining critical evidence gaps, areas for future research, and clinical implementation.

The four pillars of HFrEF therapy: is it time to treat heart failure regardless of ejection fraction?

The syndrome of heart failure (HF) has historically been dichotomized based on clinical trial inclusion criteria into patients with a reduced or preserved left ventricular ejection fraction (LVEF) using a cut-off of above or below 40%. The majority of trial evidence for the benefits of disease-modifying pharmacological therapy has been in patients with HF with reduced ejection fraction (HFrEF), i.e. those with an LVEF ≤40%. Recently, the sodium-glucose co-transporter 2 inhibitors empagliflozin and dapagliflozin have been shown to be the first drugs to improve outcomes in HF across the full spectrum of LVEF. There is, however, growing evidence that the benefits of many of the neurohumoral modulators shown to be beneficial in patients with HFrEF may extend to those with a higher LVEF above 40% but still below the normal range, i.e. HF with mildly reduced ejection fraction (HFmrEF). Whether the benefits of some of these medications also extend to patients with HF and preserved ejection fraction (HFpEF) is an area of ongoing debate. This article will review the evidence for HF treatments across the full spectrum of LVEF, provide an overview of recently updated clinical practice guidelines, and address the question whether it may now be time to treat HF with some therapies regardless of ejection fraction.

Humoral response to heterologous prime-booster vaccination in heart transplant recipients aged 18-70 years primed with a viral vector SARS-CoV-2 vaccine.

Solid organ transplant recipients have demonstrated a blunted immune response to standard 2-dose vaccination against SARS-CoV-2. This study sought to determine the humoral response to heterologous booster vaccination (viral vector vaccine dose 1 and 2 + mRNA booster). Heart transplant recipients, aged 18 to 70 years of age who initially received two doses of the viral vector ChAdOx1 nCoV-19 vaccine followed by a BNT162b2 mRNA booster were recruited. A detectable antibody response in the absence of prior SARS-CoV-2 was the primary outcome measured. This was defined as an anti-spike titre of ≥0.8 U/mL on the Elecsys anti-SARS-CoV-2 S immunoassay. A total of 80 heart transplant patients (mean age 49 ± 13 years, 28% female) were included. Blood samples were drawn at a median of 30 (IQR 28-33) days after the BNT162b2 mRNA booster. The frequency of a detectable antibody response increased from 37.5% (n = 30) after dose 2 to 56% (n = 45) post dose 3 (p < 0.001). A non-detectable antibody response was significantly more common in recipients with a shorter time interval from transplantation (p < 0.001), lower likelihood of cardiac allograft vasculopathy (p = 0.003) and in those prescribed a triple versus dual immunosuppressant regime (p = 0.009) and a tacrolimus versus cyclosporine basedregimen (p = 0.007). Despite heterologous prime-booster vaccination 44% of this vulnerable population ultimately continue to have no detectable antibodies.

A survey-based triage tool to identify patients potentially eligible for referral to an advanced heart failure centre.

AIMS: Accurate prevalence data for ambulatory advanced heart failure (HF) in European countries remains limited. This study was designed to identify the population of patients potentially eligible for referral for assessment for advanced surgical HF therapies to a National advanced HF and cardiac transplant centre. METHODS AND RESULTS: A survey comprising 13 potential clinical markers of advanced HF was developed, modified from the 'I NEED HELP' tool from the 2018 position statement of the Heart Failure Association of the European Society of Cardiology, and distributed to all HF clinic services (secondary and tertiary units) nationwide. Each HF clinic unit was asked to complete the survey on consecutive patients over a 3 month period fulfilling the following three criteria: (i) age <65 years; (ii) ejection fraction <40% and (iii) HF of >3 months duration. As a comparison, the number of actual referrals to the advanced HF clinic were also audited over a 9 month period. In all, 21 of 26 HF clinic units participated in the survey. Across the period of inclusion, 4950 all-comer HF patients were seen across all sites. Of these, 375 (7.5%) fulfilled the inclusion criteria and were surveyed (74.4% male, median age 57 years [IQR: 11 years]). In total, 246 (66%) of the surveyed patients had ≥1 potential markers for advanced HF, representing just under 5% of the total all-comer HF population seen across the same time period. Of these, 67 patients (27%) had ≥2, 48 (20%) had 3 and 40 (16%) had ≥4 potential markers. The most frequently noted markers were ≥1 HF hospitalization or unscheduled clinic review (56%), intolerance to renin-angiotensin-aldosterone system inhibitors due to hypotension or renal dysfunction (29%) and intolerance to beta-blockers due to hypotension (27%). Almost one-quarter of patients reported NYHA Class III or IV symptoms. During the advanced HF clinic audit, the number of patients actually referred to the advanced HF clinic during the same time period was <5% of this potentially eligible cohort. CONCLUSIONS: In this index prospective National survey, approximately 5% of an all-comer routine HF clinic population and two-thirds of a pre-selected HF with reduced EF under 65 years cohort were found to have at least one clinical or biochemical marker suggesting advanced or impending advanced HF. Almost one-quarter of patients in this chronic outpatient 'snapshot' population have NYHA III-IV symptoms. This simple one-page triage survey-modified from the 'I NEED HELP' tool-is useful to identify a population potentially eligible for referral to an advanced HF centre for assessment for advanced surgical therapies, thereby aiding resource and service planning.

Humoral response to SARS-CoV-2 adenovirus vector vaccination (ChAdOx1 nCoV-19 [AZD1222]) in heart transplant recipients aged 18 to 70 years of age.

BACKGROUND: Recent studies have suggested a blunted immune response to messenger RNA vaccines in solid organ transplant (SOT) recipients. Given the paucity of data on adenovirus vector vaccines use in immunosuppressed SOT recipients, we sought to describe the safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine in a heart transplant population. METHODS: Heart transplant recipients aged 18 to 70 years scheduled to receive 2 doses of the ChAdOx1 nCoV-19 vaccine were enrolled into a prospective study involving serum analysis to define their antibody response. An antibody concentration against the spike protein receptor-binding domain of ≥0.8 U/mL was deemed a detectable antibody response. RESULTS: A total of 99 heart transplant recipients (mean age 51 ± 12.5 years, 28% female) were enrolled. No major adverse events were recorded after vaccination; minor symptoms included injection site pain (24%), fatigue (21%) and headache (14%). Of 7 patients with prior SARS-CoV-2 confirmed by PCR testing, all (100%) had detectable antibody responses following first and second vaccine doses. In those with no prior SARS-CoV-2 infection (n = 92), 24% (n = 22) showed an antibody response after dose 1, increasing to 34.8% (n = 32) after dose 2, p < 0.001. Chronic kidney disease (CKD) stage ≥3 (OR 4.7, 95% CI 1.5-15, p = 0.009) and mycophenolate use (OR 4.1, 95% CI 1.2-14, p = 0.02) were independently associated with a nondetectable antibody response. CONCLUSIONS: Almost two-thirds of heart transplant recipients aged 18 to 70 years without a history of prior SARS-CoV-2 infection failed to develop a detectable antibody response following administration of the ChAdOx1 nCoV-19 vaccine. Patient phenotyping may help predict which patients are less likely to develop detectable antibody responses.

Sarcoidosis-Related Cardiomyopathy: Current Knowledge, Challenges, and Future Perspectives State-of-the-Art Review.

The prevalence of sarcoidosis-related cardiomyopathy is increasing. Sarcoidosis impacts cardiac function through granulomatous infiltration of the heart, resulting in conduction disease, arrhythmia, and/or heart failure. The diagnosis of cardiac sarcoidosis (CS) can be challenging and requires clinician awareness as well as differentiation from overlapping diagnostic phenotypes, such as other forms of myocarditis and arrhythmogenic cardiomyopathy. Clinical manifestations, extracardiac involvement, histopathology, and advanced cardiac imaging can all lend support to a diagnosis of CS. The mainstay of therapy for CS is immunosuppression; however, no prospective clinical trials exist to guide management. Patients may progress to developing advanced heart failure or ventricular arrhythmia, for which ventricular assist device therapies or heart transplantation may be considered. The existing knowledge gaps in CS call for an interdisciplinary approach to both patient care and future investigation to improve mechanistic understanding and therapeutic strategies.

The role of endomyocardial biopsy in suspected myocarditis in the contemporary era: a 10-year National Transplant Centre experience.

BACKGROUND: Diagnostic endomyocardial biopsy (EMB) in patients with suspected myocarditis helps to direct therapy and guide prognosis. This study aimed to investigate the correlation between the 2007 clinical guideline indications for EMB and the presence of a diagnostic biopsy result and associated outcomes in patients with suspected myocarditis in a national quaternary referral center in a contemporary cohort. METHODS: All cases of suspected myocarditis referred to the National Cardiac Transplant Centre who underwent EMB between 2009 and 2019 were identified retrospectively through pathology records. Outcomes including subsequent need for inotrope and/or mechanical circulatory support (MCS), heart transplantation and in-hospital mortality were recorded. RESULTS: In total, 25 (68% male, mean age of 45 ± 15 years) EMBs were performed for this indication across this time period, 64% (n = 16) of which demonstrated diagnostic results, the majority (75%, n = 12) identifying acute lymphocytic myocarditis, 13% (n = 2) giant cell, one patient (6.3%) eosinophilic and one (6.3%) an immune checkpoint inhibitor myocarditis. The majority of those with histologically confirmed myocarditis had a Class I or IIa guideline indication for EMB (n = 12, 75%). The remaining 4 patients (25%), either met Class IIb criteria (n = 2) or would not have been accounted for in this guideline. The majority of patients requiring inotropes and/or MCS (n = 9/11), and/or heart transplant (n = 3/4), or who later died (n = 4/5) were in the diagnostic biopsy group. CONCLUSIONS: In this 10-year National referral sample, 75% of patients with histologically confirmed myocarditis had a Class I or IIa indication for EMB, reinforcing the usefulness of traditional guidelines in this contemporary era. However, 25% of patients with a subsequent confirmed histological diagnosis had either none or a less well-established indication for EMB, highlighting the need for clinical suspicion outside of accepted clinical scenarios.

Dynamic Assessment of Pulmonary Artery Pulsatility Index Provides Incremental Risk Assessment for Early Right Ventricular Failure After Left Ventricular Assist Device.

BACKGROUND: The pulmonary artery pulsatility index (PAPi) has been studied to predict right ventricular failure (RVF) after left ventricular assist device (LVAD) implantation, but only as a single time point before LVAD implantation. Multiple clinical factors and therapies impact RV function in pre-LVAD patients. Thus, we hypothesized that serial PAPi measurements during cardiac intensive care unit (CICU) optimization before LVAD implantation would provide incremental risk stratification for early RVF after LVAD implantation. METHODS AND RESULTS: Consecutive patients who underwent sequential pulmonary artery catherization with cardiac intensive care optimization before durable LVAD implantation were included. Serial hemodynamics were reviewed retrospectively across the optimization period. The optimal PAPi was defined by the initial PAPi + the PAPi at optimized hemodynamics. RVF was defined as need for a right ventricular assist device or prolonged inotrope use (>14 days postoperatively). Patients with early RVF had significantly lower mean optimal PAPi (3.5 vs 7.5, P < .001) compared with those who did not develop RVF. After adjusting for established risk factors of early RVF after LVAD implantation, the optimal PAPi was independently and incrementally associated with early RVF after LVAD implantation (odds ratio 0.64, 95% confidence interval 0.532-0.765, P < .0001). CONCLUSIONS: Optimal PAPi achieved during medical optimization before LVAD implantation provides independent and incremental risk stratification for early RVF, likely identifying dynamic RV reserve.

Impact of Atrial Fibrillation on In-Hospital Mortality and Thromboembolic Complications after Left Ventricular Assist Device Implantation.

The association between atrial fibrillation (AF) and thromboembolic (TE) complications in left ventricular assist device (LVAD) recipients is controversial, and there is paucity of large-scale data evaluating the impact of AF on early outcomes after device implantation. Using the National Inpatient Sample, we identified hospitalizations where patients underwent LVAD implantation from 2010 to 2015. Multivariate logistic regression was used to evaluate the association of AF on in-hospital outcomes. A total of 18,378 patients (41.7% with AF) underwent LVAD implantation. Patients with AF were older (59.9 vs. 54.0 years, p < 0.001), more commonly male (79.9 vs. 74.1%, p < 0.001), and had a greater burden of comorbidities as measured by the Elixhauser comorbidity index (7.2 vs. 6.3, p < 0.001). Patients with AF had less incidence of ischemic stroke (3.1 vs. 4.7%, p = 0.04, OR 0.68), hemorrhagic stroke (1.0 vs. 2.4%, p = 0.006, OR 0.43), and other systemic embolism (1.8 vs. 3.7%, p = 0.01, OR 0.55). There was no significant difference in the incidence of bleeding requiring transfusion between AF and no AF cohorts (29.3 vs. 24.2%, p = 0.09, OR 1.15). LOS was shorter in patients with AF (32.9 vs. 36.7 mean days, p < 0.001). Patients with AF had lower in-hospital mortality (8.9 vs. 14.9%, p < 0.001, OR 0.48). In a large real-world US cohort of patients undergoing LVAD implantation, a diagnosis of AF was common among device recipients. After adjustment for demographics and comorbidities, AF was associated with reduced TE events and in-hospital mortality.