Rates and modulators of SARS‐CoV‐2 vaccine nonresponse and breakthrough infections remain unclear in serially vaccinated transplant recipients. In a prospective, mono‐centric, observational study, ...1878 adult solid organ and hematopoietic cell transplant recipients, with prior SARS‐CoV‐2 vaccination, were included between March 2021 and February 2022. SARS‐CoV‐2 anti‐spike IgG antibodies were measured at inclusion and details on SARS‐CoV‐2 vaccine doses and infection were collected. No life‐threatening adverse events were reported after a total of 4039 vaccine doses. In transplant recipients without prior SARS‐CoV‐2 infection (n = 1636), antibody response rates ranged widely, from 47% in lung transplant to 90% in liver transplant and 91% in hematopoietic cell transplant recipients after third vaccine dose. Antibody positivity rate and levels increased after each vaccine dose in all types of transplant recipients. In multivariable analysis, older age, chronic kidney disease and daily dose of mycophenolate and corticosteroids were negatively associated with antibody response rate. Overall rate of breakthrough infections was 25.2% and mainly (90.2%) occurred after third and fourth vaccine dose. Lung transplant recipients had the highest rates of severe breakthrough infection (10.5%) and death (2.5%). In multivariable analysis, older age, daily dose of mycophenolate and corticosteroids were associated with severe breakthrough infection. Transplant recipients with infection before first vaccine dose (n = 160) had higher antibody response rates and levels after each vaccine dose, and a significantly lower overall rate of breakthrough infections compared to those without prior infection. Antibody response after SARS‐CoV‐2 vaccination and rate of severe breakthrough infections vary largely between different transplant types and are modulated by specific risk factors. The observed heterogeneity supports a tailored approach against COVID‐19 in transplant recipients.
Abstract
OBJECTIVES
Hearts donated after circulatory determination of death are usually preserved with normothermic machine perfusion prior to transplantation. This type of preservation is costly, ...requires bench time adding to warm ischaemia, and does not provide a reliable evaluation of the unloaded donor heart. We report on 4 successful donation after circulatory death (category III) hearts transplanted after thoraco-abdominal normothermic regional perfusion (NRP) and static cold storage.
METHODS
After life sustaining therapy was withdrawn and death was declared, perfusion to thoraco-abdominal organs was restored using extracorporeal circulation via cannulas in the femoral artery and vein and clamping of supra-aortic vessels. After weaning from extracorporeal circulation, cardiac function was assessed. Once approved, the heart was retrieved and stored using classic static cold storage. Data are expressed as median min–max.
RESULTS
Donor and recipient ages were 44 years 12–60 (n = 4) and 53 years 14–64 (n = 4), respectively. Time from the withdrawal of life sustaining therapy to start of NRP was 22 min 18–31. Cold storage time was 72 min 35–129. Thirty-day survival was 100% with a left ventricle ejection fraction of 60% 50–60.
CONCLUSIONS
Donation after circulatory death heart transplantation using thoraco-abdominal NRP and subsequent cold storage preservation for up to 129 min was safe for 4 procedures and could be a way to expand the donor heart pool while avoiding costs of machine preservation.
When advanced heart failure occurs in cardiac amyloidosis, prognosis is poor. In this setting heart transplantation (HTX) is a treatment option for selected patients. We here present the results of ...post-transplantation outcomes in cardiac amyloidosis within the Eurotransplant area, investigating possible predictors of survival.
Of 115 patients undergoing HTX due to cardiac amyloidosis in the Eurotransplant region between November 1987 and May 2020, detailed assessment prior to transplantation was available in 85 patients. The present study was conducted in a retrospective approach. Primary endpoint was mortality after HTX. Baseline variables were entered in a Cox proportional hazards model with the primary endpoint as a dependent variable.
Median overall survival following HTX was 6.3 years in the overall collective and the subgroup. Univariate Cox proportional hazards model revealed a significant relationship between overall survival and the transplantation period (2008 to 2020 vs 1987 to 2007; median survival 9.7 years vs 1.8 years, hazard ratio 0.45, p = 0.01). Further predictors were albumin concentration (hazard ratio 0.92, p < 0.001), and systolic blood pressure (hazard ratio 0.96, p < 0.001). The transplant period as well as albumin concentration remained significant independent predictors in the AL sub cohort in a multivariate Cox proportional hazards model.
HTX is a viable treatment option for patients at an advanced stage of cardiac amyloidosis as overall survival after transplantation has improved in the modern age. Patients at a very advanced stage of the disease, indicated by low serum albumin and blood pressure, show worse outcomes following HTX. Optimal timing and careful patient selection may therefore be particularly important to further improve post-HTX survival in amyloidosis patients.
Objectives
As prognosis in sarcoidosis is determined by cardiac involvement, the objective was to study the added value of cardiovascular magnetic resonance (CMR) in risk stratification.
Methods
In ...114 patients (48 ± 12 years/52% male) with biopsy-proven sarcoidosis, we studied the value of clinical and CMR-derived parameters to predict future events, using sustained ventricular tachycardia, ventricular fibrillation, aborted cardiac death, implantable cardioverter-defibrillator (ICD) placement with appropriate shocks, hospitalization for heart failure, and death as composite endpoint. Median follow-up after CMR was 3.1 years (1.1–5.7 years).
Results
The ejection fraction (EF) was 58.2 ± 9.1% and 54.7 ± 10.8% for left ventricle (LV) and right ventricle (RV), respectively. LV late gadolinium enhancement (LGE) was present in 40 patients (35%) involving 5.1% of the LV mass (IQR, 3.0–12.0%), with concomitant RV involvement in 12 patients (11%). T2-weighting imaging and/or T2 mapping showed active disease in 14 patients. The composite endpoint was reached in 34 patients, with 7 deaths in the LGE-positive group (17.5%), versus two deaths in the LGE-negative group (2.7%) (
p
= 0.015). At univariate analysis, RVEF (
p
= 0.009), pulmonary arterial pressure (
p
= 0.002), and presence of LGE (
p
< 0.001) and LGE (% of LV) (
p
< 0.001) were significant. At multivariate analysis, only presence of LGE and LGE (% of LV) was significant (both
p
= 0.03). At Kaplan-Meier, presence of LGE and an LGE of 3% predicted event-free survival and patient survival. We found no difference in active versus inactive disease with regard to patient survival.
Conclusion
Myocardial enhancement at LGE-CMR adds independent prognostic value in risk stratification sarcoidosis patients. In contrast, clinical as well as functional cardiac parameters lack discriminative power.
Key Points
• Sarcoidosis often affects the heart.
• Comprehensive CMR, including T2 imaging and LGE enhancement CMR, allows to depict both active and inactive myocardial damage.
• Patient prognosis in sarcoidosis is determined by the presence and severity of myocardial involvement at LGE CMR.
Interstitial fibrosis is an important component of diastolic, and systolic, dysfunction in heart failure (HF) and depends on activation and differentiation of fibroblasts into myofibroblasts (MyoFb). ...Recent clinical evidence suggests that in late-stage HF, fibrosis is not reversible.
The study aims to examine the degree of differentiation of cardiac MyoFb in end-stage HF and the potential for their phenotypic reversibility.
Fibroblasts were isolated from the left ventricle of the explanted hearts of transplant recipients (ischemic and dilated cardiomyopathy), and from nonused donor hearts. Fibroblasts were maintained in culture without passaging for 4 or 8 days (treatment studies). Phenotyping included functional testing, immunostaining, and expression studies for markers of differentiation. These data were complemented with immunohistology and expression studies in tissue samples.
Interstitial fibrosis with cross-linked collagen is prominent in HF hearts, with presence of activated MyoFbs. Tissue levels of transforming growth factor (TGF)-β1, lysyl oxidase, periostin, and osteopontin are elevated. Fibroblastic cells isolated from HF hearts are predominantly MyoFb, proliferative or nonproliferative, with mature α-smooth muscle actin stress fibers. HF MyoFb express high levels of profibrotic cytokines and the TGF-β1 pathway is activated. Inhibition of TGF-β1 receptor kinase in HF MyoFb promotes dedifferentiation of MyoFb with loss of α-smooth muscle actin and depolymerization of stress fibers, and reduces the expression of profibrotic genes and cytokines levels to non-HF levels.
MyoFb in end-stage HF have a variable degree of differentiation and retain the capacity to return to a less activated state, validating the potential for developing antifibrotic therapy targeting MyoFb.
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Deranged energy metabolism contributes to the pathophysiology of heart failure (HF). Recent studies showed diminished free fatty acid (FFA) oxidation in experimental HF models with a shift towards ...oxidation of ketone bodies. However, conflicting clinical data on FFA metabolism and limited knowledge on ketone body metabolism in human HF mandate additional metabolic profiling studies. We, therefore, investigated cardiac uptake of FFAs and ketone bodies (β-hydroxybutyrate and acetoacetate) in patients with HF with reduced ejection fraction (HFrEF) or with aortic stenosis (AS)-induced left ventricular hypertrophy. We hypothesized that FFA oxidation is impaired in HFrEF and in AS and results in decreased concentrations of free carnitine, the necessary carrier for mitochondrial entry of activated FFAs, and in accumulation of metabolic intermediates.
We collected arterial and coronary sinus blood samples in patients with HFrEF (n=15), in AS patients with preserved systolic function (n=15), and in control patients (n=15). Plasma concentration gradients across the heart show significantly greater uptake of ketone bodies in patients with HFrEF than in controls. Patients with AS show significantly increased uptake of β-hydroxybutyrate and FFAs. Free carnitine concentration and concentration gradients of intermediates of FFA oxidation were comparable between groups.
In conclusion, our results show significantly increased cardiac uptake of ketone bodies in patients with stable HFrEF and AS and increased uptake of FFAs in AS compared with control patients. The lack of myocardial release of acyl-carnitine species or change in free carnitine uptake suggests no impairment of FFA oxidation.
Background Sudden cardiac death (SCD) is the most devastating complication of hypertrophic cardiomyopathy (HCM), but this can be prevented by an implantable cardioverter-defibrillator (ICD). The aim ...of this study is to evaluate HCM patients with ICDs for primary or secondary prevention of SCD. Methods The study population consisted of all HCM patients with an ICD in 2 tertiary referral clinics. End points during follow-up were total and cardiac mortality, appropriate and inappropriate ICD intervention, and device-related complications. Cox-regression analysis was performed to identify predictors of outcome. Results ICDs were implanted in 134 patients with HCM (mean age 44 ± 17 years, 34% women, 4.2 ± 4.8 years follow-up). Annualized cardiac mortality rate was 3.4% per year and associated with New York Heart Association class III or IV (HR 5.2 2.0-14, P = .002) and cardiac resynchronization therapy (HR 6.3 2.1-20, P = .02). Appropriate ICD interventions occurred in 38 patients (6.8%/year) and was associated with implantation for secondary prevention of SCD (HR 4.0 1.8-9.1, P = .001) and male gender (HR 3.3 1.2-9.0, P = .02). Inappropriate ICD intervention occurred in 21 patients (3.7%/year) and in 20 patients device related complications were documented (3.6%/year). Conclusion ICDs successfully abort life-threatening arrhythmias in HCM patients at increased risk of SCD with an annualized intervention rate of 6.8% per year. End-stage heart failure is the main cause of mortality in these patients. The annualized rate of inappropriate ICD intervention was 3.7% per year, whereas device-related complications occurred 3.6% per year.
Abstract Objectives The aim of this study was to compare outcomes of alcohol septal ablation (ASA) in young and elderly patients with obstructive hypertrophic cardiomyopathy (HCM). Background The ...American College of Cardiology Foundation/American Heart Association guidelines reserve ASA for elderly patients and patients with serious comorbidities. Information on long-term age-specific outcomes after ASA is scarce. Methods This cohort study included 217 HCM patients (age 54 ± 12 years) who underwent ASA because of symptomatic left ventricular outflow tract obstruction. Patients were divided into young (age ≤55 years) and elderly (age >55 years) groups and matched by age in a 1:1 fashion to nonobstructive HCM patients. Results Atrioventricular block following ASA was more common in elderly patients (43% vs. 21%; p = 0.001), resulting in pacemaker implantation in 13% and 5%, respectively (p = 0.06). Residual left ventricular outflow tract gradient, post-procedural New York Heart Association functional class, and necessity for additional septal reduction therapy was comparable between age groups. During a follow-up of 7.6 ± 4.6 years, 54 patients died. The 5- and 10-year survival following ASA was 95% and 90% in patients age ≤55 years and 93% and 82% in patients age >55 years, which was comparable to their control groups. The annual adverse arrhythmic event rate following ASA was 0.7%/year in young patients and 1.4%/year in elderly patients, which was comparable to their control groups. Conclusions ASA is similarly effective for reduction of symptoms in young and elderly patients; however, younger patients have a lower risk of procedure-related atrioventricular conduction disturbances. The long-term mortality rate and risk of adverse arrhythmic events following ASA are low, both in young and elderly patients, and are comparable to age-matched nonobstructive HCM patients.
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