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Abstract Aims Transthyretin amyloid cardiomyopathy (ATTR‐CM), a progressive and fatal cardiomyopathy, is frequently misdiagnosed or entails diagnostic delays, hindering patients from timely treatment. This study aimed to generate a systematic framework based on data from electronic health records (EHRs) to assess patients with ATTR‐CM in a real‐world population of heart failure (HF) patients. Predictive factors or combinations of predictive factors related to ATTR‐CM in a European population were also assessed. Methods and results Retrospective unstructured and semi‐structured data from EHRs of patients from OLV Hospital Aalst, Belgium (2012–20), were processed using natural language processing (NLP) to generate an Observational Medical Outcomes Partnership Common Data Model database. NLP model performance was assessed on a random subset of EHRs by comparing algorithm outputs to a physician‐generated standard (using precision, recall, and their harmonic mean, or F1‐score). Of the 3127 HF patients, 103 potentially had ATTR‐CM (age 78 ± 9 years; male 55%; ejection fraction of 48% ± 16). The mean diagnostic delay between HF and ATTR‐CM diagnosis was 1.8 years. Besides HF and cardiomyopathy‐related phenotypes, the strongest cardiac predictor was atrial fibrillation (AF; 72% in ATTR‐CM vs. 60% in non‐ATTR‐CM, P = 0.02), whereas the strongest non‐cardiac predictor was carpal tunnel syndrome (21% in ATTR‐CM vs. 3% in non‐ATTR‐CM, P

Abstract Aims The Cardiovascular Outcomes Retrospective Data analysIS in Heart Failure (CORDIS‐HF) is a single‐centre retrospective study aimed to (i) clinically characterize a real‐world population with heart failure (HF) with reduced (HFrEF) and mildly reduced ejection fraction (HFmrEF), (ii) evaluate impact of renal–metabolic comorbidities on all‐cause mortality and HF readmissions, and (iii) determine patients' eligibility for sodium–glucose cotransporter 2 inhibitors (SGLT2is). Methods and results Using a natural language processing algorithm, clinical data of patients diagnosed with HFrEF or HFmrEF were retrospectively collected from 2014 to 2018. Mortality and HF readmission events were collected during subsequent 1 and 2 year follow‐up periods. The predictive role of patients' baseline characteristics for outcomes of interest was assessed using univariate and multivariate Cox proportional hazard models. Kaplan–Meier analysis was used to determine if type 2 diabetes (T2D) and chronic kidney disease (CKD) impacted mortality and HF readmission rates. The European SGLT2i label criteria were used to assess patients' eligibility. The CORDIS‐HF included 1333 HF patients with left ventricular ejection fraction (LVEF)

Abstract Aims Risk stratification in patients with a new onset or worsened heart failure (HF) is essential for clinical decision making. We have utilized a novel approach to enrich patient level prognostication using longitudinally gathered data to develop ML‐based algorithms predicting all‐cause 30, 90, 180, 360, and 720 day mortality. Methods and results In a cohort of 2449 HF patients hospitalized between 1 January 2011 and 31 December 2017, we utilized 422 parameters derived from 151 451 patient exams. They included clinical phenotyping, ECG, laboratory, echocardiography, catheterization data or percutaneous and surgical interventions reflecting the standard of care as captured in individual electronic records. The development of predictive models consisted of 101 iterations of repeated random subsampling splits into balanced training and validation sets. ML models yielded area under the receiver operating characteristic curve (AUC‐ROC) performance ranging from 0.83 to 0.89 on the outcome‐balanced validation set in predicting all‐cause mortality at aforementioned time‐limits. The 1 year mortality prediction model recorded an AUC of 0.85. We observed stable model performance across all HF phenotypes: HFpEF 0.83 AUC, HFmrEF 0.85 AUC, and HFrEF 0.86 AUC, respectively. Model performance improved when utilizing data from more hospital contacts compared with only data collected at baseline. Conclusions Our findings present a novel, patient‐level, comprehensive ML‐based algorithm for predicting all‐cause mortality in new or worsened heart failure. Its robust performance across phenotypes throughout the longitudinal patient follow‐up suggests its potential in point‐of‐care clinical risk stratification.

Abstract Aims We investigated the prognostic relevance of serpin peptidase inhibitor, clade A member 3 (SERPINA3) in patients admitted with a de novo or worsened heart failure (HF). Methods and results In the first stage, 83 HF‐related left ventricular (LV) transcripts were examined in patients with congestive cardiomyopathy (CCMP, n = 44) who died within 5 years and compared with age‐matched and haemodynamically matched CCMP survivors (n = 39) and controls with normal LV function (n = 17). Among 14 differentially expressed transcripts, myocardial gene and circulating SERPINA3 levels were up‐regulated in non‐survivors vs. survivors (2.40 ± 3.66 vs. 0.36 ± 0.22 units, P 316 μg/mL were associated with increased all‐cause mortality {hazard ratio [HR] [95% confidence interval (CI)]: 2.4 [1.5–3.9], P = 0.0002} and its composite with unplanned cardiovascular readmission [HR (95% CI): 2.0 (1.2–3.3), P = 0.004]. Patients with elevated SERPINA3 levels and elevated either N‐terminal pro brain natriuretic peptide or ST2 showed worse freedom from both endpoints. In a multivariate analysis, including established clinical risk factors, SERPINA3 remained independent predictor of all‐cause mortality together with age, gender, ST2, glomerular filtration, and pulmonary capillary wedge pressure. Conclusion In patients with a de novo or worsened HF, increased SERPINA3 levels > 316 μg/mL are associated with increased mortality or unplanned cardiac readmission. Elevated SERPINA3 levels on top of established clinical predictors appear to identify a subgroup of HF patients at higher mortality risk. Prospective studies should further validate its value in prognostic stratification of HF.

Background. A pulmonary capillary wedge pressure (PCWP) >18 mm Hg following volume load has been proposed as a partition value for the detection of heart failure with preserved ejection fraction. As hemodynamic changes in filling pressures (FP) have been attributed to a nitric oxide (NO)-mediated rightward shift of the pressure-volume relationship, we investigated the hemodynamic response to volume load in heart transplant recipients (HTx) and examined the role of inducible NO synthase (iNOS) gene expression on diastolic function changes. Methods. In 36 HTx, FPs were measured before and after volume load, following which Starling curves were constructed using PCWP and cardiac index (CI). Patients were categorized into those with normal (group A, n = 21) and abnormal hemodynamics (group B, n = 15, PCWP >15 mm Hg at rest or >18 mm Hg following volume load). For the establishment of the potential role of NO, endomyocardial iNOS gene expression level was measured. Results. Except for PCWP (P < 0.001) and mean pulmonary artery pressure (P < 0.001) no differences in age, baseline characteristics, and ejection fraction were observed between both groups, and volume load significantly increased PCWP in both groups (group A: P < 0.001 and group B: P < 0.001) without any change in heart rate. Interestingly, volume load significantly increased CI in group A (P < 0.001) but not in group B (P = 0.654), and the Starling curves revealed a higher CI at any given PCWP in group A together with significantly higher iNOS gene expression (P = 0.009). Conclusions. In HTx, volume load increases FP and unmasks the presence of left ventricular diastolic dysfunction. Interestingly, following saline load group B shows a blunted Starling response, with higher PCWP and lack of CI increase at any given PCWP. The higher iNOS gene expression level in group A suggests a potential role of NO as mediator of diastolic function.

Introduction: Preliminary studies have suggested a low post-vaccination antibody response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in heart transplant(HTx)recipients. Although many studies have focused on the role of antibodies in vaccine-induced protection against SARS-CoV-2, the role of T cell immunity is less well characterized. To date, data regarding seroconversion and T cell response after mRNA SARS-CoV-2 vaccination in patients undergoing HTx are scarce. Therefore, the present study aimed to assess the specific memory humoral and cellular responses after two doses of the BNT162b2 vaccine in HTx recipients. Methods: Blood was drawn from heart transplant (HTx) recipients at two pre-specified time points after the first and second vaccine doses to measure both the anti-SARS-CoV-2 antibody response against the spike protein and the SARS-CoV-2-reactive T cell response. Results: Our study included 34 SARS-CoV-2 naïve HTx recipients (mean age, 61 ± 11 years). The mean time from transplantation to the first vaccine dose is 10 ± 10 years. Subgroup analysis (n = 21) demonstrated that after the first vaccine dose, only 14% had antibodies and 19% had a SARS-CoV-2-reactive T-cell response, which increased to 41% and 53%, respectively, after the second dose. Interestingly, 20% of patients with no antibodies after the second dose still had a positive SARS-CoV-2-reactive T cell response. The percentage of patients with positive S-IgG antibody titers was significantly higher 5 years after transplantation (18% 0–5 years post-TX vs. 65% 5 years post-TX, p = 0.013). Similarly, 5 years after heart transplantation, the percentage of patients with a T cell response was significantly higher (35% 0–5 years post-TX vs. 71% 5 years post-TX, p = 0.030). Conclusions: In SARS-CoV-2 naïve HTx recipients, post-vaccination antibody titers but also SARS-CoV-2 specific T cell response are low. Therefore, the protection from SARS-CoV-2 that is generally attributed to vaccination should be regarded with caution in HTx recipients.

The additional role of continuous monitoring of filling pressures and impedance in heart failure patients with chronic kidney disease remains undetermined. In this case report, the effects of diuretic therapy and renal replacement therapy by hemodialysis upon right ventricular filling pressures and impedance are described in a patient with end-stage heart failure and end-stage chronic kidney disease (grade 5). We demonstrated that unloading of the heart by hemodialysis partly restored the blunted Frank-Starling relationship.

Background. Cardiac allograft vasculopathy (CAV) remains the Achilles’ heel of long-term survival after heart transplantation (HTx). The severity and extent of CAV is graded with conventional coronary angiography (COR) which has several limitations. Recently, vessel fractional flow reserve (vFFR) derived from COR has emerged as a diagnostic computational tool to quantify the functional severity of coronary artery disease. Purpose. The present study assessed the usefulness of vFFR to detect CAV in HTx recipients. Methods. In HTx patients referred for annual check-up, undergoing surveillance COR, the extent of CAV was graded according to the criteria proposed by the international society of heart and lung transplantation (ISHLT). In addition, three-dimensional coronary geometries were constructed from COR to calculate pressure losses using vFFR. Results. In 65 HTx patients with a mean age of 53.7 ± 10.1 years, 8.5 years (IQR 1.90, 15.2) years after HTx, a total number of 173 vessels (59 LAD, 61 LCX, and 53 RCA) were analyzed. The mean vFFR was 0.84 ± 0.15 and median was 0.88 (IQR 0.79, 0.94). A vFFR ≤ 0.80 was present in 24 patients (48 vessels). HTx patients with a history of ischemic cardiomyopathy (ICMP) had numerically lower vFFR as compared to those with non-ICMP (0.70 ± 0.22 vs. 0.79 ± 0.13, p=0.06). The use of vFFR reclassified 31.9% of patients compared to the anatomical ISHLT criteria. Despite a CAV score of 0, a pathological vFFR ≤ 0.80 was detected in 8 patients (34.8%). Conclusion. The impairment in epicardial conductance assessed by vFFR in a subgroup of patients without CAV according to standard ISHLT criteria suggests the presence of a diffuse vasculopathy undetectable by conventional angiography. Therefore, we speculate that vFFR may be useful in risk stratification after HTx.

Cardiac transplant-related vasculopathy remains a leading cause of morbidity and mortality in heart transplant (HTx) recipients. Recently, coronary angiography-derived vessel fractional flow reserve (vFFR) has emerged as a new diagnostic computational tool to functionally evaluate the severity of coronary artery disease. Although vFFR estimates have been shown to perform well against invasive FFR in atherosclerotic coronary artery disease, data on the use of vFFR in heart transplant recipients suffering from cardiac transplant-related arteriopathy are lacking. The aim of the presented study was to validate coronary angiography-derived vessel fractional flow reserve to calculate fractional flow reserve in HTx patients with and without cardiac transplant-related vasculopathy. A prospective, single center study of HTx patients referred for annual check-up, undergoing surveillance coronarography was conducted. Invasive FFR was measured using a motorized device at the speed of 1.0 mm/s in all three major coronary arteries. Angiography-derived pullback FFR was derived from the angiogram and compared with invasive FFR pullback curve. Overall, 18,059 FFR values were extracted from the FFR pullback curves from 23 HTx patients. The mean age was 59.3 ± 9.7 years, the mean time after transplantation was 5.24 years [IQR 1.20, 11.25]. A total of 39 vessels from 23 patients (24 LAD, 11 LCX, 4 RCA) were analyzed. Mean distal vFFR was 0.87 ± 0.14 whereas invasive distal FFR was 0.88 ± 0.17. An excellent correlation was found between invasive distal FFR and vFFR (r = 0.92; p < 0.001). The correlation of the pullback tracing was high, with a correlation coefficient between vFFR and invasive FFR pullback values of 0.72 (95% CI 0.71 to 0.73, p < 0.001). The mean difference between vFFR and invasive FFR pullback values was −0.01 with 0.06 of SD (limits of agreements −0.12 to 0.13). In HTx patients, coronary angiography-derived FFR correlates excellently with invasively measured wire-derived FFR. Therefore, angiography derived FFR could be used as a novel diagnostic tool to quantify the functional severity of graft vasculopathy.

Background: Despite the clear benefits of cardiac rehabilitation (CR), a considerable number of patients drop out early., Objective: Therefore, we wanted to evaluate dropout in CR with a special focus on comorbidities and psychosocial background., Methods: Patients who attended CR after acute coronary syndrome, cardiac surgery, or heart failure (N = 489) were prospectively included. Dropout was defined as attending 50% of the training sessions or less (n = 96 [20%]). Demographic and clinical characteristics, exercise parameters, and psychosocial factors were analyzed according to dropout, and those with a trend toward a significant difference (P < .10) were entered in a multivariate logistic model., Results: The presence of a cerebrovascular accident (4.18 [1.39-12.52]) involved a higher risk of dropout, and a comparable trend was seen for the presence of chronic obstructive pulmonary disease (2.55 [0.99-6.54]). Attending the training program only twice per week also implicated a higher risk of an early withdrawal (3.76 [2.23-6.35]). In contrast, patients on β-blockers were less likely to withdraw prematurely (0.47 [0.22-0.98]). Singles were more likely to drop out (2.89 [1.56-5.35]), as well as those patients who were dependent on others to get to CR (2.01 [1.16-3.47]). Finally, the reporting of severe problems on the anxiety/depression subscale of the EuroQOL-5D questionnaire involved a higher odds for dropout (7.17 [1.46-35.29])., Conclusions: Neither demographic characteristics nor clinical status or exercise capacity could independently identify patients who were at risk of dropout. The presence of comorbidities and a vulnerable psychosocial background rather seem to play a key role in dropout.