Routine screening for HLA Antibodies in Heart Transplant patients-Does it affect clinical decision making?

BACKGROUND: We aimed to assess outcomes in patients with and without donor specific antibodies (DSA) and to evaluate the relationship between DSA presence and graft function, cardiac allograft vasculopathy (CAV), and mortality. METHODS: The study population comprises 193 consecutive long-term heart transplanted (HTx) patients who underwent DSA surveillance between 2016 and 2022. The patients were prospectively screened for CAV through serial coronary angiograms, graft function impairment through serial echocardiograms, and cardiac biomarkers. The patients were followed from the first DSA measurement until death, 5 years follow-up or right censuring on the 30th of June 2023. RESULTS: DSAs were detected in 50 patients using a cut-off at MFI ≥1000 and 45 patients using a cut-off at ≥2000 MFI. The median time since HTx was 9.0 years [3.0-14.4]. DSA positive patients had poorer graft function and higher values of NT-proBNP and troponin T, and more prevalent CAV than DSA negative patients. In total, 25 patients underwent endomyocardial biopsies due to DSA presence while another eight patients underwent endomyocardial biopsies for other reasons. Histological antibody mediated rejection (AMR) signs were seen in three biopsies. During a median follow-up of five years [4.7-5], a total of 41 patients died. Mortality rates did not differ between DSA positive and DSA negative patients (HR 1.2, 95% CI .6-2.4). DSA positive patients were more likely to experience CAV progression than DSA negative patients (HR 2.7, 95% CI 1.5-4.8) CONCLUSIONS: Routine screening reveals DSA in approximately 25% of long-term HTx patients but is rarely related to histopathological AMR signs. DSA presence was associated with poorer graft function and more prevalent and progressive CAV. However, DSA positive patients had similar survival rates to DSA negative patients.

Strain-derived myocardial work in wild-type transthyretin cardiac amyloidosis with aortic stenosis-diagnosis and prognosis.

BACKGROUND: Several echocardiographic parameters have been suggested to differentiate wild-type transthyretin cardiac amyloidosis (ATTRwt) from other causes of hypertrophy. These studies have all been performed in small samples of mixed cardiac amyloidosis. The purpose of this study was to investigate the role of echocardiographic parameters in patients with ATTRwt and aortic stenosis (AS) versus patients with AS. The secondary aim was to investigate the role of myocardial work in the prognosis of patients with ATTRwt. METHODS: The sensitivity and specificity of the relative apical sparing ratio (RAS), the apical-to-basal ratio (AB), the ejection-fraction-to-global-longitudinal-strain ratio (EF/GLS), and the global myocardial work index (GWI) were calculated using receiver-operated characteristics curves and area under the curve (AUC) in patients with ATTRwt and AS (n = 50) versus patients with AS (n = 354). Multivariable regression was used to assess the prognostic value of GWI in patients with ATTRwt (n = 212). RESULTS: When used to identify AS from ATTRwt + AS, GWI had a sensitivity of 80% and specificity of 70%. The AUC of GWI was larger than that of AB (p = .01) and EF/GLS (p > .01) but not RAS (p = .15). In patients with ATTRwt multivariable regression found age predicted mortality with an estimate of HR = 1.086 (CI: 1.034-1.141) while GWI predicted survival with an estimate of HR = .837 (CI: .733-.956) per 100 mmHg*% increase. CONCLUSION: GWI was demonstrated to be a viable classifier in ATTRwt and AS versus AS. GWI was demonstrated to independently predict survival in patients with ATTRwt. Further studies examining the role of myocardial work in ATTRwt are warranted.

Micro- and macrovascular cardiac allograft vasculopathy in relation to 91 cardiovascular biomarkers in heart transplant recipients-An exploratory study.

BACKGROUND: Cardiac allograft vasculopathy (CAV) limits survival after heart transplantation (HTx), and the pathogenesis is not fully clarified. We aimed to investigate a wide range of biomarkers and their correlation with micro- and macrovascular CAV and major adverse cardiac events in HTx patients. METHODS: We evaluated 91 cardiovascular disease-related proteins in 48 HTx patients using a novel proteomic panel. Patients were dichotomized according to micro- and macrovascular CAV burden determined by coronary angiography, optical coherence tomography, and 15 O-H2 O positron emission tomography imaging. Major adverse cardiac events included significant CAV progression, heart failure, treated rejection, and cardiovascular death. RESULTS: We found consistent differences in two proteins involved in cholesterol homeostasis: significantly increased proprotein convertase subtilisin/kexin type 9 (PCSK9) (p < .05) and significantly decreased paraoxonase 3 (PON3) (p < .05). N-terminal pro-brain natriuretic peptide (NT-proBNP) was significantly increased in patients with microvascular CAV (p < .05) and borderline significantly increased in patients experiencing major adverse cardiac events (p = .10) and patients with macrovascular CAV (p = .05). CONCLUSIONS: We identified consistent changes in two proteins involved in cholesterol homeostasis which may be important players in the pathogenesis of CAV: PON3 and PCSK9. NT-proBNP also showed consistent changes across all groups but only reached statistical significance in patients with microvascular CAV. Our results warrant further validation in future studies.

Reverse remodeling of tricuspid valve morphology and function in chronic thromboembolic pulmonary hypertension patients following pulmonary thromboendarterectomy: a cardiac magnetic resonance imaging and invasive hemodynamic study.

BACKGROUND: To investigate changes in tricuspid annulus (TA) and tricuspid valve (TV) morphology among chronic thromboembolic pulmonary hypertension (CTEPH) patients before and 12 months after pulmonary thromboendarterectomy (PEA) and compare these findings to normal control subjects. METHODS: 20 CTEPH patients and 20 controls were enrolled in the study. The patients were examined with echocardiography, right heart catherization and cardiac magnetic resonance imaging prior to PEA and 12 months after. RESULTS: Right atrium (RA) volume was significantly reduced from baseline to 12 months after PEA (30 ± 9 vs 23 ± 5 ml/m2, p < 0.005). TA annular area in systole remained unchanged (p = 0.11) and was comparable to controls. The leaflet area, tenting volume and tenting height in systole were significantly increased at baseline but decreased significantly with comparable values to controls after 12 months (p < 0.005). There was correlation between the changes of right ventricular-pulmonary artery coupling and changes of TV tenting height (r = - 0.54, p = 0.02), TV tenting volume (r = - 0.73, p < 0.001) and TV leaflet area (- 0.57, p = 0.01) from baseline to 12 months after PEA. Tricuspid regurgitation jet area/RA area was significantly (p < 0.01) reduced from baseline (30 ± 13%) to 12 months after PEA (9 ± 10%). CONCLUSION: In CTEPH patients selected for PEA, TV tenting height, volume and valve area are significantly increased whereas annulus size and shape are less affected. The alterations in TV morphology are fully reversed after PEA and correlates to improvements of right ventricular-pulmonary arterial coupling.

Burden of arrhythmia and silent ischemia in heart transplant patients with cardiac allograft vasculopathy.

BACKGROUND: The incidence of sudden cardiac death (SCD) following heart transplantation (HTx) accounts for approximately 10% of post-HTx deaths. Ischemia, brady- and tachy-arrhythmias caused by rejection and cardiac allograft vasculopathy (CAV) seem related to SCD. Hence, we aimed to investigate the relation between CAV, arrhythmias and silent ischemia in long-term HTx patients. Methods. 49 HTx patients were included. Patients were CAV classified in accordance with guidelines from the International Society of Heart and Lung Transplantation. Patients were divided into predefined CAV groups (CAV 0, CAV 1, CAV 2 + 3). Incidences of arrhythmia and silent ischemia were detected by 48-h electrocardiogram monitoring and analyzed blinded to CAV-status. Results. Median time since transplantation was 9 years [IQR 4-14]. We observed a higher incidence of non-sustained ventricular tachycardia (NSVT) in CAV 2 + 3 patients than CAV 0 and 1 patients (p = .01). Likewise, isolated premature ventricular complexes (PVC) (p = .01) and PQ-interval prolongation (p = .01) were more frequent in CAV 2 + 3 patients than CAV 0 and 1 patients. Silent ischemia was only observed among CAV 3 patients (p = .04). We saw no significant difference in the incidence of supraventricular tachycardia among CAV groups (p = .21). Likewise, no difference in the right bundle branch block was observed (p = .68). Conclusion. NSVT was associated with CAV status in long-term HTx patients. Patients with moderate to severe CAV showed higher incidences of PVCs and PQ-interval prolongation than patients with mild or no CAV. Silent ischemia was only seen in patients with severe CAV.

Long-term changes of resting and exercise right ventricular systolic performance in patients with chronic thromboembolic pulmonary hypertension following pulmonary thromboendarterectomy - A two-dimensional and three-dimensional echocardiographic study.

AIMS: To characterize right ventricular (RV) geometry and function in chronic thromboembolic pulmonary hypertension (CTEPH) patients at rest and during exercise before pulmonary thromboendarterectomy (PEA), and at 3 and 12 months after PEA using two-dimensional and three-dimensional echocardiography with reference to clinical performance and exercise capacity. METHODS AND RESULTS: Forty subjects (20 CTEPH patients and 20 controls) were enrolled between December 2014 and January 2017. Three-dimensional echocardiography demonstrated a significant reduction and normalization of end-diastolic and end-systolic RV volumes in CTEPH patients 12 months after PEA. RV systolic function improved after PEA; however, tricuspid annular plane systolic excursion (TAPSE) (baseline 18 ± 6 mm vs 15 ± 3 mm at 12 months after PEA, P < .05) and tricuspid lateral annular systolic velocity (RV-S') (baseline -8.3 ± 2.1 cm/s vs -7.2 ± 1.3 cm/s at 12 months after PEA, P < .05) declined significantly after PEA. Tricuspid regurgitation gradient was 64 ± 21 mm Hg at baseline, 40 ± 14 mm Hg at 3 months, and 30 ± 13 at 12 months, P < .00001. RV free-wall longitudinal strain at peak exercise was significantly increased from baseline (-10.6 ± 5.5%) to 12 months of follow-up (-15.8 ± 5.2%), P < .005. Physical exercise capacity, measured as peak oxygen uptake, was significantly increased and correlated directly with improvement of resting and exercise-induced RV-EF. CONCLUSION: Improvement of RV geometry and systolic function, along with the reduction of systolic pulmonary pressure, can be expected following PEA in CTEPH patients during long-term follow-up. Improvement of RV myocardial contractility after PEA was only revealed at peak exercise over time. Importantly, physical exercise capacity was significantly increased and was found to be directly correlated with improvement of resting and exercise-induced RV-EF.

Donor-specific antibodies are associated with micro- and macrovascular coronary disease, restrictive myocardial damage, and poor outcome in heart-transplanted patients.

AIMS: We examined the relationship between donor-specific HLA antibody (DSA) presence and graft function, hemodynamics, cardiac allograft vasculopathy (CAV), and major adverse cardiac events (MACE) in stable long-term heart-transplanted (HTx) patients. METHODS: Sera from 79 patients (median 7.5 years after HTx) were analyzed for DSA presence. Graft function was evaluated by echocardiography and right heart catheterization. CAV burden was determined by coronary angiography, optical coherence tomography (OCT), and coronary flow velocity reserve (CFVR). Patients were prospectively followed after DSA assessment. MACE included significant CAV progression, heart failure, treated rejection, and cardiovascular death. RESULTS: Sixty patients had no DSA, and 19 patients were sensitized. The vasculopathy burden by angiography, OCT, and CFVR was more pronounced in DSA-positive patients than in DSA-negative patients. DSA-positive patients had higher pulmonary capillary wedge pressure (16 [8; 21] vs 9 mm Hg [7; 11], P<.05) and right atrial pressure (8 [6; 9] vs 4 mm Hg [2; 6], P<.01) and lower global longitudinal strain (-13% [-10; -15] vs -16% [-14; -17], P<.01) than DSA-negative patients. DSA presence was a strong MACE predictor (HR 4.7 (95% CI 2.0-11.4), P<.001). CONCLUSIONS: DSA-positive patients had higher vasculopathy burden, higher filling pressures, and lower longitudinal myocardial deformation than DSA-negative patients. The DSA presence was a strong MACE predictor.

Echocardiographic assessment of right heart function in heart transplant recipients and the relation to exercise hemodynamics.

This study aimed to characterize right heart function in heart transplantation (HTx) patients using advanced echocardiographic assessment and simultaneous right heart catheterization (RHC). Comprehensive two-dimensional (2D) and three-dimensional (3D) echocardiographic assessment of right heart function was performed in 105 subjects (64 stable HTx patients and 41 healthy controls). RHC was performed at rest and during semi-supine maximal exercise test. Compared with controls, in conclusion, HTx patients had impaired right ventricle (RV) systolic function in terms of decreased RV-free wall (FW) global longitudinal strain (GLS) (-20 ± 5% vs. -28 ± 5%, P < 0.0001) and 3D-ejection fraction (EF) (50 ± 8% vs. 60 ± 6%, P < 0.0001). In HTx patients, echocardiographic RV systolic function was significantly correlated with NYHA-class (3D-RVEF: r = -0.62, P < 0.0001; RV-FW-GLS: r = -0.41, P = 0.0009) and cardiac allograft vasculopathy (3D-RVEF: r = -0.42, P = 0.0005; RV-FW-GLS: r = -0.25, P = 0.0444). RHC demonstrated a good correlation between invasively assessed resting RV-stroke volume index and exercise capacity (r = 0.58, P < 0.0001) and NYHA-class (r = -0.41, P = 0.0009). RV systolic function is reduced in HTx patients compared with controls. 3D RVEF and 2D longitudinal deformation analyses are associated with clinical performance in stable HTx patients and seem suitable in noninvasive routine right heart function evaluation after HTx. Invasively assessed RV systolic reserve was strongly associated with exercise capacity.

Clinical features, exercise hemodynamics, and determinants of left ventricular elevated filling pressure in heart-transplanted patients.

This study aimed to assess clinical, functional, and hemodynamic characteristics of heart-transplanted (HTX) patients during exercise. We performed comprehensive echocardiographic graft function assessment during invasive hemodynamic semi-supine exercise test in 57 HTX patients. According to hemodynamics findings, patients were divided into Group A: normal left ventricular (LV) filling pressure (FP): pulmonary capillary wedge pressure (PCWP) <15 mmHg at rest and <25 mmHg at peak exercise, and Group B: elevated LV-FP: PCWP ≥15 mmHg at rest or ≥25 mmHg at peak exercise. Thirty-one patients (54%) had normal LV-FP and 26 patients (46%) had elevated LV-FP. The latter had higher cumulative rejection burden (P < 0.01) and were more symptomatic (NYHA class >1) (P < 0.05), and cardiac allograft vasculopathy (CAV) was more prevalent (P < 0.05). With exercise, the changes in both left- and right-sided filling pressures were significantly increased, whereas LV longitudinal myocardial deformation was lower (P < 0.05) in patients with elevated LV-FP than in patients with normal LV-FP. No between-group difference was observed for cardiac index or LV ejection fraction (LVEF) during exercise. In conclusion, elevated LV-FP can be demonstrated in approximately 50% of HTX patients. Patients with elevated LV-FP have impaired myocardial deformation capacity, higher prevalence of CAV, and higher rejection burden, and were more symptomatic. Exercise test with the assessment of longitudinal myocardial deformation should be considered in routine surveillance of HTX patients as a marker of restrictive filling (ClinicalTrials.gov Identifier: NCT02077764).

Coronary Flow Reserve Predicts Longitudinal Myocardial Deformation Capacity in Heart-Transplanted Patients.

AIMS: This study aimed to evaluate the role of microvascular dysfunction on left ventricular (LV) longitudinal deformation, filling pressures, and exercise capacity in heart-transplanted (HTx) patients. METHODS AND RESULTS: Fifty-seven HTx patients underwent comprehensive echocardiographic graft function assessment during symptom-limited, semisupine exercise test with simultaneous right heart catheterization. Coronary flow velocity reserve (CFVR) was measured in the left anterior descending artery using pulsed Doppler echocardiography. We divided patients into two groups based on upper and lower median of CFVR. Twenty-six healthy subjects served as controls. Compared with healthy controls, HTx patients had reduced CFVR (P < 0.0001), exercise capacity (P < 0.0001), and LV longitudinal deformation capacity (P < 0.0001). HTx patients in the reduced CFVR group (CFVR < 2.73) were more symptomatic (P < 0.0001) and had higher prevalence of coronary cardiac allograft vasculopathy (CAV) (P < 0.0001) than patients in the high CFVR group. Systolic function improved in both HTx groups during exercise. However, LV longitudinal myocardial deformation improved significantly more in the high CFVR group (P < 0.0001). Peak exercise LV global longitudinal strain and CFVR were strongly correlated (r = 0.8, P < 0.0001). A weak correlation was observed between CFVR and invasive cardiac index at peak exercise (r = 0.35, P < 0.01) and CFVR and LV filling measured by E/e' ratio (r = -0.41, P < 0.01) and pulmonary capillary wedge pressure (r = -0.30, P < 0.05). CONCLUSION: HTx patients have reduced CFVR, exercise capacity, and LV longitudinal myocardial deformation capacity compared with healthy individuals. HTx patients with reduced CFVR are more symptomatic and have increased prevalence of CAV. Furthermore, reduced CFVR is correlated with reduced LV longitudinal myocardial deformation and exercise capacity.

The long-term influence of repetitive cellular cardiac rejections on left ventricular longitudinal myocardial deformation in heart transplant recipients.

The aim of the study was to evaluate the long-term influence of repeated acute cellular rejections on left ventricular longitudinal deformation in heart transplantation (HTX) patients. One hundred and seventy-eight HTX patients were included in the study. Rejections were classified according to the International Society of Heart and Lung Transplantation (ISHLT) classification (0R-3R). Patients were divided into three groups according to rejection scores (RSs). Group 1: <50% of biopsies with 1R rejection and no ≥2R rejections; Group 2: ≥50% of biopsies with 1R rejection or one biopsy with ≥2R rejection; Group 3: ≥Two biopsies with ≥2R rejections. All patients had a comprehensive echocardiographic examination and coronary angiography. We found significantly decreasing global longitudinal strain (GLS) comparing to rejection groups (GLS group 1: -16.8 ± 2.4 (%); GLS group 2: -15.9 ± 3.3 (%); GLS group 3: -14.5 ± 2.9 (%), P = 0.0003). After excluding patients with LVEF < 50% or vasculopathy, GLS was still significantly reduced according to RS groups (P = 0.0096). Total number of 1R and 2R rejections correlated significant to GLS in a linear regression model. In contrast, we found fractional shortening and LVEF to be unaffected by repeated rejections. In conclusion, repeated cardiac rejections lead to impaired graft function as detected by decreasing magnitude of GLS. In contrast, traditional systolic graft function surveillance by LVEF did not correlate to rejection burden.

Myocardial work across different etiologies of right ventricular dysfunction and healthy controls.

Evaluating right ventricular (RV) function remains a challenge. Recently, novel echocardiographic assessment of RV myocardial work (RVMW) by non-invasive pressure-strain loops was proposed. This enables evaluation of right ventriculoarterial coupling and quantifies RV dyssynchrony and post-systolic shortening. We aimed to assess RVMW in patients with different etiologies of RV dysfunction and healthy controls. We investigated healthy controls (n=17), patients with severe functional tricuspid regurgitation (FTR; n=22), and patients with precapillary pulmonary hypertension (PCPH; n=20). Echocardiography and right heart catheterization were performed to assess 1) RV global constructive work (RVGCW; work needed for systolic myocardial shortening and isovolumic relaxation), 2) RV global wasted work (RVGWW; myocardial shortening following pulmonic valve closure), and 3) RV global work efficiency (RVGWE; describes the relation between RV constructive and wasted work). RVGCW correlated with invasive RV stroke work index (r=0.66, P<0.001) and increased in tandem with higher afterload, i.e., was low in healthy controls (454±73 mmHg%), moderate in patients with FTR (687±203 mmHg%), and highest among patients with PCPH (881±255 mmHg%). RVGWE was lower and RVGWW was higher in patients with FTR (86±8% and 91 mmHg% [53-140]) or PCPH (86±10% and 110 mmHg% [66-159]) as compared with healthy controls (96±3% and 10 mmHg%). RVMW by echocardiography provides a promising index of RV function to discriminate between patients with RV volume or pressure overload. The prognostic value of this measure needs to be settled in future studies.

Twenty years' experience at the Heart Transplant Center, Aarhus University Hospital, Skejby, Denmark.

OBJECTIVES: The Heart Transplantation Center, Aarhus University Hospital, Skejby, now has 20 years' experience with heart transplantation (HTX). This study aims to evaluate long-term outcome after HTX including incidences of cancer and severe renal dysfunction. DESIGN: Outcomes were reviewed using the transplant database of our department, the Scandiatransplant database, hospital medical records, and national database of biopsies. RESULTS: From December 31, 1992 to February 27, 2013, a total of 258 patients underwent index HTX. Survival for the whole patient cohort at 1 month and 1 year was 95% and 88%. Long-term survival estimates of 5, 10, 15, and 20 years were 80%, 70%, 55%, and 40%, respectively. Median survival time was 15.6 years. Significant improvement in survival was observed from the 1992-1998 vs. 1999-2005 era and the 1992-1998 vs. the 2006-2012 era. Three patients (1%) underwent renal transplantation, and 29 patients (11%) developed severe renal dysfunction requiring dialysis. Sixty-four (25%) patients developed cancer, with skin cancer being most common. CONCLUSION: HTX is an excellent treatment for selected patients with end-stage heart failure. The prognosis has improved in the latest transplantation eras. With balanced immunosuppressive treatment, severe renal dysfunction and cancer can be limited to an acceptable level.

Heart transplantation after acute myocardial infarction due to focal coronary Takayasu arteritis: a case report.

Background: Takayasu arteritis is a chronic vasculitis of unknown aetiology primarily affecting medium to large arteries, particularly the aorta and arch vessels, and is predominantly seen in younger patients. Coronary artery involvement has been reported in 10-45% of autopsy cases, but isolated coronary Takayasu arteritis is extremely rare. Case summary: This case report describes the course of a previously healthy 22-year-old woman who suffered an acute myocardial infarction complicated by cardiogenic shock requiring temporary mechanical support subsequently urgent heart transplantation. The patient was bridged to transplant by the use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO). The explanted heart showed evidence of Takayasu arteritis in the left coronary artery. Discussion: The case illustrates the importance of VA-ECMO treatment for cardiogenic shock, the importance of the Scandiatransplant collaboration for urgent organ allocation and the diagnostic difficulties associated with Takayasu arteritis.

Wild-type transthyretin amyloid cardiomyopathy: expect the unexpected-a case report.

Background: General interest and incidence are increasing in wild-type transthyretin amyloidosis (ATTRwt) in recent time. As patient population increases, further knowledge of the management of the frequently encountered interacting cardiac comorbidities is requested to improve treatment of ATTRwt patients. Case summary: A 73-year-old male ATTRwt patient presented to the outpatient clinic (Day 0) with dyspnoea, leg swelling, and palpitations. At diagnosis, 3 years prior to presentation, he exhibited only minor signs of ATTRwt. At Day 0, clinical examination revealed atrial fibrillation and mild peripheral oedema. Anticoagulant and symptomatic treatment with beta-blocker and diuretics was initiated, and the patient was planned for sub-acute direct cardioversion, and the patient was discharged with a Holter monitor to outpatient care. At Day 7, analysis of the monitoring demonstrated spontaneous conversion to sinus rhythm and, unexpectedly, episodes of high-rate self-remittent sustained monomorphic ventricular tachycardia (VT) and frequent ventricular ectopic beats. At Day 8, a sub-acute coronary angiography was performed which revealed a significant proximal left anterior descending artery stenosis which was treated with percutaneous coronary intervention (PCI) and subsequently an internal defibrillator was implanted. Following visits at 1- and 3-month post-PCI at the outpatient clinic revealed no VT and suppression of ventricular ectopic beats. Discussion: The case illustrates some of the frequently encountered cardiac comorbidities (e.g. atrial fibrillation, ventricular arrhythmia, and ischaemic heart disease) associated with ATTRwt. A high level of suspicion is warranted to identify treatable cardiac conditions [atrial fibrillation, atrioventricular (AV) block, and ischaemic heart disease] and to uncover potentially fatal cardiac conditions in patients with ATTRwt.

Clinical characteristics and prognostic implications of orthopedic ligament disorders in patients with wild-type transthyretin amyloidosis cardiomyopathy.

BACKGROUND: Wild-type transthyretin amyloidosis (ATTRwt) is associated with multiple ligament disorders (LD) such as carpal tunnel syndrome (CTS), lumbar spinal stenosis (LSS), and spontaneous tendon rupture (STR). No studies have investigated the prevalence of these LD in the same cohort of ATTRwt patients. Furthermore, the clinical characteristics and prognostic implications of such disorders have not been studied. METHODS: From 2017 to 2022, 206 consecutive patients with ATTRwt were diagnosed and followed prospectively to the time of death or the censoring date of September 1st, 2022. Patients with and without LD were compared, and the presence of LD was used along with the baseline clinical, biochemical, and echocardiographic characteristics to predict hospitalization with worsening heart failure and death. RESULTS: CTS surgery was performed in 34 % of the patients, 8 % were treated for LSS, and 10 % had experienced an STR. The median follow-up time was 706 days (312-1067). Hospitalization with worsening heart failure occurred more frequently in patients with LD compared to patients without LD (p = 0.035). Presence of LD or surgery for CTS were found to be independent predictors of worsening heart failure with a hazard ratio of 2.0 (p = 0.01). The mortality was comparable between patients with and without LD (p = 0.10). CONCLUSION: Orthopedic disorders are prevalent in ATTRwt cardiomyopathy, and presence of LD was an independent predictor of hospitalization with worsening heart failure.

Validation of a semi-automatic software for optical coherence tomography - analysis in heart transplanted patients.

Optical Coherence Tomography (OCT) is an intravascular imaging modality enabling detailed evaluation of cardiac allograft vasculopathy (CAV) after heart transplantation (HTx). However, its clinical application remains hampered by time-consuming manual quantitative analysis. We aimed to validate a semi-automated quantitative OCT analysis software (Iowa Coronary Wall Analyzer, ICWA-OCT) to improve OCT-analysis in HTx patients. 23 patients underwent OCT evaluation of all three major coronary arteries at 3 months (3M) and 12 months (12M) after HTx. We analyzed OCT recordings using the semiautomatic software and compared results with measurements from a validated manual software. For semi-automated analysis, 31,228 frames from 114 vessels were available. The validation was based on a subset of 4287 matched frames. We applied mixed model statistics to accommodate the multilevel data structure with method as a fixed effect. Lumen (minimum, mean, maximum) and media (mean, maximum) metrics showed no significant differences. Mean and maximum intima area were underestimated by the semi-automated method (ß-methodmean = - 0.289 mm2, p < 0.01; ß-methodmax = - 0.695 mm2, p < 0.01). Bland-Altman analyses showed increasing semi-automatic underestimation of intima measurements with increasing intimal extent. Comparing 3M to 12M progression between methods, mean intimal area showed minor underestimation (ß-methodmean = - 1.03 mm2, p = 0.04). Lumen and media metrics showed excellent agreement between the manual and semi-automated method. Intima metrics and progressions from 3M to 12M were slightly underestimated by the semi-automated OCT software with unknown clinical relevance. The semi-automated software has the future potential to provide robust and time-saving evaluation of CAV progression.

Assessment of Acute Rejection by Global Longitudinal Strain and Cardiac Biomarkers in Heart-Transplanted Patients.

Aims: The aim of this study was to evaluate left ventricular global longitudinal strain (LVGLS), N-terminal pro brain natriuretic peptide (Nt-ProBNP), and Troponin T as non-invasive markers for acute cellular rejection (ACR) diagnosis and severity assessment after heart transplantation (HTx). Methods: We retrospectively included all HTx patients transplanted from 2013 to 2019. At each visit, the patients were subjected to endomyocardial biopsy (EMB), measurement of Nt-ProBNP and Troponin T, and protocoled echocardiography with assessment of LVGLS. Sudden drop in graft function (SDGF) was defined as a drop in LVGLS ≥-2% in combination with either an increase in Troponin T ≥20% or Nt-ProBNP ≥30% compared with levels at the latest visit. Results: We included 1,436 EMBs from 83 HTx patients. The biopsies were grouped as 0R (n = 857), 1R (n = 538), and ≥2R (n = 41). LVGLS was lower and Troponin T and Nt-ProBNP higher in the 2R group than in the 0R and 1R groups (LVGLS: -12.9 ± 3.8% versus -16.9 ± 3.1% and -16.1 ± 3.3%; Troponin T: 79 [33;230] ng/l versus 27 [13;77] ng/l and 27 [14;68] ng/l; Nt-ProBNP: 4,174 [1,095;9,510] ng/l versus 734 [309;2,210] ng/l and 725 [305;2,082], all p < 0.01). A SDGF was seen at 45 visits of which 19 had ≥2R ACR. EMBs showed ACR in 20 cases without SDGF. Finally, neither was SDGF seen nor did the EMB show rejection in 1,136 cases. Thus, the sensitivity of SDGF for ≥2R ACR detection was 49% (32-65) and specificity 98% (97-99). The positive predictive value (PPV) was 42% (31-55) and the negative predictive value (NPV) 98% (98-99). The diagnostic value improved in a sub-analysis excluding EMBs within 3 months after HTx, clinically interpreted false positive ≥2R ACR cases, and cases with ≥2R ACR who recently (<2 weeks) were treated with intravenous methylprednisolone due to ≥2R ACR (sensitivity 75% (48-93), specificity 97% (96-98), NPV 99% (99-100), and PPV 39% (27-52). Conclusions: Patients with ≥2R ACR have lower LVGLS and higher Troponin T and Nt-ProBNP than patients without 2R rejection. A non-invasive model combining changes in LVGLS and Troponin T or Nt-ProBNP showed excellent negative predictive value and moderate sensitivity and may be used as a gatekeeper to invasive biopsies after HTx.

Incidence and predictors of worsening heart failure in patients with wild-type transthyretin cardiac amyloidosis.

BACKGROUND: Prognostic markers of survival have been identified in wild-type transthyretin amyloidosis (ATTRwt), but limited data exist with respect to hospitalizations with worsening heart failure (WHF). Predictive markers of WHF have yet to be identified. METHODS: From April 2017 to February 2021, 104 patients with ATTRwt were diagnosed and prospectively followed from the time of diagnosis to the time of death or the censoring date of 1 February 2021. Baseline patient characteristics, biomarkers, and advanced echocardiography were used to predict hospitalization with WHF. RESULTS: During the median follow-up period of 23 months, 51% of patients were hospitalized due to WHF. Seventy-three per cent of patients with WHF were admitted at least twice. Patients with WHF during the first year had significantly poorer survival (P < 0.001). Independent predictors of WHF during follow-up were pacemaker implantation prior to diagnosis (PMI, P = 0.037) and right atrial volume index (RAVi, P = 0.008). Patients with PMI had a higher left ventricular mass index and poorer left ventricular and right ventricular systolic function indicating a more advanced stage of amyloid disease. CONCLUSIONS: A high incidence and recurrence of hospital admissions with WHF were demonstrated in contemporary patients with ATTRwt, which was associated with reduced survival. Patients with pacemaker devices prior to ATTRwt diagnosis experienced more frequent hospitalizations with WHF. PMI and right atrial enlargement were identified as independent predictors of WHF during follow-up.

Impaired left and right systolic ventricular capacity in corrected atrial septal defect patients.

Resting right ventricular (RV) systolic function has in some studies been shown to be impaired after correction of an atrial septal defect (ASD) whereas impairment of left ventricular (LV) systolic function is uncertain. In the present study we examine the LV and RV systolic response to exercise in patients with a previously corrected ASD in order to investigate the myocardial capacity. Thirty-six adult ASD patients with a corrected isolated secundum ASD and eighteen adult age-matched controls underent a semi-supine exercise stress echocardiographic examination. At rest, LV parameters were comparable between groups, and RV global longitudinal strain (RV-GLS) was lower for the ASD group (-18.5%, 95% CI -20.0--17.0%) compared with controls (-24.5%, 95% CI -27.7--22.4%, p < 0.001). At peak exercise, LV ejection fraction (LVEF) was lower for ASD patients (61%, 95% CI 58-65%) compared with controls (68%, 95% CI 64-73% p = 0.01). Peak LV global longitudinal strain (LV-GLS) was borderline significantly lower (ASD: -18.4%, 95% CI -20.2--16.6%, controls: -21.3%, 95% CI -23.6--19.0%, p = 0.059). Both RVEF (ASD: 64%, 95% CI 60-68%, controls: 73%, 95% CI 65-80%, p = 0.05) and tricuspid annular plane systolic excursion (TAPSE) (ASD: 2.5 cm, 95% CI 2.3-2.7 cm, controls: 3.2 cm, 95% CI 2.9-3.6 cm, p < 0.001) at peak exercise were lower for ASD patients. Exercise assessed peak oxygen uptake was comparable between groups (ASD: 32.8 mL O2/kg/min, 95% CI 30.3-35.5 mL O2/kg/min, controls: 35.2 mL O2/kg/min, 95% CI 31.6-38.8 mL O2/kg/min, p = 0.3). Corrected ASD patients demonstrate a reduced LV and RV systolic exercise response decades after ASD correction whereas resting parameters of LV and RV systolic function were within normal range. The presence of subclinical systolic myocardial dysfunction during exercise might be associated with the long-term morbidities documented in this patient group.