Preliminary results of the austrian national registry with the novel iCover bridging stentgraft in fenestrated endovascular aortic repair.

OBJECTIVE: Bridging stentgrafts (BSGs) are one of the primary limiting factors regarding long-term results after fenestrated endovascular aortic repair (fEVAR). This study aims to report for the first time the outcome of a novel BSG called iCover from a national, multicentric retrospective database. METHODS: A cohort of 58 patients received 212 BSGs for the renovisceral arteries in fEVAR. Patients were followed-up clinically and with computed-tomography angiography. Study end points were mortality, occurrence of complications, technical success of the BSG implantation, defined as successful deployment with vessel patency and absence of type 1c, 3b, and 3c endoleak, and stability over the follow-up. RESULTS: Three BSG unrelated mortalities (5.1 %), four BSG unrelated major complications (6.8 %) and five minor complications (8.6 %) occurred. The technical success of iCover was 207/212 (97.6 %), target vessel patency was 100 % over a follow-up of 4.0 months, and no late BSG related endoleak was detected. In two cases, the BSG was dislodged from the balloon and could be parked in a safe position without further sequelae (0.9 %). CONCLUSION: The iCover represents a feasible BSG for fEVAR with an excellent safety profile and technical success rate in the early phase. Prudent post-dilatation and monitoring of the proximal and distal stent ends can potentially further improve outcome. Longer follow-up series are necessary.

Myocardial structural and functional changes in cardiac amyloidosis: insights from a prospective observational patient registry.

AIMS: The pathophysiological hallmark of cardiac amyloidosis (CA) is the deposition of amyloid within the myocardium. Consequently, extracellular volume (ECV) of affected patients increases. However, studies on ECV progression over time are lacking. We aimed to investigate the progression of ECV and its prognostic impact in CA patients. METHODS AND RESULTS: Serial cardiac magnetic resonance (CMR) examinations, including ECV quantification, were performed in consecutive CA patients. Between 2012 and 2021, 103 CA patients underwent baseline and follow-up CMR, including ECV quantification. Median ECVs at baseline of the total (n = 103), transthyretin [(ATTR) n = 80], and [light chain (AL) n = 23] CA cohorts were 48.0%, 49.0%, and 42.6%, respectively. During a median period of 12 months, ECV increased significantly in all cohorts [change (Δ) +3.5% interquartile range (IQR): -1.9 to +6.9, P < 0.001; Δ +3.5%, IQR: -2.0 to +6.7, P < 0.001; and Δ +3.5%, IQR: -1.6 to +9.1, P = 0.026]. Separate analyses for treatment-naïve (n = 21) and treated (n = 59) ATTR patients revealed that the median change of ECV from baseline to follow-up was significantly higher among untreated patients (+5.7% vs. +2.3%, P = 0.004). Survival analyses demonstrated that median change of ECV was a predictor of outcome [total: hazard ratio (HR): 1.095, 95% confidence interval (CI): 1.047-1.0145, P < 0.001; ATTR: HR: 1.073, 95% CI: 1.015-1.134, P = 0.013; and AL: HR: 1.131, 95% CI: 1.041-1.228, P = 0.003]. CONCLUSION: The present study supports the use of serial ECV quantification in CA patients, as change of ECV was a predictor of outcome and could provide information in the evaluation of amyloid-specific treatments.

Monitoring tafamidis treatment with quantitative SPECT/CT in transthyretin amyloid cardiomyopathy.

AIMS: Tafamidis treatment positively affects left ventricular (LV) structure and function and improves outcomes in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). We aimed to investigate the relationship between treatment response and cardiac amyloid burden identified by serial quantitative 99mTc-DPD SPECT/CT. We furthermore aimed to identify nuclear imaging biomarkers that could be used to quantify and monitor response to tafamidis therapy. METHODS AND RESULTS: Forty wild-type ATTR-CM patients who underwent 99mTc-DPD scintigraphy and SPECT/CT imaging at baseline and after treatment with tafamidis 61 mg once daily [median, 9.0 months (interquartile range 7.0-10.0)] were divided into two cohorts based on the median (-32.3%) of the longitudinal percent change in standardized uptake value (SUV) retention index. ATTR-CM patients with a reduction greater than or equal to the median (n = 20) had a significant decrease in SUV retention index (P < 0.001) at follow-up, which translated into significant benefits in serum N-terminal prohormone of brain natriuretic peptide levels (P = 0.006), left atrial volume index (P = 0.038), as well as LV [LV global longitudinal strain: P = 0.028, LV ejection fraction (EF): P = 0.027, LV cardiac index (CI): P = 0.034] and right ventricular (RV) [RVEF: P = 0.025, RVCI: P = 0.048] functions compared with patients with a decrease less than the median (n = 20). CONCLUSION: Treatment with tafamidis in ATTR-CM patients results in a significant reduction in SUV retention index, associated with significant benefits for LV and RV function and cardiac biomarkers. Serial quantitative 99mTc-DPD SPECT/CT imaging with SUV may be a valid tool to quantify and monitor response to tafamidis treatment in affected patients. TRANSLATIONAL PERSPECTIVE: 99mTc-DPD SPECT/CT imaging with determination of SUV retention index as part of a routine annual examination can provide evidence of treatment response in ATTR-CM patients receiving disease-modifying therapy. Further long-term studies with 99mTc-DPD SPECT/CT imaging may help to evaluate the relationship between tafamidis-induced reduction in SUV retention index and outcome in patients with ATTR-CM and will demonstrate whether highly disease-specific 99mTc-DPD SPECT/CT imaging is more sensitive than routine diagnostic monitoring.

Endovascular repair in type A aortic dissection: Anatomical candidacy for currently manufactured stent grafts and conceptual valve-carrying devices for an Endo-Bentall procedure.

OBJECTIVES: Endovascular treatment has been suggested as an alternative for open surgery for type A aortic dissection, but current devices have severe anatomical limitations. This study assesses the computed tomography-based anatomical suitability of currently manufactured stent grafts as well as 2 embodiments of valve-carrying devices. METHODS: In a retrospective single-centre cohort of 200 consecutive ascending/arch operations between 2009 and 2018, a total of 112 patients with type A aortic dissections were identified and evaluated for endovascular candidacy based on the locations of the entries, the landing zone diameters/lengths and the supra-aortic vessel origins according to the anatomical instructions for use criteria of 6 commercially available (tubular, branched or fenestrated) stent grafts. Two suggested valve-carrying devices with inner branches or fenestrations for the coronary arteries and branches for the supra-aortic vessels were also evaluated. RESULTS: The anatomical feasibility for commercial stent grafts ranged from 4% to 21%. The main limitations were proximal landing zone diameter (considering oversizing <15%), length due to dilatation and an entry too close to the sinotubular junction. For the valve-carrying conduits, anatomical feasibility was between 31% and 80%, with the main limiting factors being the diameter of the aortic annulus and its distance to the coronary arteries. CONCLUSIONS: The anatomical applicability of currently manufactured stent grafts for the treatment of type A aortic dissection is limited mainly by the absence of a suitable proximal landing zone in the ascending aorta and might substantially be improved by anchoring in the aortic annulus using a valve-carrying device that uses either fenestrations or branches for the coronary arteries.

Impact of tafamidis on myocardial strain in transthyretin amyloid cardiomyopathy.

AIMS: The impact of tafamidis on myocardial strain in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) have been barely investigated. We aimed to determine tafamidis-induced changes using serial speckle tracking echocardiography and to identify imaging parameters for specific therapy monitoring. METHODS AND RESULTS: ATTR-CM patients underwent serial TTE with two-dimensional (2 D) speckle tracking imaging. Patients receiving tafamidis free acid 61 mg (n = 62) or tafamidis meglumine 20 mg (n = 21) once daily (QD) showed stable measurements at follow-up (61 mg: 8.5 months, 20 mg: 7.0 months) in LV global longitudinal strain (GLS) (61 mg: -11.75% vs. -11.58%, p = 0.534; 20 mg: -10.61% vs. -10.12%, p = 0.309), right ventricular (RV) GLS (61 mg: -14.18% vs. -13.72%, p = 0.377; 20 mg: -14.53% vs. -13.99%, p = 0.452) and left atrial (LA) reservoir strain (LASr; 61 mg: 8.80% vs. 9.42%, p = 0.283; 20 mg: 8.23% vs. 8.67%, p = 0.589), whereas treatment-naïve ATTR-CM patients (n = 54) had clear signs of disease progression at the end of the observation period (10.5 months; LV-GLS: -11.71% vs. -10.59%, p = 0.001; RV-GLS: -14.36% vs. -12.99%, p = 0.038; LASr: 10.67% vs. 8.41%, p = 0.005). Between-group comparison at follow-up revealed beneficial effects of tafamidis free acid 61 mg on LASr (p = 0.003) and the LV (LV-GLS: p = 0.030, interventricular septum (IVS): p = 0.006), resulting in clinical benefits (six-minute walk distance (6-MWD): p = 0.006, NT-proBNP: p= <0.001), while patients treated with tafamidis meglumine 20 mg QD showed positive effects on LASr (p = 0.039), but no differences with respect to the LV (LV-GLS: p = 0.274, IVS: p = 0.068) and clinical status (6-MWD: p = 0.124, NT-proBNP: p = 0.053) compared to the natural course. CONCLUSIONS: Treatment with tafamidis free acid 61 mg in ATTR-CM patients delays the deterioration of LA and LV longitudinal function, resulting in significant clinical benefits compared with natural history. Serial TTE with 2 D speckle tracking imaging may be appropriate for disease-specific therapy monitoring.

Applicability of endovascular branched and fenestrated aortic arch repair devices to treat residual type A dissection after ascending replacement.

OBJECTIVE: Endovascular repair of post-type A aortic dissection (PTAD) after open ascending replacement has recently been shown as safe and feasible, but with limited anatomic applicability because only one stent graft was evaluated. We assessed anatomic and clinical applicability of six commercially available branched/fenestrated stent grafts for endovascular repair of PTAD. METHODS: On postoperative CT scans of 101 patients, we measured the aortic diameter at the sinutubular junction, supra-aortic vessels, and descending aorta, as well as the distances between these landmarks along the outer curvature of the arch and the diameters of the supra-aortic vessel. Anatomic applicability was evaluated according to the instructions for use, clinical applicability with regard to supra-aortic and iliac arteries. Assessed devices were the Cook aortic double branch, Terumo double branch, Najuta fenestrated, Endospan Nexus, Medtronic Mona LSA, and Gore TAG thoracic branch. RESULTS: Single devices were anatomically and clinically applicable between 19 of 101 (Mona LSA) and 83 of 101 (Najuta) cases. Reasons for rejection varied considerably across devices. With all devices available, anatomic applicability was 97 of 101 and clinical applicability 95 of 101. Combinations of a fenestrated and a branched device showed the most favorable clinical applicability for a pair of two devices, ranging from 86 of 101 to 94 of 101. CONCLUSIONS: Anatomic and clinical applicability of endovascular devices for the repair of PTAD is high for fenestrated and branched devices, and very high for the combination of fenestrated and branched devices. Manufacturers should amend specific device requirements for PTAD. Surgeons should emphasize the need for a sufficiently long and straight graft as a potential landing zone.

Impact of Tafamidis and Optimal Background Treatment on Physical Performance in Patients With Transthyretin Amyloid Cardiomyopathy.

BACKGROUND: In patients with transthyretin amyloid cardiomyopathy, tafamidis was shown to slow the decline in 6-minute walking distance as compared with placebo. We aimed to define the impact of tafamidis and optimal background treatment on functional capacity as determined by cardiopulmonary exercise testing (CPET). METHODS: Seventy-eight consecutive patients were enrolled in the study. They underwent CPET at baseline, and outcome defined as death or heart failure hospitalization was obtained for a time period of up to 30 months. Fifty-four patients completed a follow-up CPET at 9±3 months (range, 4-16 months). Improvement in peak VO2 at follow-up was defined as ∆peak VO2≥1.0 mL/(kg·min), stable peak VO2 was defined as 0≤∆peak VO2<1.0 mL/(kg·min), and decline in peak VO2 was defined by ∆peak VO2<0 mL/(kg·min). RESULTS: Baseline peak VO2>14 mL/(kg·min) as well as minute ventilation/carbon dioxide production slope≤34 were associated with a lower risk of death or heart failure hospitalization (P=0.002, P=0.007, respectively). In 54 patients, who received tafamidis and underwent repeat CPET testing, an improvement in physical performance (P=0.002) was observed at follow-up. When comparing pre and post-treatment parameters, 29 patients (54%) showed an increase in percent predicted peak VO2 (P<0.0001), an improvement of peak VO2 (P<0.0001), and better physical performance at follow-up (P<0.0001). Patients with stable or improved peak VO2 had less advanced heart disease at baseline (P=0.046). CONCLUSIONS: Our findings demonstrate that baseline peak VO2 and baseline minute ventilation/carbon dioxide production slope predict outcomes and an improvement in physical performance as measured by CPET was observed in patients receiving tafamidis, who had less advanced disease at baseline, emphasizing the importance of early diagnosis.

Use of a Steerable Sheath for Completely Femoral Access in Branched Endovascular Aortic Repair Compared to Upper Extremity Access.

PURPOSE: To compare bridging stent graft (BSG) implantation in downward oriented branches in branched endovascular aortic repair (bEVAR), using a commercially available steerable sheath from an exclusively femoral access (TFA) with traditional upper extremity access (UEA). METHODS: In a retrospective cohort study, 7 patients with 19 branches in the TFA cohort received BSG insertion using the Medtronic Heli FX steerable sheath from a femoral access, and 10 patients with 32 branches in the UEA cohort from a brachial approach. Technical success, total intervention time, fluoroscopy time, branch cannulation time, and complication rate were recorded. RESULTS: Technical success was 19/19 branches in the TFA and 31/32 in the UEA cohort. The mean branch cannulation time was considerably shorter in the TFA group (17 vs. 29 min, p = 0.003), and total intervention time tended to be shorter (169 vs. 217 min, p = 0.176). CONCLUSION: Using a commercially available steerable sheath allowed successful cannulation of all branches in this cohort and was associated with significantly shorter branch cannulation times. Potentially, this technique can lower the stroke and brachial puncture site complication risk as well as reduce total intervention time and radiation dose. LEVEL OF EVIDENCE: 2b, retrospective cohort study.

Machine learning-derived electrocardiographic algorithm for the detection of cardiac amyloidosis.

BACKGROUND: Diagnosis of cardiac amyloidosis (CA) requires advanced imaging techniques. Typical surface ECG patterns have been described, but their diagnostic abilities are limited. OBJECTIVE: The aim was to perform a thorough electrophysiological characterisation of patients with CA and derive an easy-to-use tool for diagnosis. METHODS: We applied electrocardiographic imaging (ECGI) to acquire electroanatomical maps in patients with CA and controls. A machine learning approach was then used to decipher the complex data sets obtained and generate a surface ECG-based diagnostic tool. FINDINGS: Areas of low voltage were localised in the basal inferior regions of both ventricles and the remaining right ventricular segments in CA. The earliest epicardial breakthrough of myocardial activation was visualised on the right ventricle. Potential maps revealed an accelerated and diffuse propagation pattern. We correlated the results from ECGI with 12-lead ECG recordings. Ventricular activation correlated best with R-peak timing in leads V1-V3. Epicardial voltage showed a strong positive correlation with R-peak amplitude in the inferior leads II, III and aVF. Respective surface ECG leads showed two characteristic patterns. Ten blinded cardiologists were asked to identify patients with CA by analysing 12-lead ECGs before and after training on the defined ECG patterns. Training led to significant improvements in the detection rate of CA, with an area under the curve of 0.69 before and 0.97 after training. INTERPRETATION: Using a machine learning approach, an ECG-based tool was developed from detailed electroanatomical mapping of patients with CA. The ECG algorithm is simple and has proven helpful to suspect CA without the aid of advanced imaging modalities.

Tafamidis treatment delays structural and functional changes of the left ventricle in patients with transthyretin amyloid cardiomyopathy.

AIMS: Tafamidis improves outcomes in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). However, it is not yet known whether tafamidis affects cardiac amyloid deposition and structural changes in the myocardium. We aimed to determine disease-modifying effects on myocardial amyloid progression and to identify imaging parameters that could be applied for specific therapy monitoring. METHODS AND RESULTS: ATTR-CM patients underwent serial cardiac magnetic resonance (CMR) imaging using T1 mapping techniques to derive extracellular volume (ECV). Patients receiving tafamidis 61 mg (n = 35) or 20 mg (n = 15) once daily showed stable measurements at follow-up (FU) {61 mg: 9.0 [interquartile range (IQR) 7.0-11.0] months, 20 mg: 11.0 (IQR 8.0-18.0) months} in left ventricular (LV) ejection fraction (LVEF; 61 mg: 47.6% vs. 47.5%, P = 0.935; 20 mg: 52.4% vs. 52.1%, P = 0.930), LV mass index (LVMI; 61 mg: 110.2 vs. 106.2 g/m2, P = 0.304; 20 mg: 114.5 vs. 115.4 g/m2, P = 0.900), and ECV (61 mg: 47.5% vs. 47.7%, P = 0.861; 20 mg: 56.7% vs. 57.5%, P = 0.759), whereas treatment-naïve ATTR-CM patients (n = 19) had clear signs of disease progression at the end of the observation period [12.0 (IQR 10.0-21.0) months; LVEF: 53.3% vs. 45.7%, P = 0.031; LVMI: 98.9 vs. 106.9 g/m2, P = 0.027; ECV: 49.3% vs. 54.6%, P = 0.023]. Between-group comparison at FU revealed positive effects in tafamidis 61 mg-treated compared to treatment-naïve patients (LVEF: P = 0.035, LVMI: P = 0.036, ECV: P = 0.030), while those treated with 20 mg showed no difference in the above LV measurements when compared with treatment-naïve (P = 0.120, P = 0.287, P = 0.158). However, both treatment groups showed clinically beneficial effects compared to the natural course [61 mg, 6-min walk distance (6-MWD): P = 0.005, N-terminal prohormone of brain natriuretic peptide (NT-proBNP): P = 0.002; 20 mg, 6-MWD: P = 0.023, NT-proBNP: P = 0.003]. CONCLUSION: Tafamidis delays myocardial amyloid progression in ATTR-CM patients, resulting in structural, functional, and clinical benefits compared to the natural course. Serial CMR including measurement of ECV may be appropriate for disease-specific therapy monitoring.

Convolutional Neural Networks for Fully Automated Diagnosis of Cardiac Amyloidosis by Cardiac Magnetic Resonance Imaging.

AIMS: We tested the hypothesis that artificial intelligence (AI)-powered algorithms applied to cardiac magnetic resonance (CMR) images could be able to detect the potential patterns of cardiac amyloidosis (CA). Readers in CMR centers with a low volume of referrals for the detection of myocardial storage diseases or a low volume of CMRs, in general, may overlook CA. In light of the growing prevalence of the disease and emerging therapeutic options, there is an urgent need to avoid misdiagnoses. METHODS AND RESULTS: Using CMR data from 502 patients (CA: n = 82), we trained convolutional neural networks (CNNs) to automatically diagnose patients with CA. We compared the diagnostic accuracy of different state-of-the-art deep learning techniques on common CMR imaging protocols in detecting imaging patterns associated with CA. As a result of a 10-fold cross-validated evaluation, the best-performing fine-tuned CNN achieved an average ROC AUC score of 0.96, resulting in a diagnostic accuracy of 94% sensitivity and 90% specificity. CONCLUSIONS: Applying AI to CMR to diagnose CA may set a remarkable milestone in an attempt to establish a fully computational diagnostic path for the diagnosis of CA, in order to support the complex diagnostic work-up requiring a profound knowledge of experts from different disciplines.

Prognostic implications of pericardial and pleural effusion in patients with cardiac amyloidosis.

BACKGROUND: Pericardial and pleural effusion are common findings in patients with cardiac amyloidosis (CA). It is not known, whether effusions correlate with right ventricular (RV) function in these patients. Furthermore, data on the prognostic significance of pleural and pericardial effusion in CA is scarce. METHODS: Patients with transthyretin (ATTR) and light chain (AL) CA were included in a clinical registry. All patients underwent transthoracic echocardiography at baseline. The presence of pericardial and pleural effusion was determined in every patient. The clinical endpoint was defined as cardiac death or heart failure hospitalization. RESULTS: In total, 143 patients were analysed. Of these, 85 patients were diagnosed with ATTR and 58 patients with AL. Twenty-four patients presented with isolated pericardial effusion and 35 with isolated pleural effusion. In 19 patients, both pericardial and pleural effusion were found and in 65 patients no effusion was present at baseline. The presence of pleural effusion correlated well with poor RV function, measured by global RV free-wall strain (p = 0.007) in patients with AL, but not in ATTR. No such correlation could be found for pericardial effusion in either amyloidosis subtype. Patients with AL presenting with pleural effusion had worse outcomes compared to patients with pericardial effusion alone or no effusion at baseline. In the ATTR group, there was no difference in outcomes according to presence and type of effusion. CONCLUSION: More than 50% of patients with CA presented with pleural and/or pericardial effusions. While pleural effusion was clearly associated with poor RV function in AL, we were not able to detect this association with pericardial effusion.

Machine Learning Enables Prediction of Cardiac Amyloidosis by Routine Laboratory Parameters: A Proof-of-Concept Study.

(1) Background: Cardiac amyloidosis (CA) is a rare and complex condition with poor prognosis. While novel therapies improve outcomes, many affected individuals remain undiagnosed due to a lack of awareness among clinicians. This study was undertaken to develop an expert-independent machine learning (ML) prediction model for CA relying on routinely determined laboratory parameters. (2) Methods: In a first step, we developed baseline linear models based on logistic regression. In a second step, we used an ML algorithm based on gradient tree boosting to improve our linear prediction model, and to perform non-linear prediction. Then, we compared the performance of all diagnostic algorithms. All prediction models were developed on a training cohort, consisting of patients with proven CA (positive cases, n = 121) and amyloidosis-unrelated heart failure (HF) patients (negative cases, n = 415). Performances of all prediction models were evaluated on a separate prognostic validation cohort with 37 CA-positive and 124 CA-negative patients. (3) Results: Our best model, based on gradient-boosted ensembles of decision trees, achieved an area under the receiver operating characteristic curve (ROC AUC) score of 0.86, with sensitivity and specificity of 89.2% and 78.2%, respectively. The best linear model had an ROC AUC score of 0.75, with sensitivity and specificity of 84.6 and 71.7, respectively. (4) Conclusions: Our work demonstrates that ML makes it possible to utilize basic laboratory parameters to generate a distinct CA-related HF profile compared with CA-unrelated HF patients. This proof-of-concept study opens a potential new avenue in the diagnostic workup of CA and may assist physicians in clinical reasoning.

Hemodynamic Profiles and Their Prognostic Relevance in Cardiac Amyloidosis.

This study sought to characterize cardiac amyloidosis (CA) patients with respect to hemodynamic parameters and asses their prognostic impact in different CA cohorts. Intracardiac and pulmonary arterial pressures (PAPs) are among the strongest predictors of outcomes in patients with heart failure (HF). Despite that, the hemodynamic profiles of patients with CA and their relation to prognosis have rarely been investigated. Invasive hemodynamic, clinical, and laboratory assessment, as well as cardiac magnetic resonance imaging were performed in our CA cohort. A total of 61 patients, 35 (57.4%) with wild-type transthyretin amyloidosis (ATTRwt) and 26 (42.6%) with light-chain amyloidosis (AL) were enrolled. ATTRwt patients had lower N-terminal prohormone of brain natriuretic peptide values and were less frequently in New York Heart Association class ≥ III. Intracardiac and PAPs were elevated, but hemodynamic parameters did not differ between CA groups. Whereas in ATTRwt, the median mean PAP (hazard ratio (HR): 1.130, p = 0.040) and pulmonary vascular resistance (HR: 1.010, p = 0.046) were independent predictors of outcome, no hemodynamic parameter was associated with outcome in the AL group. Cardiac ATTRwt and AL patients feature elevated intracardiac and PAPs and show similar hemodynamic profiles. However, hemodynamic parameters are of greater prognostic relevance in ATTRwt, potentially providing a new therapeutic target.