Investigations into the stability of growth factor induced-vasculature and the effects of synthetic biomaterials on heart remodelling after myocardial infarction

This work was based on the hypothesis that optimization of growth factor delivery rate and duration, combined with a biomaterial scaffold, could lead to an improved strategy for therapeutic neovascularization. To test this hypothesis, a novel in vivo model system that allows for characterization of stability and mural cell investment of newly created vessels was designed

SGLT2 inhibitor therapy for transthyretin amyloid cardiomyopathy: early tolerance and clinical response to dapagliflozin.

AIMS Sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve clinical outcomes in heart failure patients with reduced and preserved left ventricular ejection fraction (LVEF), but have not yet been investigated in transthyretin amyloid cardiomyopathy (ATTR-CM). This study aimed to evaluate tolerability, clinical outcomes, and changes in NT-proBNP levels and glomerular filtration rate (GFR) in ATTR-CM patients treated with dapagliflozin. METHODS AND RESULTS Patients with stable, tafamidis-treated ATTR-CM were retrospectively evaluated at the initiation of dapagliflozin and 3 months thereafter. Tafamidis-treated ATTR-CM patients without SGLT2i served as a reference cohort. Overall, SLGT2i therapy was initiated in 34 patients. Seventeen patients with stable disease on tafamidis, who were subsequently started on dapagliflozin, were included in the analysis. Patients selected for SGLT2i presented with signs of advanced disease, evidenced by higher Gillmore disease stage (stage ≥2: 53% vs. 27.5%; P = 0.041), baseline median NT-proBNP [median (IQR) 2668 pg/mL (1314-3451) vs. 1424 (810-2059); P = 0.038] and loop diuretic demand (76.5% vs. 45% of patients; P = 0.044), and lower LVEF (46.6 ± 12.9 vs. 53.7 ± 8.7%; P = 0.019) and GFR (51.8 ± 16.5 vs. 68.5 ± 18.6 mL/min; P = 0.037) compared with the reference cohort. At 3-month follow-up, a numerical decrease in NT-proBNP levels was observed in 13/17 (76.5%) patients in the dapagliflozin (-190 pg/mL, IQR: -1,028-71, P = 0.557) and 27/40 (67.5%) of patients in the control cohort (-115 pg/mL, IQR: -357-105, P = 0.551). Other disease parameters remained stable and no adverse events occurred. CONCLUSIONS In tafamidis-treated ATTR-CM patients, initiation of dapagliflozin was well tolerated. The efficacy of SGLT2i therapy in patients with ATTR-CM needs to be studied in randomized controlled trials

Diagnostic performance of cardiac magnetic resonance segmental myocardial strain for detecting microvascular obstruction and late gadolinium enhancement in patients presenting after a ST-elevation myocardial infarction.

Background Microvascular obstruction (MVO) and Late Gadolinium Enhancement (LGE) assessed in cardiac magnetic resonance (CMR) are associated with adverse outcome in patients with ST-elevation myocardial infarction (STEMI). Our aim was to analyze the diagnostic performance of segmental strain for the detection of MVO and LGE. Methods Patients with anterior STEMI, who underwent additional CMR were enrolled in this sub-study of the CARE-AMI trial. Using CMR feature tracking (FT) segmental circumferential peak strain (SCS) was measured and the diagnostic performance of SCS to discriminate MVO and LGE was assessed in a derivation and validation cohort. Results Forty-eight STEMI patients (62 ± 12 years old), 39 (81%) males, who underwent CMR (i.e., mean 3.0 ± 1.5 days) after primary percutaneous coronary intervention (PCI) were included. All patients presented with LGE and in 40 (83%) patients, MVO was additionally present. Segments in all patients were visually classified and 146 (19%) segments showed MVO (i.e., LGE+/MVO+), 308 (40%) segments showed LGE and no MVO (i.e., LGE+/MVO-), and 314 (41%) segments showed no LGE (i.e., LGE-). Diagnostic performance of SCS for detecting MVO segments (i.e., LGE+/MVO+ vs. LGE+/MVO-, and LGE-) showed an AUC = 0.764 and SCS cut-off value was -11.2%, resulting in a sensitivity of 78% and a specificity of 67% with a positive predictive value (PPV) of 30% and a negative predictive value (NPV) of 94% when tested in the validation group. For LGE segments (i.e., LGE+/MVO+ and LGE+/MVO- vs. LGE-) AUC = 0.848 and SCS with a cut-off value of -13.8% yielded to a sensitivity of 76%, specificity of 74%, PPV of 81%, and NPV of 70%. Conclusion Segmental strain in STEMI patients was associated with good diagnostic performance for detection of MVO+ segments and very good diagnostic performance of LGE+ segments. Segmental strain may be useful as a potential contrast-free surrogate marker to improve early risk stratification in patients after primary PCI

Is It Safe to Irradiate the Newest Generation of Ventricular Assist Devices? A Case Report and Systematic Literature Review.

An increasing number of mechanical assist devices, especially Left Ventricular Assist Devices (VAD), are being implanted for prolonged periods and as destination therapy. Some VAD patients require radiotherapy due to concomitant oncologic morbidities, including thoracic malignancies. This raises the potential of VAD malfunction via radiation-induced damage. So far, only case reports and small case series on radiotherapy have been published; most of them on HeartMate IITM (HMII, Abbott, North Chicago, IL, USA). Significantly, the effects of irradiation on the HeartMate 3TM (HM3, Abbott, North Chicago, IL, USA) remain undefined, despite the presence of controller components engineered within the pump itself. We report the first case of a patient with a HM3 who successfully underwent stereotactic hypo-fractionated radiotherapy due to an early stage non-small-cell lung cancer. The patient did not suffer from any complications; including toxicity or VAD malfunction. Based on this case report and on published literature, we think that performing radiotherapy after VAD implantation with the aid of a multidisciplinary team could be performed, but more in-vitro and cases series are needed to reinforce this statement

Impact of route of access and stenosis subtype on outcome after transcatheter aortic valve replacement

Introduction: Previous analyses have reported the outcomes of transcatheter aortic valve replacement (TAVR) for patients with low-flow, low-gradient (LFLG) aortic stenosis (AS), without stratifying according to the route of access. Differences in mortality rates among access routes have been established for high-gradient (HG) patients and hypothesized to be even more pronounced in LFLG AS patients. This study aims to compare the outcomes of patients with LFLG or HG AS following transfemoral (TF) or transapical (TA) TAVR. Methods: A total of 910 patients, who underwent either TF or TA TAVR with a median follow-up of 2.22 (IQR: 1.22-4.03) years, were included in this multicenter cohort study. In total, 146 patients (16.04%) suffered from LFLG AS. The patients with HG and LFLG AS were stratified according to the route of access and compared statistically. Results: The operative mortality rates of patients with HG and LFLG were found to be comparable following TF access. The operative mortality rate was significantly increased for patients who underwent TA access [odds ratio (OR): 2.91 (1.54-5.48), p = 0.001] and patients with LFLG AS [OR: 2.27 (1.13-4.56), p = 0.02], which could be corroborated in a propensity score-matched subanalysis. The observed increase in the risk of operative mortality demonstrated an additive effect [OR for TA LFLG: 5.45 (2.35-12.62), p < 0.001]. LFLG patients who underwent TA access had significantly higher operative mortality rates (17.78%) compared with TF LFLG (3.96%, p = 0.016) and TA HG patients (6.36%, p = 0.024). Conclusions: HG patients experienced a twofold increase in operative mortality rates following TA compared with TF access, while LFLG patients had a fivefold increase in operative mortality rates. TA TAVR appears suboptimal for patients with LFLG AS. Prospective studies should be conducted to evaluate alternative options in cases where TF is not possible

Impact of route of access and stenosis subtype on outcome after transcatheter aortic valve replacement.

INTRODUCTION Previous analyses have reported the outcomes of transcatheter aortic valve replacement (TAVR) for patients with low-flow, low-gradient (LFLG) aortic stenosis (AS), without stratifying according to the route of access. Differences in mortality rates among access routes have been established for high-gradient (HG) patients and hypothesized to be even more pronounced in LFLG AS patients. This study aims to compare the outcomes of patients with LFLG or HG AS following transfemoral (TF) or transapical (TA) TAVR. METHODS A total of 910 patients, who underwent either TF or TA TAVR with a median follow-up of 2.22 (IQR: 1.22-4.03) years, were included in this multicenter cohort study. In total, 146 patients (16.04%) suffered from LFLG AS. The patients with HG and LFLG AS were stratified according to the route of access and compared statistically. RESULTS The operative mortality rates of patients with HG and LFLG were found to be comparable following TF access. The operative mortality rate was significantly increased for patients who underwent TA access [odds ratio (OR): 2.91 (1.54-5.48), p = 0.001] and patients with LFLG AS [OR: 2.27 (1.13-4.56), p = 0.02], which could be corroborated in a propensity score-matched subanalysis. The observed increase in the risk of operative mortality demonstrated an additive effect [OR for TA LFLG: 5.45 (2.35-12.62), p < 0.001]. LFLG patients who underwent TA access had significantly higher operative mortality rates (17.78%) compared with TF LFLG (3.96%, p = 0.016) and TA HG patients (6.36%, p = 0.024). CONCLUSIONS HG patients experienced a twofold increase in operative mortality rates following TA compared with TF access, while LFLG patients had a fivefold increase in operative mortality rates. TA TAVR appears suboptimal for patients with LFLG AS. Prospective studies should be conducted to evaluate alternative options in cases where TF is not possible

A Neuronal Network-Based Score Predicting Survival in Patients Undergoing Aortic Valve Intervention: The ABC-AS Score.

Background: Despite being the most commonly performed valvular intervention, risk prediction for aortic valve replacement in patients with severe aortic stenosis by currently used risk scores remains challenging. The study aim was to develop a biomarker-based risk score by means of a neuronal network. Methods: In this multicenter study, 3595 patients were divided into test and validation cohorts (70% to 30%) by random allocation. Input variables to develop the ABC-AS score were age, the cardiac biomarker high-sensitivity troponin T, and a patient history of cardiac decompensation. The validation cohort was used to verify the scores' value and for comparison with the Society of Thoracic Surgery Predictive Risk of Operative Mortality score. Results: Receiver operating curves demonstrated an improvement in prediction by using the ABC-AS score compared to the Society of Thoracic Surgery Predictive Risk of Operative Mortality (STS prom) score. Although the difference in predicting cardiovascular mortality was most notable at 30-day follow-up (area under the curve of 0.922 versus 0.678), ABC-AS also performed better in overall follow-up (0.839 versus 0.699). Furthermore, univariate analysis of ABC-AS tertiles yielded highly significant differences for all-cause (p < 0.0001) and cardiovascular mortality (p < 0.0001). Head-to-head comparison between both risk scores in a multivariable cox regression model underlined the potential of the ABC-AS score (HR per z-unit 2.633 (95% CI 2.156-3.216), p < 0.0001), while the STS prom score failed to reach statistical significance (p = 0.226). Conclusions: The newly developed ABC-AS score is an improved risk stratification tool to predict cardiovascular outcomes for patients undergoing aortic valve intervention

Evaluation of the 2021 ESC recommendations for family screening in hereditary transthyretin cardiac amyloidosis

AIMS: The 2021 European Society of Cardiology (ESC) screening recommendations for individuals carrying a pathogenic transthyretin amyloidosis variant (ATTRv) are based on expert opinion. We aimed to (i) determine the penetrance of ATTRv cardiomyopathy (ATTRv-CM) at baseline; (ii) examine the value of serial evaluation; and (iii) establish the yield of first-line diagnostic tests (i.e. electrocardiogram, echocardiogram, and laboratory tests) as per 2021 ESC position statement.METHODS AND RESULTS: We included 159 relatives (median age 55.6 [43.2-65.9] years, 52% male) at risk for ATTRv-CM from 10 centres. The primary endpoint, ATTRv-CM diagnosis, was defined as the presence of (i) cardiac tracer uptake in bone scintigraphy; or (ii) transthyretin-positive cardiac biopsy. The secondary endpoint was a composite of heart failure (New York Heart Association class ≥II) and pacemaker-requiring conduction disorders. At baseline, 40/159 (25%) relatives were diagnosed with ATTRv-CM. Of those, 20 (50%) met the secondary endpoint. Indication to screen (≤10 years prior to predicted disease onset and absence of extracardiac amyloidosis) had an excellent negative predictive value (97%). Other pre-screening predictors for ATTRv-CM were infrequently identified variants and male sex. Importantly, 13% of relatives with ATTRv-CM did not show any signs of cardiac involvement on first-line diagnostic tests. The yield of serial evaluation (n = 41 relatives; follow-up 3.1 [2.2-5.2] years) at 3-year interval was 9.4%.CONCLUSIONS: Screening according to the 2021 ESC position statement performs well in daily clinical practice. Clinicians should adhere to repeating bone scintigraphy after 3 years, as progressing to ATTRv-CM without signs of ATTRv-CM on first-line diagnostic tests or symptoms is common.</p

Evaluation of the 2021 ESC recommendations for family screening in hereditary transthyretin cardiac amyloidosis

AIMS: The 2021 European Society of Cardiology (ESC) screening recommendations for individuals carrying a pathogenic transthyretin amyloidosis variant (ATTRv) are based on expert opinion. We aimed to (i) determine the penetrance of ATTRv cardiomyopathy (ATTRv-CM) at baseline; (ii) examine the value of serial evaluation; and (iii) establish the yield of first-line diagnostic tests (i.e. electrocardiogram, echocardiogram, and laboratory tests) as per 2021 ESC position statement.METHODS AND RESULTS: We included 159 relatives (median age 55.6 [43.2-65.9] years, 52% male) at risk for ATTRv-CM from 10 centres. The primary endpoint, ATTRv-CM diagnosis, was defined as the presence of (i) cardiac tracer uptake in bone scintigraphy; or (ii) transthyretin-positive cardiac biopsy. The secondary endpoint was a composite of heart failure (New York Heart Association class ≥II) and pacemaker-requiring conduction disorders. At baseline, 40/159 (25%) relatives were diagnosed with ATTRv-CM. Of those, 20 (50%) met the secondary endpoint. Indication to screen (≤10 years prior to predicted disease onset and absence of extracardiac amyloidosis) had an excellent negative predictive value (97%). Other pre-screening predictors for ATTRv-CM were infrequently identified variants and male sex. Importantly, 13% of relatives with ATTRv-CM did not show any signs of cardiac involvement on first-line diagnostic tests. The yield of serial evaluation (n = 41 relatives; follow-up 3.1 [2.2-5.2] years) at 3-year interval was 9.4%.CONCLUSIONS: Screening according to the 2021 ESC position statement performs well in daily clinical practice. Clinicians should adhere to repeating bone scintigraphy after 3 years, as progressing to ATTRv-CM without signs of ATTRv-CM on first-line diagnostic tests or symptoms is common.</p