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Aims Quantification of cardiac [99mTc]-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) uptake enhances diagnostic capabilities and may facilitate prognostic stratification in patients with transthyretin cardiac amyloidosis (ATTR-CA). This study aimed to evaluate the association of quantitative left ventricular (LV) DPD uptake with myocardial structure and function, and their implications on outcome in ATTR-CA. Methods and results Consecutive ATTR-CA patients (n = 100) undergoing planar DPD scintigraphy with Perugini grade 2 or 3, alongside quantitative DPD single-photon emission computed tomography/computed tomography imaging and speckle-tracking echocardiography between 2019 and 2023, were included and divided into two cohorts based on median DPD retention index (low DPD uptake: ≤5.4, n = 50; high DPD uptake: >5.4, n = 50). The DPD retention index showed significant, albeit weak to modest, correlations with LV global longitudinal strain (LV-GLS: r = 0.366, P < 0.001), right ventricular free wall longitudinal strain (RV-FW-LS: r = 0.316, P = 0.002), LV diastolic function (E/e′ average: r = 0.304, P = 0.013), NT-proBNP (r = 0.332, P < 0.001), troponin T (r = 0.233, P = 0.022), 6 min walk distance (6MWD: r = −0.222, P = 0.033), and National Amyloidosis Centre (NAC) stage (r = 0.294, P = 0.003). ATTR-CA patients in the high DPD uptake cohort demonstrated more advanced disease severity regarding longitudinal cardiac function (LV-GLS: P = 0.012, RV-FW-LS: P = 0.036), LV diastolic function (E/e′ average: P = 0.035), cardiac biomarkers (NT-proBNP: P = 0.012, troponin T: P = 0.044), exercise capacity (6MWD: P = 0.035), and disease stage (NAC stage I: P = 0.045, III: P = 0.006), and experienced adverse outcomes compared with the low DPD uptake cohort [composite endpoint: all-cause death or heart failure hospitalization, HR: 2.873 (95% CI: 1.439–5.737), P = 0.003; DPD retention index: adjusted HR 1.221 (95% CI: 1.078–1.383), P = 0.002]. Conclusion In ATTR-CA, enhanced quantitative LV DPD uptake indicates advanced disease severity and is associated with adverse outcome. DPD quantification may facilitate prognostic stratification when diagnosing patients with ATTR-CA. [ABSTRACT FROM AUTHOR]

Background: Extracellular volume (ECV) by cardiovascular magnetic resonance (CMR) imaging is associated with disease burden and clinical outcomes. Recent studies in patients with valvular heart disease (VHD) have suggested that the indexed total ECV (iECV) = ECVx(LVmass/1.05)/body surface area may supersede ECV in terms of prognostication. In this study, we aimed to compare the prognostic capability of conventional ECV and iECV in an all-comer CMR cohort. Methods: From January 2012 to 2023, ECV and iECV were measured in consecutive CMR patients. Adverse outcomes were defined as a composite of hospitalization for heart failure (HF) and/or death. All patients underwent transthoracic echocardiography within 3 weeks of CMR. Results: Overall, 1525 patients (44% female, mean age 65 ± 18 years) were included. The mean ECV was 29 ± 9% and the mean iECV was 21 ± 13 mL/m2. During 52 ± 36 months of follow-up, 414 (27%) events occurred. Both ECV (HR = 1.04, 95% CI = 1.04–1.05, p < 0.001) and iECV (HR = 1.03, 95% CI = 1.02–1.03, p < 0.001) were significantly associated with outcomes. Having been stratified for ECV and iECV tertiles, Kaplan-Meier analyses showed a significant association with event-free survival for both parameters (log-rank, p < 0.001 for both; central illustration). Regarding multivariate analysis, adjusted for age, sex, left ventricular function, and NT-proBNP, both ECV and iECV remained independently associated with the composite endpoint (ECV: HR = 1.31, 95% CI = 1.20–1.44, p < 0.001; iECV: HR = 1.17, 95% CI = 1.06–1.29, p = 0.002). In addition, ECV was significantly associated with aortic valve velocity (p < 0.001) pertaining to echocardiography, whereas iECV did not show an association (p = 0.41). Conclusions: Both conventional ECV and iECV provided profound prognostic information regarding the risk of HF hospitalizations and death. However, iECV, which is more complex to determine, did not add value. [ABSTRACT FROM AUTHOR]

Background: Renal disease is common in patients with cardiovascular disease (CVD) and is associated with adverse outcomes. Cardiac magnetic resonance (CMR) with advanced mapping techniques is the gold standard for characterizing myocardial tissue, and renal tissue is often visualized on these maps. However, it remains unclear whether renal T1 times accurately reflect renal dysfunction or predict adverse outcomes. Aim: To analyze the relationship between renal T1 times, renal dysfunction, and adverse outcomes. Adverse outcomes were defined as all-cause and cardiovascular death. Methods: Renal T1 times were measured in the native short-axis view in an all-comers cohort undergoing CMR. Renal function parameters were assessed at the time of CMR. Results: A total of 506 patients (mean age 60 ± 15 years, 53% male) were included in the analysis. A significant correlation was observed between log10 renal cortical T1 times and eGFR (r = −0.701, p < 0.001) and creatinine (r = 0.615, p < 0.001). Kaplan–Meier analysis showed an increased risk of all-cause (p < 0.001 by log-rank test) and cardiovascular mortality (p = 0.004 by log-rank test) in patients with renal cortical T1 times above the median. In the univariable Cox regression analysis, there was a significant association between renal cortical T1 times and increased risk of all-cause (HR = 1.73 [95% CI, 1.42–2.11] per every 100 ms increase p < 0.001) and cardiovascular mortality (HR = 1.41 [95% CI, 1.05–1.90] per every 100 ms increase, p = 0.021). This association remained statistically significant after adjustment for prespecified clinical factors (adjusted HR for all-cause death = 1.49 [95% CI, 1.10–2.02] per every 100 ms increase, p = 0.01; adjusted HR for cardiovascular death = 1.42 [95% CI, 1.05–1.90] per every 100 ms increase, p = 0.021). Conclusions: Our results indicate that there is a significant association between increased renal cortical T1 times and impaired renal function, as well as an increased risk of all-cause and cardiovascular mortality, although it should be noted that our results are preliminary and need to be validated in external cohorts performing renal biopsies. [ABSTRACT FROM AUTHOR]

Aims: Quantification of cardiac [99mTc]-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) uptake enhances diagnostic capabilities and may facilitate prognostic stratification in patients with transthyretin cardiac amyloidosis (ATTR-CA). This study aimed to evaluate the association of quantitative left ventricular (LV) DPD uptake with myocardial structure and function, and their implications on outcome in ATTR-CA., Methods and Results: Consecutive ATTR-CA patients (n = 100) undergoing planar DPD scintigraphy with Perugini grade 2 or 3, alongside quantitative DPD single-photon emission computed tomography/computed tomography imaging and speckle-tracking echocardiography between 2019 and 2023, were included and divided into two cohorts based on median DPD retention index (low DPD uptake: ≤5.4, n = 50; high DPD uptake: >5.4, n = 50). The DPD retention index showed significant, albeit weak to modest, correlations with LV global longitudinal strain (LV-GLS: r = 0.366, P < 0.001), right ventricular free wall longitudinal strain (RV-FW-LS: r = 0.316, P = 0.002), LV diastolic function (E/e' average: r = 0.304, P = 0.013), NT-proBNP (r = 0.332, P < 0.001), troponin T (r = 0.233, P = 0.022), 6 min walk distance (6MWD: r = -0.222, P = 0.033), and National Amyloidosis Centre (NAC) stage (r = 0.294, P = 0.003). ATTR-CA patients in the high DPD uptake cohort demonstrated more advanced disease severity regarding longitudinal cardiac function (LV-GLS: P = 0.012, RV-FW-LS: P = 0.036), LV diastolic function (E/e' average: P = 0.035), cardiac biomarkers (NT-proBNP: P = 0.012, troponin T: P = 0.044), exercise capacity (6MWD: P = 0.035), and disease stage (NAC stage I: P = 0.045, III: P = 0.006), and experienced adverse outcomes compared with the low DPD uptake cohort [composite endpoint: all-cause death or heart failure hospitalization, HR: 2.873 (95% CI: 1.439-5.737), P = 0.003; DPD retention index: adjusted HR 1.221 (95% CI: 1.078-1.383), P = 0.002]., Conclusion: In ATTR-CA, enhanced quantitative LV DPD uptake indicates advanced disease severity and is associated with adverse outcome. DPD quantification may facilitate prognostic stratification when diagnosing patients with ATTR-CA., Competing Interests: Conflict of interest: R.R. received speaker fees and congress support from Akcea Therapeutics, Alnylam Pharmaceuticals, and Pfizer Inc., as well as well as research grants from Pfizer Inc. F.D. received speaker fees and congress support from AOP Orphan Pharmaceuticals GmbH, Alnylam Pharmaceuticals, Bayer AG, Novartis AG, and Pfizer Inc., as well as research grants from the Austrian Society of Cardiology and Pfizer Inc. C.N. receives speaker fees and research grants from Pfizer Inc. R.B.E. received speaker fees from Merck Sharp & Dohme Ges.m.b.H., AOP Orphan Pharmaceuticals GmbH, and OrphaCare GmbH, as well as research grants from OrphaCare GmbH and Astra Zeneca GmbH. All other authors have nothing to declare., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Less pronounced calcification of the aortic valve (AVC) was observed in women with aortic stenosis (AS) as compared to men. Since women have smaller aortic valves (AV), this could explain a lower calcium load. We aimed to analyze the association of AV size with AVC independent from sex., Methods & Results: Consecutive patients with high-gradient AS, who underwent cardiac computed tomography (CT), were assessed. AV annulus area and AVC with the Agatston score were measured on CT. In total, 601 patients (mean age 80±7 years, 45% female) were included. Women had smaller AV annulus areas (4.12±0.67cm2 vs 5.15 ±0.78cm2, p<0.001) and lower Agatston scores (2018 [1456-3017] vs. 3394 [2562-4530]; p<0.001) than men. We found a significant correlation (r=0.594, p<0.001) and independent association (β=926.20, p<0.001) of AV annulus area with AVC. On separate regression analyses for men and women, AVC was independently associated with AV annulus area in both sexes (βmen=887.77; βwomen=863.48, both p<0.001). When patients were stratified into AV size quartiles, patients in the lower quartiles were more likely to have AVC values below recommended sex-specific AVC thresholds. In the lowest quartile 28% of female and 27% of male patients had Agatston scores below 1200AU (women) and 2000AU (men) while this proportion decreased to 6% and 2%, respectively, in the quartiles with the largest annulus areas., Conclusion: In high-gradient AS, AVC strongly depends on AV annulus area. This association is not dependent on sex. Thus, AVC should be indexed to AV size in addition to sex., (© The Author(s) 2025. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Degenerative severe aortic stenosis (AS) is treated by valve replacement to improve outcome. Despite diagnostic advancements, many AS patients are still diagnosed late with advanced heart failure., Objectives: The aim of the study was to assess multiorgan dysfunction in severe AS using blood biomarkers and their association with quantitative fluid levels and clinical outcomes after transcatheter aortic valve implantation (TAVI)., Methods: Consecutive AS patients undergoing TAVI received comprehensive preinterventional assessment with serum biomarker profiles reflecting organ dysfunction and quantitative fluid overload (FO) using bioelectrical impedance spectroscopy. FO by bioelectrical impedance spectroscopy was defined according to a previously established cut-off (≥1.0 L). Time to first heart failure hospitalization or death served as composite primary endpoint., Results: Among 880 patients (age 81 ± 7 years, 47% female), 41% had FO and 89% had biomarker abnormalities of at least one domain. Ascending fluid levels were independently associated with distorted biomarkers across domains of myocyte stress, hepatic dysfunction, renal dysfunction, inflammation, and anemia. After 2.4 ± 1.0 years of follow-up, 27% had reached the primary endpoint (29 heart failure hospitalization, 194 deaths, 13 both). Biomarkers across all domains were individually and independently associated with outcomes. In a multidomain approach, every affected extra-cardiac domain was associated with a 71% increase in event hazard (adjusted HR: 1.71; 95% CI: 1.39-2.11). Also, for each domain, the combination of distorted biomarkers and FO had the highest event risk., Conclusions: Biomarker abnormalities are highly prevalent in severe AS, influenced by congestion, and associated with impaired prognosis post-TAVI. Multiorgan dysfunction faces a particularly dismal outcome., Competing Interests: Dr Dannenberg is a proctor/speaker for Edwards and Abbott. Dr Andreas is a proctor/consultant/speaker for Edwards, Abbott, Medtronic, Boston, Zoll, AbbVie, and Braun; and receives institutional research grants from 10.13039/100006520Edwards, 10.13039/100000046Abbott, 10.13039/100004374Medtronic, and LSI. Dr Kammerlander receives research grants from 10.13039/100004319Pfizer; receives speaker fees from Bayer and Boehringer Ingelheim; and on the advisory board honoraria of Boehringer Ingelheim. Dr Hengstenberg is a proctor/speaker for Edwards Lifesciences and Boston Scientific; and receives institutional research grants from 10.13039/100000046Abbott, 10.13039/100008497Boston Scientific, 10.13039/100006520Edwards Lifesciences, and 10.13039/100004374Medtronic. Dr Nitsche is a speaker and receives institutional research grants from 10.13039/100004319Pfizer; and on the advisory board honoraria of Prothena. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2025 The Authors.)