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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]

Variant transthyretin amyloidosis cardiomyopathy (ATTRv-CM) is a rare form of cardiac amyloidosis associated with many possible mutations in the transthyretin gene, presenting as various distinct clinical phenotypes. Among these, the His108Arg mutation is the most prevalent TTR variant in Austria. However, data describing its clinical phenotype are lacking. This study aims to describe the characteristics, clinical manifestations, and outcomes of patients with the His108Arg variant focusing on cardiac involvement, disease progression, response to therapy, and imaging findings. Methods: Patients were enrolled from a prospective cardiac amyloidosis registry. The baseline assessment included comprehensive echocardiography, cardiac magnetic resonance imaging, a biomarker analysis, and a clinical evaluation. Patients were followed longitudinally, with outcomes such as arrhythmias, heart failure hospitalizations, and response to disease-targeted therapies recorded. Results: Between March 2012 and June 2024, a total of 20 carriers of the His108Arg variant were identified, with 12 exhibiting clear cardiac involvement and 8 remaining asymptomatic. The median age at diagnosis was 62.3 years with significant heterogeneity in the clinical presentation. Patients with ATTRv-CM had a high prevalence of atrial and ventricular arrhythmias, a reduced left ventricular ejection fraction, and elevated cardiac biomarkers. The majority received specific disease-modifying therapies, with varying tolerance and responses. A longitudinal follow-up indicated frequent arrhythmic events, heart failure exacerbations, and three cases of heart transplantation, underscoring the need for stringent monitoring and individualized management strategies. Conclusions: This study represents a unique, comprehensive analysis of the His108Arg variant in ATTR-CM, highlighting its clinical heterogeneity and significant impact on cardiac function and clinical outcomes. [ABSTRACT FROM AUTHOR]

Background and Aims To assess sex differences in disease characteristics and treatment of patients with severe native valvular heart disease (VHD) included in the VHD II EURObservational Research Programme. Methods A total of 5219 patients were enrolled in 208 European and North African centres and followed for 6 months [41.2% aortic stenosis (AS), 5.3% aortic regurgitation (AR), 4.5% mitral stenosis (MS), 21.3% mitral regurgitation (MR), 2.7% isolated right-sided VHD, 24.9% multiple left-sided VHD]. Indications for intervention were considered concordant if corresponding to class I recommendations specified in the 2012 ESC or 2014 AHA/ACC VHD guidelines. Results Overall, women were older, more symptomatic, and presented with a higher EuroSCORE II. Bicuspid aortic valve and AR were more prevalent among men while mitral disease, concomitant tricuspid regurgitation (TR), and AS above age 65 were more prevalent among women. On multivariable regression analysis, concordance with recommended treatment was significantly poorer in women with MS and primary MR (both P <.001). Age, patient refusal, and decline of symptoms after conservative treatment were reported significantly more often as reasons to withhold the intervention in females. Concomitant tricuspid intervention was performed at a similar rate in both sexes although prevalence of significant TR was significantly higher in women. In-hospital and 6-month survival did not differ between sexes. Conclusions (i) Valvular heart disease subtype varied between sexes; (ii) concordance with recommended intervention for MS and primary MR was significantly lower for women; and (iii) survival of men and women was similar at 6 months. [ABSTRACT FROM AUTHOR]

Background: The pathophysiology of heart failure (HF) with preserved ejection fraction (HFpEF) is suggested to be influenced by inflammation. Leukocyte indices, including the neutrophil–lymphocyte ratio (NLR), the monocyte–lymphocyte ratio (MLR), and the pan-immune inflammation value (PIV), can be utilized as biomarkers of systemic inflammation. Their prognostic utility is yet to be fully understood. Methods: Between December 2010 and May 2023, patients presenting to a tertiary referral center for HFpEF were included into a prospective registry. The association of the NLR, MLR, and PIV with the composite endpoint of all-cause mortality and HF-related hospitalization was tested utilizing Cox regression analysis. Results: In total, 479 patients (median 74.3, interquartile range (IQR): 69.22–78.3 years, 27.8% male) were included. Patients were observed for 43 (IQR: 11–70) months, during which a total of 267 (55.7%) patients met the primary endpoint. In a univariate Cox regression analysis, an above-the-median NLR implied a hazard ratio (HR) of 1.76 (95%-confidence interval (CI): 1.38–2.24, p < 0.001), an MLR of 1.46 (95%-CI: 1.14–1.86, p = 0.003), and a PIV of 1.67, 95%-CI: 1.30–2.13, p < 0.001) for the composite endpoint. After adjustment in a step-wise model, the NLR (HR: 1.81, 95%-CI: 1.22–2.69, p = 0.003), the MLR (HR: 1.57, 95%-CI: 1.06–2.34, p = 0.026), and the PIV (HR: 1.64, 95%-CI: 1.10–2.46, p = 0.015) remained significantly associated with the combined endpoint. Conclusions: The NLR, the MLR, and the PIV are simple biomarkers independently associated with outcomes in patients with HFpEF. [ABSTRACT FROM AUTHOR]

Objective: Epicardial adipose tissue (EAT) quantity is associated with poor cardiovascular outcomes. However, the quality of EAT may be of incremental prognostic value. Cardiac magnetic resonance (CMR) is the gold standard for tissue characterization but has never been applied for EAT quality assessment. We aimed to investigate EAT quality measured on CMR T1 mapping as a predictor of poor outcomes in an all‐comer cohort. Methods: We investigated the association of EAT area and EAT T1 times (EAT‐T1) with a composite endpoint of nonfatal myocardial infarction, heart failure hospitalization, and all‐cause death. Results: A total of 966 participants were included (47.2% female; mean age: 58.4 years) in this prospective observational CMR registry. Mean EAT area and EAT‐T1 were 7.3 cm2 and 268 ms, respectively. On linear regression, EAT‐T1 was not associated with markers of obesity, dyslipidemia, or comorbidities such as diabetes (p > 0.05 for all). During a follow‐up of 57.7 months, a total of 280 (29.0%) events occurred. EAT‐T1 was independently associated (adjusted hazard ratio per SD: 1.202; 95% CI: 1.022–1.413; p = 0.026) with the composite endpoint when adjusted for established clinical risk. Conclusions: EAT quality (as assessed via CMR T1 times), but not EAT quantity, is independently associated with a composite endpoint of nonfatal myocardial infarction, heart failure hospitalization, and all‐cause death. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Transcatheter aortic valve replacement (TAVR) has evolved as first-line therapy for severe aortic valve stenosis (AS), with pre-procedural computed tomography (CT) providing critical anatomical information. While primarily used for anatomical planning, TAVR-CT also offers an opportunity to assess low bone mineral density (BMD), a known indicator of frailty. Despite this, the prognostic role of BMD in TAVR patients remains unknown. This study aimed to evaluate BMD on routine TAVR-CT and its impact on long-term survival. Methods: In this retrospective study, 770 consecutive TAVR patients (mean age 80.7 ± 6.7 years, 54.0% males) between November 2015 and March 2022 were included. BMD was measured from a single axial image at the thoracic vertebral level on unenhanced CT scans. Cox regression models assessed the impact of BMD on mortality, and Restricted Cubic Spline models identified potential mortality thresholds. Results: The mean BMD value, as measured on non-contrast CT, was 147.5 ± 5.4 Hounsfield units, demonstrating a noteworthy association with mortality (adjusted hazard ratio per 100 HU decrease: 1.27 [95%CI: 1.01–1.59], p = 0.041). Restricted cubic spline analysis indicated that BMD below 200 HU was linked to a substantial increase in mortality risk. Upon crude Cox regression analysis, every 100 HU decrease was associated with a 32% increase in risk for death (HR 1.32 [95%CI: 1.068–1.65)], p = 0.010). Conclusions: In conclusion, low BMD on TAVR-CT is independently associated with reduced survival, suggesting its potential as a tool for comprehensive frailty assessment and improved risk prediction in TAVR patients. [ABSTRACT FROM AUTHOR]

Aims: Novel ribonucleic acid interference (RNAi) therapeutics such as patisiran and inotersen have been shown to benefit neurologic disease course and quality of life in patients with hereditary transthyretin amyloidosis (ATTRv). We aimed to determine the impact of RNAi therapeutics on myocardial amyloid load using quantitative single photon emission computed tomography/computed tomography (SPECT/CT) imaging in patients with ATTRv-related cardiomyopathy (ATTRv-CM). We furthermore compared them with wild-type ATTR-CM (ATTRwt-CM) patients treated with tafamidis. Methods and results: ATTRv-CM patients underwent [99mTc]-radiolabeled diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) scintigraphy and quantitative SPECT/CT imaging before and after 12 months (IQR: 11.0–12.0) of treatment with RNAi therapeutics (patisiran: n = 5, inotersen: n = 4). RNAi treatment significantly reduced quantitative myocardial uptake as measured by standardised uptake value (SUV) retention index (baseline: 5.09 g/mL vs. follow-up: 3.19 g/mL, p =.028) in ATTRv-CM patients without significant improvement in cardiac function. Tafamidis treatment resulted in a significant reduction in SUV retention index (4.96 g/mL vs. 3.27 g/mL, p <.001) in ATTRwt-CM patients (historical control cohort: n = 40) at follow-up [9.0 months (IQR: 7.0–10.0)] without beneficial impact on cardiac function. Conclusions: RNAi therapeutics significantly reduce quantitative myocardial uptake in ATTRv-CM patients, comparable to tafamidis treatment in ATTRwt-CM patients, without impact on cardiac function. Serial 99mTc-DPD SPECT/CT imaging may be a valuable tool to quantify and monitor response to disease-specific therapies in both ATTRv-CM and ATTRwt-CM. [ABSTRACT FROM AUTHOR]