Abstract Objective The objective of this study is to evaluate the current control of diabetes in patients that have completed contemporary cardiac rehabilitation (CR) programs across Spain, using data from the prospective, multicentre ReCardio national registry. Methods We conducted a prospective, multicentre, cross-sectional registry including consecutive adult patients with ischaemic heart disease (acute coronary syndrome, chronic coronary syndrome, or prior coronary revascularization) who completed a CR program in seven Spanish centres between October 2024 and October 2025. Each centre enrolled the first five consecutive eligible patients attending their discharge visit every month. Data were pseudonymized and captured in a unified web-based platform, enabling structured data entry, semantic interoperability through SNOMED CT, and optional natural-language processing for automated variable extraction. This interim analysis included the first 244 patients. An external independent company performed the statistical analysis. Continuous variables were summarized as mean ± SD or median (IQR), and categorical variables as frequencies and percentages. Paired comparisons between baseline and discharge metrics were conducted using the Wilcoxon paired-samples test. Results Among patients with diabetes (n=53, 21.5%), mean fasting glucose showed no significant change from start of CR to end of CR (116.5 ± 27.1 vs. 117.0 ± 9.3 mg/dL). In the overall cohort, fasting glucose remained within the normal range (99.8 ± 20.1 vs. 99.1 ± 24.6 mg/dL, p = no significant difference). Blood pressure improved during CR, with reductions in both systolic (134.6 ± 17.4 to 123.5 ± 17.3 mmHg) and diastolic values (81.8 ± 9.5 to 74.4 ± 9.5 mmHg). Renal function remained stable, with no significant changes in creatinine (0.9 ± 0.2 at start of CR to 1.1 ± 1.9 mg/dL at end of CR) or in glomerular filtration rate CKD-EPI (93.3±18.0 at start of CR to 91.8±15.0 at end of CR). Among individuals with diabetes, antidiabetic therapy was widely prescribed (89.3%). SGLT2 inhibitors were the most frequently used agents (82.1%), predominantly empagliflozin (37.5%) and dapagliflozin (16.1%). Metformin was prescribed in more than half of diabetic patients (55.4%), followed by GLP-1 receptor agonists (30.4%), primarily semaglutide (21.4%). DPP-4 inhibitors were prescribed in 10.7% of diabetic patients, and insulin in 8.9% of the diabetic population. Conclusions Patients with diabetes completing contemporary CR programs in Spain show good overall glycaemic control, with stable fasting glucose and HbA1c levels throughout the CR program. These findings suggest that while current CR frameworks support maintenance of acceptable diabetes control, further strategies—such as targeted metabolic interventions or closer glucose-focused follow-up—may be required to achieve additional glycaemic optimization within CR pathways.For image description, please refer to the figure legend and surrounding text.

Abstract Background Cardiopulmonary exercise testing (CPET) provides objective assessment of functional capacity, yet remains underused despite potential to guide intervention timing when clinical-imaging discordance exists in valvular heart disease (VHD). Purpose Following the 2025 ESC Guidelines for Management of VHD, which support earlier intervention for severe aortic stenosis, we evaluated whether CPET influences management beyond echocardiographic assessment in severe asymptomatic VHD. Methods We performed a prospective descriptive analysis of 70 consecutive patients with severe asymptomatic VHD undergoing CPET (January-September 2025). Trained cardiologists classified tests as clinically normal/abnormal. Pathological VO2 was defined as peak VO2 ≤80% predicted. VE/VCO2 slope differences between groups were assessed. Results The cohort included 14 patients with mitral regurgitation (MR), 4 with aortic regurgitation (AR), 47 with aortic stenosis (AS; mean aortic valve gradient 46.2±11.4mmHg, aortic valve area 0.81±0.2cm²), 4 with tricuspid regurgitation (TR), and 1 with mitral stenosis (MS). The median age was 70.0 years (Q1 62.5, Q3 76.8), and 41% were female. Overall, CPET results were clinically normal in 64% of patients, abnormal in 32%, and non-conclusive in 4%. Patients with clinically normal tests had significantly lower VE/VCO2 slope (31.0 ± 5.3 %) compared with those with clinically abnormal tests (36.0 ± 5.9 %; p <0.001). Among regurgitant lesions, functional performance was largely preserved: 93% of MR and 100% of AR patients had clinically normal CPETs, with no pathological VO2 values. In contrast, functional capacity was reduced in TR, where only 50% had clinically normal CPETs and 75% displayed a pathological VO2. Among stenotic lesions, AS patients, representing two-thirds of the cohort, showed the lowest functional capacity: 55% had clinically normal CPETs, while 38% were abnormal. 57% of AS patients had a pathological VO2 ≤80% of predicted. The single MS patients had a clinically abnormal CPET but displayed a normal VO2. After CPET, the management plan changed in 24% of patients, predominantly shifting from conservative to interventional approaches, most notably in AS. Conclusions In this prospective case series of 70 patients with severe asymptomatic VHD, CPET provided objective physiological insight and guided intervention decisions through individualized assessment of patient performance, influencing management in nearly one in four patients. The test was particularly informative in severe AS, where it confirmed functional limitation and supported early intervention. The observed discrepancy between clinically normal CPETs and pathological VO2 values underscores the need to define which CPET parameters should serve as key pathological thresholds in this population, as some patients with apparently normal exercise responses may still demonstrate subclinical functional impairment.For image description, please refer to the figure legend and surrounding text. For image description, please refer to the figure legend and surrounding text.

Abstract Objective The objective of this study is to evaluate the clinical characteristics and body composition profile of patients completing contemporary cardiac rehabilitation (CR) programs across Spain, using data from the prospective, multicentre ReCardio national registry. Methods We conducted a prospective, multicentre, cross-sectional registry including consecutive adult patients with ischaemic heart disease (acute coronary syndrome, chronic coronary syndrome, or prior coronary revascularization) who completed a CR program in seven Spanish centres between October 2024 and October 2025. Each centre enrolled the first five consecutive eligible patients attending their discharge visit every month. Data were pseudonymized and captured in a unified web-based platform (NaeviaMedical®), enabling structured data entry, semantic interoperability through SNOMED CT, and optional natural-language processing for automated variable extraction. This interim analysis included the first 244 patients. An external independent company performed the statistical analysis. Continuous variables were summarized as mean ± SD or median (IQR), and categorical variables as frequencies and percentages. Paired comparisons between baseline and discharge metrics were conducted using the Wilcoxon paired-samples test. Results Our findings show significant improvements across all evaluated body composition parameters. Mean body weight decreased from 82 ± 14 kg at baseline to 80 ± 13 kg at discharge (–1.9 kg, p < 0.001), paralleled by a reduction in BMI from 28.9 ± 4.5 to 28.2 ± 4.1 kg/m² (–0.63 kg/m², p < 0.001). Waist circumference also improved, decreasing from 102.8 ± 17 cm to 99.1 ± 11 cm (–3.6 cm, p < 0.001). Body fat percentage declined as well, from 30.8 ± 9.4% to 28.6 ± 8.7% (–2.2%, p < 0.001). Despite these positive changes in body composition, 30% of patients remained with a BMI > 30 kg/m². Only 9.3% of our population was receiving treatment with GLP-1 receptor agonists. This finding underscores a meaningful opportunity for improvement and highlights the need for extended follow-up to optimize obesity management in Phase III CR. Conclusions CR programs evaluated in Spain, enabled patients to significantly improve their body composition, underscoring the value of CR as a comprehensive tool for achieving weight-management goals as a cornerstone of secondary prevention in patients with ischaemic heart disease.For image description, please refer to the figure legend and surrounding text. For image description, please refer to the figure legend and surrounding text.

Abstract Objective The objective of this study is to evaluate the clinical characteristics and changes in functional capacity of patients completing contemporary cardiac rehabilitation (CR) programs across Spain, using data from the prospective, multicentre ReCardio national registry. Methods We conducted a prospective, multicentre, cross-sectional registry including consecutive adult patients with ischaemic heart disease (acute coronary syndrome, chronic coronary syndrome, or prior coronary revascularization) who completed a CR program in seven Spanish centres between October 2024 and October 2025. Each centre enrolled the first five consecutive eligible patients attending their discharge visit every month. Data were pseudonymized and captured in a unified web-based platform, enabling structured data entry, semantic interoperability through SNOMED CT, and optional natural-language processing for automated variable extraction. This interim analysis included 77 patients that performed a cardiopulmonary exercise test. An external independent company performed the statistical analysis. Continuous variables were summarized as mean ± SD or median (IQR), and categorical variables as frequencies and percentages. Paired comparisons between baseline and discharge metrics were conducted using the Wilcoxon paired-samples test. Results Participation in a comprehensive CR program resulted in significant improvements in functional capacity. Mean peak oxygen consumption (VO2 peak) increased from 23.4 ± 5.8 at start of CR to 25.6 ± 6.1 ml/kg/min at end of CR, reflecting a mean gain of +2.1 ml/kg/min (p < 0.001). This gain is equivalent to nearly 1 MET, representing a clinically relevant enhancement in aerobic capacity. The percentage of predicted VO2 also improved significantly, rising from 97.4 ± 21.0% at start of CR to 102.0 ± 25.1% at end of CR (mean change +4.6%, p < 0.001). Among patients who began CR with a predicted VO2 <80%, 50% improved above this threshold at end of CR, highlighting the capacity of CR programs to reverse low-baseline functional performance. RER and VE/VCO2 slope values were recorded at both time points, with trends indicating physiological improvement, although between-time differences did not reach statistical significance. Conclusions Patients participating in contemporary CR programs in Spain already show a generally preserved baseline functional capacity as assessed by VO2 peak during maximal cardiopulmonary exercise testing at start of CR. Despite these favourable starting values, participation in a comprehensive, exercise-based CR program was associated with additional clinically meaningful improvements in aerobic fitness, including an improvement in VO2 peak approaching 1 MET at end of CR. These results highlight the sustained value of exercise based CR in enhancing functional capacity even among patients with good initial performance.For image description, please refer to the figure legend and surrounding text.

Abstract Objective The objective of this study is to evaluate the clinical characteristics and lipid control of patients completing contemporary cardiac rehabilitation (CR) programs across Spain, using data from the prospective, multicentre ReCardio national registry. Methods We conducted a prospective, multicentre, cross-sectional registry including consecutive adult patients with ischaemic heart disease (acute coronary syndrome, chronic coronary syndrome, or prior coronary revascularization) who completed a cardiac rehabilitation program in seven participating Spanish centres between October 2024 and October 2025. Baseline data at start of CR (such as total cholesterol) refers to the recorded value upon first visit to CR, that is, after the patient has been discharged from hospital and medical treatment has been optimised post acute event of ischaemic heart disease. Results A total of 244 patients were included in the study, of whom 82% were male, with a mean age of 61.3 ± 10.3 years. Contact with tobacco was reported in 67% of the cohort. 94% presented with acute coronary syndrome, comprising 53% with STEMI and 40% with NSTEMI. 56% of patients had hypertension, 24% had diabetes mellitus, and 26% had pre-diabetes. Dyslipidaemia was present in 84% of patients, 20% had a normal body mass index (BMI 18.5–24.9 kg/m²), 50% were overweight (BMI 25–29.9 kg/m²), and 30% were classified as obese (BMI > 30 kg/m²). Significant improvements in lipid parameters were observed during the cardiac rehabilitation (CR) program. Mean total cholesterol decreased from 141.8 ± 48.9 mg/dL at start of CR to 113.8 ± 21.9 mg/dL, corresponding to a mean reduction of −28.0 ± 51.4 mg/dL, (p < 0.001). Median LDL cholesterol dropped from 70.5 mg/dL (Q1–Q3: 46.5–114.2) at start of CR to 52.0 mg/dL (Q1–Q3: 41.2–60.0) at end of CR. The median change was −12.9 mg/dL (Q1–Q3: −60.7 to −0.2), (p < 0.001). Triglycerides also improved, decreasing from a mean of 123.9 ± 50.7 mg/dL at start of CR to 101.2 ± 78.8 mg/dL at end of CR, with a mean reduction of −22.6 ± 70.4 mg/dL, (p < 0.001). Lipoprotein(a), measured in mg/dL had a median concentration of 31.5 mg/dL (IQR 73), of which 40.4% were over 50mg/dL. Lipoprotein (a) values measured in nmol/L were 85 nmol/L (IQR 157.2), of which 32.7% had values above 150 nmol/L. At the end of the CR program, the vast majority of patients were receiving intensive lipid-lowering therapy. Statins were prescribed in 96% of the cohort, and ezetimibe in 83%. Additional lipid-modifying agents included, icosapent ethyl in 5%, PCSK9 inhibitors in 4% of patients, and inclisiran in 1%. Conclusions This preliminary assessment of a contemporary cohort of patients that participate in CR in Spain, shows a significant improvement in lipid profile, underscoring the value of CR as a comprehensive tool for achieving lipid-management goals and optimizing treatment in patients with ischaemic heart disease. The use of new lipid lowering therapies remains low.For image description, please refer to the figure legend and surrounding text. For image description, please refer to the figure legend and surrounding text.

Abstract Background eHealth solutions may optimize personalized care and support disease management for patients with coronary artery disease (CAD) throughout the course of the condition. TIMELY is the first artificial intelligence (AI)-driven eHealth approach based on cardiac rehabilitation (CR) components and integrated with Internet of Things (IoT) devices. Purpose To report the primary outcome of the TIMELY RCT. Methods TIMELY is a multicenter RCT (Germany, Spain, The Netherlands) involving 360 CAD patients. Patients randomized to the intervention group (IG, n=180) received a 6-month, app-based, behavior change program, as part of their CR aftercare (phase III CR). Patients in the control group (CG) received care as usual. Assessments were performed at baseline, 6, and 12 months. The TIMELY platform and app provide support for behavior change and self-management. TIMELY integrates clinical and psychosocial data, evaluates risk, and supports healthy behaviors via app-based feedback and prompts. Engagement in physical activity is supported by a chatbot and personalized exercise prescription based on weekly activity profiles. Ecological Momentary Assessment (EMA) is used. Patients were equipped with an activity tracker, BP monitor, and a 3-channel Holter monitor connected to the integrative platform using a cloud computing environment. AI in TIMELY is primarily used to optimize prediction of CAD risk and behavior. Data are provided in a dashboard to case managers supporting patients. Primary outcomes were changed 1) mortality risk (via composite biomarker score), 2) 6-minute walking test (6MWT) distance. Secondary outcomes included physical fitness, physical activity, dietary habits, body weight, smoking cessation, medication adherence, and psychological stress. Results Patients’ mean age was 60.5±9.2 years, 34% had experienced MI, ~21% were women. At 6 months, 161 (89%) and 156 (87%) patients were assessed for the primary outcome in the IG and CG, respectively. Severe adverse events (n=28) were unrelated to the intervention. In the intention-to-treat analysis, no significant difference between the groups was seen for the tested outcomes. The per-protocol (PP) analysis revealed that the IG sustained a significant ~7% better mean performance in the 6MWT over 12 months (IG=567.5±90.3 m, CG=529.6±111.7 m; p<0.05). The IG also showed larger improvements in physical fitness (PP, time×group p=0.027), with higher values at 6 months (IG=144.5±39.6 W, CG=130.9±44.0 W) and 12 months (IG=141.9±45.2 W, CG=130.3±45.2 W). A significant group difference was also seen for medication adherence (MARS-5 Score) which remained higher in the IG at 12 months (PP, time×group p=0.0071). No other significant differences in secondary outcomes were detected. Conclusions The AI-driven eHealth intervention TIMELY offers personalized support for CAD patients during phase III CR and shows potential specifically in terms of improving physical exercise capacity.TIMELYFor image description, please refer to the figure legend and surrounding text.

Aortic stenosis (AS) is the most prevalent valvular disease requiring intervention. While therapeutic options have expanded, clinical decision-making is challenged by the diversity of patients’ profiles. Existing risk models often fail to account for population-specific factors and healthcare system variations. Developing predictive models tailored to specific populations and focused on robust endpoints may improve treatment decision-making. To develop an easy-to-use predictive model for overall mortality in patients with severe AS, integrating patient characteristics and possible therapeutic approaches based on a prospective AS cohort. This prospective observational study included patients with severe AS enrolled in the AS Integrated Care Process at a tertiary hospital in Spain from 2018 to 2022, with follow-up data updated to November 2024 (PROCEAS cohort). Clinical, echocardiographic and laboratory parameters were analysed alongside with treatment modality and clinical outcomes. A stratified cox proportional hazards model was elaborated to predict overall mortality (dependant variable). Patients were categorized into three subgroups based on treatment type: surgical or transcatheter (TAVR) valve replacement or conservative. Initially, only candidate variables meeting the proportional hazard’s assumption across all subgroups were included in a first stratified Cox model. The best possible model was then selected on the basis of Akaike information criterion (AIC). The performance of the model was evaluated using the area under the receiver operating characteristic curve (AUC). The PROCEAS cohort comprised 988 patients, of whom 984 were included in the final analysis (mean age: 77±8.4 years; 42.2% female). Treatment distribution was as follows: surgery in 432 patients, TAVR in 490 patients, and conservative in 62 patients. Overall mortality was 26.8% during a mean follow-up of 39±19.4 months, highest in the conservative group, followed by TAVR and surgery (p<0.0001). Five relevant predictors were included in the treatment-stratified final cox model: diabetes mellitus, atrial fibrillation, cardiac damage stage in AS (as defined by Généreux et al.), sex, and age (Table 1). A nomogram was elaborated to facilitate clinical application, providing individualized 1-year and 2-year mortality risk estimates based on treatment strategy (Figure 2). Model performance metrics showed an AUC of 0.69 for 1-year mortality (sensitivity: 57%, specificity: 76%) and 0.72 for 2-year mortality (sensitivity: 70%, specificity: 65%). This study presents a pilot clinically applicable predictive model for overall mortality in severe AS patients, depending on the treatment modality. The PROCEAS nomogram may aid personalised risk assessment and guide therapeutic decisions in a Spanish population. External validation is needed to confirm broader applicability. Figure 1.PROCEAS Mortality risk nomogram

The knowledge-based clinical decision support system (CDSS) used in this study provides diagnostic and therapeutic recommendations based on patient’s clinical data. It relies on an expert system of clinical rules that are modelled, validated, and peer-reviewed by healthcare professionals based on reliable knowledge sources. Clinical validation of CDSS is crucial to assess their accuracy, reliability, and potential impact on patient outcomes. To assess the clinical benefit of this CDSS in patients with valvular heart disease (VHD), by evaluating its ability to increase the number of appropriate clinical recommendations and reduce the number of the inappropriate or missing relevant recommendations compared to conventional management. The CDSS product for VHD includes 4122 rules derived from 64 internationally recognised knowledge sources. A clinical validation study was conducted using a pre-test-post-test design with longitudinal repeated measures. A total of 106 clinical cases of aortic stenosis, aortic insufficiency, mitral stenosis, mitral insufficiency and tricuspid insufficiency were selected from a tertiary hospital database through stratified random sampling. Conventional clinical management was retrospectively assessed by a panel of three cardiologist experts using updated clinical guidelines, who labelled clinical decisions as appropriate or inappropriate and identified the missing relevant ones. Assessments were conducted at baseline (conventional management) and after CDSS activation across 4 domains: short-term and long-term diagnostic plans (STD and LTD), cardiological medical treatment (CMT), and indicated therapeutic interventions (ITI). The experts rated their agreement with the CDSS suggestions on a 5-level Likert scale, with higher scores indicating stronger agreement. Following CDSS activation, the average number of appropriate recommendations significantly increased (6.20 vs. 2.35, p<0.001), and the number of inappropriate and missing relevant ones significantly decreased (0.07 vs 0.29, p<0.01 and 0.49 vs 3.80, p<0.001, respectively; 0.49 vs 3.80, p<0.001 when pooled together) (Fig. 1). Experts’ agreement with the CDSS was very high, with mean Likert scale scores above 4 in all domains (STD: 4.53, LTD: 4.68, CMT: 4.58, ITI: 4.62). The probability of strong agreement (score 5) was significantly higher than for any other rating category (z.ratio (5|1)=30.88, p-value <0.001, z.ratio (5|2)=31.67, p-value <0.001, z.ratio (5|3)=30.21, p-value <0.001, z.ratio (5|4)=22.54, p-value <0.001). The CDSS demonstrated a significant clinical benefit by increasing the number of appropriate clinical recommendations while reducing inappropriate and missing relevant ones compared to conventional management. Cardiologist experts showed a high level of agreement with the CDSS, underscoring its potential as a reliable decision-support tool for clinicians in managing VHD.Assessment before and after CDSS support

Abstract Background and Purpose A longitudinal strain pattern characterized by apical sparing (RELAPS>1) has been identified as indicative of cardiac amyloidosis (CA). We conducted an analysis to assess its diagnostic accuracy in individuals with severe aortic stenosis (AS) and explored novel echocardiographic variables for predictive value. Methods All patients diagnosed with AS who underwent transcatheter aortic valve implantation (TAVI) were prospectively enrolled. 2D-Speckle-tracking echocardiography was utilized to assess myocardial deformation parameters. Subsequent to TAVI, screening for CA was conducted through 99mTc-DPD scintigraphy and protein electrophoresis. Results A total of 324 patients were included (mean age 81.5 ± 5.8 years, 51% women). Among them, 38 individuals (11.7%) exhibited cardiac uptake in scintigraphy: 14 patients (4.3%) with grade 1, 13(4%) grade 2, and 11(3.4%) grade 3. RELAPS>1 was more prevalent in patients with AS-CA (74%vs.44%,p=0.006). We propose an echocardiographic prediction model (GRAM score) for CA in the context of AS that is more sensitive and specific than RELAPS >1 alone. This model incorporates the left ventricular mass index, maximum transvalvular aortic pressure gradient, RELAPS>1, and age (AUC: 0.85, 95% CI: 0.77–0.93). Conclusions While RELAPS >1 is more commonly observed in individuals with AS-CA, it is noteworthy that this pattern can also manifest in nearly half of AS patients without CA, diminishing its utility as a standalone screening tool. In light of this, our study puts forth a more sensitive and specific prediction score for identifying CA in patients with severe AS.GRAM score for predicting AS-CA

Abstract Background/Introduction Exercise-based cardiac rehabilitation (CR) is an integral component in the management of coronary artery disease (CAD). While the efficacy of CR in reducing cardiovascular mortality and hospitalizations is well-established, challenges persist in the individualization of guideline-based exercise (re-)prescriptions. Decision Support Systems (DSS) may assist cardiologists and general practitioners (GPs), in particular during phase III CR maintenance, to prescribe effective exercise programs to CAD patients. Purpose To develop a tool that enables GPs and other healthcare professionals (HPs) to generate informed, safe, and personalized exercise prescriptions based on current ESC guidelines for CAD patients in phase III CR. Methods Within the scope of the EU-funded project "TIMELY", we have developed the Rule-Based Exercise Prescription Tool (REPT), a DSS aligned with the ESC Guidelines on Exercise Prescription. A Knowledge Base (KB) was generated based on extracted rules from textual guidelines. The system integrated 112 rules, encoded, and organized to be both human-readable and machine-interpretable to facilitate active participation, extensibility, and error-proofing by HPs involved in the system's design using a Delphi approach. Since various medical conditions, comorbidities and medication need to be considered, REPT was split into two functionalities: the Permissibility Report (PR), generating a report with patient-specific exercise limitations based on medical history, and the Exercise Prescription (EP) which formulates weekly exercise plans tailored to these limitations. The programmed REPT algorithm includes a compilation of activated rules, the tabulation of PRs, and the parameter-level comparison. A representative sample of 12 patients was used to generate PRs and EPs, which were evaluated by HPs from four different countries. Results Upon input of patient data, the PR automatically generates permissible exercise volume, cautionary insights, suitable sports disciplines, and proficiency levels. The EP functionality suggests an initial exercise program and weekly progressions, considering limitations from the PR. Activity calories are used to define weekly goals. The output is a comprehensive report for endurance and resistance exercise according to the FITT criteria, encompassing minimum/maximum values for weekly frequency, intensity, and duration. The REPT was implemented in a remotely operated integrative care platform to produce a PR to health care professionals. HPs completely/mostly agreed with generated PRs and EPs in terms of safety and guideline consistency (95%) and indicated usability in real life (84%). Conclusion REPT is a safe and useful DSS to assist cardiologists and GPs to bring guideline-based and individualized exercise prescription to CAD patients during phase III CR. Its implementation could help to improve secondary prevention in CAD patients across Europe.

Prior research indicates PTSD is associated with cardiovascular and metabolic disease. A number of different treatments for PTSD can be effective in reducing PTSD symptoms. The aim of this study is to systematically review studies which determine whether treatment for PTSD is associated with better cardiovascular and metabolic outcomes.Five different databases were searched in a systematic manner, and 11 relevant studies were recovered and analyzed.Treatments associated with PTSD improvement and found to be effective in improving cardiovascular or metabolic outcomes among individuals with PTSD include cognitive behavioral therapy (heart rate variability and blood pressure), prolonged exposure (heart rate and heart rate variability) and SSRIs (blood pressure).Multiple PTSD treatment modalities were associated with improved cardiovascular health and reduced risk of cardiovascular-related mortality. Given the small sample sizes, lack of follow-up studies and the extensive use of military populations in studies on PTSD and chronic diseases, these results should be interpreted with caution. More studies are needed that assess and verify whether PTSD treatments mitigate the risk for metabolic, diabetic and cardiovascular disease.

Abstract Background Longitudinal Strain (LS) pattern in cardiac amyloidosis (CA) typically spares the apex of the heart, which is a sensitive and specific finding that can be used to distinguish CA from other causes of left ventricular (LV) hypertrophy. RELAPS >1 suggests with high specificity CA, and shows a bright red in the apical segments of the polar map. Purpose To identify differential echocardiographic characteristics of aortic stenosis (AS) with concomitant TTR-CA (AS-CA) compared to AS alone. Methods Patients with severe symptomatic AS undergoing TAVI were prospectively and consecutively included between Jan-19 and Dec-20. Pre-procedure, a complete echocardiogram was performed that included deformation parameters using Speckle-Tracking. Strain derived Indices accepted for CA screening were calculated: RELAPS: relative apical LS (average apical LS/average basal+mid LS); SAB: (apical-septal/basal-septal LS); EFSR: (LVEF/GLS). After TAVI, a 99Tc-DPD scintigraphy and a proteinogram were performed to screen for CA. Results 324 patients were included. The mean age was 81 yo, 52% women. 39 (12%) patients presented cardiac uptake on scintigraphy: 14 (4.3%) grade 1; 13 (4%) grade 2, and 11 (3.4%) grade 3. Strain analysis could be performed in 243 patients due to acoustic window and covid19 pandemic restrictions. Echocardiographic characteristics between AS alone and those with grade 1 (AS-DTD1) and grade 2/3 (AS-CA) are shown in Table 1. Compared with AS alone, patients with AS-CA had significantly lower transvalvular gradients, although similar AVA, and low flow-low gradient (LF-LG) AS was more prevalent. AS-CA exhibited slightly worse cardiac remodeling (LV mass ind: 202 g/m2 vs 176 g/m2, p=0.032), and worse diastolic dysfunction, but without significant differences in thickness, diameters or volumes, with similar relative wall thickness (RWT: 0.53 vs. 0.51 mm, p=0.52). LVEF was similar, however myocardial contraction fraction (MCF= stroke volume/myocardial volume) and MAPSE were worse in AS-CA. GLS, RELAPS, SAB and EFSR were not different, but RELAPS >1 pattern was more prevalent in AS-CA (74% vs 44%, p=0,006) (Figure 1). Mass/strain ratio (RMS) was similar. There were no differences in size and fractional emptying of left atrium, or atrial septum thickness. Right ventricle (RV) size was similar, as well as conventional function parameters (TAPSE and S'). However, RV LS was worse in AS-CA. Pericardial effusion was more prevalent in AS-CA (25% vs 7.4%, p=0.013). In the multivariate analysis, predictors of AS-CA were: age (OR: 1,2, p=0,02), BG (OR: 0,2, p=0,01), E/A (OR: 4,7, p=0,02), LV Mass index (OR: 1,02, p=0,04) and RELAPS >1 (OR: 0,12, p=0,01). Conclusion Dual pathology of AS-AC is common in older patients referred for TAVI. Although it is more prevalent in patients with AS-CA, RELAPS>1 pattern can be present in almost 50% of patients with severe AS alone, which reduces its value as screening tool for CA in this clinical setting respect to others. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Pfizer Table 1. Echocardiographic parameters Figsure 1. LV Longitudinal strain RELAPS phenotype

Abstract Background The impact of the COVID-19 pandemic on multimodal cardiac rehabilitation (CR) programmes has forced a continuous readjustment of clinical practice. Our regional healthcare system was faced with providing quality remote CR to ischaemic heart disease (IHD) patients in a scattered, mostly rural population, for which three new CR modalities replaced the previous in-person CR program: 1) telephone follow-up programme, 2) TELEA online platform for patient follow-up and 3) TELEA online follow-up & online training sessions. Purpose To study the impact of the COVID-19 pandemic on CR offering and acceptance and the reasons for patient refusal, and to assess the outcome of new remote CR modalities in this setting. Methods Single center, observational retrospective study from all consecutive patients with IHD eligible for CR from 2015 to 2021. A descriptive analysis of patient baseline characteristics, CR modality, offering and acceptance rates, and reasons for refusal per year was performed. Additionally, a comparative analysis of “pre-COVID period” (Jan 2015–Feb 2020) vs. “COVID period” (Mar 2020–Dec 2021) was performed to assess the impact of the pandemic on patient recruitment and the usefulness of remote CR modalities to enhance participation. Results N=2626 patients (20% women, 69.7±45.8 years) were offered CR from 2015 to 2021. CR offering decreased from the pre-COVID (78.6%) to the COVID period (52.6%), while participation increased (67.9% and 79.7%, respectively) Figure 1. Reasons for CR refusal significantly changed with an odds ratio (OR) of 5.63 and confidence interval (CI) 95% (3.2–9.9). In the pre-COVID period main reasons for CR refusal was “transportation difficulties” (47%); while during the COVID-19 period, the main reason shifted to “lack of interest” (78.2%) (Table 1). Conclusions Offering CR decreased during the COVID pandemic possibly due to stricter inclusion criteria. However, the implementation of new remote CR modalities allowed not only to maintain similar levels of acceptance but also to improve it despite the unfavourable setting, and helped to amend transportation difficulties as the leading reason for refusal. Remote CR may be a useful tool, combined with in-person programs, to enhance participation in CR. Funding Acknowledgement Type of funding sources: None.

Abstract Introduction Coronary artery disease (CAD) may progress to left ventricular dysfunction (LVD) and chronic heart failure. A reduced ventilatory efficiency in these patients is associated with worse outcome. However, breathing patterns at rest and during exercise and their change during exercise-based cardiac rehabilitation (exCR) have been poorly described in this population. We aimed to analyse respiratory and gas-exchange parameters in elderly patients with CAD included in a multicentre study on effectiveness of exCR across seven European countries (EU-CaRE). Methods Patients aged 65 years and older with acute (ACS) and chronic coronary syndromes (CCS) who participated in exCR were included. Cardiopulmonary exercise testing (CPET) was performed before (T0) and at termination of exCR (T1), and 12 months after start of exCR (T2). Ventilation (VE), breathing frequency (BF), and end-expiratory carbon dioxide pressure (PetCO2) were measured at rest, at first ventilatory threshold and peak exercise. Ventilatory efficiency, expressed as VE/VCO2 slope and the nadir of VE/VCO2 ratio were measured during the ramp test. Peak oxygen uptake was averaged over 30 s. Breathing parameters over time were compared between patients without and with left ventricular dysfunction (LVD, defined as LV ejection fraction <45%) by mixed linear models corrected for age, sex and body mass index. Results 818 out of 1633 patients of the EU-CaRE study fulfilled inclusion criteria, 151 (18%) had LVD, of these, 86% were in New York Heart Association (NYHA) functional class I. Mean age was 72.5±5.4 years, 21.9% were women, and 79.8% had acute ACS. Compared to patients without LVD, in patients with LVD resting VE was increased 9%, VE/VCO2 slope 14%, and nadir VE/VCO2 ratio 9%, while PetCO2 was reduced at rest and peak exercise by 6%. From before to after exCR, resting ventilation and breathing frequency, as well as VE/VCO2 slope and nadir VE/VCO2 during exercise decreased significantly more in patients with LVD compared to patients without, while improvement in peak oxygen uptake was similar (Figure 1). Conclusions In contrast to their own perception based on NYHA class, patients with LVD had exaggerated breathing at rest and as response to exercise with consistently reduced PetCO2 and ventilatory efficiency. Abnormal breathing patterns may be an early and clinically relevant sign of LVD and linked to increased chemosensitivity and/or abnormal ergoreflex. Exercise-based CR may contribute to improvements of breathing patterns and ventilator efficiency in this population. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Union's Horizon 2020 research and innovation program and Swiss State Secretariat for Education, Research and Innovation for the Swiss consortium partner

Abstract Background Knowledge-based clinical decision support systems (CDSS) are technological tools that analyze patient information and present justified diagnostic and therapeutic suggestions to the user. They improve adherence to evidence-based medicine and reduce medical errors. Material and methods We have developed an advanced CDSS with the following components: 1. Knowledge Management System, which allows the introduction of interoperable clinical variables organized in taxonomies, and the generation, validation and direct maintenance of decision rules by experts doctors. 2. Smart Assistant for Medical Reports Generation, which facilitates user interaction for the introduction of clinical data (natural language and/or data entry forms) and decission making supported by real-time suggestions that are automatically generated by 3. Inference Engine. Rules and variables derived from the most relevant cardiovascular Clinical Practice Guidelines (CPGs) are introduced by cardiologists into the system. The rules undergo a process of peer review and internal and external validation with anonymized clinical cases. Results More than 2,000 clinical variables and more than 5,000 rules corresponding to more than 80 CPGs and consensuns papers have been created and validated. An internal and external pilot validation of the system has been successfully carried out for the main cardiovascular problems, such as heart failure, atrial fibrillation, valvulopathies, coronary syndromes, cardiomyopathies, hypertension, diabetes and dyslipidaemias, using more than 400 cases. Conclusion Our CDSS is capable of providing real-time diagnostic and therapeutic recommendations for complex scenarios in cardiovascular disease, combining thousands of variables and decision rules in a single system. Prospective evaluation of the system in real clinical environments, certification and integration in Electronic Medical Records for clinical use is required. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): DILEMMA solutions, SL

Abstract Background Improvement in functional capacity (FC) is one of the most notable benefits patients experience after cardiac rehabilitation (CR) and it is highly important as low levels of FC are associated with a high risk of cardiovascular (CV) disease and all cause mortality. Purpose To study the changes in FC after a CR program in Spain and to define the profile of those patients that improve. Methods Single-centre observational study from 793 patients with ischaemic heart disease (15.3% women, age 61.79±10.70 years), participating in a CR program from 2015 to 2020 with a stress test performed, both at beginning of CR (conventional stress test, n=436; CPET, n=340; imaging stress test, n=17) and at end of CR (conventional stress test, n=468; CPET, n=322; imaging stress test, n=3). A comparative analysis of patients with “improved FC” and “non-improved FC” at end of CR, was performed. Relevant clinical improvement was defined as a 10% increase of VO2, in accordance with reviewed literature. Additionally, a descriptive analysis of patient exercise capacity parameters was performed at beginning of CR and at end CR, for the complete sample. Results A total of 1586 exercise tests were analysed. All exercise capacity parameters analysed showed significant improvement at end of CR, with p values <0.01, (Graph 1). Clinically relevant FC improvement was observed in 54.2% of patients that participated in CR; 45.5% of all women and 55.8% of all men. Patients that improved FC completed significantly more CR training sessions (p<0.05) than those who did not improve FC (21.39±4.53, 20.37±5.84). Those who improved FC were significantly older (62.74±10.90), presented with significantly more STEMI (n=197, 45.8%), and achieved significantly less METS (7.42±3.01) at baseline, (p<0.05, Table 1). Conclusions Our CR rehabilitation program improves patient's functional capacity significantly. Patients with clinically relevant functional capacity improvement, are significantly older patients with STEMI as diagnosis at CV event, complete significantly more CR training sessions and showed significantly worst physical performance (METS) at baseline. Funding Acknowledgement Type of funding sources: None.

Abstract Background A lot of studies have shown a positive effect of transcatheter aortic valve implantation (TAVI) on left ventricular ejection fraction (LVEF). However, the association between long-term outcomes and LVEF recovery after TAVI has not yet been well investigated. Purpose To detect differences in long-term all cause mortality between patients who recover LVEF at six mounths after TAVI and those who do not. Methods This is a retrospective, single-center study of 1092 patients undergoing TAVI. LVEF was determined before the intervention and at 6 months. The primary outcome was long-term all-cause mortality. Left ventricular dysfunction was defined as LVEF <50% and recovered LVEF as LVEF >50%. Results Of the 1.092 patients included, 250 (22.8%) had LVD. Of these, adequate follow-up was only achieved in 188, which were the ones included in the analysis. At 6 months, 86 patients (45.7%) had RLVEF. Table 1 shows the baseline characteristics of patients with RLVEF versus those who did not. No significant differences were found between the two groups in terms of comorbidity, procedural complications, or discharge therapy. There were no differences in baseline LVEF or severity of aortic valve disease, although the transaortic peak gradient (63.9±15.6 vs 73.6±19.7; p=0.019) and transaortic mean peak gradient (38.7±11.2 vs 45±12.7; P=0.026) were significantly higher in the RLVEF group. On the other hand, the group where the LVEF did not recover presented a higher percentage of moderate-severe mitral regurgitation (MR) (25.4 vs 8.1; p=0.005). These data could explain a more advanced state of cardiomyopathy and be an explanation for the different evolution of LVEF. In the multivariate analysis, only moderate-severe MR was associated as a predictor of non-recovery of LVEF after TAVI (HR 1.12; (1.09–1.45); p=0.023). During follow-up RLVEF was associated with a reduction in long-term all-cause mortality (p<0.001) (Figure 1) Conclusions Up to 25% of patients undergoing TAVI have baseline LVD. Of these, almost half recover it within six months. Patients who recover LVEF have a significant reduction in mortality in the medium term. The presence of a moderate-severe MR was associated with the non-recovery of LVEF after TAVI, probably because it was a more advanced cardiomyopathy. Funding Acknowledgement Type of funding sources: None.

Abstract Background Cigarette smoking is a major cardiovascular (CV) risk factor and aids to the development and progression of CV disease. Purpose To study the prevalence of smoking in a contemporary Spanish cardiac rehabilitation (CR) cohort, study changes in smoking status over time and define smoker's profile after CR. Methods Single-centre, observational retrospective study from all consecutive patients with ischaemic heart disease (n=1379, 6.6% women, age 65.78±11.02 years) that participated in a CR program from 2015 to 2020. Prevalence of smokers was studied over time, from CV event to 6 months after end of CR, including a stratified description of smokers per age group at CV event. Additionally, a comparative analysis of patient profile for those who continued smoking and patients that quitted smoking after CR, was performed. Results N=516 patients (37.4%) were active smokers at CV event, including 72 women (31% of all women) and 444 men (38.6% of all men). Highest percentage of smokers was distributed among the youngest age groups: with a 72.6% prevalence among those aged <45 years and 57.9% among those aged 45–55 years. Smoking prevalence decreased with age. Also, there were less female than male smokers in all analysed age groups (Figure 1). At the beginning of CR, the global proportion of active smokers decreased significantly (p<0.01) to a 15.3% (n=210) and continued to significantly decrease at end of CR (10%, n=124), maintaining similar levels at 6 months follow-up (9.9%, n=96). 58% of active smokers at CV event quitted smoking by end of CR. Ongoing smokers were significantly more (p<0.05) depressed (n=20, 16.3%); and had significantly worse (p<0.05) HADS scores at beginning of CR (anxiety: 6.49±3.98, depression: 5.41±4.46), Table 1. Conclusions Smoking is nowadays still highly prevalent among CR patients in our setting, especially among young men. Despite a significant fall in the prevalence of smokers after the end of the CR program, there is a non-negligible percentage of patients that keep smoking. Targeted smoking cessation interventions should be aimed at smokers that have more depression and have worse HADS scores at baseline. Funding Acknowledgement Type of funding sources: None.

Abstract Introduction It is estimated that 15% of patients with AS have concomitant cardiac amyloidosis (CA). Left ventricular (LV) longitudinal strain (LS) pattern with relative apical sparing (RELAPS>1), shown as bright red in the apical segments on the polar map, has been strongly associated with CA. Its presence and its significance in AS is yet to be determined. Purpose To determine the prevalence of the RELAPS>1 pattern in patients with severe AS with and without concomitant CA, and to analyze the echocardiographic phenotype associated with this strain pattern and its prognostic value. Methods Patients with severe symptomatic AS undergoing TAVI were prospectively and consecutively included between Jan-19 and Dec-20. Pre-procedure, a complete echocardiogram was performed that included deformation parameters using Speckle-Tracking. Strain derived Indices accepted for CA screening were calculated: RELAPS: relative apical LS (average apical LS/average basal+mid LS); SAB: (apical-septal/basal-septal LS); EFSR: (LVEF/GLS). After TAVI, a 99Tc-PYP scintigraphy and a proteinogram were performed to screen for CA. Results 324 patients were included. The mean age was 81 yo, 52% women. Strain analysis could be performed in 243 patients due to acoustic window and covid19 pandemic restrictions. Among those, 111 (46%) presented relative apical sparing (RELAPS>1). There were no differences in clinical characteristics between patients with RELAPS <1 and >1: similar age, sex, cardiovascular risk factors and funcional class, renal function or NT-proBNP. Among patients with RELAPS>1 there was more frecuently CA with uptake grade 2 and 3 on scintigraphy (15% vs. 4.5%, P=0.006) (Figure 1). RELAPS>1 group showed greater LV hypertrophic remodeling: thicker myocardial wall with smaller ventricular cavity, especially concentric hypertrophy; LVEF and GLS was similar, however, MAPSE and myocardial contraction fraction (MCF) were worse in RELAPS >1 group, and EFSR was significantly higher (4.2 vs 3.9, p=0.002). RELAPS >1 group had smaller aortic valve area (AVA: 0.6 vs 0.7 cm2, p=0.045), but similar transvalvular gradients due to lower stroke volume. It had larger atria and less left atrial (LA) fractional emptying, as well as higher prevalence of atrial fibrillation (AF: 41% vs 27%, p=0.03). Right ventricle (RV) size were similar, however, RV function was worse in RELAPS >1 group (TAPSE: 19 vs 21 mm, p=0.003; free Wall LS: −24 vs −27%, p=0.008). There was no difference in all-cause mortality at 1 year of follow-up between groups (6.4% vs. 6.3%, p=1). Figure 2 represents the morphological characteristics according to the LS phenotype. Conclusions In severe AS, RELAPS >1 is present in almost half of the patients. It is associated with worse cardiac remodeling, as well as higher prevalence of AF. However, it wasn't associated with higher mortality at 1 year. 1 in 7 patients with AS and RELAPS >1 have concomitant ATTR CA grade 2/3. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Pfizer