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Aims: Amyloid cardiomyopathy is caused by the deposition of light chain (AL) or transthyretin amyloid (ATTR) fibrils, that leads to a restrictive cardiomyopathy, often resulting in heart failure (HF) with preserved or reduced ejection fraction. This study aimed to determine whether cardiac output reduction or ventilation inefficiency plays a predominant role in limiting exercise in patients with amyloid cardiomyopathy., Methods: We conducted a multicentre prospective study in patients with AL or ATTR cardiomyopathy who underwent cardiopulmonary exercise testing across four centres. Patients were compared with a propensity-score matched HF cohort based on age, gender, left ventricular ejection fraction (LVEF), and peak oxygen consumption (VO 2 )., Results: Data from 267 amyloid patients aged 77 (72, 81) years, 86% male, with a median N-terminal pro B-type natriuretic peptide (NT-proBNP) of 2187 (1140, 4383) ng/L, exercise parameters of peak VO 2 of 14.1 (11.6;16.9) mL/min/kg, a minute ventilation to carbon dioxide production (VE/VCO 2 ) slope of 37.4 (32.5, 42.6) and a LVEF of 50% (44%, 59%) were analysed. We identified 251 amyloid cardiomyopathy-HF matches. Amyloid patients had a signifnicantly higher VE/VCO 2 slope [37.4, inter quartile range (IQR): 32.7, 43.1 vs. 32.1, IQR: 28.7, 37.0, P < 0.0001], NT-proBNP (2249, IQR: 1187, 4420 vs. 718, IQR: 405, 2161 ng/L, P < 0.001), peak heart rate (121 ± 28 vs. 115 ± 27 beats/min, P = 0.007) and peak ventilation (51, IQR: 42, 62 vs. 43, IQR: 33, 53 L/min, P < 0.0001) with earlier anaerobic threshold (VO 2 at AT: 8.9, IQR: 6.8, 10.8 vs. 10.8, IQR: 8.9, 12.7 mL/min/kg, P < 0.0001) compared with HF. Between amyloid patients, AL patients (n = 27) were younger (63, IQR: 58, 70 vs. 78, IQR: 72, 81 years, P < 0.0001), had lower VE/VCO 2 slope (35.0, IQR: 30.0, 38.7 vs. 38.0, IQR: 32.8, 43.1, P = 0.019), higher end-tidal carbon dioxide partial pressure both at AT (35.1 ± 4.8 vs. 31.4 ± 4.7 mmHg, P < 0.001) and peak exercise (32, IQR: 28, 35 vs. 30, IQR: 26, 33 mmHg, P = 0.039) as compared with ATTR (n = 233)., Conclusions: A higher VE/VCO 2 slope and an earlier AT, determining functional capacity impairment, was assessed in patients with amyloid cardiomyopathy compared with the matched HF cohort. Additionally, patients with ATTR might display more severe exercise limitations as compared with AL., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Long-COVID symptoms remain incompletely defined due to a large heterogeneity in the populations studied, case definitions, and settings of care. The aim of this study was to assess, in patients accessing care for Long-COVID, the profile of symptoms reported, the possible clustering of symptoms and cases, the functional status compared to pre-infection, and the impact on working activity., Methods: Multicentre cohort study with a collection of both retrospective and prospective data. Demographics, comorbidities, severity and timing of acute COVID, subjective functional status, working activity and presence of 30 different symptoms were collected using a shortened version of the WHO Post COVID-19 Case Report Form. The impact on working activity was assessed in multivariable logistic regression models. Clustering of symptoms was analysed by hierarchical clustering and the clustering of cases by two-step automatic clustering., Results: The study evaluated 1297 individuals (51.5% women) from 30 clinical centres. Men and women had different profiles in terms of comorbidities, vaccination status, severity and timing of acute SARS-CoV-2 infection. Fatigue (55.9%) and dyspnea (47.2%) were the most frequent symptoms. Women reported more symptoms (3.6 vs. 3.1, p < 0.001), with a significantly higher prevalence of memory loss, difficult concentration, cough, palpitation or tachycardia, dermatological abnormalities, brain fog, headache and visual disturbances. Dyspnea was more common in men. In the cluster analysis of the 19 more common symptoms, five aggregations were found: four two-symptom clusters (smell and taste reduction; anxiety and depressed mood; joint pain or swelling and muscle pain; difficult concentration and memory loss) and one six-symptom cluster (brain fog, equilibrium/gait disturbances, headache, paresthesia, thoracic pain, and palpitations/tachycardia). In a multivariable analysis, headache, dyspnea, difficult concentration, disturbances of equilibrium or gait, visual disturbances and muscular pain were associated with reduced or interrupted working activity. Clustering of cases defined two clusters, with distinct characteristics in terms of phase and severity of acute infection, age, sex, number of comorbidities and symptom profile., Conclusions: The findings provide further evidence that Long-COVID is a heterogeneous disease with manifestations that differ by sex, phase of the pandemic and severity of acute disease, and support the possibility that multiple pathways lead to different clinical manifestations., Competing Interests: Declarations Ethics approval and consent to participate The Italian National Ethics Committee approved the project (AOO-ISS—19/04/2022–0015066 Class: PRE BIO CE 01.00). Written informed consent was required for patient inclusion, using a patient information and consent form also approved by the Italian National Ethics Committee. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Limited temporal data on in-hospital mortality trends of patients hospitalized with acute heart failure (AHF) have been reported. We evaluated whether, in AHF hospitalized patients, the rate of in-hospital and 30-day mortality, and 30-day re-hospitalization for AHF have changed in the past 15 years., Methods and Results: We examined administrative data from the Lombardy region, Italy and analysed data of all adults hospitalized for AHF from 2003 to 2018. Patients were stratified according to the hospitalization period: 2003-2006; 2007-2010; 2011-2014; 2015-2018. Primary endpoint was the comparison of in-hospital mortality rates among periods. Secondary endpoints were 30-day mortality rates and temporal trends of re-hospitalization for AHF. During this period, 414,164 hospitalizations with a primary diagnosis of AHF were identified, involving 286,028 patients aged 18 and older. In-hospital and 30-day mortality in the entire cohort showed a progressive increase over time (from 6.7 % to 8.5 % and from 12.4 % to 14.5 %, respectively). Thirty-day re-hospitalization for AHF was 2 %, showing a progressive decrease over the years. However, patient' age and complexity increased in the most recently hospitalized patients. After adjusting for major confounders, in-hospital and 30-day mortality risks were similar moving from one study period to the next (relative risk for trend 1.00 [95 % CI 0.99-1.01] and 1.00 [95 % CI 0.98-1.01], respectively), while that of 30-day AHF re-hospitalization decreased progressively (hazard ratio for trend 0.86 [95 % CI 0.84-0.88])., Conclusions: In our study, the increasing age and complexity of patients largely accounted for the continued rise in early mortality observed in patients hospitalized with AHF., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Distal trans-radial access (dTRA) for percutaneous coronary interventions (PCI) is increasingly gaining attention due to its potential to mitigate radial artery occlusion (RAO). However, a comprehensive understanding of the mechanical impact of the devices on the radial artery (RA) wall remains limited. Using a complete intravascular ultrasound (IVUS) evaluation of the RA, including also the vascular access site, we aimed to evaluate all the consequences related to the catheterization on the RA wall, starting from the vascular access, comparing conventional sheath and sheathless approaches., Methods: This is an observational, prospective, multicenter study aimed to assess the entire RA wall immediately after IVUS-guided PCI via-dTRA. IVUS assessment included quantitative measurements (minimal lumen area [MLA], minimal vessel area [MVA]) and qualitative observations (dissections, vasospasm). Study objectives included delineating RA wall structure post-PCI and comparing findings between conventional and sheathless approaches., Results: Fifty patients (21 [42%] with conventional sheath, 29 [58%] sheathless) were enrolled between March 2023 and February 2024. Female patients were more prevalent in the convention sheath group (38% vs. 7%, p < 0.001). Sheathless approach utilized 7-French guiding catheters more frequently (33% vs. 86%, p < 0.001). Post-procedural IVUS identified dissections in 12% of cases, with no significant difference between approaches. Arterial vasospasm was present in a quarter of patients, numerically higher in the conventional sheath group (29% vs. 21%, p = 0.5). MLA and MVA were comparable between groups, though MLA and MVA were lowest at the proximal segment of the RA only in the conventional sheath group (p < 0.001). No RAO was documented during the IVUS evaluation., Conclusions: The intravascular assessment of dTRA after coronary interventions, utilizing either conventional or sheathless approaches, including large-bore guiding catheters, demonstrated a relatively low incidence of access-related complications such as dissection and vasospasm, without affecting the flow and patency of the proximal RA., (© 2024 Wiley Periodicals LLC.)

Background: Acute mediastinitis is rarely caused by haematogenous spread of a remote infection. In this respect, since the only medical therapy is usually unsuccessful, treating acute mediastinitis with no source of infection detected is very challenging and management not standardized. In this case report, we describe non-surgical management experience of acute mediastinitis caused by methicillin-sensitive Staphylococcus aureus ., Case Presentation: In a 79-year-old man judged not eligible for cardiac surgery, we attempted the infection source control through vacuum-assisted closure therapy, together with antimicrobial therapy. We observed gradual clinical, laboratory and radiologic improvements: reduced swelling and normalization of the white blood cell count and C-reactive protein level were associated with reduction in size of a periaortic abscess., Conclusion: We managed a clinical condition with high mortality risk with chronic antimicrobial therapy alone, a strategy that is rarely considered. With this medical strategy we achieved an optimal response to a clinical picture that does not allow any other approach., Learning Points: Mediastinitis is a rare but severe infection with a high mortality rate.Chronic antimicrobial therapy can be an effective strategy in high surgical risk patients.The present case demonstrates good tolerability of lifelong antibiotic therapy., Competing Interests: Conflicts of Interests: The Authors declare that there are no competing interests., (© EFIM 2024.)

Background: The CTO-ARC (Chronic Total Occlusion Academic Research Consortium) recognized that a nonstandardized definition of chronic total occlusion (CTO) percutaneous coronary intervention approaches can bias the complications' attribution to each crossing strategy., Objectives: The study sought to describe the numbers, efficacy, and safety of each final CTO crossing strategy according to CTO-ARC recommendations., Methods: In this cross-sectional study, data were retrieved from the European Registry of Chronic Total Occlusions between 2021 and 2022., Results: Out of 8,673 patients, antegrade and retrograde approach were performed in 79.2% and 20.8% of cases, respectively. The antegrade approach included antegrade wiring and antegrade dissection and re-entry, both performed with or without retrograde contribution (antegrade wiring without retrograde contribution: n = 5,929 [68.4%]; antegrade wiring with retrograde contribution: n = 446 [5.1%]; antegrade dissection and re-entry without retrograde contribution: n = 353 [4.1%]; antegrade dissection and re-entry with retrograde contribution: n = 137 [1.6%]). The retrograde approach included retrograde wiring (n = 735 [8.4%]) and retrograde dissection and re-entry (n = 1,073 [12.4%]). Alternative antegrade crossing was associated with lower technical success (70% vs 86% vs 93.1%, respectively; P < 0.001) and higher complication rates (4.6% vs 2.9% vs 1%, respectively; P < 0.001) as compared with retrograde and true antegrade crossing. However, alternative antegrade crossing was applied mostly as a rescue strategy (96.1%)., Conclusions: The application of CTO-ARC definitions allowed the reclassification of 6.7% of procedures as alternative antegrade crossing with retrograde or antegrade contribution which showed higher MACCE and lower technical success rates, as compared with true antegrade and retrograde crossing., Competing Interests: Funding Support and Author Disclosures Dr Bufe has received speaker honoraria from Biotronik and Shockwave Medical. Dr Pyxaras has received consulting/speaker/proctorship honoraria from Abiomed, AstraZeneca, Asahi Intecc, Biotronik, Boston Scientific, and Terumo. Dr Ladwiniec has received consulting/speaker/proctoring honoraria from Abbott, Biotronik, Boston Scientific, Cordis, Shockwave Medical, and SMT. Dr Werner has received speaker honoraria from Abbott, Asahi Intecc, OrbusNeich, Philips, Siemens, and Terumo. Dr Mashayekhi has received consulting/speaker/proctoring honoraria from Abbott, Abiomed, Asahi Intecc, AstraZeneca, Biotronik, Boston Scientific, Cardinal Health, Daiichi-Sankyo, Medtronic, OrbusNeich, Shockwave Medical, Teleflex, and Terumo. Dr Ayoub has received consultant/proctor honoraria from Boston Scientific, Teleflex, Asahi Intecc, Cordis, Terumo, and SIS Medical. Dr Goktekin has received consulting/speaker/proctoring honoraria from Boston Scientific, Medtronik, MicroPort, and Asahi Inc. Dr Agostoni has received consulting honoraria from Abbott, Boston Scientific, Cordis, iVascular, Medtronic, Neovasc, Seven Sons, Teleflex, and Terumo. Dr Diletti has received consultant/proctoring honoraria from Asahi Intecc, Terumo, IMDS, Boston Scientific, Teleflex, and Philips. Dr Rathore has received honoraria for speaker and proctoring from Abbott Vascular and Translumina Therapeutics. Dr Bozinovic has served as a speaker or proctor and/or received honoraria from Orbus Neich and Medtronic. Dr Galassi has received consulting/speaker honoraria from Asahi Intecc and Ivascular. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The HF syndrome is characterized by an autonomic unbalance with sympathetic hyperactivity which contributes to increased myocardial oxygen demand, oxidative stress, peripheral vasoconstriction, afterload mismatch with a progressive desensitization and down-regulation of cardiac β1-receptors. These changes, together with a few other structural and peripheral changes, lead to chronotropic incompetence (CI), such as the inability to increase heart rate (HR) consistently with activity or demand. CI, regardless of the method and cut-off adopted to define it, is associated with reduced exercise capacity and a worse prognosis. Furthermore, different pharmacological classes might interfere with the physiologic exercise-induced HR response, thus generating some confusion. In particular, the β-blockers, albeit lowering peak HR, are known to improve prognosis and left ventricular inotropic reserve so that their withdrawal should be avoided at least in HF with reduced and mildly reduced ejection fraction. Similarly, a still debated strategy to counterbalance a blunted exercise-induced HR response, is represented by rate-adapting pacing. The present review, besides supplying an overview on possible CI definitions, discusses the clinical impact of CI and potential pharmacological and non-pharmacological therapeutic strategies., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Peak oxygen uptake (pVO 2 ) predicts mortality in patients with heart failure on left ventricular assist device (LVAD) support. This follow-up of the PRO-VAD study examines the prognostic value of repeated pVO 2 measurements during long-term follow-up., Methods: This multicenter follow-up study included patients from the original PRO-VAD cohort who performed a cardiopulmonary exercise test (CPET) twice. Patients were categorized into 4 groups based on pVO 2 levels at the 2 CPETs: low at both tests, low at the first and high at the second test, high at the first and low at the second test, and high at both tests. Low pVO 2 was defined as ≤14 ml/kg/min (or ≤12 ml/kg/min if beta-blocker tolerant), while values above these thresholds were considered high. Survival outcomes were analyzed using the Kaplan-Meier method and cause-specific Cox analysis., Results: The study included 152 patients with repeated CPETs at approximately 6 and 12 months following LVAD implantation. The cohort showed slight but significant pVO 2 improvement (median change: 0.4 ml/kg/min, p = 0.04). Persistently high pVO 2 (76 patients) was associated with a 5-fold reduction in mortality hazard (hazard ratio [HR] 0.20, p = 0.002), compared with persistently low pVO 2 (46 patients). Improvement from low to high pVO 2 (21 patients) displayed similar benefits (HR 0.21, p = 0.02)., Conclusions: pVO 2 measurements remain predictive of mortality upon reiteration in patients with LVAD, with changes in pVO 2 providing additional prognostic value in identifying patients with an excellent outcome on ongoing LVAD support and in identifying patients requiring further interventions., (Copyright © 2024 International Society for the Heart and Lung Transplantation. All rights reserved.)

Aims: Limited evidence exists regarding the outcomes of cancer patients hospitalized with new onset acute heart failure (AHF). We assessed the in-hospital mortality and 1 year outcomes of cancer patients admitted for new onset AHF, taking into account both past and active cancer status as well as cancer site., Methods: We examined administrative data of adult patients hospitalized with a first episode of AHF from 2003 to 2018 in Lombardy, Italy. Patients were categorized based on their cancer history. The primary endpoint was in-hospital mortality with secondary endpoints including 1 year all-cause mortality and 1 year re-hospitalization for AHF., Results: Among 283 144 patients AHF hospitalizations, 55 145 (19%) involved patients with a history of cancer (60% past cancer, 40% active cancer). Both in-hospital and 1 year mortality rates were higher among cancer patients compared with those without (9.3% vs. 6.4% and 34.9% vs. 22.3%, respectively; P < 0.0001). After adjustment, cancer patients exhibited increased risk of in-hospital mortality [odds ratio (OR) 1.40; 99% confidence interval (CI) 1.34-1.46] and 1 year mortality (HR 1.35; 99% CI 1.32-1.39), particularly among those with lung cancer. Patients with active and past cancer had a similar in-hospital mortality risk (OR 0.99; 99% CI 0.91-1.07) while 1 year mortality risk was higher among those with active cancer (HR 1.26; 99% CI 1.21-1.31)., Conclusions: Cancer is a prevalent comorbidity in patients hospitalized with new onset AHF, and it is associated with a poorer prognosis. Mortality risk appears to vary based on cancer status and type., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Competing Interests: Conflict of interest: None declared.

Background: Coronary chronic total occlusions (CTO) are associated with an increased chance of untreatable symptoms and worse prognosis. However, limited data are available about the interaction between treatment strategy, potential ischemia burden reduction and quality of life (QoL) improvement., Methods: Our prospective registry aims to assess the potentially different impacts of treatment strategies (coronary artery bypass grafting vs.. percutaneous coronary intervention vs. optimal medical therapy) on clinical outcomes and QoL domains. This article specifically focuses on describing the registry's rationale, design, and baseline characteristics of the enrolled patients., Results: A total of 157 patients were enrolled. Every patient was evaluated for baseline symptoms, ischemic burden and QoL and allocated to a treatment arm. In 112 patients (71.3%) ischemia baseline assessment was performed and for 116 (73.9%) Seattle Angina Questionnaire (SAQ) was available. At baseline, a significant functional limitation was evident, especially in terms of angina stability (mean score 69±31%) and disease perception (mean score 69±27%). In 49.1% of patients, ischemia testing was positive. Patients with documented ischemia were generally more symptomatic (CCS class 1 36.4% vs.. 57.9%, P=0.023) and a significant inverse correlation between CCS class and SAQ domains was found. No association between ischemia burden and self-reported QoL scores was found., Conclusions: The PETS-CTO registry is the first prospective registry investigating the impact of different treatment strategies on QoL and ischemia burden in patients with CTOs. At baseline, the severity of symptoms was directly associated with ischemia burden and inversely associated with self-reported QoL evaluation.

Aims: Individual prognostic assessment and disease evolution pathways are undefined in chronic heart failure (HF). The application of unsupervised learning methodologies could help to identify patient phenotypes and the progression in each phenotype as well as to assess adverse event risk., Methods and Results: From a bulk of 7948 HF patients included in the MECKI registry, we selected patients with a minimum 2-year follow-up. We implemented a topological data analysis (TDA), based on 43 variables derived from clinical, biochemical, cardiac ultrasound, and exercise evaluations, to identify several patients' clusters. Thereafter, we used the trajectory analysis to describe the evolution of HF states, which is able to identify bifurcation points, characterized by different follow-up paths, as well as specific end-stages conditions of the disease. Finally, we conducted a 5-year survival analysis (composite of cardiovascular death, left ventricular assist device, or urgent heart transplant). Findings were validated on internal (n = 527) and external (n = 777) populations. We analyzed 4876 patients (age = 63 [53-71], male gender n = 3973 (81.5%), NYHA class I-II n = 3576 (73.3%), III-IV n = 1300 (26.7%), LVEF = 33 [25.5-39.9], atrial fibrillation n = 791 (16.2%), peak VO 2 % pred = 54.8 [43.8-67.2]), with a minimum 2-year follow-up. Nineteen patient clusters were identified by TDA. Trajectory analysis revealed a path characterized by 3 bifurcation and 4 end-stage points. Clusters survival rate varied from 44% to 100% at 2 years and from 20% to 100% at 5 years, respectively. The event frequency at 5-year follow-up for each study cohort cluster was successfully compared with those in the validation cohorts (R = 0.94 and R = 0.84, P < 0.001, for internal and external cohort, respectively). Finally, we conducted a 5-year survival analysis (composite of cardiovascular death, left ventricular assist device, or urgent heart transplant observed in 22% of cases)., Conclusions: Each HF phenotype has a specific disease progression and prognosis. These findings allow to individualize HF patient evolutions and to tailor assessment., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

We report the case of an athlete who, despite facing the challenges of laryngectomy, underwent a comprehensive cardiopulmonary exercise test to assess both his ability to participate in sports and his cardiopulmonary fitness. We not only highlight the individualized approach to sports assessment in a challenging medical context but also emphasize the feasibility of employing cardiopulmonary testing in evaluating subjects in unusual settings.

Aims: We analysed baseline characteristics and guideline-directed medical therapy (GDMT) use and decisions in the European Society of Cardiology (ESC) Heart Failure (HF) III Registry., Methods and Results: Between 1 November 2018 and 31 December 2020, 10 162 patients with acute HF (AHF, 39%, age 70 [62-79], 36% women) or outpatient visit for HF (61%, age 66 [58-75], 33% women), with HF with reduced (HFrEF, 57%), mildly reduced (HFmrEF, 17%) or preserved (HFpEF, 26%) ejection fraction were enrolled from 220 centres in 41 European or ESC-affiliated countries. With AHF, 97% were hospitalized, 2.2% received intravenous treatment in the emergency department, and 0.9% received intravenous treatment in an outpatient clinic. AHF was seen by most by a general cardiologist (51%) and outpatient HF most by a HF specialist (48%). A majority had been hospitalized for HF before, but 26% of AHF and 6.1% of outpatient HF had de novo HF. Baseline use, initiation and discontinuation of GDMT varied according to AHF versus outpatient HF, de novo versus pre-existing HF, and by ejection fraction. After the AHF event or outpatient HF visit, use of any renin-angiotensin system inhibitor, angiotensin receptor-neprilysin inhibitor, beta-blocker, mineralocorticoid receptor antagonist and loop diuretics was 89%, 29%, 92%, 78%, and 85% in HFrEF; 89%, 9.7%, 90%, 64%, and 81% in HFmrEF; and 77%, 3.1%, 80%, 48%, and 80% in HFpEF., Conclusion: Use and initiation of GDMT was high in cardiology centres in Europe, compared to previous reports from cohorts and registries including more primary care and general medicine and regions more local or outside of Europe and ESC-affiliated countries., (© 2024 European Society of Cardiology.)

Chronic total occlusions (CTOs) are frequent in patients with previous coronary artery bypass graft (CABG) surgery. Percutaneous coronary intervention (PCI) is the usual revascularization strategy. Whether or not the presence of a graft on a CTO vessel and post-PCI graft patency impacts outcomes after CTO-PCI is unknown. We sought to evaluate the impact of post-PCI graft patency on the durability of CTO-PCI. In total, 259 patients with previous CABG who underwent CTO-PCI in 12 international centers in 2019 to 2023 were categorized into "grafted" and "ungrafted" groups based on the presence of graft on a CTO vessel. The grafted group was subdivided into "graft-occluded" and "graft-patent" groups, depending on graft patency. The primary end points were (1) technical success rate, (2) target vessel failure, and (3) CTO failure rates at 1 year. CTO failure was defined as target vessel revascularization and/or significant in-stent restenosis. A total of 199 patients (77%) were in the grafted group. Grafted CTOs showed higher complexity and lower technical success rates (70% vs 80%, p = 0.004) than nongrafted CTOs. Of the grafted CTOs, 140 (70%) were in the grafted-occluded group and 59 (30%) were in the grafted-patent group. The technical success was lower in the former group (65% vs 81%, p = 0.022). An occluded graft was an independent predictor of technical failure (odds ratio 2.04, 95% confidence interval 1.03 to 4.76, p = 0.049) and persistent post-PCI graft patency was a strong independent predictor of CTO failure at 1 year (hazard ratio 5.6, 95% confidence interval 1.2 to 27.5, log-rank p = 0.033). In conclusion, in patients with previous CABG who underwent CTO-PCI, post-PCI graft patency was a significant predictor of CTO failure., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Fractional flow reserve (FFR) represents the gold standard in guiding the decision to proceed or not with coronary revascularization of angiographically intermediate coronary lesion (AICL). Optical coherence tomography (OCT) allows to carefully characterize coronary plaque morphology and lumen dimensions., Objectives: We sought to develop machine learning (ML) models based on clinical, angiographic and OCT variables for predicting FFR., Methods: Data from a multicenter, international, pooled analysis of individual patient's level data from published studies assessing FFR and OCT on the same target AICL were collected through a dedicated database to train (n = 351) and validate (n = 151) six two-class supervised ML models employing 25 clinical, angiographic and OCT variables., Results: A total of 502 coronary lesions in 489 patients were included. The AUC of the six ML models ranged from 0.71 to 0.78, whereas the measured F1 score was from 0.70 to 0.75. The ML algorithms showed moderate sensitivity (range: 0.68-0.77) and specificity (range: 0.59-0.69) in detecting patients with a positive or negative FFR. In the sensitivity analysis, using 0.75 as FFR cut-off, we found a higher AUC (0.78-0.86) and a similar F1 score (range: 0.63-0.76). Specifically, the six ML models showed a higher specificity (0.71-0.84), with a similar sensitivity (0.58-0.80) with respect to 0.80 cut-off., Conclusions: ML algorithms derived from clinical, angiographic, and OCT parameters can identify patients with a positive or negative FFR., (© 2024 The Author(s). Catheterization and Cardiovascular Interventions published by Wiley Periodicals LLC.)

Aims: Patients with transthyretin amyloid cardiomyopathy (ATTR-CM) experience reduced functional capacity. We evaluated changes in functional capacity over extensive follow-up using cardiopulmonary exercise testing (CPX)., Methods: ATTR-CM patients underwent CPX and blood testing at baseline, first [V1, 8 (6-10) months] and second follow-up (V2) at 35 (26-41) months after start of disease-specific therapy., Results: We included 34 ATTR-CM patients, aged 77 (±6) years (88.2% men). CPX showed two patterns with functional capacity improvement at V1 and deterioration at V2. Peak work capacity ( P = 0.005) and peak oxygen consumption (VO 2 , P = 0.012) increased at V1 compared with baseline and decreased at V2. The ventilation to carbon dioxide relationship slope (VE/VCO 2 ) increased at V2 compared with baseline and V1 ( P = 0.044). A cut-off for peak VO 2 at 14 ml/kg·min showed more events (composite of death and heart failure hospitalization): less than 14 vs. greater than 14 ml/kg·min ( P  = 0.013). Cut-offs for VE/VCO 2 slope at 40 showed more events greater than 40 vs. less than 40 ( P  = 0.009)., Conclusion: ATTR-CM patients showed an improvement and deterioration in the short-term and long-term follow-up, respectively, with a better prognosis for those with peak VO 2 above 14 ml/kg·min and for a VE/VCO 2 slope below 40., (Copyright © 2024 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Background: One third of patients undergoing transcatheter aortic-valve implantation (TAVI) have an indication for oral anticoagulation owing to concomitant diseases. Interruption of oral anticoagulation during TAVI may decrease the risk of bleeding, whereas continuation may decrease the risk of thromboembolism., Methods: We conducted an international, open-label, randomized, noninferiority trial involving patients who were receiving oral anticoagulants and were planning to undergo TAVI. Patients were randomly assigned in a 1:1 ratio to periprocedural continuation or interruption of oral anticoagulation. The primary outcome was a composite of death from cardiovascular causes, stroke from any cause, myocardial infarction, major vascular complications, or major bleeding within 30 days after TAVI., Results: A total of 858 patients were included in the modified intention-to-treat population: 431 were assigned to continuation and 427 to interruption of oral anticoagulation. A primary-outcome event occurred in 71 patients (16.5%) in the continuation group and in 63 (14.8%) in the interruption group (risk difference, 1.7 percentage points; 95% confidence interval [CI], -3.1 to 6.6; P = 0.18 for noninferiority). Thromboembolic events occurred in 38 patients (8.8%) in the continuation group and in 35 (8.2%) in the interruption group (risk difference, 0.6 percentage points; 95% CI, -3.1 to 4.4). Bleeding occurred in 134 patients (31.1%) in the continuation group and in 91 (21.3%) in the interruption group (risk difference, 9.8 percentage points; 95% CI, 3.9 to 15.6)., Conclusions: In patients undergoing TAVI with a concomitant indication for oral anticoagulation, periprocedural continuation was not noninferior to interruption of oral anticoagulation during TAVI with respect to the incidence of a composite of death from cardiovascular causes, stroke, myocardial infarction, major vascular complications, or major bleeding at 30 days. (Funded by the Netherlands Organization for Health Research and Development and the St. Antonius Research Fund; POPular PAUSE TAVI ClinicalTrials.gov number, NCT04437303.)., (Copyright © 2024 Massachusetts Medical Society.)

Aims: Patients with heart failure (HF) remain often undertreated for multiple reasons, including treatment inertia, contraindications, and intolerance. The OPTIimal PHARMacological therapy for patients with Heart Failure (OPTIPHARM-HF) registry is designed to evaluate the prevalence of evidence-based medical treatment prescription and titration, as well as the causes of its underuse, in a broad real-world population of consecutive patients with HF across the whole ejection fraction spectrum and among different clinical phenotypes., Methods: The OPTIPHARM-HF registry (NCT06192524) is a prospective, multicenter, observational, national study of adult patients with symptomatic HF, as defined by current international guidelines, regardless of ejection fraction. Both outpatients and inpatients with chronic and acute decompensated HF will be recruited. The study will enroll up to 2500 patients with chronic HF at approximately 35 Italian HF centres. Patients will be followed for a maximum duration of 24 months. The primary objective of the OPTIPHARM-HF registry is to assess prescription and adherence to evidence-based guideline-directed medical therapy (GDMT) in patients with HF. The primary outcome is to describe the prevalence of GDMT use according to target guideline recommendation. Secondary objectives include implementation of comorbidity treatment, evaluation of sequence of treatment introduction and up-titration, description of GDMT implementation in the specific HF population, main causes of GDMT underuse, and assessment of cumulative rate of cardiovascular events., Conclusion: The OPTIPHARM-HF registry will provide important implications for improving patient care and adoption of recommended medical therapy into clinical practice among HF patients., (© 2024 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Bifurcation involvement close to or within the occluded segment poses increasing difficulties for chronic total occlusion (CTO)-percutaneous coronary intervention (PCI). However, this variable is not considered in the angiography-based CTO scoring systems nor has been extensively investigated in large multicenter series. Accordingly, we analyzed a CTO-PCI registry involving 92 European centers to explore the incidence, angiographic and procedural characteristics, and outcomes specific to CTO-PCIs with bifurcation involvement. A total of 3,948 procedures performed between January and November 2023 were examined (33% with bifurcation involvement). Among bifurcation lesions, 38% and 37% were located within 5 mm of the proximal and distal cap, respectively, 16% within the CTO body, and in 9% of cases proximal and distal bifurcations coexisted. When compared with lesions without bifurcation involvement, CTO bifurcation lesions had higher complexity (J-CTO 2.33 ± 1.21 vs 2.11 ± 1.27, p <0.001) and were associated with higher use of additional devices (dual-lumen microcatheter in 27.6% vs 8.4%, p <0.001, and intravascular ultrasound in 32.2% vs 21.7%, p <0.001). Radiation dose (1,544 [836 to 2,819] vs 1,298.5 [699.1 to 2,386.6] mGy, p <0.001) and contrast volume (230 [160 to 300] vs 190 [130 to 250] ml, p <0.001) were also higher. Technical success was similar (91.5% with bifurcation involvement vs 90.4% without bifurcation involvement, p = 0.271). However, the bifurcation lesions within the CTO segment (intralesion) were associated with lower technical success than the other bifurcation-location subgroups (83.7% vs 93.3% proximal, 93.4% distal, and 89.0% proximal and distal, p <0.001). On multivariable analysis, the presence of an intralesion bifurcation was independently associated with technical failure (odds ratio 2.04, 95% confidence interval 1.24 to 3.35, p = 0.005). In conclusion, bifurcations are present in approximately one-third of CTOs who underwent PCI. PCI of CTOs with bifurcation can be achieved with high success rates except for bifurcations within the occluded segment, which were associated with higher technical failure., Competing Interests: Declaration of competing interest Dr. Werner: speaker honoraria from Abbott Vascular, ASAHI Intecc, Daiichi-Sankyo, Orbus-Neich, Pfizer (New York, NY, United States), Philips-Volcano, and Siemens-Healthineers. TerumoWerner: speaker honoraria from Abbott Vascular, ASAHI Intecc, Daiichi-Sankyo, Orbus-Neich, Pfizer (New York, NY, United States), Philips-Volcano, Siemens-Healthineers, and Terumo. Myron Zaczkiewicz: speaker honoraria from Orbus-Neich, Medtronic, iVascular. Proctoring for Orbus-Neich and Asahi Intecc. Institutional: Abiomed. Dr. Boudou: minor fees as consultant from ASAHI Intecc and Terumo. Dr. Avran: proctoring for Boston Scientific, Biotronik, Vascular Therapy, ASAHI Intecc, Abbott Vascular, and Teleflex. Dr. Agostoni: consulting fees from Boston Scientific, CardiaWave, iVascular, Neovasc, Seven Sons, Teleflex, and Terumo. The remaining authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: In chronic heart failure (HF), exercise-induced increase in pulmonary capillary pressure may cause an increase of pulmonary congestion, or the development of pulmonary oedema. We sought to assess in HF patients the exercise-induced intra-thoracic fluid movements, by measuring plasma brain natriuretic peptide (BNP), lung comets and lung diffusion for carbon monoxide (DLCO) and nitric oxide (DLNO), as markers of hemodynamic load changes, interstitial space and alveolar-capillary membrane fluids, respectively., Methods and Results: Twenty-four reduced ejection fraction HF patients underwent BNP, lung comets and DLCO/DLNO measurements before, at peak and 1 h after the end of a maximal cardiopulmonary exercise test. BNP significantly increased at peak from 549 (328-841) to 691 (382-1207, p < 0.0001) pg/mL and almost completely returned to baseline value 1 h after exercise. Comets number increased at peak from 9.4 ± 8.2 to 24.3 ± 16.7, returning to baseline (9.7 ± 7.4) after 1 h (p < 0.0001). DLCO did not change significantly at peak (from 18.01 ± 4.72 to 18.22 ± 4.73 mL/min/mmHg), but was significantly reduced at 1 h (16.97 ± 4.26 mL/min/mmHg) compared to both baseline (p = 0.0211) and peak (p = 0.0174). DLNO showed a not significant trend toward lower values 1 h post-exercise., Conclusions: Moderate/severe HF patients have a 2-step intra-thoracic fluid movement with exercise: the first during active exercise, from the vascular space toward the interstitial space, as confirmed by comets increase, without any effect on diffusion, and the second, during recovery, toward the alveolar-capillary membrane, clearing the interstitial space but worsening gas diffusion., Competing Interests: Declaration of competing interest The Authors report no relationships that could be construed as a conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

Background: A sex-based evaluation of prognosis in heart failure (HF) is lacking., Methods and Results: We analyzed the Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score registry, which includes HF with reduced ejection fraction (HFrEF) patients. A cross-validation procedure was performed to estimate weights separately for men and women of all MECKI score parameters: left ventricular ejection fraction (LVEF), hemoglobin, kidney function assessed by Modification of Diet in Renal Disease, blood sodium level, ventilation vs. carbon dioxide production slope, and peak oxygen consumption (peakVO 2 ). The primary outcomes were the composite of all-cause mortality, urgent heart transplant, and implant of a left ventricle assist device. The difference in predictive ability between the native and sex recalibrated MECKI (S-MECKI) was calculated using a receiver operating characteristic (ROC) curve at 2 years and a calibration plot. We retrospectively analyzed 7,900 HFrEF patients included in the MECKI score registry (mean age 61 ± 13 years, 6,456 men/1,444 women, mean LVEF 33% ± 10%, mean peakVO 2 56.2% ± 17.6% of predicted) with a median follow-up of 4.05 years (range 1.72-7.47). Our results revealed an unadjusted risk of events that was doubled in men compared to women (9.7 vs. 4.1) and a significant difference in weight between the sexes of most of the parameters included in the MECKI score. S-MECKI showed improved risk classification and accuracy (area under the ROC curve: 0.7893 vs. 0.7799, p  = 0.02) due to prognostication improvement in the high-risk settings in both sexes (MECKI score >10 in men and >5 in women)., Conclusions: S-MECKI, i.e., the recalibrated MECKI according to sex-specific differences, constitutes a further step in the prognostic assessment of patients with severe HFrEF., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor RDP declared a past co-authorship with the author GP. The authors declared that they were an editorial board member of Frontiers at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Grilli, Salvioni, Moscucci, Bonomi, Sinagra, Schaeffer, Campodonico, Mapelli, Rossi, Carriere, Emdin, Piepoli, Paolillo, Senni, Passino, Apostolo, Re, Santolamazza, Magri, Lombardi, Corrá, Raimondo, Cittadini, Iorio, Salzano, Lagioia, Vignati, Badagliacca, Passantino, Filardi, Correale, Perna, Girola, Metra, Cattadori, Guazzi, Limongelli, Parati, De Martino, Matassini, Bandera, Bussotti, Scardovi, Sciomer, Agostoni and MECKI Score Research Group.)

Cardiovascular (CV) diseases account for over 4 million deaths every year in Europe and over 220 000 deaths in Italy, representing the leading cause of morbidity and mortality worldwide. The European Society of Cardiology (ESC) guidelines have visionary included in the at very high CV risk group patients without previous acute ischemic events, such as those with subclinical atherosclerosis, chronic coronary syndrome or peripheral arterial disease, familial hypercholesterolemia, diabetes mellitus with target organ damage or multiple associated risk factors, and those with high calculated CV risk score, recommending to consider them and to achieve the same LDL-cholesterol targets as for secondary prevention patients. The aim of this position paper is to provide an updated overview of ESC guidelines that focuses on these patient categories to raise awareness within the clinical community regarding CV risk reduction in this specific epidemiological context.

Aims: The Fick principle states that oxygen uptake (V̇O2) is cardiac output (Qc)*arterial-venous O2 content difference [ΔC(a-v)O2]. Blood flow distribution is hidden in Fick principle and its relevance during exercise in heart failure (HF) is undefined.To highlight the role of blood flow distribution, we evaluated peak-exercise V̇O2, Qc and ΔC(a-v)O2, before and after HF therapeutic interventions., Methods: Symptoms-limited cardiopulmonary exercise tests with Qc measurement (inert-gas-rebreathing) was performed in 234 HF patients before and 6 months after successful exercise training, cardiac-resynchronization therapy or percutaneous-edge-to-edge mitral valve repair., Results: Considering all tests (n=468) a direct correlation between peakV̇O2 and peakQc (R2=0.47) and workload (R2=0.70) were observed. Patients were grouped according to treatment efficacy in group 1 (peakV̇O2 increase >10%, n=93), group 2 (peakV̇O2 change between 0 and 10%, n=60) and group 3 (reduction in peakV̇O2, n=81). Post-treatment peakV̇O2 changes poorly correlated with peakQc and peakΔC(a-v)O2 changes. Differently, post-procedures peakQc vs. peakΔC(a-v)O2 changes showed a close negative correlation (R2=0.46), becoming stronger grouping patients according to peakV̇O2 improvement (R2=0.64, 0.79 and 0.58 in group 1, 2 and 3, respectively). In 76% of patients peakQc and ΔC(a-v)O2 changes diverged regardless of treatment., Conclusion: The bulk of these data suggests that blood flow distribution plays a pivotal role on peakV̇O2 determination regardless of HF treatment strategies. Accordingly, for assessing HF treatment efficacy on exercise performance the sole peakV̇O2 may be deceptive and the combination of V̇O2, Qc and ΔC(a-v)O2, must be considered., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Transcatheter aortic valve implantation (TAVI) is an established treatment strategy in aortic valve disease. Infolding, as a nonuniform expansion of the prosthesis leading to introflection of part of the device circumference, is a complication specific to self-expandable prostheses. The aim of the study is to determine incidence, predictors, treatment strategy, and outcomes of infolding during Medtronic Evolut TAVI (Minneapolis, MN, US). Between January 2018 and March 2022, all patients treated with Evolut TAVI were included in a multicenter observational retrospective study. According to the occurrence of infolding, the enrolled cohort was divided into 2 groups; periprocedural characteristics and 30-day outcomes were compared. A total of 1,470 patients were included; 23 infolding cases (1.6%) were detected. Preprocedural imaging showed larger aortic anatomy and greater calcium burden in the infolding group. Infolding occurred mostly with Evolut Pro+ and size 34 mm and was diagnosed before full prosthesis release in 78.3%. The rate of moderate-to-severe paravalvular regurgitation was higher in the infolding group (21.7% vs 1.9%, p <0.001). Short-term follow-up showed greater all-cause and cardiovascular mortality (respectively, 4.3% vs 0.7% and 4.3% vs 0.6%, p <0.05) and higher rate of pacemaker implantation (33.3% vs 15.7%, p = 0.042) in case of infolding. High right cusp calcium score and resheathing maneuvers were independent predictors of infolding. In conclusion, prosthesis infolding is a TAVI complication burdened by worse cardiovascular outcomes. Prompt intraprocedural infolding diagnosis is pivotal, especially in case of great native valve calcium burden and resheathing maneuvers, to safely overcome this complication by prosthesis recapture or postdilation., Competing Interests: Declaration of competing interest Dr. Agostoni has received consulting fees from: Abbott, AorticLab, Boston Scientific, Cordis, iVascular, Medtronic, Neovasc, Seven Sons, Teleflex, and Terumo. Dr. Veulemans has received consulting fees, travel expenses or study honoraria from Medtronic, Edwards Lifesciences, and Boston Scientific. The remaining authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Valvular disease is a complex pathological condition that impacts countless individuals around the globe. Due to limited treatments, it is crucial to understand its mechanisms to identify new targets. Valve disease may result in pulmonary venous hypertension, which is linked to compromised functioning of the alveolar and capillary membranes and hindered gas exchange. Nonetheless, the correlation between surfactant proteins (SPs) and valve disease remains unexplored. A total of 44 patients were enrolled in this study, with 36 undergoing aortic valve replacement and 8 needing a second aortic valve substitution due to bioprosthetic valve degeneration. Ten healthy subjects were also included. The results showed that patients who underwent both the first valve replacement and the second surgery had significantly higher levels of immature SP-B (proSP-B) compared to control subjects. The levels of the extra-lung collectin SP-D were higher in patients who needed a second surgery due to bioprosthetic valve degeneration, while SP-A levels remained unchanged. The research also showed that there was no reciprocal relationship between inflammation and SP-D as the levels of inflammatory mediators did not differ between groups. The present study demonstrates that circulating proSP-B serves as a reliable marker of alveolar-capillary membrane damage in patients with valvular heart disease.

Background: Right ventricular dysfunction (RVD) and pulmonary hypertension have been recognized as two important prognostic features in patients with left side heart failure. Current literature does not distinguish between right heart failure (RHF) and RVD, and the two terms are used indiscriminately to describe pulmonary hypertension and RVD as well as clinical sign of RHF. Therefore, the right ventricle (RV) adaptation across the whole spectrum of left ventricular ejection fraction (LVEF) values has been poorly investigated., Methods: This is a multicenter observational prospective study endorsed by the Italian Society of Cardiology aiming to analyze the concordance between the signs and symptoms of RHF and echocardiographic features of RVD. The protocol will assess patients affected by chronic heart failure in stable condition regardless of the LVEF threshold by clinical, laboratory, and detailed echocardiographic study. During the follow-up period, patients will be observed by direct check-up visit and/or virtual visits every 6 months for a mean period of 3 years. All clinical laboratory and echocardiographic data will be recorded in a web platform system accessible for all centers included in the study., Results: The main study goals are: to investigate the concordance and discordance between clinical signs of RHF and RVD measured by ultrasonographic examination; to evaluate prognostic impact (in terms of cardiovascular mortality and heart failure hospitalization) of RVD and RHF during a mean follow-up period of 3 years; to investigate the prevalence of different right ventricular maladaptation (isolated right ventricular dilatation, isolated pulmonary hypertension, combined pattern) and the related prognostic impact., Conclusions: With this protocol, we would investigate the three main RVD patterns according to heart failure types and stages; we would clarify different RVD and pulmonary hypertension severity according to the heart failure types. Additionally, by a serial multiparametric analysis of RV, we would provide a better definition of RVD stage and how much is it related with clinical signs of RHF (ClinicalTrials.gov Identifier: NCT06002321)., (Copyright © 2024 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Background: While patients with heart failure (HF) with reduced left ventricular ejection fraction (HFrEF) constitutes a global health crisis the incidence, prevalence and prognosis of the disease may differ depending on the continent and country., Objective: To profile, analyze and compare cardiopulmonary exercise testing (CPET) data of patients with HFrEF between Italian and Brazilian cohorts., Methods: In this observational study, a total of 630 patients with clinical and functional diagnosis of HFrEF (315 patients from Brazil and 315 patients from Italy) performed CPET., Results: Although Brazilian patients were slightly younger (Brazil 60±10 vs Italy 64±11 p<0.001) with a better peak oxygen consumption (V̇O 2 ), circulatory power and left ventricular ejection fraction (LVEF) (p<0.01), ventilatory inefficiency and oscillation ventilation was higher when compared to the Italian cohort. When stratifying patients with LVEF≤30 % and age≥60 years, Brazilian patients presented worse ventilatory efficiency, and lower peak V̇O 2 compared to the Italian cohort., Conclusion: Patients with HFrEF from Brazil exhibited higher ventilatory inefficiency and a greater prevalence of oscillatory ventilation during CPET compared to patients with the same diagnosis from Italy., Competing Interests: Declaration of competing interest No potential conflict of interest was reported by the authors., (Copyright © 2024. Published by Elsevier Inc.)

Scant data exploring potential suboptimal physiological results after angiographic successful percutaneous coronary intervention (PCI) of chronic total occlusion (CTO) are available. Sixty cases of successful CTO-PCI were selected for this retrospective analysis. Post-CTO-PCI angiography-based fractional flow reserve was computed using the Murray-based fractional flow reserve (μFR) software. Vessel-specific μFR, residual trans-stent gradient (TSG) and corrected TSG stent were calculated. In physiological suboptimal results (μFR < 0.90), the virtual pullback pressure gradient (PPG) curves were analyzed to localize the main pressure drop-down and characterize the patterns of residual disease. The virtual pullback pressure gradient index (vPPGi) was then calculated to objectively characterize the predominant pattern of residual disease (diffuse vs focal). The physiological result was suboptimal in 28 cases (46.7%). The main pressure drop was localised proximal to the stent in 2 (7.1%), distal in 17 (60.7%) and intra-stent in 9 cases (32.2%). Intra-stent residual disease was diffuse in 7 cases and mixed in 2. Distal residual disease was characterised by a pure focal pattern in 12 cases, diffuse in 2 and mixed in 3. In the predominant diffuse phenotype (vPPGi < 0.65), we found a higher rate of TSG ≥ 0.04 (61.5% vs 20.0%, p = 0.025) and TSG stent  ≥ 0.009 (46.2% vs 20.0%, p = 0.017) while in the dominant focal phenotype poor-quality distal vessel was constantly present. In our cohort, post-CTO-PCI suboptimal physiological result was frequent (46.7%). Predominant focal phenotype was constantly associated with poor-quality distal vessel, while in the predominant diffuse phenotype, the rate of TSG ≥ 0.04 and TSG stent  ≥ 0.009 were significantly higher., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Aims: Although cardiopulmonary exercise testing (CPET) is the gold standard to assess exercise capacity, simpler tests (i.e., 6-min walk test, 6MWT) are also commonly used. The aim of this study was to evaluate the relationship between cardiorespiratory parameters during CPET and 6MWT in a large, multicentre, heterogeneous population., Methods: We included athletes, healthy subjects, and heart failure (HF) patients of different severity, including left ventricular assist device (LVAD) carriers, who underwent both CPET and 6MWT with oxygen consumption measurement., Results: We enrolled 186 subjects (16 athletes, 40 healthy, 115 non-LVAD HF patients, and 15 LVAD carriers). CPET-peakV̇O 2 was 41.0 [35.0-45.8], 26.2 [23.1-31.0], 12.8 [11.1-15.3], and 15.2 [13.6-15.6] ml/Kg/min in athletes, healthy, HF patients, and LVAD carriers, respectively (P < 0.001). During 6MWT they used 63.5 [56.3-76.8], 72.0 [57.8-81.0], 95.5 [80.3-109], and 95.0 [92.0-99.0] % of their peakV̇O 2 , respectively. None of the athletes, 1 healthy (2.5%), 30 HF patients (26.1%), and 1 LVAD carrier (6.7%), reached a 6MWT-V̇O 2 higher than their CPET-peakV̇O 2 . Both 6MWT-V̇O 2 and walked distance were significantly associated with CPET-peakV̇O 2 in the whole population (R 2  = 0.637 and R 2  = 0.533, P ≤ 0.001) but not in the sub-groups. This was confirmed after adjustment for groups., Conclusions: The 6MWT can be a maximal effort especially in most severe HF patients and suggest that, in absence of prognostic studies related to 6MWT metabolic values, CPET should remain the first method of choice in the functional assessment of patients with HF as well as in sport medicine., (© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Pulmonary hypertension (PH) is a frequent pathological condition worldwide, mainly secondary to cardiovascular and respiratory diseases, with a poor prognosis. Pulmonary arterial hypertension (PAH) is a rare form that affects the arterial pulmonary vasculature. PH and PAH are characterized by non-specific symptoms and a progressive increase of pulmonary vascular resistance that results in progressive, sometimes irreversible, right ventricular dysfunction. In recent years, a growing medical and social commitment on this disease allowed more accurate diagnosis in shorter times. However, the gap between guidelines and clinical practice remains a challenge for all medical doctors involved in the disease management. Considering the needs to share and describe diagnostic and therapeutic pathways, to measure the results obtained and to address the economical and organizational problems of this disease, all involved figures should collaborate to improve its prognostic impact and health expenses. In this consensus document, the PH experts of the Italian Association of Hospital Cardiologists (ANMCO) together with those of the Italian Society of Cardiology (SIC), address 1) definition, classification and unmet needs of PH and PAH; 2) classification and characteristics of centers involved in the diagnosis and treatment of the disease; 3) proposal of organization of a diagnostic-therapeutic pathway, based on robust and recent scientific evidence.

Background: The trans-radial approach for cardiac catheterization led to an increasing adoption of 5 French (F) catheters. We aim to evaluate reliability and reproducibility of coronary physiology assessment performed with 5F guiding catheter (GC)., Methods: Physiological measurements were performed in a coronary flow simulator, which provides two pulsatile flows, the baseline and hyperaemic flows. Two screws, positioned proximally and distally to the distal sensor of a pressure-temperature guidewire, were used to determine various combinations of stenoses and distal obstructions, simulating different pathophysiological conditions. For each setting, 5 measurements of fractional flow reserve (FFR), coronary flow reserve (CFR) and index of microvascular resistance (IMR) were performed with 6F and 5F GCs., Results: A total amount of 190 measurements were performed, 95 with 6F GC and 95 with 5F GC. Minimal differences between 6F and 5F GCs were detected for FFR [0.91 (IQR: 0.87-0.94) and 0.87 (IQR: 0.82-0.92) respectively, p < 0.001] and IMR (16.5 ± 8.8 and 15.4 ± 8.3 respectively, p = 0.001). Mean CFR was comparable between 6F and 5F GCs (3.6 ± 1.1 and 3.5 ± 0.7 respectively, p = 0.38). Misclassification rates were 1.0 %, 1.0 % and 0 % for FFR, CFR and IMR, respectively. According to Passing-Bablok analysis, an excellent agreement between 6F and 5F GCs was demonstrated for FFR and IMR, and a modest agreement for CFR. All measurements with 5F GC showed high reproducibility., Conclusions: In our in-vitro model, a complete physiological assessment including FFR, CFR and IMR resulted substantially comparable between 6F and 5F GCs. Further in-vivo analysis is required to support these findings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The minimalistic hybrid approach (MHA) is a recently proposed algorithm to perform chronic total occlusion (CTO) percutaneous coronary intervention (PCI), reducing the overall invasiveness of the procedure without impacting the acute results. However, data on midterm results are lacking. This study aimed to evaluate the midterm clinical outcomes of a multicenter international cohort of CTO PCI treated according to the MHA. Data from a consecutive series of patients with a CTO who underwent PCI according to the MHA between February 2019 and March 2022 were prospectively collected in 3 European centers and retrospectively analyzed. The main outcome was the first occurrence of a major adverse cardiac event (MACE), defined as a composite outcome of all-cause death, any myocardial infarction, and target vessel revascularization, at the last follow-up available. A total of 212 patients were included. The majority of the patients were symptomatic for angina (Canadian Cardiovascular Society class 2 or 3: 63.7%) at the time of the index procedure. The mean Japanese-CTO and CASTLE scores were 2.1 ± 1.2 and 2.0 ± 1.3, respectively. Technical success (CTO open with optimal flow) was achieved in 198 patients (93.9%) and procedural success (technical success without in-hospital MACEs) in 195 (91.9%). At the last follow-up available (median 677 days), the cumulative incidence rate of MACEs was 11.5%; in particular, all-cause death was 7.4%, any myocardial infarction was 4.3%, and unplanned target vessel revascularization was 6.5%. In conclusion, the midterm results of the MHA seem to be in line with contemporary results of other CTO PCI algorithms, thus potentially validating the MHA as a valuable alternative, provided that interventionalists are already expert CTO operators and accustomed to the definitions and peculiarities of MHA., Competing Interests: Declaration of competing interest The authors have no competing interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The "Minimalistic Hybrid Approach" (MHA) has been proposed to reduce the invasiveness of chronic total occlusion (CTO) percutaneous coronary intervention (PCI)., Aims: This study aims to assess whether MHA may also reduce the utilization of PCI resources (devices, radiations, and contrast) by comparing it with other conventional algorithms., Methods: We aimed to assess the impact of MHA on device, radiation, and contrast usage during CTO-PCI analyzing data from the Belgian Working Group on CTO (BWG-CTO) registry. Patients were divided, depending on the algorithm used, into two groups: Conventional versus Minimalistic. Primary objectives were procedure performance measures such as device usage (microcatheters and guidewires), radiological parameters, and contrast use. At 1-year follow-up, patients were evaluated for target vessel failure (TVF), defined as a composite of cardiac death, new myocardial infarction, and target vessel revascularization., Results: Overall, we analyzed 821 CTO-PCIs (Conventional n = 650, Minimalistic n = 171). The Minimalistic group demonstrated higher complexity of CTO lesions. After adjusting for propensity score, the Minimalistic group had a significantly lower number of microcatheters used (1.49 ± 0.85 vs. 1.24 ± 0.64, p = 0.026), while the number of guidewires was comparable (4.80 ± 3.29 vs. 4.35 ± 2.94, p = 0.30). Both groups had similar rates of success and procedural complications, as well as comparable procedural and fluoroscopic times and contrast volume used. At the 1-year follow-up, both groups showed comparable rates of TVF (hazard ratio: 0.57; 95% confidence interval: 0.24-1.34, p = 0.195)., Conclusion: The MHA may slightly reduce the number of dedicated devices used during CTO-PCI, without adversely affecting the procedural success or long-term outcome., (© 2024 Wiley Periodicals LLC.)

Background: Exercise is recommended for patients with chronic heart failure (CHF) and its intensity is usually set as a percentage of the maximal work rate (MWR) during cardiopulmonary exercise testing (CPX) or a symptom-limited incremental test (SLIT). As these tests are not always available in cardiac rehabilitation due to logistic/cost constraints, we aimed to develop a predictive model to estimate MWR at CPX (estMWR@CPX) in CHF patients using anthropometric and clinical measures and the 6-min walk test (6 MWT), the most widely used exercise field test., Methods: This is a multicentre cross-sectional retrospective study in a cardiac rehabilitation setting. Six hundred patients with HF in New York Heart Association (NYHA) functional class I-III underwent both CPX and 6 MWT and, t hrough multivariable linear regression analysis, we defined several predictive models to define estMWR@CPX., Results: The best model included 6 MWT, sex, age, weight, NYHA class, left ventricular ejection fraction (LVEF), smoking status and chronic obstructive pulmonary disease COPD (adjusted R 2  = 0.55; 95% LoA -39 to 33 W). When LVEF was excluded as a predictor, the resulting model performed only slightly worse (adjusted R 2  = 0.54; 95% LoA -42 to 34 W). Only in 34% of cases was the percentage difference between estMWR@CPX and real MWR@CPX <10% in absolute value. EstMWR@CPX tended to overestimate low values and underestimate high values of true MWR@CPX., Conclusions: Our results showed a lack of accuracy in the predictive model evaluated; therefore, for an accurate prescription of cycle-ergometer exercise training, it is necessary to assess MWR by CPX or SLIT., Competing Interests: All Authors declare no conflict of interest relevant to the research, analysis, or interpretation presented in the manuscript., (© 2024 The Authors.)

Background: Optical coherence tomography (OCT) allows to carefully characterize coronary plaque morphology and lumen dimensions. We sought to evaluate the value of OCT in predicting fractional flow reserve (FFR)., Methods: We performed a multicenter, international, pooled analysis of individual patient-level data from published studies assessing FFR and OCT on the same vessel. Data from stable or unstable patients who underwent both FFR and OCT of the same coronary artery were collected through a dedicated database. Predefined OCT parameters were minimum lumen area (MLA), percentage area stenosis (%AS), and presence of thrombus or plaque rupture. Primary end point was FFR ≤0.80. Secondary outcome was the incidence of major adverse cardiac events in patients not undergoing revascularization based on negative FFR (>0.80)., Results: A total of 502 coronary lesions in 489 patients were included. A significant correlation was observed between OCT-MLA and FFR values (R = 0.525; P < .001), and between OCT-%AS and FFR values (R = -0.482; P < .001). In Receiver operating characteristic analysis, MLA <2.0 mm 2 showed a good discriminative power to predict an FFR ≤0.80 (AUC, 0.80), whereas %AS >73% showed a moderate discriminative power (AUC, 0.73). When considering proximal coronary segments, the best OCT cutoff values predicting an FFR ≤0.80 were MLA <3.1 mm 2 (AUC, 0.82), and %AS >61% (AUC, 0.84). In patients with a negative FFR not revascularized, the combination of lower MLA and higher %AS had a trend toward worse outcome (which was statistically significant in the analysis restricted to proximal vessels)., Conclusions: OCT lumen measures (MLA, %AS) may predict FFR, and different cutoffs are needed for proximal vessels., (© 2024 The Author(s).)

Background: Post COVID-19 syndrome is characterized by several cardiorespiratory symptoms but the origin of patients' reported symptomatology is still unclear., Methods: Consecutive post COVID-19 patients were included. Patients underwent full clinical evaluation, symptoms dedicated questionnaires, blood tests, echocardiography, thoracic computer tomography (CT), spirometry including alveolar capillary membrane diffusion (DM) and capillary volume (Vcap) assessment by combined carbon dioxide and nitric oxide lung diffusion (DLCO/DLNO) and cardiopulmonary exercise test. We measured surfactant derive protein B (immature form) as blood marker of alveolar cell function., Results: We evaluated 204 consecutive post COVID-19 patients (56.5 ± 14.5 years, 89 females) 171 ± 85 days after the end of acute COVID-19 infection. We measured: forced expiratory volume (FEV 1 ) 99 ± 17%pred, FVC 99 ± 17%pred, DLCO 82 ± 19%, DM 47.6 ± 14.8 mL/min/mmHg, Vcap 59 ± 17 mL, residual parenchymal damage at CT 7.2 ± 3.2% of lung tissue, peakVO 2 84 ± 18%pred, VE/VCO 2 slope 112 [102-123]%pred. Major reported symptoms were: dyspnea 45% of cases, tiredness 60% and fatigability 77%. Low FEV 1 , Vcap and high VE/VCO 2 slope were associated with persistence of dyspnea. Tiredness was associated with high VE/VCO 2 slope and low PeakVO 2 and FEV 1 while fatigability with high VE/VCO 2 slope. SPB was fivefold higher in post COVID-19 than in normal subjects, but not associated to any of the referred symptoms. SPB was negatively associated to Vcap., Conclusions: In patients with post COVID-19, cardiorespiratory symptoms are linked to VE/VCO 2 slope. In these patients the alveolar cells are dysregulated as shown by the very high SPB. The Vcap is low likely due to post COVID-19 pulmonary endothelial/vasculature damage but DLCO is only minimally impaired being DM preserved., (© 2024. The Author(s).)

Background: Percutaneous coronary interventions (PCI) of chronic total occlusions (CTO) have reached high procedural success rates thanks to dedicated equipment, evolving techniques, and worldwide adoption of state-of-the-art crossing algorithms., Aims: We report the contemporary results of CTO PCIs performed by a large European community of experienced interventionalists. Furthermore, we investigated the impact of different risk factors for procedural major adverse cardiac and cerebrovascular events (MACCE) and trends of employment of specific devices like dual lumen microcatheters, guiding catheter extensions, intravascular ultrasound and calcium-modifying tools., Methods: We evaluated data from 8,673 CTO PCIs included in the European Registry of Chronic Total Occlusion (ERCTO) between January 2021 and October 2022., Results: The overall technical success rate was 89.1% and was higher in antegrade as compared with retrograde cases (92.8% vs 79.3%; p<0.001). Compared with antegrade procedures, retrograde procedures had a higher complexity of attempted lesions (Japanese CTO [J-CTO] score: 3.0±1.0 vs 1.9±1.2; p<0.001), a higher procedural and in-hospital MACCE rate (3.1% vs 1.2%; p<0.018) and a higher perforation rate with and without tamponade (1.5% vs 0.4% and 8.3% vs 2.1%, respectively; p<0.001). As compared with mid-volume operators, high-volume operators had a higher technical success rate in antegrade and retrograde procedures (93.4% vs 91.2% and 81.5% vs 69.0%, respectively; p<0.001), and had a lower MACCE rate (1.47% vs 2.41%; p<0.001) despite a higher mean complexity of the attempted lesions (J-CTO score: 2.42±1.28 vs 2.15±1.27; p<0.001)., Conclusions: The adoption of different recanalisation techniques, operator experience and the use of specific devices have contributed to a high procedural success rate despite the high complexity of the lesions documented in the ERCTO.

Aims: Chronotropic incompetence (CI) is a strong predictor of outcome in heart failure with reduced ejection fraction, however no data on its clinical and prognostic impacts in heart failure with mildly reduced ejection fraction (HFmrEF) are available. Therefore, the study aims to investigate, in a large multicentre HFmrEF cohort, the prevalence of CI as well as its relationship with exercise capacity and its prognostic role over the cardiopulmonary exercise testing (CPET) parameters., Methods and Results: Within the Metabolic Exercise combined with Cardiac and Kidney Indexes (MECKI) database, we analysed data of 864 HFmrEF out of 1164 stable outpatients who performed a maximal CPET at the cycle ergometer and who had no significant rhythm disorders or comorbidities. The primary study endpoint was cardiovascular (CV) death. All-cause death was also explored. Chronotropic incompetence prevalence differed depending on the method (peak heart rate, pHR% vs. pHR reserve, pHRR%) and the cut-off adopted (pHR% from ≤75% to ≤60% and pHRR% ≤ 65% to ≤50%), ranging from 11% to 62%. A total of 84 (9.7%) CV deaths were collected, with 39 (4.5%) occurring within 5 years. At multivariate analysis, both pHR% [hazard ratio 0.97 (0.95-0.99), P < 0.05] and pHRR% [hazard ratio 0.977 (0.961-0.993), P < 0.01] were associated with the primary endpoint. A pHR% ≤ 75% and a pHRR% ≤ 50% represented the most accurate cut-off values in predicting the outcome., Conclusion: The study suggests an association between blunted exercise-HR response, functional capacity, and CV death risk among patients with HFmrEF. Whether the CI presence might be adopted in daily HFmrEF management needs to be addressed in larger prospective studies., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Heart failure (HF) is a chronic condition in which the heart does not pump enough blood to meet the body's demands. Diffusing capacity of the lung for nitric oxide ( D LNO ) and carbon monoxide ( D LCO ) may be used to classify patients with HF, as D LNO and D LCO are lung function measurements that reflect pulmonary gas exchange. Our objectives were to determine 1) if D LNO added to D LCO testing predicts HF better than D LCO alone and 2) whether the binary classification of HF is better when D LNO z-scores are combined with D LCO z-scores than using D LCO z-scores alone., Methods: This was a retrospective secondary data analysis in 140 New York Heart Association Class II HF patients (ejection fraction <40%) and 50 patients without HF. z-scores for D LNO , D LCO and D LNO + D LCO were created from reference equations from three articles. The model with the lowest Bayesian Information Criterion was the best predictive model. Binary HF classification was evaluated with the Matthews Correlation Coefficient (MCC)., Results: The top two of 12 models were combined z-score models. The highest MCC (0.51) was from combined z-score models. At most, only 32% of the variance in the odds of having HF was explained by combined z-scores., Conclusions: Combined z-scores explained 32% of the variation in the likelihood of an individual having HF, which was higher than models using D LNO or D LCO z-scores alone. Combined z-score models had a moderate ability to classify patients with HF. We recommend using the NO-CO double diffusion technique to assess gas exchange impairment in those suspected of HF., Competing Interests: Conflict of interest: None declared., (Copyright ©The authors 2024.)

Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

The presence of collateral channels providing distal blood supply is a distinctive characteristic of chronic total occlusion (CTO) lesions. However, data about the distinct baseline and procedural characteristics of each collateral subset are scarce. Accordingly, we sought to explore the procedural aspects specific for each collateral typology (ipsilateral collaterals [ICs], contralateral collaterals [CCs] or mixed) in CTO-percutaneous coronary intervention (PCI). A retrospective analysis of our CTO-PCI registry was performed to investigate the prevalence, procedural characteristics, and outcomes specific for each CTO-PCI subset, defined according to the inter-arterial connection anatomy. A total of 209 cases were included. Of the included cases, 45 (22%) and 92 (44%) patients displayed solely IC or CC, respectively, whereas in 72 (34%) both IC and CC were present (mixed). The procedural success rate was high (91.1%) and comparable among the different groups, despite greater lesion complexity in the CC group. The most frequent target vessel was the left circumflex in the IC group (51% of cases) and the right coronary artery in the CC (63%) and mixed (57%) groups. Among the IC cases, 42% showed a poor collateral connection function (2% and 10% for the CC and mixed group, respectively), and 46% showed a suboptimal collateral recipient artery filling (21% and 20% for the CC and mixed group, respectively). Most of the IC cases were performed using a single access (96%). In conclusion, the success and complication rates were comparable among the collateral typology groups, irrespective of the differences in the baseline and procedural characteristics. Phenotyping CTO as hereby proposed might be helpful for targeted procedural considerations., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aims: In the EXPLORER-HCM trial, mavacamten reduced left ventricular outflow tract obstruction (LVOTO) and improved functional capacity of symptomatic hypertrophic obstructive cardiomyopathy (HOCM) patients. We sought to define the potential use of mavacamten by comparing real-world HOCM patients with those enrolled in EXPLORER-HCM and assessing their eligibility to treatment., Methods and Results: We collected information on HOCM patients followed up at 25 Italian HCM outpatient clinics and with significant LVOTO (i.e. gradient ≥30 mmHg at rest or ≥50 mmHg after Valsalva manoeuvre or exercise) despite pharmacological or non-pharmacological therapy. Pharmacological or non-pharmacological therapy resolved LVOTO in 1044 (61.2%) of the 1706 HOCM patients under active follow-up, whereas 662 patients (38.8%) had persistent LVOTO. Compared to the EXPLORER-HCM trial population, these real-world HOCM patients were older (62.1 ± 14.3 vs. 58.5 ± 12.2 years, p = 0.02), had a lower body mass index (26.8 ± 5.3 vs. 29.7 ± 4.9 kg/m 2 , p < 0.0001) and a more frequent history of atrial fibrillation (21.5% vs. 9.8%, p = 0.027). At echocardiography, they had lower left ventricular ejection fraction (LVEF, 66 ± 7% vs. 74 ± 6%, p < 0.0001), higher left ventricular outflow tract gradients at rest (60 ± 27 vs. 52 ± 29 mmHg, p = 0.003), and larger left atrial volume index (49 ± 16 vs. 40 ± 12 ml/m 2 , p < 0.0001). Overall, 324 (48.9%) would have been eligible for enrolment in the EXPLORER-HCM trial and 339 (51.2%) for treatment with mavacamten according to European guidelines., Conclusions: Real-world HOCM patients differ from the EXPLORER-HCM population for their older age, lower LVEF and larger atrial volume, potentially reflecting a more advanced stage of the disease. About half of real-world HOCM patients were found eligible to mavacamten., (© 2023 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)