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Heart failure with reduced ejection fraction (HFrEF) and chronic obstructive pulmonary disease (COPD) individually cause significant morbidity and mortality. Their coexistence is associated with even worse outcomes, partly due to suboptimal heart failure therapy, especially underutilisation of beta-blockers. Our aim was to investigate outcomes in HFrEF patients with and without COPD, and the effects of mineralocorticoid receptor antagonists (MRAs) on outcomes.\ud \ud Methods and results:\ud \ud We studied the effect of MRA therapy in a post-hoc pooled analysis of 4397 HFrEF patients in the RALES and EMPHASIS-HF trials. The primary endpoint was the composite of heart failure hospitalisation or cardiovascular death. A total of 625 (14.2%) of the 4397 patients had COPD. Patients with COPD were older, more often male, and smokers, but less frequently treated with a beta-blocker. In patients with COPD, event rates (per 100 person-years) for the primary endpoint and for all-cause mortality were 25.2 (95% confidence interval 22.1–28.7) and 17.2 (14.9–19.9), respectively, compared with 19.9 (18.8–21.1) and 12.8 (12.0–13.7) in participants without COPD. The risks of all-cause hospitalisation and sudden death were also higher in patients with COPD. The benefit of MRA, compared with placebo, was consistent in patients with or without COPD for all outcomes, e.g. hazard ratio for the primary outcome 0.66 (0.50–0.85) for COPD and 0.65 (0.58–0.73) for no COPD (interaction p = 0.93). MRA-induced hyperkalaemia was less frequent in patients with COPD.\ud \ud Conclusions:\ud \ud In RALES and EMPHASIS-HF, one-in-seven patients with HFrEF had coexisting COPD. HFrEF patients with COPD had worse outcomes than those without. The benefits of MRAs were consistent, regardless of COPD status.

Aims To perform evaluation of widely embraced bone scintigraphy-based non-biopsy diagnostic criteria (NBDC) for ATTR amyloid cardiomyopathy (ATTR-CM) in clinical practice, and to refine serum free light chain (sFLC) ratio cut-offs that reliably exclude monoclonal gammopathy (MG) in chronic kidney disease. Methods and results A multi-national retrospective study of 3354 patients with suspected or histologically proven cardiac amyloidosis (CA) referred to specialist centres from 2015 to 2021; evaluations included radionuclide bone scintigraphy, serum and urine immunofixation, sFLC assay, eGFR measurement and echocardiography. Seventy-nine percent (1636/2080) of patients with Perugini grade 2 or 3 radionuclide scans fulfilled NBDC for ATTR-CM through absence of a serum or urine monoclonal protein on immunofixation together with a sFLC ratio falling within revised cut-offs incorporating eGFR; 403 of these patients had amyloid on biopsy, all of which were ATTR type, and their survival was comparable to non-biopsied ATTR-CM patients (p = 0.10). Grade 0 radionuclide scans were present in 1091 patients, of whom 284 (26%) had CA, confirmed as AL type (AL-CA) in 276 (97%) and as ATTR-CM in only one case with an extremely rare TTR variant. Among 183 patients with grade 1 radionuclide scans, 122 had MG of whom 106 (87%) had AL-CA; 60/61 (98%) without MG had ATTR-CM. Conclusion The NBDC for ATTR-CM are highly specific [97% (95% CI 0.91-0.99)] in clinical setting, and diagnostic performance was further refined here using new cut-offs for sFLC ratio in patients with CKD. A grade 0 radionuclide scan all but excludes ATTR-CM but occurs in most patients with AL-CA. Grade 1 scans in patients with CA and no MG are strongly suggestive of early ATTR-type, but require urgent histologic corroboration.

The therapy of transthyretin (TTR)-related cardiac amyloidosis consists, on the one hand, of the prevention and management of complications (supportive therapy) and on the other of treatments aimed at interrupting or slowing down the production and deposition of fibrils (disease-modifying therapy). This definition includes drugs that act on different phases of amyloidogenesis: (i) silencing of the gene encoding TTR (small interfering RNA: patisiran, vutrisiran; antisense oligonucleotides: inotersen, eplontersen; new CRISPR Cas-9 drug technology for editing in vivo DNA); (ii) stabilization of circulating TTR to inhibit its dissociation and subsequent assembly of the resulting monomers in amyloidotic fibrils (tafamidis, acoramidis, and tolcapone); (iii) destruction and re-absorption of already formed amyloid tissue deposits. Drugs related to the latter strategy (antibodies) are still the subject of Phase 1 or 2 studies.

Aims In patients undergoing cardiac implantable electronic device (CIED) intervention, routine pre-procedure antibiotic prophylaxis is recommended. A more powerful antibiotic protocol has been suggested in patients at high risk of infection. Stratification of individual infective risk could guide the prophylaxis before CIED procedure. Methods and results Patients undergoing CIED surgery were stratified according to the Shariff score in low and high infective risk. Patients in the ‘low-risk’ group were treated with only two antibiotic administrations while patients in the ‘high-risk’ group were treated with a prolonged 9-day protocol, according to renal function and allergies. We followed-up patients for 250 days with clinical outpatient visit and electronic control of the CIED. As primary endpoint, we evaluated CIED-related infections. A total of 937 consecutive patients were enrolled, of whom 735 were stratified in the ‘low-risk’ group and 202 in the ‘high-risk’ group. Despite different risk profiles, CIED-related infection rate at 250 days was similar in the two groups (8/735 in ‘low risk’ vs. 4/202 in ‘high risk’, P = 0.32). At multivariate analysis, active neoplasia, haematoma, and reintervention were independently associated with CIED-related infection (HR 5.54, 10.77, and 12.15, respectively). Conclusion In a large cohort of patients undergoing CIED procedure, an antibiotic prophylaxis based on individual stratification of infective risk resulted in similar rate of infection between groups at high and low risk of CIED-related infection.

This meta-analysis aims to compare direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) in the setting of left ventricular thrombosis (LVT).We systematically searched MEDLINE, Cochrane Library, Biomed Central and Web of Science for trials comparing DOACs versus VKAs in the setting of LVT and reporting outcome data on thrombosis resolution, stroke and bleeding. Fourteen studies were finally selected. The Mantel-Haenszel method with a random effect model was used for the pooled analysis. The primary outcome was the occurrence of LVT resolution. The secondary outcomes were the occurrence of stroke or bleeding during treatment. One thousand three hundred and thirty-two patients were included in the analysis for the primary outcome. Of these, 424 were treated with DOACs and 908 with VKAs. The pooled odds ratio (OR) for the primary outcome was 1.00 [95% confidence interval (95% CI) 0.77-1.31, I2 0.0%], reflecting equal effect in terms of thrombus resolution. Overall, 2290 patients, 608 on DOACs and 1682 on VKAs were included in the analysis of stroke occurrence, showing reduced risk of events in patients treated with DOACs (pooled OR 0.58, 95% CI 0.36-0.93; I2 0.0%) as well as for bleeding occurrence (number of patients included 2139; pooled OR 0.64, 95% CI 0.44-0.94; I2 0.0%).Compared with VKAs, we found DOACs to have similar efficacy on thrombus resolution and favorable effects on stroke reduction and bleedings. DOACs should be considered as an alternative treatment for LVT. Large prospective randomized clinical trials are needed to confirm this exploratory finding.

Ile68Leu transthyretin-related amyloidosis (ATTR) is known as a mainly or exclusively cardiogenic variant. We hypothesized that an accurate specialized neurological evaluation could reveal a consistent frequency of mixed phenotypes.Forty-six consecutive subjects with transthyretin (TTR) Ile68Leu (p.Ile88Leu) mutation (29 patients and 17 unaffected carriers) underwent an in-depth cardiac and neurologic evaluation at a single center.All 29 patients showed cardiac involvement. In 20 (69%) cases, it was associated with neurological abnormalities (i.e. a mixed phenotype): 10 (35% of the total) had signs and symptoms of neuropathy, 5 (17%) had abnormalities at the neurologic specialist examination but without symptoms, and 5 (17%) had abnormal nerve conduction study only. None of the asymptomatic carriers showed neurological abnormalities or cardiac involvement. The Neuropathy Impairment Score was5 in seven patients at baseline, and became5 in six more patients during follow-up. The probability of experiencing a major adverse cardiac event (MACE) during follow-up was higher in the mixed than cardiologic phenotype (At least two-thirds of patients with Ile68Leu ATTR and amyloidotic cardiomyopathy show an associated - definite or probable - neurologic impairment of variable degree if accurately evaluated in a neurologic setting. This proportion can rise during follow-up. The mixed phenotype carries a worse prognosis compared to the exclusively cardiologic one. These observations show that more patients could be eligible for treatment with gene silencers than currently indicated and highlight the need for an in-depth and continuous multidisciplinary evaluation of Ile68Leu ATTR patients.

ObjectiveThe study was designed to: (1) confirm safety and feasibility of mini-invasive radial balloon aortic valvuloplasty (BAV); (2) assess its impact in terms of quality of life and frailty; and (3) evaluate whether changes in frailty after BAV are associated with death in patients undergoing transcatheter aortic valve implantation (TAVI).Methods330 patients undergoing BAV in 16 Italian centres were prospectively included. The primary endpoint was the occurrence of major and minor Valve Academic Research Consortium (VARC)-2 bleeding. Secondary endpoints were scales of quality of life, frailty, evaluated at baseline and 30 days, and their relationship with the occurrence of all-cause death.ResultsBAV was performed by radial access in 314 (95%) patients. No VARC-2 major and six (1.8%) VARC-2 minor bleedings occurred in the study population. Quality of life, as well as frailty status, significantly improved 30 days after BAV. At 1 year, patients undergoing TAVI with baseline essential frailty toolset (EFT) ConclusionsMini-invasive radial BAV is safe, feasible and associated with a low rate of vascular complications. Patients improving EFT 30 days after BAV showed a favourable outcome after TAVI.Trial registration numberNCT03087552.

This study compiles data to determine if procalcitonin (PCT) values may predict both the risk of bacterial infection and potentially negative long-term outcomes in patients with acute coronary syndromes (ACS). All patients with a diagnosis of ACS that had PCT levels assessed during the first 24 h of hospitalization were enrolled in this study. The primary outcome was to detect the presence of bacterial infection defined as the occurrence of fever and at least one positive blood or urinary culture with clinical signs of infection. The secondary outcome was to monitor the occurrence after 1 year of the composite outcome of all-cause mortality, stroke and myocardial infarction. Overall, 569 patients were enrolled (mean age 69.37 ± 14 years, 30% females). Of these, 44 (8%) met the criteria for bacterial infection. After multivariate analysis, PCT and SBP were found to be independent predictors of bacterial infections (OR for PCT above the cut-off 2.67, 95% CI 1.09–6.53, p = 0.032 and OR for SBP 0.98, 95% CI 0.97–0.99, p = 0.043). After 1 year, the composite outcome of all-cause death, MI and stroke occurred in 104 patients (18%). PCT was not found to be an independent predictor of these outcomes. In conclusion, when assessing ACS, we found that testing for PCT levels during hospital admissions procedures was a good predictor of bacterial infections but not of all-cause mortality, stroke, or myocardial infarction. Clinicaltrial.org identifier: NCT02438085.

The number of elderly patients undergoing cardiac surgery is increasing. Age greater than 80 years has been identified as a strong independent risk factor for shortand long-term survival. The current study is aimed to identify the impact of preoperative comorbidities on early and late outcomes in older patients undergoing cardiac surgery.Baseline characteristics, procedurals and postoperative complications of all patients undergoing cardiac surgery at our institution are collected. The current analysis is focused on patients aged at least 80 years at the time of intervention and treated from January 2010 to December 2019.In-hospital mortality resulted as 6.3%. Redo intervention [odds ratio (OR) 2.49, 95% confidence interval (CI) 1.13-5.48], chronic obstructive pulmonary disease (COPD) (OR 2.99, 95% CI 1.75-5.12) and peripheral arterial disease (PAD) (OR 2.23, 95% CI 1.30-3.81) were independent baseline predictors of outcome in the multivariate analysis. Prolonged extracorporeal circulation time, need for transfusion and prolonged intubation time strongly and independently predicted in-hospital mortality. During a mean follow-up of 3.6 years 34.3% of patients died and unplanned admission (HR 1.33, 95% CI 1.05-1.67), NYHA class III-IV (HR 1.35, 95% CI 1.12-1.64), diabetes (HR 1.27, 95% CI 1.01-1.59), COPD (HR 1.60, 95% CI 1.25-2.04) and PAD (HR 1.32, 95% CI 1.03-1.71) resulted as independent predictors of all-cause death.Cardiac surgery is feasible in octogenarians, with an acceptable risk of mortality. Chronological age itself should not be the main determinant of choice while referring patients for cardiac surgical intervention. Comorbidities such as COPD, PAD and diabetes need to be taken into account for risk stratification.

Aims To investigate the prognostic role of sex and physical performance on long-term mortality in older adults hospitalized for acute coronary syndrome (ACS). Methods and results The analysis is based on older (≥70 years) ACS patients included in the FRASER, HULK, and LONGEVO SCA prospective studies. Physical performance was assessed with the Short Physical Performance Battery (SPPB). The primary outcome was all-cause mortality. The study included 1388 patients, 441 (32%) were women. At presentation, women were older and more compromised than men. After a median follow-up of 998 (730–1168) days, all-cause death occurred in 334 (24.1%) patients. At univariate analysis, female sex was related to increased risk of death. After adjustments for confounding factors, female sex was no longer associated with mortality. Women showed poor physical performance compared with men (P Conclusions Two key findings emerged from the present real-life cohort of older ACS patients: (i) physical performance strongly influences long-term mortality and (ii) women with preserved physical performance have a better outcome compared to men.

About one in seven elderly patients with severe calcific aortic stenosis (AS) also have ATTR amyloid cardiomyopathy (AC-TTR). The reasons for this close association are not fully known, but the two entities are not only related by common epidemiology. For example, it is possible to hypothesize that an amyloidotic infiltration of the aortic valve, even partial, can act as a trigger for the development of endothelial damage and subsequent calcification. Another hypothesis is the increased myocardial strain induced by AS may locally favour the process of amyloidogenesis and tissue infiltration. In a patient with AS, the coexistence of AC-TTR can be suspected by careful analysis of the echocardiogram and the ECG, especially if a clinical history of carpal tunnel syndrome coexists. Bone tracer scintigraphy allows a diagnosis of certainty. Recently, several studies have evaluated the prognostic implications of the coexistence of the two entities in candidates for percutaneous aortic valve replacement, showing how amyloidosis would not significantly impact the results of the procedure, but would only be associated with a greater risk of distant heart failure. In patients with AS associated with AC-TTR, valve replacement should not be ruled out in the presence of the usual clinical-haemodynamic indications.

Background Glucagon-like Peptide-1 receptor agonists (GLP-1RAs) have been shown to lower cardiovascular risk, and they are likely to reduce the incidence of all-cause and cardiovascular mortality in patients with type 2 diabetes. In this study-level analysis we investigated how metabolic and blood pressure changes are related to the reduction of cardiovascular events with GLP-1RAs. Methods We included seven randomized, placebo-controlled trials (ELIXA, LEADER, SUSTAIN-6, REWIND, EXSCEL, PIONEER 6, Harmony Outcomes) reporting incidence of one or more of the following outcomes: MACE, stroke, myocardial infarction, cardiovascular death, all-cause death, for a total of 56004 patients. A Pearson correlation analysis between logHR for the occurrence of outcome and placebo-corrected changes in Hb1Ac, systolic blood pressure and weight was performed. Findings Reduction of HbA1c level was significantly related to the reduction of MACE, Pearson R 0.86 (p=0.006) and stroke, Pearson R 0.79 (p=0.018). The reduction of weight instead, showed a robust correlation, not only with reduction of MACE, Pearson R 0.75 (p=0.032) and stroke, Pearson R 0.71 (p=0.047), but also with reduction of both cardiovascular death, Pearson R 0.95 (p=0.003; Picture 1) and all-cause death, Pearson R 0.91 (p=0.013). Reduction of SBP was significantly related to the reduction of both cardiovascular death, Pearson R 0.84 (p=0.036) and all-cause death, Pearson R 0.88 (p=0.020), but not of MACE. Discussion Mechanism of GLP-1RAs in preventing MACE is not fully understood. Other drugs that improve glycemic control did not showed convincing effect on cardiovascular outcome. Our finding prompts some considerations: both weight loss and control of HbA1c levels could play a role in MACE reduction. On the other hand, GLP1-RAs could act through other mechanisms and the metabolic effect could be a marker of the drug potency and dosage. Based on mechanistic studies, a theorized mechanism of cardiovascular benefit seen with GLP-1 RA is thought to be an anti-atherothrombotic and lipid plaque stabilization effect. This seems particularly convincing seeing the strong relationship of weight change and major events reduction. Notably, reduction in cardiovascular mortality and all-cause mortality was not related to the anti-hyperglycemic effect. Contrarily the body weight and SBP reduction were strongly related to both cardiovascular and all-cause mortality. These features could support the presumption of a hypothetic GLP1-RAs mechanism in modulation of lipidic profile and in RAAS inhibition, which have been already proved as beneficial for primary and secondary cardiovascular prevention. Conclusion Cardiovascular protection from GLP1-RAs is not primarily related to HbA1c reduction itself. Our data suggest that GLP-1RAs with the greater metabolic impact, such as liraglutide and semaglutide, should be used to treat diabetic patients to prevent MACE and CV death. Funding Acknowledgement Type of funding sources: None.

Hitherto, no study has yielded important information on whether the scales of frailty may improve the ability to discriminate the risk of haemorrhages in older adults admitted to hospital for acute coronary syndrome (ACS). The aim of this study is to investigate whether frailty scales would predict the 1-year occurrence of haemorrhagic events and if they confer a significant incremental prognostic value over the bleeding risk scores. The present study involved 346 ACS patients aged ≥ 70 years enrolled in the FRASER study. Seven different scales of frailty and PARIS, PRECISE-DAPT and BleeMACS bleeding risk scores were available for each patient. The outcomes were the 1-year BARC 3-5 and 2 bleeding events. Adherence to antiplatelet treatment at 1, 6 and 12 months was 98%, 87% and 78%, respectively. At 1-year, 14 (4%) and 30 (9%) patients presented BARC 3-5 and 2 bleedings, respectively. Bleeding risk scores and four scales of frailty (namely Short Physical Performance Battery, Columbia, Edmonton and Clinical Frailty Scale) significantly discriminated the occurrence of BARC 3-5 events. The addition of the scales of frailty to bleeding risk scores did not lead to a significant improvement in the ability to predict BARC 3-5 bleedings. Neither the bleeding risk scores nor the scales of frailty predicted BARC 2 bleedings. Both the bleeding risk scores and the scales of frailty predicted BARC 3-5 haemorrhages. However, integrating the scales of frailty with the bleeding risk scores did not improve their discriminative ability. www.clinicaltrials.gov: NCT02386124

Background Early administration of P2Y12-receptor inhibitors is recommended in all patients with acute coronary syndrome undergoing invasive management, with the aim to achieve the fastest and most effective platelet inhibition. Several trials investigated alternative methods of P2Y12-receptor inhibitor administration (mainly chewed or crushed) aimed at ensuring faster and higher platelet inhibition. Thus, we decided to perform a systematic review and meta-analysis analyzing efficacy and safety of alternative P2Y12-receptor inhibitor administration strategies. Methods Systematic research was performed on Pubmed, Cochrane Library, Biomed Central, and Web of Science databases. We included randomized or observational trials testing at least one P2Y12-receptor inhibitor alternative administration. The primary outcome of the study was the value of the platelet reactivity unit (PRU) at 1 h after drug administration, assessed by VerifyNow P2Y12 test (Accumetrics, Inc., San Diego, CA). Secondary outcomes were adverse bleeding events (safety outcome). Results and discussion Fourteen studies were selected for qualitative analysis. Five studies, all focused on ticagrelor, were selected for quantitative efficacy analyses. These five studies compared the administration of crushed/chewed ticagrelor 180 mg loading dose (LD) with the standard whole tablets LD. The pooled mean difference between the two administrations was -59.24 PRU (95% CI from -30.61 to -87.87 PRU) in favor of the crushed/chewed administration, corresponding to a 25% mean relative PRU reduction between alternative and standard P2Y12-receptor inhibitor administrations at 1 h after drug intake. A similar relationship was found in other studies on alternative administration of clopidogrel and prasugrel, not included in the quantitative analysis.

The association of chronic obstructive pulmonary disease (COPD) and ischaemic heart disease (IHD) is challenging both in terms of prognosis and of pharmacological treatment. An 83-year-old Caucasian male patient has chronic kidney disease, COPD, previous myocardial infarction, coronary artery bypass graft with left internal mammary artery (LIMA) on left anterior descending (LAD), saphenous vein graft (SVG) on obtuse marginal (OM)1 and on right coronary artery, and percutaneous coronary intervention (PCI) on LAD (occlusion of LIMA) and on SVG for OM1 (SVG critical stenosis). Recently, the patient complained worsening angina [Canadian Cardiovascular Society (CCS) III] and had residual ischaemia in the anterior wall after an unsuccessful attempt of PCI was performed on LAD for in-stent occlusion due to restenosis. Bisoprolol uptitration failed due to worsening of pulmonary function at spirometry. For this reason, ivabradine 5 mg b.i.d. was added to bisoprolol. Afterwards, the patient referred amelioration of symptoms and he is actually in CCS Class I. The control spirometry showed moderate obstruction comparable to his chronic situation. Patients with IHD and COPD often do not receive β-blockers due to the fear of adverse effects. However, cardioselective β-blockers do not worsen pulmonary function while they reduce mortality in COPD patients. In this setting, ivabradine could be extremely helpful in order to control symptoms since it is effective in patients with asthma and COPD, with no alteration in respiratory function or symptoms and improves exercise capacity and functional class in COPD patients.

Background Sex influences outcome of patients with acute coronary syndrome (ACS). If there is a relationship between sex and physical performance is unknown. Methods The analysis is based on older (≥70 years) ACS patients included in the FRASER, HULK, and LONGEVO SCA prospective studies. Physical performance was assessed by Short Physical Performance Battery (SPPB). The primary outcome was all-cause mortality. Results The study included 1388 patients, and 441 (32%) were women. At presentation, women were older and more compromised than men. After a median follow-up of 998 [730–1168] days, all-cause death occurred in 334 (24.1%) patients. At univariate analysis, female sex was related to increased risk of death. After adjustments for confounding factors, female sex was no longer associated with mortality. Women showed poor physical performance compared with men (p < 0.001). SPPB values emerged as an independent predictor of death. Including clinical features and SPPB in the multivariable model, we observed a paradigm shift in the prognostic role of female sex that becomes a protective factor (HR 0.73, 95% CI 0.56–0.96). Sex and physical performance showed a significant interaction (p = 0.03). For lower SPPB values (poor physical performance), sex-related changes in mortality were not recorded, while in patients with higher SPPB values (preserved physical performance), female sex was associated with better survival. Conclusions Two key findings emerged from the present real-life cohort of older ACS patients: (i) physical performance strongly influences long-term mortality; (ii) women with preserved physical performance have a better outcome compared to men. Trial registration www.clinicaltrials.gov NCT02386124 and NCT03021044

Funding Acknowledgements Type of funding sources: None. Background novel oral anticoagulants (NOACs) are not guideline-recommanded treatment for left ventricular thrombus. Purpose: the aim of this meta-analysis is to compare NOACs versus vitamin-K atagonsits (VKAs) efficacy in treating left ventricular thrombus (LVT). Methods: we systematically searched MEDLINE, Cochrane Library, Biomed Central, and Web of Science for trials comparing NOACs versus VKAs in the setting of LVT. Five studies, out of the 74 initially selected after first screening, were included in the meta-analysis. For the development of this meta-analysis, the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines were followed. The shortlisted studies were retrieved as full articles and appraised independently by two unblinded reviewers. The Mantel-Haensel method with a random effect model was used for the pooled analysis. The primary outcome was the occurrence of stroke and systemic embolism. Secondary outcome was occurrence of left ventricular thrombosis resolution during treatment. Results: 707 patients were included in the analysis for the primary outcome. Of these, 230 were treated with NOACs and 477 with VKAs. The pooled OR for the primary outcome was 0.71 (95% CI 0.18-2.86, I2 67%), thus showing similar effect in term of ischaemic protection. A total of 698 patients, 228 on NOACs and 470 on VKAs were included in the analysis of the secondary outcome. The pooled OR for the secondary outcome pooled OR 0.97, 95% CI 0.56-1.68, I2 46%. Conclusions and Relevance: NOACs seem to have a similar efficacy profile compare to VKAs and so they should be considered as an alternative treatment for left ventricular thrombosis. Large prospective randomized clinical trials are needed to confirm this exploratory finding. Abstract Figure 1

BACKGROUND COPD patients have higher recurrence of adverse events and worse prognosis after acute coronary syndrome (ACS). The underlying pathophysiological mechanism is not fully elucidated. METHODS In screening for COPD in ACS (SCAP) trial (NCT02324660), ACS patients with smoking habit underwent a predischarge screening procedure to detect undiagnosed chronic obstructive pulmonary disease (UCOPD) confirmed with spirometry at 60 days. Patients were then categorized as UCOPD or no-COPD. In 65 NSTE-ACS patients, we performed near infrared spectroscopy (NIRS) in the culprit and at least one non-culprit vessel (151 vessels overall), and we calculated the SYNTAX I score. Primary endpoint was max lipid core burden index (LCBI) 4 mm. Secondary endpoints were SYNTAX score I and vessel LCBI. RESULTS Max LCBI 4 mm and vessel LCBI were significantly higher in the UCOPD compared to the no-COPD group (UCOPD 388±122, no-COPD 264±131, p

Background Amyloid transthyretin (ATTR) amyloidosis is caused by the systemic deposition of transthyretin molecules, either normal (wild‐type ATTR, ATTRwt) or mutated (variant ATTR, ATTRv). ATTR amyloidosis is a disease with a severe impact on patients’ quality of life (QoL). Nonetheless, limited attention has been paid to QoL so far, and no specific tools for QoL assessment in ATTR amyloidosis currently exist. QoL can be evaluated through patient‐reported outcome measures (PROMs), which are completed by patients, or through scales, which are compiled by clinicians. The scales investigate QoL either directly or indirectly, i.e., by assessing the degree of functional impairment and limitations imposed by the disease. Design Search for the measures of QoL evaluated in phase 2 and phase 3 clinical trials on ATTR amyloidosis. Results Clinical trials on ATTR amyloidosis have used measures of general health status, such as the Short Form 36 Health Survey (SF‐36), or tools developed in other disease settings such as the Kansas City Cardiomyopathy Questionnaire (KCCQ) or adaptations of other scales such as the modified Neuropathy Impairment Score +7 (mNIS+7). Conclusions Scales or PROMs for ATTR amyloidosis would be useful to better characterize newly diagnosed patients and to assess disease progression and response to treatment. The ongoing ITALY (Impact of Transthyretin Amyloidosis on Life qualitY) study aims to develop and validate 2 PROMs encompassing the whole phenotypic spectrum of ATTRwt and ATTRv amyloidosis, that might be helpful for patient management and may serve as surrogate endpoints for clinical trials.

Background To investigate the relationship between 1-year outcome and diastolic dysfunction (DD) and frailty and/or physical performance (PP) in older adults admitted to hospital for acute coronary syndrome (ACS). Methods and results Older (age ≥ 70 years) hospitalized for ACS and receiving coronary artery angiography ± percutaneous coronary intervention were included. Before discharge a complete transthoracic echocardiogram (TTE) was performed with the assessment of DD, following the 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging algorithm. Seven different scales of frailty and PP were assessed. The relationship between DD and tests of frailty and PP was investigated, as well as the association with the 1-year occurrence of all-cause death or re-hospitalization. Overall, 329 patients were included in the analysis. Patients were stratified in two groups: DD grade 0–1 versus 2–3. Those with undetermined degree of DD have been excluded by the analysis (n = 106). Mean age of the groups was 77 ± 5 vs 79 ± 6 years, respectively. Scales of frailty and/or PP were significantly poor in patients with DD grade 2–3 compared to the others. After multivariate Cox regression (considering age, female sex, haemoglobin, albumin, clinical presentation, LVEF and SPPB) DD (degree 2–3 vs. 0–1) emerged as an independent predictor of the composite endpoint (HR 1.69, 95%CI 1.04–2.75, p = 0.033). This was mainly driven by 1-year re-hospitalization (HR 2.01, 95%CI 1.22–3.27, p Conclusions In older ACS patients the assessment of DD is related to parameters of frailty and PP and it is an independent predictor of 1-year outcome.

Background The 12‐lead ECG plays a key role in the diagnosis of Brugada syndrome (BrS). Since the spontaneous type 1 ECG pattern was first described, several other ECG signs have been linked to arrhythmic risk, but results are conflicting. Methods and Results We performed a systematic review to clarify the associations of these specific ECG signs with the risk of syncope, sudden death, or equivalents in patients with BrS. The literature search identified 29 eligible articles comprising overall 5731 patients. The ECG findings associated with an incremental risk of syncope, sudden death, or equivalents (hazard ratio ranging from 1.1–39) were the following: localization of type 1 Brugada pattern (in V2 and peripheral leads), first‐degree atrioventricular block, atrial fibrillation, fragmented QRS, QRS duration >120 ms, R wave in lead aVR, S wave in L1 (≥40 ms, amplitude ≥0.1 mV, area ≥1 mm 2 ), early repolarization pattern in inferolateral leads, ST‐segment depression, T‐wave alternans, dispersion of repolarization, and Tzou criteria. Conclusions At least 12 features of standard ECG are associated with a higher risk of sudden death in BrS. A multiparametric risk assessment approach based on ECG parameters associated with clinical and genetic findings could help improve current risk stratification scores of patients with BrS and warrants further investigation. Registration URL: https://www.crd.york.ac.uk/prospero/ . Unique identifier: CRD42019123794.

Whether contrast-associated acute kidney injury (CA-AKI) is only a bystander or a risk factor for mortality in older patients undergoing percutaneous coronary intervention (PCI) is not well understood. Data from FRASER (NCT02386124) and HULK (NCT03021044) studies have been analysed. All patients enrolled underwent coronary angiography. The occurrence of CA-AKI was defined based on KDIGO criteria. The primary outcome of the study was to test the relation between CA-AKI and 3-month mortality. Overall, 870 older ACS adults were included in the analysis (mean age 78 ± 5 years, 28% females). CA-AKI occurred in 136 (16%) patients. At 3 months, 13 (9.6%) patients with CA-AKI died as compared with 13 (1.8%) without it (p &lt, 0.001). At multivariable analysis, CA-AKI emerged as independent predictor of 3-month mortality (HR 3.51, 95%CI 1.05–7.01). After 3 months, renal function returned to the baseline value in 78 (63%) with CA-AKI. Those without recovered renal function (n = 45, 37%) showed an increased risk of mortality as compared to recovered renal function and no CA-AKI subgroups (HR 2.01, 95%CI 1.55–2.59, p = 0.009 and HR 2.71, 95%CI 1.45–5.89, p &lt, 0.001, respectively). In conclusion, CA-AKI occurs in a not negligible portion of older MI patients undergoing invasive strategy and it is associated with short-term mortality.

Background The number of older patients presenting with acute coronary syndrome (ACS) is increasing. Routine percutaneous coronary intervention (PCI) is performed in order to improve outcome, but comorbidities associated with aging lead to a higher risk of treatment complications. Contrast-induced acute kidney injury (CI-AKI) represents potential harm in older and frail patients, but its impact on long term prognosis is not clear. Purpose To evaluate occurrence, predictors, and impact on long term outcome of CI-AKI in elderly patients presenting with ACS. Methods A prospective cohort of 392 older (≥70 years) ACS patients who underwent coronary angiography was enrolled. CI-AKI was defined as a serum creatinine increase at least ≥0.3 mg/dl in 48 h or at least ≥50% in 7 days. According to our department protocol, prophylactic hydration was performed to all patients with isotonic saline, given intravenously at a rate of 1 ml/kg body weight/h (0.5 ml/kg for patients with left ventricular ejection fraction Results CI-AKI was observed in 72 patients (18.4%). Among patients who developed or not CI-AKI, no difference was found between clinical presentation (Non-ST segment elevation myocardial infarction (NSTEMI) vs. STEMI), left ventricular ejection fraction and multivessel coronary disease. Estimated glomerular filtration rate (odd ratio (OR) 3.59, confidence interval (CI) 1.79–7.20, p1 (HR 2.20, CI 1.32–3.67, p=0.003) and haemoglobin level (HR 0.84, CI 0.76–0.92, p Conclusions CI-AKI is a common complication among older adults undergoing coronary angiography for ACS. Patients who developed CI-AKI had worse outcome at long term follow-up. Actually, the occurrence of CI-AKI was not identified as an independent predictor for long-term adverse outcome, while it may represent a marker of severity of comorbidity and consequent poor prognosis, rather than a causal agent itself. Figure 1. Kaplan-Maier Curve Funding Acknowledgement Type of funding source: None

Aims Concern about hypotension often leads to withholding of beneficial therapy in patients with heart failure and reduced ejection fraction (HFrEF). We evaluated the efficacy and safety of dapagliflozin, which lowers systolic blood pressure (SBP),according to baseline SBP in Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial (DAPA-HF). Methods and results Key inclusion criteria were: New York Heart Association Class II−IV, left ventricular ejection fraction ≤ 40%, elevated N-terminal pro-B-type natriuretic peptide level, and SBP ≥95 mmHg. The primary outcome was a composite of worsening heart failure or cardiovascular death. The efficacy and safety of dapagliflozin were examined using SBP as both a categorical and continuous variable. A total of 1205 patients had a baseline SBP, Graphical Abstract

Background The number of older adults admitted to hospital for acute coronary syndrome (ACS) has increased worldwide. The aim of this study was to determine which scale of frailty or physical performance provides incremental improvements in risk stratification of older adults after ACS. Methods A prospective cohort of 402 older (≥70 years) ACS patients were enrolled. Data about baseline characteristics, Global Registry of Acute Coronary Events (GRACE), and Thrombolysis in Myocardial Infarction (TIMI) risk scores were collected. Before hospital discharge, seven scales of frailty and physical performance were measured. The 1-year occurrence of adverse events (cardiac death, reinfarction, and cerebrovascular accident [MACCE] and all-cause mortality) was recorded. Results Out of the 402 patients, 43 (10.5%) had a MACCE and 35 (8.7%) died. Following adjustment for confounding factors, scales of frailty and physical performance were associated with adverse events. Among the scales, the addition of short physical performance battery (SPPB) produced the highest incremental value over the initial model generated by baseline characteristics both for MACCE (ΔC-statistic 0.043, p = .04; integrated discrimination improvement (IDI) 0.054, p = .001; net reclassification improvement (NRI) 0.752, p < .001) and all-cause mortality (ΔC-statistic 0.063, p = .02; IDI 0.061, p < .001; NRI 1.022, p < .001). The addition of SPPB scale on top of GRACE or TIMI risk scores led to a considerable improvement in the prediction of MACCE and all-cause mortality (about 15% and 20%, respectively). Conclusions The assessment of the physical performance with SPPB scale before hospital discharge increases the ability to predict adverse events in older ACS patients and may be useful in the clinical decision-making process. Clinical trial registration www.clinicaltrials.gov NCT02386124.

Objective: We sought to demonstrate that the combination of a local vasodilator (verapamil), modern materials, patent hemostasis, and intravenous anticoagulant only in the case of percutaneous coronary intervention, as compared to default heparin administration after sheath insertion, may optimize a combined endpoint, including radial artery oc­clusion (RAO), radial artery spasm (RAS), and access site complication. Methods: This is a prospective, single-center, double-blind randomized trial. Overall, 418 patients undergoing a transradial approach (TRA) for coronary procedures were randomized 1: 1 to receive intraradial verapamil (5 mg) or heparin (5,000 IU) after a 6-Fr sheath insertion. The primary outcome was the 24-h occurrence of RAO (ultrasound confirmation), access site complication, and RAS requiring the bailout administration of vasodilators. Results: The combined primary outcome occurred in 127 (30%) patients. It was significantly lower in patients randomized to verapamil as compared to others (26 vs. 35%, p = 0.03). This was mainly due to a significant reduction in RAS (3 vs. 10%, p = 0.006). The 24-h and 30-day occurrence of RAO did not differ between the study groups. Conclusion: Local administration of verapamil versus heparin reduces RAS, without increasing RAO, which appears to be strictly related to radial artery diameter and hemostasis time.

BACKGROUND No study has evaluated the clinical consequences of stent fracture (SF) detected during the index percutaneous coronary intervention (PCI). Thus, we sought to investigate the relationship between SF detected during PCI and clinical outcome.Methods and Results:We consecutively enrolled 832 patients with SF-predisposing factors undergoing 2nd-generation drug-eluting stent implantation and enhanced stent visualization (ESV) system evaluation to detect SF at index PCI. The primary endpoint was a 9-month device-oriented endpoint (DOCE, including cardiac death, target vessel myocardial infarction, and target lesion revascularization). We observed 136 SF in 115 patients (14% of study population). SF I-II was present in 78 patients (68% of patients with SF), and SF III-IV occurred in 37 patients (32%). DOCE at 9 months occurred in 135 patients (16% of the overall population). There was a significant difference in DOCE occurrence between the 3 groups (P=0.006 at log-rank), driven by the SF III-IV group (P=0.001 vs. no SF group, and P=0.01 vs. SF I-II group). In 23 cases of SF III-IV (62%) a further stent was implanted. DOCE occurrence was significantly higher in patients with "untreated" type III-IV SF as compared with the "treated" ones (9% vs. 79%, P

ObjectiveTo establish the benefits of an early, tailored and low-cost exercise intervention in older patients hospitalised for acute coronary syndrome (ACS).MethodsThe study was a multicentre, randomised assessment of an exercise intervention in patients with ACS ≥70 years with reduced physical performance (as defined by the short physical performance battery (SPPB), value 4–9). The exercise intervention included four supervised sessions (1, 2, 3, 4 months after discharge) and home-based exercises. The control group attended a health education programme only. The outcomes were the 6-month and 1-year effects on physical performance, daily activities, anxiety/depression and quality of life. Finally, 1-year occurrence of adverse events was recorded.ResultsOverall, 235 patients with ACS (median age 76 (73–81) years) were randomised 1 month after ACS. Exercise and control groups were well balanced. Exercise intervention improved 6-month and 1-year grip strength and gait speed. Exercise intervention was associated with a better quality of life (as measured by EuroQol-visual analogue scale at 6 months 80 (70–90) vs 70 (50–80) points, pConclusionsThe proposed early, tailored, low-cost exercise intervention improves mobility, daily activities, quality of life and outcomes in older patients with ACS. Larger studies are needed to confirm the clinical benefit.Trial registration numberNCT03021044.

Background: The DAPA-HF trial (Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure) showed that dapagliflozin added to other guideline-recommended therapies reduced the risk of mortality and heart failure hospitalization and improved symptoms in patients with heart failure and reduced ejection fraction. We examined the effects of dapagliflozin according to age, given potential concerns about the efficacy and safety of therapies in the elderly. Methods: Patients in New York Heart Association functional class II or greater with a left ventricular ejection fraction ≤40% and a modest elevation of NT-proBNP (N-terminal pro-B-type natriuretic peptide) were eligible. Key exclusion criteria included systolic blood pressure −1 ·1.73 m −2 . The primary outcome was the composite of an episode of worsening heart failure (heart failure hospitalization or urgent heart failure visit) or cardiovascular death, whichever occurred first. Results: A total of 4744 patients 22 to 94 years of age (mean age, 66.3 [SD 10.9] years) were randomized: 636 patients (13.4%) were P for interaction=0.76). Consistent benefits were observed for the components of the primary outcome, all-cause mortality, and symptoms. Although adverse events and study drug discontinuation increased with age, neither was significantly more common with dapagliflozin in any age group. Conclusions: Dapagliflozin reduced the risk of death and worsening heart failure and improved symptoms across the broad spectrum of age studied in DAPA-HF. There was no significant imbalance in tolerability or safety events between dapagliflozin and placebo, even in elderly individuals. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03036124.

Background & aims The present analysis investigated the prevalence and the prognostic implication of nutritional status in older adults hospitalized for acute coronary syndrome (ACS). Methods The analysis is based on older ACS patients included in the FRASER and LONGEVO SCA studies. The Global Risk of Acute Coronary Events (GRACE) risk score was computed in all patients. Nutritional status was assessed with the Mini Nutritional Assessment-Short Form (MNA-SF, normal for values between 12 and 14, at risk of malnutrition for values between 8 and 11, and malnutrition for values ≤ 7). Physical performance was assessed with the Short Physical Performance Battery (SPPB). Primary outcome was all-cause mortality. Results The study included 908 patients. Overall, 35 patients (4%) were malnourished and 361 (40%) were at risk of malnutrition. After a median follow-up of 288 [187–370] days, the primary endpoint occurred in 94 (10.5%) patients. The mortality rate was 31% in malnourished subjects, 19% in at-risk patients, 3% in patients with a normal nutritional status (p < 0.001). MNA-SF emerged as an independent predictor of all-cause mortality (HR 0.76, 95%CI 0.68–0.84 for single change unit). The MNA-SF score improved the GRACE score's ability to discriminate subjects at risk of death (ΔC-statistic = 0.076, p < 0.001; ΔBIC -28; IDI 0.052, p < 0.001; NRI 0.793, p < 0.001). The prognostic value of MNA-SF was maintained also by including the SPPB score in the predictive model. Conclusion s: The MNA-SF helped to identify malnutrition in older ACS patients. Moreover, the MNA-SF value is an independent predictor of all-cause mortality and it improves the predictive value of the GRACE risk score. Sin financiación 7.325 JCR (2020) Q1, 7/88 Nutrition & Dietetics 1.915 SJR (2020) Q1, 8/88 Critical Care and Intensive Care Medicine No data IDR 2020 UEM

Frailty has become a high-priority issue in cardiovascular medicine because of the aging of cardiovascular patients. Simple and reproducible tools to assess frailty in elderly patients are clearly on demand. Their application may help physicians in the selection of invasive and medical treatments and in the timing and modality of the follow-up. The frailty in elderly patients receiving cardiac interventional procedures (FRASER) program is designed with the aim to validate the use of the short physical performance battery (SPPB) as prognostic tools in patients admitted to hospital for acute coronary syndrome (ACS). The FRASER program is a multicenter prospective study involving 4 Italian cardiology units. The FRASER program enrolls only patients aged ≥70 years. The core of the FRASER program includes patients admitted to hospital for ACS. The aims are (1) to describe SPPB distribution before hospital discharge and (2) to investigate the prognostic role of SPPB score. The primary outcome is a composite of 1-year all-cause mortality and hospital readmission for any cause. Ancillary analyses will be focused on different study populations (patients hospitalized for arrhythmias or acute heart failure or symptomatic severe aortic stenosis) and on different tools to assess frailty (multidimensional prognostic index, clinical frailty score, grip strength). The FRASER program will fill critical gaps in the knowledge regarding the link between frailty, cardiovascular disease, interventional procedures and outcome and will help physicians in the generation of a more personalized risk assessment and in the identification of potential targets for interventions.