Complete vs. Culprit-Only Revascularization in Older Patients with ST-segment Elevation Myocardial Infarction: An Individual Patient Meta-Analysis.

Background: Complete revascularization is the standard treatment for patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease. The Functional Assessment in Elderly MI Patients with Multivessel Disease (FIRE) trial confirmed the benefit of complete revascularization in a population of older patients, but the follow-up is limited to 1 year. Therefore, the long-term benefit ( > 1-year) of this strategy in older patients is debated. To address this, an individual patient data meta-analysis was conducted in STEMI patients aged 75 years or older enrolled in randomized clinical trials investigating complete vs. culprit-only revascularization strategies. Methods: PubMed, Embase, and the Cochrane database, were systematically searched to identify randomized clinical trials comparing complete vs. culprit-only revascularization. Individual patient-level data were collected from the relevant trials. The primary endpoint was death, myocardial infarction (MI), or ischemia-driven revascularization. The secondary endpoint was cardiovascular death or myocardial infarction. Results: Data from seven RCTs, encompassing 1733 patients (917 randomized to culprit-only and 816 to complete revascularization), were analyzed. The median age was 79 [77-83] years. Females were 595 (34%). Follow-up ranged from a minimum of six months to a maximum of 6.2 years (median 2.5 [1-3.8] years). Complete revascularization reduced the primary endpoint up to four years (HR 0.78, 95%CI 0.63-0.96), but not at the longest available follow-up (HR 0.83, 95%CI 0.69-1.01). Complete revascularization significantly reduced the occurrence of cardiovascular death or MI at the longest available follow-up (HR 0.76, 95%CI 0.58-0.99). This was observed even when censoring the follow-up at each year. Long-term rate of death did not differ between complete and culprit-only revascularization arms. Conclusions: In this individual patient data meta-analysis of older STEMI patients with multivessel disease, complete revascularization reduced the primary endpoint of death, MI or ischemia-driven revascularization up to 4-year. At the longest follow-up, complete revascularization reduced the composite of cardiovascular death or MI, but not the primary endpoint. Clinical Study Registration: PROSPERO CRD42022367898.

Tc-99m labelled bone scintigraphy in suspected cardiac amyloidosis.

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.

Clinical Outcome of FFR-Guided Revascularization Strategy of Coronary Lesions: The HALE-BOPP Study.

Background: Recently, questions around the efficacy and effectiveness of Fractional Flow Reserve (FFR) have arisen in various clinical settings. Methods: The Clinical Outcome of FFR-guided Revascularization Strategy of Coronary Lesions (HALE-BOPP) study is an investigator-initiated, multicentre, international prospective study enrolling patients who underwent FFR measurement on at least one vessel. In accordance with the decision-making workflow and treatment, the vessels were classified in three subgroups: (i) angio-revascularized, (ii) FFR-revascularized, (iii) FFR-deferred. The primary endpoint was the occurrence of target vessel failure (TVF, cardiac death, target vessel myocardial infarction and ischemia-driven target vessel revascularization). The analysis was carried out at vessel- and patient-level. Results: 1305 patients with 2422 diseased vessels fulfilled the criteria for the present analysis. Wire-related pitfalls and transient adenosine-related side effects occurred in 0.8% (95% CI: 0.4%-1.4%) and 3.3% (95% CI: 2.5%-4.3%) of cases, respectively. In FFR-deferred vessels, the overall incidence rate of TVF was 0.024 (95% CI: 0.019-0.031) lesion/year. After a median follow-up of 3.6 years, the occurrence of TVF was 6%, 7% and 11.7% in FFR-deferred, FFR-revascularized and angio-revascularized vessels, respectively. Compared to angio-revascularized vessels, FFR-guided vessels (both FFR-revascularized and FFR-deferred vessels) showed a lower TVF incidence rate lesion/year (0.029, 95% CI: 0.024-0.034 vs. 0.049, 95% CI: 0.040-0.061 respectively, p = 0.0001). The result was consistent after correction for confounding factors and across subgroups of clinical interest. The patient-level analysis confirmed the lower occurrence of TVF in negative-FFR vs. positive-FFR subgroups. Conclusions: In a large prospective observational study, an FFR-based strategy for the deferral of coronary lesions is a reliable and safe tool, associated with good outcomes. Clinical Trial Registration: NCT03079739.

Cardiovascular prevention: sometimes dreams can come true.

Cardiovascular disease (CVD) is a chronic condition driven by the complex interaction of different risk factors including genetics, lifestyle, environment, etc. which, differently from other pathologies, can be prevented. Treatment of CVD has been inconceivably successful but now it seems that it has reached a plateau suggesting that prevention is the way forward. However, the COVID-19 pandemic has spotted all the limits of the actual health system regarding territorial and, particularly, of preventive medicine. To this end, recently, the SCORE2 risk prediction algorithms, a contemporary model to estimate 10 years risk of CVD in Europe and the new guidelines on prevention have been released. The present review article describes a dream: how prevention of CVD should be addressed in the future. New concepts and paradigms like early genetically personalized and imaging driven risk factors, cardiac risk cartography, measurements of the exposome, estimation of costs of a delayed outcome vs. healthy lifespan, are all addressed. We highlight the importance of technologies and the concept of being engaged in a 'healthy' and not just 'sick' system as it is today. The concept of 'clearing house' with a 'care health team' instead of a 'heart team' is described. Finally, we articulate the four points necessary for the dream to come true.

The impact of sex and physical performance on long-term mortality in older patients with myocardial infarction.

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.

Complete versus culprit-only strategy in older MI patients with multivessel disease.

AIMS: The revascularization strategy to pursue in older myocardial infarction (MI) patients with multivessel disease (MVD) is currently unknown. For this reason, while waiting for the results of dedicated trials, we sought to compare a complete versus a culprit-only strategy in older MI patients by merging data from four registries. METHODS AND RESULTS: The inclusion criteria for the target population of the present study were (i) age ≥ 75 years; (ii) MI (STE or NSTE); (iii) MVD; (iv) successful treatment of culprit lesion. Propensity scores (PS) were derived using logistic regression (backward stepwise selection, p < 0.2). The primary outcome was all-cause mortality. Secondary outcomes were cardiovascular (CV) death, MI, and major bleeding. Multivariable adjustment included the PS and inverse probability of treatment weighting (IPTW). The Kaplan-Meier plots were weighted for IPT. Among 2087 patients included, 1362 (65%) received culprit-only treatment whereas 725 (35%) complete revascularization. The mean age was 81.5 years, while the mean follow-up was 419 ± 284 days. Seventy-four patients (10%) died in the complete group and 223 in the culprit-only one (16%). The adjusted cumulative 1-year mortality was 9.7% in the complete and 12.9% in the culprit-only group (adjusted HR: 0.67, 95% CI: 0.50-0.89). Complete revascularization was associated with lower incidence of CV death (adjusted HR: 0.68, 95% CI: 0.48-0.95) and MI (adjusted HR 0.67, 95% CI: 0.48-0.95). CONCLUSIONS: Culprit-only is the default strategy in older MI patients with MVD. In our analysis, complete revascularization was associated with lower all-cause and CV mortality and with a lower MI rate.

Antibiotic prophylaxis based on individual infective risk stratification in cardiac implantable electronic device: the PRACTICE study.

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.

The treatment of amyloidosis is being refined.

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.

Efficacy and Safety of Dapagliflozin in Heart Failure With Reduced Ejection Fraction According to Age: Insights From DAPA-HF.

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 <95 mm Hg and estimated glomerular filtration rate <30 mL·min-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 <55 years of age, 1242 (26.2%) were 55 to 64 years of age, 1717 (36.2%) were 65 to 74 years of age, and 1149 (24.2%) were ≥75 years of age. The rate of the primary outcome (per 100 person-years, placebo arm) in each age group was 13.6 (95% CI, 10.4-17.9), 15.7 (95% CI, 13.2-18.7), 15.1 (95% CI, 13.1-17.5), and 18.0 (95% CI, 15.2-21.4) with corresponding dapagliflozin/placebo hazard ratios of 0.87 (95% CI, 0.60-1.28), 0.71 (95% CI, 0.55-0.93), 0.76 (95% CI, 0.61-0.95), and 0.68 (95% CI, 0.53-0.88; 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.

Quality of life assessment in amyloid transthyretin (ATTR) amyloidosis.

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.

Transthyretin amyloidosis in aortic stenosis: clinical and therapeutic implications.

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.

Effect of dapagliflozin according to baseline systolic blood pressure in the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial (DAPA-HF).

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 <110 mmHg; 981 ≥ 110 < 120; 1149 ≥ 120 < 130; and 1409 ≥ 130 mmHg. The placebo-corrected reduction in SBP from baseline to 2 weeks with dapagliflozin was -2.54 (-3.33 to -1.76) mmHg (P < 0.001), with a smaller between-treatment difference in patients in the lowest compared to highest SBP category. Patients in the lowest SBP category had a much higher rate (per 100 person-years) of the primary outcome [20.6, 95% confidence interval (95% CI) 17.6-24.2] than those in the highest SBP category (13.8, 11.7-16.4). The benefit and safety of dapagliflozin was consistent across the range of SBP; hazard ratio (95% CI) in each SBP group, lowest to highest: 0.76 (0.60-0.97), 0.76 (0.57-1.02), 0.81 (0.61-1.08), and 0.67 (0.51-0.87), P interaction = 0.78. Study drug discontinuation did not differ between dapagliflozin and placebo across the SBP categories examined. CONCLUSION: Dapagliflozin had a small effect on SBP in patients with HFrEF and was superior to placebo in improving outcomes, and well tolerated, across the range of SBP included in DAPA-HF. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT03036124.

Bleeding Risk Scores and Scales of Frailty for the Prediction of Haemorrhagic Events in Older Adults with Acute Coronary Syndrome: Insights from the FRASER study.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov: NCT02386124.

Angina and chronic obstructive pulmonary disease: facing the perfect storm.

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 ß-blockers due to the fear of adverse effects. However, cardioselective ß-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.

Comparison of Verapamil versus Heparin as Adjunctive Treatment for Transradial Coronary Procedures: The VERMUT Study.

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 oc-clusion (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.

Physical activity intervention for elderly patients with reduced physical performance after acute coronary syndrome (HULK study): rationale and design of a randomized clinical trial.

BACKGROUND: Reduced physical performance and impaired mobility are common in elderly patients after acute coronary syndrome (ACS) and they represent independent risk factors for disability, morbidity, hospital readmission and mortality. Regular physical exercise represents a means for improving functional capacity. Nevertheless, its clinical benefit has been less investigated in elderly patients in the early phase after ACS. The HULK trial aims to investigate the clinical benefit of an early, tailored low-cost physical activity intervention in comparison to standard of care in elderly ACS patients with reduced physical performance. DESIGN: HULK is an investigator-initiated, prospective multicenter randomized controlled trial (NCT03021044). After successful management of the ACS acute phase and uneventful first 1 month, elderly (≥70 years) patients showing reduced physical performance are randomized (1:1 ratio) to either standard of care or physical activity intervention. Reduced physical performance is defined as a short physical performance battery (SPPB) score of 4-9. The early, tailored, low-cost physical intervention includes 4 sessions of physical activity with a supervisor and an home-based program of physical exercise. The chosen primary endpoint is the 6-month SPPB value. Secondary endpoints briefly include quality of life, on-treatment platelet reactivity, some laboratory data and clinical adverse events. To demonstrate an increase of at least one SPPB point in the experimental arm, a sample size of 226 patients is needed. CONCLUSIONS: The HULK study will test the hypothesis that an early, tailored low-cost physical activity intervention improves physical performance, quality of life, frailty status and outcome in elderly ACS patients with reduced physical performance. TRIAL REGISTRATION: Clinicaltrials.gov, identifier NCT03021044 , first posted January, 13th 2017.

The frailty in elderly patients receiving cardiac interventional procedures (FRASER) program: rational and design of a multicenter prospective study.

BACKGROUND: 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). METHODS: 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). DISCUSSION: 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.

Prospective Identification of Stent Fracture by Enhanced Stent Visualization System During Percutaneous Coronary Intervention.

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<0.01). CONCLUSIONS: The ESV system is helpful in detecting SF during the index PCI. Type III-IV SFs are associated with a higher incidence of DOCE.

Diagnostic accuracy of baseline troponin and troponin change for the diagnosis of myocardial infarction complicated with heart failure.

BACKGROUND: The diagnosis of myocardial infarction (MI) in the presence of heart failure (HF) presents a clinical problem. While diagnostic algorithms using high-sensitivity cardiac troponin have been established for suspected MI, their accuracy in patients with HF remains uncertain. This study aims to assess the diagnostic accuracy of high-sensitivity troponin I (TnI) levels in identifying acute MI among patients with HF, focusing on baseline, absolute and relative TnI changes. METHODS: Data from 562 individuals admitted to the emergency department with suspected MI were retrospectively analysed. Two-point TnI and baseline brain natriuretic peptide (BNP) test results were available. HF status was determined based on clinical, laboratory and instrumental criteria. RESULTS: Among the 562 patients, 299 (53.2%) were confirmed having MI. Baseline TnI demonstrated predictive capability for MI in the overall population (area under the curve (AUC) 0.63), while TnI relative change exhibited superior performance (AUC 0.83). Baseline TnI accuracy varied significantly by group, notably decreasing in the third group (severe HF) (AUC 0.54) compared with the first and second groups (AUC 0.67 and AUC 0.71, respectively). TnI relative change demonstrated consistent accuracy across all groups, with AUCs of 0.79, 0.79 and 0.89 for the first, second and third groups, respectively, even after adjustment for age, sex and glomerular filtration rate. DISCUSSION: Troponin relative change is a reliable predictor of MI, even in patients with acute HF. Baseline TnI accuracy is influenced by HF severity. It is essential to consider HF status and BNP levels when employing high-sensitivity cardiac troponin testing to rule out suspected MIs.