Coronary artery disease management in older adults: revascularization and exercise training.

The mean age of patients with coronary artery disease (CAD) is steadily increasing. In older patients, there is a tendency to underutilize invasive approach, coronary revascularization, up-to-date pharmacological therapies, and secondary prevention strategies, including cardiac rehabilitation. Older adults with CAD commonly exhibit atypical symptoms, multi-vessel disease involvement, complex coronary anatomy, and a higher presence of risk factors and comorbidities. Although both invasive procedures and medical treatments are characterized by a higher risk of complications, avoidance may result in a suboptimal outcome. Often, overlooked factors, such as coronary microvascular disease, malnutrition, and poor physical performance, play a key role in determining prognosis, yet they are not routinely assessed or addressed in older patients. Historically, clinicians have relied on sub-analyses or observational findings to make clinical decisions, as older adults were frequently excluded or under-represented in clinical studies. Recently, dedicated evidence through randomized clinical trials has become available for older CAD patients. Nevertheless, the management of older CAD patients still raises several important questions. This review aims to comprehensively summarize and critically evaluate this emerging evidence, focusing on invasive management and coronary revascularization. Furthermore, it seeks to contextualize these interventions within the framework of improved risk stratification tools for older CAD patients, through user-friendly scales along with emphasizing the importance of promoting physical activity and exercise training to enhance the outcomes of invasive and medical treatments. This comprehensive approach may represent the key to improving prognosis in the complex and growing patient population of older CAD patients.

Future of invasive and non-invasive hemodynamic assessment for coronary artery disease management.

Coronary artery disease represents a global health challenge. Accurate diagnosis and evaluation of hemodynamic parameters are crucial for optimizing patient management and outcomes. Nowadays a wide range of both non-invasive and invasive methods are available to assess the hemodynamic impact of both epicardial coronary stenosis and vasomotor disorders. In fact, over the years, important developments have reshaped the nature of both invasive and non-invasive diagnostic techniques, and the future holds promises for further innovation and integration. Non-invasive techniques have progressively evolved and currently a broad spectrum of methods are available, from cardiac magnetic resonance imaging with pharmacological stress and coronary computed tomography (CT) to the newer application of FFR-CT and perfusion CT. Invasive methods, on the contrary, have developed to a full-physiology approach, able not only to identify functionally significant lesions but also to evaluate microcirculation and vasospastic disease. The aim of this review is to summarize the current state-of-the-art of invasive and non-invasive hemodynamic assessment for CAD management.

Complete vs Culprit-Only Revascularization in Older Patients With Myocardial Infarction and High Bleeding Risk: A Randomized Clinical Trial.

Importance: Patients with high bleeding risk (HBR) have a poor prognosis, and it is not known if they may benefit from complete revascularization after myocardial infarction (MI). Objective: To investigate the benefit of physiology-guided complete revascularization vs a culprit-only strategy in patients with HBR, MI, and multivessel disease. Design, Setting, and Participants: This was a prespecified analysis of the Functional Assessment in Elderly MI Patients With Multivessel Disease (FIRE) randomized clinical trial data. FIRE was an investigator-initiated, open-label, multicenter trial. Patients 75 years or older with MI and multivessel disease were enrolled at 34 European centers from July 2019 through October 2021. Physiology treatment was performed either by angiography- or wire-based assessment. Patients were divided into HBR or non-HBR categories in accordance with the Academic Research Consortium HBR document. Interventions: Patients were randomized to either physiology-guided complete revascularization or culprit-only strategy. Main Outcomes and Measures: The primary outcome comprised a composite of death, MI, stroke, or revascularization at 1 year. Secondary outcomes included a composite of cardiovascular death or MI and Bleeding Academic Research Consortium (BARC) types 3 to 5. Results: Among 1445 patients (mean [SD] age, 81 [5] years; 917 male [63%]), 1025 (71%) met HBR criteria. Patients with HBR were at higher risk for the primary end point (hazard ratio [HR], 2.01; 95% CI, 1.47-2.76), cardiovascular death or MI (HR, 1.89; 95% CI, 1.26-2.83), and BARC types 3 to 5 (HR, 3.28; 95% CI, 1.40-7.64). The primary end point was significantly reduced with physiology-guided complete revascularization as compared with culprit-only strategy in patients with HBR (HR, 0.73; 95% CI, 0.55-0.96). No indication of interaction was noted between revascularization strategy and HBR status for primary and secondary end points. Conclusions and Relevance: HBR status is prevalent among older patients with MI, significantly increasing the likelihood of adverse events. Physiology-guided complete revascularization emerges as an effective strategy, in comparison with culprit-only revascularization, for mitigating ischemic adverse events, including cardiovascular death and MI. Trial Registration: ClinicalTrials.gov Identifier: NCT03772743.

The role of echocardiography in pulmonary embolism for the prediction of in-hospital mortality: a retrospective study.

PURPOSE: Pulmonary Embolism (PE) is the third leading cause of cardiovascular death, following myocardial infarction and stroke. The latest European Society of Cardiology (ESC) guidelines on PE recommend short-term prognostic stratification based on right ventricular (RV) overload detected by transthoracic echocardiography (TTE) or contrast-enhanced chest CT. The aim of the study is to find out which of the signs of right ventricular dysfunction best predicts in-hospital mortality (IHM). METHODS: This is a monocentric, retrospective study including adult patients admitted from the emergency department with a c-e cCT confirmed diagnosis of PE between January 2018 and December 2022 who underwent a TTE within 48 h. RESULTS: 509 patients (median age 76 years [IQR 67-84]) were included, with 7.1% IHM. At univariate analysis, RV/LV ratio > 1 (OR 2.23, 95% CI 1.1-4.5), TAPSE < 17 mm (OR 4.73, 95% CI 2.3-9.8), the D-shape (OR 3.73, 95% CI 1.71-8.14), and LVEF < 35% (OR 5.78, 95% CI 1.72-19.47) resulted significantly correlated with IHM. However, at multivariate analysis including also haemodynamic instability, PESI class > II, and abnormal hs-cTnI levels, only LVEF < 35% (OR 5.46, 95% CI 1.32-22.61) resulted an independent predictor of IHM. CONCLUSION: Despite the recognised role of TTE in the early management of patients with circulatory shock and suspected PE, signs of RV dysfunction have been shown to be poor predictors of IHM, whereas severely reduced LVEF is an independent risk factor for in-hospital death.

Impact of pre-admission physical activity on benefits of physiology-guided complete revascularization in older patients with myocardial infarction: insights from the FIRE trial.

AIMS: The present analysis from the Functional Assessment in Elderly Myocardial Infarction Patients with Multivessel Disease (FIRE) trial aims to explore the significance of pre-admission physical activity and assess whether the benefits of physiology-guided complete revascularization apply consistently to sedentary and active older patients. METHODS AND RESULTS: Patients aged 75 years or more with myocardial infarction (MI) and multivessel disease were randomized to receive physiology-guided complete revascularization or culprit-only strategy. The primary outcome was a composite of death, MI, stroke, or any revascularization within a year. Secondary endpoints included the composite of cardiovascular death or MI, as well as single components of the primary endpoint. Pre-admission physical activity was categorized into three groups: (i) absent (sedentary), (ii) light, and (iii) vigorous. Among 1445 patients, 692 (48%) were sedentary, whereas 560 (39%) and 193 (13%) performed light and vigorous physical activity, respectively. Patients engaging in light or vigorous pre-admission physical activity exhibited a reduced risk of the primary outcome compared with sedentary individuals [light hazard ratio (HR) 0.70, 95% confidence interval (CI) 0.55-0.91 and vigorous HR 0.14, 95% CI 0.07-0.91, respectively]. These trends were also observed for death, cardiovascular death, or MI. When comparing physiology-guided complete revascularization vs. culprit-only strategy, no significant interaction was observed for primary and secondary endpoints when stratified by sedentary or active status. CONCLUSION: In older patients with MI, pre-admission physical activity emerges as a robust and independent prognostic determinant. Physiology-guided complete revascularization stands out an effective strategy in reducing ischaemic adverse events, irrespective of pre-admission physical activity status. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT03772743.

The Functional Assessment in Elderly Myocardial Infarction Patients with Multivessel Disease (FIRE) trial has shown that physiology-guided complete revascularization reduces ischaemic adverse events in older patients with myocardial infarction (MI) and multivessel disease. Older patients who engage in light or vigorous physical activity before hospitalization for MI have a reduced risk of the primary composite outcome of death, MI, stroke, or ischaemia-driven revascularization. These benefits extend to all secondary cardiovascular outcomes as well. In the present subanalysis of the FIRE trial, we find that the positive prognosis associated with physiology-guided complete revascularization holds true even for patients with a sedentary lifestyle. This means that this type of revascularization can effectively reduce ischaemic adverse events in older patients with MI and multivessel disease, regardless of their physical activity levels.

ECG/echo indexes in the diagnostic approach to amyloid cardiomyopathy: A head-to-head comparison from the AC-TIVE study.

BACKGROUND AND AIMS: The discordance between QRS voltages on electrocardiogram (ECG) and left ventricle (LV) wall thickness (LVWT) on echocardiogram (echo) is a recognized red flag (RF) of amyloid cardiomyopathy (AC) and can be measured by specific indexes. No head-to-head comparison of different ECG/echo indexes among subjects with echocardiographic suspicion of AC has yet been undertaken. The study aimed at evaluating the performance and the incremental diagnostic value of different ECG/echo indexes in this subset of patients. METHODS: Electrocardiograms of subjects with LV hypertrophy, preserved ejection fraction and ≥ 1 echocardiographic RF of AC participating in the AC-TIVE study, an Italian prospective multicenter study, were independently analyzed by two cardiologists. Low QRS voltages and 8 different ECG/echo indexes were evaluated. Cohort specific cut-offs were computed. RESULTS: Among 170 patients, 55 (32 %) were diagnosed with AC. Combination of low QRS voltages with interventricular septum ≥ 1,6 cm was the most specific (specificity 100 %, positive predictive value 100 %) ECG/echo index, while the ratio between the sum of all QRS voltages and LVWT <7,8 was the most sensitive and accurate (sensitivity 94 %, negative predictive value 97 %, accuracy 82 %). When the latter index was added to a model using easily-accessible clinical variables, the diagnostic accuracy for AC greatly increased (AUC from 0,84 to 0,95; p = 0,007). CONCLUSIONS: Among patients with non-dilated hypertrophic ventricles with normal ejection fraction and echocardiographic RF of AC, easily-measurable ECG/echo indexes, mainly when added to few clinical variables, can help the physician orient second level investigations. External validation of the results is warranted.

"Safe Femoral" Artery Approach in Endovascular Procedures: A Systematic Review of Its Safety and Feasibility.

Femoral access site-related bleeding represent a prognostically impactful issue in interventional cardiology. The impact of a combined use of ultrasound guidance for femoral access and vascular closure device deployment for arteriotomy closure in femoral artery procedures on bleeding complications is still largely unknown. A systematic review was conducted on Pubmed (Medline), Cochrane library and Biomed Central databases between March and April 2023. A total of 9 studies have been selected, of namely 4 registries, 4 prospective studies and one randomized clinical trial. A systematic use of US guidance to access femoral artery resulted feasible and not time consuming, reduced venipuncture and increased first attempt success. Combination of US guidance and deployment of VCD's had the capacity to further decrease vascular and bleeding combination, especially in those patients at a higher risk of post-procedural bleeding. Ultrasound can be easily used during closure device deployment to reduce device failure and major vascular complications.

Immune Checkpoint Inhibitors-Associated Myocarditis: Diagnosis, Treatment and Current Status on Rechallenge.

Immune checkpoint molecules like cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death 1 (PD-1) or its ligand, programmed cell death ligand 1 (PD-L1), play a critical role in regulating the immune response, and immune checkpoint inhibitors (ICIs) targeting these checkpoints have shown clinical efficacy in cancer treatment; however, their use is associated with immune-related adverse events (irAEs), including cardiac complications. The prevalence of cardiac irAEs, particularly myocarditis, is relatively low, but they can become a severe and potentially life-threatening condition, usually occurring shortly after initiating ICI treatment; moreover, diagnosing ICI-related myocarditis can be challenging. Diagnostic tools include serum cardiac biomarkers, electrocardiography (ECG), echocardiography, cardiac magnetic resonance (CMR) and endomyocardial biopsy (EMB). The treatment of ICI-induced myocarditis involves high-dose corticosteroids, which have been shown to reduce the risk of major adverse cardiac events (MACE). In refractory cases, second-line immunosuppressive drugs may be considered, although their effectiveness is based on limited data. The mortality rates of ICI-induced myocarditis, particularly in severe cases, are high (38-46%). Therapy rechallenge after myocarditis is associated with a risk of recurrence and severe complications. The decision to rechallenge should be made on a case-by-case basis, involving a multidisciplinary team of cardiologists and oncologists. Further research and guidance are needed to optimize the management of cancer patients who have experienced such complications, evaluating the risks and benefits of therapy rechallenge. The purpose of this review is to summarize the available evidence on cardiovascular complications from ICI therapy, with a particular focus on myocarditis and, specifically, the rechallenge of immunotherapy after a cardiac adverse event.

Effect of physical activity on left ventricular dimensions and function after myocardial infarction: a systematic review.

INTRODUCTION: Coronary artery disease is the major pathophysiological driver of ventricular remodeling. A multimodal intervention is the key strategy to promote a positive left ventricular remodeling with improvement in volumes and ejection fraction, known as "reverse remodeling." The aim of this review was to highlight the effect of physical activity (PA) on echocardiographic and cardiac magnetic resonance parameters of left ventricle in patients with myocardial infarction. EVIDENCE ACQUISITION: We performed a systematic review of the literature to summarize current evidence about the efficacy (in terms of improvement in chamber dimensions, ejection fraction, speckle tracking and diastolic function) of physical activity in patients with myocardial infarction, supported by echocardiographic or magnetic resonance data. Articles were searched in Pubmed, Cochrane Library and Biomed Central. EVIDENCE SYNTHESIS: Only papers published in English and in peer-reviewed journals up to November 2022 were selected. After an initial evaluation, 1029 records were screened; the literature search identified 20 relevant articles. From this data, some PA protocols appeared to favor left ventricular reverse remodeling. CONCLUSIONS: PA provides beneficial effects on left ventricular parameters analyzed by echocardiography and cardiac magnetic resonance.

Functional (Re)Development of SYNTAX Score II 2020: Predictive Performance and Risk Assessment.

The present study investigates the prognostic value of the Syntax Score II 2020 corrected for flow-limiting lesions and its ability to better address treatment by benefit prediction among patients with left main or multivessel disease. We analyzed 1274 patients from the HALE-BOPP cohort and integrated the Syntax Score II 2020 with the result of the fractional flow reserve (FFR) evaluation. Absolute risk difference (ARD) between surgical and percutaneous revascularization was calculated for anatomic and functional Syntax Score II 2020 predicted mortality. The ARD allowed to stratify the population into two large categories: "coronary artery bypass graft (CABG) better" with ARD ≥ 4.5% and "CABG-percutaneous coronary intervention (PCI) equipoise" with ARD < 4.5%. The mean global anatomical Syntax Score was 15.5 ± 9.2, whereas the functional one was 9.5 ± 10 (p < 0.01). Using the anatomic Syntax Score II 2020, 881 patients had a CABG-PCI equipoise. This number increased to 1041 after considering only flow-limiting lesions by FFR (p < 0.001); therefore, 40% of CABG better patients were reclassified within the CABG-PCI equipoise category. Kaplan-Maier curves showed similar actual survival rates for patients originally with CABG-PCI equipoise and those reclassified, in both cases higher than those from CABG better patients (p < 0.01). The integration between Syntax Score II 2020 and physiology is feasible, and merging clinical, anatomic and functional data allows for better risk prediction and therapeutic guidance.

Complete or Culprit-Only PCI in Older Patients with Myocardial Infarction.

BACKGROUND: The benefit of complete revascularization in older patients (≥75 years of age) with myocardial infarction and multivessel disease remains unclear. METHODS: In this multicenter, randomized trial, we assigned older patients with myocardial infarction and multivessel disease who were undergoing percutaneous coronary intervention (PCI) of the culprit lesion to receive either physiology-guided complete revascularization of nonculprit lesions or to receive no further revascularization. Functionally significant nonculprit lesions were identified either by pressure wire or angiography. The primary outcome was a composite of death, myocardial infarction, stroke, or any revascularization at 1 year. The key secondary outcome was a composite of cardiovascular death or myocardial infarction. Safety was assessed as a composite of contrast-associated acute kidney injury, stroke, or bleeding. RESULTS: A total of 1445 patients underwent randomization (720 to receive complete revascularization and 725 to receive culprit-only revascularization). The median age of the patients was 80 years (interquartile range, 77 to 84); 528 patients (36.5%) were women, and 509 (35.2%) were admitted for ST-segment elevation myocardial infarction. A primary-outcome event occurred in 113 patients (15.7%) in the complete-revascularization group and in 152 patients (21.0%) in the culprit-only group (hazard ratio, 0.73; 95% confidence interval [CI], 0.57 to 0.93; P = 0.01). Cardiovascular death or myocardial infarction occurred in 64 patients (8.9%) in the complete-revascularization group and in 98 patients (13.5%) in the culprit-only group (hazard ratio, 0.64; 95% CI, 0.47 to 0.88). The safety outcome did not appear to differ between the groups (22.5% vs. 20.4%; P = 0.37). CONCLUSIONS: Among patients who were 75 years of age or older with myocardial infarction and multivessel disease, those who underwent physiology-guided complete revascularization had a lower risk of a composite of death, myocardial infarction, stroke, or ischemia-driven revascularization at 1 year than those who received culprit-lesion-only PCI. (Funded by Consorzio Futuro in Ricerca and others; FIRE ClinicalTrials.gov number, NCT03772743.).

Pulmonary Valve Stenosis: From Diagnosis to Current Management Techniques and Future Prospects.

Pulmonary stenosis (PS) is mainly a congenital defect that accounts for 7-12% of congenital heart diseases (CHD). It can be isolated or, more frequently, associated with other congenital defects (25-30%) involving anomalies of the pulmonary vascular tree. For the diagnosis of PS an integrated approach with echocardiography, cardiac computed tomography and cardiac magnetic resonance (CMR) is of paramount importance for the planning of the interventional treatment. In recent years, transcatheter approaches for the treatment of PS have increased however, meaning surgery is a possible option for complicated cases with anatomy not suitable for percutaneous treatment. The present review aims to summarize current knowledge regarding diagnosis and treatment of PS.

[Epicardial adipose tissue: a novel cardiovascular risk factor]. / Tessuto adiposo epicardico quale nuovo fattore di rischio cardiovascolare.

Epicardial adipose tissue (EAT) has various metabolic functions aiming at heart protection. When abnormal, it is related to atherosclerotic plaque development and adverse cardiovascular outcome. Additionally, in recent years, several studies have demonstrated its role in other settings such as atrial fibrillation and heart failure with preserved ejection fraction. Future studies should aim to assess diagnostic role of EAT and the effect of medical therapy on EAT volume and attenuation.

Intranasal Fentanyl for Acute Pain Management in Children, Adults and Elderly Patients in the Prehospital Emergency Service and in the Emergency Department: A Systematic Review.

This systematic review examined the efficacy and safety of intranasal fentanyl (INF) for acute pain treatment in children, adults, and the elderly in prehospital emergency services (PHES) and emergency departments (ED). ClinicalTrials.gov, LILACS, PubMed, SCOPUS, EMBASE, Google Scholar and Cochrane databases were consulted until 31 December 2022. A total of 23 studies were included: 18 in children (1 PHES, 17 ED), 5 in adults (1 PHES, 4 ED) and 1 in older people (1 PHES subgroup analysis). In children, INF was effective in both settings and as effective as the comparator drugs, with no differences in adverse events (AEs); one randomised controlled trial (RCT) showed that INF was more effective than the comparator drugs. In adults, one study demonstrated the efficacy of INF in the PHES setting, one study demonstrated the efficacy of INF in the ED setting, two RCTs showed INF to be less effective than the comparator drugs and one RCT showed INF to be as effective as the comparator, with no difference in AEs reported. In older people, one study showed effective pain relief and no AEs. In summary, INF appears to be effective and safe in children and adults in PHES and ED. More high-quality studies are needed, especially in PHES and older people.

ObsErvatioNal prospective multicenter stuDy tO characterize the cLinical ANd DiagnoStiC feAtures of endocarditis in the contemPorary Era (ENDO-LANDSCAPE study): rationale and design.

BACKGROUND: Recent developments in the management of valvular heart disease and heart failure have resulted in a dramatic increase in percutaneous valve procedures and implanted devices. We hypothesize that this has impacted the epidemiology, diagnosis, and management of endocarditis. METHODS: The obsErvatioNal prospective multicenter stuDy tO characterize the cLinical ANd DiagnoStiC feAtures of endocarditis in the contemPorary Era (ENDO-LANDSCAPE study) is an observational, multicenter, and international study aimed to examine the epidemiology of endocarditis in the contemporary era. The study will constitute of a retrospective arm for the determination of the sample size of the prospective arm, where cases of endocarditis between 2016 to 2022 at three tertiary referral institutions will be analyzed. The prospective arm will examine all consecutive patients referred for an echocardiography with a suspected or confirmed diagnosis of endocarditis, and their clinical course followed up over 12 months for adverse outcomes. The primary aim of the study will be to characterize the epidemiology of endocarditis, focusing on patients with prosthetic or implanted devices. The secondary aims would be: the appropriateness of the requests for first-line echocardiographic imaging in exclusion of endocarditis; the role of other imaging modalities in the diagnosis of endocarditis; and the impact of a specialized endocarditis team on outcomes. IMPLICATIONS: The results of the ENDO-LANDSCAPE study will provide a contemporary update of the epidemiological trends in endocarditis. The data generated from this study would be useful in informing future clinical practice, potentially guiding future diagnostic and treatment algorithms in patients with endocarditis. CLINICALTRIALORG ID: NCT05547607.

Structural Abnormalities in Brugada Syndrome and Non-Invasive Cardiac Imaging: A Systematic Review.

The aim of this review is to identify possible structural abnormalities of BrS and their potential association with symptoms, risk stratification, and prognosis. (1) Background: BrS has always been considered a purely electrical disease and imaging techniques do not currently play a specific role in the diagnosis of this arrhythmic syndrome. Some authors have recently hypothesized the presence of structural and functional abnormalities. Therefore, several studies investigated the presence of pathological features in echocardiography and cardiac magnetic resonance imaging (MRI) in patients with BrS, but results were controversial. (2) Methods: We performed a systematic review of the literature on the spectrum of features detected by echocardiography and cardiac MRI. Articles were searched in Pubmed, Cochrane Library, and Biomed Central. Only papers published in English and in peer-reviewed journals up to November 2021 were selected. After an initial evaluation, 596 records were screened; the literature search identified 19 relevant articles. (3) Results: The imaging findings associated with BrS were as follows: right ventricular dilation, right ventricular wall motion abnormalities, delayed right ventricular contraction, speckle and feature tracking abnormalities, late gadolinium enhancement, and fat infiltration in the right ventricle. Furthermore, these features emerged more frequently in patients carrying the genetic mutation on the sodium voltage-gated channel α-subunit 5 (SCN5A) gene. (4) Conclusions: Specific imaging features detected by echocardiography and cardiac magnetic resonance are associated with BrS. However, this population appears to be heterogeneous and imaging anomalies emerged to be more frequent in patients carrying genetic mutations of SCN5A. Future studies with an evaluation of BrS patients are needed to identify the specific association linking the Brugada pattern, imaging abnormalities and their possible correlation with prognosis.