Health-Status Outcomes in Older Patients With Myocardial Infarction: Physiology-Guided Complete Revascularization Versus Culprit-Only Strategy.

BACKGROUND: The FIRE trial (Functional Assessment in Elderly Myocardial Infarction Patients With Multivessel Disease) enrolled 1445 older (aged ≥75 years) patients with myocardial infarction and multivessel disease in Italy, Spain, and Poland. Patients were randomized to physiology-guided complete revascularization or treatment of the only culprit lesion. Physiology-guided complete revascularization significantly reduced ischemic adverse events at 1 year. This prespecified analysis investigated the changes between the 2 study groups in angina status, quality of life, physical performance, and frailty. METHODS: Patients underwent validated scales at hospital discharge (baseline) and 1 year later. Angina status was evaluated using the Seattle Angina Questionnaire, health-related quality of life by EQ visual analog scale, physical performance by short physical performance battery, and frailty by the clinical frailty scale. Mixed models for repeated measures analysis were used to study the association between the treatment arms, time, and scales. RESULTS: Baseline and 1-year Seattle Angina Questionnaire, EQ visual analog scale, short physical performance battery, and clinical frailty scale were collected in around two-thirds of the entire FIRE study population. The mean age was 80.9±4.6 years (female sex, 35.9%). Overall, 35.3% were admitted for ST-segment-elevation myocardial infarction, whereas the others were admitted for non-ST-segment-elevation myocardial infarction. Physiology-guided complete revascularization, compared with culprit-only revascularization, was associated with greater improvement in terms of angina status (Seattle Angina Questionnaire summary score, 7.3 [95% CI, 6.1-8.6] points), health-related quality of life (EQ visual analog scale, 6.2 [95% CI, 4.4-8.1] points), and physical performance (short physical performance battery, 1.1 [95% CI, 0.9-1.3] points). After 1 year, patients randomized to culprit-only revascularization experienced a deterioration in frailty status (clinical frailty scale, 0.2 [95% CI, 0.1-0.3] points), which was not observed in patients randomized to physiology-guided complete revascularization. CONCLUSIONS: The present analysis suggested that a physiology-guided complete revascularization is associated with consistent benefits in terms of angina status, quality of life, physical performance, and the absence of further deterioration of the frailty status. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03772743.

QFR for the Revascularization of Nonculprit Vessels in MI Patients: Insights From the FIRE Trial.

BACKGROUND: The role of quantitative flow ratio (QFR) in the treatment of nonculprit vessels of patients with myocardial infarction (MI) is a topic of ongoing discussion. OBJECTIVES: This study aimed to investigate the predictive capability of QFR for adverse events and its noninferiority compared to wire-based functional assessment in nonculprit vessels of MI patients. METHODS: The FIRE (Functional Assessment in Elderly MI Patients With Multivessel Disease) trial randomized 1,445 older MI patients to culprit-only (n = 725) or physiology-guided complete revascularization (n = 720). In the culprit-only arm, angiographic projections of nonculprit vessels were prospectively collected, centrally reviewed for QFR computation, and associated with endpoints. In the complete revascularization arm, endpoints were compared between nonculprit vessels investigated with QFR or wire-based functional assessment. The primary endpoint was the vessel-oriented composite endpoint (VOCE) at 1 year. RESULTS: QFR was measured on 903 nonculprit vessels from 685 patients in the culprit-only arm. Overall, 366 (40.5%) nonculprit vessels showed a QFR value ≤0.80, with a significantly higher incidence of VOCEs (22.1% vs 7.1%; P < 0.001). QFR ≤0.80 emerged as an independent predictor of VOCEs (HR: 2.79; 95% CI: 1.64-4.75). In the complete arm, QFR was used in 320 (35.2%) nonculprit vessels to guide revascularization. When compared with propensity-matched nonculprit vessels in which treatment was guided by wire-based functional assessment, no significant difference was observed (HR: 0.57; 95% CI: 0.28-1.15) in VOCEs. CONCLUSIONS: This prespecified subanalysis of the FIRE trial provides evidence supporting the safety and efficacy of QFR-guided interventions for the treatment of nonculprit vessels in MI patients. (Functional Assessment in Elderly MI Patients With Multivessel Disease [FIRE]; NCT03772743).

Comparing two-year outcomes of balloon-expandable Myval and self-expanding Evolut R in severe aortic valve stenosis.

BACKGROUND: The new balloon-expandable (BE) Myval transcatheter heart valves (THV) has shown promising early results with low paravalvular leak (PVL) and permanent pacemaker implantation (PPI) rates. Limited data are available regarding its long-term performance. We aimed to compare the 2-year clinical and echocardiographic outcomes of transcatheter aortic valve replacement (TAVR) using the self-expanding (SE) Evolut R and the BE Myval THVs. METHODS: The EVAL study included 166 patients with severe aortic valve stenosis who underwent TAVR either with SE Evolut R (n = 108) or BE Myval (n = 58) THV. Primary objectives include comparison on clinical efficacy (freedom from all-cause mortality, stroke, and cardiovascular hospitalization), echocardiographic performance and PPI rates between the two THVs. RESULTS: At 2-year the BE Myval group showed higher clinical efficacy (86% vs. 66%,HR:2.62, 95%CI 2.2-5.1;p = 0.006), with fewer cardiac hospitalizations (3.4% vs. 13.9%,p = 0.03). No significant differences in all-cause mortality, cardiovascular mortality, or stroke rates were observed. The proportion of patients with ≥moderate PVL was significantly lower in the BE Myval compared to the SE Evolut R group (4%vs. 22%,p = 0.008). The mean transvalvular gradient was significantly higher in the SE group compared to the BE group (9.5 ± 4.3 vs. 6.9 ± 2.2 mmHg,p < 0.001), however there was no difference in the percentage of patients with a mean gradient ≥20 mmHg between the two groups. CONCLUSIONS: Both THVs offer similar 2-year clinical outcomes. The BE Myval THV demonstrated advantages with higher clinical efficacy and lower PVL incidence. Longer follow-up and randomized trials are needed to validate these results and assess Myval's sustained performance and durability.

Management of high and intermediate-high risk pulmonary embolism: A position paper of the Interventional Cardiology Working Group of the Italian Society of Cardiology.

Pulmonary embolism (PE) is a potentially life-threatening condition that remains a major global health concern. Noteworthy, patients with high- and intermediate-high-risk PE pose unique challenges because they often display clinical and hemodynamic instability, thus requiring rapid intervention to mitigate the risk of clinical deterioration and death. Importantly, recovery from PE is associated with long-term complications such as recurrences, bleeding with oral anticoagulant treatment, pulmonary hypertension, and psychological distress. Several novel strategies to improve risk factor characterization and management of patients with PE have recently been introduced. Accordingly, this position paper of the Working Group of Interventional Cardiology of the Italian Society of Cardiology deals with the landscape of high- and intermediate-high risk PE, with a focus on bridging the gap between the evolving standards of care and the current clinical practice. Specifically, the growing importance of catheter-directed therapies as part of the therapeutic armamentarium is highlighted. These interventions have been shown to be effective strategies in unstable patients since they offer, as compared with thrombolysis, faster and more effective restoration of hemodynamic stability with a consistent reduction in the risk of bleeding. Evolving standards of care underscore the need for continuous re-assessment of patient risk stratification. To this end, a multidisciplinary approach is paramount in refining selection criteria to deliver the most effective treatment to patients with unstable hemodynamics. In conclusion, the current management of unstable patients with PE should prioritize tailored treatment in a patient-oriented approach in which transcatheter therapies play a central role.

Visceral adipose tissue and residual cardiovascular risk: a pathological link and new therapeutic options.

Obesity is a heterogeneous disease that affects almost one-third of the global population. A clear association has been established between obesity and cardiovascular disease (CVD). However, CVD risk is known to be related more to the local distribution of fat than to total body fat. Visceral adipose tissue (VAT) in particular has a high impact on CVD risk. This manuscript reviews the role of VAT in residual CV risk and the available therapeutic strategies for decreasing residual CV risk related to VAT accumulation. Among the many pathways involved in residual CV risk, obesity and particularly VAT accumulation play a major role by generating low-grade systemic inflammation, which in turn has a high prognostic impact on all-cause mortality and myocardial infarction. In recent years, many therapeutic approaches have been developed to reduce body weight. Orlistat was shown to reduce both weight and VAT but has low tolerability and many drug-drug interactions. Naltrexone-bupropion combination lowers body weight but has frequent side effects and is contraindicated in patients with uncontrolled hypertension. Liraglutide and semaglutide, glucagon-like peptide 1 (GLP-1) agonists, are the latest drugs approved for the treatment of obesity, and both have been shown to induce significant body weight loss. Liraglutide, semaglutide and other GLP-1 agonists also showed a positive effect on CV outcomes in diabetic patients. In addition, liraglutide showed to specifically reduce VAT and inflammatory biomarkers in obese patients without diabetes. GLP-1 agonists are promising compounds to limit inflammation in human visceral adipocytes.

Understanding the role of coronary artery revascularization in patients with left ventricular dysfunction and multivessel disease.

Coronary artery disease (CAD) is the most common cause of heart failure with reduced ejection fraction (HFrEF). Advances and innovations in medical therapy have been shown to play a crucial role in improving the prognosis of patients with CAD and HFrEF; however, mortality rate in these patients remains high, and the role of surgical and/or percutaneous revascularization strategy is still debated. The Surgical Treatment for Ischemic Heart Failure (STICH) trial and the Revascularization for Ischemic Ventricular Dysfunction (REVIVED) trial have attempted to provide an answer to this issue. Nevertheless, the results of these two trials have generated further uncertainties. Their findings do not provide a definitive answer about the ideal clinical phenotype for surgical or percutaneous coronary revascularization and dispute the historical dogma on myocardial viability and the theory of myocardial hibernation, raising new questions about the proper selection of patients who are candidates for coronary revascularization. The aim of this review is to provide an overview on the actual available evidence of coronary artery revascularization in patients with CAD and left ventricular dysfunction and to suggest new insights on the proper selection and management strategies in this high-risk clinical setting.

De-escalation strategies in patients with acute coronary syndrome: a step towards precision medicine.

INTRODUCTION: Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor is a cornerstone in the treatment of patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Current international guidelines recommend the use of 12 months of DAPT with newer P2Y12 inhibitors (i.e. ticagrelor or prasugrel) as first-line therapy in this setting. However, intense and prolonged DAPT regimens are associated with an increased risk of bleeding, with relevant prognostic implications. Recently, a strategy of de-escalation of P2Y12 inhibitors has been proposed as an alternative to conventional DAPT to mitigate the risk of bleeding while preserving ischemic protection after ACS. AREAS COVERED: In this review, we summarize the available evidence on guided and unguided strategies for P2Y12 inhibitor de-escalation in patients with ACS undergoing PCI. EXPERT OPINION: Among patients with ACS, guided and unguided de-escalation strategies are safe and effective for secondary cardiovascular prevention. Although the implementation of genetic and platelet function tests is of interest for treatment personalization, the routine use of guided de-escalation strategies seems impractical. In this context, unguided de-escalation approaches appear more attractive, convenient, and suitable for contemporary practice.

Sodium-Glucose Cotransporter 2 Inhibitors in Patients with Diabetes and Coronary Artery Disease: Translating the Benefits of the Molecular Mechanisms of Gliflozins into Clinical Practice.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) were initially developed for the treatment of diabetes due to their antihyperglycemic activity. However, in the light of the most recent clinical studies, they are revolutionizing the approach to cardiovascular disease in patients with and without diabetes. We aimed to generate real-world data about the use of SGLT2i in patients with T2DM and coronary artery disease (CAD), focusing on their effectiveness in glycemic control, adherence, long-term efficacy, and safety outcomes. On the basis of the inclusion and exclusion criteria, 143 patients were enrolled. Patients were treated with canagliflozin (n = 33 patients; 23%), dapagliflozin (n = 52 patients, 36.4%), empagliflozin (n = 48 patients; 33.6%), or ertugliflozin (n = 10 patients; 7%) as monotherapy or in combination with other antidiabetic drugs. All patients performed a clinical visit, and their medical history, blood sampling, and anthropometric parameters were measured at discharge and at 1-year follow-up. The reduction in HbA1c % value at 12 months was significant (8.2 vs. 7.4; p < 0.001). Trends in body weight and body mass index also confirmed the positive effect of the treatment (p < 0.0001), as did the reduction in abdominal adiposity (expressed via waist circumference). At 1-year follow-up, 74.1% of patients were adherent to the treatment, and 81.1% were persistent to the treatment. A total of 27 patients (18.8%) had to discontinue treatment early due to drug intolerance caused by genitourinary infections (11.9%), the drub being permanently ineffective (HbA1c not at target or decreasing: 4.9%), or because of expressing. a desire not to continue (2%). No major drug-related adverse events (diabetic ketoacidosis, Fournier's gangrene, lower-limb amputations) occurred at follow-up, while MACE events occurred in 14 patients (9.8%). In real-world patients with T2DM and CAD, SGLT2i have been effective in long-term glycemic control and the improvement in anthropometric indices with good tolerance, high adherence, persistence to treatment, and no major adverse events at 1-year follow-up.

Lipid-lowering therapy in patients with coronary artery disease undergoing percutaneous coronary interventions in Italy: an expert opinion paper of Interventional Cardiology Working Group of Italian Society of Cardiology.

After percutaneous coronary interventions (PCIs), patients remain at high risk of developing recurrent cardiovascular events. Despite advances in interventional cardiology, the correct management of residual low-density lipoprotein cholesterol (LDL-C) risk continues to be crucial for improving long-term outcomes after PCI. However, several observational studies have demonstrated suboptimal LDL-C control, poor adherence to statin therapy, and underutilization of high-intensity statins, ezetimibe, and proprotein convertase subtilisin/kexin type 9 inhibitors in real-world clinical practice despite a strong endorsement from international guidelines. Recent studies have shown that early intensive lipid-lowering therapy stabilizes atheromatous plaque and increases fibrous cap thickness in patients with acute coronary syndrome. This finding emphasizes the importance of achieving therapeutic targets by establishing an effective treatment as early as possible. The aim of this expert opinion paper of the Interventional Cardiology Working Group of the Italian Society of Cardiology is to discuss the management of lipid-lowering therapy in patients undergoing PCIs according to Italian reimbursement policies and regulations, with a particular focus on the discharge phase.

Alcohol Septal Ablation in Patients with Hypertrophic Obstructive Cardiomyopathy: A Contemporary Perspective.

Alcohol septal ablation is a minimally invasive procedure for the treatment of left ventricular outflow tract (LVOT) obstruction in patients with hypertrophic obstructive cardiomyopathy (HOCM) who remain symptomatic despite optimal medical therapy. The procedure causes a controlled myocardial infarction of the basal portion of the interventricular septum by the injection of absolute alcohol with the aim of reducing LVOT obstruction and improving the patient's hemodynamics and symptoms. Numerous observations have demonstrated the efficacy and safety of the procedure, making it a valid alternative to surgical myectomy. In particular, the success of alcohol septal ablation depends on appropriate patient selection and the experience of the institution where the procedure is performed. In this review, we summarize the current evidence on alcohol septal ablation and highlight the importance of a multidisciplinary approach involving a team of clinical and interventional cardiologists and cardiac surgeons with high expertise in the management of HOCM patients-the Cardiomyopathy Team.

[New frontiers in antiplatelet therapy: guided therapy and de-escalation after acute coronary syndrome or percutaneous coronary intervention]. / Le nuove frontiere della terapia antiaggregante: terapia guidata e de-escalation dopo sindrome coronarica acuta o rivascolarizzazione coronarica percutanea.

Dual antiplatelet therapy (DAPT) is a cornerstone in the management of patients with acute coronary syndrome (ACS) and/or undergoing percutaneous coronary intervention (PCI). The use of intensified or prolonged antithrombotic regimens is invariably associated with a reduction in ischemic risk yet an increase in the risk of bleeding complications. The selection of the optimal antiplatelet therapy in each individual patient remains therefore crucial. In recent years, novel approaches alternative to the conventional DAPT and based on the escalation or de-escalation of P2Y12 antagonists have been proposed. These strategies, chosen according to clinical features, genetic factors, and platelet function, have been developed to optimize and individualize the treatment of patients with coronary artery disease and improve their prognosis. In this review, we summarize recent evidence about escalation and de-escalation strategies (guided and unguided), and discuss the utility of genetic and platelet function tests in patients with ACS and/or undergoing PCI.

Pathophysiology, Functional Assessment and Prognostic Implications of Nutritional Disorders in Systemic Amyloidosis.

Gastrointestinal involvement is a common clinical feature of patients with systemic amyloidosis. This condition is responsible for invalidating gastrointestinal symptoms, a significant macro and micronutrient deficit, and is a marker of disease severity. Gastrointestinal involvement should be actively sought in patients with systemic amyloidosis, while its diagnosis is challenging in patients with isolated gastrointestinal symptoms. The nutritional status in systemic amyloidosis plays an essential role in the clinical course and is considered a significant prognostic factor. However, the definition of nutritional status is still challenging due to the lack of internationally accepted thresholds for anthropometric and biochemical variables, especially in specific populations such as those with systemic amyloidosis. This review aims to elucidate the fundamental steps for nutritional assessment by using clinical and instrumental tools for better prognostic stratification and patient management regarding quality of life and outcomes.

Transcatheter valve-in-valve or valve-in-ring implantation with a novel balloon-expandable device in patients with bioprosthetic left side heart valves failure: 1-year follow-up from a multicenter experience.

BACKGROUND: Transcatheter aortic and mitral valve-in-valve (ViV) or valve-in-ring (ViR) implantation into failed bioprosthetic heart valves (BHVs) or rings represents an appealing, less invasive, treatment option for patients at high surgical risk. Nowadays, few data have been reported on the use of balloon-expandable Myval (Meril Life Science, Vapi, India) transcatheter heart valve (THV) for the treatment of degenerated BHVs or rings. We aimed at evaluating the early and mid-term clinical outcomes of patients with left side heart bioprosthesis deterioration treated with transcatheter ViV/ViR implantation using Myval THV. METHODS: 97 consecutive patients with symptomatic, severe aortic(n=33) and mitral(n=64) BHVs/ring dysfunction underwent transcatheter aortic ViV and mitral ViV/ViR implantation with Myval THV. RESULTS: Technical success was achieved in 95 (98%) of the patients. Two cases of acute structural trans-catheter mitral ViV/ViR dysfunction requiring a second THV implantation were reported. At 30-day, a significant reduction in prosthetic trans-valvular pressure gradients and increase in valve areas were seen following both aortic and mitral ViV/ViR implantation. Overall survival at 15 months (IQR 8-21) was 92%. Patients undergoing mitral ViV/ViR had a relatively worse survival compared with those undergoing aortic ViV implantation (89% vs. 97% respectively; HR:2.7,CI:0.33-22.7;p=0.34). At longest follow-up available a significant improvement in NYHA functional class I and II was observed in patients with aortic and mitral ViV/ViR implantation(93.8% and 92.1%). CONCLUSIONS: Despite high surgical risk, transcatheter ViV/ViR implantation for failed left side heart bioprosthesis can be performed safely using Myval THV with a high success rate and low early and mid-term mortality and morbidity.

Antithrombotic Therapy Optimization in Patients with Atrial Fibrillation Undergoing Percutaneous Coronary Intervention.

The antithrombotic management of patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) poses numerous challenges. Triple antithrombotic therapy (TAT), which combines dual antiplatelet therapy (DAPT) with oral anticoagulation (OAC), provides anti-ischemic protection but increases the risk of bleeding. Therefore, TAT is generally limited to a short phase (1 week) after PCI, followed by aspirin withdrawal and continuation of 6-12 months of dual antithrombotic therapy (DAT), comprising OAC plus clopidogrel, followed by OAC alone. This pharmacological approach has been shown to mitigate bleeding risk while preserving adequate anti-ischemic efficacy. However, the decision-making process remains complex in elderly patients and those with co-morbidities, significantly influencing ischemic and bleeding risk. In this review, we discuss the available evidence in this area from randomized clinical trials and meta-analyses for post-procedural antithrombotic therapies in patients with non-valvular AF undergoing PCI.

Pathophysiology and Treatment of the No-Reflow Phenomenon in ST-Segment Elevation Myocardial Infarction: Focus on Low-Dose Fibrinolysis during Primary Percutaneous Intervention.

Primary percutaneous coronary intervention (PCI) is the current class I therapeutic approach to treat acute ST-elevation myocardial infarction (STEMI). While primary PCI can restore adequate flow in the infarcted artery in the majority of cases, some patients experience the 'no-reflow' phenomenon, i.e., an abnormal myocardial reperfusion occurring even after the occluded coronary artery has been opened. No-reflow occurs when microvascular obstruction arises from embolization of thrombus or components of the atheromatous plaques. These embolic materials travel downstream within the infarct-related artery at time of primary PCI, leading to compromised blood flow. Currently, no expert consensus documents exist to outline an optimal strategy to prevent or treat no-reflow. Interventional cardiologists frequently employ intracoronary adenosine, calcium channel blockers, nicorandil, nitroprusside or glycoprotein IIb/IIIa inhibitors. However, evidence suggests that these interventions consistently enhance myocardial blood flow in only a specific subset of patients experiencing no-reflow. A recent and innovative therapeutic approach gaining attention is low-dose fibrinolysis during primary PCI, which offers the potential to augment coronary flow post-myocardial revascularization.

Escalation and De-Escalation of Antiplatelet Therapy after Acute Coronary Syndrome or PCI: Available Evidence and Implications for Practice.

Dual antiplatelet therapy (DAPT) is the gold standard for the antithrombotic management of patients with an acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI). Implementation of intensified or prolonged DAPT regimens has proven to lower the risk of ischemic events but at the expense of increased bleeding. Importantly, bleeding is a predictor of poor prognosis. Risk stratification and selection of tailored antiplatelet strategies to maximize the net clinical benefit in individual patients with ACS or undergoing PCI is therefore potentially beneficial. Recently, novel approaches including DAPT de-escalation or escalation have been proposed as possible alternatives to standard DAPT. These strategies, which are generally based on patient's risk profile, genetics, and/or platelet function have been proposed to offer more tailored treatments in patients with ACS or PCI, with the ultimate goal of providing adequate ischemic protection while mitigating the risk of bleeding. This review summarizes the available evidence on DAPT de-escalation or escalation (both guided and unguided) and discusses the practical implications of these strategies in the contemporary management of patients with ACS and/or undergoing PCI.

Sex-Related Differences in Long-Term Outcomes After Early-Onset Myocardial Infarction.

Importance: There is growing awareness of sex-related differences in cardiovascular risk profiles, but less is known about whether these extend to pre-menopausal females experiencing an early-onset myocardial infarction (MI), who may benefit from the protective effects of estrogen exposure. Methods: A nationwide study involving 125 Italian Coronary Care Units recruited 2,000 patients between 1998 and 2002 hospitalized for a type I myocardial infarction before the age of 45 years (male, n = 1,778 (88.9%). Patients were followed up for a median of 19.9 years (IQR 18.1-22.6). The primary composite endpoint was the occurrence of cardiovascular death, non-fatal myocardial re-infarction or non-fatal stroke, and the secondary endpoint of hospitalization for revascularisation by means of a percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG). Results: ST-elevation MI was the most frequent presentation among both men and women (85.1 vs. 87.4%, p = ns), but the men had a greater baseline coronary atherosclerotic burden (median Duke Coronary Artery Disease Index: 48 vs. 23; median Syntax score 9 vs. 7; both p < 0.001). The primary composite endpoint occurred less frequently among women (25.7% vs. 37.0%; adjusted hazard ratio: 0.69, 95% CI 0.52-0.91; p = 0.01) despite being less likely to receive treatment with most secondary prevention medications during follow up. Conclusions: There are significant sex-related differences in baseline risk factors and outcomes among patients with early-onset MI: women present with a lower atherosclerotic disease burden and, although they are less frequently prescribed secondary prevention measures, experience better long-term outcomes. Trial Registration: 4272/98 Ospedale Niguarda, Ca' Granda 03/09/1998.