Multi-domain lifestyle intervention in older adults after myocardial infarction: rationale and design of the PIpELINe randomized clinical trial.

BACKGROUND: Traditional cardiac rehabilitation (CR) is effective in improving physical performance and prognosis after myocardial infarction (MI). Anyway, it is not consistently recommended to older adults, and its attendance rate is low. Previous studies suggested that alternative, early and tailored exercise interventions are feasible and effective in improving physical performance in older MI patients. Anyway, the demonstration that they are associated also with a significant reduction of hard endpoints is lacking. AIM: To describe rationale and design of the "Physical activity Intervention in Elderly patients with myocardial Infarction" (PIpELINe) trial. METHODS: The PIpELINe trial is a prospective, randomized, multicentre study with a blinded adjudicated evaluation of the outcomes. Patients aged ≥ 65 years, admitted to hospital for MI and with a low physical performance one month after discharge, as defined as short physical performance battery (SPPB) value between 4 and 9, will be randomized to a multi-domain lifestyle intervention (including dietary counselling, strict management of cardiovascular and metabolic risk factors, and exercise training) or health education. The primary endpoint is the one-year occurrence of the composite of cardiovascular death or re-hospitalization for cardiovascular causes. RESULTS: The recruitment started in March 2020. The estimated sample size is 456 patients. The conclusion of the enrolment is planned for mid-2023. The primary endpoint analysis will be available for the end of 2024. CONCLUSIONS: The PIpELINe trial will show if a multi-domain lifestyle intervention is able to reduce adverse events in older patients with reduced physical performance after hospitalization for MI. TRIAL REGISTRATION: ClinicalTrials.gov NCT04183465.

1,3,8-Triazaspiro[4.5]decane Derivatives Inhibit Permeability Transition Pores through a FO-ATP Synthase c Subunit Glu119-Independent Mechanism That Prevents Oligomycin A-Related Side Effects.

Permeability transition pore (PTP) molecular composition and activity modulation have been a matter of research for several years, especially due to their importance in ischemia reperfusion injury (IRI). Notably, c subunit of ATP synthase (Csub) has been identified as one of the PTP-forming proteins and as a target for cardioprotection. Oligomycin A is a well-known Csub interactor that has been chemically modified in-depth for proposed new pharmacological approaches against cardiac reperfusion injury. Indeed, by taking advantage of its scaffold and through focused chemical improvements, innovative Csub-dependent PTP inhibitors (1,3,8-Triazaspiro[4.5]decane) have been synthetized in the past. Interestingly, four critical amino acids have been found to be involved in Oligomycin A-Csub binding in yeast. However, their position on the human sequence is unknown, as is their function in PTP inhibition. The aims of this study are to (i) identify for the first time the topologically equivalent residues in the human Csub sequence; (ii) provide their in vitro validation in Oligomycin A-mediated PTP inhibition and (iii) understand their relevance in the binding of 1,3,8-Triazaspiro[4.5]decane small molecules, as Oligomycin A derivatives, in order to provide insights into Csub interactions. Notably, in this study we demonstrated that 1,3,8-Triazaspiro[4.5]decane derivatives inhibit permeability transition pores through a FO-ATP synthase c subunit Glu119-independent mechanism that prevents Oligomycin A-related side effects.

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.

Promotion and maintenance of physically active lifestyle in older outpatients 2 years after acute coronary syndrome.

AIMS: To examine long-term changes in lifestyle and exercise capacity of older patients hospitalized for acute coronary syndrome (ACS) involved in an innovative centre- and home-based exercise-based secondary prevention program. METHODS: A sample of 118 patients with ACS (age 76 [72-80] years) was analysed. Long-term changes in self-reported weekly leisure-time physical activity (wLTPA), walking speed (WS), and estimated cardiorespiratory fitness (eCRF, VO2peak, mL/kg/min) were the outcome variables. The program consisted of seven individual on-site sessions including motivational interviewing to reach exercise goals. Exercise prescription was based on the results of a standardized moderate and perceptually regulated treadmill walk to estimate VO2peak. wLTPA, WS, and eCRF were assessed at 1 (baseline), 2, 3, 4, 6, 12, and 24 months after discharge. RESULTS: 87, 76, and 70 patients completed follow-up at 6, 12, and 24 months, respectively. wLTPA significantly increased during the follow-up period (median METs/H/week 2.5, 11.2, 12.0, and 13.4 at baseline, 6, 12, and 24 months, respectively; P < 0.0001). At baseline, 18% of the sample met the current international guidelines for physical activity, while 75%, 70%, and 76% of them met the recommended values at 6-, 12-, and 24-month follow-up sessions, respectively. These results were associated with increasing median WS (2.9 ± 1.0, 4.3 ± 1.2, 4.5 ± 1.1, 4.5 ± 1.2 km/h, respectively, P < 0.0001), and VO2peak (16.5, 21.4, 21.1, 21.3 mL/kg/min, respectively, P < 0.0001). CONCLUSIONS: This early, individualized exercise intervention improved long-term adherence to a physically active lifestyle, walking capacity, and eCRF in older patients after ACS. Larger studies are needed to confirm short- and long-term clinical benefits of this intervention.

Performance of Synthetic Extracellular Volume Fraction in Different Cardiac Phenotypes From a Prospective Cohort of Patients Referred for Cardiac Magnetic Resonance.

BACKGROUND: A synthetic myocardial extracellular volume fraction (sECV) can be obtained without blood hematocrit (Hct) by using the linear relationship between Hct and the longitudinal relaxation time of blood. Concerns have been raised about the widespread clinical application of this approach. PURPOSE: To assess the relationship between measured ECV (m-ECV) and sECV, using both a published model and a locally derived one. STUDY TYPE: Single-center, prospective. FIELD STRENGTH/SEQUENCE: A 1.5 T/modified Look Locker (MOLLI) sequence. SUBJECTS: Fifty-two healthy subjects and 113 patients (76 with and 37 without a hypertrophic cardiac phenotype). ASSESSMENT: Three ECV values were obtained for each patient: 1) measured ECV (m-ECV), using Hct from a venous blood sample; 2) Fent-synthetic ECV (F-sECV), using the equation proposed by Fent et al; and 3) Local-synthetic ECV (L-sECV), using the equation obtained from a local derivation cohort comprising 83 subjects. STATISTICAL TESTS: Shapiro-Wilk test, analysis of variance, Kruskal Wallis test, Pearson correlation, Bland-Altman analysis, univariate and multivariable regression analysis. RESULTS: In the validation cohort (N = 82), Bland-Altmann analysis revealed an excellent agreement between m-ECV and L-sECV with a statistically insignificant bias (-0.1%, limits of agreement: -2.8% and 2.6%; P = 0.528), while in the overall population (N = 165), the mean bias between m-ECV and F-sECV was small but significant (1.2%, limits of agreement: -1.5% and 3.9%, P < 0.05). F-sECV bias was significantly higher for measured Hct (m-Hct) values <0.372 (2.3% vs. 1.0%, P < 0.05). Among the phenotype subgroups, amyloidotic patients showed a higher bias compared to others, both with F-sECV and L-sECV (2.3% vs. 1.1%, P < 0.05 and 1.1% vs. 0.2%, P < 0.05, respectively). DATA CONCLUSION: Although synthetic ECV performs well in an external cohort, the use of a local formula further improves the accuracy of ECV estimate over a broad spectrum of cardiac phenotypes. Local sECV performs better for a wider range of Hct values, compared to the published model. Amyloidosis is the only group associated with a lower accuracy. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 2.

Snuffbox approach for balloon aortic valvuloplasty: A case series.

In the era of transcatheter aortic valve replacement (TAVR), the spectrum of indications for balloon aortic valvuloplasty is growing, especially in old and frail patients. Mini-invasive approaches via radial access reduce vascular complications and length of hospital stay. The snuffbox approach has never been described for Balloon aortic valvuloplasty (BAV). We performed a review of patients who underwent BAV using distal radial access between January 2019 and December 2019 in a single Italian Centre. All patients received a 30-day follow-up. The procedure was successfully conducted by anatomical snuffbox in all reported cases. All patients were mobilized within 10 h from the procedure without vascular access-related complications. Thirty-day color Doppler ultrasound showed distal radial artery patency in 89% of cases. In our case series, the snuffbox approach for balloon aortic valvuloplasty appeared to be safe and feasible. This approach could be a valid alternative especially in old and frail adults waiting for TAVR.

T1 mapping and cardiac magnetic resonance feature tracking in mitral valve prolapse.

OBJECTIVES: T1 mapping (T1-map) and cardiac magnetic resonance feature tracking (CMR-FT) techniques have been introduced for the early detection of interstitial myocardial fibrosis and deformation abnormalities. We sought to demonstrate that T1-map and CMR-FT may identify the presence of subclinical myocardial structural changes in patients with mitral valve prolapse (MVP). METHODS: Consecutive MVP patients with moderate-to-severe mitral regurgitation and comparative matched healthy subjects were prospectively enrolled and underwent CMR-FT analysis to calculate 2D global and segmental circumferential (CS) and radial strain (RS) and T1-map to determine global and segmental native T1 (nT1) values. RESULTS: Seventy-three MVP patients (mean age, 57 ± 13 years old; male, 76%; regurgitant volume, 57 ± 21 mL) and 42 matched control subjects (mean age, 56 ± 18 years; male, 74%) were included. MVP patients showed a lower global CS (- 16.3 ± 3.4% vs. - 17.8 ± 1.9%, p = 0.020) and longer global nT1 (1124.9 ± 97.7 ms vs. 1007.4 ± 26.1 ms, p < 0.001) as compared to controls. Moreover, MVP patients showed lower RS and CS in basal (21.6 ± 12.3% vs. 27.6 ± 8.9%, p = 0.008, and - 13.0 ± 6.7% vs. - 14.9 ± 4.1%, p = 0.013) and mid-inferolateral (20.6 ± 10.7% vs. 28.4 ± 8.7%, p < 0.001, and - 12.8 ± 6.3% vs. - 16.5 ± 4.0%, p < 0.001) walls as compared to other myocardial segments. Similarly, MVP patients showed longer nT1 values in basal (1080 ± 68 ms vs. 1043 ± 43 ms, p < 0.001) and mid-inferolateral (1080 ± 77 ms vs. 1034 ± 37 ms, p < 0.001) walls as compared to other myocardial segments. Of note, nT1 values were significantly correlated with CS (r, 0.36; p < 0.001) and RS (r, 0.37; p < 0.001) but not with regurgitant volume. CONCLUSIONS: T1-map and CMR-FT identify subclinical left ventricle tissue changes in patients with MVP. Further studies are required to correlate these subclinical tissue changes with the outcome. KEY POINTS: • T1 mapping (T1-map) and cardiac magnetic resonance feature tracking (CMR-FT) techniques have been introduced for the early detection of interstitial myocardial fibrosis and deformation abnormalities. • In MVP patients, we demonstrated a longer global nT1 with associated reduced global circumferential (CS) and radial strain (RS) as compared to control subjects. • Among MVP patients, the mid-basal left ventricle inferolateral wall showed longer nT1 with reduced CS and RS as compared to other myocardial segments. Further studies are required to correlate these subclinical tissue changes with the outcome.

COX-2 Is Downregulated in Human Stenotic Aortic Valves and Its Inhibition Promotes Dystrophic Calcification.

Calcific aortic valve disease (CAVD) is the result of maladaptive fibrocalcific processes leading to a progressive thickening and stiffening of aortic valve (AV) leaflets. CAVD is the most common cause of aortic stenosis (AS). At present, there is no effective pharmacotherapy in reducing CAVD progression; when CAVD becomes symptomatic it can only be treated with valve replacement. Inflammation has a key role in AV pathological remodeling; hence, anti-inflammatory therapy has been proposed as a strategy to prevent CAVD. Cyclooxygenase 2 (COX-2) is a key mediator of the inflammation and it is the target of widely used anti-inflammatory drugs. COX-2-inhibitor celecoxib was initially shown to reduce AV calcification in a murine model. However, in contrast to these findings, a recent retrospective clinical analysis found an association between AS and celecoxib use. In the present study, we investigated whether variations in COX-2 expression levels in human AVs may be linked to CAVD. We extracted total RNA from surgically explanted AVs from patients without CAVD or with CAVD. We found that COX-2 mRNA was higher in non-calcific AVs compared to calcific AVs (0.013 ± 0.002 vs. 0.006 ± 0.0004; p < 0.0001). Moreover, we isolated human aortic valve interstitial cells (AVICs) from AVs and found that COX-2 expression is decreased in AVICs from calcific valves compared to AVICs from non-calcific AVs. Furthermore, we observed that COX-2 inhibition with celecoxib induces AVICs trans-differentiation towards a myofibroblast phenotype, and increases the levels of TGF-ß-induced apoptosis, both processes able to promote the formation of calcific nodules. We conclude that reduced COX-2 expression is a characteristic of human AVICs prone to calcification and that COX-2 inhibition may promote aortic valve calcification. Our findings support the notion that celecoxib may facilitate CAVD progression.

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.

Right Ventricle Function in Patients with Acute Coronary Syndrome and Concomitant Undiagnosed Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is frequently undiagnosed in patients with ischemic heart disease. Nowadays, it is still unknown whether undiagnosed concomitant COPD is related to early structural changes of the heart, as detectable by trans-thoracic echocardiography (TTE). Starting from the study population of the Screening for COPD in ACS Patients (SCAP) trial, we sought to investigate potential differences in echocardiographic parameters in patients with acute coronary syndromes (ACS), with or without undiagnosed concomitant COPD. Overall, 137 patients were included. Undiagnosed COPD was detected by spirometry in 39 (29%) patients. TTE was performed at inclusion (before hospital discharge) and after six months. Several echocardiographic parameters including fractional area change (FAC) and RV strain (RVS), were measured. Patients with undiagnosed COPD, as compared to those without COPD, showed lower FAC and reduced RVS both at inclusion (37 ± 6% vs. 44 ± 9%, p < 0.001; -15 ± -4 vs. -20 ± -5, p < 0.001, respectively) and after six months (38 ± 7% vs. 45 ± 9%, p < 0.001; -16 ± -4 vs. -20 ± -5, p < 0.001, respectively). After multivariate analysis undiagnosed COPD was independently associated with lower FAC and reduced RVS at baseline and at TTE after six months. Early impairment of RV function can be detected in ACS patients with concomitant undiagnosed COPD. If these alterations may be changed by an early diagnosis and an early treatment, should be evaluated in future studies. Clinical trial registration: NCT02324660.

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.

Extracorporeal Circulatory Support in Acute Coronary Syndromes: A Systematic Review and Meta-Analysis.

OBJECTIVES: Extracorporeal circulatory support is a life-saving technique, and its use is increasing in acute coronary syndromes. A meta-analysis on pooled event rate of short-term mortality and complications of acute coronary syndrome patients treated with extracorporeal circulatory support was performed. DATA SOURCES: Articles were searched in MEDLINE, Cochrane Library, Google Scholar, and Biomed Central. STUDY SELECTION: Inclusion criteria were observational studies on acute coronary syndrome patients treated with extracorporeal circulatory support. Primary outcome was short-term mortality. Secondary outcomes were extracorporeal circulatory support-related complications, causes of death, long-term mortality, and bridge therapy. DATA EXTRACTION: Sixteen articles were selected. Data about clinical characteristics, acute coronary syndrome diagnosis and treatment, extracorporeal circulatory support setting, outcome definitions, and event rate were retrieved from the articles. Random effect meta-analytic pooling was performed reporting results as a summary point estimate and 95% CI. DATA SYNTHESIS: A total of 739 patients were included (mean age, 59.8 ± 2.9). The event rate of short-term mortality was 58% (95% CI, 51-64%), 6-month mortality was affecting 24% (95% CI, 5-63%) of 1-month survivors, and 1-year mortality 17% (95% CI, 6-40%) of 6-month survivors. The event rates of extracorporeal circulatory support-related complications were acute renal failure 41%, bleeding 25%, neurologic damage in survivors 21%, sepsis/infections 21%, and leg ischemia 12%. Between causes of death, multiple organ failure and brain death affected respectively 40% and 27% of patients. Bridge to ventricular assistance device was offered to 14% of patients, and 7% received a transplant. CONCLUSIONS: There is still a high rate of short-term mortality and complications in acute coronary syndrome patients treated with extracorporeal circulatory support. New studies are needed to optimize and standardize extracorporeal circulatory support.

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.

Acute Hemodynamic Response to Cardiac Resynchronization in Dilated Cardiomyopathy: Effect on Late Mitral Regurgitation.

BACKGROUND: Functional mitral regurgitation (FMR) is associated with reduced survival in dilated cardiomyopathy (DCM). Cardiac resynchronization therapy (CRT) can improve FMR. We sought to identify the predictors of FMR improvement after CRT in DCM. METHODS: From January 2003 to December 2013, 430 DCM patients consecutively enrolled were retrospectively analyzed. Inclusion criteria were successful CRT implantation in the presence of conventional indications (i.e., left bundle branch block, left ventricular ejection fraction ≤35%, New York Heart Association functional class ≥II) and moderate-to-severe FMR at the time of procedure. Early echocardiographic evaluation after CRT implantation (median 2.5 days) has been performed in each patient. Improvement in FMR (absent/mild) at midterm (7 months; interquartile range 4-10) was considered as the primary study end point. RESULTS: A total of 44 patients (10% of the overall cohort) were included. A significant reduction in FMR severity was observed in 21 patients (48%) at midterm after CRT (median time 7 months). No preimplantation variables predicted FMR evolution, but FMR improvement at midterm was strongly predicted by an acute favorable hemodynamic response (persistence/development of normal right ventricular function and 10-mm Hg decrease or normalization [≤35 mm Hg] of systolic pulmonary artery pressure) at postimplantation echocardiography (odds ratio: 13.7; 95% confidence interval: 1.27-42.8; P = 0.016). FMR improvement at midterm was stable during follow-up and was associated with superior long-term transplant-free survival (P = 0.022). CONCLUSIONS: Stable FMR improvement frequently occurs after CRT implantation in DCM and is associated with improved transplant-free survival. Echocardiographic evaluation of acute hemodynamic response to CRT is helpful to early identification of the favorable FMR evolution.

[Percutaneous revascularization in non-ST-elevation acute coronary syndromes: complete or incomplete?] / Rivascolarizzazione percutanea nelle sindromi coronariche acute senza sopraslivellamento del tratto ST: completa o incompleta?

Non-ST-elevation myocardial infarction with multivessel coronary disease is increasing in patients presenting with acute coronary syndrome (ACS) and it is associated with a high rate of mortality. Complete revascularization may reduce major adverse cardiac events in patients with ACS. However, the preferred revascularization strategies (complete vs incomplete) of non-culprit lesions in this setting, as well as the correct timing of revascularization are still matters of debate. This is mostly related to the heterogeneity of patients with this clinical presentation, who are often older and affected by multiple comorbidities. The present review aims to evaluate this topic highlighting the pros and cons of complete revascularization according to anatomical or functional and imaging evaluation and based on timing and patient's clinical phenotype.

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.

Prognostic Electrocardiographic Signs in Arrhythmogenic Cardiomyopathy.

Arrhythmogenic cardiomyopathy (ACM) is a rare cardiac disease, characterized by the progressive replacement of myocardial tissue with fibrous and fatty deposits. It can involve both the right and left ventricles. It is associated with the development of life-threatening arrhythmias and culminates in sudden cardiac death. Electrocardiography (ECG) has emerged as a pivotal tool, offering diagnostic insights and prognostic information. The specific ECG abnormalities observed in ACM not only contribute to early detection but also hold the key to the prediction of the likelihood of severe complications. The recognition of these nuanced ECG manifestations has become imperative for clinicians as it guides them in the formulation of tailored therapeutic strategies that address both the present symptoms and the potential future risks.

Coronary Plaque in Athletes.

The relationship between vigorous physical activity (PA) and the development of coronary atherosclerosis has remained less explored for many years. Recently, literature data have focused on coronary atherosclerosis in athletes showing that prevalence is not trivial, that there are differences among various types of sport, and that there are some peculiar features. As a matter of fact, plaque composition in athletes seems to be characterized by calcium rather than soft components. Specific mechanisms through which vigorous PA influences coronary artery disease are not yet fully understood. However, the prevalent calcific nature of coronary plaques in athletes could be related with a trend in a lower cardiovascular event rate.

Association between Epicardial Adipose Tissue and Atrial Fibrillation in Patients with Transfusion-Dependent ß-Thalassemia.

Background: Modern treatments for transfusion-dependent ß-thalassemia (TDßT) have allowed patients to reach high life expectancy with no iron overload. Despite survival improvement, atrial fibrillation (AF) has emerged as a relevant issue. AF pathophysiology and characteristics in TDßT are different than in the general population. Epicardial adipose tissue (EAT) may play a role but its relationship with AF in patients with TDßT has not been explored. Methods: A monocentric, cross-sectional study, enrolling consecutive patients with TDßT. Epicardial adipose tissue (EAT) was evaluated at magnetic resonance. Characteristics of patients with and without history of AF were investigated. Factors independently associated with AF prevalence were analyzed. Results: A total of 116 patients were enrolled. All patients were treated with regular chelation therapy. The prevalence of AF was 29.3% (34/116). Cardiac T2* and liver iron concentration were no different between patients with and without AF. EAT thickness was significantly higher in patients with AF at left atrium, right atrium and right ventricle (5.0 vs. 4.0 mm, p < 0.01, 4.4 vs. 4.0, p = 0.02 and 5.0 vs. 4.3, p = 0.04). Patients with AF presented with older age, (53 vs. 49 years, p < 0.01), more hypothyroidism (44.1 vs. 20.7%, p = 0.01), pulmonary hypertension (23.5 vs. 2.4% p < 0.01), splenectomy (88.2 vs. 64.6%, p = 0.01), higher right and left atrial volume (61 vs. 40 and 74 vs. 43 mL, both p < 0.01). At multivariable analysis, hypothyroidism, left atrial volume and left atrial EAT were independently associated with AF (odds ratio 9.95, 1.09 and 1.91, respectively). Conclusions: In a contemporary cohort of patients with TDßT, treated with regular chelation therapy, prevalence of AF was unrelated to iron overload. EAT was independently associated with AF.