Cardiovascular safety of testosterone replacement therapy in men: an updated systematic review and meta-analysis.

INTRODUCTION: The cardiovascular (CV) safety of testosterone (T) replacement therapy (TRT) is still conflicting. Recent data suggested a TRT-related increased risk of atrial fibrillation (AF). The aim of this study was to systematic review and meta-analyze CV risk related to TRT as derived from placebo controlled randomized trials (RCTs). AREAS COVERED: An extensive Medline, Embase, and Cochrane search was performed. All placebo-controlled RCTs reporting data on TRT-related CV safety were considered. To better analyze the role of T on AF, population-based studies investigating the relationship between endogenous circulating T levels and AF incidence were also included and analyzed. EXPERT OPINION: Out of 3.615, 106 studies were considered, including 8.126 subjects treated with TRT and 7.310 patients allocated to placebo. No difference between TRT and placebo was observed when major adverse CV events were considered. Whereas the incidence of non-fatal arrhythmias and AF was increased in the only trial considering CV safety as the primary endpoint, this was not confirmed when all other studies were considered (MH-OR 1.61[0.84;3.08] and 1.44[0.46;4.46]). Similarly, no relationship between endogenous T levels and AF incidence was observed after the adjustment for confounders Available data confirm that TRT is safe and it is not related to an increased CV risk.

Efficacy and safety of a minimalistic balloon aortic valvuloplasty strategy in a centre without heart surgery.

Background: Balloon aortic valvuloplasty (BAV) is a palliative tool for patients with symptomatic severe aortic stenosis (AS) at prohibitive risk for surgery or as a bridge to surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR). BAV is traditionally performed in hospitals with onsite cardiac surgery due to its potential complications. Aims: The aim of this study was to evaluate the safety of BAV procedures performed by trained high-volume operators in a centre without onsite surgery and to assess the effect of a minimalistic approach to reduce periprocedural complications. Methods: From 2016 to 2021, 187 BAV procedures were performed in 174 patients. Patients were elderly (mean age: 85.0±5.4 years) and had high-risk (mean European System for Cardiac Operative Risk Evaluation score [EuroSCORE] II: 10.1±9.9) features. According to the indications, 4 cohorts were identified: 1) bridge to TAVR (n=98; 56%); 2) bridge to SAVR (n=8; 5%); 3) cardiogenic shock (n=11; 6%); and 4) palliation (n=57; 33%). BAV procedures were performed using the standard retrograde technique via femoral access in 165 patients (95%), although radial access was used in 9 patients (5%). Ultrasound-guided vascular puncture was performed in 118 patients (72%) and left ventricular pacing was administered through a stiff guidewire in 105 cases (60%). Results: BAV safety was confirmed by 1 periprocedural death (0.6%), 1 intraprocedural stroke (0.6%), 2 major vascular complications (1%) and 9 minor vascular complications (5%). Nine cases of in-hospital mortality occurred (5%), predominantly in patients with cardiogenic shock. Conclusions: BAV is a safe procedure that can be performed in centres without onsite cardiac surgery using a minimalistic approach that can reduce periprocedural complications.

Combined use of intra-aortic balloon pump and impella in cardiogenic shock: A systematic review.

BACKGROUND: Use of Intra-Aortic Balloon Pump (IABP) in combination with Impella has been described as an alternative strategy for mechanical circulatory support (MCS) in patients with cardiogenic shock (CS). We provide a systematic review aimed to explore the effectiveness of this paired MCS approach. METHODS: We conducted a comprehensive systematic search in MEDLINE, Scopus, and Cochrane databases to identify all studies that investigated dual MCS with IABP and Impella. RESULTS: Our search strategy identified 12 articles, including 1 randomized controlled trial, 1 retrospective study, 1 case series, 7 case report and 2 animal studies. Rationale for this combined MCS strategy stems from an observed reduction in myocardial oxygen demand/supply ratio compared to the use of each device alone, without determining significant variations in left ventricular work. Nonetheless, this combined approach also leads to a 30-40 % decline in Impella flow, increasing the risk of bleeding, Impella displacement, as well as triggering positioning and pressure alarms. Additionally, hemolytic risk data yielded inconclusive results. Importantly, there were no notable disparities in mortality rates when comparing the combined strategy to the use of each device individually. CONCLUSION: At the current state-of-the-art, there are no conclusive data demonstrating net clinical benefits of combining Impella with IABP. Considering the substantial risks of morbidity associated, we recommend against its use in clinical practice.

"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.

[Conduction disorders after transcatheter aortic valve implantation: incidence, characteristics, and clinical management]. / I disturbi di conduzione dopo impianto transcatetere di protesi aortica: incidenza, caratteristiche e gestione clinica.

Transcatheter aortic valve implantation may be complicated by the development of conduction disturbances, including left bundle branch block and high-grade atrioventricular blocks, especially in patients with predisposing risk factors, such as pre-existing right bundle branch block. Permanent pacemaker implantation is a procedure with potential short- and long-term complications, and it should be reserved to patients with appropriate indications. Electrophysiological testing and/or prolonged ambulatory ECG monitoring are valuable tools for stratifying the risk of pacemaker implantation. However, the management of new-onset conduction disorders is not always straightforward, and there are different approaches depending on the center's attitude. Therefore, the purpose of this review is to define clinical management based on current evidence, while awaiting data from randomized trials.

A COVID-19 specific multiparametric and ECG-based score for the prediction of in-hospital mortality: ELCOVID score.

We aimed to develop and validate a COVID-19 specific scoring system, also including some ECG features, to predict all-cause in-hospital mortality at admission. Patients were retrieved from the ELCOVID study (ClinicalTrials.gov identifier: NCT04367129), a prospective, multicenter Italian study enrolling COVID-19 patients between May to September 2020. For the model validation, we randomly selected two-thirds of participants to create a derivation dataset and we used the remaining one-third of participants as the validation set. Over the study period, 1014 hospitalized COVID-19 patients (mean age 74 years, 61% males) met the inclusion criteria and were included in this analysis. During a median follow-up of 12 (IQR 7-22) days, 359 (35%) patients died. Age (HR 2.25 [95%CI 1.72-2.94], p < 0.001), delirium (HR 2.03 [2.14-3.61], p = 0.012), platelets (HR 0.91 [0.83-0.98], p = 0.018), D-dimer level (HR 1.18 [1.01-1.31], p = 0.002), signs of right ventricular strain (RVS) (HR 1.47 [1.02-2.13], p = 0.039) and ECG signs of previous myocardial necrosis (HR 2.28 [1.23-4.21], p = 0.009) were independently associated to in-hospital all-cause mortality. The derived risk-scoring system, namely EL COVID score, showed a moderate discriminatory capacity and good calibration. A cut-off score of ≥ 4 had a sensitivity of 78.4% and 65.2% specificity in predicting all-cause in-hospital mortality. ELCOVID score represents a valid, reliable, sensitive, and inexpensive scoring system that can be used for the prognostication of COVID-19 patients at admission and may allow the earlier identification of patients having a higher mortality risk who may be benefit from more aggressive treatments and closer monitoring.

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.

Long-term impact of intravascular ultrasound-guidance for percutaneous coronary intervention on unprotected left main. The IMPACTUS-LM, an observational, multicentric study.

INTRODUCTION: The potential benefit on long term outcomes of Percutaneous Coronary Intervention (PCI) on Unprotected Left Main (ULM) driven by IntraVascular UltraSound (IVUS) remains to be defined. METHODS: IMPACTUS LM-PCI is an observational, multicenter study that enrolled consecutive patients with ULM disease undergoing coronary angioplasty in 13 European high-volume centers from January 2002 to December 2015. Major Adverse Cardiovascular Events (MACEs) a composite of cardiovascular (CV) death, target vessel revascularization (TVR) and myocardial infarction (MI) were the primary endpoints, while its single components along with all cause death the secondary ones. RESULTS: 627 patients with ULM disease were enrolled, 213 patients (34%) underwent IVUS-guided PCI while 414 (66%) angioguided PCI. Patients in the two cohorts had similar prevalence of risk factors except for active smoking and clinical presentation. During a median follow-up of 7.5 years, 47 (22%) patients in the IVUS group and 211 (51%) in the angio-guided group underwent the primary endpoint (HR 0.42; 95% CI [0.31-0.58] p < 0.001). After multivariate adjustment, IVUS was significantly associated with a reduced incidence of the primary endpoint (adj HR 0.39; 95% CI [0.23-0.64], p < 0.001), mainly driven by a reduction of TVR (ad HR 0.30, 95% CI [0.15-0.62], p = 0.001) and of all-cause death (adj HR 0.47, 95% CI [0.28-0.82], p = 0.008). IVUS use, age, diabetes, side branch stenosis, DES and creatinine at admission were independent predictors of MACE. CONCLUSIONS: In patients undergoing ULM PCI, the use of IVUS was associated with a reduced risk at long-term follow-up of MACE, all-cause death and subsequent revascularization.

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).

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.

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.

Beta Blockers Improve Prognosis When Used Early in Patients with Cardiogenic Shock: An Analysis of the FRENSHOCK Multicenter Prospective Registry.

BACKGROUND: Beta blockers (BBs) are a cornerstone for patients with heart failure (HF) and ventricular dysfunction. However, their use in patients recovering from a cardiogenic shock (CS) remains a bone of contention, especially regarding whether and when to reintroduce this class of drugs. METHODS: FRENSHOCK is a prospective multicenter registry including 772 CS patients from 49 centers. Our aim was to compare outcomes (1-month and 1-year all-cause mortality) between CS patients taking and those not taking BBs in three scenarios: (1) at 24 h after CS; (2) patients who did or did not discontinue BBs within 24 h; and (3) patients who did or did not undergo the early introduction of BBs. RESULTS: Among the 693 CS included, at 24 h after the CS event, 95 patients (13.7%) were taking BB, while 598 (86.3%) were not. Between the groups, there were no differences in terms of major comorbidities or initial CS triggers. Patients receiving BBs at 24 h presented a trend toward reduced all-cause mortality both at 1 month (aHR = 0.61, 95% CI 0.34 to 1.1, p = 0.10) and 1 year, which was, in both cases, not significant. Compared with patients who discontinued BBs at 24 h, patients who did not discontinue BBs showed lower 1-month mortality (aHR = 0.43, 95% CI 0.2 to 0.92, p = 0.03) and a trend to lower 1-year mortality. No reduction in outcomes was observed in patients who underwent an early introduction of BB therapy. CONCLUSIONS: BBs are drugs of first choice in patients with HF and should also be considered early in patients with CS. In contrast, the discontinuation of BB therapy resulted in increased 1-month all-cause mortality and a trend toward increased 1-year all-cause mortality.

To Treat or Not to Treat? This Is the Question… About the Incidental Finding of Double Sinus of Valsalva Aneurysm in A 91-Year-Old Woman

ABSTRACT Sinus of Valsalva aneurysm is a very uncommon clinical finding and often requires emergency surgery due to its high risk of rupture. This educational text reports the case of a 91-year-old Italian women who was incidentally discovered to have a huge double aneurysm of the sinuses of Valsalva.