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Resumen Introduccion y objetivos La puntuacion de calcio arterial coronario (CAC) mejora la precision de la estratificacion del riesgo de enfermedad cardiovascular ateroesclerotica (ECVA) en comparacion con los factores de riesgo cardiovascular tradicionales. Se evaluo la interaccion de la carga ateroesclerotica coronaria determinada por la puntuacion de CAC con el beneficio pronostico de los tratamientos hipolipemiantes en el contexto de la prevencion primaria. Metodos Se revisaron las bases de datos MEDLINE, EMBASE y Cochrane en busca de estudios que incluyeran a individuos sin ECVA previa y con datos sobre la puntuacion de CAC y el tratamiento hipolipemiante segun los valores de CAC. El objetivo primario fue la aparicion de ECVA. Se evaluo el efecto del tratamiento hipolipemiante agrupado y estratificado por grupos de CAC (0, 1-100 y > 100) mediante un modelo de efectos aleatorios. Resultados Se incluyeron 5 estudios (1 aleatorizado, 2 de cohortes prospectivas y 2 retrospectivas) que incluyeron a 35.640 individuos (el 38,1% mujeres) con medias de edad de 62,2 (rango, 49,6-68,9) anos, colesterol unido a lipoproteinas de baja densidad de 128 (114-146) mg/dl y seguimiento de 4,3 (2,3-11,1) anos. La aparicion de la ECVA aumento de manera constante en los estratos crecientes de CAC tanto en los pacientes con como en aquellos sin tratamiento hipolipemiante. Al comparar a los pacientes con (34,9%) y sin (65,1%) exposicion al tratamiento hipolipemiante, este se asocio con menos aparicion de ECVA en los pacientes con CAC > 100 (OR = 0,70; IC95%, 0,53-0,92), pero no en aquellos con CAC de 1-100 o 0. Los resultados concordaron al agrupar los datos ajustados. Conclusiones Entre los individuos sin ECVA previa, una puntuacion de CAC > 100 identifica a los sujetos con mayor probabilidad de beneficiarse del tratamiento hipolipemiante, mientras que un CAC indetectable indica ausencia de beneficio.

Introduction and objectives Coronary artery calcium (CAC) score improves the accuracy of risk stratification for atherosclerotic cardiovascular disease (ASCVD) events compared with traditional cardiovascular risk factors. We evaluated the interaction of coronary atherosclerotic burden as determined by the CAC score with the prognostic benefit of lipid-lowering therapies in the primary prevention setting. Methods We reviewed the MEDLINE, EMBASE, and Cochrane databases for studies including individuals without a previous ASCVD event who underwent CAC score assessment and for whom lipid-lowering therapy status stratified by CAC values was available. The primary outcome was ASCVD. The pooled effect of lipid-lowering therapy on outcomes stratified by CAC groups (0, 1-100, > 100) was evaluated using a random effects model. Results Five studies (1 randomized, 2 prospective cohort, 2 retrospective) were included encompassing 35 640 individuals (female 38.1%) with a median age of 62.2 [range, 49.6-68.9] years, low-density lipoprotein cholesterol level of 128 (114-146) mg/dL, and follow-up of 4.3 (2.3-11.1) years. ASCVD occurrence increased steadily across growing CAC strata, both in patients with and without lipid-lowering therapy. Comparing patients with (34.9%) and without (65.1%) treatment exposure, lipid-lowering therapy was associated with reduced occurrence of ASCVD in patients with CAC > 100 (OR, 0.70; 95%CI, 0.53-0.92), but not in patients with CAC 1-100 or CAC 0. Results were consistent when only adjusted data were pooled. Conclusions Among individuals without a previous ASCVD, a CAC score > 100 identifies individuals most likely to benefit from lipid-lowering therapy, while undetectable CAC suggests no treatment benefit.

Aims The Heart Failure Association of the European Society of Cardiology (HFA-ESC) proposed a definition of advanced heart failure (HF) that has not been validated, yet. We assessed its prognostic impact in a consecutive series of patients with high-risk HF. Methods and results The HELP-HF registry enrolled consecutive patients with HF and at least one high-risk 'I NEED HELP' marker, evaluated at four Italian centres between 1(st) January 2020 and 30(th) November 2021. Patients meeting the HFA-ESC advanced HF definition were compared to patients not meeting this definition. The primary endpoint was the composite of all-cause mortality or first HF hospitalization. Out of 4753 patients with HF screened, 1149 (24.3%) patients with at least one high-risk 'I NEED HELP' marker were included (mean age 75.1 +/- 11.5 years, 67.3% male, median left ventricular ejection fraction [LVEF] 35% [interquartile range 25%-50%]). Among them, 193 (16.8%) patients met the HFA-ESC advanced HF definition. As compared to others, these patients were younger, had lower LVEF, higher natriuretic peptides and a worse clinical profile. The 1-year rate of the primary endpoint was 69.3% in patients with advanced HF according to the HFA-ESC definition versus 41.8% in the others (hazard ratio [HR] 2.23, 95% confidence interval [CI] 1.82-2.74, p < 0.001). The prognostic impact of the HFA-ESC advanced HF definition was confirmed after multivariable adjustment for relevant covariates (adjusted HR 1.98, 95% CI 1.57-2.50, p < 0.001). Conclusions The HFA-ESC advanced HF definition had a strong prognostic impact in a contemporary, real-world, multicentre high-risk cohort of patients with HF.

In contemporary Cardiac Intensive Care Unit (CICU), bedside intra-aortic balloon pump (IABP) insertion under echocardiographic guidance may be an attractive option for selected patients with cardiogenic shock (CS). Currently available data on this approach are limited.This study aimed to assess the feasibility and safety of bedside IABP insertion, as compared to fluoroscopic-guided insertion in the Catheterization Laboratory (CathLab), and to describe the clinical features of patients receiving bedside IABP insertion using a standardized technique in real-world CICU practice.We prospectively evaluated all patients admitted the CICU who received transfemoral IABP between June 2020 and October 2021. The overall study cohort was divided according to implant strategy in bedside and CathLab groups. The primary outcome was correct radiographic IABP positioning at the first bedside chest X-ray obtained after insertion. Secondary outcomes included IABP-related complications.Among 115 patients, bedside IABP insertion was performed in 35 (30.4%) cases, mainly presenting with CS-related to acute decompensated heart failure (ADHF) (68.6 vs 33.8%; p 0.001), with lower LVEF, higher proportion of right ventricular involvement and higher need of inotropes/vasopressors, compared to those receiving CathLab insertion. Bedside IABP insertion resulted feasible and safe, with similar rates of correct IABP positioning (82.9 vs. 82.5%; p = 0.963) and IABP-related major vascular complications (5.7 vs. 5.0%; p = 0.874), as compared to CathLab positioning.This study suggests the feasibility and safety of bedside IABP insertion, which could be of relevant interest in patients with ADHF-related CS who may not need coronary angiography or other urgent CathLab procedures.

Ventricular arrhythmias still represent an important cause of morbidity and mortality, especially in patients with heart failure and reduced left ventricular ejection fraction. Amiodarone is a Class III Vaughan-Williams anti-arrhythmic drug widely used in ventricular arrhythmias for its efficacy and low pro-arrhythmogenic effect. On the other hand, a significant limitation in its use is represented by toxicity. In this review, the pharmacology of the drug is discussed to provide the mechanistic basis for its clinical use. Moreover, all the latest evidence on its role in different clinical settings is provided, including the prevention of sudden cardiac death, implanted cardioverter defibrillators, ischemic and non-ischemic cardiomyopathies. A special focus is placed on everyday clinical practice learning points, such as dosage, indications, and contraindications from the latest guidelines.

Background and aim Measurement of cardiac index (CI) is crucial in the hemodynamic assessment of critically ill patients in the intensive care unit (ICU). The most reliable trans-thoracic echocardiography (TTE) technique for CI estimation is the left ventricular outflow tract (LVOT) Doppler method that requires, among other parameters, the LVOT cross-sectional area (CSA) measurement. However, geometrical assumptions inherent limitations and practical disadvantages related to the ICU setting, hamper LVOT-CSA assessment. In this study, we aimed to validate a simplified formula, leveraging only on LVOT-velocity time integral (VTI) and heart rate (HR) variables, for the non-invasive estimation of CI in ICU patients. Methods and Results We prospectively enrolled 50 consecutive patients admitted to our ICU requiring PAC over a one-year period. For each patient we measured the CI by PAC (CIPAC) and TTE. The latter was obtained both with the “traditional formula” (traditional CITTE), requiring LVOT-CSA assessment, and our new “simplified formula” (simplified CITTE). The correlation between the simplified CITTE and CIPAC was strong (r = 0.81) and resulted significantly greater than the traditional CITTE and CIPAC correlation (r = 0.70; p < 0.05 for Pearson r coefficients comparison). Both TTE-based CI showed an acceptable agreement (+0.19±0.48 L/min/m2 for simplified CITTE and -0.18±0.58 L/min/m2 for traditional CITTE) with the reference CIPAC. Conclusion In this study, we propose an easy-to-use and practical approach, leveraging on TTE LVOT-VTI and HR only, for non-invasive estimation of CI in ICU patients.

The procedural planning of transcatheter mitral valve replacement (TMVR) requires a specific imaging assessment to establish patient eligibility. Computed tomography (CT) is considered the reference method. In this setting, data regarding the role of transesophageal echocardiography (TEE) are lacking. Aims To evaluate the feasibility and reliability of a comprehensive 3D-TEE screening in TMVR candidates. Methods we performed a retrospective observational study including 72 consecutive patients who underwent a pre-procedural CT and 3D-TEE for TMVR evaluation. The measurements of mitral annulus (MA), length of anterior mitral leaflet (AML), native left ventricular outflow tract (LVOT) and predicted neo-LVOT acquired with CT and 3DTEE were compared using a novel semi-automated software for post processing analysis (3mensio Structural Heart 10.1 - 3mSH, Pie Medical Imaging, Bilthoven, Netherlands). The final suitability decision was given by the valve manufacturer based on CT measurements and clinical conditions. Results Among 72 patients screened, all patients had adequate image quality for 3D-TEE analysis. 3D-TEE and CT measurements for AML length (r=0.97), MA area (r=0.90), perimeter (r=0.68), anteroposterior (r=0.88) and posteromedial-anterolateral (r=0.74) diameters were found highly correlated, as well as for native LVOT (r=0.86) and predicted neo-LVOT areas (r=0.96) (all P -values Conclusions 3D-TEE appraisements showed good correlations with CT measurements and high accuracy to predict TMVR screening success. Central Illustration. Mitral annulus segmentation and neo-LVOT area measurement performed by means of the 3mensio software (Pie Medical Imaging, Bilthoven, Netherlands) in a step-by-step fashion by TEE and CT imaging. After the virtual simulation of a valve implantation, the minimal systolic neo-LVOT area is manually measured by planimetry on a plane orthogonal to the centerline.

Background The inodilator levosimendan has shown improved outcomes in acute heart failure (AHF) and cardiac surgery. Its hemodynamic effect is persistent, owing to a long (70-80 hours) elimination half-life of its active metabolites. No robust data is available of the use of levosimendan in patients with severe renal failure (SRF), thus its use is contraindicated in patients with estimated glomerular filtration rate (eGFR≤30 mL/min). Hypothesis Different pharmacokinetics due to renal failure may alter levosimendan active metabolites elimination, causing more pronounced hemodynamic effects. We aimed to characterize the hemodynamic effect of levosimendan in a real-world cohort of SRF patients. Methods We reviewed patients who received levosimendan (12.5 mg) for AHF or cardiogenic shock in our CICU (N=132), excluding those without invasive hemodynamics (n=85), and those without data before and during levosimendan infusion (n=11), a total of 36 patients were finally included in this analysis. We compared hemodynamics before and during levosimendan infusion in the study cohort with CKD-EPI eGFR≤30 mL/min/1.73 m2 or CRRT and those without. Results Patients with low eGFR (n=11) were older, they had similar LVEF and invasive hemodynamics before levosimendan infusion to the higher eGFR cohort. Visual inspection of the LOESS regression plots (Figure) revealed an higher drop in mean arterial pressure (MAP) and diastolic arterial pressure (DAP) in the low eGFR cohort. The maximum drop was observed at day 4 from levosimendan initiation, invasive hemodynamics at this timepoint revealed a lower DAP (44.6±8.8 vs 62.6±11.9 mmHg; p=0.014) and a tendentially lower MAP (73.6±5.5 vs 84.4±11.5 mmHg; p=0.079) while systolic arterial pressure (125.0±24.6 vs 121.3±21.8 mmHg; p=0.779), cardiac index (2.1±0.5 vs 2.5±0.7 L/m2; p=0.211), and mean pulmonary arterial pressure (25.8±8.3 vs 24.8±9.6 mmHg; p=0.844) did not differ between groups. In-hospital death was not different in the two cohorts (27.3 vs 16.0%; p=0.650). Conclusions Patient with eGFR≤30 mL/min/1.73 m2 demonstrated a higher drop in DAP and MAP four days after levosimendan infusion start, without impact on hospital mortality. These findings may suggest a more pronounced hemodynamic effect of levosimendan in patients with SRF, possibly due to altered pharmacokinetics of its active metabolites.

Background Acute heart failure (AHF) with left ventricle (LV) dysfunction is characterized by a condition of afterload mismatch without preload reserve. LV ejection fraction (LVEF) and stroke volume (SV) become thus dependent on the afterload. Owing to its arteriolar vasodilator properties, sodium nitroprusside (SNP) may reduce LV afterload and result particularly beneficial in this setting, improving LV ejection and ventriculo-arterial coupling (VAC). Hypothesis We aimed to assess the effect of SNP on LV afterload (arterial elastance, Ea), LV contractility (end-systolic elastance, Ees) and VAC (Ea/Ees ratio) in AHF patients. Methods Patients with AHF receiving SNP were prospectively enrolled and underwent Ea and Ees estimation with a single-beat echocardiographic method, before and after SNP infusion. The method was described by Chen et al (J Am Coll Cardiol, 2001) and Kelly et al (Circulation, 1992). Echocardiography was analyzed by a physician blinded to the images timing. Results A total of 36 AHF patients [69% male, age 70 (68, 76) years] received SNP infusion and were enrolled. Patients were admitted for acute coronary syndrome (47%) and for worsening heart failure (53%). SNP median dose was low: 0.30 (0.21-0.57) mcg/kg/min. SNP led to a trend to SBP reduction [140 (131-150) vs 158 (140-168) mmHg; p=0.002]. Heart rate did not change: 84 (75, 92) vs 83 (72, 94) bpm; p=0.800. Afterload (Ea) was reduced following SNP infusion: 2.2 (1.9, 2.7) vs 2.8 (2.4, 3.4) mmHg/mL; p Conclusion In this report on consecutive AHF, low-dose SNP did not significantly affect VAC but led to a significant reduction in LV afterload and to a significant increase in SV and LVEF.

Introduction In cardiogenic shock (CS) patients with temporary mechanical circulatory support (TMCS) the weaning process is crucial to verify patients’ myocardial recovery or device dependency. To date, there are no specific guidelines on weaning strategies. Hypothesis We investigated clinical predictors of successful weaning from TMCS and developed with them a novel prognostic scoring system. Methods Eighty CS patients (62.5 ± 11.8 years, 86.2% male, 63.7% with ACS) with Impella support were evaluated. Hemodynamic, echocardiographic and laboratory data were collected at admission (T0), 24 (T1), 48 (T2), 96 (T3) hours after TMCS implantation. CS patients were classified according to successful or unsuccessful weaning, defined as hemodynamic/myocardial recovery, and death/need for LVAD/heart transplant, respectively. Independent predictors of weaning and their discriminating cut-off values were identified. Finally, a prognostic weaning score (W-Score) was derived. Results Thirty-eight (47.5%) CS patients showed successful (SW-group) while 42 (52.5%) unsuccessful (UW-group) weaning from TMCS. Clinical characteristics were similar between the two groups. SW-group showed higher T1, T2, T3 LVEF (p=0.013, p=0.001, p=0.001), T1 CPO (p=0.04), T2 MAP (p=0.019) and lower T1, T2 inotropic score values (p=0.001, p=0.001), T2 HR and PCWP (p=0.01, p=0.008), T1 and T3 creatinine (p=0.018, p=0.009), lactate (p=0.009, p=0.002) and NT-proBNP (p=0.017, p=0.001). T1 LVEF, NT-proBNP and inotropic score together with T3 creatinine and lactate resulted independent predictors of SW (p Conclusions W-Score, based on T1 LVEF/inotropic score/NT-proBNP, T3 creatinine/lactate values may be useful to identify CS patients undergoing successful weaning from TMCS.

Background Intra-Aortic Balloon Pump (IABP) efficacy is critically affected by the inflation/deflation timing. Balloon deflation may cause a sucking effect, and a steal phenomenon on carotid flow. Delaying IABP deflation reduces the degree of this flow reversal, but at the same time exposes patients to the risk of increased proto-systolic afterload with detrimental effects on the LV. Hypothesis To investigate the effects of a delayed IABP deflation timing on cerebral blood flow and LV hemodynamics. Methods We prospectively evaluated 20 consecutive patients who received transfemoral IABP for cardiogenic shock (CS). Central aortic pressures (augmented diastolic [ADP], end-diastolic [EDP], assisted systolic [ASP] and mean aortic [MAP] pressures) were recorded from the IABP console simultaneously with ultrasound data. First ultrasound and haemodynamic measurements were collected during conventional IABP deflation timing (balloon deflation completed before onset of LV systole by automated ECG gating). Then, IABP deflation was manually delayed to the beginning of the QRS (early LV systole). After adjustment, counterpulsation was performed for a minimum of 2 minutes to achieve steady hemodynamics, then the same ultrasound and haemodynamic measurements were recollected. Results Mean age was 67±13 years, LVEF was 25±11%. At the carotid ultrasound, the delayed deflation increased the net forward velocity time integral (VTI) in the common carotid artery (18±9 vs 15±8 cm; p=0.001), by reducing the end-diastolic backward VTI (1±1 vs 4±2 cm; p Conclusions In our cohort, a delayed IABP deflation strategy, evaluated by a multi-parametric yet relatively simple approach, demonstrated to be safe and was associated with both an increase cerebral perfusion and an improvement in cardiac mechanics.

VA-ECMO is commonly used for patients in cardiogenic shock (CS) or refractory cardiac arrest (CA) undergoing PCI for ACS. In this setting at high risk of both thrombotic and hemorrhagic complications, optimal anti-thrombotic therapy remains ill-defined. We hypothesized that an anti-thrombotic therapy comprising a parenteral anticoagulant (bivalirudin) and a parenteral anti-platelet agent (cangrelor) may prove safe and effective in this scenario. From November 2019 to December 2021, 14 patients received at least one dose of cangrelor (starting dose: 0.125 μg/kg/min) plus bivalirudin, without background aspirin, in the context of PCI and VA-ECMO for ACS-related CS/CA, and were included in this study. Efficacy endpoint was occurrence of thrombotic events and safety endpoint was major bleeding occurrence. Median age was 58 years. The majority (64%) presented with refractory CA. A thrombotic event occurred in 14%, while major bleeding occurred in 21% patients. One patient experienced arterial thrombosis after VA-ECMO arterial cannula removal, another experienced ischemic cerebellar stroke without functional sequelae. Bleeding events were: 29% BARC 3a, 14% BARC 3b, and 7% BARC 5b. Overall in-hospital mortality was 50%. Cangrelor was continued for 5 (4-10) days; temporary discontinuation was necessary in 36%, either for VA-ECMO cannula removal or for bleeding events. A low dose of cangrelor, associated with standard-intensity anticoagulation with bivalirudin was a feasible anti-thrombotic strategy in patients undergoing PCI during VA-ECMO support for ACS-related CS/CA. Bleeding events rates outweighed thrombotic events rates in this critically-ill population, although the observed rates were lowest among available studies.

Measurement of cardiac index (CI) is crucial in the hemodynamic assessment of critically ill patients in the intensive care unit (ICU). The most reliable trans-thoracic echocardiography (TTE) technique for CI estimation is the left ventricular outflow tract (LVOT) Doppler method that requires, among other parameters, the LVOT cross-sectional area (CSA) measurement. However, inherent and practical disadvantages, mostly related to the ICU setting, hamper LVOT-CSA assessment. In this study, we aimed to validate a simplified formula, leveraging on LVOT-velocity time integral (VTI) and heart rate (HR) only, for non-invasive estimation of CI in ICU patients.We prospectively enrolled 50 consecutive patients admitted to our ICU requiring pulmonary artery catheterization (PAC) over a one-year period. For each patient we measured the CI by PAC (CIIn this study, we validated a practical approach, leveraging on TTE LVOT-VTI and HR only, for non-invasive estimation of CI in ICU patients.

AIMS: Controversial data have been published regarding the prognostic role of cardiac troponins in patients who need hospitalization because of coronavirus disease 2019 (COVID-19). The aim of the study was to assess the role of high-sensitivity troponin plasma levels and of respiratory function at admission on all-cause deaths in unselected patients hospitalized because of COVID-19. METHODS: We pooled individual patient data from observational studies that assessed all-cause mortality of unselected patients hospitalized for COVID-19. The individual data of 722 patients were included. The ratio of partial pressure arterial oxygen to fraction of inspired oxygen (PaO2/FiO2) and high-sensitivity troponins was reported at admission in all patients. This meta-analysis was registered on PROSPERO (CRD42020213209). RESULTS: After a median follow-up of 14 days, 180 deaths were observed. At multivariable regression analysis, age [hazard ratio (HR) 1.083, 95% confidence interval (CI) 1.061-1.105, P 

Introduction Recently, observational data have raised concerns about safety of selfexpandable (SE) compared to balloon-expandable (BE) valves in TAVI, although potentially limited by patient selection bias. Methods. All Randomized Controlled Trials (RCTs) comparing BE vs. SE TAVI or/and vs. aortic valve replacement (AVR) were included and compared through Network Meta Analysis (NMA). All-cause and cardiovascular (CV) mortality were the primary endpoints, stroke, rates of permanent pacemaker implantation (PPI), moderate/severe paravalvular leak (PVL) and reintervention were the secondary endpoints. Results We obtained data from 11 RCTs, encompassing 9752 patients. After one and two years, no significant differences for allcause and CV mortality were observed. Compared to surgical bioprostheses, both BE and SE TAVI reduced the risk of acute kidney injury (OR 0.42; CI 95% 0.30–0.60 and OR 0.44; CI 95% 0.32–0.60), new-onset atrial fibrillation (OR 0.24; CI 95% 0.14–0.42 and OR 0.21; CI 95% 0.13–0.34) and major bleedings (OR 0.32; CI 95% 0.16–0.65 and OR 0.47; CI 95% 0.25–0.89). The BE prostheses reduced the risk of moderate/severe PVL at 30-day (OR 0.31; CI 95% 0.17–0.55) and of PPI both at 30-day (OR 0.51; CI 95% 0.33–0.79) and 1 year (OR 0.40; CI 95% 0.30–0.55) as compared to SE TAVI. Conclusions A TAVI strategy, independently from BE or SE prostheses, offers a midterm survival comparable to AVR. The BE prostheses are associated with a reduction of PPI and PVL compared to SE prostheses without any differences in all-cause and CV mortality during two years of follow up. PROSPERO ID CRD42020182407.

Extracorporeal membrane oxygenation (ECMO) represents a therapeutic option for cardiopulmonary support in patients with high-risk pulmonary embolism (PE); however, no definite consensus exists on ECMO use in high-risk PE. Hence, we aim to provide insights into its real-world use pooling together all available published experiences. We performed a systematic review and pooled analysis of all published studies (up to April 17, 2020) investigating ECMO support in high-risk PE. All studies including at least four patients were collectively analyzed. Study outcomes were early all-cause death (primary endpoint) and relevant in-hospital adverse events. A total of 21 studies were included in the pooled analysis (n = 635 patients). In this population (mean age 47.8 ± 17.3 years, 44.5% females), ECMO was indicated for cardiac arrest in 62.3% and immediate ECMO support was pursued in 61.9% of patients. Adjunctive reperfusion therapies were implemented in 57.0% of patients. Pooled estimate rate of early all-cause mortality was 41.1% (95% CI 27.7%-54.5%). The most common in-hospital adverse event was major bleeding, with an estimated rate of 28.6% (95%CI 21.0%-36.3%). At meta-regression analyses, no significant impact of multiple covariates on the primary endpoint was found. In this systematic review of patients who received ECMO for high-risk PE, pooled all-cause mortality was 41.1%. Principal indication for ECMO was cardiac arrest, cannulation was chiefly performed at presentation, and major bleeding was the most common complication.

Background The placebo effect is a well described phenomenon in blinded studies evaluating anti-anginal therapeutics, although its impact on clinical research metrics remains unknown. We conducted a systematic review and meta-analysis to quantify the impact of placebo on endpoints of symptoms, life-quality and functional outcomes in randomized placebo-controlled trials (RCTs) of symptomatic stable coronary artery disease. Methods We systematically reviewed MEDLINE, EMBASE, and the Cochrane database for double-blind RCTs of anti-angina therapeutics. Patients randomized to the placebo-arm were the study population. Main outcomes were the changes in exercise performance (exercise treadmill test [ETT] parameters), quality of life (Seattle Angina Questionnaire domains), symptoms (Canadian Cardiovascular Society angina class) and drug usage (nitroglycerin tabs/week) between baseline and following placebo. The primary outcome was ETT total duration time. Data were pooled with a random effect model. Results Seventy-eight RCTs (83% drug-controlled, 17% procedure-controlled) were included encompassing 4,925 patients randomized to placebo. ETT total duration time was significantly improved following placebo as compared to baseline (mean [95% confidence interval]: 29.2 [20.6-37.8] seconds) with evidence of high heterogeneity (I 2 = 98%) At subgroup analysis, crossover design was associated with a smaller placebo effect on ETT performance than parallel study design (p for interaction=0.001). A significant placebo effect was observed for all secondary outcomes with overall high heterogeneity. Conclusion A substantial placebo effect was present in angina RCTs across a variety of functional and life-quality metrics. High variability in placebo effect size was present, mostly unexplained by differences in study and patient characteristics (PROSPERO CRD42019132797).

For acute coronary syndrome (ACS) patients treated with percutaneous coronary intervention (PCI), the choice of the duration and kind of dual antiplatelet therapy (DAPT) offering the most accurate balance between ischemic and bleeding risk remains unknown.A network meta-analysis was performed including all Randomized Controlled Trials (RCTs) comparing different DAPT regimens and duration in ACS patients undergoing PCI. Trial-defined MACE and major bleedings were the primary endpoints. Stroke, stent thrombosis (ST), all-cause and cardiovascular death, myocardial infarction (MI) represented secondary endpoints.13 RCTs encompassing 46145 patients were included. Mean age was 62 (61-64) years old, 42% being admitted with STEMI, 33% with NSTEMI and 25% with UA. The competitive arms were: clopidogrel and aspirin for 12 months (6 arms/18183 patients), clopidogrel and aspirin for 6 months (4/3329), clopidogrel and aspirin12 months (3/2238), ticagrelor and aspirin for 12 months (6/12942) and prasugrel and aspirin for 12 months (3/9453). Trial-defined MACE and major bleedings, stroke and death were similar among the different arms. DAPT with prasugrel and aspirin for 12 months reduced MI compared to aspirin and clopidogrel for 12 months (OR 0.71, 95%CI 0.54.0.94), and reduced the risk of ST compared to ticagrelor (OR 0.66, 95%CI 0.49-0.90). Both prasugrel and ticagrelor reduced ST as compared to clopidogrel and aspirin for 12 months.Different DAPT strategies yield similar risk of MACE, major bleeding, death and stroke in ACS patients. Prasugrel and aspirin for 12 months proved to be the most effective strategy regarding ST and MI.

ObjectiveTo assess the prevalence, characteristics and prognostic value of pulmonary hypertension (PH) and right ventricular dysfunction (RVD) in hospitalised, non-intensive care unit (ICU) patients with coronavirus disease 2019 (COVID-19).MethodsThis single-centre, observational, cross-sectional study included 211 patients with COVID-19 admitted to non-ICU departments who underwent a single transthoracic echocardiography (TTE). Patients with poor acoustic window (n=11) were excluded. Clinical, imaging, laboratory and TTE findings were compared in patients with versus without PH (estimated systolic pulmonary artery pressure >35 mm Hg) and with versus without RVD (tricuspid annular plane systolic excursion ResultsA total of 200 patients were included in the final analysis (median age 62 (IQR 52–74) years, 65.5% men). The prevalence of PH and RVD was 12.0% (24/200) and 14.5% (29/200), respectively. Patients with PH were older and had a higher burden of pre-existing cardiac comorbidities and signs of more severe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (radiological lung involvement, laboratory findings and oxygenation status) compared with those without PH. Conversely, patients with RVD had a higher burden of pre-existing cardiac comorbidities but no evidence of more severe SARS-CoV-2 infection compared with those without RVD. The presence of PH was associated with a higher rate of in-hospital death or ICU admission (41.7 vs 8.5%, pConclusionsAmong hospitalised non-ICU patients with COVID-19, PH (and not RVD) was associated with signs of more severe COVID-19 and with worse in-hospital clinical outcome.Trial registration numberNCT04318366

Dual antiplatelet therapy combining aspirin with a P2Y12-receptor inhibitor reduces atherothrombotic events following an acute coronary syndromes (ACS), but the relative merits of different P2Y12 inhibitors remain unclear, despite several recent large-scale trials. We performed a network meta-analysis, representing the largest evidence to date to inform P2Y12 inhibitor choice in patients with ACS. Fourteen studies were included, for a total population of 145,019 patients. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used in this systematic review. A network meta-analysis using a frequentist approach with surface under the cumulative ranking probability calculation was performed. Major adverse cardiovascular events (MACE), all-cause death, myocardial infarction (MI), definite stent thrombosis (ST) and major bleeding at 30-day and 1-year all-cause death and MI were the study endpoints. At 30-day, prasugrel was superior to both clopidogrel and ticagrelor in MACE, all-cause death and definite ST endpoints. Both prasugrel and ticagrelor were superior to clopidogrel in MI endpoint. Ticagrelor also reduced all-cause death compared with clopidogrel. Ticagrelor, prasugrel, and clopidogrel resulted equivalent in terms of the safety outcome of 30-day major bleeding. No significant difference was found among clopidogrel, prasugrel, and ticagrelor with respect to 1-year MACE outcome. Both prasugrel and ticagrelor reduced the occurrence of 1-year all-cause death compared with clopidogrel. Prasugrel reduced 1-year MI rate as compared with clopidogrel, while ticagrelor did not. At probability analyses, prasugrel ranked best in all 30-day and 1-year efficacy and safety endpoints. In conclusion, in this network meta-analysis, prasugrel showed the highest efficacy in reducing adverse outcomes in ACS patients and had the highest probability of being the best P2Y12 inhibitor to reduce hard adverse events both at 30-day and 1-year follow-up.

Refractory angina is a growing problem, predominantly due to advanced coronary artery disease, associated with a reduced quality of life and an increased hospitalisation rate with a corresponding impact on healthcare resources. There is an unmet clinical need to be addressed by novel therapeutic approaches. Over the last few years, a treatment approach causing a controlled coronary sinus narrowing by implantation of a balloon-expandable, hourglass-shaped, stainless steel mesh (i.e., the coronary sinus Reducer) has arisen with promising initial short-term and midterm results, in terms of reducing angina and ischaemia burden and improving quality of life. Guidance with proper implantation algorithms and knowledge on how to address potential complications will improve interventional outcomes and foster a wider application of this novel therapeutic approach. In this review, we summarise the implantation technique, the causes of potential complications, and algorithms focusing upon their practical management, based on the experience of the authors.

Background The ULISSE registry evaluated the real-world performance of the Ultimaster® biodegradable polymer sirolimus-eluting stent (BP-SES) in a multicenter-independent cohort of patients undergoing percutaneous coronary intervention, including a large proportion of diabetes mellitus (DM) patients. Methods In this subgroup analysis, 1,660 consecutive patients, 2,422 lesions, treated with BP-SES enrolled in the ULISSE registry were divided in two groups: DM (485 patients, 728 lesions) and non-DM (1,175 patients, 1,694 lesions). Primary endpoint was target lesion failure (TLF), a composite endpoint of cardiac-death, target-vessel myocardial infarction (TV-MI), and clinically driven target lesion revascularization (TLR) at 1-year. Secondary endpoint was TLR at 1-year. Results At 1-year follow-up TLF occurred in 5% overall patients and was significantly higher in DM patients (8 vs. 3.7%; p = .001), due to more cardiac deaths (3.4 vs. 1.1%; p = .002). TLR occurred in 3.2% overall patients, and it was not significantly higher in DM compared to non-DM patients (4.4 vs. 2.8%; p = .114). The incidence of stent thrombosis was low and similar between groups (0.4 vs. 0.9%; p = .526). Insulin-treated DM (ITDM) patients showed higher rate of TLF as compared to non-ITDM patients (13 vs. 6.5%; p = .041), but similar rate of TLR (6 vs. 4%; p = .405). After adjustment for relevant comorbidities, DM was not significantly associated with TLF or cardiac death in patients undergoing BP-SES implantation. Conclusions This study is the first all-comers evaluation of BP-SES in DM patients. Our findings show that DM patients, mostly those with ITDM, still represent a vulnerable population and experience significantly higher rate of TLF. Overall BP-SES efficacy is considerable, although not statistically significant higher rate of TLR is still present in DM compared to non-DM patients.

Highlights •Refractory angina may be prevalent in 5% to 10% of stable coronary artery disease patients. •Many emerging therapeutics may be suitable and efficacious to improve quality of life in refractory angina. •Standardized sham-controlled trials’ design will be key to these treatments’ wide implementation.

Introduction Coronary Sinus Reducer emerged as promising therapeutic option for patients with refractory angina. While recent literature reports short-term benefits of Reducer implantation, there is paucity of evidence regarding its safety and efficacy at longer follow-up. Methods In the original cohort of 50 refractory angina patients treated with Reducer at San Raffaele Hospital (Milan, Italy) between March 2015 and August 2016, we reassessed angina symptoms, quality of life and recorded adverse events at 2-year (mean ± SD: 748 ± 84 days) follow-up. Results Canadian Cardiovascular Society (CCS) score improved of ≥1 class in 34 patients (75.6%), and of ≥2 classes in 16 patients (35.6%), translating into a significant mean CCS score reduction at 2-year follow-up (1.74 ± 0.86 vs. 2.98 ± 0.52; p Conclusions Safety and efficacy observed in the short follow-up period after Reducer implantation are maintained at two years. Ten patients underwent PCI during follow-up, underlining that Reducer does not affect coronary artery disease progression.

Trials on intra-aortic balloon pump (IABP) use in cardiogenic shock related to acute myocardial infarction have shown disappointing results. The role of IABP in cardiogenic shock treatment remains unclear, and new (potentially more potent) mechanical circulatory supports with arguably larger device profile are emerging. A reappraisal of the physiological premises of intra-aortic counterpulsation may underpin the rationale to maintain IABP as a valuable therapeutic option for patients with acute decompensated heart failure and tissue hypoperfusion. Several pathophysiological features differ between myocardial infarction- and acute decompensated heart failure–related hypoperfusion, encompassing cardiogenic shock severity, filling status, systemic vascular resistances rise, and adaptation to chronic (if preexisting) left ventricular dysfunction. IABP combines a more substantial effect on left ventricular afterload with a modest increase in cardiac output and would therefore be most suitable in clinical scenarios characterized by a disproportionate increase in afterload without profound hemodynamic compromise. The acute decompensated heart failure syndrome is characterized by exquisite afterload-sensitivity of cardiac output and may be an ideal setting for counterpulsation. Several hemodynamic variables have been shown to predict response to IABP within this scenario, potentially guiding appropriate patient selection. Finally, acute decompensated heart failure with hypoperfusion may frequently represent an end stage in the heart failure history: IABP may provide sufficient hemodynamic support and prompt end-organ function recovery in view of more definitive heart replacement therapies while preserving ambulation when used with a transaxillary approach.

Background Contrast‐induced acute kidney injury (CI‐AKI) is a serious complication after percutaneous coronary intervention. The mainstay of CI‐AKI prevention is represented by intravenous hydration. Tailoring infusion rate to patient volume status has emerged as advantageous over fixed infusion‐rate hydration strategies. Methods and Results A systematic review and network meta‐analysis with a frequentist approach were conducted. A total of 8 randomized controlled trials comprising 2312 patients comparing fixed versus tailored hydration strategies to prevent CI‐AKI after percutaneous coronary intervention were included in the final analysis. Tailored hydration strategies included urine flow rate–guided, central venous pressure–guided, left ventricular end‐diastolic pressure–guided, and bioimpedance vector analysis–guided hydration. Primary endpoint was CI‐AKI incidence. Safety endpoint was incidence of pulmonary edema. Urine flow rate–guided and central venous pressure–guided hydration were associated with a lower incidence of CI‐AKI compared with fixed‐rate hydration (odds ratio [OR], 0.32 [95% CI, 0.19–0.54] and OR, 0.45 [95% CI, 0.21–0.97]). No significant difference in pulmonary edema incidence was observed between the different hydration strategies. P score analysis showed that urine flow rate–guided hydration is advantageous in terms of both CI‐AKI prevention and pulmonary edema incidence when compared with other approaches. Conclusions Currently available hydration strategies tailored on patients' volume status appear to offer an advantage over guideline‐supported fixed‐rate hydration for CI‐AKI prevention after percutaneous coronary intervention. Current evidence suggests that urine flow rate–guided hydration as the most convenient strategy in terms of effectiveness and safety.

Funding Acknowledgements Type of funding sources: None. Aims and Methods Aim of this study was to assess the feasibility of a bolus-free, low-dose levosimendan infusion for acute decompensated heart failure (ADHF) with hypoperfusion. All consecutive patients who received levosimendan without intravenous bolus at our Department for ADHF in the last 6 months were included in this is a single-center retrospective study. To avoid abrupt drop in blood pressure, all patients started infusion at 0.01 mcg/kg/min, and gradual titration was achieved, up to 0.1 mcg/kg/min. Continuous variables are reported as medians (IQR), categorical as proportions. Paired measures were compared with the Wilcoxon signed-rank test. p-value was set at 5%. Analyses were performed using RStudio v1.3. Results We included 26 patients [males 84.6%; age 72 (59-76) years]. Patients had severe LV dysfunction [LVEF of 20 (20-25)%] and moderate/severe RV dysfunction in 46.2%. Most patients were admitted for cardiogenic shock (26.9%) or low-output state (61.5%); baseline serum lactate was 1.6 (1.2-3.2) mmol/L. Etiology was ACS in 26.9% patients, worsening HF in 53.8%, and valvular disease in 26.9%. All patients required inotropes: 73.1% required adrenaline [max dose 0.10 (0.05-0.15) mcg/kg/min]; 50.0% required noradrenaline [max dose 0.10 (0.05-0.18) mcg/kg/min]; 26.9% received levosimendan alone [max dose 0.05 (0.03-0.10) mcg/kg/min]. Levosimendan was used in combination with adrenaline in 69.2%, after 3 (0-4) days of adrenaline initiation. Duration of levosimendan infusion was 3 (1-4) days. MCS was pursued in 69.2% [57.7% IABP, 15.4% Impella CP, and 3.8% VA-ECMO]. Oro-tracheal intubation was required in 50.0%, CVVHDF was required in 11.5% patients. No patient required levosimendan interruption for hypotension/arrhythmia. In-hospital mortality was 7.7%. One patients underwent successful LVAD implantation, and one patient was referred for HTx. Invasive hemodynamic data, before and during levosimendan, was available for 7 patients. Initiation of levosimendan led to a non-significant drop in SVR [14.8 (13.3-16.9) vs 19.5 (14.6-25.4) WU; p = 0.093], but SBP was unchanged (p = 0.470). Left ventricular systolic performance was improved: CI [2.6 (2.4-2.7) vs 2.2 (2.0-2.3) Lt/min/m²; p = 0.016]; CPO [0.9 (0.8-1.0) vs 0.8 (0.8-0.9) W; p = 0.031]. Mean PAP (p = 0.297), and PCWP (p = 0.149) remained unchanged. Notably, no significant adjustments in diuretic (p = 0.422) or adrenaline (p = 0.999) doses, IABP counterpulsation ratio (p = 0.999), or Impella flow (p = 0.999) were recorded between these longitudinal assessments. As a result of improved myocardial function, LVEF increased from admission to discharge [20 (20-25) vs 25 (20-32)%; p = 0.024]. Discussion This preliminary study reports on a bolus-free, low-intensity levosimendan regimen for ADHF with hypoperfusion. Levosimendan improved indexes of myocardial performance. In this cohort, levosimendan often required concomitant inopressor and was started at a very low dose to avoid abrupt drop in blood pressure. Abstract Figure 1

Sudden cardiac death (SCD) is the leading cause of cardiovascular mortality in patients with coronary artery disease without severe systolic dysfunction and in heart failure with preserved ejection fraction. From a global health perspective, while risk may be lower, the absolute number of SCDs in patients with left ventricle ejection fraction >35% is higher than in those with severely reduced left ventricle ejection fraction (defined as ≤35%). Despite these observations and the high amount of available data, to date there are no clear recommendations to reduce the sudden cardiac death burden in the population with mid-range or preserved left ventricle ejection fraction. Ongoing improvements in risk stratification based on electrophysiological and imaging techniques point towards a more precise identification of patients who would benefit from ICD implantation, which is still an unmet need in this subset of patients. The aim of this review is to provide a state-of-the-art approach in sudden cardiac death risk stratification of patients with mid-range and preserved left ventricular ejection fraction and one of the following etiologies: ischemic cardiomyopathy, heart failure, atrial fibrillation or myocarditis.

Transcatheter aortic valve replacement (TAVR) is the gold standard for severe valvular aortic stenosis in patients at high/prohibitive surgical risk. This procedure has also been used in patients with previous mitral valve (MV) prostheses, with contrasting outcomes reported. The aim of this study is to describe procedural and early outcomes of patients with previous MV prostheses undergoing TAVR.This is a retrospective registry of 154 patients with previous MV prostheses who underwent TAVR across high-volume medical centres at a mean of 11.7 ± 8.4 years after mitral surgery.Mean mitroaortic distance at computed tomography was 9.7 ± 4.8 mm. Procedural success was achieved in 150 (97.4%) patients, with reduction of aortic gradients (42.6 ± 14.2 to 10.0 ± 7.0 mm Hg; P0.001). Device success was achieved in 133 (86.3%) patients. MV prosthesis interference by the TAVR device was observed in 2 patients; in both, the mitroaortic distance was5 mm, with 1 complicated by TAVR prosthesis embolization. Periprocedural complications included 4 (2.6%) cerebrovascular accidents, 10 (6.6%) major vascular complications, 22 (14.4%) severe bleedings, 1 (0.7%) myocardial infarction, and 5 (3.2%) in-hospital deaths (all cases cardiovascular or procedure related). At a median follow-up of 13.5 (interquartile range 1.0 to 36.0) months, 26 (16.9%) deaths occurred; 15 (9.7%) were cardiac related. Late fatal mitral prosthesis thromboses occurred in 2 patients. We recorded a case of fatal hemorrhagic stroke; hospital readmission was observed in 25 (16.2%) patients due to worsening heart failure.TAVR in patients with previous mitral prostheses appears to be safe and feasible, with good hemodynamic results at 30-day and at longer-term follow-up.