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Electrical storm (ES) is a life-threatening condition characterized by at least three separate episodes of ventricular arrhythmias (VAs) over 24 h, each requiring therapeutic intervention, including implantable cardioverter defibrillator (ICD) therapies. Patients with ICDs in secondary prevention are at higher risk of ES and the most common presentation is that of scar-related monomorphic VAs. Electrical storm represents a major unfavourable prognostic marker in the history of patients with structural heart disease, with an associated two- to five-fold increase in mortality, heart transplant, and heart failure hospitalization. Early recognition and prompt treatment are crucial to improve the outcome. Yet, ES management is complex and requires a multidisciplinary approach and well-defined protocols and networks to guarantee a proper patient care. Acute phase stabilization should include a comprehensive clinical assessment, resuscitation and sedation management skills, ICD reprogramming, and acute sympathetic modulation, while the sub-acute/chronic phase requires a comprehensive heart team evaluation to define the better treatment option according to the haemodynamic and overall patient’s condition and the type of VAs. Advanced anti-arrhythmic strategies, not mutually exclusive, include invasive ablation, cardiac sympathetic denervation, and, for very selected cases, stereotactic ablation. Each of these aspects, as well as the new European Society of Cardiology guidelines recommendations, will be discussed in the present review.

Brugada syndrome is an inherited channelopathy with an increased risk of sudden cardiac death (SCD) due to ventricular arrhythmias (VA) and an increased incidence of supraventricular arrhythmias, as compared with the general population. For the prevention of SCD, the guidelines recommend the implantable cardioverter-defibrillator (ICD); however, ICD does not prevent VA. In this article, we provide a brief review of the literature on the Brugada syndrome pharmacological therapy, mainly focusing on quinidine treatment. The efficacy of quinidine therapy in the prevention of VA in Brugada syndrome has been demonstrated by several small studies in patients with ICD and recurrent shocks or in asymptomatic patients with inducible ventricular fibrillation (VF) at electrophysiological study. Quinidine has also been tested for the prophylaxis of supraventricular arrhythmias, especially atrial fibrillation/flutter, and in paediatric patients. In these studies, quinidine proved highly effective in preventing re-induction of VF and spontaneous recurrences of both ventricular and supraventricular arrhythmias. Unfortunately, this therapy is burdened by a high incidence of side effects, which may lead to drug discontinuation.

Autonomic imbalance with a sympathetic dominance is acknowledged to be a critical determinant of the pathophysiology of chronic heart failure with reduced ejection fraction (HFrEF), regardless of the etiology. Consequently, therapeutic interventions directly targeting the cardiac autonomic nervous system, generally referred to as neuromodulation strategies, have gained increasing interest and have been intensively studied at both the pre-clinical level and the clinical level. This review will focus on device-based neuromodulation in the setting of HFrEF. It will first provide some general principles about electrical neuromodulation and discuss specifically the complex issue of dose-response with this therapeutic approach. The paper will thereafter summarize the rationale, the pre-clinical and the clinical data, as well as the future prospectives of the three most studied form of device-based neuromodulation in HFrEF. These include cervical vagal nerve stimulation (cVNS), baroreflex activation therapy (BAT), and spinal cord stimulation (SCS). BAT has been approved by the Food and Drug Administration for use in patients with HfrEF, while the other two approaches are still considered investigational; VNS is currently being investigated in a large phase III Study.

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.

The adoption of Computed tomography (CT)-defined sarcopenia to risk stratify transcatheter aortic valve implantation (TAVI) candidates remains limited by a lack of both standardized definition and evidence of independent value over currently adopted mortality prediction tools.391 consecutive TAVI patients with pre-procedural CT scan were included (81 ​± ​6 years, 57.5% male, STS-PROM score 4.4 ​± ​3.6%) and abdominal muscle retrospectively quantified. The two definitions of radiologic sarcopenia previously adopted in TAVI studies were compared (psoas muscle area [PMA] at the L4 vertebra level: "PMA-sarcopenia"; indexed skeletal muscle area at the L3 vertebra level: "SMI-sarcopenia"). The primary endpoint was longer available-term all-cause mortality. Secondary endpoints were Valve Academic Research Consortium-2-defined in-hospital and 30-day outcomes.SMI- and PMA-sarcopenia were present in 192 (49.1%) and 117 (29.9%) patients, respectively. After a median of 24 (12-30) months follow-up, 83 (21.2%) patients died. PMA-(adj-HR 1.81, 95%CI 1.12-2.93, p ​= ​0.015), but not SMI-sarcopenia (adj-HR 1.23, 95%CI 0.76-2.00, p ​= ​0.391), was associated with all-cause mortality independently of age, sex and in-study outcome predictors (atrial fibrillation, hemoglobin, history of peripheral artery disease, cancer and subcutaneous adipose tissue). PMA-defined sarcopenia provided additive prognostic value over current post-TAVI mortality risk estimators including STS-PROM (p ​= ​0.001), Euroscore II (p ​= ​0.025), Charlson index (p ​= ​0.025) and TAVI2-score (p ​= ​0.020). Device success, early safety, clinical efficacy and 30-day all-cause death were unaffected by sarcopenia status regardless of definition.PMA-sarcopenia (but not SMI-sarcopenia) is predictive of 2 year mortality among TAVI patients. The prognostic information provided by PMA-sarcopenia is independent of the tools currently adopted to predict post-TAVI mortality in clinical practice.

Glucagon-like peptide 1 receptor agonists (GLP1-RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) were individually proven to reduce major adverse cardiovascular events (MACE) in type 2 diabetes mellitus (T2DM) patients, but the relative magnitude of benefits from these two drug classes is debated. We aimed to review current available data on GLP1-RA and SGLT2i in T2DM patients and compare their efficacy and safety in this population.We systematically searched MEDLINE/PubMed, the Cochrane Library, Google Scholar, Embase, www.tctmd.com, www.clinicaltrials.gov, www.clinicaltrialresults.org, from inception to September 17, 2020 for randomized controlled trials (RCTs) comparing the effects of GLP1-RA vs SGLT2i vs optimal medical therapy (OMT) in adult T2DM patients. Three authors independently screened references and extracted data using a predefined data collection form. Outcomes were analyzed using an indirect comparison meta-analysis of aggregate study-level data. The primary combined efficacy outcome comprised cardiovascular death, nonfatal myocardial infarction (MI), or nonfatal stroke. Secondary efficacy outcomes included all-cause mortality, cardiovascular mortality, non-fatal MI, non-fatal stroke, heart failure hospitalizations (HFH), and worsening renal function (WRF).11 RCTs enrolling a total of 98572 patients were included; 56004 (57%) patients were derived from GLP1-RA RCTs and 42568 (43%) from SGLT2i RCTs. At a median follow-up of 3.0±1.3 years, compared with OMT, both GLP1-RA and SGLT2i similarly reduced the rate of the composite primary outcome (risk ratio [RR] 0.88; 95% confidence interval [95%CI] 0.83-0.93 and RR 0.88, 95%CI 0.82-0.95, respectively) with no difference between the drug classes (RR 1.00, 95%CI 0.92-1.10). Both classes similarly reduced MI rate, cardiovascular and all-cause mortality compared with OMT; stroke reduction was only observed with GLP1-RA with no difference in the indirect comparison with SGLT2i; conversely, only SGLT2i were effective in preventing HFH. Both GLP1-RA and SGLT2i were protective against WRF, with a major efficacy of SGLT2i in the indirect comparison.This meta-analysis report that GLP1-RA and SGLT2i reduced with a similar efficacy not only MACE as MI, but also cardiovascular mortality and all-cause mortality at a median 3 years follow-up. SGLT2i were more protective in HFH and WRF than GLP1RA. These new data highlight the efficacy of SGLT2i not only in HF and chronic kidney disease (CKD) but also in ischemic heart diseases (IHD), with a homogeneity among the class, whereas the results observed with GLP1-RA are heterogenous. These findings will help clinical's decisions to optimize therapeutic strategies for diabetic patients.

Few data are available regarding the prevalence of left atrium (LA) thrombi in atrial fibrillation (AF) patients treated with non-vitamin K antagonist oral anticoagulants (NOACs). Methods: We evaluated the prevalence and predictors of LA/LA appendage (LAA) thrombi in non-valvular AF patients treated with NOACs referring to a single centre for a scheduled electrical cardioversion (ECV) or catheter ablation (CA). Transesophageal echocardiography (TEE) was performed within 12 h prior to the index procedure. A total of 352 consecutive patients with non-valvular AF treated with NOACs were included in this analysis (ECV group n = 176 and CA group n = 176) between 2013 and 2018. 85 patients (24.2%) were on dabigatran, 150 (42.7%) on rivaroxaban, 104 (29.6%) on apixaban and 13 (3.7%) on edoxaban. A LA/LAA thrombus was detected by TEE in 27 (7.7%) patients, 18 in the ECV group and nine in the ablation group; 18 (5.1%) patients presented dense LA/LAA spontaneous echo contrast (SEC). Predictors of LA/LAA thrombi were a CHA2DS2-VASc score > 3 (OR 4.54, 95% CI 1.50 − 13.70, p value = .007) and obesity (OR 6.01, 95% CI 1.95 − 18.50, p value = .001). Among real-world patients with non-valvular AF treated with NOACs, we found a high incidence of LA/LAA thrombi compared to previous reports. The main predictors of LA/LAA thrombosis were a CHA2DS2-VASc score > 3 and obesity.

OBJECTIVES We aimed to compare the incidence and timing of major adverse cardiovascular events (MACE) within the first year after spontaneous coronary artery dissection (SCAD) according to the management strategy: conservative versus invasive. BACKGROUND Treatment of SCAD remains controversial. METHODS A pooled analysis of studies providing separate individual clinical outcomes for conservative and invasive treatment strategies within 1 year after SCAD was performed. The primary outcome measure was MACE incidence within three predefined study periods after SCAD, namely "in-hospital", "discharge-to-6-months" and "6-to-12-months". MACE was defined as a composite of all-cause death, myocardial infarction, target vessel revascularization, heart failure and SCAD recurrence. RESULTS A total of 16 studies (444 patients) were included; 277 (62%) patients were treated conservatively and 167 (38%) invasively. Within 1-year follow-up, 39 (67%) MACE occurred during the in-hospital period compared to 10 (17%) in the "discharge-to-6 months" period and 9 (16%) in the "6-to-12-months" period (p

Objectives The aim of this study was to assess the pooled clinical and echocardiographic outcomes of different isolated transcatheter tricuspid valve repair (ITTVR) strategies for signific...

A 38-year-old woman with curly hair was admitted at the Emergency Department of our Hospital for typical thoracic pain associated with dyspnea and palpitations. Electrocardiogram showed sinus rhythm, 65 bpm, low voltages in the peripheral leads with fragmented QRS complex in the inferior leads and negative T-waves in anterior leads. Initial high-sensitivity cardiac troponin level was 46326 ng/L (n.v. < 16 ng/L). At presentation the patient was treated with Anakinra (anti-interleukin 1) and Metoprolol 200 mg/die because of a past medical history characterized by multiple myocarditis recurrences since 2012. Various therapies had been tested (Aspirin, Ibuprofen, Colchicine, Prednisone, Azathioprine), with a good efficacy of Mycophenolic acid, recently stopped to plan a pregnancy. Transthoracic echocardiography documented normal left ventricle (LV) ejection fraction and no alteration wall motion abnormalities; cardiac-MRI demonstrated LV late gadolinium enhancement with a non-ischemic subepicardial “ring-like” pattern. Endomyocardial biopsy was performed, and the ultrastructural analysis showed mitochondrial hyperplasia with focal swelling and marked alterations of intercalated disks. A high ventricular extrasystolic burden was registered at EKG monitoring. Gene sequencing revealed a pathogenetic variant of the gene coding for Desmoplakin. This is involved in the anchoring of intermediate filaments to desmosomal plaques and its pathogenetic variants are associated with an inflammatory and fibrotic LV predominant cardiomyopathy with an arrhythmogenic evolution (see Padua criteria). In the absence of approved therapies, in agreement with the limited available data and considering patient's history, Micofenolic acid was restarted. At 1-, 3- and 6-month follow-up the patient has remained asymptomatic with progressive declining in troponin levels after discharge.

The aim of the present analysis was to evaluate the incidence and predictors of in-hospital adverse outcomes in nonagenarian patients undergoing primary percutaneous coronary intervention (pPCI) for ST-segment elevation myocardial infarction (STEMI).Consecutive nonagenarian patients undergoing pPCI for STEMI from 2009 to 2019 were retrospectively included in an international multicenter registry. In-hospital all-cause death was the primary outcome.A total of 308 patients were included (mean age 92.5±2.5 years, 65.6% female). Mean systolic blood pressure (SBP) at hospital admission was 130.7±33.5 mmHg, 46 (17%) patients presented with a Killip class III-IV, mean left ventricle ejection fraction (LVEF) was 40.0±11.5% and 147 (58%) patients were independent in everyday activities. In-hospital death occurred in 99 patients (32%). After multivariate adjustment, lower LVEF (OR per unit reduction 1.08, 95% CI: 1.03-1.11, P value0.001), lower SBP (OR 1.02 per mmHg reduction, 95% CI: 1.01-1.03, P value 0.001) and being not independent at home (OR 2.56, 95% CI: 1.25-5.26, P value 0.01) resulted independent predictors of in-hospital mortality. A sensitivity analysis performed in final TIMI 3 flow population confirmed the prognostic role of LVEF and independency on in-hospital mortality.Nonagenarian patients presenting with STEMI and undergoing pPCI have high in-hospital mortality. Independency in everyday life is a strong independent predictor of survival to hospital discharge.

Background There is a paucity of data regarding the best treatment for spontaneous coronary artery dissection (SCAD). Purpose To compare the prognostic impact of conservative versus invasive treatment in patients with SCAD. Methods We systematically searched the literature for studies evaluating the comparative efficacy and safety of invasive revascularization versus medical therapy for the treatment of SCAD from 1990 to 2019. Random-effect meta-analysis was performed comparing clinical outcomes between the two groups. Results 24 observational studies with 1720 patients were included. After 28±14 months, a conservative approach reduced target vessel revascularization rate compared with invasive treatment (OR=0.50; 95% CI 0.28–0.90; P=0.02). No difference was found regarding all-cause mortality (OR=0.81; 95% CI 0.31–2.08; P=0.66), cardiovascular mortality (OR=0.89; 95% CI 0.15–5.40; P=0.89), myocardial infarction (OR=0.95; 95% CI 0.50–1.81; P=0.87), heart failure (OR 0.96; 95% CI 0.41–2.22; P=0.92) and SCAD recurrence (OR=0.94; 95% CI 0.52–1.72; P=0.85). The meta-regression analysis suggested that male gender, diabetes mellitus, smoking habit, prior coronary artery disease, left main coronary artery involvement and lower ejection fraction at admission are related with higher overall mortality, whereas SCAD recurrence was higher among patients with fibromuscular dysplasia. Conclusion A conservative approach provides similar clinical outcomes and lower target vessel revascularization rates compared to an invasive strategy in the setting of SCAD; therefore, when feasible, it should be preferred in this scenario. Forest plots on the study outcomes Funding Acknowledgement Type of funding source: None

The continuous progress in cardiovascular (CV) risk prevention strategies has led to an impressive reduction in mortality and recurrent ischemic events in patients with coronary artery disease (CAD). However, the control of several CV risk factors remains suboptimal in many CAD patients, with a high rate of recurrent events, underlying the need for more new prevention strategies. The GAPS-I (GLP1 analogues, Antithrombotic agents, PCSK9 inhibitors, SGLT2 inhibitors and Immunomodulators) strategy offers a promising potential in patients with a high-residual CV risk, who are frequently encountered in daily practice, by offering an individualised and structured approach to addressing their individual risk factors. The current review summarises the evidence to date on each of its components, with respect to clinical outcomes and economic feasibility. The current evidence points to an efficacy of GAPS-I in reducing MACE and mortality, without a compromise on safety, albeit with the need for longer follow-up data. Key Points: - Secondary prevention remains suboptimal in many CAD patients, highlighting the need for innovative prevention strategies. - The present review discusses the current evidence on efficacy of the GAPS-I strategy in reducing MACE and mortality in patients with CAD. - The GAPS-I strategy, if widely adopted, provides a promising potential to assist cardiologists in managing patients at a heightened risk for further CV events.

Background and Purpose: Clinical trials on stroke prevention in patients with atrial fibrillation have consistently shown clinical benefit from either warfarin or non–vitamin K antagonist oral anticoagulants (NOACs). NOAC-treated patients have consistently reported to be at lower risk for intracerebral hemorrhage (ICH) than warfarin-treated patients. The aims of this prospective, multicenter, multinational, unmatched, case-control study were (1) to investigate for risk factors that could predict ICH occurring in patients with atrial fibrillation during NOAC treatment and (2) to evaluate the role of CHA 2 DS 2 -VASc and HAS-BLED scores in the same setting. Methods: Cases were consecutive patients with atrial fibrillation who had ICH during NOAC treatment. Controls were consecutive patients with atrial fibrillation who did not have ICH during NOAC treatment. As within the CHA 2 DS 2 -VASc and HAS-BLED scores there are some risk factors in common, several multivariable logistic regression models were performed to identify independent prespecified predictors for ICH events. Results: Four hundred nineteen cases (mean age, 78.8±8.1 years) and 1526 controls (mean age, 76.0±10.3 years) were included in the study. From the different models performed, independent predictors of ICH were increasing age, concomitant use of antiplatelet agents, active malignancy, high risk of fall, hyperlipidemia, low clearance of creatinine, peripheral artery disease, and white matter changes. Low doses of NOACs (given according to label or not) and congestive heart failure were inversely associated with the risk of ICH. HAS-BLED and CHA 2 DS 2 -VASc scores performed poorly in predicting ICH with areas under the curves of 0.496 (95% CI, 0.468–0.525) and 0.530 (95% CI, 0.500–0.560), respectively. Conclusions: Several risk factors were associated to ICH in patients treated with NOACs for stroke prevention but not HAS-BLED and CHA 2 DS 2 -VASc scores.

Left atrial volume index (LAVI) is a predictor of heart failure and adverse events, irrespective of left ventricular systolic function. The role of LAVI in the prediction of appropriate implantable cardioverter-defibrillator (ICD) therapies is currently unclear and was the focus of this study.Consecutive heart failure patients with ischaemic (ICM) or idiopathic (DCM) aetiology receiving ICD for primary prevention were included. The primary endpoint was the occurrence of appropriate ICD therapies (ATs): shocks or antitachycardia pacing (ATP). Inappropriate ICD shocks were also assessed as secondary endpoint.Among 198 included patients, severe left atrial dilatation (SLAE = LAVI ≥ 60 ml/mIn DCM or ICM patients candidate to receive an ICD for primary prevention, a severely enlarged left atrium is a predictive factor for ATs (shocks or ATP). The risk of inappropriate shocks was increased in patients with atrial fibrillation, rather than SLAE.

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).

BACKGROUND Risk stratification for transcatheter edge-to-edge mitral valve repair (TEER) is paramount in the decision-making process for treating severe mitral regurgitation (MR). OBJECTIVES This study sought to create and validate a user-friendly score (MitraScore) to predict the risk of mortality in patients undergoing TEER. METHODS The derivation cohort was based on a multicentric international registry that included 1,119 patients referred for TEER between 2012 and 2020. Score discrimination was assessed using Harrell's c-statistic, and the calibration was evaluated with the Gronnesby and Borgan goodness-of -fit test. An external validation was carried out in 725 patients from the GIOTTO registry. RESULTS After multivariate analysis, we identified 8 independent predictors of mortality during the follow-up (2.1 +/- 1.8 years): age $75 years, anemia, glomerular filtrate rate

Aims: Despite evidence of hemodynamic benefit of sodium nitroprusside (SNP) treatment for acute heart failure (AHF), there are limited data about its efficacy and safety. This study aimed to assess the effectiveness and safety of SNP treatment, to explore the impact of N-terminal pro-B natriuretic peptide (NT-proBNP) reduction on clinical endpoints and to identify possible predictors of clinical response. Methods and results: Multicenter retrospective cohort study of 200 patients consecutively admitted for AHF in 2 Italian Centers. Primary endpoint was the reduction of NT-proBNP levels ≥25% from baseline values within 48 h from the onset of SNP infusion. Secondary and safety endpoints included all-cause mortality, rehospitalization for HF at 1, 3 and 6 months, length of hospital stay (LOS) and severe hypotension. 131 (66%) patients experienced a NT-proBNP reduction ≥25% within 48 h from treatment onset, irrespective of initial systolic blood pressure (SBP). Left ventricular end diastolic diameter (LVEDD) was the only independent predictor of treatment efficacy. Patients who achieved the primary endpoint (i.e., ‘responders’) had lower LOS (median 15 [IQR:10–27] vs 19 [IQR:12–35] days, p-value = 0.033) and a lower incidence of all-cause mortality and rehospitalization for HF at 1 and 3 months compared to “non responders” (p-value

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.

Objective The aim of the present analysis was to evaluate the incidence and predictors of in-hospital adverse outcomes in nonagenarian patients undergoing primary percutaneous coronary intervention (pPCI) for ST-segment elevation myocardial infarction (STEMI). Methods Consecutive nonagenarian patients undergoing pPCI for STEMI from 2009 to 2019 were retrospectively included in an international multicenter registry. In-hospital all-cause death was the primary outcome. Results A total of 308 patients were included (mean age 92.5±2.5 years, 65.6% female). Mean systolic blood pressure (SBP) at hospital admission was 130.7±33.5 mmHg, 46 (17%) patients presented with a Killip class III-IV, mean left ventricle ejection fraction (LVEF) was 40.0±11.5% and 147 (58%) patients were independent in everyday activities. In-hospital death occurred in 99 patients (32%). [Figure 1] After multivariate adjustment, lower LVEF (OR per unit reduction 1.08, 95% CI 1.03–1.11, p-value Conclusion Nonagenarian patients presenting with STEMI and undergoing pPCI have high in-hospital mortality. Independency in everyday life is a strong independent predictor of survival to hospital discharge. Funding Acknowledgement Type of funding sources: None. Figure 1Figure 2

Objectives This is a protocol for a Cochrane Review (intervention). The objectives are as follows: The objective of this review is to evaluate the available evidence in order to identify an optimal de‐escalation strategy in terms of duration and type of therapy for patients with ACS treated with PCI. We will perform a NMA to appraise the safest and most efficacious combination of type and length of DAPT de‐escalation.

Funding Acknowledgements Type of funding sources: None. Background Non-invasive ventilation (NIV) is an established treatment for acute decompensated heart failure (ADHF). Purpose The aim of the present analysis was to evaluate the feasibility of continuous positive airway pressure (CPAP) in patients with myocardial infarction (MI) and ADHF, during percutaneous coronary intervention (PCI). Methods Consecutive patients admitted for MI, receiving CPAP for ADHF in the cath lab during PCI were retrospectively included. The main study outcome was the feasibility of CPAP, intended as well tolerated by the patient and exclusive cardiology staff management. Results Between December 2018 and October 2020, 15 patients were included; median age was 79 (40-87 IQR) years, 8 (53%) were males, 9 (60%) presented with STEMI and 10 (67%) in cardiogenic shock. At admission median ejection fraction was 35 (20-60 IQR) % and 6 (40%) patients had severe mitral regurgitation. Mean PaO2/ FiO2 was 188.1 ± 74.9 mmHg/%, mean lactate level was 2.6 ± 1.5 mmol/L and NTproBNP 7882 (3139-35000 IQR) ng/L. The CPAP was set with a median FiO2 of 50 (35-80 IQR) % with a PEEP of 7.5 (5-10 IQR) mmHg. CPAP was feasible in 14 (93%) patients, as in only one case it was interrupted for patient’s intolerance. CPAP was always managed by nurses of the cath lab, without the support of anesthetist. One patient suffered cardiac arrest that led to CPAP interruption for resuscitation maneuvers. No patients underwent intubation in the cath lab. Post-procedural PaO2/FiO2 ratio substantially improved to 259.4 ± 96.9 mmHg/% (p = 0.03) and lactate decreased to 1.5 ± 0.5 mmol/L (p = 0.01, 42% median reduction). One patient died in-hospital due to underlying disease, unrelated to study procedure. Conclusion CPAP during PCI in patients with MI and ADHF was feasible, well tolerated and easily manageable. Larger studies are warranted to confirm these results.

Background and Purpose— Despite treatment with oral anticoagulants, patients with nonvalvular atrial fibrillation (AF) may experience ischemic cerebrovascular events. The aims of this case-control study in patients with AF were to identify the pathogenesis of and the risk factors for cerebrovascular ischemic events occurring during non–vitamin K antagonist oral anticoagulants (NOACs) therapy for stroke prevention. Methods— Cases were consecutive patients with AF who had acute cerebrovascular ischemic events during NOAC treatment. Controls were consecutive patients with AF who did not have cerebrovascular events during NOACs treatment. Results— Overall, 713 cases (641 ischemic strokes and 72 transient ischemic attacks; median age, 80.0 years; interquartile range, 12; median National Institutes of Health Stroke Scale on admission, 6.0; interquartile range, 10) and 700 controls (median age, 72.0 years; interquartile range, 8) were included in the study. Recurrent stroke was classified as cardioembolic in 455 cases (63.9%) according to the A-S-C-O-D (A, atherosclerosis; S, small vessel disease; C, cardiac pathology; O, other causes; D, dissection) classification. On multivariable analysis, off-label low dose of NOACs (odds ratio [OR], 3.18; 95% CI, 1.95–5.85), atrial enlargement (OR, 6.64; 95% CI, 4.63–9.52), hyperlipidemia (OR, 2.40; 95% CI, 1.83–3.16), and CHA 2 DS 2 -VASc score (OR, 1.72 for each point increase; 95% CI, 1.58–1.88) were associated with ischemic events. Among the CHA 2 DS 2 -VASc components, age was older and presence of diabetes mellitus, congestive heart failure, and history of stroke or transient ischemic attack more common in patients who had acute cerebrovascular ischemic events. Paroxysmal AF was inversely associated with ischemic events (OR, 0.45; 95% CI, 0.33–0.61). Conclusions— In patients with AF treated with NOACs who had a cerebrovascular event, mostly but not exclusively of cardioembolic pathogenesis, off-label low dose, atrial enlargement, hyperlipidemia, and high CHA 2 DS 2 -VASc score were associated with increased risk of cerebrovascular events.

Cardiac resynchronization therapy (CRT) was shown to improve cardiac function, reduce heart failure hospitalizations, improve quality of life and prolong survival in patients with severe left ventricular dysfunction and intraventricular conduction disturbances, mainly left bundle branch block, on optimal medical therapy with ACE-inhibitors, β-blockers and mineralocorticoid receptor antagonists up-titrated to maximum tolerated evidence-based doses. CRT can be achieved by means of pacemaker systems (CRT-P) or devices with defibrillation capabilities (CRT-D). CRT-Ds offer an undoubted advantage in the prevention of arrhythmic death, but such an advantage may be of lesser degree in nonischemic heart failure etiologies. Moreover, the higher CRT-D hardware complexity compared to CRT-P may predispose to device/lead malfunctions and the higher current drainage may cause a shorter battery duration with consequent premature replacements and the well-known incremental complications. In a period of financial constraints, also device costs should be carefully evaluated, with recent reports suggesting that CRT-Ps may be favored over CRT-Ds in patients with nonischemic cardiomyopathy and no prior history of cardiac arrhythmias from a cost-effectiveness point of view. The choice between a CRT-P or a CRT-D device should be patient-tailored whenever straightforward defibrillator indications are not present. The Goldenberg score may facilitate this decision-making process in ambiguous settings. Age, comorbidities, kidney disease, atrial fibrillation, advanced functional class, inappropriate therapy risk, implantable device infections, and malfunctions are factors potentially reducing the expected benefit from defibrillating capabilities. In the future, prospective randomized controlled trials are warranted to directly compare the efficacy and safety of CRT-Ps and CRT-Ds.

The relevance of extracellular vesicles (EV) as mediators of cardiac damage or recovery upon Ischemia Reperfusion Injury (IRI) and Remote Ischemic PreConditioning (RIPC) is controversial. This study aimed to investigate whether serum-derived EV, recovered from patients with Acute Coronary Syndrome (ACS) and subjected to the RIPC or sham procedures, may be a suitable therapeutic approach to prevent IRI during Percutaneous-Coronary-Intervention (PCI). A double-blind, randomized, sham-controlled study (NCT02195726) has been extended, and EV were recovered from 30 patients who were randomly assigned (1:1) to undergo the RIPC- (EV-RIPC) or sham-procedures (EV-naive) before PCI. Patient-derived EV were analyzed by TEM, FACS and western blot. We found that troponin (TnT) was enriched in EV, compared to healthy subjects, regardless of diagnosis. EV-naive induced protection against IRI, both in-vitro and in the rat heart, unlike EV-RIPC. We noticed that EV-naive led to STAT-3 phosphorylation, while EV-RIPC to Erk-1/2 activation in the rat heart. Pre-treatment of the rat heart with specific STAT-3 and Erk-1/2 inhibitors led us to demonstrate that STAT-3 is crucial for EV-naive-mediated protection. In the same model, Erk-1/2 inhibition rescued STAT-3 activation and protection upon EV-RIPC treatment. 84 Human Cardiovascular Disease mRNAs were screened and DUSP6 mRNA was found enriched in patient-derived EV-naive. Indeed, DUSP6 silencing in EV-naive prevented STAT-3 phosphorylation and cardio-protection in the rat heart. This analysis of ACS-patients’ EV proved: (i) EV-naive cardio-protective activity and mechanism of action; (ii) the lack of EV-RIPC-mediated cardio-protection; (iii) the properness of the in-vitro assay to predict EV effectiveness in-vivo.

Patients with patent foramen ovale (PFO) and cryptogenic ischemic stroke (CS) are at risk for stroke recurrence. The optimal antithrombotic strategy in patients who undergo medical management is still debated. We systematically searched the literature for studies that reported on cerebrovascular event recurrences and/or death in patients with PFO treated with oral anticoagulation (OAC) or antiplatelet therapy (APT) for secondary prevention of CS. The efficacy endpoints were stroke recurrence and the composite of stroke, transient ischemic attack or all-cause death. Major bleedings represented the safety endpoint. A total of 16 studies with 3953 patients (OAC = 1527, APT = 2426) were included. Weighted mean follow-up was 2.9 years. OAC was associated with a significant reduction in the risk of stroke compared with APT (RR 0.65; 95% CI 0.44–0.95; ARR 2%, NNT 49), while no difference was found regarding the composite outcome (RR 0.78; 95% CI 0.57–1.07) and the safety outcome (RR 1.57; 95% CI 0.85–2.90; p = 0.15). OAC was more effective than APT in reducing the risk of stroke recurrence in patients with PFO and CS, without a significant increase in the risk of major bleedings. Our findings support the need for further randomized data focused on the comparison of antithrombotic strategies in this setting.

Background Significant tricuspid regurgitation (TR) is a common valvular heart disease worldwide. Purpose We aimed to assess the pooled clinical and echocardiographic outcomes of different isolated transcatheter tricuspid valve repair (ITTVR) strategies for significant (≥ moderate) TR. Methods We systematically searched the literature for studies evaluating the efficacy and safety of ITTVR for significant TR in adult. The primary outcomes were the improvement of New York Heart Association (NYHA) functional class and 6-minutes walking distance (6MWD) and the presence of severe or greater TR at the last available follow-up of each individual study. Random-effect meta-analysis was performed comparing outcomes before and after ITTVR. Results 14 studies with 771 patients were included. Mean age was 77±8 years and mean EuroScore II was 6.8%±5.4%. At a weighted mean follow-up of 212 days, 209 (35%) patients had a NYHA III to IV functional class compared to 586 (84%) patients at baseline (risk ratio: 0.23, 95% CI 0.13 to 0.40, P-value Conclusion Patients undergoing ITTVR for significant TR experienced a significant improvement in NYHA functional status and 6MWD and a significant reduction in TR severity at mid-term follow-up. Funding Acknowledgement Type of funding sources: None.

Extracellular vesicles (EVs) are promising therapeutic tools in the treatment of cardiovascular disorders. We have recently shown that EVs from patients with Acute Coronary Syndrome (ACS) undergoing sham pre-conditioning, before percutaneous coronary intervention (PCI) were cardio-protective, while EVs from patients experiencing remote ischemic pre-conditioning (RIPC) failed to induce protection against ischemia/reperfusion Injury (IRI). No data on EVs from ACS patients recovered after PCI are currently available. Therefore, we herein investigated the cardio-protective properties of EVs, collected after PCI from the same patients. EVs recovered from 30 patients randomly assigned (1:1) to RIPC (EV-RIPC) or sham procedures (EV-naive) (NCT02195726) were characterized by TEM, FACS and Western blot analysis and evaluated for their mRNA content. The impact of EVs on hypoxia/reoxygenation damage and IRI, as well as the cardio-protective signaling pathways, were investigated in vitro (HMEC-1 + H9c2 co-culture) and ex vivo (isolated rat heart). Both EV-naive and EV-RIPC failed to drive cardio-protection both in vitro and ex vivo. Consistently, EV treatment failed to activate the canonical cardio-protective pathways. Specifically, PCI reduced the EV-naive Dusp6 mRNA content, found to be crucial for their cardio-protective action, and upregulated some stress- and cell-cycle-related genes in EV-RIPC. We provide the first evidence that in ACS patients, PCI reprograms the EV cargo, impairing EV-naive cardio-protective properties without improving EV-RIPC functional capability.

Introduction The impact of Covid-19 on the survival of patients presenting with acute coronary syndrome (ACS) remains to be defined. Methods Consecutive patients presenting with ACS at 18 Centers in Northern-Italy during the Covid-19 outbreak were included. In-hospital all-cause death was the primary outcome. In-hospital cardiovascular death along with mechanical and electrical complications were the secondary ones. A case period (February 20, 2020-May 3, 2020) was compared vs. same-year (January 1–February 19, 2020) and previous-year control periods (February 20–May 3, 2019). ACS patients with Covid-19 were further compared with those without. Results Among 779 ACS patients admitted during the case period, 67 (8.6%) tested positive for Covid-19. In-hospital all-cause mortality was significantly higher during the case period compared to the control periods (6.4% vs. 3.5% vs. 4.4% respectively; p 0.026), but similar after excluding patients with COVID-19 (4.5% vs. 3.5% vs. 4.4%; p 0.73). Cardiovascular mortality was similar between the study groups. After multivariable adjustment, admission for ACS during the COVID-19 outbreak had no impact on in-hospital mortality. In the case period, patients with concomitant ACS and Covid-19 experienced significantly higher in-hospital mortality (25% vs. 5%, p Conclusion ACS patients presenting during the Covid-19 pandemic experienced increased all-cause mortality, driven by Covid-19 positive status due to higher rates of cardiogenic shock and sustained ventricular tachycardia. No differences in cardiovascular mortality compared to non-pandemic scenarios were reported.

Background Brugada syndrome (BrS) is an inherited channelopathy with an increased risk of supraventricular, ventricular arrhythmias (VAs) and sudden cardiac death (SCD). Implantable cardioverter-defibrillator (ICD) is a cornerstone of SCD prevention, but it does not reduce the incidence of life-threatening VAs and it can carry substantial complications. Hydroquinidine (HQ) is a class IA antiarrhythmic drug used for electrical storms, to reduce ICD's appropriate discharges and as an alternative to ICD in children with BrS or in patients with a contraindication to ICD. Nevertheless, HQ's side effects may undermine treatment compliance. Purpose The aim of this study was to evaluate the efficacy and safety of HQ in reducing VAs (ventricular fibrillation, sustained and non-sustained ventricular tachycardia) inducibility at electrophysiology study (EPS) and atrial fibrillation/flutter (AF/AFL) or VAs recurrence in patients with BrS. Methods From the prospective Piedmont Brugada Registry, patients treated with HQ were selected and divided into three groups according to the indication for HQ initiation: index EPS positive for VAs induction (group 1), secondary prevention of AF/AFl (group 2), secondary prevention of VAs (group 3). In group 3 recurrence of VAs was monitored by implantable devices or by periodic 24-hour ECG Holter monitoring. In 5 patients HQ was started for reasons different from the above mentioned, so they were considered only for safety outcomes. Safety was assessed considering the occurrence of HQ side effects and their impact on treatment discontinuation. Results A total of 98 patients (79 males, 80,6%) were included. Median follow-up was 61 months (IQR 31–89 months). None of the baseline clinical characteristics was associated with arrhythmic recurrences. Among 46 patients in group 1 HQ was effective in reducing EPS inducibility in 91.9% of patients (p Overall, 28.6% of patients presented HQ-related side effects, mainly due to gastrointestinal intolerance (18.3%). Treatment discontinuation rate was 25% but only about half of these patients discontinued HQ for adverse events (29.2% for GI intolerance, 16.7% for drug-induced QTc prolongation, 8.3% for elevated liver enzymes; 45.8% self-discontinuation). Conclusions In patients with BrS, HQ was effective in reducing VAs inducibility at EPS, AF/AFL and VAs recurrences; moreover, it was effective in reducing symptoms. Overall, HQ proved to be safe and well-tolerated. Funding Acknowledgement Type of funding source: None

Introduction 5-year survival of patients with ULM (Unprotected Left Main) stenosis according to the choice of revascularization (percutaneous vs. surgical) remains to be defined. Methods and results Randomized Controlled Trials (RTCs) comparing Percutaneous Coronary Intervention (PCI) vs. Coronary Artery Bypass Graft (CABG) with a follow-up of at least 5 years were included. All-cause death was the primary endpoint. MACCE (a composite endpoint of all-cause mortality, myocardial infarction [MI], stroke and repeat revascularization) along with its single components and cardiovascular (CV) death were the secondary ones. Analyses were stratified according to use of first vs. last generation coronary stents. Subgroup comparisons were performed according to Syntax Score (below or above 33) and to age (using cutoffs of each trial's subgroup analysis). 4 RCTs with 4394 patients were identified: 2197 were treated with CABG, 657 with first generation and 1540 with last generation stents. At 5 years rates of all-cause death did not differ (OR 0.93: 0.71–1.21), as those of CV death and stroke. CABG reduced rates of MACCE (OR 0.69: 0.60–0.79), mainly driven by MI (OR 0.48: 0.36–0.65) and revascularization (OR 0.53: 0.45–0.64). Benefit of CABG for MACCE was consistent, although with different extent, across values of Syntax Score (OR 0.76: 0.59–0.97 for values Conclusion For patients with ULM disease, PCI and CABG yielded same survival benefit at 5 years. CABG reduced risk of MI, revascularization and MACCE especially in older patients and in those with diffuse coronary disease. Funding Acknowledgement Type of funding source: None