Mixed Shock Complicating Cardiogenic Shock: Frequency, Predictors, and Clinical Outcomes.

BACKGROUND: Patients presenting with cardiogenic shock (CS) are at risk of developing mixed shock (MS), characterized by distributive-inflammatory phenotype. However, no objective definition exists for this clinical entity. METHODS: We assessed the frequency, predictors, and prognostic relevance of MS complicating CS, based on a newly proposed objective definition. MS complicating CS was defined as an objective shock state secondary to both an ongoing cardiogenic cause and a distributive-inflammatory phenotype arising at least 12 hours after the initial CS diagnosis, as substantiated by predefined longitudinal changes in hemodynamics, clinical, and laboratory parameters. RESULTS: Among 213 consecutive patients admitted at 2 cardiac intensive care units with CS, 13 with inflammatory-distributive features at initial presentation were excluded, leading to a cohort of 200 patients hospitalized with pure CS (67±13 years, 96% Society of Cardiovascular Angiography and Interventions CS stage class C or higher). MS complicating CS occurred in 24.5% after 120 (29-216) hours from CS diagnosis. Lower systolic arterial pressure (P=0.043), hepatic injury (P=0.049), and suspected/definite infection (P=0.013) at CS diagnosis were independent predictors of MS development. In-hospital mortality (53.1% versus 27.8%; P=0.002) and hospital stay (21 [13-48] versus 17 [9-27] days; P=0.018) were higher in the MS cohort. At logistic multivariable analysis, MS diagnosis (odds ratio [OR], 3.00 [95% CI, 1.39-6.63]; Padj=0.006), age (OR, 1.06 [95% CI, 1.03-1.10] years; Padj<0.001), admission systolic arterial pressure <100 mm Hg (OR, 2.41 [95% CI, 1.19-4.98]; Padj=0.016), and admission serum creatinine (OR, 1.61 [95% CI, 1.19-2.26]; Padj=0.003) conferred higher odds of in-hospital death, while early temporary mechanical circulatory support was associated with lower in-hospital death (OR, 0.36 [95% CI, 0.17-0.75]; Padj=0.008). CONCLUSIONS: MS complicating CS, objectively defined leveraging on longitudinal changes in distributive and inflammatory features, occurs in one-fourth of patients with CS, is predicted by markers of CS severity and inflammation at CS diagnosis, and portends higher hospital mortality.

Comprehensive non-invasive Hemodynamic Assessment in Acute Decompensated Heart Failure-Related Cardiogenic Shock. A step towards echodynamics.

BACKGROUND: Hemodynamic assessment can be determinant in phenotyping cardiogenic shock (CS) and guiding patient management. Aim of this study was to evaluate the correlation between echocardiographic and invasive assessment of hemodynamics in acute decompensated heart failure-related CS (ADHF-CS). METHODS: All consecutive ADHF-CS patients (SCAI shock stage ≥B) undergoing right heart catheterization (RHC) between 2020 and 2022 were prospectively enrolled. Patients underwent echocardiography 30 minutes before RHC. The evaluated hemodynamic parameters and their echocardiographic estimates ("e") comprised cardiac index (CI), wedge pressure (WP), pulmonary artery pressures (PAP), cardiac power output (CPO) and pulmonary artery pulsatility index (PAPi). RESULTS: 101 ADHF-CS patients (56±11 years, 64% SCAI shock stage C, left ventricular ejection fraction 29±5%) were included. Good correlation was found for CI, systolic PAP, RAP and CPO (Pearson r > 0.8 for all), moderate correlation for ePAPi (r=0.67) and PVR (r=0.51), while estimation of WP was weak. The sensitivity and specificity of eCI to identify low output state (CI ≤2.2 l/min/m2) were 0.97 and 0.73 respectively, those of eWP for elevated filling pressures (WP >15 mmHg) were 0.84 and 0.55, those of ePAPs for PAPs ≥35 mmHg were 0.87 and 0.63, those of eCPO for CPO<0.6 W were 0.76 and 0.85, those of ePAPi for PAPi <1.85 were 0.89 and 0.92. Echocardiographic phenotyping of CS showed a good agreement with invasive classification (K value 0.457, p<0.001). CONCLUSIONS: Echocardiographic estimation of hemodynamics and subsequent phenotypization of CS is feasible with good agreement with invasive evaluation.

Spontaneous coronary artery dissection (SCAD) with cardiac arrest at presentation: A subanalysis from the DISCO registry.

INTRODUCTION: Spontaneous coronary artery dissection (SCAD) is a rare cause of acute myocardial infarction (AMI), which primarily affects young women without traditional cardiovascular risk factors, often presenting as sudden cardiac death. This study aims to investigate the prevalence, characteristics, predictors, and outcomes of cardiac arrest in SCAD patients. METHODS: The DISCO IT/SPA registry, an international retrospective multicenter study, enrolled 375 SCAD patients from 26 centers in Italy and Spain. Patients were categorized based on the presence or absence of cardiac arrest at admission. Data on demographics, clinical presentation, treatment, angiographic findings, and outcomes were collected. Angiograms were independently reviewed, and outcomes included major adverse cardiovascular events (MACE) and in-hospital bleeding. RESULTS: Among 375 SCAD patients, 20 (5.3%) presented with cardiac arrest. Both groups were similar in age, gender distribution, and conventional risk factors, except for a lower prevalence of dyslipidemia in the cardiac arrest group. ST-segment elevation myocardial infarction (STEMI) presentation and angiographic type 2b were independent predictors of cardiac arrest. Revascularization was more frequent in the cardiac arrest group. In-hospital outcomes, except for longer hospitalization, did not differ. On follow-up (average 21 months), MACE rates were similar between groups. CONCLUSIONS: Cardiac arrest is a notable complication in SCAD, mostly presenting with ventricular fibrillation. The prognosis of SCAD patients presenting with cardiac arrest did not differ from those without, reporting a similar rate of events both in-hospital and during long-term follow-up. STEMI presentation and angiographic type 2b were identified as independent predictors of cardiac arrest in SCAD.

Transcatheter Ablation of Atrial Fibrillation in Patients With Hypertrophic Cardiomyopathy: A Multicenter Propensity Score-Based Analysis.

Background: The prognostic impact of catheter ablation (CA) of atrial fibrillation (AF) in hypertrophic cardiomyopathy (HCM) patients has not yet been satisfactorily elucidated. Objectives: The aim of the study was to assess the impact of CA of AF on clinical outcomes in a large cohort of HCM patients. Methods: In this retrospective multicenter study, 555 HCM patients with AF were enrolled, 140 undergoing CA and 415 receiving medical therapy. 1:1 propensity score matching led to the inclusion of 226 patients (113 medical group, 113 intervention group) in the final analysis. The primary outcome was a composite of all-cause mortality, heart transplant and acute heart failure exacerbations. Secondary outcomes included AF recurrence and transition to permanent AF. Additionally, an inverse probability weighted (IPW) model was examined. Results: At propensity score matching analysis, after a median follow-up of 58.1 months, the primary endpoint occurred in 29 (25.7%) patients in intervention group vs 42 (37.2%) in medical group (P = 0.9). Thromboembolic strokes and major arrhythmic events in intervention vs medical group were 9.7% vs 7.1% (P = 0.144) and 4.4 vs 8.0% (P = 0.779), respectively. Fewer patients in intervention vs medical group experienced AF recurrences (63.7% vs 84.1%, P = 0.001) and transition to permanent AF pattern (20.4% vs 33.6%, P = 0.026). IPW analysis showed consistent results. Severe complications related to CA were uncommon (0.7%). Conclusions: After 5 years of follow-up, CA did not improve major adverse cardiac outcomes in a large cohort of patients with HCM and AF. Nevertheless, CA seems to facilitate the maintenance of sinus rhythm and slow the progression to permanent AF, without significant safety concerns.

Role of the vessel morphology on the lenticulostriate arteries hemodynamics during atrial fibrillation: A CFD-based multivariate regression analysis.

BACKGROUND AND OBJECTIVE: Atrial fibrillation (AF) is the most common cardiac arrhythmia, inducing accelerated and irregular beating. Beside well-known disabling symptoms - such as palpitations, reduced exercise tolerance, and chest discomfort - there is growing evidence that an alteration of deep cerebral hemodynamics due to AF increases the risk of vascular dementia and cognitive impairment, even in the absence of clinical strokes. The alteration of deep cerebral circulation in AF represents one of the least investigated among the possible mechanisms. Lenticulostriate arteries (LSAs) are small perforating arteries mainly departing from the middle cerebral artery (MCA) and susceptible to small vessel disease, which is one of the mechanisms of subcortical vascular dementia development. The purpose of this study is to investigate the impact of different LSAs morphologies on the cerebral hemodynamics during AF. METHODS: By combining a computational fluid dynamics (CFD) analysis of LSAs with 7T high-resolution magnetic resonance imaging (MRI), we performed different CFD-based multivariate regression analyses to detect which geometrical and morphological vessel features mostly affect AF hemodynamics in terms of wall shear stress. We exploited 17 cerebral 7T-MRI derived LSA vascular geometries extracted from 10 subjects and internal carotid artery data from validated 0D cardiovascular-cerebral modeling as inflow conditions. RESULTS: Our results revealed that few geometrical variables - namely the size of the MCA and the bifurcation angles between MCA and LSA - are able to satisfactorily predict the AF impact. In particular, the present study indicates that LSA morphologies exhibiting markedly obtuse LSA-MCA inlet angles and small MCA size downstream of the LSA-MCA bifurcation may be more prone to vascular damage induced by AF. CONCLUSIONS: The present MRI-based computational study has been able for the first time to: (i) investigate the net impact of LSAs vascular morphologies on cerebral hemodynamics during AF events; (ii) detect which combination of morphological features worsens the hemodynamic response in the presence of AF. Awaiting necessary clinical confirmation, our analysis suggests that the local hemodynamics of LSAs is affected by their geometrical features and some LSA morphologies undergo greater hemodynamic alterations in the presence of AF.

Echocardiographic and clinical features of patients developing prosthesis-patient mismatch after transcatheter aortic valve replacement: Insights from the Recovery-TAVR registry.

BACKGROUND: The impact of prosthesis-patient mismatch (PPM) on major endpoints after transcatheter aortic valve replacement (TAVR) is controversial and the effects on progression of heart damage are poorly investigated. Therefore, our study aims to evaluate the prevalence and predictors of PPM in a "real world" cohort of patients at intermediate and low surgical risk, its impact on mortality and the clinical-echocardiographic progression of heart damage. METHODS: 963 patients who underwent TAVR procedure between 2017 and 2021, from the RECOVERY-TAVR international multicenter observational registry, were included in this analysis. Multiparametric echocardiographic data of these patients were analyzed at 1-year follow-up (FU). Clinical and echocardiographic features were stratified by presence of PPM and PPM severity, as per the most current international recommendations, using VARC-3 criteria. RESULTS: 18% of patients developed post-TAVR. PPM, and 7.7% of the whole cohort had severe PPM. At baseline, 50.3% of patients with PPM were male (vs 46.2% in the cohort without PPM, P = .33), aged 82 (IQR 79-85y) years vs 82 (IQR 78-86 P = .46), and 55.6% had Balloon-Expandable valves implanted (vs 46.8% of patients without PPM, P = .04); they had smaller left ventricular outflow tract (LVOT) diameter (20 mm, IQR 19-21 vs 20 mm, IQR 20-22, P = .02), reduced SVi (34.2 vs 38 mL/m2, P < .01) and transaortic flow rate (190.6 vs 211 mL/s, P < .01). At predischarge FU patients with PPM had more paravalvular aortic regurgitation (moderate-severe AR 15.8% vs 9.2%, P < .01). At 1-year FU, maladaptive alterations of left ventricular parameters were found in patients with PPM, with a significant increase in end-systolic diameter (33 mm vs 28 mm, P = .03) and a significant increase in left ventricle end systolic indexed volume in those with moderate and severe PPM (52 IQR 42-64 and 52, IQR 41-64 vs 44 IQR 35-59 in those without, P = .02)). No evidence of a significant impact of PPM on overall (P = .71) and CV (P = .70) mortality was observed. Patients with moderate/severe PPM had worse NYHA functional class at 1 year (NYHA III-IV 13% vs 7.8%, P = .03). Prosthesis size≤23 mm (OR 11.6, 1.68-80.1) was an independent predictor of PPM, while SVi (OR 0.87, 0.83-0.91, P < .001) and LVOT diameter (OR 0.79, 0.65-0.95, P = .01) had protective effect. CONCLUSIONS: PPM was observed in 18% of patients undergoing TAVR. Echocardiographic evaluations demonstrated a PPM-related pattern of early ventricular maladaptive alterations, possibly precursor to a reduction in cardiac function, associated with a significant deterioration in NYHA class at 1 year. These findings emphasize the importance of prevention of PPM of any grade in patients undergoing TAVR procedure, especially in populations at risk.

Role of cardiac magnetic resonance in stratifying arrhythmogenic risk in mitral valve prolapse patients: a systematic review and meta-analysis.

OBJECTIVES: To perform a systematic review and meta-analysis of studies investigating the diagnostic value of cardiac magnetic resonance (CMR) features for arrhythmic risk stratification in mitral valve prolapse (MVP) patients. MATERIALS AND METHODS: EMBASE, PubMed/MEDLINE, and CENTRAL were searched for studies reporting MVP patients who underwent CMR with assessment of: left ventricular (LV) size and function, mitral regurgitation (MR), prolapse distance, mitral annular disjunction (MAD), curling, late gadolinium enhancement (LGE), and T1 mapping, and reported the association with arrhythmia. The primary endpoint was complex ventricular arrhythmias (co-VAs) as defined by any non-sustained ventricular tachycardia, sustained ventricular tachycardia, ventricular fibrillation, or aborted sudden cardiac death. Meta-analysis was performed when at least three studies investigated a CMR feature. PROSPERO registration number: CRD42023374185. RESULTS: The meta-analysis included 11 studies with 1278 patients. MR severity, leaflet length/thickness, curling, MAD distance, and mapping techniques were not meta-analyzed as reported in < 3 studies. LV end-diastolic volume index, LV ejection fraction, and prolapse distance showed small non-significant effect sizes. LGE showed a strong and significant association with co-VA with a LogORs of 2.12 (95% confidence interval (CI): [1.00, 3.23]), for MAD the log odds-ratio was 0.95 (95% CI: [0.30, 1.60]). The predictive accuracy of LGE was substantial, with a hierarchical summary ROC AUC of 0.83 (95% CI: [0.69, 0.91]) and sensitivity and specificity rates of 0.70 (95% CI: [0.41, 0.89]) and 0.80 (95% CI: [0.67, 0.89]), respectively. CONCLUSIONS: Our study highlights the role of LGE as the key CMR feature for arrhythmia risk stratification in MVP patients. MAD might complement arrhythmic risk stratification. CLINICAL RELEVANCE STATEMENT: LGE is a key factor for arrhythmogenic risk in MVP patients, with additional contribution from MAD. Combining MRI findings with clinical characteristics is critical for evaluating and accurately stratifying arrhythmogenic risk in MVP patients. KEY POINTS: MVP affects 2-3% of the population, with some facing increased risk for arrhythmia. LGE can assess arrhythmia risk, and MAD may further stratify patients. CMR is critical for MVP arrhythmia risk stratification, making it essential in a comprehensive evaluation.

OPTImal PHARMacological therapy for patients with heart failure: Rationale and design of the OPTIPHARM-HF registry.

AIMS: Patients with heart failure (HF) remain often undertreated for multiple reasons, including treatment inertia, contraindications, and intolerance. The OPTIimal PHARMacological therapy for patients with Heart Failure (OPTIPHARM-HF) registry is designed to evaluate the prevalence of evidence-based medical treatment prescription and titration, as well as the causes of its underuse, in a broad real-world population of consecutive patients with HF across the whole ejection fraction spectrum and among different clinical phenotypes. METHODS: The OPTIPHARM-HF registry (NCT06192524) is a prospective, multicenter, observational, national study of adult patients with symptomatic HF, as defined by current international guidelines, regardless of ejection fraction. Both outpatients and inpatients with chronic and acute decompensated HF will be recruited. The study will enroll up to 2500 patients with chronic HF at approximately 35 Italian HF centres. Patients will be followed for a maximum duration of 24 months. The primary objective of the OPTIPHARM-HF registry is to assess prescription and adherence to evidence-based guideline-directed medical therapy (GDMT) in patients with HF. The primary outcome is to describe the prevalence of GDMT use according to target guideline recommendation. Secondary objectives include implementation of comorbidity treatment, evaluation of sequence of treatment introduction and up-titration, description of GDMT implementation in the specific HF population, main causes of GDMT underuse, and assessment of cumulative rate of cardiovascular events. CONCLUSION: The OPTIPHARM-HF registry will provide important implications for improving patient care and adoption of recommended medical therapy into clinical practice among HF patients.

Takotsubo syndrome: Impact of medical therapies on prognosis. A state of art review.

Tako-Tsubo syndrome (TTS) presents as transient ventricular dysfunction, yet its underlying pathophysiology remains enigmatic. The prognosis of patients presenting with TTS appears to be impaired as compared to the general population and is similar to patients with acute coronary syndromes. Recent investigations have predominantly focused on elucidating therapeutic strategies associated with improved outcomes, particularly among post-menopausal female patients. Current evidence suggests that angiotensin-converting enzyme inhibitors (ACEi) may confer a survival advantage in TTS. Notably, ACEi emerges as the sole therapeutic modality demonstrating efficacy in both acute and chronic clinical courses of TTS. Despite this, the magnitude of survival benefit remains less pronounced than anticipated. This underscores the need for further research to explore additional therapeutic pathways and optimize management strategies for this unique patient cohort. Randomized clinical trials and meta-analysis are paramount in discerning the most effective therapeutic interventions aimed at enhancing survival and ameliorating outcomes in TTS. This review aims to comprehensively synthesize evidence pertaining to the prognostic implications of cardiovascular medications in TTS management.

Epicardial Atrial Fat at Cardiac Magnetic Resonance Imaging and AF Recurrence after Transcatheter Ablation.

The relationship between epicardial adipose tissue (EAT) and atrial fibrillation (AF) has gained interest in recent years. The previous literature on the topic presents great heterogeneity, focusing especially on computed tomography imaging. The aim of the present study is to determine whether an increased volume of left atrial (LA) EAT evaluated at routine pre-procedural cardiac magnetic resonance imaging (MRI) relates to AF recurrences after catheter ablation. A total of 50 patients undergoing AF cryoballoon ablation and pre-procedural cardiac MRI allowing quantification of LA EAT were enrolled. In one patient, the segmentation of LA EAT could not be achieved. After a median follow-up of 16.0 months, AF recurrences occurred in 17 patients (34%). The absolute volume of EAT was not different in patients with and without AF recurrences (10.35 mL vs. 10.29 mL; p-value = 0.963), whereas the volume of EAT indexed on the LA volume (EATi) was lower, albeit non-statistically significant, in patients free from arrhythmias (12.77% vs. 14.06%; p-value = 0.467). The receiver operating characteristic curve testing the ability of LA EATi to predict AF recurrence after catheter ablation showed sub-optimal performance (AUC: 0.588). The finest identified cut-off of LA EATi was 10.65%, achieving a sensitivity of 0.5, a specificity of 0.82, a positive predictive value of 0.59 and a negative predictive value of 0.76. Patients with values of LA EATi lower than 10.65% showed greater survival, free from arrhythmias, than patients with values above this cut-off (84% vs. 48%; p-value = 0.04). In conclusion, EAT volume indexed on the LA volume evaluated at cardiac MRI emerges as a possible independent predictor of arrhythmia recurrence after AF cryoballoon ablation. Nevertheless, prospective studies are needed to confirm this finding and eventually sustain routine EAT evaluation in the management of patients undergoing AF catheter ablation.

Is Conduction System Pacing a Valuable Alternative to Biventricular Pacing for Cardiac Resynchronization Therapy?

Cardiac resynchronization therapy (CRT) significantly improves clinical outcomes in patients with ventricular systolic dysfunction and dyssynchrony. Biventricular pacing (BVP) has a class IA recommendation for patients with symptomatic heart failure with reduced ejection fraction (HFrEF) and left bundle branch block (LBBB). However, approximately 30% of patients have a poor therapeutic response and do not achieve real clinical benefit. Pre-implant imaging, together with tailored programming and dedicated device algorithms, have been proposed as possible tools to improve success rate but have shown inconsistent results. Over the last few years, conduction system pacing (CSP) is becoming a real and attractive alternative to standard BVP as it can restore narrow QRS in patients with bundle branch block (BBB) by stimulating and recruiting the cardiac conduction system, thus ensuring true resynchronization. It includes His bundle pacing (HBP) and left bundle branch area pacing (LBBAP). Preliminary data coming from small single-center experiences are very promising and have laid the basis for currently ongoing randomized controlled trials comparing CSP with BVP. The purpose of this review is to delve into the emerging role of CSP as an alternative method of achieving CRT. After framing CSP in a historical perspective, the pathophysiological rationale and available clinical evidence will be examined, and crucial technical aspects will be discussed. Finally, evidence gaps and future perspectives on CSP as a technique of choice to deliver CRT will be summarized.

Stroke outcomes following durable left ventricular assist device implant in patients bridged with micro-axial flow pump: Insights from a large registry.

BACKGROUND: Stroke after durable left ventricular assist device (d-LVAD) implantation portends high mortality. The incidence of ischemic and hemorrhagic stroke and the impact on stroke outcomes of temporary mechanical circulatory support (tMCS) management among patients requiring bridge to d-LVAD with micro-axial flow-pump (mAFP, Abiomed) is unsettled. METHODS: Consecutive patients, who underwent d-LVAD implantation after being bridged with mAFP at 19 institutions, were retrospectively included. The incidence of early ischemic and hemorrhagic stroke after d-LVAD implantation (<60 days) and association of pre-d-LVAD characteristics and peri-procedural management with a specific focus on tMCS strategies were studied. RESULTS: Among 341 patients, who underwent d-LVAD implantation after mAFP implantation (male gender 83.6%, age 58 [48-65] years, mAFP 5.0/5.5 72.4%), the early ischemic stroke incidence was 10.8% and early hemorrhagic stroke 2.9%. The tMCS characteristics (type of mAFP device and access, support duration, upgrade from intra-aortic balloon pump, ECMELLA, ECMELLA at d-LVAD implantation, hemolysis, and bleeding) were not associated with ischemic stroke after d-LVAD implant. Conversely, the device model (mAFP 2.5/CP vs. mAFP 5.0/5.5: HR 5.6, 95%CI 1.4-22.7, p = 0.015), hemolysis on mAFP support (HR 10.5, 95% CI 1.3-85.3, p = 0.028) and ECMELLA at d-LVAD implantation (HR 5.0, 95% CI 1.4-18.7, p = 0.016) were associated with increased risk of hemorrhagic stroke after d-LVAD implantation. Both early ischemic (HR 2.7, 95% CI 1.9-4.5, p < 0.001) and hemorrhagic (HR 3.43, 95% CI 1.49-7.88, p = 0.004) stroke were associated with increased 1-year mortality. CONCLUSIONS: Among patients undergoing d-LVAD implantation following mAFP support, tMCS characteristics do not impact ischemic stroke occurrence, while several factors are associated with hemorrhagic stroke suggesting a proactive treatment target to reduce this complication.

Single versus dual antiplatelet therapy following percutaneous left atrial appendage closure-A systematic review and meta-analysis.

BACKGROUND: In the last few years, percutaneous LAA occlusion (LAAO) has become a plausible alternative in atrial fibrillation (AF) patients with contraindications to anticoagulation therapy. Nevertheless, the optimal antiplatelet strategy following percutaneous LAAO remains to be defined. METHODS: Studies comparing single antiplatelet therapy (SAPT) versus dual antiplatelet therapy (DAPT) following LAAO were systematically searched and screened. The outcomes of interest were ischemic stroke, device-related thrombus (DRT) and major bleeding. A random-effect meta-analysis was performed comparing outcomes in both groups. The moderator effect of baseline characteristics on outcomes was evaluated by univariate meta-regression analyses. RESULTS: Sixteen observational studies with 3255 patients treated with antiplatelet therapy (SAPT, n = 1033; DAPT, n = 2222) after LAAO were included. Mean age was 74.5 ± 8.3 years, mean CHA2DS2-VASc and HAS-BLED scores were 4.3 ± 1.5 and 3.2 ± 1.0, respectively. At a weighted mean follow-up of 12.7 months, the occurrence of stroke (RR 1.33; 95% CI 0.64-2.77; p =.44), DRT (RR 1.52; 95% CI 0.90-2.58; p =.12), and the composite of stroke and DRT (RR 1.26; 95% CI 0.67-2.37; p =.47) did not differ significantly between SAPT and DAPT groups. The rate of major bleedings was also not different between groups (RR 1.41; 95% CI 0.64-3.12; p =.39). CONCLUSIONS: Among AF patients at high bleeding risk undergoing percutaneous LAAO, a post-procedural minimalistic antiplatelet strategy with SAPT did not significantly differ from DAPT regimens regarding the rate of stroke, DRT and major bleeding.

Association of Renin-Angiotensin-Aldosterone System Inhibitors With Clinical Outcomes, Hemodynamics, and Myocardial Remodeling Among Patients With Advanced Heart Failure on Left Ventricular Assist Device Support.

BACKGROUND: We evaluated the potential benefits of renin-angiotensin-aldosterone system inhibitors (RAASi) in patients with left ventricular assist device support. METHODS AND RESULTS: A total of 165 consecutive patients undergoing left ventricular assist device implant and alive at 6-month on support were studied. RAASi status after 6-month visit along with clinical reasons for nonprescription/uptitration were retrospectively assessed. The primary outcome was a composite of heart failure hospitalization or cardiovascular death between 6 and 24 months after left ventricular assist device implant. Remodeling and hemodynamic outcomes were explored by studying the association of RAASi new prescription/uptitration versus unmodified therapy at 6-month visit with the change in echocardiographic parameters and hemodynamics between 6 and 18 months. After the 6-month visit, 76% of patients were on RAASi. Patients' characteristics among those receiving and not receiving RAASi were mostly similar. Of 85 (52%) patients without RAASi new prescription/uptitration at 6-month visit, 62% had no apparent clinical reason. RAASi were independently associated with the primary outcome (adjusted hazard ratio, 0.31 [95% CI, 0.16-0.69]). The baseline rates of optimal echocardiographic profile (neutral interventricular septum, mitral regurgitation less than mild, and aortic valve opening) and hemodynamic profile (cardiac index ≥2.2 L/min per m2, wedge pressure <18 mm Hg, and right atrial pressure <12 mm Hg) were similar between groups. At 18 months, patients receiving RAASi new prescription/uptitration at 6 months had higher rates of optimal hemodynamic profile (57.5% versus 37.0%; P=0.032) and trends for higher rates of optimal echocardiographic profile (39.6% versus 22.9%; P=0.055) compared with patients with 6-month unmodified therapy. Optimal 18-month hemodynamic and echocardiographic profiles were associated with the primary outcome (log-rank=0.022 and log-rank=0.035, respectively). CONCLUSIONS: RAASi are associated with improved outcomes and improved hemodynamics among mechanically unloaded patients.

An innovative artificial intelligence-based method to compress complex models into explainable, model-agnostic and reduced decision support systems with application to healthcare (NEAR).

BACKGROUND AND OBJECTIVE: In everyday clinical practice, medical decision is currently based on clinical guidelines which are often static and rigid, and do not account for population variability, while individualized, patient-oriented decision and/or treatment are the paradigm change necessary to enter into the era of precision medicine. Most of the limitations of a guideline-based system could be overcome through the adoption of Clinical Decision Support Systems (CDSSs) based on Artificial Intelligence (AI) algorithms. However, the black-box nature of AI algorithms has hampered a large adoption of AI-based CDSSs in clinical practice. In this study, an innovative AI-based method to compress AI-based prediction models into explainable, model-agnostic, and reduced decision support systems (NEAR) with application to healthcare is presented and validated. METHODS: NEAR is based on the Shapley Additive Explanations framework and can be applied to complex input models to obtain the contributions of each input feature to the output. Technically, the simplified NEAR models approximate contributions from input features using a custom library and merge them to determine the final output. Finally, NEAR estimates the confidence error associated with the single input feature contributing to the final score, making the result more interpretable. Here, NEAR is evaluated on a clinical real-world use case, the mortality prediction in patients who experienced Acute Coronary Syndrome (ACS), applying three different Machine Learning/Deep Learning models as implementation examples. RESULTS: NEAR, when applied to the ACS use case, exhibits performances like the ones of the AI-based model from which it is derived, as in the case of the Adaptive Boosting classifier, whose Area Under the Curve is not statistically different from the NEAR one, even the model's simplification. Moreover, NEAR comes with intrinsic explainability and modularity, as it can be tested on the developed web application platform (https://neardashboard.pythonanywhere.com/). CONCLUSIONS: An explainable and reliable CDSS tailored to single-patient analysis has been developed. The proposed AI-based system has the potential to be used alongside the clinical guidelines currently employed in the medical setting making them more personalized and dynamic and assisting doctors in taking their everyday clinical decisions.

A Quantitative Assessment of Cerebral Hemodynamic Perturbations Associated with Long R-R Intervals in Atrial Fibrillation: A Pilot-Case-Based Experience.

Background and Objectives: Atrial fibrillation (AF) results in systemic hemodynamic perturbations which impact cerebral circulation, possibly contributing to the development of dementia. However, evidence documenting effects in cerebral perfusion is scarce. The aim of this study is to provide a quantitative characterization of the magnitude and time course of the cerebral hemodynamic response to the short hypotensive events associated with long R-R intervals, as detected by near-infrared spectroscopy (NIRS). Materials and Methods: Cerebral NIRS signals and arterial blood pressure were continuously recorded along with an electrocardiogram in twelve patients with AF undergoing elective electrical cardioversion (ECV). The top 0.5-2.5% longest R-R intervals during AF were identified in each patient and used as triggers to carry out the triggered averaging of hemodynamic signals. The average curves were then characterized in terms of the latency, magnitude, and duration of the observed effects, and the possible occurrence of an overshoot was also investigated. Results: The triggered averages revealed that long R-R intervals produced a significant drop in diastolic blood pressure (-13.7 ± 6.1 mmHg) associated with an immediate drop in cerebral blood volume (THI: -0.92 ± 0.46%, lasting 1.9 ± 0.8 s), followed by a longer-lasting decrease in cerebral oxygenation (TOI: -0.79 ± 0.37%, lasting 5.2 ± 0.9 s, p < 0.01). The recovery of the TOI was generally followed by an overshoot (+1.06 ± 0.12%). These effects were progressively attenuated in response to R-R intervals of a shorter duration. Conclusions: Long R-R intervals cause a detectable and consistent cerebral hemodynamic response which concerns both cerebral blood volume and oxygenation and outlasts the duration of the systemic perturbation. These effects are compatible with the activation of dynamic autoregulatory mechanisms in response to the hypotensive stimulus.

Safety and effectiveness of glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: insights from the SPUM-ACS study.

AIMS: Data on Glycoprotein IIb/IIIa inhibitors (GPI) use in real world ACS patients following the introduction of potent P2Y12 inhibitors and newer generation stents are scant. Here, we aimed to assess the utilization, effectiveness, and safety of GPI in a large prospective multi-centre cohort of contemporary ACS patients. METHODS AND RESULTS: SPUM-ACS prospectively recruited patients presenting with ACS between 2009 and 2017. The primary endpoint of the present study was major adverse cardiovascular events (MACE), a composite of all-cause death, non-fatal myocardial infarction (MI) and non-fatal stroke at one year. Secondary endpoints were defined as any bleeding events, BARC 3-5 bleeding, and net adverse cardiovascular events (NACE). A total of 4395 ACS patients were included in the analysis. GPI-treated patients had more total coronary artery occlusion (56% vs 35%, p<0.001) and thrombus (60% vs 35%, p<0.001) at angiography. Among the propensity score matched (PSM) population (1992 patients equally split into two groups), GPI-treated patients showed lower risk of MACE (PSM adjusted HR 0.70, 95% CI 0.49-0.99), but a higher risk of any (PSM adj HR 1.46, 95% CI 1.06-1.99) and major bleedings (PSM adj HR 1.73, 95% CI 1.09-2.76), resulting in a neutral effect on NACE (PSM adj HR 0.87, 95% CI 0.65-1.17). These results remained consistent across all subgroups. CONCLUSION: In patients with ACS undergoing PCI and receiving potent P2Y12 inhibitors, we observed a reduced risk of MACE and an increased risk of major bleedings at 1 year in patients treated with GPI. Although the routine use of GPI is currently not recommended, they might be considered in selected patients following a personalized balancing between ischaemic and bleeding risks.

Impact of endothelial shear stress on coronary atherosclerotic plaque progression and composition: A meta-analysis and systematic review.

BACKGROUND AND AIMS: Intracoronary pressure gradients and translesional flow patterns have been correlated with coronary plaque progression and lesion destabilization. In this study, we aimed to determine the relationship between endothelial shear stress and plaque progression and to evaluate the effect of shear forces on coronary plaque features. METHODS: A systematic review was conducted in medical on-line databases. Selected were studies including human participants who underwent coronary anatomy assessment with computational fluid dynamics (CFD)-based wall shear stress (WSS) calculation at baseline with anatomical evaluation at follow-up. A total of six studies were included for data extraction and analysis. RESULTS: The meta-analysis encompassed 31'385 arterial segments from 136 patients. Lower translesional WSS values were significantly associated with a reduction in lumen area (mean difference -0.88, 95% CI -1.13 to -0.62), an increase in plaque burden (mean difference 4.32, 95% CI 1.65 to 6.99), and an increase in necrotic core area (mean difference 0.02, 95% CI 0.02 to 0.03) at follow-up imaging. Elevated WSS values were associated with an increase in lumen area (mean difference 0.78, 95% CI 0.34 to 1.21) and a reduction in both fibrofatty (mean difference -0.02, 95% CI -0.03 to -0.01) and fibrous plaque areas (mean difference -0.03, 95% CI -0.03 to -0.03). CONCLUSION: This meta-analysis shows that WSS parameters were related to vulnerable plaque features at follow-up. These results emphasize the impact of endothelial shear forces on coronary plaque growth and composition. Future studies are warranted to evaluate the role of WSS in guiding clinical decision-making.