Composite Of Cardiovascular Mortality Research Articles

Vericiguat in heart failure with reduced ejection fraction: hope or solid reality?

In recent years, thanks to the advent of new classes of drugs (ARNI and SGLT2-i), the prognosis of patients suffering from heart failure with reduced ejection fraction (HFrEF) has gradually improved. Nonetheless, there is a residual risk that is not targeted by these therapies. Currently, it is recognized that vericiguat, an oral stimulator of soluble guanylate cyclase (sGC), can restore the NO-sGC-cGMP pathway, through stimulation and activation of sGC, aiming to increase cGMP levels with a reduction in heart failure-related oxidative stress and endothelial dysfunction. Even though the Victoria trial demonstrated that HFrEF patients in treatment with vericiguat showed a 10% reduction in the composite of cardiovascular mortality and rehospitalization for heart failure, statistically significantly reducing heart failure hospitalization, the international guidelines limit its use as a second-line drug for patients with worsening symptomatology despite optimized medical therapy. Furthermore, vericiguat has proved to be a valid therapeutic ally especially in those patients with comorbidities such that they cannot receive the classic four-pillar therapy of HF (in particular renal failure). In this review, the authors report on randomized clinical trials, substudies, and meta-analysis about vericiguat in HFrEF, emphasizing the strengths that would suggest the possible role of vericiguat as the fifth pillar of the HFrEF treatment, acknowledging that there are still gaps in the evidence that need to be clarified.

P2Y12 adenosine receptor inhibitors preloading among patients with non-ST-elevation acute coronary syndromes; insights from a nationwide multicenter registry.

The safety and efficacy of treatment with P2Y12 adenosine-diphosphate receptor inhibitors (P2Y12-RI) before coronary angiography among patients with non-ST-segment elevation acute coronary syndromes (NSTEACS) are questionable. To assess the pretreatment rate with P2Y12-RI and its association with ischemic and bleeding risks among patients with NSTEACS. The study comprised patients with NSTEACS referred for coronary angiography and included in the Acute Coronary Syndrome Israeli Surveys between 2013 and 2021. Patients were divided into two groups according to the timing of P2Y12-RI loading concerning coronary angiography: pretreatment and posttreatment. The primary endpoints were 30-day major adverse cardiovascular events (MACE; composite of cardiovascular mortality, myocardial infarction, stroke, stent thrombosis, and urgent revascularization) and 1-year all-cause mortality. Of 3076 patients, 2423 (78.8%) received pretreatment with a P2Y12-RI, and 653 (21.2%) received P2Y12-RI posttreatment. Prasugrel and ticagrelor were used more in the posttreatment group compared to the pretreatment group (16% vs. 6% and 38% vs. 25%, respectively, p < 0.001 for both). No difference was observed in the rate of 30-day MACE comparing pretreatment and posttreatment (5.3% vs. 2.2%, respectively, p = 0.62). A sensitivity analysis of 30-day MACE among patients from the 2021 survey demonstrated similar results (2.5% in the posttreatment group vs. 8.0% in the pretreatment group, p = 0.13). There were no differences in 1-year all-cause mortality rates between the pretreatment and posttreatment groups (4.8% vs. 3.8%, p = 0.31). Among patients with NSTEACS referred for an invasive strategy, the P2Y12-RI posttreatment strategy was associated with similar 30-day and 1-year MACE as the pretreatment strategy. These large-scale, multicenter, real-world data provide reassurance on the safety and efficacy of delaying P2Y12-IR until after coronary stratification to improve clinical decision-making.

Rationale and design of the early valve replacement in severe asymptomatic aortic stenosis trial

Aortic valve replacement in asymptomatic severe aortic stenosis is controversial. The Early valve replacement in severe ASYmptomatic Aortic Stenosis (EASY-AS) trial aims to determine whether early aortic valve replacement improves clinical outcomes, quality of life and cost-effectiveness compared to a guideline recommended strategy of 'watchful waiting'. In a pragmatic international, open parallel group randomized controlled trial (NCT04204915), 2844 patients with severe aortic stenosis will be randomized 1:1 to either a strategy of early (surgical or transcatheter) aortic valve replacement or aortic valve replacement only if symptoms or impaired left ventricular function develop, or other cardiac surgery becomes nessessary. Exclusion criteria include other severe valvular disease, planned cardiac surgery, ejection fraction <50%, previous aortic valve replacement or life expectancy <2 years. The primary outcome is a composite of cardiovascular mortality or heart failure hospitalization. The primary analysis will be undertaken when 663 primary events have accrued, providing 90% power to detect a reduction in the primary endpoint from 27.7% to 21.6% (hazard ratio 0.75). Secondary endpoints include disability-free survival, days alive and out of hospital, major adverse cardiovascular events and quality of life. Recruitment commenced in March 2020 and is open in the UK, Australia, New Zealand, and Serbia. Feasibility requirements were met in July 2022, and the main phase opened in October 2022, with additional international centers in set-up. The EASY-AS trial will establish whether a strategy of early aortic valve replacement in asymptomatic patients with severe aortic stenosis reduces cardiovascular mortality or heart failure hospitalization and improves other important outcomes.

Clinical impact of multiple resheathing during transcatheter aortic valve implantation with Evolut self-expanding valves

BackgroundThe possibility to resheath some transcatheter heart valves (THV) facilitates the optimization of self-expandable devices implantation. However, resheating manoeuvres (expecially when repeated) increase the interaction between the transcatheter prosthesis and the patient's tissues potentially causing side-effects. AimsTo assess the clinical outcomes of resheathing at midterm follow-up with a focus on the safety of multiple resheathing. MethodsThis retrospective observational study included all consecutive patients who underwent TAVI with a self-expandable supra-annular THV between December 2018 and December 2022. Primary endpoint was a composite of cardiovascular (CV) mortality, neurological events, non-fatal acute myocardial infarction and CV rehospitalizations. All clinical endpoints were assessed according to VARC-3 criteria. Results469 TAVI procedures with self-expandable supra-annular THV were included in the study. The attempt to resheath and the resheath manoeuvres number was prospectively recorded into an electronic database. Resheating was attempted in 253 (53.9%) cases; 1, 2 and ≥ 3 resheathing were performed in respectively 122 (26.0%), 63 (13.4%) and 68 (14.5%) procedures. At a median follow-up of 640 days (interquartile range 340–1033 days), the incidence of the primary endpoint did not differ between 0 vs. ≥1 (22.7 vs. 26.1%, LogRank p = 0.584) and < 3 vs. ≥3 resheathing groups (24.2 vs. 26.5% LogRank p = 0.963). Furthermore, no significant differences in the primary endpoint were observed between 0, 1–2 and ≥ 3 resheathing (p = 0.84). ConclusionsOur study found that resheathing of self-expandable THVs during TAVI did not result in worse clinical outcomes compared with no resheathing at mid-term follow-up. These results are independent from the number of resheathing, underling the safety of multiple resheathing in terms of peri-procedural and mid-term outcome. Condensed abstractIn this retrospective observational study of 469 patients undergoing transcatheter aortic valve implantation (TAVI) for symptomatic severe aortic stenosis with self-expanding valves, we investigated the influence of resheathing on mid-term clinical outcomes. Specifically, we focused on the safety of multiple resheathing procedures. Our findings revealed no significant impact of resheathing on medium-term outcomes. The primary endpoint, a composite of cardiovascular mortality, neurological events, non-fatal acute myocardial infarction, and cardiovascular rehospitalizations, did not show statistically significant differences between no resheathing, single resheathing and multiple resheathing groups. Our study suggests that resheathing, even when performed multiple times, does not appear to significantly affect clinical outcomes at mid-term follow-up.

Non-invasive assessment of left ventricular contractility by myocardial work index in veno-arterial membrane oxygenation patients: rationale and design of the MIX-ECMO multicentre observational study.

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is an increasingly utilized therapeutic choice in patients with cardiogenic shock, however, high complication rate often counteracts with its beneficial cardiopulmonary effects. The assessment of left ventricular (LV) function in key in the management of this population, however, the most commonly used measures of LV performance are substantially load-dependent. Non-invasive myocardial work is a novel LV functional measure which may overcome this limitation and estimate LV function independent of the significantly altered loading conditions of VA-ECMO therapy. The Usefulness of Myocardial Work IndeX in ExtraCorporeal Membrane Oxygenation Patients (MIX-ECMO) study aims to examine the prognostic role of non-invasive myocardial work in VA-ECMO-supported patients. The MIX-ECMO is a multicentric, prospective, observational study. We aim to enroll 110 patients 48-72 h after the initiation of VA-ECMO support. The patients will undergo a detailed echocardiographic examination and a central echocardiography core laboratory will quantify conventional LV functional measures and non-invasive myocardial work parameters. The primary endpoint will be failure to wean at 30 days as a composite of cardiovascular mortality, need for long-term mechanical circulatory support or heart transplantation at 30 days, and besides that other secondary objectives will also be investigated. Detailed clinical data will also be collected to compare LV functional measures to parameters with established prognostic role and also to the Survival After Veno-arterial-ECMO (SAVE) score. The MIX-ECMO study will be the first to determine if non-invasive myocardial work has added prognostic value in patients receiving VA-ECMO support.

Effectiveness and safety of empagliflozin: final results from the EMPRISE study.

Limited evidence exists on the comparative safety and effectiveness of empagliflozin against alternative glucose-lowering medications in individuals with type 2 diabetes with the broad spectrum of cardiovascular risk. The EMPagliflozin compaRative effectIveness and SafEty (EMPRISE) cohort study was designed to monitor the safety and effectiveness of empagliflozin periodically for a period of 5 years with data collection from electronic healthcare databases. We identified individuals ≥18 years old with type 2 diabetes who initiated empagliflozin or dipeptidyl peptidase-4 inhibitors (DPP-4i) from 2014 to 2019 using US Medicare and commercial claims databases. After 1:1 propensity score matching using 143 baseline characteristics, we identified four a priori-defined effectiveness outcomes: (1) myocardial infarction (MI) or stroke; (2) hospitalisation for heart failure (HHF); (3) major adverse cardiovascular events (MACE); and (4) cardiovascular mortality or HHF. Safety outcomes included lower-limb amputations, non-vertebral fractures, diabetic ketoacidosis (DKA), acute kidney injury (AKI), severe hypoglycaemia, retinopathy progression, and short-term kidney and bladder cancers. We estimated HRs and rate differences (RDs) per 1000 person-years, overall and stratified by age, sex, baseline atherosclerotic cardiovascular disease (ASCVD) and heart failure. We identified 115,116 matched pairs. Compared with DPP-4i, empagliflozin was associated with lower risks of MI/stroke (HR 0.88 [95% CI 0.81, 0.96]; RD -2.08 [95% CI (-3.26, -0.90]), HHF (HR 0.50 [0.44, 0.56]; RD -5.35 [-6.22, -4.49]), MACE (HR 0.73 [0.62, 0.86]; RD -6.37 [-8.98, -3.77]) and cardiovascular mortality/HHF (HR 0.57 [0.47, 0.69]; RD -10.36 [-12.63, -8.12]). Absolute benefits were larger in older individuals and in those with ASCVD/heart failure. Empagliflozin was associated with an increased risk of DKA (HR 1.78 [1.44, 2.19]; RD 1.59 [1.08, 2.09]); decreased risks of AKI (HR 0.62 [0.54, 0.72]; RD -2.39 [-3.08, -1.71]), hypoglycaemia (HR 0.75 [0.67, 0.84]; RD -2.46 [-3.32, -1.60]) and retinopathy progression (HR 0.78 [0.63, 0.96)]; RD -9.49 [-16.97, -2.10]); and similar risks of other safety events. Empagliflozin relative to DPP-4i was associated with risk reductions of MI or stroke, HHF, MACE and the composite of cardiovascular mortality or HHF. Absolute risk reductions were larger in older individuals and in those who had history of ASCVD or heart failure. Regarding the safety outcomes, empagliflozin was associated with an increased risk of DKA and lower risks of AKI, hypoglycaemia and progression to proliferative retinopathy, with no difference in the short-term risks of lower-extremity amputation, non-vertebral fractures, kidney and renal pelvis cancer, and bladder cancer.

Vericiguat treatment of heart failure: A systematic review and meta-analysis.

Heart failure (HF), an end-stage manifestation of various cardiac diseases, poses an enormous economic and health burden on society. Vericiguat may be an effective drug in the treatment of HF. To explore by meta-analysis the efficacy and safety of Vericiguat in treating chronic heart failure. Databases, including PubMed, EMBASE, Web of Science, and Cochrane Library, were searched to collect all published randomized controlled trials (RCTs) on Vericiguat treatment of chronic heart failure from the earliest electronic records to those published in March 2023. Two investigators independently screened the literature according to inclusion and exclusion criteria, evaluated the quality of the studies, and extracted valid data before conducting a meta-analysis using RevMan5.4. Four RCTs with 5919 patients were included, and the meta-analysis showed that treatment with 10 mg Vericiguat reduced the incidence of the primary endpoint (a composite of cardiovascular mortality and first heart-failure-related hospitalization) in patients with chronic heart failure compared to placebo [relative risk (RR) = 0.91, 95% confidence interval (CI): 0.85-0.98, P = 0.01], and reduced the incidence of heart-failure-related hospitalization (RR = 0.92, 95%CI: 0.84-1.00, P = 0.05). However, for the incidence of cardiovascular and all-cause death, there were no significant differences between the Vericiguat and placebo groups. In addition, the two groups did not show significant differences in blood pressure, heart rate, and Kansas Cardiomyopathy Questionnaire physical limitation score. In terms of safety, 10 mg Vericiguat did not increase the risk of adverse effects in patients with chronic heart failure. Vericiguat may increase the risk of symptomatic hypotension (RR = 1.17, 95%CI: 0.98-1.39, P = 0.08) and syncope (RR = 1.18, 95%CI: 0.90-1.55, P = 0.24), but not significantly. Vericiguat (10 mg) was more effective than placebo in treating patients with chronic heart failure and had a better safety profile.

Long-Term Major Adverse Cardiovascular Events in Patients with Moderate and Severe COVID-19: A Focus on Early Statin Use and Previous CVD.

Limited data exist regarding the status of long-term cardiovascular disease (CVD) outcomes of hospitalized COVID-19 patients. We aimed to examine the efficacy of early statin use after SARS-CoV-2 pneumonia and the impact of prior CVD on the incidence of cardiovascular events. A prospective cohort study was performed on hospitalized COVID-19 patients. The primary endpoint was major adverse cardiovascular events (MACE) as a composite of cardiovascular mortality, stroke, heart failure, venous thromboembolism (VTE), revascularization, and nonfatal myocardial infarction (MI). The secondary endpoints comprised MACE components, all-cause mortality, readmission for COVID-19, and impaired functional classes. The mean age of the 858 participants was 55.52±13.97 years, and the median follow-up time was 13 months (11.5-15). Men comprised 63.9% of the patients. Overall, MACE occurred in 84 subjects (9.8%), and 98 patients (11.4%) received ventilation. A multivariate Cox regression model was employed to explore the association between statin use and outcomes, and the following hazard ratios were obtained: MACE (0.831 [0.529 to 0.981]; P=0.044), All-cause mortality (1.098 [0.935 to 1.294]; P=0.255), stroke (0.118 [0.029 to 0.48]; P=0.003), revascularization (0.103 [0.029 to 0.367]; P<0.0001), poor functional capacity (0.827 [0.673 to 1.018]; P=0.073), nonfatal MI (0.599 [0.257 to 1.394]; P=0.234), VTE (0.376 [0.119 to 1.190]; P=0.096), and decompensated heart failure (0.137 [0.040 to 0.472]; P=0.002). Prior CVD predicted MACE (2.953 [1.393 to 6.271]; P=0.005), all-cause death (1.170 [0.960 to 1.412]; P=0.102), and VTE (2.770 [0.957 to 8.955]; P=0.051). Previous CVD is a robust predictor of long-term MACE and VTE. Early statin use might decrease the incidence rates of MACE, ischemic stroke, revascularization, and readmission for heart failure.

Long-term outcome and characteristics of patients with NSTEMI and non-obstructive coronary arteries

Abstract Introduction Discordant data have been reported on the prognosis of myocardial infarction with nonobstructive coronary arteries (MINOCA). Purpose The objectives of this study were to assess characteristics and prognostic impact on the long-term follow-up of the diagnosis of MINOCA. Methods We included 274 consecutive patients with non–ST-segment elevation myocardial infarction (NSTEMI) who underwent coronary angiography between November 2015 and October 2016. MINOCA was classified according to angiographic findings as smooth coronary arteries, mild irregularities (&amp;lt; 30% stenosis), and moderate atherosclerosis (30%-49% stenosis). The primary endpoint was a composite of cardiovascular mortality, nonfatal myocardial infarction, and revascularization (MACE) at a median of 6 years of follow-up. Results A total of 74 patients (27.0%) showed no obstructive lesions. Patients with MINOCA are characterized by younger age, a predominance of females, less diabetes mellitus, dyslipidemia, and smoking, lower GRACE score at admission, less marked electrocardiographic and echocardiographic changes, and lower troponin levels. MINOCA was associated with a lower occurrence of MACE (P&amp;lt; 10-3; HR, 0.085; 95%CI, 0.031-0.231) and was confirmed as an independent factor in the multivariate analysis (P&amp;lt; 10-3; HR, 0.121; 95%CI, 0.042-0.354). On analysis of the separate components of the main endpoint, MINOCA was significantly associated with a lower rate of cardiovascular mortality, myocardial infarction, and revascularization. Conclusions MINOCA is characterized by a low-risk profile at admission except for the positivity of troponin and is associated with a lower rate of MACE at the long-term follow-up.Table:Characteristics6-year outcomes

Biventricular or conduction system pacing for cardiac resynchronization therapy: a proposed treatment algorithm based on interventricular conduction delays

Abstract Background Cardiac resynchronization therapy (CRT) is usually performed with biventricular pacing (BiVP), but recently conduction system pacing (CSP) has been proposed as an alternative in case of unsuccessful coronary sinus lead implantation. However , further evidence is needed to determine when CSP should be used in lieu of BiVP to improve clinical benefit. Purpose To assess the clinical benefit of a treatment algorithm based on interventricular conduction delays (IVCD) to choose between BiVP or CSP in candidates to CRT. Methods Consecutive patients presenting at our Institution from January 2018 to December 2020 with an indication to CRT were prospectively enrolled in the study group (delays-guided resynchronization group, DRG). IVCD were measured after left ventricle (LV) lead positioning in a lateral or posterior-lateral cardiac vein, when feasible, using endocavitary electrogram. Treatment algorithm based on IVCD was used to decide whether to leave LV lead to perform BiVP or pull it out and perform CSP. An historical cohort of patients who underwent CRT from January 2016 to December 2017 independently from IVCD was used as a control group (standard resynchronization group, SRG). The primary endpoint was a composite of cardiovascular mortality, heart failure (HF) hospitalization, or urgent unplanned clinic visits at 1 year after the date of intervention. Results Study population consisted in 292 patients, of which 160 (54.8%) in the DRG and 132 (45.2%) in the SRG. Age, sex, HF etiology, NYHA class, left ventricular ejection fraction and QRS duration and morphology did not differ between the two groups. In the DRG 41 of 160 patients underwent CSP based on treatment algorithm (25.6%). The primary endpoint was significantly reduced in the DRG (35/160, 21.8%) compared to SRG (48/132, 36.4%)(hazard ratio (HR): 1.72; 95% confidence interval (CI):1.12-2.65; p=0.013). Conclusion A treatment algorithm based on IVCD shifted 1 patient every 4 from BiVP to CSP, with consequent reduction in cardiovascular deaths, HF hospitalizations or urgent unplanned clinic visits after implantation. Therefore, its application could be useful to determine whether to perform BiVP or CSP in CRT candidates.Treatment Algorithm

Predictive capacity of a genetic risk score for coronary artery disease in assessing recurrences and cardiovascular mortality among patients with myocardial infarction.

This study aimed to evaluate the capacity of a genetic risk score (GRS) for coronary artery disease (CAD) independent of classical cardiovascular risk factors to assess the risk of recurrence in patients with first myocardial infarction. The secondary aim was to determine the predictive value of this GRS. We performed a meta-analysis of individual data from three studies, namely, a prospective study including 75 patients aged <55 years, a prospective study including 184 patients with a mean age of 60.5 years, and a case-control study (77 cases and 160 controls) nested in a cohort of patients with first myocardial infarction. A GRS including 12 CAD genetic variants independent of classical cardiovascular risk factors was developed. The outcome was a composite of cardiovascular mortality and recurrent acute coronary syndrome. The GRS was associated with a higher risk of recurrence [hazard ratio = 1.24; 95% confidence interval (CI): 1.04-1.47]. The inclusion of the GRS in the clinical model did not increase the model's discriminative capacity (change in C-statistic/area under the curve: 0.009; 95% CI: -0.007 to 0.025) but improved its reclassification (continuous net reclassification index: 0.29; 95% CI: 0.08-0.51). The GRS for CAD, independent of classical cardiovascular risk factors, was associated with a higher risk of recurrence in patients with first myocardial infarction. The predictive capacity of this GRS identified a subgroup of high-risk patients who could benefit from intensive preventive strategies.

Quantitative flow ratio-based outcomes in patients undergoing transcatheter aortic valve implantation quaestio study.

Coronary artery disease (CAD) is common in patients with aortic valve stenosis (AS) ranging from 60% to 80%. The clinical and prognostic role of coronary artery lesions in patients undergoing Transcatheter Aortic Valve Implantation (TAVI) remains unclear. The aim of the present observational study was to estimate long-term clinical outcomes by Quantitative Flow Ratio (QFR) characterization of CAD in a well-represented cohort of patients affected by severe AS treated by TAVI. A total of 439 invasive coronary angiographies of patients deemed eligible for TAVI by local Heart Teams with symptomatic severe AS were retrospectively screened for QFR analysis. The primary endpoint of the study was all-cause mortality. The secondary endpoint was a composite of cardiovascular mortality, stroke/transient ischemic attack (TIA), acute myocardial infarction (AMI), and any hospitalization after TAVI. After exclusion of patients with no follow-up data, coronary angiography not feasible for QFR analysis and previous surgical myocardial revascularization (CABG) 48/239 (20.1%) patients had a QFR value lower or equal to 0.80 (QFR + value), while the remaining 191/239 (79.9%) did not present any vessel with a QFR positive value. In the adjusted Cox regression analysis, patients with positive QFR were independently associated with an increased risk of all-casual mortality (Model 1, HR 3.47, 95% CI, 2.35-5.12; Model 2, HR 5.01, 95% CI, 3.17-7.90). In the adjusted covariate analysis, QFR+ involving LAD (37/48, 77,1%) was associated with the higher risk of the composite outcome compared to patients without any positive value of QFR or non-LAD QFR positive value (11/48, 22.9%). Pre-TAVI QFR analysis can be used for a safe, simple, wireless functional assessment of CAD. QFR permits to identify patients at high risk of cardiovascular mortality or MACE, and it could be considered by local Heart Teams.

Long-Term Prognosis of Different Subtypes of Left Ventricular Noncompaction Cardiomyopathy Patients: A Retrospective Study in China.

Left ventricular noncompaction (LVNC) is a heterogeneous cardiomyopathy that can be classified into different subtypes based on morphologic and functional features. However, the prognosis of the dilated and isolated subtypes of non-pediatric LVNC remains unknown. We retrospectively studied 101 patients with LVNC diagnosed at Peking Union Medical College Hospital from 2006 to 2022 using the Jenni criteria of transthoracic echocardiography. The patients were grouped into those with dilated LVNC (n = 64) or isolated LVNC (n = 37), and 88 patients (54 with dilated LVNC and 34 with isolated LVNC) were followed up successfully. The primary outcome was major adverse cardiovascular events (a composite of cardiovascular mortality, heart failure, severe ventricular arrhythmia, and systolic embolism). The median follow-up time was 5.24 years. The incidence of major adverse cardiovascular events was 43.2%; patients with dilated LVNC had a higher risk (adjusted hazard ratio, 4.43; 95% confidence interval, 1.24-15.81; p = 0.02) than those with isolated LVNC. None of the isolated LVNC patients had cardiovascular deaths or severe ventricular arrhythmias. The risk of systemic embolism was similar between patients with dilated and isolated LVNC. Our findings indicate that transthoracic echocardiography is a useful tool for classifying LVNC into subtypes with distinct clinical outcomes. Dilated LVNC is associated with a poor prognosis, while the isolated subtype is probably a physiological condition.

Impact of diabetes on remodelling, microvascular function and exercise capacity in aortic stenosis

ObjectiveTo characterise cardiac remodelling, exercise capacity and fibroinflammatory biomarkers in patients with aortic stenosis (AS) with and without diabetes, and assess the impact of diabetes on outcomes.MethodsPatients with moderate or...

Global Longitudinal Strain Predicts Clinical Outcomes in Patients with Heart Failure with Preserved Ejection Fraction.

Patients with HFpEF are at high risk for hospitalization and mortality and many of these patients experience a deterioration in left ventricular ejection fraction (LVEF) over time. Global longitudinal strain (GLS) is a sensitive marker of myocardial dysfunction that could help predict risk for future events in this population. We assessed whether GLS can predict adverse clinical outcomes and future deterioration in LVEF in patients with heart failure with preserved ejection fraction (HFpEF). In this retrospective cohort study, patients with HFpEF were subdivided into groups according to abnormal GLS (> -15.8%) or normal GLS (<-15.8%).The primary outcomes were: a composite of cardiovascular mortality or HF hospitalization and deterioration in LVEF to <40%. Among the 311 patients with HFpEF, 128 patients (41%) had normal GLS and 183 patients (59%) had abnormal GLS. After median 4.6 years follow-up, the composite outcome occurred more commonly in patients with abnormal GLS compared to patients with normal GLS (62% vs 44%; HR 1.74, 95% CI 1.3-2.4, p<0.001). Patients with abnormal GLS were also more likely to experience a deterioration in LVEF (19% vs 10%; HR 2.2, 95% CI 1.2-4.3, p=0.018). When assessed as a continuous variable, each 1% increase in GLS was associated with 10% increased odds for the composite outcome and 13% increased odds for deterioration in LVEF. In patients with HFpEF, abnormal GLS is common and is a strong predictor for clinical events and future deterioration in LVEF. This article is protected by copyright. All rights reserved.

HFrEF subphenotypes based on 4210 repeatedly measured circulating proteins are driven by different biological mechanisms.

HFrEF is a heterogenous condition with high mortality. We used serial assessments of 4210 circulating proteins to identify distinct novel protein-based HFrEF subphenotypes and to investigate underlying dynamic biological mechanisms. Herewith we aimed to gain pathophysiological insights and fuel opportunities for personalised treatment. In 382 patients, we performed trimonthly blood sampling during a median follow-up of 2.1 [IQR:1.1-2.6] years. We selected all baseline samples and two samples closest to the primary endpoint (PEP; composite of cardiovascular mortality, HF hospitalization, LVAD implantation, and heart transplantation) or censoring, and applied an aptamer-based multiplex proteomic approach. Using unsupervised machine learning methods, we derived clusters from 4210 repeatedly measured proteomic biomarkers. Sets of proteins that drove cluster allocation were analysed via an enrichment analysis. Differences in clinical characteristics and PEP occurrence were evaluated. We identified four subphenotypes with different protein profiles, prognosis and clinical characteristics, including age (median [IQR] for subphenotypes 1-4, respectively:70 [64, 76], 68 [60, 79], 57 [47, 65], 59 [56, 66]years), EF (30 [26, 36], 26 [20, 38], 26 [22, 32], 33 [28, 37]%), and chronic renal failure (45%, 65%, 36%, 37%). Subphenotype allocation was driven by subsets of proteins associated with various biological functions, such as oxidative stress, inflammation and extracellular matrix organisation. Clinical characteristics of the subphenotypes were aligned with these associations. Subphenotypes 2 and 3 had the worst prognosis compared to subphenotype 1 (adjHR (95%CI):3.43 (1.76-6.69), and 2.88 (1.37-6.03), respectively). Four circulating-protein based subphenotypes are present in HFrEF, which are driven by varying combinations of protein subsets, and have different clinical characteristics and prognosis. ClinicalTrials.gov Identifier: NCT01851538https://clinicaltrials.gov/ct2/show/NCT01851538. EU/EFPIA IMI2JU BigData@Heart grant n°116074, Jaap Schouten Foundation and Noordwest Academie.

Left atrial appendage occlusion in the absence of intraprocedural product specialist monitoring: is it time to proceed alone? Results from a multicenter real-world experience.

Percutaneous left atrial appendage occlusion (LAAO) presents many technical complex features, and it is often performed under the intraprocedural surveillance of a product specialist (PS). Our aim is to assess whether LAAO is equally safe and effective when performed in high-volume centers without PS support. Intraprocedural results and long-term outcome were retrospectively assessed in 247 patients who underwent LAAO without intraprocedural PS monitoring between January 2013 and January 2022 at three different hospitals. This cohort was then matched to a population who underwent LAAO with PS surveillance. The primary end point was all-cause mortality at 1 year. The secondary end point was a composite of cardiovascular mortality plus nonfatal ischemic stroke occurrence at 1 year. Of the 247 study patients, procedural success was achieved in 243 patients (98.4%), with only 1 (0.4%) intraprocedural death. After matching, we did not identify any significant difference between the two groups in terms of procedural time (70 ± 19 min vs. 81 ± 30 min, p = 0.106), procedural success (98.4% vs. 96.7%, p = 0.242), and procedure-related ischemic stroke (0.8% vs. 1.2%, p = 0.653). Compared to the matched cohort, a significant higher dosage of contrast was used during procedures without specialist supervision (98 ± 19 vs. 43 ± 21, p < 0.001), but this was not associated with a higher postprocedural acute kidney injury occurrence (0.8% vs. 0.4%, p = 0.56). At 1 year, the primary and the secondary endpoints occurred in 21 (9%) and 11 (4%) of our cohort, respectively. Kaplan-Meier curves showed no significant difference in both primary (p = 0.85) and secondary (p = 0.74) endpoint occurrence according to intraprocedural PS monitoring. Our results show that LAAO, despite the absence of intraprocedural PS monitoring, remains a long-term safe and effective procedure, when performed in high-volume centers.

Predicting 5-Year Clinical Outcomes After Transcatheter or Surgical Aortic Valve Replacement (a Risk Score from the SURTAVI Trial)

Risk prediction scores for long-term outcomes after transcatheter aortic valve implantation (TAVI) or surgical aortic valve replacement (SAVR) are lacking. This study aimed to develop preprocedural risk scores for 5-year clinical outcomes after TAVI or SAVR. This analysis included 1,660 patients at an intermediate surgical risk with severe aortic stenosis randomly assigned to TAVI (n=864) or SAVR (n=796) from the SURTAVI (Surgical Replacement and Transcatheter Aortic Valve Implantation) trial. The primary end point was a composite of all-cause mortality or disabling stroke at 5 years. The secondary end point was a composite of cardiovascular mortality or hospitalizations for valve disease or worsening heart failure at 5 years. Preprocedural multivariable predictors of clinical outcomes were used to calculate a simple risk score for both procedures. At 5 years, the primary end point occurred in 31.3% of the patients with TAVI and 30.8% of the patients with SAVR. Preprocedural predictors differed between TAVI and SAVR. Baseline anticoagulant use was a common predictor for events in both procedures, whereas male sex and a left ventricular ejection fraction <60% were significant predictors for events in patients with TAVI and SAVR, respectively. A total of 4 simple scoring systems were created based on these multivariable predictors. The C-statistics of all models were modest but performed better than the contemporary risk scores. In conclusion, preprocedural predictors of events differ between TAVI and SAVR, necessitating separate risk models. Despite the modest predictive value of the SURTAVI risk scores, they appeared superior to other contemporary scores. Further research is needed to strengthen and validate our risk scores, possibly by including biomarker and echocardiographic parameters.

Biventricular or conduction system pacing for cardiac resynchronization therapy: a proposed treatment algorithm based on interventricular conduction delays

Abstract Funding Acknowledgements Type of funding sources: None. Background Cardiac resynchronization therapy (CRT) is usually performed with biventricular pacing (BiVP), but recently conduction system pacing (CSP) has been proposed as an alternative in case of unsuccessful coronary sinus lead implantation. CSP was performed as His Bundle pacing or Left bundle branch pacing(1). However, further evidence is needed to determine when CSP should be used in lieu of BiVP to improve clinical benefit. Purpose To assess the clinical benefit of a treatment algorithm based on interventricular conduction delays (IVCD) to choose between BiVP or CSP in candidates to CRT(figure1). Methods Consecutive patients presenting at our Institution from January 2018 to December 2020 with an indication to CRT were prospectively enrolled in the study group (delays-guided resynchronization group, DRG). IVCD were measured after left ventricle (LV) lead positioning in a lateral or posterior-lateral cardiac vein, when feasible, using endocavitary electrogram(2). Treatment algorithm based on IVCD was used to decide whether to leave LV lead to perform BiVP or pull it out and perform CSP. Outcomes from the DRG group were compared to a historical cohort of CRT patients (resynchronization standard guide group,SRG). The primary endpoint was a composite of cardiovascular mortality, heart failure (HF) hospitalization, or HF event at 1 year after the date of intervention. Results Study population consisted in 292 patients, of which 160 (54.8%) in the DRG and 132 (45.2%) in the SRG. In the DRG 41 of 160 patients underwent CSP based on treatment algorithm (25.6%). The primary endpoint was significantly reduced in the DRG (35/160, 21.8%) compared to SRG (48/132, 36.4%) (hazard ratio(HR):1.72;95% confidence interval(CI):1.12-2.65;p=0.013)(figure2). Conclusion A treatment algorithm based on IVCD shifted 1 patient every 4 from BiVP to CSP, with consequent reduction in cardiovascular deaths, HF hospitalizations or HF event after implantation. Therefore, its application could be useful to determine whether to perform BiVP or CSP in CRT candidates.

Impact of Right Ventricular Pacing in Patients With TAVR Undergoing Permanent Pacemaker Implantation

BackgroundLong-term right ventricular pacing (VP) has been related to negative left ventricular remodeling and heart failure (HF), but there is a lack of evidence regarding the prognostic impact on transcatheter aortic valve replacement (TAVR) patients. ObjectivesThe aim of the PACE-TAVI registry is to evaluate the association of high percentage of VP with adverse outcomes in patients with pacemaker implantation after TAVR. MethodsPACE-TAVI is an international multicenter registry of all consecutive TAVR patients who underwent permanent pacemaker implantation for conduction disturbances in the first 30 days after the procedure. Patients were divided into 2 subgroups according to the percentage of VP (<40% vs ≥40%) at pacemaker interrogation. The primary endpoint was the composite of cardiovascular mortality or hospitalization for HF. ResultsA total of 377 patients were enrolled, 158 with VP <40% and 219 with VP ≥40%. After multivariable adjustment, VP ≥40% was associated with a higher incidence of the primary endpoint (HR: 2.76; 95% CI: 1.39-5.51; P = 0.004), first HF hospitalization (HR: 3.37; 95% CI: 1.50-7.54; P = 0.003), and cardiovascular death (HR: 3.77; 95% CI: 1.02-13.88; P = 0.04), while the incidence of all-cause death was not significantly different (HR: 2.17; 95% CI: 0.80-5.90; P = 0.13). Patients with VP ≥ 40% showed a higher New York Heart Association functional class both at 1 year (P = 0.009) and at last available follow-up (P = 0.04) and a nonsignificant reduction of left ventricular ejection fraction (P = 0.18) on 1-year echocardiography, while patients with VP <40% showed significant improvement (P = 0.009). ConclusionsIn TAVR patients undergoing permanent pacemaker implantation, a high percentage of right VP at follow-up is associated with an increased risk for cardiovascular death and HF hospitalization. These findings suggest the opportunity to minimize right VP through dedicated algorithms in post-TAVR patients without complete atrioventricular block and to evaluate a more physiological VP modality in patients with persistent complete atrioventricular block.