Combined Endpoint Of Death Research Articles

Assessment of Arterial Stiffness by Cardio-Ankle Vascular Index for Prediction of Five-Year Cardiovascular Events After Coronary Artery Bypass Surgery.

The study aim was to investigate the possibility of cardiovascular complications development predicting during a five-year follow-up of patients after coronary artery bypass grafting (CABG) using the cardio-ankle vascular index (CAVI) assessment.Methods:Three hundred and fifty–six patients after elective CABG were enrolled in the study. Prior to surgery, arterial stiffness was assessed in all patients using CAVI. The follow-up was performed five years after the surgery, information was obtained on 238 patients, who were divided into two groups: patients with pathological (≥9.0, n = 88), and normal (<9.0, n = 150) CAVI.Results:Pathological CAVI (≥9.0) was detected in 33% patients before CABG, in stepwise analyses only age and left atrium dimensions statistically significantly predicted CAVI. In patients with pathological CAVI the combined endpoint (major adverse cardiovascular events and hospitalization) and cardiovascular death developed more often in a five-year follow-up after CABG compared with normal CAVI (48.86% versus 34.9%, p = 0.034 and 4.55% versus 0.67%, p = 0.049, respectively). Pathological CAVI (p = 0.021) and the number of coronary bypass grafts (p = 0.023) were independent factors associated with the combined endpoint.Conclusions:Patients with pathological CAVI before CABG surgery are more likely to develop cardiovascular complications and cardiovascular death within a subsequent five-year follow-up. Evaluation of CAVI after CABG in dynamics deserves further study, it is important for monitoring the effects of secondary prevention and the possibility of influencing the prognosis.

A real-world comparison of outcomes between fractional flow reserve-guided versus angiography-guided percutaneous coronary intervention.

BackgroundFractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) has been shown to be superior to angiography-guided PCI in randomized controlled studies. However, real-world data on the use and outcomes of FFR-guided PCI remain limited. Thus, we investigated the outcomes of patients undergoing FFR-guided PCI compared to angiography-guided PCI in a large, state-wide unselected cohort.Methods and resultsAll patients undergoing PCI between June 2017 and June 2018 in New South Wales, Australia, were included. The cohort was stratified into the FFR-guided group when concomitant FFR was performed, and the angiography-guided group when no FFR was performed. The primary outcome was a combined endpoint of death or myocardial infarction (MI). Secondary outcomes included all-cause death, cardiovascular (CVS) death, and MI. The cohort comprised 10,304 patients, of which 542 (5%) underwent FFR-guided PCI. During a mean follow-up of 12±4 months, the FFR-guided PCI group had reduced occurrence of the primary outcome (hazard ratio [HR] 0.34, 95% confidence intervals [CI] 0.20–0.56, P<0.001), all-cause death (HR 0.18, 95% CI 0.07–0.47, P = 0.001), CVS death (HR 0.21, 95% CI 0.07–0.66, P = 0.01), and MI (HR 0.46, 95% CI 0.25–0.84, P = 0.01) compared to the angiography-guided PCI group. Multivariable Cox regression analysis showed FFR-guidance to be an independent predictor of the primary outcome (HR 0.45, 95% CI 0.27–0.75, P = 0.002), all-cause death (HR 0.22, 95% CI 0.08–0.59, P = 0.003), and CVS death (HR 0.27, 95% CI 0.09–0.83, P = 0.02).ConclusionsIn this real-world study of patients undergoing PCI, FFR-guidance was associated with lower rates of the primary outcome of death or MI, as well as the secondary outcomes of all-cause death and CVS death.

Iatrogenic Atrial Septal Defects Following Transcatheter Mitral Valve Repair and Implications of Interventional Closure.

The authors investigated whether iatrogenic atrial septal defect (iASD) closure post-transcatheter mitral valve edge-to-edge repair (TMVR) is superior to conservative therapy (CT) and whether outcomes (death/heart failure [HF] hospitalization) differ between patients with and without an iASD post-TMVR. Transseptal access for TMVR can create an iASD, which is associated with impaired outcomes. Controversially, the creation of an iASD in HF has been linked to improved hemodynamics. 80 patients with an iASD and relevant left-to-right shunting (Qp:Qs≥1.3) 30days following TMVR were randomized to CT or interventional closure of the iASD (MITHRAS [Closure of Iatrogenic Atrial Septal Defect Following Transcatheter Mitral Valve Repair] cohort), and 235 patients without an iASD served as a comparative cohort. All patients of the MITHRAS cohort (mean age 77 ± 9 years, 39% women) received their allocated treatment, and follow-up was completed for all MITHRAS and comparative cohort (mean age 77 ± 8 years, 47% women) patients. Twelve months post-TMVR, there was no significant difference in the combined endpoint of death or HF hospitalization within the MITHRAS cohort (iASD closure: 35% vs CT 50%; P=0.26). The combined endpoint was more frequent among patients within the MITHRAS cohort as opposed to the comparative cohort (43% vs 17%; P< 0.0001), primarily driven by a higher rate of HF hospitalization (34% vs 8%; P=0.004). In this randomized controlled trial, interventional closure of a relevant iASD 1month after TMVR didnot result in improved clinical outcomes at 12months post-TMVR. Patients with an iASD are at higher risk for HFhospitalization independent of iASD management and warrant close follow-up. (Closure of Iatrogenic Atrial Septal Defect Following Transcatheter Mitral Valve Repair [MITHRAS]; NCT03024268).

Neopterin and kynurenic acid as predictors of stroke recurrence and mortality: a multicentre prospective cohort study on biomarkers of inflammation measured three months after ischemic stroke

BackgroundChronic low-grade inflammation is associated with both ischemic stroke and sedentary behaviour. The aim of this study was to investigate the predictive abilities of biomarkers of inflammation and immune modulation associated with sedentary behaviour for ischemic stroke recurrence and mortality in a stroke population.MethodsPatients admitted to hospital for acute stroke were recruited to the prospective multicentre cohort study, the Norwegian Cognitive Impairment After Stroke (Nor-COAST) study, from May 2015 until March 2017. Patients with ischemic stroke, blood samples available from the three-month follow-up, and no stroke recurrence before the three-month follow-up were included. Serum was analysed for C-reactive protein (CRP) with high-sensitive technique, and plasma for interleukin-6 (IL-6), neopterin, pyridoxic acid ratio index (PAr-index: 4-pyridoxic acid: [pyrioxal+pyridoxal-5′-phosphate]) and kynurenic acid (KA). Ischemic stroke recurrence and death were identified by the Norwegian Stroke Registry and the Cause of Death Registry until 31 December 2018.ResultsThe study included 354 patients, 57% male, mean age 73 (SD 11) years, mean observation time 2.5 (SD 0.6) years, and median National Institute of Health Stroke Scale of 0 (IQR 1) at three months. CRP was associated with mortality (HR 1.40, CI 1.01, 1.96, p = 0.046), and neopterin was associated with the combined endpoint (recurrent ischemic stroke or death) (HR 1.52, CI 1.06, 2.20, p = 0.023), adjusted for age, sex, prior cerebrovascular disease, modified Rankin Scale, and creatinine. When adding neopterin and KA to the same model, KA was negatively associated (HR 0.57, CI 0.33, 0.97, p = 0.038), and neopterin was positively associated (HR 1.61, CI 1.02, 2.54, p = 0.040) with mortality. Patients with cardioembolic stroke at baseline had higher levels of inflammation at three months.ConclusionNeopterin might be a valuable prognostic biomarker in stroke patients. The use of KA as a measure of anti-inflammatory capacity should be investigated further.Trial registrationThe study was registered at Clinicaltrials.gov (NCT02650531). First posted on 08/01/2016.

Fast-Strain Encoded Cardiac Magnetic Resonance During Vasodilator Perfusion Stress Testing.

Background: Cardiac magnetic resonance perfusion imaging during vasodilator stress is an established modality in patients with suspected and known coronary artery disease (CAD).Aim: This study aimed to evaluate the performance of fast-Strain-Encoded-MRI (fast-SENC) for the diagnostic classification and risk stratification of patients with ischemic heart disease.Methods: Perfusion and fast-SENC cardiac magnetic resonance (CMR) images were retrospectively analyzed in 111 patients who underwent stress CMR. The average myocardial perfusion score index, global and segmental longitudinal and circumferential strain (GLS and GCS and SLS and SCS, respectively), were measured at rest and during stress. The combination of SLS and SCS was referred to as segmental aggregate strain (SAS). Segments exhibiting perfusion defects or SAS impairment during stress were defined as “ischemic.” All-cause mortality, non-fatal infarction, and urgent revascularization were deemed as our combined clinical endpoint.Results: During adenosine stress testing, 44 of 111 (39.6%) patients exhibited inducible perfusion abnormalities. During a mean follow-up of 1.94 ± 0.65 years, 25 (22.5%) patients reached the combined endpoint (death in n = 2, infarction in n = 3 and urgent revascularization in n = 20). Inducible perfusion defects were associated with higher number of segments with inducible SAS reduction ≥6.5% (χ2 = 37.8, AUC = 0.79, 95% CI = 0.71–0.87, p < 0.001). In addition, patients with inducible perfusion defects or SAS impairment exhibited poorer outcomes (AUCPerf = 0.81 vs. AUCSAS = 0.74, p = NS vs. each other, and χ2 = 30.8, HR = 10.3 and χ2 = 9.5, HR = 3.5, respectively, p < 0.01 for both).Conclusion: Purely quantitative strain analysis by fast-SENC during vasodilator stress was related to the diagnosis of ischemia by first-pass perfusion and is non-inferior for the risk stratification of patients with ischemic heart disease. This may bear clinical implications, especially in patients with contraindications for contrast agent administration.

Abstract 9994: SVEAT Score Outperforms the HEART Score for Acute Chest Pain Risk Stratification in Patients Admitted to the Clinical Decision Unit

Introduction: Timely and accurate identification of subgroups at risk for major adverse cardiovascular events (MACE) among patients presenting with acute chest pain remains a challenge. The HEART score is one of the most used risk stratification tools in the United States. Recently, a new scoring system based on clinical symptoms (S), history of vascular disease (V), electrocardiography (E), age (A), and serum troponin (T), SVEAT score was shown to outperform the HEART score. Hypothesis: We predicted that the SVEAT score is superior to the HEART score in predicting a 30-day MACE in patients admitted to the clinical decision unit for chest pain evaluation. Methods: Medical records of 330 consecutive patients admitted to our clinical decision unit for acute chest pain between January 1st to April 17th, 2019, were retrospectively reviewed. The 30-day MACE was the combined endpoint of death, acute myocardial infarction, or confirmed coronary artery disease that required revascularization or medical therapy. The investigators assigned to calculate the SVEAT, and HEART scores were blinded to the results of the 30-day MACE. An area under the receiver-operator characteristic curve (AUC) for each score was then calculated. The C-statistic and a logistic model were used to compare the predictive performance of the two scores. Results: A total of 11 patients (3.33%) experienced the endpoint. The AUC of the SVEAT score (0.8876, 95% C.I. 0.82 - 0.96) was significantly higher than the HEART score (0.7960, 95% C.I. 0.71 - 0.88), p = 0.03 (Fig 1). Using logistic model, a SVEAT score with a cut-off of ≤ 4 as low-risk significantly predicts 30-day MACE (odd ratio 1.52, C.I. 1.19-1.95, p = 0.001), but the HEART score did not (odd ratio 1.29, C.I. 0.78-2.14, p = 0.32). Conclusion: The SVEAT score is a superior risk stratification tool to the HEART score in low-to-intermediate-risk acute chest pain patients without apparent acute coronary syndrome.

Abstract 12643: Sub-Endocardial Viability Index and Survival in the HF-ACTION Trial

Introduction: Myocardial perfusion relative to left-ventricular workload may be estimated by the sub-endocardial viability index (SVI). This can be calculated myocardial oxygen supply-demand balance, which is the ratio of diastolic to systolic pressure-time indices, i.e. [(DBP - PAWP) x (60sec/heart rate - 0.2sec)] / (SBP x 0.2sec), assuming fixed 0.2sec for systole. Low SVI indicates reduced sub-endocardial perfusion and was hypothesized to associate with negative outcomes in HFrEF patients. Methods: HF-ACTION was a randomized trial evaluating the efficacy of aerobic exercise training and usual care versus usual care in chronic HFrEF patients. SVI was calculated in HF-ACTION trial patients with complete hemodynamic data. PAWP was calculated using the Nagueh formula from echocardiographic-derived measurements ([PAWP=1.24*(E/e’) +1.9] with e’ = [(e’lateral + e’septal)/2]). The association of SVI with the combined endpoint of death or hospitalization, as well as all-cause death, was assessed. Results: Of 2331 patients in HF-ACTION, 807 had complete data. The mean SVI was 1.59 ± 0.47. The Cox proportional hazards model for the combined endpoint and all-cause death had HR of 0.66 per unit increase in SVI (p&lt;0.00001, 95% CI 0.55-0.79) and 0.67 (p=0.04, 95% CI 0.46-0.98), respectively. Survival during 4 year follow-up was worse below the mean SVI (p=0.0073) ( Figure 1) . In 26 patients below the critical sub-endocardial ischemia SVI of 0.7, survival was worse (p=0.0013) ( Figure 2) . Conclusion: Reduced SVI, a metric of the adequacy of sub-endocardial perfusion, is associated with negative outcomes in HFrEF patients. Figure 1. Figure 2.

The Right Heart Network and Risk Stratification in Pulmonary Arterial Hypertension

BackgroundPrognosis in pulmonary arterial hypertension (PAH) is closely related to indexes of right ventricular function. A better understanding of their relationship may provide important implications for risk stratification in PAH.Research QuestionCan clinical network graphs inform risk stratification in PAH?Study Design and MethodsThe study cohort consisted of 231 patients with PAH followed up for a median of 7.1 years. An undirected, correlation network was used to visualize the relationship between clinical features in PAH. This network was enriched for right heart parameters and included N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP), comprehensive echocardiographic parameters, and hemodynamics, as well as 6-min walk distance (6MWD), vital signs, laboratory data, and diffusing capacity for carbon monoxide (Dlco). Connectivity was assessed by using eigenvector and betweenness centrality to reflect global and regional connectivity, respectively. Cox proportional hazards regression was used to model event-free survival for the combined end point of death or lung transplantation.ResultsA network of closely intertwined features centered around NT-proBNP with 6MWD emerging as a secondary hub were identified. Less connected nodes included Dlco, systolic BP, albumin, and sodium. Over the follow-up period, death or transplantation occurred in 92 patients (39.8%). A strong prognostic model was achieved with a Harrell’s C-index of 0.81 (0.77-0.85) when combining central right heart features (NT-proBNP and right ventricular end-systolic remodeling index) with 6MWD and less connected nodes (Dlco, systolic BP, albumin, sodium, sex, connective tissue disease etiology, and prostanoid therapy). When added to the baseline risk model, serial change in NT-proBNP significantly improved outcome prediction at 5 years (increase in C-statistic of 0.071 ± 0.024; P = .003).InterpretationNT-proBNP emerged as a central hub in the intertwined PAH network. Connectivity analysis provides explainability for feature selection and combination in outcome models.

Leuko-platelet index as an independent predictor of in-hospital events in patients with non-ST elevation acute coronary syndrome

Abstract Background Platelet activation and aggregation plays a fundamental role in the pathophysiology of acute coronary syndrome (ACS). Added to this is the activation of the coagulation cascade and a local and systemic inflammatory response. Both the white blood cell count and the platelet count were associated with a worse prognosis in ACS. The leuko-platelet index (LPI) combines the platelet and white blood cell count and has been described as a prognostic marker in these patients. Purpose The aim of this study is to evaluate if LPI is a predictor of in-hospital events and mortality in patients with non-ST elevation ACS (NSTEACS). Materials and methods A retrospective analysis of a multicentre registry of 25 coronary units of Argentina was performed. It was included patients witch diagnostic of NSTEACS. GRACE score and LPI was calculated with admission data. For LPI it was used the following formula: white blood cell count x platelet count/108. The upper quartile of LPI was chosen as the cut-off point for the LPI (LPI&amp;gt;24). According to GRACE and LPI was divided in 4 groups: Group 1 (GRACE&amp;lt;140 and LIP&amp;lt;24), Group 2 (GRACE&amp;lt;140 and LPI&amp;gt;24), group 3 (GRACE &amp;gt;140 and LPI&amp;lt;24) and group 4 (GRACE &amp;gt;140 and LPI &amp;gt;24). In-hospital follow-up was performed and was considered the combined end point of death from any cause, heart failure, and shock as primary end point and in-hospital mortality as secondary end point. Univariate and multivariate analysis was performed by logistic regression. Results 2170 patients with an age 65±11 years were included, 27.3% women, 63% non-ST infarction and 37% unstable angina, 37% had GRACE&amp;gt;140 (n=803) and 25% had LPI&amp;gt;24 (n=542). The combined end point was presented in 9.3% (n=203) with a in hospital mortality of 2.3% (n=50). The figure 1 shows the gradient of events according to the groups with GRACE 140 and ILP 24 (chi of trend: p=0.001 of combined end point and p=0.01 for in-hospital mortality). In the multivariate analysis, the LPI &amp;gt;24 and the GRACE score were independent predictors of the combined end point (OR 1.48 (95% CI 1.04–2.09), p=0.02 and OR 1.02 (95% CI 1.01–1.03), p&amp;lt;0.001; respectively) and mortality (OR 1.29 (95% CI 1.01–1.72), p=0.03 and OR 1.01 (1.003–1.03), p&amp;lt;0.001; respectively). C-Statistic of LPI and GRACE were similar both for the combined end point (LPI: 0.73 versus GRACE: 0.72, p=0.3) and for mortality (LPI: 0.70 versus GRACE: 0.73, p=0.4). Conclusions The LPI was an independent predictor of the combined point and in-hospital mortality, with a similar discrimination capacity as the GRACE score. The presence of LPI&amp;gt;24 in patients with GRACE&amp;gt;140 identifies a very high-risk subgroup. LPI is a very easily obtained marker that could be useful in risk stratification in patients with NSTEACS. Funding Acknowledgement Type of funding sources: None. Gradient of events according groups

Insights on clinical outcomes in according to age in patients undergoing Transcatheter Aortic Valve Replacement

Abstract Transcatheter Aortic Valve Replacement (TAVR) is considered the treatment in patients older or at high or intermediate risk. Results form contemporary randomized trials in low-risk patients will likely broaden the indication of TAVR, but the data regarding long-term are limited by older population. The aim of this study was to evaluate the survival and the factors predicting mortality after TAVR in according to age. Methods From April 2008 to December 2019, the self-expandable and balloon-expandable prostheses were was implanted in 765 patients with symptomatic severe aortic stenosis with deemed high risk on base to age, &amp;lt;80 years and ≥80 years old. The rate of acute complications was defined by the combined endpoint of death, vascular complications, myocardial infarction, majopr bleeding or stroke. Results The mean age in patients &amp;lt;80 compared with ≥80 years, was 73.69±6.5 vs. 83.4±2.1 years and the logistic EuroSCORE and STS score were 15.9±11% vs. 18±11%, 4.8±3 vs. 6.3±4, p&amp;gt;0.001, respectively In-hospital mortality was 4% vs. 3.4%, p=0.404, and the rate of acute complications was 19.6 vs. 16.5%, p=0.168. The late mortality (beyond 30 days) was 36.9 vs. 35.2%, p=0.352. When compared in both groups, there were no differences for the presence of threatening bleeding 3.4% vs. 3.2% (HR = 1.028 [IC95% 0.722–1.463], p=0.516), myocardial infarction 4% vs. 2.5% (HR = 1.263 [IC95% 0.814–1.960], p=0.167), stroke 8% vs. 9.1% (HR = 1.149 [IC95% 0.686–1.925], p=0.347) and acute kidney innjury 14.1% vs. 19.1% (HR=0.1.14 [IC95% 0.969–2.141], p=0.071) and there was difference in between groups in hospitalizations for heart failure 14.6% vs. 7.9% (HR = 1.398 [IC95% 1.075–1.817], p=0.008 Survival at 1, 3, and 5were similar in both groups (88% vs. 89.5%, 73.3 vs. 78.2%, 58.8 vs. 62.6%, log Rank 0.992, p=0.319), respectively, after a mean follow-up of 42.3±27 months. The main predictors of cumulative mortality in young patients were: Charlson index [HR 1.18 (95% CI 1.06–1.30), p=0.001], Acute Kidney Injury [HR 2.21 (95% CI 1.42–3.47), p=0.001], Left ventricular ejection fraction [HR 1.02 (95% CI 1.009–1.035), p=0,001], and protective factor was a higher Karnosfky index [HR 0.98 (95% CI 0.97–0.99) p=0.006]. And in older patients were: Frailty [HR 1.67 (95% CI 1.13–2.47), p=0.010], COPD [HR 2.09 (95% CI 1.41–2.91), p=0,001], Stroke [HR 3.01 (95% CI 1.54–5.89), p=0.001] Charlson index [HR 1.14 (95% CI 1.02–1.27), p=0.015], Acute Kidney Injury [HR 1.57 (95% CI 1.06–2.32), p=0.001. Conclusions TAVR is associated with low complications rate in young and older patients. Survival during follow-up was similar in both groups, but the predictive factors of mortality differ, with greater impact on the comorbidtiy in the elderly patients Funding Acknowledgement Type of funding sources: None.

Prognostic value of three dimensional-vena contracta area in patients with secondary mitral regurgitation

Abstract Background Effective regurgitant orifice area (EROA) is an important quantitative measurement for mitral regurgitation (MR) grading. Yet, the accuracy of this method is limited in patients with secondary mitral regurgitation (SMR). Three-dimensional (3D) color Doppler echocardiography allows for the direct assessment of the vena contracta area (VCA). The prognostic value of 3D-VCA in patients with secondary MR has not been investigated. Purpose The aim of the present study was to assess the association between 3D-VCA and prognosis of patients with SMR. Methods A total of 218 patients (69% men, median age 74 years) with significant SMR were retrospectively analyzed. 3D-VCA was measured offline with dedicated software, from restored 3D color Doppler full volume datasets of the mitral valve (Figure 1). The population was divided according to the American College of Cardiology expert recommendation for the grading of severe MR (VCA ≥50 mm2 and VCA &amp;lt;50 mm2). Patients were followed up for the combined end point of all-cause mortality or heart failure hospitalization. Results Of the total population, 63% had an ischemic etiology, 60% had atrial fibrillation and 25% cardiac resynchronization therapy. Patients with 3D-VCA ≥50 mm2 needed more diuretic therapy, had a larger left ventricle and atrium, and had more post-procedural residual MR. A total of 82% of patients underwent MitraClip device implantation, 17% had mitral valve repair and 1% had mitral valve replacement. During a median follow-up of 28 months, 130 (60%) met the combined end point (101 (46%) patients died and 81 (37%) were hospitalized due to heart failure). When dividing the population according to the cut-off of 3D-VCA, patients with a 3D-VCA≥50 mm2 had a worse prognosis compared with their counterparts (Figure 2). In a multivariable Cox regression analysis, 3D-VCA≥50 mm2 remained independently associated with the composite endpoint of all-cause mortality or heart failure hospitalization (HR=1.454, 95% CI 1.020–2.072, p=0.038). Conclusion In patients with SMR, a 3D-VCA ≥50 mm2 was independently associated with a combined endpoint of death or heart failure hospitalization. Funding Acknowledgement Type of funding sources: None. Figure 1. Method of 3D-VCA measurementFigure 2. Kaplan-Meier survival curve

Long-Term survival and functional status in patients with elevated mitral valve pressure gradient after transcatheter mitral valve repair

Abstract Background A growing number of patients are currently treated for severe mitral regurgitation (MR) using a transcatheter mitral valve repair (TMVr). In clinical routine, the potential risk of elevated post-procedural mitral valve pressure gradient (MPG) may prohibit optimal MR reduction driven by the avoidance of additional clip implantations. Thus, the unfavorable impact on survival and functional outcome of increased MPG in patients undergoing TMVr is currently debatable. Methods In this single-center, prospective study, survival and functional outcome of 780 consecutive patients with severe MR undergoing TMVr between September 2008 and January 2020 were investigated. After exclusion of patients with unsuccessful procedure and those lost to follow-up, data of 676 patients with a median follow-up time of 5.26 (5.11, 5.51) years were analyzed. MPG was determined by transthoracic echocardiography at discharge and considered elevated in excess of 4.5 mmHg. Kaplan-Meier analysis as well as multivariable Cox regression models were performed for the impact on elevated MPG on 5-year outcomes for the subgroups of functional MR (FMR) and degenerative MR (DMR). The primary outcome measure was a combined endpoint of death or rehospitalization for congestive heart failure. Results Among 676 patients undergoing TMVr (mean age 74.6±8.5 years, 59.0% male, median STS Score 3.9 [interquartile range 2.5; 6.0]), 179 (26.4%) patients had elevated MPG &amp;gt;4.5 mmHg. FMR was present in 426 (63.0%) patients. In the overall patient cohort, Kaplan-Meier and Cox Regression analyses could not demonstrate significant differences for the combined endpoint (p=0.99). In contrast, subgroup analysis according to MR etiology indicated a significant adverse influence of elevated MPG on the combined endpoint as well as functional outcome in patients with DMR, but not with FMR (Figure 1). After adjustment, multivariate Cox Regression analysis showed an inferior prognosis in patients with DMR and elevated MVPG &amp;gt;4.5 mmHg (hazard ratio 1.79 [1.17, 2.72], p=0.0069, Figure 2). Conclusions TMVr-patients with DMR and measurable elevated post-procedural MVPG face an inferior prognosis and reduced functional outcomes compared to patients with FMR. Funding Acknowledgement Type of funding sources: None. Figure 1Figure 2

Long-term outcomes in patients undergoing transcatheter aortic valve implantation: insights on clinical outcomes and prognostic markers from a large cohort of patients

Abstract Transcatheter Aortic valve Replacement (TAVR) has emerged as paradigm shift in the treatment of patients with severe symptomatic aortic stenosis. Clinical and performance data on long-term TAVR are still limited. The aim of this study was to determine the survival and the factors predicting mortality after TAVR with the first and second generation of prostheses. Methods From April 2008 to December 2019, the auto-expandible prostheses were implanted in 765 patients with symptomatic severe aortic stenosis with deemed high risk. The first generation prostheses included CoreValve and Accutrak System and the second prostheses included Evolut R and Pro. Results The mean age was 79.4±6.6 years. The logistic EuroSCORE and STS score were 17.1±11% and 5.7±3.9%, respectively. The implantation success rate was 98.87%. In-hospital mortality was 3.7%, and the combined endpoint of death, vascular complications, myocardial infarction or stroke had a rate of 15.1%. The clinical outcomes in according to prosthesis generation were, for pacemaker requirement (CoreValve vs. Accutrak system vs. Evolut R vs. and Evolut pro) 35.3% vs. 26.1% vs. 14.3% vs. 14%, p=0.001; and the paravalvular aortic regurgitation, were: none 28% vs. 44.8% vs. 43.3% vs. 58; mild 40% vs. 32.3% vs. 30.8% vs. 35.2%; moderate 32% vs. 20.3 vs. 23.9% vs. 5.7%; severe 0% vs. 2.6% vs. 0% vs. 1.1, p 0.001 The late mortality (beyond 30 days) was 35.9%. Survival at 1, 3, 5, 7 and 9 years were 88.9%, 76.1%, 61.1%, 44% and 32.6% respectively, after a mean follow-up of 42.3±27 months. The NYHA functional class improved from 3.1±0.6 to 1.77±0.7 in the follow-up. At 5 years, 5 patients had severe prosthetic valve dysfunction (severe stenosis and moderate transvalvular regurgitation The predictors of cumulative mortality were: Charlson index [HR 1.25 (95% CI 1.077–1.461), p=0.004], Readmision Heart Failure [HR 3.02 (95% CI 1.554–5.879), p=0.001], stroke post-TAVR [HR 3.472 (95% CI 1.115–10.53), p=0.032], residual aortic regurgitation [HR 1.45 (95% CI 1.093–1.934), p=0,010], and severe pulmonary hypertension [HR −0.983 (95% CI 0.645–0.423) p=0.032]. Conclusions TAVR is associated with significant survival benefit throughout 3.09 years of follow-up. Survival during follow-up depends particularly among patients with associated comorbidities and cardiac markers such as aortic regurgitation or pulmonary hypertension Funding Acknowledgement Type of funding sources: None.

The ISCHEMIA trial: optimal medical therapy against PTCA in the stable patient: the endless story.

In patients with acute coronary syndrome, an aggressive approach with coronary angiography and revascularization leads to important benefits compared to medical therapy alone. On the contrary, the prognostic impact of coronary revascularization in patients suffering from stable coronary artery disease has long been the subject of debate. The pivotal study in this area is COURAGE, published in 2007, in which coronary revascularization showed no benefit about the combined endpoint of death from all causes and acute myocardial infarction (AMI), compared to medical therapy. The ISCHEMIA study, published in 2020, compared selective coronary angiography and revascularization vs. a non-invasive approach. By protocol, the patients were initially evaluated with coronary computed axial tomography angiography: in case of coronary stenosis >50%, they were then randomized to the two strategies. While in the invasive arm patients were revascularized, in the non-invasive arm revascularization was used only in case of patient destabilization. As in COURAGE, the results of ISCHEMIA did not demonstrate superiority of revascularization over medical therapy alone for a combined endpoint of cardiovascular death, AMI, or hospitalization for unstable angina, heart failure, or cardiac arrest. Based on recent evidence from ISCHEMIA, it is therefore confirmed that coronary revascularization in stable patients does not seem to improve the prognosis compared to medical therapy alone.

Pre-medication with oral anticoagulants is associated with better outcomes in a large multinational COVID-19 cohort with cardiovascular comorbidities

AimsCoagulopathy and venous thromboembolism are common findings in coronavirus disease 2019 (COVID-19) and are associated with poor outcome. Timely initiation of anticoagulation after hospital admission was shown to be beneficial. In this study we aim to examine the association of pre-existing oral anticoagulation (OAC) with outcome among a cohort of SARS-CoV-2 infected patients.Methods and resultsWe analysed the data from the large multi-national Lean European Open Survey on SARS-CoV-2 infected patients (LEOSS) from March to August 2020. Patients with SARS-CoV-2 infection were eligible for inclusion. We retrospectively analysed the association of pre-existing OAC with all-cause mortality. Secondary outcome measures included COVID-19-related mortality, recovery and composite endpoints combining death and/or thrombotic event and death and/or bleeding event. We restricted bleeding events to intracerebral bleeding in this analysis to ensure clinical relevance and to limit reporting errors. A total of 1 433 SARS-CoV-2 infected patients were analysed, while 334 patients (23.3%) had an existing premedication with OAC and 1 099 patients (79.7%) had no OAC. After risk adjustment for comorbidities, pre-existing OAC showed a protective influence on the endpoint death (OR 0.62, P = 0.013) as well as the secondary endpoints COVID-19-related death (OR 0.64, P = 0.023) and non-recovery (OR 0.66, P = 0.014). The combined endpoint death or thrombotic event tended to be less frequent in patients on OAC (OR 0.71, P = 0.056).ConclusionsPre-existing OAC is protective in COVID-19, irrespective of anticoagulation regime during hospital stay and independent of the stage and course of disease.Graphic abstract

PROGNOSTIC VALUE OF SERUM URIC ACID IN PATIENTS WITH ACUTE HEART FAILURE:A META-ANALYSIS

Our meta-analysis aimed to determine the prognostic significance of SUA level in patients with AHF.We made a comprehensive search in databases from inception to April 6, 2018. All available observational studies that evaluated the prognostic value of SUA level in patients with AHF were eligible. Outcome of interests were all-cause mortality and the combined endpoint of death or readmission. Prognostic values of SUA level were summarized as higher vs lower SUA category or per 1 mg/ml SUA rise.Eleven studies involving 12,854 AHF patients were identified and analyzed. AHF patients with the highest SUA level had an increased risk of all-cause mortality (risk ratio [RR] 1.43; 95% confidence intervals [CI] 1.31–1.56) and combined endpoint of death or readmission (RR 1.68; 95% CI 1.33–2.13) after adjusting potential variables. In addition, per 1 mg/ml SUA rise significantly increased by 11% and 12% higher risk all-cause mortality and combined endpoint of death or readmission, respectively..This meta-analysis indicates that elevated SUA level independently predicts all-cause mortality and the combined endpoint of death or readmission in AHF patients. Measurement of SUA level may improve risk stratification of adverse outcomes in these patients

Hypothermia for moderate or severe neonatal encephalopathy in low-income and middle-income countries (HELIX): a randomised controlled trial in India, Sri Lanka, and Bangladesh

SummaryBackgroundAlthough therapeutic hypothermia reduces death or disability after neonatal encephalopathy in high-income countries, its safety and efficacy in low-income and middle-income countries is unclear. We aimed to examine whether therapeutic hypothermia alongside optimal supportive intensive care reduces death or moderate or severe disability after neonatal encephalopathy in south Asia.MethodsWe did a multicountry open-label, randomised controlled trial in seven tertiary neonatal intensive care units in India, Sri Lanka, and Bangladesh. We enrolled infants born at or after 36 weeks of gestation with moderate or severe neonatal encephalopathy and a need for continued resuscitation at 5 min of age or an Apgar score of less than 6 at 5 min of age (for babies born in a hospital), or both, or an absence of crying by 5 min of age (for babies born at home). Using a web-based randomisation system, we allocated infants into a group receiving whole body hypothermia (33·5°C) for 72 h using a servo-controlled cooling device, or to usual care (control group), within 6 h of birth. All recruiting sites had facilities for invasive ventilation, cardiovascular support, and access to 3 Tesla MRI scanners and spectroscopy. Masking of the intervention was not possible, but those involved in the magnetic resonance biomarker analysis and neurodevelopmental outcome assessments were masked to the allocation. The primary outcome was a combined endpoint of death or moderate or severe disability at 18–22 months, assessed by the Bayley Scales of Infant and Toddler Development (third edition) and a detailed neurological examination. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT02387385.FindingsWe screened 2296 infants between Aug 15, 2015, and Feb 15, 2019, of whom 576 infants were eligible for inclusion. After exclusions, we recruited 408 eligible infants and we assigned 202 to the hypothermia group and 206 to the control group. Primary outcome data were available for 195 (97%) of the 202 infants in the hypothermia group and 199 (97%) of the 206 control group infants. 98 (50%) infants in the hypothermia group and 94 (47%) infants in the control group died or had a moderate or severe disability (risk ratio 1·06; 95% CI 0·87–1·30; p=0·55). 84 infants (42%) in the hypothermia group and 63 (31%; p=0·022) infants in the control group died, of whom 72 (36%) and 49 (24%; p=0·0087) died during neonatal hospitalisation. Five serious adverse events were reported: three in the hypothermia group (one hospital readmission relating to pneumonia, one septic arthritis, and one suspected venous thrombosis), and two in the control group (one related to desaturations during MRI and other because of endotracheal tube displacement during transport for MRI). No adverse events were considered causally related to the study intervention.InterpretationTherapeutic hypothermia did not reduce the combined outcome of death or disability at 18 months after neonatal encephalopathy in low-income and middle-income countries, but significantly increased death alone. Therapeutic hypothermia should not be offered as treatment for neonatal encephalopathy in low-income and middle-income countries, even when tertiary neonatal intensive care facilities are available.FundingNational Institute for Health Research, Garfield Weston Foundation, and Bill & Melinda Gates Foundation.TranslationsFor the Hindi, Malayalam, Telugu, Kannada, Singhalese, Tamil, Marathi and Bangla translations of the abstract see Supplementary Materials section.

Valor pronóstico de un nuevo modelo de evaluación clínica de pacientes ambulatorios con insuficiencia cardiaca

Introduction and objectivesTo assess the prognostic value of a 5-item clinical model based in the IC-BERG recommendations to evaluate ambulatory patients with heart failure (HF) in the clinic. MethodsObservational study based on the historical cohort of patients with HF referred to a specific facility since 2010 to 2019. The presence of 5 clinical ítems was evaluated: NYHA III-IV class, signs of congestion, admission due to decompensation in the previous year, daily dose≥40mg furosemide or equivalent, and NT-proBNP≥1,000pg/ml. The incidence of adverse clinical events was assessed by means of the Kaplan-Meier method and multivariable Cox's regression. ResultsWe studied 1909 patients, whose mean number of clinical ítems indicating risk was 2.29. Kaplan-Meier survival analysis showed an incremental trend between an increasing number of clinical ítems of risk and the combined event death or admission due to HF, overall mortality, and cardiovascular mortality (P<.001). Adjusted hazard-ratio for the combined end-point death or admission due to HF, as estimated by means of multivariable Cox's regression, were 1.47 (95%CI, 1–2.15), 2.03 (95%CI, 1.41–2.92), 2.98 (95%CI, 2.08–4.28), 5.07 (95%C,: 3.51–7.32), and 7.73 (95%CI, 5.21–11.45) for patients who showed 1, 2, 3, 4, or 5 clinical ítems indicating risk, respectively. The proportional weight of cardiovascular causes of risk, especially refractory HF, was higher in patients with a higher number of clinical ítems of risk. ConclusionsThis study supports the prognostic value of a 5-item clinical model based on IC-BERG recommendations in ambulatory patients with HF.

Relation of Guideline Adherence to Outcomes in Patients With Asymptomatic Severe Primary Mitral Regurgitation

Current guidelines empirically recommend serial clinical evaluations for asymptomatic patients with severe mitral regurgitation (MR). However, there is a paucity of data on the effectiveness of such monitoring. This study sought to examine the potential benefit of guideline adherence among asymptomatic patients with severe primary MR. Asymptomatic patients with severe primary MR who had been evaluated in the Allina Health system between January 1, 2012 and May 30, 2018 were examined. The medical records were manually reviewed for demographics, comorbidities, echocardiographic data, subsequent interventions, and clinical outcomes. Patients were grouped according to occurrence of guideline adherence, which was defined as a serial clinical evaluation with echocardiography every 12 ± 1 month until mitral valve surgery, or death. Over the study period, 246 patients (67.3 ± 15.5 years, 61.4% men) with severe, asymptomatic primary MR were identified, including 154 patients (62.6%) with and 92 patients (37.4%) without guideline adherence. Overall, there were no differences in demographics, morbidities, MR severity, or left ventricular function between patient adherence groups. During follow-up (40.9; 21.2, 58.3 months), patients with adherence more frequently had surgery or transcatheter therapy performed (64.3% vs 18.5%; p <0.001) and the time to intervention was earlier (13.6 [3.9-22.7] vs 44.2[25.6-57.3] months; p <0.001). Compared to non-adherent patients, those with guideline adherence had a significantly higher five-year survival free from all-cause mortality (92.0% vs 74.3%, p=0.002), and freedom from death or hospitalization for heart failure (90.1% vs 69.3%, p=0.001). Adherent patients also had a significantly better survival free from combined endpoint of death, re-hospitalization for heart failure, myocardial infarction, and stroke (84.5% vs 63.2%, p=0.002). In patients with asymptomatic severe primary MR, guideline adherence with serial evaluations every 12 months or less is associated with earlier therapy and improved long-term outcomes. These data support educational efforts to promote guideline adherence.

Better outcome at lower costs after implementing a CRT-care pathway: a comprehensive evaluation of real-world data

Abstract Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Medtronic plc. Background Cardiac resynchronization therapy (CRT) requires intensive, complex and multi-disciplinary care to maximize clinical benefit in heart failure patients. In current practice, this is often incomplete due to limitations in time, resources and coordination of care. Purpose We evaluated the effect of the introduction of a novel multidisciplinary, standardized CRT care pathway (CRT-CPW) compared with usual care, on clinical outcome and costs. Methods The CRT care pathway (CRT-CPW) design, based on an expert consensus of experienced European CRT specialists; focussed on structuring patient selection, implantation and follow-up heart failure treatment and device management. To facilitate and guarantee quality, checklists fitted to each moment in the care pathway were designed, to aid contributors. The CRT-CPW was implemented in the Maastricht University Medical Centre in 2014. Data from patients receiving usual care (2012-2014, 222 patients) and patients receiving care under the CRT-CPW (2015-2018, 241 patients) were compared. Data was extracted from the hospital information system. The primary outcome was the composite of all-cause mortality and heart failure (HF) hospitalization. Hospital-related costs of cardiovascular care after CRT implantation was analysed to address cost-effectiveness. Results Patient demographics were comparable in both groups, except that the CRT-CPW group showed more AF and previous myocardial infarction at baseline. The combined endpoint of death from any cause and admission for HF occurred in 127 patients (57.2%) in the usual care group and 64 patients (26.6%) in the CRT- CPW group (adjusted HR 0.68 (95% CI, 0.49 to 0.93), p = 0.015) (Figure 1A). Total costs for cardiology related hospitalizations reduced significantly in the CRT care pathway group (€ 19.177 ± 9.692 vs 20.613 ± 7.066, p&amp;lt; 0.001, Table 4). Bootstrap analyses revealed that 90.7% of samples would show improved outcomes as well as reduction in costs in the CRT-CPW treatment group (Figure 1B). Conclusion The introduction of a novel CRT-CPW resulted in improved clinical outcome and reduced costs. Abstract Figure 1 Clinical outcome and costs