Composite Endpoint Of All-cause Death Research Articles

Breaking the 30-day barrier: Long-term effectiveness of a nurse-led 7-step transitional intervention program in heart failure.

Heart failure (HF) programs successfully reduce 30-day readmissions. However, conflicting data exist about its sustained effects afterwards and its impact on mortality. We evaluated whether the impact of a new nurse-led coordinated transitional HF program extends to longer periods of time, including 90 and 180 days after discharge. We designed a natural experiment to undertake a pragmatical evaluation of the implementation of the program. We compared outcomes between patients discharged with HF as primary diagnosis in Period #1 (pre-program; Jan 2017-Aug 2017) and those discharged during Period #2 (HF program; Sept 2017-Jan 2019). Primary endpoint was the composite of all-cause death or all-cause hospitalization 90 and 180 days after discharge. 440 patients were enrolled: 123 in Period #1 and 317 in Period #2. Mean age was 75±9 years. There were more females in Period #2 (p = 0.025), with no other significant differences between periods. The primary endpoint was significantly reduced in the HF program group, at 90 [adjusted OR 0.31 (0.18-0.53), p <0.001] and at 180 days [adjusted OR 0.18 (CI 0.11-0.32), p <0.001]. Such a decrease was due to a reduction in cardiovascular (CV) and HF hospitalization. All-cause death was reduced when a double check discharge planning was implanted compared to usual care [0 (0%) vs. 7 (3.8%), p = 0.022]. A new nurse-led coordinated transitional bundle of interventions model reduces the composite endpoint of all-cause death and all-cause hospitalization both at 90 and 180 days after a discharge for HF, also in high-risk populations. Such a decrease is driven by a reduction of CV and HF hospitalization. Reduction of all-cause mortality was also observed when the full model including a more exhaustive discharge planning process was implemented.

βeta blocker interruption after uncomplicated myocardial infarction: rationale and design of the randomized ABYSS trial

The long-term use of β-blocker after myocardial infarction (MI) when global left ventricular ejection fraction (LVEF) is preserved has not been studied in the era of modern myocardial reperfusion and secondary prevention therapies. It is unknown whether β-blockers are useful in stable post-MI patients without reduced LVEF and without heart failure. The Assessment of β-blocker interruption 1 Year after an uncomplicated myocardial infarction on Safety and Symptomatic cardiac events requiring hospitalization (ABYSS) Trial enrolled in 49 centers in France, 3,700 patients with a prior (>6 months) history of MI and a LVEF >40%, chronically treated with a β-blocker and without any major cardiovascular event (MACE) in the past 6 months. These patients were randomized to interruption or continuation of their β-blocker therapy. The primary objective is to demonstrate the noninferiority of interruption vs continuation of the β-blocker therapy on the primary composite endpoint of all-cause death, stroke, MI, hospitalization for any cardiovascular reason at the end of follow-up (accrual follow-up) with a one-year minimum follow-up for the last randomized patient. Secondary objectives will focus on patient reported outcomes with the evaluation of the quality of life before and after randomization with the EQ5D-5L questionnaire. Enrolment has been completed. The ABYSS trial evaluates the cardiovascular safety of β-blocker interruption in stabilized post-MI patients without heart failure nor reduced LVEF. ABYSS trial is a reappraisal of β-blockers life-long therapy in stable post-MI patients without reduced LVEF. NCT03498066 (clinicaltrials.gov).

Prognostic Value of RV Abnormalities on CMR in Patients With Known or Suspected Cardiac Sarcoidosis

BackgroundLeft ventricular abnormalities in cardiac sarcoidosis (CS) are associated with adverse cardiovascular events, whereas the prognostic value of right ventricular (RV) involvement found on cardiac magnetic resonance is unclear. ObjectivesThis study aimed to systematically assess the prognostic value of right ventricular ejection fraction (RVEF) and RV late gadolinium enhancement (LGE) in known or suspected CS. MethodsThis study was prospectively registered in PROSPERO (CRD42022302579). PubMed, Embase, and Web of Science were searched to identify studies that evaluated the association between RVEF or RV LGE on clinical outcomes in CS. A composite endpoint of all-cause death, cardiovascular events, or sudden cardiac death (SCD) was used. A meta-analysis was performed to determine the pooled risk ratio (RR) for these adverse events. The calculated sensitivity, specificity, and area under the curve with 95% CIs were weighted and summarized. ResultsEight studies including a total of 899 patients with a mean follow-up duration of 3.2 ± 0.7 years were included. The pooled RR of RV systolic dysfunction was 3.1 (95% CI: 1.7-5.5; P < 0.01) for composite events and 3.0 (95% CI: 1.3-7.0; P < 0.01) for SCD events. In addition, CS patients with RV LGE had a significant risk for composite events (RR: 4.8 [95% CI: 2.4-9.6]; P < 0.01) and a higher risk for SCD (RR: 9.5 [95% CI: 4.4-20.5]; P < 0.01) than patients without RV LGE. Furthermore, the pooled area under the curve, sensitivity, and specificity of RV LGE for identifying patients with CS who were at highest SCD risk were 0.8 (95% CI: 0.8-0.9), 69% (95% CI: 50%-84%), and 90% (95% CI: 70%-97%), respectively. ConclusionsIn patients with known or suspected CS, RVEF and RV LGE were both associated with adverse events. Furthermore, RV LGE shows good discrimination in identifying CS patients at high risk of SCD.

Functional Insufficiency of Mitral and Tricuspid Valves Associated With Atrial Fibrillation: Impact of Postoperative Atrial Fibrillation Recurrence on Surgical Outcomes.

To identify the factors associated with adverse outcomes following surgery for functional insufficiency of the mitral valve (MV) or tricuspid valve (TV) associated with atrial fibrillation (AF). We evaluated 100 patients (age, 66.5±10.0 years; 47 males) who consecutively underwent surgery for functional insufficiency of the MV or TV associated with AF between January 2000 and December 2020 at our center. The primary outcome was a composite endpoint of all-cause death, valve reoperation, congestive heart failure (CHF) requiring rehospitalization, and stroke. During follow-up (532 patients-years [PYs]), adverse events included death in 16 (3.0%/yr), MV reoperation in 1 (0.2%/yr), CHF in 14 (2.6%/yr), and stroke in 5 (0.9%/yr) patients, demonstrating a 5-year rate of freedom from the primary endpoint of 69.5%. The rate of postoperative AF was high even in those who underwent AF ablation (n=92), with cumulative rates of 48.1% at 1 year and 60.2% at 5 years. In multivariable analyses, the primary outcome was significantly associated with age (adjusted hazard ratio [aHR], 1.06; 95% confidence interval [CI], 1.02-1.10; p=0.005), chronic kidney disease (aHR, 7.76; 95% CI, 2.28-26.38; p=0.001), left atrial appendage exclusion (aHR, 0.35; 95% CI, 0.16-1.78; p=0.010), and postoperative AF as a time-varying covariate (aHR, 3.33; 95% CI, 1.50-7.40; p=0.003). Among patients undergoing surgery for functional atrioventricular insufficiency associated with AF, a significant proportion showed recurrence of AF over time after concomitant AF ablation, which was significantly associated with poor clinical outcomes.

306 HEART FAILURE AS THE CANCER FOR THE HEART: THE PROGNOSTIC ROLE OF THE HLM SCORE

Abstract Background The multiorgan involvement of heart failure is similar to the spread observed in cancer. We proposed a new score, named HLM, analogous to TNM classification used in oncology. HLM refers to (i) H: heart damage, instead of “T” for tumor; (ii) L: lung involvement, instead of “N” for lymph nodes; (iii) M: systemic multiorgan involvement, instead of “M” for metastasis. Objectives to compare HLM score to NYHA class, ACC/AHA stages and left ventricular ejection fraction (LVEF) classification, to assess the most accurate prognostic tool for HF patients. Methods We performed a multicentric, observational, prospective study of consecutive patients admitted for HF, or at risk for HF. Parameters for heart, lungs and organs’ function were collected. Each patient was classified according to HLM, NYHA, ACC/AHA stages and LVEF classification. Patients were followed up for 12 months. The primary composite endpoint was all-cause death and rehospitalization due to HF. Results We enrolled 1720 patients who completed the 12-month follow-up. As shown by Kaplan Meier curves, HLM was the most accurate score to predict primary endpoint at 12- month. The area under the ROC curve (AUC) was greater for HLM score than NYHA, ACC/AHA stages and LVEF classification, regarding the composite endpoint (HLM=0.645; NYHA=0.580; ACC/AHA=0.589; LVEF=0.572) (Figure 1). HLM score related AUC showed statistically significant differences compared to LVEF (p=0.002), ACC/AHA (p=0.029) and NYHA (p=0.009). Conclusions HLM score has a greater prognostic power compared to other nosologies, in terms of the composite endpoint of all-cause death and rehospitalization due to HF, at 12-month follow-up. Key words: heart failure; HLM score; prognosis; mortality; rehospitalization. Figure 1.

Abstract 9964: Clinical Impact of Handgrip Strength on Prognosis After Percutaneous Coronary Intervention

Introduction: Sarcopenia is defined as age-related loss of skeletal muscle mass and strength, and has been reportedly associated with cardiovascular disease. However, the impact of handgrip strength (HGS) on clinical outcomes after percutaneous coronary intervention (PCI) in patients with coronary artery disease has not been well investigated. Methods: This was a retrospective, single center, observational study. A total of 469 patients who underwent PCI were included. Periprocedural HGS of both hands were measured and of which better value was used for assessment. Patients were divided into 2 groups, low HGS group (men;&lt;28kg, women;&lt;18kg) and high HGS group (men;≥28kg, women;≥18kg) according to the consensus of Asian Working Group for Sarcopenia. The primary outcome was the composite endpoint of all-cause death, myocardial infarction, and heart failure readmission. Results: There were 151 patients in the low HGS group and 318 patients in the high HGS group. The age of patients in the low HGS group was significantly higher (78 [71-82] vs. 70 [61-75] years, p&lt;0.001), while the body mass index and serum albumin level were significantly lower than those in the high HGS group. During the median follow-up period of 778 days, composite endpoint occurred in 35 patients with low HGS and 29 patients with high HGS. The low HGS group had a higher incidence of composite endpoint than the high HGS group (p&lt;0.001) (Figure). The low HGS group had a higher risk of individuals of all-cause, cardiac, and non-cardiac death (p&lt;0.001, respectively). Multivariate Cox proportional hazards analysis showed that low HGS was an independent predictor for the composite endpoint (HR 1.86, 95% CI 1.04-3.33, p=0.04). Conclusions: Low HGS was independently related with long-term cardiac events after PCI.

Abstract 10126: Impact of Albuminuria on Prognosis After Transcatheter Aortic Valve Replacement for Aortic Stenosis

Introduction: Albuminuria is a well-known risk factor of cardiovascular events. However, the impact of albuminuria on the prognosis in patients with aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI) has not been studied. Methods: This is a single-center retrospective observational study. Consecutive patients who underwent TAVI for severe AS and whose preoperative urinary data were available were included. Finally, 228 patients were investigated. Patients were divided into two groups according to the preoperative urinary albumin-to-creatinine ratio (ACR): high (ACR≥ 30 mg/g) and low (ACR&lt;30 mg/g). Total protein to creatinine ratio (PCR) and dipstick proteinuria were also evaluated. The primary outcome was a composite endpoint of all-cause death and readmission due to heart failure. Results: There were 117 patients with a high ACR and 111 patients with a low ACR. At baseline, patients with a high ACR had significantly lower eGFR than those with a low ACR. During the median follow-up period of 467 days, the patients with a high ACR had higher incidence of a primary endpoint than those with a low ACR (p&lt;0.001). The individual incidence of all-cause death, cardiac death and heart failure readmission were also significantly higher in patients with a high ACR than those with a low ACR. Patients with PCR≥150mg/g or positive dipstick proteinuria were at a higher risk of primary endpoint as well (p&lt;0.001 and p=0.008, respectively), however, there was no significant difference between the patients with eGFR&lt;60 and ≥60 mL/min/1.73m 2 (Figure). Multivariate Cox proportional hazards analysis showed a high ACR was independently associated with a primary endpoint (HR, 4.98; 95% CI, 1.84-13.49; p=0.002). Conclusions: Preoperative albuminuria (ACR≥ 30 mg/g) is an independent predictor of cardiac events in the patients with severe AS undergoing TAVI. PCR≥150 mg/g and positive dipstick albuminuria are also useful for risk prediction.

Abstract 14664: Heart Failure as the Cancer for the Heart: The Prognostic Role of the New HLM Score

Introduction: The multiorgan involvement of heart failure is similar to the spread observed in cancer. We proposed a new score system, named HLM, analogous to TNM classification used in oncology. HLM refers to (i) H: heart damage, instead of “T” for tumor; (ii) L: lung involvement, instead of “N” for lymph nodes; (iii) M: involvement of peripheral organs, instead of “M” for metastasis. Hypothesis: to compare HLM score to NYHA class, ACC/AHA stages and HF classification by left ventricular ejection fraction (LVEF), to assess the most accurate prognostic tool for HF patients. Methods: We performed a multicentric, observational, prospective study of consecutive patients admitted for HF, or at risk for HF. All parameters for heart, lungs and organs’ function were collected. HLM score, made up of 4 stages of severity, was built starting from HLM classification. Each patient was classified according to HLM, NYHA, ACC/AHA stages and LVEF. The primary composite endpoint was all-cause death and rehospitalization due to HF; patients were followed up for 12 months. Results: We enrolled 1720 patients who completed the 12-months follow-up. As showed by Kaplan Meier curves, HLM was the most accurate score to predict primary endpoint at 12 months. The area under the ROC curve (AUC) was greater for HLM score than NYHA, ACC/AHA stages and LVEF classification, regarding the composite endpoint (HLM=0.645; NYHA=0.580; ACC/AHA=0.572; LVEF=0.572). HLM score related AUC showed statistically significant differences compared to LVEF (p=0.002), ACC/AHA (p=0.002) and NYHA (p=0.009). Conclusions: HLM score has a greater prognostic power compared to other nosologies, in terms of the composite endpoint of all-cause death and rehospitalization, at 12 months follow up.

Coronary angiography- or fractional flow reserve-guided complete revascularization in multivessel disease STEMI: A Bayesian hierarchical network meta-analysis

AimsTo identify the best strategy to achieve complete revascularization (CR) in patients with ST-elevation myocardial infarction (STEMI) and multi-vessel disease (MVD). Methods and resultsWe systematically reviewed the literature for randomized controlled trials (RCTs) comparing IRA-only PCI and CR guided by angiography or fractional flow reserve (FFR) in MVD-STEMI. Both frequentist (classical) and Bayesian network meta-analysis were performed, including a comparative hierarchy estimation of the probability to reduce the primary composite endpoint of all-cause death and new myocardial infarction (MI). We identified 11 RCTs, including 8193 STEMI patients. Compared with IRA-only strategy, CR significantly reduced the primary endpoint (OR: 0.73; 95%CI0.55–0.97). We observed non-significant difference between angiography and FFR guidance in reducing the primary endpoint (OR: 0.73, 95% CI 0.35–1.57). The Bayesian probability analysis ranked angio-guided CR as the best intervention yielding lowest risk of all-cause death or new MI (SUCRA92%). ConclusionsIn patients with MVD-STEMI, CR is associated with a reduction in all-cause mortality and new MI compared with IRA-only PCI. Angio-guided CR is associated with the lowest risk of all-cause death or new MI, therefore the role of FFR-guidance in this setting is questionable. Condensed abstractBoth frequentist and Bayesian network meta-analysis were performed to compare infarct-related artery (IRA)-only percutaneous coronary intervention (PCI) and complete revascularization (CR) guided by angiography or fractional flow reserve (FFR) in multivessel disease (MVD) and acute ST-elevation myocardial infarction (STEMI). Eleven randomized controlled trials were identified, including 8193 STEMI patients. Compared with IRA-only strategy, CR significantly reduced the incidence of the composite endpoint of all-cause death and new myocardial infarction without significant difference in angio-guided and FFR-guided CR. The Bayesian probability analysis ranked angio-guided CR as the best intervention yielding lowest risk of the composite endpoint and, therefore the role of FFR-guidance in this setting is questionable.

Antiplatelet therapy at discharge and long-term prognosis in Takotsubo syndrome: Insights from the Spanish National Registry (RETAKO)

IntroductionEndothelial dysfunction and platelet activation have been highlighted as possible mediators in Takotsubo syndrome (TTS). Nevertheless, to date, evidence on the usefulness of antiplatelet therapy in TTS remains controversial. The aim of our study is to evaluate long-term prognosis in TTS patients treated with antiplatelet therapy (APT) at hospitalization discharge. Material and methodsAn ambispective cohort study from the Spanish National Takotsubo Registry database was performed (June 2002 to March 2017). Patients were divided into two groups: those who received APT at hospital discharge (APT cohort) and those who did not (non-APT cohort). Primary endpoint was all-cause death. Secondary endpoints included the composite of recurrence or readmission and a composite of death, recurrence or readmission. ResultsFrom a total of 741 patients, 728 patients were alive at discharge. Follow-up was performed in 544 patients, who were included in the final analysis: 321 patients (59.0%) in the APT cohort and 223 patients (41.0%) in the non-APT cohort. The APT cohort had a better clinical presentation and received more heart failure and acute coronary syndrome-like therapies (angiotensin converting enzyme inhibitors/angiotensin receptor blockers: 75.1% vs. 51.1%; p<0.001, betablockers: 71.3% vs. 50.7%; p<0.001, statins: 67.9% vs. 33.2%; p<0.001). After adjusting for confounder factors, APT at discharge was a protective factor for all-cause death (adjusted hazard ratio (HR) 0.315, 95% confidence interval (CI): 0.106-0.943; p=0.039) and the composite endpoint of all-cause death, recurrence or readmission (adjusted HR 0.318, 95% CI: 0.164-0.619; p=0.001) at month 25 of follow-up. ConclusionPatients with TTS receiving APT at discharge presented better prognosis up to two-years of follow-up compared with their counterparts not receiving APT.

Reduced Incidence of Severe Coronary Atherosclerosis in Obese Subjects With Type 2 Diabetes – An Obesity Paradox?

An obesity paradox wherein a lower incidence of cardiovascular (CV) morbidity and mortality is seen in overweight/ obese patients compared with patients with a ‘normal’ body mass index (BMI) has been reported in patients with type 2 diabetes mellitus (T2DM). We evaluated the relationship between BMI and coronary atherosclerosis in a cohort of subjects with T2DM who were asymptomatic for CV disease using computed tomography coronary angiography. Subjects were followed up for a composite endpoint of all-cause death, non-fatal myocardial infarction or late coronary artery revascularisation. Of the 258 patients enrolled, 226 were eligible for follow-up over a median of 22.8 months. In patients with a normal BMI (&lt;25 kg/m2), 53% had ≥1 significantly stenotic plaque compared with 26% of patients with a BMI &gt;30 kg/m2 at baseline. Subjects with a BMI ≥35 kg/m2 were 82% less likely to present with significant coronary artery plaque at baseline compared with those with a BMI &lt;25 kg/m2 (p=0.01). The risk of a composite CV endpoint event in the overweight/obese group (&gt;25 kg/m2) was approximately 70% lower than in subjects with normal weight. In conclusion, higher BMI may be associated with a lower prevalence of coronary atherosclerosis in patients with T2DM.

Long-Term prognosis of radiofrequency catheter ablation for atrial fibrillation with different subtypes of heart failure in the era of ablation index guidance.

BackgroundThe long-term outcomes of ablation index (AI)-guided radiofrequency catheter ablation (RFCA) on atrial fibrillation (AF) and different subtypes of heart failure (HF) remain unknown. The aim of the study was to evaluate the long-term prognosis of AI-guided RFCA procedures in patients with AF and concomitant HF.MethodsWe retrospectively included consecutive patients with AF and HF who underwent the initial RFCA procedure with AI guidance from March 2018 to June 2021 in our institution. The patients were categorized into two groups: HF with preserved ejection fraction (HFpEF) group and HF with mid-range ejection fraction (HFmrEF) +HF with reduced ejection fraction (HFrEF) group.ResultsA total of 101 patients were included. HFpEF and HFmrEF + HFrEF groups consisted of 71 (70.3%) and 30 patients (29.7%), respectively. During a median follow-up of 32.0 (18.2, 37.6) months, no significant difference was detected in AF recurrence between groups (21.1 vs. 33.3%) after multiple procedures, whereas the incidence of the composite endpoint of all-cause death, thromboembolic events, and HF hospitalization was significantly lower in HFpEF group (9.9 vs. 25.0%, Log-rank p = 0.018). In multivariable analysis, a history of hypertension [hazard ratio (HR) 4.667, 95% confidence interval (CI) 1.433–15.203, p = 0.011], left ventricular ejection fraction (LVEF) < 50% (HR 5.390, 95% CI 1.911–15.203, p = 0.001) and recurrent AF after multiple procedures (HR 7.542, 95% CI 2.355–24.148, p = 0.001) were independently associated with the incidence of the composite endpoint.ConclusionLong-term success could be achieved in 75% of patients with AF and concomitant HF after AI-guided RFCA procedures, irrespective of different HF subtypes. Preserved LVEF was associated with a reduction in the composite endpoint compared with impaired LVEF. Patients with recurrent AF tend to have a poorer prognosis.

Adverse events prediction in nonischemic dilated cardiomyopathy by two machine learning models integrating clinical and cardiovascular magnetic resonance data

Abstract Funding Acknowledgements Type of funding sources: None. Background Risk stratification of patients with nonischemic dilated cardiomyopathy (NIDCM) is challenging. Machine learning (ML) models represent novel technologic tools that promise to improve predictive ability of cardiovascular adverse outcomes. Purpose To implement two ML models to predict the risk of adverse outcome (composite endpoint of all-cause death, heart transplantation, implantation of ventricular assistant device), in patients with NIDCM using clinical and radiological data. Methods We retrospective collected data from patients affected by NIDCM referred to our cardiologic unit between 2002 and 2018. Two ML models, an extreme gradient boosting machine (XGBoost) and an artificial neural network (ANN), were developed using cardiovascular magnetic resonance (CMR) and clinical parameters. Both models were trained on 67% of patients and evaluated based on the other 33% as internal validation. To investigate the contribution of different features in our models, we used Shapley additive explanations (SHAP) analysis. Results The final cohort resulted of 161 patients (mean age 48.9±13.6 years, 71% males), with a mean follow up duration of 79.1 months. During the follow-up 29 adverse event were observed (16 deaths, 12 heart transplantation, 1 implantation of ventricular assistant device). ANN model resulted in an accuracy of 76% with an area under the receiver operating characteristic (ROC) curve of 0.66; SHAP analysis identified male sex, percentage of late gadolinium enhancement (LGE) and LGE distribution in the lateral wall of myocardium as the main markers of adverse outcomes. XGBoost model resulted in an accuracy of 78% with a ROC curve of 0.76; SHAP analysis identified NT-proBNP level, age and serum creatinine mainly related with adverse outcomes. About CMR parameters, left ventricular diameter and ejection fraction better related with adverse outcomes. Conclusions Our models achieved a good performance in prediction of adverse events, suggesting that ML could improve our ability of risk stratification of NIDCM. XGBoost better performed than ANN, and SHAP analysis suggested that both CMR parameters and clinical parameters contribute to the definition of risk. ANN performance and SHAP analysisXGBoost performance and SHAP analysis

High-sensitivity troponin I with or without ultra-sensitive copeptin for the instant rule-out of acute myocardial infarction.

BackgroundThe instant, single-sampling rule-out of acute myocardial infarction (AMI) is still an unmet clinical need. We aimed at testing and comparing diagnostic performance and prognostic value of two different single-sampling biomarker strategies for the instant rule-out of AMI.MethodsFrom the Biomarkers in Acute Cardiac Care (BACC) cohort, we recruited consecutive patients with acute chest pain and suspected AMI presenting to the Emergency Department of the University Medical Center Hamburg-Eppendorf, Hamburg, Germany. We compared safety, effectiveness and 12-month incidence of the composite endpoint of all-cause death and myocardial infarction between (i) a single-sampling, dual-marker pathway combining high-sensitivity cardiac troponin I (hs-cTnI) and ultra-sensitive copeptin (us-Cop) at presentation (hs-cTnI ≤ 27 ng/L, us-Cop < 10 pmol/L and low-risk ECG) and (ii) a single-sampling pathway based on one-off hs-cTnI determination at presentation (hs-cTnI < 5 ng/L and low-risk ECG). As a comparator, we used the European Society of Cardiology (ESC) 0/1-h dual-sampling algorithm.ResultsWe enrolled 1,136 patients (male gender 65%) with median age of 64 years (interquartile range, 51–75). Overall, 228 (20%) patients received a final diagnosis of AMI. The two single-sampling instant rule-out pathways yielded similar negative predictive value (NPV): 97.4% (95%CI: 95.4–98.7) and 98.7% (95%CI: 96.9–99.6) for dual-marker and single hs-cTnI algorithms, respectively (P = 0.11). Both strategies were comparably safe as the ESC 0/1-h dual-sampling algorithm and this was consistent across subgroups of early-comers, low-intermediate risk (GRACE-score < 140) and renal dysfunction. Despite a numerically higher rate of false-negative results, the dual-marker strategy ruled-out a slightly but significantly higher percentage of patients compared with single hs-cTnI determination (37.4% versus 32.9%; P < 0.001). There were no significant between-group differences in 12-month composite outcome.ConclusionsInstant rule-out pathways based on one-off determination of hs-cTnI alone or in combination with us-Cop are comparably safe as the ESC 0/1 h algorithm for the instant rule-out of AMI, yielding similar prognostic information. Instant rule-out strategies are safe alternatives to the ESC 0/1 h algorithm and allow the rapid and effective triage of suspected AMI in patients with low-risk ECG. However, adding copeptin to hs-cTn does not improve the safety of instant rule-out compared with the single rule-out hs-cTn at very low cut-off concentrations.

Prognostic value of N-terminal Pro-B-Type natriuretic peptide in patients with intermediate coronary lesions.

BackgroundThe optimal treatment strategy for patients with coronary intermediate lesions, defined as diameter stenosis of 50–70%, remains a great challenge for cardiologists. Identification of potential biomarkers predictive of major adverse cardiovascular events (MACEs) risk may assist in risk stratification and clinical decision.MethodsA total of 1,187 patients with intermediate coronary lesions and available N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were enrolled in the current study. A baseline NT-proBNP level was obtained. The primary endpoint was defined as MACEs, the composite endpoint of all-cause death and non-fatal myocardial infarction. A multivariate Cox regression model was used to explore the association between NT-proBNP level and MACE risk.ResultsThe mean age of the study cohort was 59.2 years. A total of 68 patients experienced MACE during a median follow-up of 6.1 years. Restricted cubic spline analysis delineated a linear relationship between the baseline NT-proBNP level and MACE risk. Both univariate and multivariate analyses demonstrated that an increased NT-proBNP level was associated with an increased risk of MACE [adjusted hazard ratio (HR) per doubling: 1.412, 95% confidence interval (CI): 1.022–1.952, p = 0.0365]. This association remains consistent in clinical meaningful subgroups according to age, sex, body mass index (BMI), and diabetes.ConclusionAn increased NT-proBNP level is associated with an increased risk of MACE in patients with intermediate coronary lesions and may serve as the potential biomarker for risk stratification and treatment decision guidance.

Effect of β-blocker on patients with moderate functional mitral regurgitation undergoing surgical aortic valve replacement.

The optimal treatment for severe aortic valve disease complicated with moderate function mitral regurgitation (FMR) remains controversial. Although isolated surgical aortic valve replacement (SAVR) is reasonable, previous studies also show that moderate FMR might deteriorate after surgical treatment and result in poorer prognosis. Because the left ventricular remodelling plays a critical role in the development of FMR, these patients might potentially benefit from the administration of β-blocker (BB). Unfortunately, relevant clinical evidence is lacking. This study aimed to investigate the impact of post-operative administration of BB on the outcomes of moderate FMR patients undergoing isolated SAVR. In this single-centre cohort study, patients who underwent isolated SAVR and complicated with pre-operative moderate FMR during 2010 and 2019 at our centre were retrospectively recruited. Patients were divided into two groups according to postoperative administration of BB (BB group vs. control group). The cumulative survival rates were calculated using the Kaplan-Meier method and tested by the log-rank test, followed by inverse probability treatment weighting (IPTW) analysis to further control the between-group imbalances. The primary outcome was the major adverse cardiovascular and cerebrovascular events (MACCE), a composite endpoint of all-cause death, repeat heart valve surgery, non-fatal myocardial infarction, stroke, and hospitalization for heart failure. A total of 165 patients were enrolled, 57 (34.6%) of whom were female, and the mean age was 59.2±12.2years. Eighty (48.5%) patients received post-operative BB therapy. The median follow-up time was 18.4months. The administration of BB was not associated with lower risk of MACCE [hazard ratio (HR): 0.68, 95% confidence interval (CI): 0.29-1.62, P=0.388] or all-cause death (HR: 1.03, 95% CI: 0.30-0.56, P=0.967). In the IPTW dataset, the total number of patients were 326.89, and the outcomes regarding the risk of MACCE (HR: 0.79, 95% CI: 0.31-1.97, P=0.607) and all-cause death (HR: 1.33, 95% CI:0.35-5.05, P=0.674) were in line with the unmatched analysis. The follow-up echocardiographic results were available for 72.2% of the overall cohort, and the use of BB was observed to be associated with higher improvement rate of follow-up FMR according to the IPTW analysis (92.2% vs. 98.3%, P=0.033). The administration of BB after SAVR was not associated with lower risk of MACCE for patients of severe aortic valve disease complicated with moderate FMR, but was potentially beneficial for improving FMR.

Leaflet Thickening and Motion After Transcatheter Aortic Valve Replacement: Design and Rationale of the Rotterdam Edoxaban Trial

BackgroundMultislice computed tomography (MSCT) may reveal hypo-attenuated leaflet thickening (HALT) and/or reduced leaflet motion (RELM) in approximately 15 % of patients after transcatheter aortic valve replacement (TAVR). These supposedly thrombogenic phenomena may be associated with neurological events and increased transprosthetic gradients. It is unclear whether oral anticoagulant therapy -specifically a factor Xa inhibitor- could affect the incidence of HALT/RELM. Study designThe Rotterdam EDOXaban (REDOX) trial is an investigator-initiated, single-center, prospective registry in which 100 patients with no formal indication for oral anticoagulant drugs or dual antiplatelet therapy, will receive a 3-month treatment with edoxaban, followed by a MSCT to detect HALT/RELM. The primary endpoint is the incidence of HALT at 3-months follow-up. Secondary endpoints include the incidence of RELM at 3 months; change in transprosthetic gradients at 1 year and the clinical composite endpoint of all-cause death, myocardial infarction (MI), ischemic stroke, systemic thromboembolism, valve thrombosis and major bleeding (International Society on Thrombosis and Hemostasis [ISTH] definition) at 1 year follow up.The study is powered to demonstrate with 90 % statistical power and a 0.025 alpha a 4 % incidence of HALT with edoxaban as compared to the expected 15 % rate with an antiplatelet regimen and will enroll 100 patients to account for loss of follow-up or CT-drop out. ConclusionThe REDOX trial will investigate the short-term effect of an Xa-inhibitor on the incidence of HALT after TAVR. (ClinicalTrials.gov Identifier: NCT04171726).

Lack of correlation between different congestion markers in acute decompensated heart failure

BackgroundHospitalizations for acute decompensated heart failure (ADHF) are commonly associated with congestion-related signs and symptoms. Objective and quantitative markers of congestion have been identified, but there is limited knowledge regarding the correlation between these markers.MethodsPatients hospitalized for ADHF irrespective of left ventricular ejection fraction were included in a prospective registry. Assessment of congestion markers (e.g., NT-proBNP, maximum inferior vena cava diameter, dyspnea using visual analogue scale, and a clinical congestion score) was performed systematically on admission and at discharge. Telephone interviews were performed to assess clinical events, i.e., all-cause death or readmission for cardiovascular cause, after discharge. Missing values were handled by multiple imputation.ResultsIn total, 130 patients were prospectively enrolled. Median length of hospitalization was 9 days (interquartile range 6 to 16). All congestion markers declined from admission to discharge (p < 0.001). No correlation between the congestion markers could be identified, neither on admission nor at discharge. The composite endpoint of all-cause death or readmission for cardiovascular cause occurred in 46.2% of patients. Only NT-proBNP at discharge was predictive for this outcome (hazard ratio 1.48, 95% confidence interval 1.15 to 1.90, p = 0.002).ConclusionNo correlation between quantitative congestion markers was observed. Only NT-proBNP at discharge was significantly associated with the composite endpoint of all-cause death or readmission for cardiovascular cause. Findings indicate that the studied congestion markers reflect different aspects of congestion.Graphical abstract

Comparative Safety and Effectiveness of Ticagrelor versus Clopidogrel in Patients With Acute Coronary Syndrome: An On-Treatment Analysis From a Multicenter Registry.

Background:The net clinical benefit of ticagrelor over clopidogrel in acute coronary syndrome (ACS) has recently been questioned by observational studies which did not account for time-dependent confounders. We aimed to assess the comparative safety and effectiveness of ticagrelor vs. clopidogrel accounting for non-adherence in a real-life setting.MethodsThis is a prospective, multicenter cohort study of patients with ACS discharged on ticagrelor or clopidogrel between 2015 and 2019. Major exclusions were previous intracranial bleeding, and the use of prasugrel or oral anticoagulation. Association of P2Y12 inhibitor therapy with 1-year risk of Bleeding Academic Research Consortium Type 3 or 5 bleeding; major adverse cardiac events (MACEs), a composite endpoint of all-cause death, nonfatal myocardial infarction (MI), nonfatal stroke, or urgent target lesion revascularization; definite/probable stent thrombosis; vascular death; and net adverse clinical event (a composite endpoint of major bleeding and MACE) were analyzed according to the “on-treatment” principle, using fully adjusted Cox and Fine-Gray regression models with doubly robust inverse probability of censoring weighted estimators.ResultsAmong 2,070 patients (mean age 63 years, 27% women, 62.5% ST-elevation MI), 1,035 were discharged on ticagrelor and clopidogrel, respectively. Ticagrelor-treated patients were younger and had few comorbidities, but high rates of medication non-compliance, compared with clopidogrel users. After comprehensive multivariate adjustments, ticagrelor did not increase the risk of major bleeding compared with clopidogrel [subhazard ratio, 1.40; 95% confidence interval (CI), 0.96–2.05], while proved superior in reducing MACE (hazard ratio 0.62; 95% CI, 0.43–0.90), vascular death (subhazard ratio, 0.71; 95% CI, 0.52–0.97) and definite/probable stent thrombosis (subhazard ratio, 0.54; 95% CI, 0.30-0.79); thereby resulting in a favorable net clinical benefit (hazard ratio 0.78; 95% CI, 0.60–0.98) compared with clopidogrel. Results from sensitivity analyses were consistent with those from the primary analysis, whereas those from the intention-to-treat (ITT) analysis went in the opposite direction.ConclusionAmong all-comers with ACS, ticagrelor did not significantly increase the risk of major bleeding, while resulting in a net clinical benefit compared with clopidogrel. Further research is warranted to confirm these findings in high bleeding risk populations.CREA-ARIAM Andalucía(ClinicalTrials.gov Identifier: NCT02500290); Current pre-specified analysis (ClinicalTrials.gov Identifier: NCT04630288).

Effects of the Atrial fibrillation Better Care (ABC) pathway on outcomes among clinically complex chinese patients with atrial fibrillation with multimorbidity and polypharmacy

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Patients with atrial fibrillation (AF) commonly have complex clinical backgrounds. In this ancillary analysis we assessed the adherence to and the effectiveness of the Atrial fibrillation Better Care (ABC) pathway in reducing adverse outcomes in Chinese AF patients with a complex clinical background of multimorbidity and/or polypharmacy. Methods The ChiOTEAF registry[1] is a prospective, multicentre nationwide study conducted from October 2014 to December 2018. The primary outcomes of interest were the composite endpoint of all-cause death and thromboembolic (TE) events, as well as individual endpoints of all-cause death, TE events, and major bleeding. ’Multimorbidity’ was defined as the presence of ≥2 co-morbidities, ’polypharmacy’ was defined as the concomitant use of ≥5 medications. The participants were assessed against the ABC pathway criteria: patients qualified for the ‘A’ criterion (Avoid stroke) if they were treated with oral anticoagulants according to their TE risk; ‘B’ criterion (Better symptom control) if they demonstrated optimal symptom control defined as European Heart Rhythm Association score of I/II at baseline; ‘C’ criterion (Cardiovascular risk factor and Comorbidity optimisation) if they received disease-specific treatment(s) according to current guidelines at baseline. Patients were considered as ABC-adherent if they fulfilled all three criteria. Results The eligible cohort included 4644 patients with multimorbidity and 2262 patients with polypharmacy (Fig 1.), of whom 56.2% (mean age 74.4±10.2; 42.8% female) and 58.7% (mean age 74.6±10.1; 43.3% female) respectively had available data to assess the ABC pathway utilisation. Adherence to the ABC pathway was associated with lower odds ratio (OR) of the primary composite outcome in the multimorbidy (OR: 0.48; 95% CI: 0.29-0.79) and polypharmacy (OR: 0.39; 95% CI: 0.19-0.78) groups (Table 1.). Adherence to the ABC pathway was associated with a lower risk of all-cause death in multimorbid patients (OR: 0.51; 95% CI: 0.27-0.95) and TE events in patients with polypharmacy (OR: 0.31; 95% CI: 0.10-0.95). In a subgroup of patients with concomitant multimorbidity and polypharmacy the risk of composite outcome (OR: 0.38; 95% CI: 0.18-0.79) and TE events (OR: 0.31; 95% CI: 0.10-0.94) were lower in the ABC-adherent patients. There were no significant differences in the incidence of major bleeding among patients with multimorbidity, polypharmacy or both in the ABC-adherent compared to the non-ABC adherent groups. Health-related quality of life (QoF) was lower in the non-ABC adherent compared to the ABC-adherent patients. Conclusion This study shows that adherence to the ABC pathway is associated with improved clinical outcomes and QoF in Chinese AF patients with multimorbidity and/or polypharmacy. There is no evidence to suggest that adhering to the ABC pathway is associated with a higher risk of major bleeding events compared to standard practice.