Composite Of Cardiovascular Mortality Research Articles

Prediction of cardiac events with non-contrast magnetic resonance feature tracking in patients with ischaemic cardiomyopathy.

AimsThe aim of this study was to evaluate the prognostic value of feature tracking (FT) derived cardiac magnetic resonance (CMR) strain parameters of the left ventricle (LV)/right ventricle (RV) in ischaemic cardiomyopathy (ICM) patients treated with an implantable cardioverter‐defibrillator (ICD). Current guidelines suggest a LV‐ejection fraction ≤35% as major criterion for ICD implantation in ICM, but this is a poor predictor for arrhythmic events. Supplementary parameters are missing.Methods and resultsIschaemic cardiomyopathy patients (n = 242), who underwent CMR imaging prior to primary and secondary implantation of ICD, were classified depending on EF ≤ 35% (n = 188) or >35% (n = 54). FT parameters were derived from steady‐state free precession cine views using dedicated software. The primary endpoint was a composite of cardiovascular mortality (CVM) and/or appropriate ICD therapy. There were no significant differences in FT‐function or LV‐/RV‐function parameters in patients with an EF ≤ 35% correlating to the primary endpoint. In patients with EF > 35%, standard CMR functional parameters, such as LV‐EF, did not reveal significant differences. However, significant differences in most FT parameters correlating to the primary endpoint were observed in this subgroup. LV‐GLS (left ventricular‐global longitudinal strain) and RV‐GRS (right ventricular‐global radial strain) revealed the best diagnostic performance in ROC curve analysis. The combination of LV‐GLS and RV‐GRS showed a sensitivity of 85% and a specificity of 76% for the prediction of future events.ConclusionsThe impact of FT derived measurements in the risk stratification of patients with ICM depends on LV function. The combination of LV‐GLS/RV‐GRS seems to be a predictor of cardiovascular mortality and/or appropriate ICD therapy in patients with EF > 35%.

Abstract 12408: Fragmented QRS is Independently Predictive of Long-Term Adverse Clinical Outcomes in Asian Patients Hospitalized for Heart Failure: A Retrospective Cohort Study

Introduction: Fragmented QRS (fQRS) results from myocardial scarring and predicts cardiovascular mortality and ventricular arrhythmia (VA). We evaluated the prevalence and prognostic value of fQRS in Asian patients hospitalized for heart failure. Hypothesis: fQRS is predictive of adverse clinical outcomes. Methods: This was a retrospective cohort study of adult patients hospitalized for heart failure between 1st January 2000 and 31st December 2019 at a tertiary center in Hong Kong. The baseline ECG was analysed. QRS complexes (<120 ms) with fragmented morphology in ≥2 contiguous leads were defined as fQRS. The primary outcome was a composite of cardiovascular mortality, VA, and sudden cardiac death (SCD). The secondary outcomes were the components of the primary outcome, myocardial infarction, and new-onset atrial fibrillation. Results: In total, 2192 patients were included, of whom 179 (8.20%) exhibited fQRS. The follow-up duration was 5.63±4.09 years. fQRS in any leads was associated with a higher risk of the primary outcome (adjusted hazard ratio (HR) 1.541 [1.185, 2.004], p=0.001; Figure A), but not myocardial infarction or new-onset atrial fibrillation. fQRS in >2 contiguous leads was an independent predictor of the primary outcome (HR 1.841 [1.119, 3.029], p=0.016; Figure B), driven by a higher risk of SCD (adjusted HR 2.679 [1.252, 5.729], p=0.011). In patients without ischaemic heart disease (N=1396), fQRS in any leads remained predictive of VA and SCD (adjusted HR 3.336 [1.343, 8.282], p=0.009, and 1.928 [1.135, 3.278], p=0.015, respectively), but not cardiovascular mortality (adjusted HR 1.049 [0.662, 1.662], p=0.839). Conclusions: fQRS is an independent predictor of cardiovascular mortality, VA, and SCD. Higher fQRS burden increased SCD risk. The implications of fQRS in heart failure patients without ischaemic heart disease require further studies.

Fragmented QRS Is Independently Predictive of Long-Term Adverse Clinical Outcomes in Asian Patients Hospitalized for Heart Failure: A Retrospective Cohort Study.

Background: Fragmented QRS (fQRS) results from myocardial scarring and predicts cardiovascular mortality and ventricular arrhythmia (VA). We evaluated the prevalence and prognostic value of fQRS in Asian patients hospitalized for heart failure.Methods and Results: This was a retrospective cohort study of adult patients hospitalized for heart failure between 1st January 2010 and 31st December 2016 at a tertiary center in Hong Kong. The baseline ECG was analyzed. QRS complexes (<120 ms) with fragmented morphology in ≥2 contiguous leads were defined as fQRS. The primary outcome was a composite of cardiovascular mortality, VA, and sudden cardiac death (SCD). The secondary outcomes were the components of the primary outcome, myocardial infarction, and new-onset atrial fibrillation. In total, 2,182 patients were included, of whom 179 (8.20%) had fQRS. The follow-up duration was 5.63 ± 4.09 years. fQRS in any leads was associated with a higher risk of the primary outcome (adjusted hazard ratio (HR) 1.428 [1.097, 1.859], p = 0.001), but not myocardial infarction or new-onset atrial fibrillation. fQRS in >2 contiguous leads was an independent predictor of SCD (HR 2.679 [1.252, 5.729], p = 0.011). In patients without ischaemic heart disease (N = 1,396), fQRS in any leads remained predictive of VA and SCD (adjusted HR 3.526 [1.399, 8.887], p = 0.008, and 1.873 [1.103, 3.181], p = 0.020, respectively), but not cardiovascular mortality (adjusted HR 1.064 [0.671, 1.686], p = 0.792).Conclusion: fQRS is an independent predictor of cardiovascular mortality, VA, and SCD. Higher fQRS burden increased SCD risk. The implications of fQRS in heart failure patients without ischaemic heart disease require further studies.

Echocardiographic Global Longitudinal Strain Is Associated With Myocardial Fibrosis and Predicts Outcomes in Aortic Stenosis.

Aims: Left ventricular ejection fraction is the conventional measure used to guide heart failure management, regardless of underlying etiology. Left ventricular global longitudinal strain (LV-GLS) by speckle tracking echocardiography (STE) is a more sensitive measure of intrinsic myocardial function. We aim to establish LV-GLS as a marker of replacement myocardial fibrosis on cardiovascular magnetic resonance (CMR) and validate the prognostic value of LV-GLS thresholds associated with fibrosis.Methods and results: LV-GLS thresholds of replacement fibrosis were established in the derivation cohort: 151 patients (57 ± 10 years; 58% males) with hypertension who underwent STE to measure LV-GLS and CMR. Prognostic value of the thresholds was validated in a separate outcome cohort: 261 patients with moderate-severe aortic stenosis (AS; 71 ± 12 years; 58% males; NYHA functional class I–II) and preserved LVEF ≥50%. Primary outcome was a composite of cardiovascular mortality, heart failure hospitalization, and myocardial infarction. In the derivation cohort, LV-GLS demonstrated good discrimination (c-statistics 0.74 [0.66–0.83]; P < 0.001) and calibration (Hosmer-Lemeshow χ2 = 6.37; P = 0.605) for replacement fibrosis. In the outcome cohort, 47 events occurred over 16 [3.3, 42.2] months. Patients with LV-GLS > −15.0% (corresponding to 95% specificity to rule-in myocardial fibrosis) had the worst outcomes compared to patients with LV-GLS < −21.0% (corresponding to 95% sensitivity to rule-out myocardial fibrosis) and those between −21.0 and −15.0% (log-rank P < 0.001). LV-GLS offered independent prognostic value over clinical variables, AS severity and echocardiographic LV mass and E/e′.Conclusion: LV-GLS thresholds associated with replacement myocardial fibrosis is a novel approach to risk-stratify patients with AS and preserved LVEF.

Beta-blockers in patients without heart failure after myocardial infarction.

Beta-blockers in patients without heart failure after myocardial infarction.

Paravalvular leaks: short and long-term outcomes of surgical versus percutaneous closure

Abstract Introduction Paravalvular leaks (PVL) appear in 5–17% of patients who undergo surgical valve replacement, causing heart failure (HF), haemolytic anaemia, or both in 2–5% of cases. Surgical intervention (SI) is the first line treatment, although transcatheter intervention (TI) is gaining ground as an alternative. However, there are no randomized studies comparing both techniques. Purpose The aim of this study is to compare the short and long-term outcomes in patients with symptomatic PVL undergoing SI or TI. Methods We conducted a retrospective analysis of all patients who underwent SI or TI for PVL between 2004 and 2020 in our institution. The primary endpoint (PE) was the composite of cardiovascular mortality, readmission for HF and reintervention for PVL up to 24 months after the procedure. The secondary endpoints were admission length, technical and procedural success, and rate of complications. The definition of technical success was the correct placement of the device with no impaired function of the valve prosthesis and with ≤ grade II residual regurgitation. Procedural success was defined when there was technical success with no presentation of intervention-related complications. Results Picture 1 provides information about the clinical and procedural characteristics, initial outcome and outcome during follow-up. A total 85 procedures, 39 transcatheter (45.9%) and 46 surgical (54.1%), were performed on 67 patients. The patients who underwent TI were older (67.5 versus 61.4 years; p=0.03) had a worse functional class (NYHA III-IV 100% versus 80%; p=0.02), a lower frequency of previous endocarditis (22.2% versus 52.2%; p=0.03) and higher surgical risk (EuroScore 18.7 versus 10.4 and EuroScore II 8.6 versus 5.6; both p=0.001). The hospital stay was significantly shorter for TI (10.2 versus 30.4 days; p=0.009). Additionally, although without statistical significance, there was a lower frequency of complications (41% versus 58.7; p=0.16) and less technical success (69.2% versus 86.7%; p=0.052). There were no differences between procedure success (61.5% versus 71.1%, p=0.49). Regarding PE, at 24 months there were no differences in event-free survival (TI 55.9% versus SI 64.1%; Log-Rank p=0.8) (Picture 2). Conclusion The main finding of our study was the absence of significant differences in the short and long-term outcomes (composite of cardiovascular mortality, readmission for HF and reintervention) between surgical versus percutaneous closure. In conclusion, transcatheter intervention must be considered as a good alternative, particularly in high-risk surgical patients. Funding Acknowledgement Type of funding sources: None. Picture 1. Baseline characteristicsPicture 2

Myocardial Work and long-term prognosis in patients after ST-segment elevation acute myocardial infarction

Abstract Background Left ventricular (LV) global longitudinal strain has demonstrated incremental prognostic value over LV ejection fraction (LVEF) in patients with ST-segment-elevation acute myocardial infarction. However, LV global longitudinal strain (GLS) does not take into consideration the effect of afterload. Myocardial work (MW) by speckle-tracking echocardiography integrates blood pressure measurements (afterload) with LV GLS and it has been recently demonstrated that Global Work Efficiency (GWE) is associated with long-term all-cause mortality. It remains to be demonstrated if MW indices are associated with hard cardiovascular endpoints. The present study aimed to investigate the prognostic value of global LV MW obtained from pressure-strain loops with echocardiography in patients with ST-segment-elevation myocardial infarction. Methods A total of 100 consecutive ST-segment-elevation myocardial infarction patients (mean age, 61±12 years; 75% men) that survived to discharge were retrospectively analysed. LVEF, GLS and all LVMW indices were measured by transthoracic echocardiography before discharge (4.6±2.0 days after admission). All patients had at least a two-year follow-up (mean follow-up of 833±172 days). Outcomes: all-cause mortality, major acute cardiovascular events (a composite of cardiovascular mortality, myocardial infarction, stroke, unplanned cardiovascular admission) and heart failure hospitalization. Results In the two-year follow-up, 6 patients died, there were 17 patients with MACE, and 3 patients were hospitalized with heart failure. We confirmed that for all-cause mortality, GWE showed higher discrimination, compared to GLS (Table 1), with a cut-off of 83% (log-rank &amp;lt;0,001). For MACE, the performance of all methods is suboptimal, with an AUC &amp;lt;0.65 for all variables, except for GLS. For heart failure admission, performance is slightly better, but GLS is still the better parameter to predict this event. Conclusions LVGWE is a better predictor of all-cause mortality compared to GLS, but MW indices failed to demonstrate a prognostic impact in long-term cardiovascular events. Prospective studies are warranted to confirm this finding. Funding Acknowledgement Type of funding sources: None. Table 1

Prognostic value of baseline versus 6-month follow infarct size in patients with reperfused STEMI

Abstract Background Acute infarct size is a predictor of clinical outcomes in acute ST segment elevation myocardial infarction (STEMI) patients, although its prognostic value has differed between studies. In acute STEMI, infarct size is often overestimated due to the presence of extensive myocardial oedema, a confounder that is no longer present at a 6-month follow-up study. It was our purpose to assess whether infarct size in the acute phase or at 6-months follow-up provided superior prognostic information in STEMI patients. Methods STEMI patients who underwent successful primary percutaneous revascularization were included and a cardiac magnetic resonance (CMR) was performed between 5–7 days after STEMI and at 6 months to study infarct size (as a % of myocardial mass). The primary endpoint was a composite of cardiovascular mortality, hospitalization for heart failure and ventricular arrhythmia. Results A total of 796 patients were included (mean age 58.3±11.5 years, 82.4% male, 52.3% anterior infarction). During a mean follow-up of 59 months, 59 patients (7.4%) presented with the primary end-point (cardiovascular death n=7, hospitalization for heart failure n=52, ventricular arrhythmia n=1). ROC curve analysis (figure 1) showed a non-significant difference between baseline and 6-month infarct size for the prediction of the primary endpoint (baseline AUC 0.685 95% CI 0.610–0.760, 6-month AUC 0.713 95% CI 0.643–0.782, p=0.60). Optimal cut-off values for baseline and 6-months follow-up infarct size for prediction of outcomes, respectively 22% and 17.5%, were used for Kaplan-Meier curve analysis (figure 2). Conclusion Infarct size estimated during the first week after STEMI and at 6-months follow-up showed similar predictive value and with similar cut-off values. Therefore, the prognostic information provided by infarct size can be obtained during initial STEMI admission and does not require a waiting period for infarct size stabilization. Funding Acknowledgement Type of funding sources: None. ROC curve analysisKaplan-Meier analysis

Reperfusion in high-risk acute pulmonary embolism: can the PESI score predict outcomes?

Abstract Introduction Acute pulmonary embolism (PE) is one of the leading causes of cardiovascular death worldwide. Haemodynamic (HD) instability defines high risk (HR) of early mortality and reperfusion treatment is the standard of care for rapid relieve of right ventricle (RV) overload in these situations. The impact of reperfusion in long-term outcomes is not well established. The PE Severity Index (PESI) score is used to stratify the risk of early death in HD stable patients (pts) and was not validated to predict outcomes in HR-PE. Purpose Estimate the prognostic performance of the PESI score in HR-PE and study its possible interaction in acute and long-term outcomes of reperfusion in HR-PE pts. Methods Retrospective single-centre study of consecutive HR-PE pts, defined by the 2019 ESC guidelines criteria, between 2008–2018. Logistic regression analysis was performed to test for an interaction between tertiles of the PESI score and reperfusion in early-mortality (during hospitalization and at 30 days) as well as 1-year MACE (a composite of cardiovascular mortality, PE recurrence or chronic thromboembolic pulmonary hypertension). Results Of a total of 1955 PE pts, 102 fulfilled the inclusion criteria (72.5% pts initially presented with HD instability with the remaining developing HR-PE after hospital admission). Mean age was 68±15 years and 60% were females. In-hospital and 30-day mortality were 39.6% and 43.0%, respectively. At one-year follow-up, MACE was 55.0%. Mean PESI at the time of HR-PE diagnosis was 200±39 and showed significant differences for in-hospital mortality (189±38 vs 217±34; OR 1.02, 95% CI 1.00–1.03, p&amp;lt;0.001), 30-day mortality (191±38 vs 214±36; OR 1.02, 95% CI 1.00–1.03, p=0.004) and 1y-MACE (186±41 vs 214±32; OR 1.02, 95% CI 1.01–1.03, p&amp;lt;0.001). Total reperfusion rate was 57.8% and was also associated with lower in-hospital mortality (OR 0.45, 95% CI 0.20–1.02; p=0.057), 30-day mortality (OR 0.35, 95% CI 0.15–0.80; p=0.012) and 1y-MACE (OR 0.35, 95% CI 0.15–0.80; p=0.014). The benefit of reperfusion was significantly influenced by the PESI score categorized by tertiles (figure 1). Conclusions Although the PESI score stratifies HD stable pts, in this population it was able to predict cardiovascular outcomes in HR-PE pts. Furthermore, it showed a significant interaction with the prognostic impact of reperfusion in early and late cardiovascular outcomes. Funding Acknowledgement Type of funding sources: None. Figure 1. Interaction between PESI and reperfusion

Prognostic impact of treatment with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in the acute phase and medium-term on COVID-19 infected patients

Abstract Introduction The first case of COVID-19 infection was described in Wuhan, China, in December 20191. Shortly after, cases of limited human-to-human transmission were reported in other countries, which made the WHO declare the outbreak a Public Health Emergency of International Concern (ESPII) on January 30, 20202. Recent studies suggest that treatment with angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARAB) during acute COVID-19 infection has no effect on mortality3, but it is no evidence regarding the medium-term clinical implication of previous treatment with ACEI/ARAB on the prognosis of patients with COVID-19 infection. Purpose The aim of this study is to evaluate the clinical implication of the use of ACEI/ARB in the acute moment and in medium-term follow-up in patients after COVID-19. Methods It is a single-centre, retrospective, analytical observational study of cohorts based on all consecutive patients diagnosed with COVID-19 who were admitted during the first wave (March 10th until May 31st), of the pandemic in our health area. Survival analysis of main outcomes (mortality, heart failure, and major acute cardiovascular events [a composite of cardiovascular mortality, myocardial infarction and stroke]) were adjusted by multivariate logistic regression. Results Of the total population studied, 447,979 inhabitants, 1,030 (0.23%) were diagnosed with COVID-19 infection, of which 196 (19%) were under treatment with ACEI/ARB at the time of diagnosis. The main results showed that ACEI/ARB treatment (combined and individually) had no effect on mortality (Hazard Ratio [HR]: 1.64, 95% Confidence Interval [CI] 0.98 2.76, p=0.062), heart failure (HR: 0.98, 95% CI 0.53 1.79, p=0.942), thrombotic events (HR: 1.02, 95% CI 0.22 4.83, p=0.98) and major acute cardiovascular events (HR: 0.88, 95% CI 0.48 1.60, p=0.665). Conclusions In conclusion, previous treatment with ACEI/ARB in patients with COVID-19 had no effect on the 6-month prognosis, defined as mortality, heart failure, or major acute cardiovascular events. Withdrawal of ACEI/ARB in patients testing positive for COVID-19 would not be justified, in line with current recommendations of scientific societies and government agencies. Funding Acknowledgement Type of funding sources: None.

Changes in Left atrial strain in patients with aortic stenosis after TAVI

Abstract Background Evaluation of left atrial (LA) function is an emerging biomarker of cardiovascular disease (CVD). LA strain by 2D speckle tracking echocardiography (LA strain, LAS) is feasible and reliable, and has been recently associated with adverse long-term outcomes in CVD, including aortic stenosis (AS). Purpose To evaluate the changes in left atrial strain (LAS) after correction of severe AS with transcatheter aortic valve replacement (TAVR) and assess its prognostic impact. Methods One hundred consecutive patients with severe symptomatic AS who underwent TAVR at the Magna Graecia University of Catanzaro have been enrolled. Echocardiographic examination before and after TAVR was performed using Vivid E95 system and analysed using the EchoPAC 112.99 workstation (GE Healthcare). Patients underwent clinical follow up visits regularly. The primary study outcome was the difference in ΔLAS (postTAVR-preTAVR) between patients that met the main clinical endpoint (a composite of cardiovascular mortality and heart failure hospitalization) and those not meeting the endpoint. Statistical analyses were performed using JASP (version 0.14.1) and KMWin (version 1.52). Continuous variables were presented as mean and standard deviation and were compared through the unpaired Student's t test or the Mann-Whitney U test in case of a non-normal distribution. Differences between categorical variables were tested with the chi-square test. Multiple logistic regression analysis was performed to identify independent correlates of ΔLAS and to calculate Hazard Ratios (HR) with 95% CI. Kaplan-Meier was used to assess adverse event. Results During a median follow-up of 31 months, 35 patients (35%) met the composite clinical endpoint. The difference between LAS post-TAVR and LAS pre-TAVR (ΔLAS) was significantly larger in patients who met the combined endpoint (HR=0.76 [0.67–0.86]; p&amp;lt;0.001). Multivariate logistic regression analysis including ΔLAS, EuroSCORE II and left ventricular ejection fraction (LVEF) showed that ΔLAS (HR=0.80, p&amp;lt;0.001) was the only independent predictor of the combined clinical endpoint. Kaplan-Maier analysis showed that patients with a ΔLAS above its median value had a significantly better event-free survival compared to those below the median (p&amp;lt;0.001). Conclusions A lower reduction in ΔLAS after TAVR was an independent predictor of the primary composite outcome of cardiovascular death and hospitalization for HF. Funding Acknowledgement Type of funding sources: None.

COVID-19 infection impact on cardiovascular and thrombotic events during acute phase and medium-term of the disease

BackgroundCoronavirus disease (COVID-19) was labelled a global pandemic in April 2020 by the World Health Organisation. By December of the same year the disease caused by SARS-COV-2, known as COVID-19 (Coronavirus disease 2019), had spread over 200 countries, infecting more than 70 million people, causing more that 1.5 million of deaths.Recent studies suggest SARS-CoV-2 infection may be related to cardiovascular and thrombotic events although the strength of association remains unclear.AimsEvaluate the emergence of cardiovascular and thrombotic events (such as major acute cardiovascular events, ictus and other thrombosis) in the acute moment and in medium-term follow-up in COVID-19 patients.MethodsSingle-Center, retrospective, observational study of cohorts based on all the inhabitants of the health area. Survival analysis of main outcomes (mortality, heart failure [HF], and major acute cardiovascular events – MACE - [a composite of cardiovascular mortality, myocardial infarction and stroke]) were adjusted by multivariate logistic regression.ResultsOf the total population studied, 447,979 inhabitants, 1,030 (0.23%) were diagnosed with COVID-19 infection, of which 14,8% were smokers, 31,2% had high blood pressure (HTA), 12,8% had diabetes, 29,2% had dyslipidaemia, 2,7% had peripheral artery disease, 4,7% had ischemic heart disease, 3,3% had had a previous transient ischemic attack, 10% were in anti-aggregation treatment and 5,8% were in anticoagulation treatment at the time of diagnosis. Concerning the analytics middle values, the group treated with ACEI/ARAB had higher troponins and ferritin than the group without ACEI/ARAB treatment, whereas higher reactive C protein and D-dimer were found in this last group. The main results showed that COVID-19 infection had no effect regarding to cardiovascular and thrombotic disease on mortality (OR: 1.64, 95% CI 0.98 2.76, p=0.062), heart failure (OR: 0.98, 95% CI 0.53 1.79, p=0.942), thrombotic events (OR: 1.02, 95% CI 0.22 4.83, p=0.98) and major acute cardiovascular events (OR: 0.88, 95% CI 0.48 1.60, p=0.665).ConclusionsIn conclusion, COVID-19 infection had no effect on the emergence of cardiovascular or thrombotic events taking into account the 6-month prognosis, defined as mortality, heart failure, or major acute cardiovascular events.FUNDunding AcknowledgementType of funding sources: None.

Echocardiographic global longitudinal strain as a marker of myocardial fibrosis predicts outcomes in aortic stenosis

Abstract Background Left ventricular global longitudinal strain (LV-GLS) by speckle tracking echocardiography (STE) reflects intrinsic myocardial function, influenced by interstitial abnormalities. Cardiovascular magnetic resonance (CMR) detects myocardial fibrosis non-invasively, but it is limited for widespread use. We aim to establish LV-GLS as a marker of replacement myocardial fibrosis on CMR and validate the prognostic value of LV-GLS thresholds associated with fibrosis. Methods LV-GLS thresholds of replacement fibrosis were established in the derivation cohort: 151 patients (57±10 years; 58% males) with hypertension who underwent STE to measure LV-GLS and CMR for replacement myocardial fibrosis. Prognostic value of the thresholds was validated in a separate outcome cohort: 261 patients with moderate-severe aortic stenosis (AS; 71±12 years; 58% males; NYHA functional class I-II) and preserved LVEF ≥50%. Primary outcome was a composite of cardiovascular mortality, heart failure hospitalization, myocardial infarction and cerebrovascular events. Results In the derivation cohort, LV-GLS demonstrated good discrimination (c-statistics 0.74; 95% confidence interval: 0.66–0.83; P&amp;lt;0.001) and calibration (Hosmer-Lemeshow X2=6.37; P=0.605) for replacement fibrosis. In the outcome cohort, 52 events occurred over 16 [3.1, 42.0] months of follow-up. Patients with LV-GLS &amp;gt;−15.0% (corresponding to 95% specificity to rule-in myocardial fibrosis) had the worst outcomes compared to patients with LV-GLS &amp;lt;−21.0% (corresponding to 95% sensitivity to rule-out myocardial fibrosis) and those between −21.0 and −15.0% (log-rank P&amp;lt;0.001; Figure 1). Furthermore, LV-GLS offered independent prognostic value over clinical variables, AS severity, echocardiographic LVEF and E/e' (hazard ratio 1.18; 95% confidence interval: 1.07 to 1.30; P=0.001). Conclusions LV-GLS thresholds associated with replacement myocardial fibrosis is a novel approach to risk-stratify patients with AS and preserved LVEF (Figure 2). Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Medical Research Council Figure 1Figure 2

Sodium-glucose cotransporter 2 inhibitors in patients with heart failure: a systematic review and meta-analysis of randomized trials.

Sodium-glucose cotransporter 2 (SGLT-2) inhibitors have now been evaluated for the treatment of heart failure in several placebo-controlled randomized controlled trials (RCTs) across various ejection fraction ranges, but these trials were powered for composite outcomes rather than individual clinical endpoints. We therefore performed a meta-analysis to assess their safety and efficacy on all-cause mortality, cardiovascular mortality, and heart failure hospitalizations. We performed a prospectively registered random-effects meta-analysis of all RCTs comparing SGLT-2 inhibitors to placebo in patients with heart failure. The pre-specified primary endpoint was all-cause mortality. Secondary endpoints included cardiovascular mortality, heart failure hospitalizations, and the composite of cardiovascular mortality or heart failure hospitalization. Four trials with 15684 patients were eligible. The SGLT-2 inhibitor tested was empagliflozin in two trials, dapagliflozin in one trial, and sotagliflozin in one trial. The weighted-mean follow-up was 20.0 months. The hazard ratio (HR) for all-cause mortality was 0.91, 95% confidence interval (CI) 0.82-1.01, P=0.071. There was a 12% reduction in cardiovascular mortality (HR 0.88, 95% CI 0.79 to 0.97, P = 0.012), and a 30% reduction in heart failure hospitalization (HR 0.70, 95% CI 0.64 to 0.77, P <0.001). SGLT-2 inhibitors significantly reduced cardiovascular mortality and heart failure hospitalizations in patients with heart failure. The effect appears consistent across three drugs studied in four trials. SGLT-2 inhibitors should become standard care for patients with heart failure.

Machine Learning-Derived Echocardiographic Phenotypes Predict Heart Failure Incidence in Asymptomatic Individuals

ObjectivesThis study sought to identify homogenous echocardiographic phenotypes in community-based cohorts and assess their association with outcomes. BackgroundAsymptomatic cardiac dysfunction leads to a high risk of long-term cardiovascular morbidity and mortality; however, better echocardiographic classification of asymptomatic individuals remains a challenge. MethodsEchocardiographic phenotypes were identified using K-means clustering in the first generation of the STANISLAS (Yearly non-invasive follow-up of Health status of Lorraine insured inhabitants) cohort (N = 827; mean age: 60 ± 5 years; men: 48%), and their associations with vascular function and circulating biomarkers were also assessed. These phenotypes were externally validated in the Malmö Preventive Project cohort (N = 1,394; mean age: 67 ± 6 years; men: 70%), and their associations with the composite of cardiovascular mortality (CVM) or heart failure hospitalization (HFH) were assessed as well. ResultsThree echocardiographic phenotypes were identified as “mostly normal (MN)” (n = 334), “diastolic changes (D)” (n = 323), and “diastolic changes with structural remodeling (D/S)” (n = 170). The D and D/S phenotypes had similar ages, body mass indices, cardiovascular risk factors, vascular impairments, and diastolic function changes. The D phenotype consisted mainly of women and featured increased levels of inflammatory biomarkers, whereas the D/S phenotype, consisted predominantly of men, displayed the highest values of left ventricular mass, volume, and remodeling biomarkers. The phenotypes were predicted based on a simple algorithm including e′, left ventricular mass and volume (e′VM algorithm). In the Malmö cohort, subgroups derived from e′VM algorithm were significantly associated with a higher risk of CVM and HFH (adjusted HR in the D phenotype = 1.87; 95% CI: 1.04 to 3.37; adjusted HR in the D/S phenotype = 3.02; 95% CI: 1.71 to 5.34). ConclusionsAmong asymptomatic, middle-aged individuals, echocardiographic data-driven classification based on the simple e′VM algorithm identified profiles with different long-term HF risk. (4th Visit at 17 Years of Cohort STANISLAS-Stanislas Ancillary Study ESCIF [STANISLASV4]; NCT01391442)

Body weight changes in patients with type 2 diabetes and a recent acute coronary syndrome: an analysis from the EXAMINE trial

BackgroundPatients with type 2 diabetes (T2D) may experience frequent body weight changes over time. The prognostic impact of these weight changes (gains or losses) requires further study.AimsTo study the associations between changes in body weight (intentional or unintentional) with subsequent outcomes.MethodsThe EXAMINE trial included 5380 patients with T2D and a recent acute coronary syndrome, who were randomized to alogliptin or placebo. Time-updated Cox models and mixed effects models were used to test the associations between changes in body weight and subsequent outcomes over a median follow-up of 1.6 (1.0–2.1) years.ResultsDuring the post-randomization follow-up period, 1044 patients (19.4%) experienced a weight loss ≥ 5% of baseline weight, 2677 (49.8%) had a stable weight, and 1659 (30.8%) had a ≥ 5 % weight gain. Patients with weight loss were more frequently women and had more co-morbid conditions. In contrast, patients who gained ≥ 5% weight were more frequently men with less co-morbid conditions. A weight loss ≥ 5% was independently associated with a higher risk of subsequent adverse outcomes, including all-cause mortality: adjusted HR (95% CI) = 1.79 (1.33–2.42), P < 0.001. Similar associations were found for cardiovascular mortality, the composite of cardiovascular mortality or heart failure hospitalization, and the primary outcome. A weight gain ≥ 5% was independently associated with an increase in the risk of subsequent cardiovascular mortality or heart failure hospitalization only: adjusted HR (95% CI) = 1.34 (1.02–1.76), P = 0.033.ConclusionsIn patients with T2D who had a recent ACS/MI, a ≥ 5% loss of body weight was associated with a higher risk of subsequent cardiovascular events and mortality.

Guided and unguided de-escalation from potent P2Y12 inhibitors among patients with acute coronary syndrome: a meta-analysis

Optimal dual antiplatelet therapy (DAPT) in patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) intends to balance ischemic and bleeding risks. Various DAPT de-escalation strategies, defined as switching from a full-dose potent to a reduced dose or less potent P2Y12 inhibitor, have been evaluated in several ACS-PCI trials. We aimed to compare DAPT de-escalation to standard DAPT with full-dose potent P2Y12 inhibitors in ACS patients who underwent PCI. PubMed, Google Scholar, and Cochrane Central Register of Controlled Trials were searched for eligible randomized controlled trials. Aspirin monotherapy trials were excluded. Five randomized trials (n=10779 patients) that assigned DAPT de-escalation (genetically guided to clopidogrel n=1242; platelet function guided to clopidogrel n=1304; unguided to clopidogrel n=1672; unguided to lower dose n=1170) vs. standard DAPT (control group n=5391) were included in this analysis. DAPT de-escalation was associated with a significant reduction in Bleeding Academic Research Consortium≥2 bleeding (HR 0.57, 95% CI 0.42-0.78; I2=77%) as well as major adverse cardiac events, represented in most trials by the composite of cardiovascular mortality, myocardial infarction, stent thrombosis, and stroke (HR 0.77, 95% CI 0.62-0.96; I2=0%). Notwithstanding the limited power, consistency was noted across various de-escalation strategies. De-escalation of DAPT after PCI for ACS, both unguided and guided by genetic or platelet function testing (PFT), was associated with lower rates of clinically relevant bleeding and ischemic events as compared to standard DAPT with potent P2Y12 inhibitors based on five open-label RCTs reviewed.

Increased ratio of sST2/LVMI predicted cardiovascular mortality and heart failure rehospitalization in heart failure with reduced ejection fraction patients: a prospective cohort study

BackgroundInflammation is one of the principal triggering mechanisms for left ventricular fibrosis and remodeling in heart failure, leading to adverse clinical outcomes. Soluble suppression of tumorigenicity 2 (sST2), a member of the interleukin-1 receptor family, is assumed to play a significant role in the fibrotic response to inflammation. Left ventricular mass index (LVMI) is a parameter of the prefibrotic inflammatory phase of heart failure preceding remodeling. The present study aimed to investigate the prognostic value of the sST2/LVMI ratio in heart failure with reduced ejection fraction.MethodsThis was a prospective cohort study. A total of 45 consecutive patients with heart failure with reduced ejection fraction, treated between September 2015 and December 2016, were enrolled. The sST2/LVMI ratio was measured at baseline. The primary endpoint was a composite of cardiovascular mortality and readmission for heart failure. The prognostic impact of the sST2/LVMI ratio was evaluated using a multivariable Cox proportional hazards regression model.ResultsForty-five patients were enrolled in this study. Their average age was 48 ± 14 years, and approximately 20% of them were men. Patients were followed for 9 months, during which the primary outcome occurred in 15 patients. Kaplan–Meier analysis showed that patients with a high sST2/LVMI ratio (≥ 0.39) had shorter event-free survival than those with intermediate (between 0.39 and 0.24) and low ratios (< 0.24) (log-rank, P = 0.022). The fully adjusted multivariable Cox regression analysis showed that the sST2/LVMI ratio was positively associated with the composite outcome in patients with heart failure with reduced ejection fraction after adjusting for confounders (hazard ratio 1.64, 95% confidence interval 1.06 to 2.54). By subgroup analysis, a stronger association was found with age between 40 and 55 years, systolic blood pressure < 115 or ≥ 129 mmHg, diastolic blood pressure < 74 mmHg, hematocrit < 44.5%, and interventricular septum thickness ≥ 8.5 mm.ConclusionIn patients with heart failure with reduced ejection fraction, the relationship between the sST2/LVMI ratio and the composite outcome was linear. A higher baseline ratio of sST2/LVMI was associated with an increased risk of cardiovascular mortality and heart failure rehospitalization in the short-term follow-up.

Early reduction of left atrial function predicts adverse clinical outcomes in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement

AimsTo investigate the changes in left atrial strain (LAS) after correction of severe aortic stenosis (AS) with transcatheter aortic valve replacement (TAVR) and assess its prognostic impact.Methods and resultsOne hundred...

Impact of type 2 diabetes and microvascular complications on mortality and cardiovascular outcomes in a multiethnic Asian population

IntroductionDiabetes mellitus is a growing public health epidemic in Asia. We examined the impact of type 2 diabetes, glycemic control and microvascular complications on mortality and cardiovascular outcomes in a...