History Of Coronary Artery Disease Research Articles

Prediction of 10-year risk for recurrent atherosclerotic cardiovascular events in a secondary prevention population: Insights from CHART-2 and Suita studies in the Japanese population

Abstract Background Despite the European Society of Cardiology (ESC) guidelines advocating risk prediction models for secondary prevention in established atherosclerotic cardiovascular disease (ASCVD) patients, such models for Japanese individuals remain limited, owing to their comparatively lower ASCVD risk than Western populations. Given this gap, there is a need to develop tailored risk assessment tools for Japanese ASCVD patients to optimize secondary prevention strategies. Purpose Leveraging data from two large-scale, long-term cardiovascular cohorts in Japan, our aim was to develop and externally validate a 10-year risk model predicting recurrent cardiovascular events among patients with established ASCVD. Methods The CHART-2 and Suita studies, large-scale prospective observational multicenter cohort studies in Japan, served as the primary data sources for this investigation. From the CHART-2 study, which comprised 3,560 patients with a history of coronary artery disease or ischemic stroke, we derived our risk model. External validation was conducted using data from the Suita study, which included 445 patients with similar ASCVD backgrounds. The primary outcome of interest was a composite endpoint encompassing cardiovascular death, myocardial infarction, or stroke. Variable selection was performed based on clinically relevant factors previously employed in established risk scores (SMART, REACH, and TRS 2°P risk scores). Logistic regression was utilized for model development, and the predictive performance was assessed using the C-index. Results Over a median follow-up of 10.1 years, the derivation cohort experienced 756 cardiovascular events. Patients in the derivation cohort had an average age of 68.9 ± 10.6 years, with 91% and 24% having a history of coronary artery disease and ischemic stroke, respectively. Using logistic regression, the multivariate model revealed a higher recurrent risk associated with several factors including age, smoking status, systolic blood pressure, diabetes, renal function, number of ASCVD events, atrial fibrillation, lipid levels, left ventricular systolic dysfunction, and statin use. A simple risk score based on these predictors demonstrated a >5-fold gradient of 10-year recurrent risk with a C-index of 0.65 (95% CI 0.63-0.68, Figure). The prediction model was externally validated in the Suita study wit 245 cardiovascular events and a median follow-up of 10.4 years, showing good discriminative ability with a C-index of 0.64 (95% CI 0.60–0.68). Conclusion Our newly developed prediction model offers a valuable tool for identifying individuals at heightened risk of recurrent cardiovascular events over a 10-year period, thereby facilitating more targeted and effective secondary prevention strategies tailored to the unique characteristics of Japanese ASCVD patients.

Imaging human coronary cholesterol/urate crystals with cross-polarized micro-optical coherence tomography

IntroductionBirefringent crystals such as monosodium-urate (MSU) and cholesterol crystals (CC) likely contribute to the progression of coronary artery disease (CAD) due to their potential to exacerbate inflammation through inflammatory cytokine activation. Here, we present cross-polarized micro-optical coherence tomography (CP-µOCT) for visualizing individual birefringent crystals in human coronary arteries.Methods and resultsHuman cadaver coronary arteries with a history of CAD with or without gout were dissected for CP-µOCT imaging. Specimens were processed for histological identification of birefringence under polarization light microscopy (PLM). CP-µOCT visualized needle-crystals that appeared as long projections in orthogonal planes, and PLM confirmed that CP-µOCT-delineated needle-crystals demonstrated negative birefringence. The needle-crystals were dissolved after immersion in uricase (p < 0.05), and thus were MSU. CP-µOCT was three-dimensionally volume-rendered for counting MSU and CCs in 79 regions of interest sized [750 (x) × 500 (y) × 400 (z) µm]. Crystal counts were normalized by the total coronary length utilized. The relationship between CP-µOCT-delineated MSU counts and those seen in corresponding histology, and the difference in coronary MSU amongst gout vs. non-gout patients was analyzed. CP-µOCT-delineated MSU counts were significantly correlated with MSU counted by PLM-based histology (R = 0.98, p < 0.01), and with histology-derived intimal thickening (R = 0.51, p < 0.01). MSU and CCs were both significantly greater in gout patients compared with non-gout patients (p < 0.05).DiscussionThese results demonstrate a significant increase in CP-µOCT-delineated crystals in gout vs. non-gout patients, suggesting that this technology can be used to improve our understanding of crystal-driven coronary pathogenesis.

Impact of neutrophil-to-lymphocyte ratio on clinical outcomes in patients with acute or chronic coronary syndrome undergoing percutaneous coronary intervention

Abstract Background Neutrophil-to-lymphocyte ratio (NLR) has recently emerged as an inflammatory biomarker associated with atherosclerosis and cardiovascular events. However, its role in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) remains unclear. Purpose We aimed to evaluate the clinical impact of baseline NLR in patients undergoing PCI for acute coronary syndrome (ACS) and chronic coronary syndrome (CCS). Methods We retrospectively evaluated all consecutive patients undergoing PCI between 2012-2022 in a large tertiary US hospital. We excluded patients for whom NLR was not available and those who were deemed to have active hematological or infective diseases, including patients presenting with extremely low or high lymphocyte and neutrophil counts or with hs-CRP above 10 mg/L. Quartiles of NLR were derived in the overall population and patients were stratified according to clinical presentation. Within each group, we estimated the risk of 12-month adverse events using the lowest NLR quartile as reference. The primary endpoint was major adverse cardiovascular events (MACE), defined as the composite of all-cause death, myocardial infarction (MI), or stroke. Secondary endpoints were MACE individual components and any periprocedural or post-discharge clinically relevant bleeding. Results A total of 7,201 patients were included in the analysis; of these 3,975 (55.2%) had ACS and 3,226 (44.8%) CCS. Patients in the 4th quartile (NLR > 5.0) were more frequently male, older, and presented more often with chronic kidney disease and complex coronary artery disease. Smoking, diabetes and history of CAD, as well as triglycerides, LDL, non-HDL and total cholesterol levels were lower in the 4th NLR quartile. In patients presenting with CCS, the risk of MACE, all-cause death, MI was similar across NLR quartiles, while the risk of bleeding increased stepwise (Figure 1). In patients presenting with ACS, the 4th NLR quartile had the highest adjusted risk of MACE (HRadj 1.82, 95% CI 1.25-2.67; P=0.002), all cause death (HRadj 2.56, 95% CI 1.41-4.66; P<0.001), and bleeding (HRadj 1.82 95% CI 1.25-2.63, P<0.001) at 1 year, as compared to the lowest quartile (Table 1). Conclusions Among patients undergoing PCI, elevated NLR is strongly associated with risk of MACE and all-cause mortality in patients presenting with ACS but not in those with CCS. Conversely, the risk of bleeding was augmented with higher NLR in both ACS and CCS patients undergoing PCI. In this setting, NLR may inform risk stratification at the time of PCI.

A regional multicentre prospective survey addressing sport-related myocardial infarction: clinical characteristics of 155 patients and one year follow-up

Abstract Background Exercise is a keystone of cardiovascular prevention; however, it is also a powerful trigger of acute cardiovascular events including sudden cardiac arrest and acute myocardial infarction. Contemporary studies addressing these sport-related myocardial infarction (SR-MI) are scarce. Aim To describe clinical characteristics and follow-up of SR-MI. Methods We conducted a regional multicentric prospective survey addressing patients admitted for a SR-MI in 2 intensive coronary units. SR-MI was defined as MI onset occurring during sport or within the 1st hour of recovery. A one-year follow-up was performed by phone call. Results From April 1st 2018 to February 23th 2023, 155 SRMI were included, of whom 13 (8.4%) were female, median age was 61-y. (IQR 54-66). Cycling was the most frequent sport (32.5%) followed by fitness and hiking (12.6% each) then jogging (11.3%) (Figure). Most were ST elevation MI (68.8%). The main risk factors were dyslipidaemia (33.8%), hypertension (27.3%) and tobacco smoking (24.5%). No cardiovascular risk factor other than age was identified in 38 patients (25.7%). Prodromal symptoms were reported by 66 subjects (42.6%). SR-MI occurred mostly during exercise (60.6%). Out of hospital cardiac arrest (OHCA) occurred in 20 (12.6%) patients, more commonly among patients with prior coronary artery disease (CAD) (p = 0.02) and tobacco smoking (p=0.047). A significant single vessel disease was observed in 67 patients (43.2%); revascularization was performed by stenting in 134 patients (86.5%) and surgery in 11 (7.1%). In-hospital death occurred in 4 patients and was associated to OHCA (p=0.007). Among the survivors at time of discharge (151 patients), 141 were eligible to follow-up, none one lost: one patient died suddenly at home, one suffered from a recurrent MI, one experienced a cardioversion from his implantable cardioverter defibrillator (ICD) and an ICD was implanted in 4 others. A cardiovascular rehabilitation was performed in 101 patients (65.2%); from the 30 smokers at the time of SRMI, 26 declared smoking cessation. Conclusions Among patients admitted for a SR-MI, most were male. Prodromal symptoms were common but neglected. OHCA occurred in 1 patient out of 8 and was associated with history of CAD, tobacco smoking and in-hospital death. Such findings highlight the need for mass education to prevention including recognition of prodromal symptoms and management of cardiac arrest. In this exercising population, rehabilitation rate was high and quitting tobacco was commonly achieved.Table

Sex differences in clinical characteristics, phenotypes, management, and long-term outcomes of myocardial injury: an international cohort study

Abstract Background Several studies have demonstrated sex differences in patients presenting to the emergency department (ED) with myocardial infarction, heart failure or syncope. Whether sex-specific differences in chest pain patients with myocardial injury exist is unknown. Purpose To determine whether sex-specific differences in the clinical characteristics, phenotypes, management, and long-term outcomes of patients with myocardial injury exist. Methods Patients presenting to the ED with chest pain suggestive of MI were consecutively enrolled into a prospective multicenter international diagnostic study. Final diagnoses were centrally adjudicated by two independent cardiologists, applying the fourth universal definition of myocardial infarction, using all available medical records, including serial hs-cTn and cardiac imaging. Follow-ups were performed at 3 months, 1-, 2- and 5-years. The primary outcome was 5-year all-cause mortality. Secondary outcomes included 5-year cardiovascular mortality and non-cardiovascular mortality. Multivariable flexible parametric (Royston-Parmar) models assuming proportional hazards were fitted. Models were adjusted for age, history of coronary artery disease, history of malignancy, diabetes, hypertension, smoking status, history of liver disease, and renal function. Results Among 8046 chest pain patients presenting to the ED, 1158 (14.4%) had myocardial injury, of which 358 (31%) were females and 800 (69%) males. Women were older (79 years, vs. 73 years), had fewer cardiovascular risk factors and comparable non-cardiovascular comorbidities except for lung disease which was more commonly found in men. Myocardial injury phenotypes varied between sexes (Figure). The most common phenotype in both sexes was heart failure, yet it was more common in men (37.2%) than in women (22.3%). The second most common phenotype in women was hypertension (15.4%) and arrhythmia (15.4 %), while in men was myocarditis (17.8 %), followed by arrhythmia (15.8%). Women underwent less invasive coronary angiography (19.8% vs 26.9%) or stress testing (12% vs 21.5%). In the angiographic findings, women presented more often with normal findings (30.4% vs. 19.6%) or mild CAD (20.3% vs. 11.2%) whereas men displayed more frequently 3-vessel disease (14.5% vs. 36.4%), Table. After adjusting for known confounders, women were associated with a lower 5-years risk for all-cause mortality (HR 0.69; 95%CI: 0.56–0.83) and cardiovascular mortality (HR 0.61; 95%CI: 0.46–0.79). No statistically significant difference in non-cardiovascular mortality risk was found (HR 0.79; 95%CI: 0.59-1.04). Conclusions Women presenting with chest pain to the ED and having myocardial injury were less likely than men to undergo coronary angiography or non-invasive cardiac imaging. Long-term risk for all-cause or cardiovascular mortality was lower for women compared to men.Myocardial Injury phenotypesPatient management

Propensity score-matched analysis in isolated left ventricular dilation and non-ischaemic dilated cardiomyopathy

Abstract Background The presence and extent of late gadolinium enhancement (LGE) assessed by cardiac magnetic resonance imaging (CMR) are strong prognosticators of death in patients with non-ischaemic dilated cardiomyopathy (DCM), defined by the current guidelines as left ventricular (LV) dilation and left ventricular ejection fraction (LVEF)<50%. Although the current guidelines defined the concept of "isolated LV dilation" as LV dilation with preserved LVEF≥50%, the prognostic value of the LGE granularity including its extent, location and pattern is not established in this population. Purpose To assess the prognostic value of the concept of "LGE granularity" including its extent, location, and pattern for predicting all-cause death above traditional prognosticators in patients with LV dilation and reduced LVEF (i.e. DCM) or preserved LVEF (i.e. isolated LV dilation), separately. Methods Between 2008 and 2021, all consecutive patients with DCM and isolated LV dilation without ICD or history of sustained ventricular arrhythmia referred for CMR were included in two centres. All patients with history of coronary artery disease or myocarditis were excluded. The primary outcome was all-cause death using the French National Registry of Death. A 1:1 propensity score matching was performed to balance baseline characteristics in patients with DCM vs. those with isolated LV dilation. Cox regressions were performed to determine the prognostic value of each LGE findings. Results Of 2,752 patients analysed (age 52±8 years, 56% male), 408 (15%) patients died after a median (interquartile range) follow-up of 9 (7-12) years. A total of 737 (27%) patients had LGE. Patients with DCM had a higher rate of death than patients with isolated LV dilation (16% versus 13%, p=0.02). In the propensity-score matched population (N=1,084 in DCM subgroup and N=1,084 in isolated LV dilation), the LGE presence was associated with death (HR=2.98, 95%CI: 1.97-4.50, p<0.001). In isolated LV dilation patients with LGE (N=265), the LGE extent (HR=1.41, 95%CI:1.09-1.83, p=0.009), the presence of LGE in multiple areas (HR=3.86, 95%CI: 1.73-8.61, p<0.001) and the septal location (HR=2.97, 95%CI:1.37-6.46, p=0.006) were strong prognosticators of death after adjustment for traditional prognosticators. Similarly, in DCM patients with LGE (N=268), the LGE extent (HR=1.42, 95% CI:1.07-1.89, p=0.014), the presence of LGE in multiple areas (HR=8.41, 95%CI: 3.32-21.3, p<0.001) and the septal location (HR=6.65, 95% CI: 3.02-14.6, p<0.001) were strongly associated with death after adjustment. Conclusion In a large cohort of DCM and isolated LV dilation patients, the concept of "LGE granularity" was independently associated with all-cause death after adjustment for all traditional prognosticators in both DCM and isolated LV dilation. These results suggest the existence of a continuum between isolated LV dilation and DCM, and that CMR assessment could improve the risk stratification in this population.

Hemoglobin/creatinine ratio as long- term prognostic marker in acute coronary syndromes: a praise registry study

Abstract Introduction Anemia and renal impairment are key determinants of adverse outcomes in patients with acute coronary syndrome (ACS). The hemoglobin/creatinine (Hb/Cr) ratio, a simple and universally accessible index that combines these two factors, was found to predict adverse outcomes in patients with cardiovascular disease. There is limited evidence on the performance of the Hb/Cr ratio in predicting long-term adverse outcomes in the specific setting of ACS. Purpose To evaluate the long-term prognostic impact of the Hb/Cr ratio in patients with ACS. Methods Out of the 23,270 ACS patients enrolled in the international PRAISE registry between 2003 and 2019, 3.465 were excluded due to missing data and 19.805 were included in this analysis. The primary endpoint was all-cause mortality at one year follow-up. Secondary endpoints were major bleeding and the composite of all-cause mortality or reinfarction at one year follow-up. A cut-point analysis according to Liu’s method was run to evaluate the best discriminative value of the Hb/Cr ratio for the prediction of all-cause mortality. Results The cut-point analysis showed that a cut-off value of 13.79 represented the most discriminative in predicting all-cause mortality at one year (CI 13.35–14.23; AUC 0.66), and that mortality increased exponentially when the ratio was <12.4. On the basis of this discriminative value, we divided our population into low vs. high Hb/Cr groups. The former included 5,874 (29.7%) patients, while the latter included 13,931 (70.3%). Patients in the low Hb/Cr group were older, more frequently female, and had a higher prevalence of cardiovascular risk factors, comorbidities, and history of coronary artery disease. Conversely, patients in the high Hb/Cr group were mostly men and more frequently admitted with a STEMI diagnosis. One year post-discharge from ACS, all-cause mortality (8.3% vs. 2.3%; p < 0.001), major bleeding (5.4% vs. 2.2%; p < 0.001) and the composite of all-cause mortality or reinfarction (11.6% vs. 4.7%; p < 0.001) were significantly higher in the low Hb/Cr group. Bivariate regression analysis showed that Hb/Cr ratio was inversely associated with all-cause mortality (OR 0.85; CI 0.84 – 0.86; p < 0.0001), major bleeding (OR 0.91; CI 0.89-0.92; p < 0.0001), and the composite of all-cause mortality or reinfarction (OR 0.89; CI 0.88-0.90; p < 0.0001). This association held strongly true even after an extensive adjustment for several covariates, including cardiovascular risk factors, comorbidities, and discharge medical therapy: all-cause mortality (OR 0.95; CI 0.92 – 0.97; p < 0.0001), major bleeding (OR 0.92; CI 0.89-0.95; p < 0.0001), composite of all-cause mortality or reinfarction (OR 0.96; CI 0.94-0.98; p < 0.0001). Conclusions HB/Cr ratio appears to be inversely associated with long-term adverse outcomes among ACS patients. Further research is warranted before routinely considering this index in clinical practice.

Prognostic value of C-reactive protein / albumin ratio for amputation and/or mortality after lower extremity revascularization in haemodialysis patients with peripheral artery disease

Abstract Background Hypoalbuminemia, a manifestation of protein-energy wasting (PEW) or malnutrition, which is commonly observed in patients with chronic kidney disease, is associated with increasing cardiovascular risk. Recently, C-reactive protein (CRP) / albumin ratio has been developed as a newly surrogate marker of the PEW because the PEW seems to result not only from an inadequate diet but also rather be induced by chronic inflammatory status. The aim of this study was to clarify whether pre-procedural CRP/albumin ratio levels could predict amputation and/or mortality after lower extremity revascularization for peripheral artery disease (PAD) in patients on haemodialysis (HD). Methods A total of consecutive 1,850 HD patients successfully undergoing lower extremity revascularization (494 bypass surgery and 1,356 endovascular therapy) were enrolled in this study. Patients were divided into tertiles according to pre-procedural CRP/albumin ratio levels; low (<0.6, n=619), middle (0.6-3.7, n=609) and high tertile (>3.7, n=622). They were followed up for up to 8-year. The primary endpoint was defined as amputation and/or mortality. Results During follow-up period (median of 53 months), 162 major amputation (8.8%) was performed and 508 patients (27.5%) died. Cumulative incidence rates of amputation and/or mortality at 8-year were 47.4%, 56.2% and 70.0% in low, middle and high tertile of CRP/albumin ratio, respectively (p<0.0001). After adjustment for male, age, traditional risk factors, body mass index, history of coronary artery disease or stroke, procedure (bypass vs. endovascular therapy), infrapopliteal disease and ulcer/gangrene, the CRP/albumin ratio was identified as an independent predictor for amputation and/or mortality [adjusted hazard ratio (aHR) 1.39, 95% confidence interval (CI) 1.12-1.72, p=0.0028 for middle vs. low tertile, and aHR 2.53, 95% CI 2.07-3.09, p<0.0001 for high vs. low tertile, respectively]. Similar results were also observed even for major amputation and mortality, respectively (aHR 2.73, 95% CI 1.77-4.31 for amputation and aHR 2.32, 95% CI 1.82-2.97 for mortality with p<0.0001 for high vs. low tertile in both, respectively, Figure). Conclusion Pre-procedural CRP/albumin ratio could predict both of amputation and mortality after lower extremity revascularization, and could stratify the risk in HD patients with PAD. Measurement of CRP/albumin ratio in such high-risk population may be useful because this newly surrogate marker of the PEW is simple and can be easily obtained in daily practice.

Stratification of residual thromboembolic risk among anticoagulated atrial fibrillation patients: a hierarchical cluster analysis from a global, real-world population

Abstract Background Assessment of residual thromboembolic risk among atrial fibrillation (AF) patients despite being on oral anticoagulants (OACs) poses a significant challenge. This study utilises a hierarchical cluster analysis approach to identify risk phenotypic profiles in a global prospective AF registry. Methods Data were drawn from recently diagnosed non-valvular AF patients receiving OACs, as recorded in phases II and III of the GLORIA-AF (Global Registry on Long-Term Oral Anti-thrombotic Treatment in Patients With Atrial Fibrillation) registry. A hierarchical cluster analysis based on patient demographics was performed to identify distinct phenotypes. The incidence and risks of thromboembolic events (ischaemic stroke, transient ischaemic attack, or systemic embolism) and relevant events (major bleeding and all-cause death) were compared across clusters. Results The study included 22,410 patients (mean age 70±8 years; 56% male), from which 5 phenotypes were delineated: Cluster 1 ("uncontrolled hypertension"), Cluster 2 ("young with a history of coronary artery disease"), Cluster 3 ("young and obese"), Cluster 4 ("frailty"), and Cluster 5 ("non-paroxysmal AF with tachycardia"). Cluster 4 was associated with the highest rates of thromboembolic events (1.66/100 person-years), major bleeding (1.92/100 person-years), and all-cause mortality (6.02/100 person-years). Conversely, Cluster 3 showed the lowest risk profiles across all outcomes (thromboembolic events: 0.64 events/100 person-years, major bleeding: 0.83 events/100 person-years, and all-cause death: 1.44 events/100 person-years). Cluster 1 displayed a moderate thromboembolic event rate (1.04/100 person-years), although lower rates were observed in Clusters 2 and 5 (Figure 1). Conclusions Hierarchical cluster analysis effectively identified distinct phenotypes within a global AF population, offering valuable insights for stratifying the risks of residual thromboembolic events and other significant outcomes in anticoagulated AF patients (Figure 2).Figure 1Figure 2

Incremental prognostic value of late gadolinium enhancement granularity in patients with hypertrophic cardiomyopathy

Abstract Background The prognostic stratification of hypertrophic cardiomyopathy (HCM) using cardiac magnetic resonance (CMR) is based on the extent of late gadolinium enhancement (LGE). To enhance risk stratification for sudden cardiac death (SCD), the ESC has recently added LGE extent in the guidelines, at ≥15% of LV mass. However, SCD has become an uncommon event in this population, and mortality is now mostly related to other phenotypes, such as atrial fibrillation, stroke, and heart failure. While previous studies have showed the prognostic value of LGE to predict all-cause mortality, the prognostic impact of additional LGE features is not well established. Therefore, we aimed to assess the incremental prognostic value of the granularity of LGE including extent, location, and pattern in patients with HCM to predict all-cause death. Methods Between 2008 and 2021, all patients referred for HCM assessment using CMR, without history of coronary artery disease (CAD) or clinical history of myocarditis were prospectively recruited in two French centers. The outcome was all-cause death using the French National Registry of Death. The concept of "LGE granularity" was defined as a comprehensive model combining all the following LGE features with extent (by segment), location (septal or others), and pattern (midwall and/or subepicardial). Using nested Cox proportional hazard models, the additional predictive value of LGE features was assessed by the C-statistic increment, the continuous net reclassification improvement (NRI), the integrative discrimination index (IDI) and the global Chi-2. Results Among the 2,672 included patients (52±7 years, 56% males), 862 (32%) had LGE. After a median (IQR) follow-up of 9 (7–11) years, 447 (17%) patients died. Survival curves show an increased risk for LGE presence (log-rank p<0.001, Figure 1A). After adjustment for traditional prognosticators in the overall population (N=2,672), the presence of LGE was strongly associated with all-cause death (adjusted hazard ratio (HR) 3.96, 95% CI: 3.26-4.80, p<0.001). In the subgroup of patients with LGE (n=862), survival curves showed that all parameters defining the LGE granularity were associated with a higher risk of all-cause death (all p<0.001, Figure 1B). A nested Cox model adjusted on traditional prognosticators showed that the LGE extent, location and pattern were all independently associated with all-cause death (all p<0.001, Figure 2). The model of "LGE granularity" combining all independently significative LGE features showed the best improvement in model discrimination and reclassification above traditional prognosticators (C-statistic improvement: 0.90; NRI=41.9%; IDI=13.2%, Chi-2 global=450, all p<0.001; LR-test p<0.001, Figure 2). Conclusion In a large cohort of HCM patients, the "LGE granularity" model combining the extent, location, and pattern of LGE had an incremental prognostic value over and above traditional prognosticators to predict all-cause death.Prognostic value of LGE granularityIncremental prognostic value LGE granula

Standard modifiable risk factors (SMuRF) paradox for the prognosis in the patients with acute myocardial infarction

Abstract Background Hypertension, diabetes, dyslipidemia and smoking are recognized as standard modifiable risk factors (SMuRFs) for adverse cardiovascular events such as acute myocardial infarction (AMI). Recent studies have shown that AMI patients without SMuRFs are associated with increased mortality compared to those with SMuRFs. However, the relationship between the number of SMuRFs in patients with AMI and mortality has not been well evaluated. Purpose The purpose of this study was to evaluate the clinical characteristics and prognosis of AMI patients stratified by the number of SMuRFs. Methods We studied 6,706 AMI patients between 2013 and 2021 using data from the Mie ACS registry, a retrospective and multicenter registry. For the purpose of this study, only AMI patients as their first cardiovascular events were included in this analysis. Therefore, after excluding patients with a known history of coronary artery disease (n=982), 5724 AMI patients were included in the current analysis. All-cause mortality was compared with 30-day and after 30-day mortality in AMI patients stratified by the number of SMuRFs as the primary outcome. In addition, all-cause mortality rate was compared in AMI patients without and with SMuRFs after propensity score matching on age, sex, body mass index, Killip classification, cardiac arrest before presentation, multivessel disease, left main truck disease, hemoglobin and emergent percutaneous coronary intervention. Results Among 5,724 AMI patients, 672 patients (11.7%) did not have SMuRFs. The median age of patients without SMuRFs was higher than that of patients with any SMuRFs (73 y.o. vs. 70 y.o, P<0.001), and higher prevalence of female and severe Killip class was observed in patients without SMuRFs compared with those with any SMuRFs (P<0.001, respectively). According to the KM survival curves stratified by number of SMURFs, an increased number of SMURFs was associated with higher 30-day survival rates (P=0.035), and the 30-day landmark analysis showed a trend toward higher survival in patients with the highest number of SMURFs, although not statistically significant (Figure1). Multivariate Cox regression analysis showed that 0 SMuRF was an independent prognostic factor for 30-day mortality with hazard ratio of 1.55 (95%CI; 1.13-2.13, P<0.001). In addition, KM survival curves after propensity score matched analysis showed the poor 30-day mortality in 0 SMuRF group (P=0.036), there was no significant difference in after 30-day mortality between the two groups (Figure 2). Conclusions Patients without SMuRFs had a high 30-day mortality rate, but once they survived the acute phase, their prognosis was comparable to patients with SMuRFs. Moreover, the SMuRF paradox was recognized in the acute phase. This finding highlights the need for early identification of the individuals at risk of developing MI despite the absence of SMuRFs and strict acute management regardless of the number of SMuRFs.

Outcomes of post-acute coronary syndrome patients enrolled in a phase 2 cardiac rehabilitation program

Abstract Introduction Cardiac rehabilitation (CR) is a class I recommendation in the management of patients with acute coronary syndrome (ACS), namely ST-elevation myocardial infarction (STEMI) and non-ST acute coronary syndrome (NST-ACS). Reported mortality and recurrent cardiovascular (CV) events are still unacceptably high in these patients. Purpose To assess CV outcomes of patients enrolled in a CR program and its association with ACS presentation. Methods Single-center, retrospective observational study that included all consecutive post-ACS patients enrolled in a phase 2 CR program in 2017, with a follow-up of 24 months. Group 1 were patients with STEMI; group 2 were patients with NST-ACS. Major adverse cardiovascular events (MACE) were defined as a composite of death, non-fatal ACS, non-fatal stroke, and unplanned revascularization. Results Of the 202 ACS patients who attended the CR program in 2017, 4 were excluded due to missing data. Of the 198 patients analyzed (age 60.3±10.7 years, 82% male), 101 patients had a STEMI and 97 NST-ACS. STEMI patients were significantly younger (57±9.5 vs. 63±10, p<0.001), with fewer CV risk factors (diabetes 16% vs. 32%, p=0.008; hypertension 51% vs. 72%, p=0.002; obesity 17% vs. 31%, p=0.020; dyslipidemia 54% vs. 77%, p<0.001), except for active smoking (53% vs. 29%, p=0.001), and were less likely to have previous history of coronary artery disease (9% vs. 31%, p<0.001). During the 3-month CR program, both groups achieved significant reduction in body mass index, LDL-Cholesterol, functional capacity, and smoking cessation rates. At 3-, 12-, and 24-months evaluation, both groups showed no differences in risk factor management, nor differences in lipid-lowering therapy, namely percentage of high-intensity statin and ezetimibe use. STEMI patients were treated more frequently with ticagrelor (86% vs. 67%, p=0.001) at baseline. MACE occurrence was significantly lower in STEMI patients (11% vs. 28%, p=0.003), driven mainly by recurrent ACS (4% vs. 15%, p=0.006). Conclusions In our study, NST-ACS patients had significantly higher CV disease burden and worse outcomes at 24-month follow-up. Despite the heightened CV risk in this group, secondary prevention treatment intensity was similar in both groups.

The impact of a dedicated heart failure clinic on patients with heart failure with reduced ejection fraction

Abstract Introduction Heart failure (HF) is not a diagnosis but rather a syndrome with a variety of potential causes and once a patient has been diagnosed as having HF, the underlying etiology should be sought and treated. Thus, patients with HF should be engaged in a disease management program that includes a dedicated wider healthcare team which is critical for delivering the best care for patients. A dedicated HF clinic is one of the cornerstones of this ultimate management program. This clinic is specifically made to make sure of the proper management and follow-up of those patients. There is a scarce evidence of weather a dedicated HF clinic can alter the long-term outcomes of HF patients or not. Thus, the aim of this study is to search for the impact of a dedicated HF clinic on patients with HF with reduced ejection fraction (HFrEF) regarding the symptoms, management received according to latest guidelines, the patients’ quality of life and impact on health care resources. Patients and Methods This is a single center retrospective study that included patients presented to a dedicated heart failure clinic at a secondary care hospital through a one-year period. The study group included patients with diagnosis of HFrEF only who had one or more visit to the HF clinic. These patients served as their own control. Hospital admissions and emergency room visits in the 12-month period preceding enrollment was compared to the number in the following year after enrollment. Patients with incomplete data and those with ejection fraction >40% were excluded. Results The study included 48 patients with a mean age of 65 years, 70.8% of them were males. Most of the patients were hypertensive (77.1%), diabetic (75%) and with history of coronary artery disease (60.4%). Symptoms improved significantly in all patients, left ventricular volumes and ejection fraction improved (31±8.1% vs 40.7±10.5%) (P<0.0001). NT-ProBNP level improved significantly (5927 ng/L vs 3135 ng/L) (P = 0.03). The guideline directed medical therapy was used properly before and after the clinic. There was a significant improvement in the quality of life where the KCCQ-12 score improved from 71.25±13.2 to 83.3±13.3 (P<0.0001), six-minute walk test also improved significantly from 362±184 meters to 479±211 meters (P = 0.005). Regarding the economic impact, there was no significant difference in the number of unplanned visits (20.8% vs 10.4%) (P = 0.16) but there was a significant reduction in the number of HF hospitalizations within one year (20.8% vs 6.25%) (P = 0.038) Conclusion Dedicated HF clinics are very important now for the proper management of HF patients where it is proved that it can improve HF symptoms, improve the quality of life measurements, maintain the proper guideline directed therapy and reduce the economic burden of HF through reducing the number of HF hospitalizations.Clinical dataOutcomes

Iron deficiency and all-cause mortality after myocardial infarction

Abstract Introduction Iron deficiency (ID) is commonly associated with cardiovascular diseases, including myocardial infarction (MI). However, the data on the clinical significance of ID in patients with MI are conflicting. This may be related to the use of various ID criteria. Purpose Our study aimed to compare the association of different ID criteria with all-cause mortality after MI. Methods Consecutive patients hospitalized at a large tertiary heart center for type 1 MI without previous history of coronary artery disease were included. We evaluated the association of different iron metabolism parameters measured on the first day after hospital admission with all-cause mortality during the follow-up. Results Of a cohort of 1,156 patients included (aged 64±12 years, 25% women), 194 (16.8%) died during the median follow-up of 3.4 years (IQR 626-1782 days). A total of 51,7% of post-MI patients had low iron levels (≤13 µmol/L), and 16,3% of them had iron level ≤12.8 µmol/L and soluble transferrin receptor (sTfR) ≥3 mg/L. After multivariate adjustment, iron level ≤13 µmol/L (HR 1.67, 95% CI 1.19-2.34) and the combination of iron level ≤12.8 µmol/L and sTfR ≥3 mg/L (HR 2.56, 95% CI 1.64-3.99) were associated with an increased risk of mortality. This information provided additional predictive value to the GRACE score. No association between ferritin level and mortality was found. Compared to the model which contains iron level, the addition of sTfR improved risk stratification (net reclassification improvement 0.61, 95% CI 0.52-0.69) by reclassifying patients into a higher-risk group. Conclusion ID is common among patients with the first MI. The criteria based on iron and soluble transferrin receptor levels provide the best prediction of mortality, and should be evaluated in future interventional studies with intravenous iron therapy.Kaplan-Meier survival for iron levelsK-M survival for combined ID parameters

Prevalence and incidence of heart failure in patients with type 2 diabetes mellitus. Results of the prospective DIABET-IC study

Abstract Introduction Heart failure (HF) is one of the major health problems in our environment today. Type 2 diabetes mellitus (DM2) is an important cardiovascular risk factor and can increase the burden of HF through various mechanisms. The incidence of HF in DM2 has not been well studied. Purpose The aim of our study was to evaluate the prevalence and incidence of HF in patients with DM2 followed in hospital cardiology and endocrinology departments. Methods The DIABET-IC study is a longitudinal cohort, prospective, multicenter follow-up study that included 1,249 consecutive patients with DM2 in 2018-2019 in 30 Spanish centers in cardiology and endocrinology outpatient clinics. HF was diagnosed according to the clinical records and following the criteria of the European Society of Cardiology. The prevalence of HF at the inclusion visit was analyzed, as well as the incidence of HF (new diagnoses) during a 3-year follow-up. Results Mean age was 67.3±+9.9 years, with 31.7% of the patients being women. Cardiology clinics included 61.9% of patients and endocrinology clinics the remaining 38.1%. There was a previous history of coronary artery disease in 38.6%, hypertensive heart disease in 21% and atrial fibrillation in 31.9%. Cardiovascular and antidiabetic drugs prescribed at the baseline and 3-year visits are shown in figure 1. Figure 2 summarizes the results of the study. The prevalence of HF at the baseline visit was 39.2%, 490 cases (with reduced LVEF 17.3%, mildly reduced 8.1% and preserved 13.8%). After a follow-up of 1,935/100 persons-year of cases without baseline HF, 58 incident cases of HF were diagnosed, 7.6% (32 in the first year, 13 in the second and 13 in the third year of follow-up). The incidence rate was 3.01/100 person-years (95%CI: 2.30-3.92). Of these 58 cases, 23.7% were with reduced LVEF, 28.9% with slightly reduced LVEF and 47.4% preserved. The incidence was higher in patients followed by endocrinology (3.90 vs 2.90/100 persons-year; p=0.042). At the end of the 3-year follow-up, including baseline prevalence, 46.8% of all patients had HF. Conclusions The prevalence and incidence of HF in patients with DM2 are very high. The incidence of HF is around 3% per year, which is almost 8 times higher than the rate found in large studies in the general population. Approximately half of the new cases were HF with preserved LVEF, and the other half with LVEF < 50%. The use of new antidiabetic drugs, such as iSGLT2, which have been shown to reduce the incidence of HF, should be encouraged.

Prognostic impact of the concept of late gadolinium enhancement granularity in non-ischaemic dilated cardiomyopathy

Abstract Background The prognostic stratification of non-ischaemic dilated cardiomyopathy (DCM) to predict the risk of death is mainly driven by the left ventricular ejection fraction (LVEF). Indeed, LVEF<35% is currently the only indication for primary prevention with implantable cardioverter-defibrillator (ICD) in these patients. Beyond LVEF, several cardiac magnetic resonance imaging (MRI) studies have suggested the strong prgnostic impact of late gadolinium enhancement (LGE), and particularly its extent and location. Therefore, we assumed that a more granular approach combining detailed LGE findings including extent, location and pattern could improve risk stratification in this population. Purpose To assess the additional prognostic value of the concept of "Late Gadolinium Enhancement (LGE) Granularity" that includes extent, location, and pattern in non-ischaemic dilated cardiomyopathy (DCM) patients to predict all-cause death. Methods Between 2008-2021, all consecutive patients with DCM without ICD or history of sustained ventricular arrythmia referred for cardiac MRI were included in two French centres. In line with the current ESC and AHA guidelines, DCM was defined by the LV dilation and LVEF< 50% using cardiac MRI. All patients with history of coronary artery disease or clinical history of myocarditis were excluded. The primary outcome was all-cause death using the French National Registry of Death. Cox regressions were performed to determine the prognostic value of each LGE findings. The additional prognostic value of the LGE granularity was assessed by the C-statistic increment, the continuous net reclassification improvement (NRI), and the integrative discrimination index (IDI). Results Of 1,668 DCM patients (age 52±8 years, 54% males), 268 (16%) died after a median (interquartile range) follow-up of 9 (7-12) years. With a median LVEF value of 39% (30-46), 472 (28%) patients had non-ischemic LGE. Using survival curves, patients with LVEF>35% but the LGE septal location showed a higher risk of death compared to all patients with LVEF≤35% with or without LGE (except for the septal location, all p<0.001). In DCM patients with LGE (N=472), LGE extent (adjusted HR: 4.27, 95% CI: 2.22-8.22), septal location (HR: 5.74, 95% CI: 3.35-9.85) and multiple areas of LGE (HR: 4.38, 95% CI: 2.08-9.22; all p<0.001) were all independently associated with death after adjustment for prognosticators. The concept of "LGE granularity" combining all these LGE features showed the best improvement in model discrimination and reclassification over traditional prognosticators including LVEF (C-statistic improvement: 0.14; net reclassification improvement=64.3%; integrative discrimination index=29.0%; all p<0.05). Conclusion In a large cohort of DCM patients, the concept of "LGE granularity" combining LGE extent, location and the presence of multiple areas had an additional prognostic value above traditional prognosticators including LVEF to predict all-cause death.

Regadenoson stress echocardiography: a road ahead

Abstract Introduction Drugs used in stress echocardiography (SE) have important limitations due to side effects and contraindications. Since its approval in 2008, Regadenoson has seen a significant increase in usage. This is largely attributed to its good safety profile and diagnostic accuracy, making it the preferred drug for stress tests in many European centers. However, despite its expanding use and major advantages, current guidelines don't place it as the first choice for SE, probably because the reported experience with this drug remains limited. The aim of the present study was to assess the safety and short-medium term prognosis of patients who underwent Regadenoson SE. Methods Retrospective observational study. Patients who underwent Regadenoson SE between 2017 and 2023 were included. Safety was assessed by monitoring immediate adverse effects following Regadenoson infusion and the need for using an antidote (Aminophylline). A positive test result was defined by the occurrence of any of the following: wall motion abnormalities, left ventricle dilatation, electrocardiographic changes or symptoms of ischemia. During the follow up, we registered the incidence of ischaemic events (admission for unstable angina, acute myocardial infarction (AMI) or cardiovascular (CV) death) and other CV events such as admission for heart failure (HF) and stroke. Additionally, we evaluated patients in both groups who underwent coronary angiography (by computerized tomography or coronary catheterization) during the follow up period. The groups with negative SE (NSE) and positive SE (PSE) were compared. Results The total number of patients was 344, with a median follow up of 29 months. Basal population characteristics and events by group (NSE and PSE) are shown in Figure 1. We needed to use the antidote in only one case, because of ventricular bigeminism, with no other major adverse effects reported. SE was positive in 37 (11%) patients. In this group, patients were more likely to present ischaemic events (16% vs. 3%, p<0.01) and admissions for HF (24% vs. 5%, p <0.01), compared to the NSE one. In those who underwent coronary angiography, revascularization was needed in 14 patients of the PSE group, and only in 7 of the NSE group (38% vs 2%, p < 0.05). The indications for these last cases were persistent angina in 5 patients (2 of them with history of coronary artery disease) and revascularization following an AMI in 2 patients. (Figure 2). Conclusions The probability of an ischaemic event after a negative Regadenoson SE remains very low, unlike positive studies. Regadenoson SE showed to be both safe in assessing ischemic cardiomyopathy and very useful for its prognostic value. These findings encourage its expanding use in the stress echo lab.

Evaluation of coronary microvascular dysfunction and vasospasm in patients with angina and non-obstructive coronary artery disease

Abstract Background Angina in the absence of obstructive coronary artery disease (CAD) is a growing cause of morbidity and mortality, exceeding the economic burden of CAD. Roughly 50-70% of patients undergoing invasive angiography for anginal symptoms have non-obstructive CAD. Within this category, there are distinct sub-populations including patients with angina without evidence of ischemia on prior stress testing (ANOCA), evidence of ischemia on stress testing (INOCA), or history of obstructive CAD with prior revascularization (ANOCA-HxCAD). Coronary microvascular dysfunction (CMD) and/or epicardial vasospasm are common causes of angina in the absence of epicardial CAD despite optimal medical therapy. Differences between these groups, in terms of risk factors and diagnoses remain relatively unknown. Purpose To compare clinical characteristics, symptoms, and diagnoses between patients with ANOCA, INOCA, and ANOCA-HxCAD. Methods In a prospective registry-based cohort study of 306 patients without obstructive CAD (<50% stenosis in epicardial artery) undergoing coronary functional angiography (CFA), we assessed differences in clinical characteristics, symptoms, and CFA diagnoses: (1) endothelial-independent CMD (coronary flow reserve [CFR] <2.5) to adenosine testing, (2) endothelial-dependent CMD (coronary blood flow [CBF]<50% or no change in vessel diameter to 54 mcg intracoronary acetylcholine [ACH]), (3) epicardial vasospasm to 108 mcg intracoronary ACH in 3 groups of patients (ANOCA, INOCA, and ANOCA-HxCAD). Results Among the 306 patients undergoing CFA, 89% were female with a median age of 58 years (49, 67). Patients with ANOCA-HxCAD had a significantly higher prevalence of hypertension, diabetes, heart failure with preserved ejection fraction, and experienced worse dyspnea on exertion as measured by University of San Diego Shortness of Breath (UCSD SOB) in comparison to ANOCA or INOCA patients. However, there were no differences between the groups in terms of anginal severity, functional capacity, or quality of life. In terms of CFA diagnoses, vasospasm was more prevalent in ANOCA-HxCAD (p<0.001) and CMD was more prevalent in ANOCA and INOCA patients (p=0.034) (Table 1). Conclusions Despite differences in clinical characteristics, patients without obstructive CAD have similar anginal severity, functional capacity, and quality of life regardless of evidence of ischemia on prior stress imaging or history of revascularization. There are differences in CFA diagnoses with higher prevalence of CMD in ANOCA and INOCA patients and higher prevalence of vasospasm in ANOCA-HxCAD patients. Determining the underlying diagnoses changes clinical management; therefore, CFA should be considered in all patients without obstructive CAD.

Myocardial SGLT2 expression and cardiac remodeling in patients with severe aortic stenosis: the BIO-AS Study

Abstract Background Cardiac remodeling plays a major role in the prognosis of patients with aortic stenosis (AS) and could impact the benefits of aortic valve replacement. Blood and tissue biomarkers have a differential pattern and expression level in patients with AS, which may retain a pathophysiological role in cardiac remodeling and metabolism. However, the data available are limited and contradictory. Aim Our study aimed to evaluate the expression of sodium-glucose cotransporter 2 (SGLT2) gene and protein in patients with severe AS stratified in high gradient (HG) and low flow-low gradient (LF-LG) AS and its association with cardiac functional impairments. Methods Gene expression and protein levels of main biomarkers of cardiac fibrosis (Galectin-3, sST2, Serpin-4, PINP, PICP, Collagen, TGF-b), inflammation (GDF-15, IL-6, NF-kB), oxidative stress (SOD1, SOD2), and cardiac metabolism (NHE, PPAR-a, PPAR-g, GLUT1, and GLUT4) were evaluated in blood samples and heart biopsies of 45 patients with AS. Results Our study showed SGLT2 gene and protein hyper-expression in patients with LF-LG AS, compared to controls and HG AS (p<0.05). These differences remained significant even after adjusting for age, gender, body mass index, history of diabetes mellitus, arterial hypertension, and coronary artery disease. SGLT2 gene expression was positively correlated with: i) TGF-b (r=0.72, p<0.001) and collagen (r=0.73, p<0.001) as markers of fibrosis; ii) NF-kB (r=0.36, p<0.01) and myocardial IL-6 (r=0.68, p<0.001) as markers of inflammation: iii) SOD2 (r=-0.38, p<0.006) as a marker of oxidative stress; iv) GLUT4 (r= 0.33, p<0.02) and PPAR-a (r=0.36, p<0.01) as markers of cardiac metabolism (Figure 1). Conclusion In patients with LF-LG AS, SGLT2 gene and protein were hyper-expressed in cardiomyocytes and associated with myocardial fibrosis, inflammation, and oxidative stress. The hyper-expression of the SGLT2 gene and protein in patients with LF-LG might pave the way for using SGLT2-Is in this subset population, with the potential to improve the outcomes of AVR and reduce the likelihood of re-hospitalization within one year.Figure 1

Atrial and ventricular mitral regurgitation in the general population

Abstract Background Functional mitral valve regurgitation (FMR) is the result of two concurrent pathomechanisms: (1) the dilatation of mitral valve annulus (atrial) or (2) remodelling of the left ventricle (ventricular) in the absence of relevant leaflet degeneration¹. Even though FMR has been reported to be the most common cause of relevant MR², there is no general accepted definition of the two subtypes, nor are there population-based data regarding their prevalence, distribution and risk profiles¹. Purpose We aimed to evaluate the prevalence of FMR and to provide an in-depth characterisation of the subtypes aFMR and vFMR in the general population. Methods The study included the first 10,000 participants of the population-based Hamburg City Health Study enrolled between 2016 and 2019. Of these, 8.543 echocardiographic samples were available for analysis. Mitral valve was assessed by two independent investigators. Isolated degenerative MRs as determined by valve mobility (prolapse or restrictive) were excluded. FMR was classified as ventricular when fulfilling one of the following criteria: history of myocardial infarction or coronary artery disease, left ventricular ejection fraction (LVEF) ≤ 40%, restrictive leaflet, tenting area ≥ 150 mm² or coaptation depth ≥ 10 mm. All FMR with LVEF > 55% were classified as atrial. Results After excluding the samples with an insufficient image quality or missing data and re-assessment by the second investigator, 216 of 282 participants with a relevant MR (i.e. moderate or severe) remained (2,6% of the total cohort, see figure 1). In the next step, 153 participants were classified as pure FMR (68.9%), the remaining were mainly functional with minor degenerative features. A total of 31 (14.4%) MRs were classified as vFMR, the remaining 185 participants had an aFMR. Female gender was significantly more common in the aFMR cohort. The remaining demographic variables (age, body mass index) as well as established cardiovascular risk factors (i.e., diabetes, smoking, hypertension) were comparable between the vFMR and aFMR cohort. However, vFMR patients had significantly higher levels of NT-proBNP or NHYA state and presented more frequently with an atrial fibrillation (see figure 2). LVEF and LV stroke volume, TAPSE, left atrial ejection fraction and E/A ratio as a parameter of diastolic dysfunction were lower in the vFMR cohort whereas tenting area and left atrial endsystolic volume was significantly increased. Conclusion In our population-based study, aFMR was found to be the predominant subtype of FMR. The established cardiovascular risk factors were comparable in the vFMR and aFMR cohort. Echocardiographic variables differed significantly and indicate more advanced heart failure and LV remodelling in the vFMR cohort. Further categorization of FMR, in particular regarding the prognostic impact and long-term outcomes, is strongly warranted to allow a clinically relevant definition of aFMR and vFMR.Figure 1:Overview of sample sizeFigure 2:Baseline characteristics