Rate Of Nonfatal Myocardial Infarction Research Articles

Prognostic impact of quantitative flow ratio (QFR)-consistent complete revascularization in patients with myocardial infarction and multivessel coronary artery disease

Complete revascularization is associated with improved outcomes in patients with myocardial infarction and multivessel coronary artery disease. Quantitative flow ratio (QFR) represents an emerging angiography-based tool for functional lesion assessment. The present study investigated the prognostic impact of QFR-consistent complete revascularization in patients with myocardial infarction and multivessel disease. A total of 792 patients with myocardial infarction and multivessel disease were enrolled in the analysis. Post-hoc QFR analyses of 1320 non-culprit vessels were performed by investigators blinded to clinical outcomes. The primary endpoint was a composite of all-cause death, non-culprit vessel related non-fatal myocardial infarction, and ischemia-driven revascularization at two years after index myocardial infarction. Patients were stratified into a QFR-consistent PCI group (n=646) and a QFR-inconsistent PCI group (n=146), based on whether the intervention was congruent with the QFR-determined functional significance of the non-culprit lesions. The primary endpoint occurred in a total of 22 patients (3.4%) in the QFR-consistent PCI group and in 27 patients (18.5%) in the QFR-inconsistent group (HR 0.17, 95%CI 0.10-0.30, p<0.001).The difference in the primary endpoint was driven by reduced rates of non-fatal myocardial infarction (2.0% vs. 15.1%; HR 0.13, 95%CI 0.06-0.25; p<0.001) and ischemia-driven revascularization (1.2% vs. 5.5%; HR 0.21, 95%CI 0.08-0.57; p=0.001) in the QFR-consistent PCI group. Among patients with myocardial infarction and multivessel disease, a QFR-consistent complete revascularization was associated with a reduced risk of all-cause mortality, non-fatal myocardial infarction, and ischemia-driven revascularization. These findings underline the value of angiography-based functional lesion assessment for personalized revascularization strategies.

Myocardial infarction with nonobstructive coronary arteries: a single-center retrospective study by sex and race.

In myocardial infarction with nonobstructive coronary arteries (MINOCA), there are limited patient-level data on outcomes by sex and race. The aim of this study was to assess baseline demographics and 3-year outcomes by sex and race for MINOCA patients. Patients admitted to a single center with acute myocardial infarction (MI) between 1 January 2012 and 31 December 2018, were identified by chart and angiographic review. The primary outcome was nonfatal MI with secondary outcomes including nonfatal cerebrovascular accident (CVA), chest pain readmission, and repeat coronary angiography. During the study period, 304 patients were admitted with MINOCA. The cohort was predominantly female (66.4%), and women were significantly older (64.6 vs. 59.2). One-sixth of the total population were Black patients, and nearly half of Black patients (47.2%) were male. Prior CVA (19.7%) and comorbid anxiety, depression, or post-traumatic stress disorder (41.1%) were common. Rates of nonfatal MI were 6.3% without difference by sex or race. For secondary outcomes, rates of CVA were 1.7%, chest pain readmission was 22.4%, and repeat angiography was 8.9%. Men were significantly more likely to have repeat angiography (13.7 vs. 6.4%), and Black patients were more likely to be readmitted for angina (34.0 vs. 19.1%). Over one-quarter of patients underwent repeat stress testing, with 8.9% ultimately undergoing repeat angiograms and low numbers (0.7%) undergoing revascularization. Men were more likely to be referred for a repeat angiogram (13.7 vs. 6.4%, P = 0.035). In multivariate analysis, Black race [odds ratio (OR), 2.31; 95% confidence interval (CI), 1.06-5.03] was associated with an increased risk of readmission for angina, while female sex was associated with decreased odds of repeat angiography (OR, 0.36; 95% CI, 0.14-0.90) and current smoking was associated with increased odds of repeat angiography (OR, 4.07; 95% CI, 1.02-16.29)] along with hyperlipidemia (OR, 4.65; 95% CI, 1.22-17.7). White women presented more frequently with MINOCA than White men, however, Black men are equally as affected as Black women. Rates of nonfatal MI were low without statistical differences by sex or race.

Evaluating risk-based allocation strategies for PCSK9 inhibitors: results from a simulation study in a contemporary ASCVD cohort

Abstract Background/Aim Targeting PCSK9 inhibitors (PCSK9i) to patients with high LDL-cholesterol (LDL-C) as well as a high cardiovascular event rate yields the highest therapeutic effect and is thus reasonable from a health economic perspective. The current European dyslipidaemia guideline determines PCSK9i eligibility solely by LDL-C, whereas guidelines from the US/the UK additionally use a set of clinical risk factors. Such selection criteria require evaluation. Methods We determined the cardiovascular event rate and calculated the cost/preventable cardiovascular event for PCSK9i initiation in the target populations according to three scenarios: (i) European Society of Cardiology (ESC) 2019 dyslipidaemia guideline (PCSK9i recommended for all patients with residual LDL-C &amp;gt;55 mg/dl), (ii) American Heart Association/American College of Cardiology (AHA/ACC) 2018 cholesterol guideline (use of PCSK9i restricted to patients with residual LDL-C &amp;gt;70 mg/dl and clinical risk factors) and (iii) UK National Institute for Health and Care (NICE) recommendation (use of PCSK9i restricted to patients with residual LDL-C &amp;gt;155 mg/dl or &amp;gt;135 mg/dl with clinical risk factors). A Monte Carlo simulation taking into account statin intolerance was used to simulate uptitration of lipid lowering medications according to the different scenarios. Analyses were based on patients with atherosclerotic cardiovascular disease (ASCVD) from a contemporary all-comers cohort recruited at a large tertiary care center in Germany. Major adverse cardiovascular events (MACE, defined as the composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke) were recorded over a median follow-up of 4.2 years. Results We included 1922 patients with ASCVD (mean age 69.3 years, median baseline LDL-C 86.0 mg/dl, 75.0% male). Eligibility for PCSK9i was simulated to be 39.6% (ESC 2019), 6.2% (AHA/ACC 2018) and 1.4% (NICE). The 3 year cardiovascular event rates in the corresponding PCSK9i target populations were 11.4%, 13.8% and 13.8% respectively. Event rate differences were driven by a higher rate of non-fatal myocardial infarction in the risk-based target populations (5.2%, 8.2%, 7.2%). Annual cost/preventable event differed by up to a factor 3 (689,000 €, 515,000 € and 215,000 €), driven mainly by pre-PCSK9i LDL-C levels in the different target populations (68.8 mg/dl, 76.0 mg/dl and 182.7 mg/dl). (Table 1) Conclusion The AHA/ACC and NICE guidelines, based on both residual LDL-C and clinical risk factors, reduced the eligibility for PCSK9i as well as the cost/preventable cardiovascular event compared to the ESC guideline. However, the clinical criteria used for risk classification yielded limited discrimination for the identification of subpopulations at highest cardiovascular risk. Development of accurate risk prediction tools and their integration into risk-based allocation strategies, both requisites for a cost-effective use of PCSK9i, remain a challenge.Table 1

Cardiovascular events in patients treated with bempedoic acid vs. placebo: systematic review and meta-analysis.

Reduction of low-density lipoprotein cholesterol (LDL-C) decreases cardiovascular mortality and morbidity. Bempedoic acid represents a promising novel lipid-modifying agent for patients who cannot reach guideline recommended LDL-C goals or statin-intolerant patients, but data on safety and cardiovascular outcomes are limited. We therefore aimed to systematically review randomized controlled trials investigating bempedoic acid vs. placebo in patients with hyperlipidaemia. A systematic search on the databases PubMed, Web of Science, and Embase until 20 March 2023 was performed. All randomized trials comparing bempedoic acid (180mg daily) with placebo in patients with an indication for lipid-lowering therapy were included. As a primary endpoint, we analysed three-point major adverse cardiovascular events (MACEs) consisting of cardiovascular death, non-fatal myocardial infarction (MI), or non-fatal stroke. The analysis was carried out using the odds ratio (OR) as the outcome measure. Due to the expected heterogeneity across studies, a random-effects model was fitted to the data. Out of 258 manuscripts, 10 manuscripts fulfilled the inclusion criteria. In total, these trials included 18200 patients (9765 on bempedoic acid, 8435 on placebo). Bempedoic acid significantly reduced MACEs compared with placebo (OR 0.84 [95% confidence interval (CI) 0.76-0.96]; P<0.001; I2=0%). The endpoint reduction was driven by a lower rate of non-fatal MI, whereas bempedoic acid had no significant effect on stroke (OR 0.86 [95% CI 0.69-1.08]; P=0.20, I2=0%) and all-cause mortality (OR 1.19 [95% CI 0.73-1.93]; P=0.49; I2=18%). Bempedoic acid reduced non-fatal MI in patients with hyperlipidaemia, whereas it had no significant effect on stroke and all-cause mortality.

Prognostic impact of fractional flow reserve measurements in patients with acute coronary syndromes: a subanalysis of the FLORIDA study

Randomized trials suggest benefits for fractional flow reserve (FFR)-guided vs. angiography-guided treatment strategies in well-defined and selected patient cohorts with acute coronary syndromes (ACS). The long-term prognostic value of FFR measurement in unselected all-comer ACS patients, however, remains unknown. This subanalysis of the Fractional FLOw Reserve In cardiovascular DiseAses (FLORIDA) study sought to investigate the long-term effects of FFR in the management of lesions in patients with acute coronary syndrome (ACS). FLORIDA was an observational all-comer cohort study performed in Germany, that was population-based and unselected. Patients enrolled into the anonymized InGef Research Database presenting with ACS and undergoing coronary angiography between January 2014 and December 2015 were included in the analysis. Patients were stratified into either the FFR-guided or the angiography-guided treatment arm, based on the treatment received. A matched cohort study design was used. The primary endpoint was all-cause mortality. The secondary endpoint was major adverse cardiovascular events (MACE), a composite of death, non-fatal myocardial infarction (MI), and repeat revascularization. Follow-up time was 3 years. Rates of 3-year mortality were 10.2 and 14.0% in the FFR-guided and the angiography-guided treatment arms (p = 0.04), corresponding to a 27% relative risk reduction for FFR in ACS patients. Rates of MACE were similar in both arms (47.7 vs. 51.5%, p = 0.14), including similar rates of non-fatal MI (27.7 vs. 25.4%, p = 0.47) and revascularization (9.9 vs. 12.1%, p = 0.17). In this large, all-comer observational study of ACS patients, FFR-guided revascularization was associated with a lower mortality at 3 years. This finding encourages the routine use of FFR to guide lesion revascularization in patients presenting with ACS.

Warranty period of coronary computed tomography angiography and [15O]H2O positron emission tomography in symptomatic patients.

Data on the warranty period of coronary computed tomography angiography (CTA) and combined coronary CTA/positron emission tomography (PET) are scarce. The present study aimed to determine the event-free (warranty) period after coronary CTA and the potential additional value of PET. Patients with suspected but not previously diagnosed coronary artery disease (CAD) who underwent coronary CTA and/or [15O]H2O PET were categorized based upon coronary CTA as no CAD, non-obstructive CAD, or obstructive CAD. A hyperaemic myocardial blood flow (MBF) ≤ 2.3 mL/min/g was considered abnormal. The warranty period was defined as the time for which the cumulative event rate of death and non-fatal myocardial infarction (MI) was below 5%. Of 2575 included patients (mean age 61.4 ± 9.9 years, 41% male), 1319 (51.2%) underwent coronary CTA only and 1237 (48.0%) underwent combined coronary CTA/PET. During a median follow-up of 7.0 years 163 deaths and 68 MIs occurred. The warranty period for patients with no CAD on coronary CTA was ≥10 years, whereas patients with non-obstructive CAD had a 5-year warranty period. Patients with obstructive CAD and normal hyperaemic MBF had a 2-year longer warranty period compared to patients with obstructive CAD and abnormal MBF (3 years vs. 1 year). As standalone imaging, the warranty period for normal coronary CTA is ≥10 years, whereas patients with non-obstructive CAD have a warranty period of 5 years. Normal PET yielded a 2-year longer warranty period in patients with obstructive CAD.

Estimated versus observed 10-year atherosclerotic cardiovascular event rates in a rural population-based health initiative: The Heart of New Ulm Project

ObjectiveAssess discrepancy between estimated 10-year atherosclerotic cardiovascular disease (ASCVD) risk and observed 10-year event rates in a rural population participating in cardiovascular health initiative. MethodsThe study included a rural sample of individuals participating in the Heart of New Ulm (HONU), a population-based health initiative aimed at reducing ASCVD risk in a rural community. HONU conducted over 100 baseline screening events with 5221 individuals participating in 2009. For this analysis, we included participants who were aged 40–79 years, free of ASCVD at baseline, and had adequate data to calculate 10-year ASCVD risk. Electronic health record data and state death records were used to determine rates of non-fatal myocardial infarction and stroke, and ASCVD death from 2010–2019. ASCVD event rates were compared to estimated 10-year risks calculated using the Pooled Cohort Equations, stratified by sex and clinically relevant risk categories. ResultsThe sample (n = 2819, mean ± SD age 56.1 ± 9.9 years, 59.6% female) had a low prevalence of tobacco use (8.1% current smokers) and diabetes (6.5%) and a high prevalence of hypertension (44.4%) and hyperlipidemia (56.6%). The median estimated 10-year ASCVD risk for the entire sample was 5.7% (IQR 2.3–13.5%) with an observed 10-year ASCVD event rate of 3.4%. The largest gap between observed and estimated risk was in those at intermediate/high (≥7.5%) ASCVD risk (median 10-year risk 15.8% [IQR 10.4–29.0], observed ASCVD event rate 6.4%). ConclusioIn a sample of rural participants exposed to a multifaceted ASCVD prevention initiative, observed rates of ASCVD were substantially lower compared to estimated ASCVD risk. The potential for significantly lower than predicted ASCVD event rates in certain populations should be included in the clinician-patient risk discussion.

Clinical and Anamnestic Characteristics, Cardiovascular Pharmacotherapy and Long-term Outcomes in Multimorbid Patients after COVID-19

Aim. To study the clinical and anamnestic characteristics, pharmacotherapy of cardiovascular diseases (CVD) and long-term outcomes in post-COVID-19 patients with cardiovascular multimorbidity (CVMM), enrolled in the prospective hospital registry.Material and methods. In patients with confirmed COVID-19 included in the TARGET-VIP registry, the CVMM criterion was the presence of two or more CVDs: arterial hypertension (AH), coronary heart disease (CHD), chronic heart failure (CHF), atrial fibrillation (AF). There were 163 patients in the CVMM group and 382 – in the group without CVD. The information was obtained initially from hospital history sheet, and afterwards – from a telephone survey of patients after 30-60 days, 6 and 12 months, from electronic databases. The follow-up period was 13.0±1.5 months.Results. The age of post-COVID patients with CVMM was 73.7±9.6 years, without CVD – 49.4±12.4 years (p&lt;0.001), the proportion of men was 53.9% and 58.4% (p=0.34). In the group with CVMM the majority of patients had AH (92.3-93.3%), CHD (90.4-91.4%), and minority – CHF (42.7-46.0%) and AF (42.9-43.4%). The combination of 3-4 CVDs prevailed (58.9-60.3%). The proportion of cases of chronic non-cardiac pathologies was higher in the CVMM group (80.9%) compared to the group without CVD (36.7%; p&lt;0.001). The frequency of proper cardiovascular pharmacotherapy during the follow-up period decreased from 56.8% to 51.3% (p for trend = 0.18). The frequency of anticoagulant therapy in AF decreased significantly: from 89.1% at the discharge from the hospital to 56.4% after 30-60 days (p=0.001), 57.1% and 53.6% after 6 and 12 months of monitoring (p for a trend &lt;0.001). There were no other significant changes in the frequency of other kinds of the proper cardiovascular pharmacotherapy (p&gt;0.05). There were higher rate of all-cause mortality among patients with CMMM (12.9% vs 2.9%, p&lt;0.001) as well as rates of hospitalization (34.7% and 9.9%, p&lt;0.001) and non-fatal myocardial infarction (MI) – 2.5% vs 0.5% (p=0.048). The proportion of new cases of CVD in the groups with CVMM and without CVD was 5.5% and 3.7% (p=0.33). The incidence of acute respiratory viral infection (ARVI)/influenza was higher in the group without CVD – 28.3% vs 19.0% (p=0.02). The proportion of cases of recurrent COVID-19 in groups with CVMM and without CVD was 3.7 % and 1.8% (p=0.19).Conclusion. Post COVID-19 patients with CVMM were older and had the bigger number of chronic non-cardiac diseases than patients without CVD. The quality of cardiovascular pharmacotherapy in patients with CVMM was insufficient at the discharge from the hospital with following non-significant decrease during 12 months of follow-up. The frequency of anticoagulant therapy in AF decreased by 1.6 times after 30-60 days and by 1.7 times during the year of follow-up. The proportion of new cases of CVD was 5.5% and 3.7% with no significant differences between compared groups. The rate of all-cause mortality, hospitalizations and non-fatal MI was significantly higher in patients with CVMM, but the frequency of ARVI/influenza was significantly higher in patients without CVD. Recurrent COVID-19 was registered in 3.7% and 1.8% of cases, there were no significant differences between compared groups.

Implications of transient ischemic dilatation and impaired left ventricular ejection fraction reserve in patients with normal stress myocardial perfusion imaging and elevated coronary artery calcium.

Guidelines recommend stress only (SO) myocardial perfusion imaging (MPI) without follow-up rest imaging if perfusion and left ventricular ejection fraction (LVEF) are normal. However additional rest imaging may show transient ischaemic dilation (TID) and/or impaired LVEF reserve (iLVEFr) suggestive of 'balanced ischemia'. Concurrent coronary artery calcium (CAC) scoring helps to identify subclinical atherosclerosis. The safety of SO MPI when CAC is elevated is unclear. We aim to assess the incidence and outcomes of TID and iLVEFr amongst stress/rest MPIs with normal SO images and elevated CAC. Retrospective analysis of normal stress/rest MPIs performed between 1 March 2016 to 31 January 2017 with concurrently measured CAC >300. Cases were stratified by presence of TID and/or iLVEFr. Major adverse cardiac events (MACE, defined as cardiac death, non-fatal myocardial infarction and revascularization) within 24 months were compared. There were 230 cases included of which 43 (18.7%) had TID and/or iLVEFr. Presence of TID and/or iLVEFr was associated with higher 24-month MACE (23.3 vs. 8.6%, p = 0.013), driven by more elective revascularizations (18.6 vs. 4.3%, p = 0.001). Cardiac death and non-fatal myocardial infarction rates were similar. TID and/or iLVEFr significantly predicted overall MACE after multivariate analysis (OR 2.933 [1.214 - 7.087], p = 0.017). TID and/or iLVEFr is seen in the minority of normal stress MPI with elevated CAC, and is associated with higher 24-month MACE, driven by higher elective revascularizations. Overall cardiac death and non-fatal myocardial infarction rates were low and not significantly different between both groups.

Elevated Cystatin-C Levels Are Associated with Increased Mortality in Acute Coronary Syndrome Patients: An HIJ-PROPER Sub-Analysis

Background and Aims: We investigated the association between serum cystatin-C (Cys-C) levels and cardiovascular events in patients with acute coronary syndrome (ACS). Methods: Data of 1,100 patients from the prospective parent study were included. Patients hospitalized for ACS were divided into 4 groups based on quartiles (Q) of Cys-C levels (mg/L) within 24 h of admission: Q1, ≤0.82; Q2, 0.82 < estimated level ≤0.95; Q3, 0.95< estimated level ≤1.12; and Q4, >1.12. The primary endpoint of this study was all-cause mortality, and the secondary endpoint was composite of all-cause mortality, nonfatal myocardial infarction, nonfatal stroke, unstable angina pectoris, or ischemia-driven revascularization. Results: During a median observation period of 4.0 years, the primary endpoint was noted in 5, 12, 18, and 36 patients in Q1–Q4, respectively, with corresponding incidence rates of 1.8%, 4.4%, 6.5%, and 13.5%, respectively (p < 0.0001 for difference among 4 groups). This association persisted even after adjusting for patient characteristics and other laboratory results at baseline (p = 0.04). A stepwise increase in the incidence rate of the secondary endpoint with an incline in Cys-C levels was observed in the nonadjusted model (26.6%, 33.3%, 32.3%, and 39.1% in Q1–Q4, respectively; p = 0.01) but not in the adjusted model (p = 0.3). No difference was observed in the incidence rate of nonfatal myocardial infarction (p = 0.89), nonfatal stroke (p = 0.3), unstable angina pectoris (p = 0.49), and ischemia-driven revascularization (p = 0.47) with an incline in Cys-C levels. Conclusion: Elevated Cys-C levels were associated with increased all-cause mortality but not cardiovascular events other than mortality in ACS patients.

Outcomes in the ISCHEMIA Trial Based on Coronary Artery Disease and Ischemia Severity.

The ISCHEMIA trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) postulated that patients with stable coronary artery disease (CAD) and moderate or severe ischemia would benefit from revascularization. We investigated the relationship between severity of CAD and ischemia and trial outcomes, overall and by management strategy. In total, 5179 patients with moderate or severe ischemia were randomized to an initial invasive or conservative management strategy. Blinded, core laboratory-interpreted coronary computed tomographic angiography was used to assess anatomic eligibility for randomization. Extent and severity of CAD were classified with the modified Duke Prognostic Index (n=2475, 48%). Ischemia severity was interpreted by independent core laboratories (nuclear, echocardiography, magnetic resonance imaging, exercise tolerance testing, n=5105, 99%). We compared 4-year event rates across subgroups defined by severity of ischemia and CAD. The primary end point for this analysis was all-cause mortality. Secondary end points were myocardial infarction (MI), cardiovascular death or MI, and the trial primary end point (cardiovascular death, MI, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest). Relative to mild/no ischemia, neither moderate ischemia nor severe ischemia was associated with increased mortality (moderate ischemia hazard ratio [HR], 0.89 [95% CI, 0.61-1.30]; severe ischemia HR, 0.83 [95% CI, 0.57-1.21]; P=0.33). Nonfatal MI rates increased with worsening ischemia severity (HR for moderate ischemia, 1.20 [95% CI, 0.86-1.69] versus mild/no ischemia; HR for severe ischemia, 1.37 [95% CI, 0.98-1.91]; P=0.04 for trend, P=NS after adjustment for CAD). Increasing CAD severity was associated with death (HR, 2.72 [95% CI, 1.06-6.98]) and MI (HR, 3.78 [95% CI, 1.63-8.78]) for the most versus least severe CAD subgroup. Ischemia severity did not identify a subgroup with treatment benefit on mortality, MI, the trial primary end point, or cardiovascular death or MI. In the most severe CAD subgroup (n=659), the 4-year rate of cardiovascular death or MI was lower in the invasive strategy group (difference, 6.3% [95% CI, 0.2%-12.4%]), but 4-year all-cause mortality was similar. Ischemia severity was not associated with increased risk after adjustment for CAD severity. More severe CAD was associated with increased risk. Invasive management did not lower all-cause mortality at 4 years in any ischemia or CAD subgroup. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01471522.

Ischemic Burden Reduction and Long-Term Clinical Outcomes After Chronic Total Occlusion Percutaneous Coronary Intervention

The authors sought to evaluate the impact of ischemic burden reduction after chronic total occlusion (CTO) percutaneous coronary intervention (PCI) on long-term prognosis and cardiac symptom relief. The clinical benefit of CTO PCI is questioned. In a high-volume CTO PCI center, 212 patients prospectively underwent quantitative [15O]H2O positron emission tomography perfusion imaging before and three months after successful CTO PCI between 2013-2019. Perfusion defects (PD) (in segments) and hyperemic myocardial blood flow (hMBF) (in ml · min-1 · g-1) allocated to CTO areas were related to prognostic outcomes using unadjusted (Kaplan-Meier curves, log-rank test) and risk-adjusted (multivariable Cox regression) analyses. The prognostic endpoint was a composite of all-cause death and nonfatal myocardial infarction. After a median [interquartile range] of 2.8 years [1.8 to 4.3 years], event-free survival was superior in patients with≥3 versus<3 segment PD reduction (p<0.01; risk-adjusted p=0.04; hazard ratio [HR]: 0.34 [95% confidence interval (CI): 0.13 to 0.93]) and with hMBF increase above (Δ≥1.11ml · min-1 · g-1) versus below the population median (p<0.01; risk-adjusted p<0.01; HR: 0.16 [95%CI: 0.05 to 0.54]) after CTO PCI. Furthermore, event-free survival was superior in patients without versus any residual PD (p<0.01; risk-adjusted p=0.02; HR: 0.22 [95%CI: 0.06 to 0.76]) or with a residual hMBF level >2.3 versus≤2.3ml · min-1 · g-1 (p<0.01; risk-adjusted p=0.03; HR: 0.25 [95%CI: 0.07 to 0.91]) at follow-up positron emission tomography. Patients with residual hMBF >2.3ml · min-1 · g-1 were more frequently free of angina and dyspnea on exertion at long-term follow-up (p=0.04). Patients with extensive ischemic burden reduction and no residual ischemia after CTO PCI had lower rates of all-cause death and nonfatal myocardial infarction. Long-term cardiac symptom relief was associated with normalization of hMBF levels after CTO PCI.

Advances in Myocardial Perfusion MR Imaging: Physiological Implications, the Importance of Quantitative Analysis, and Impact on Patient Care in Coronary Artery Disease.

Stress myocardial perfusion imaging (MPI) is the preferred test in patients with intermediate-to-high clinical likelihood of coronary artery disease (CAD) and can be used as a gatekeeper to avoid unnecessary revascularization. Cardiac magnetic resonance (CMR) has a number of favorable characteristics, including: (1) high spatial resolution that can delineate subendocardial ischemia; (2) comprehensive assessment of morphology, global and regional cardiac functions, tissue characterization, and coronary artery stenosis; and (3) no radiation exposure to patients. According to meta-analysis studies, the diagnostic accuracy of perfusion CMR is comparable to positron emission tomography (PET) and perfusion CT, and is better than single-photon emission CT (SPECT) when fractional flow reserve (FFR) is used as a reference standard. In addition, stress CMR has an excellent prognostic value. One meta-analysis study demonstrated the annual event rate of cardiovascular death or non-fatal myocardial infarction was 4.9% and 0.8%, respectively, in patients with positive and negative stress CMR. Quantitative assessment of perfusion CMR not only allows the objective evaluation of regional ischemia but also provides insights into the pathophysiology of microvascular disease and diffuse subclinical atherosclerosis. For accurate quantification of myocardial perfusion, saturation correction of arterial input function is important. There are two major approaches for saturation correction, one is a dual-bolus method and the other is a dual-sequence method. Absolute quantitative mapping with myocardial perfusion CMR has good accuracy in detecting coronary microvascular dysfunction. Flow measurement in the coronary sinus (CS) with phase contrast cine CMR is an alternative approach to quantify global coronary flow reserve (CFR). The measurement of global CFR by quantitative analysis of perfusion CMR or flow measurement in the CS permits assessment of microvascular disease and diffuse subclinical atherosclerosis, which may provide improved prediction of future event risk in patients with suspected or known CAD. Multi-institutional studies to validate the diagnostic and prognostic values of quantitative perfusion CMR approaches are required.

Semaglutide as an Antidiabetic Medication: A Summary of the Evidence from the Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes Clinical Trial Program

<i>Background</i>: The Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes (SUSTAIN) clinical trial program was a phase III, multinational, multicenter program comprising 13 trials. <i>Objective</i>: Investigate the safety and efficacy of once-weekly, subcutaneous semaglutide versus other antidiabetic comparators, both as a monotherapy and in addition to other antidiabetic medications. <i>Methods</i>: This review summarizes the 10 trials that comprise the bulk of the evidence which led to FDA approval of semaglutide as an antidiabetic drug. Most articles were accessed via the National Center for Biotechnology Information database using pertinent search terms. <i>Results</i>: Semaglutide 0.5 mg and 1 mg weekly subcutaneous injection led to HA1c reductions by 1.1%–1.5% and 1.5%–1.8%, respectively. Bodyweight reduction with 0.5 mg and 1 mg dose of semaglutide ranged from 3.47–4.6 kg and 4.53–6.5 kg, respectively. SUSTAIN 6, in particular, found cardiovascular risk factor benefits, including the rate of nonfatal myocardial infarction, cardiovascular death and nonfatal strokes in high-risk patients correlated with the use of semaglutide in patients with type 2 diabetes. <i>Conclusions</i>: Semaglutide is superior to other glucagon-like peptide-1 receptor agonists, including exenatide, dulaglutide, and liraglutide in hemoglobin A1c reduction. It is also helpful for chronic weight loss and has cardioprotective effects.

Durable Polymer Versus Biodegradable Polymer Drug-Eluting Stents After Percutaneous Coronary Intervention in Patients with Acute Coronary Syndrome: The HOST-REDUCE-POLYTECH-ACS Trial.

Large-scale randomized comparison of drug-eluting stents (DES) based on durable polymer versus biodegradable polymer technology is currently insufficient in patients with acute coronary syndrome (ACS). The present study aimed to prove the noninferiority of the durable polymer DES (DP-DES) compared with the biodegradable polymer DES (BP-DES) in such patients. The HOST-REDUCE-POLYTECH-ACS (Harmonizing Optimal Strategy for Treatment of Coronary Artery Diseases-Comparison of Reduction of Prasugrel Dose or Polymer Technology in ACS Patients) trial is an investigator-initiated, randomized, open-label, adjudicator-blinded, multicenter, noninferiority trial comparing the efficacy and safety of DP-DES and BP-DES in patients with ACS. The primary end point was a patient-oriented composite outcome (a composite of all-cause death, nonfatal myocardial infarction, and any repeat revascularization) at 12 months. The key secondary end point was device-oriented composite outcome (a composite of cardiac death, target-vessel myocardial infarction, or target lesion revascularization) at 12 months. A total of 3413 patients were randomized to receive the DP-DES (1713 patients) and BP-DES (1700 patients). At 12 months, patient-oriented composite outcome occurred in 5.2% in the DP-DES group and 6.4% in the BP-DES group (absolute risk difference, -1.2%; Pnoninferiority<0.001). The key secondary end point, device-oriented composite outcome, occurred less frequently in the DP-DES group (DP-DES vs BP-DES, 2.6% vs 3.9%; hazard ratio, 0.67 [95% CI, 0.46-0.98]; P=0.038), mostly because of a reduction in target lesion revascularization. The rate of spontaneous nonfatal myocardial infarction and stent thrombosis were extremely low, with no significant difference between the 2 groups (0.6% versus 0.8%; P=0.513 and 0.1% versus 0.4%; P=0.174, respectively). In ACS patients receiving percutaneous coronary intervention, DP-DES was noninferior to BP-DES with regard to patient-oriented composite outcomes at 12 months after index percutaneous coronary intervention. Registration: URL: https://wwwclinicaltrials.gov; Unique identifier: NCT02193971.

Abstract 16350: Predicted versus Observed 10-year Cardiovascular Event Rates in a Rural Population-Based Health Program: The Heart of New Ulm Project

Introduction: Assessment of 10-year ASCVD risk via the Pooled Cohorts Equation (PCE) is a standard component of the clinician-patient risk discussion to aid treatment decisions for the primary prevention of ASCVD. However, calibration of the PCE to modern populations remains a concern. Methods: We studied a sample of individuals participating in the Heart of New Ulm (HONU) Project, a population-based health program aimed at reducing ASCVD risk in a rural, agricultural community of New Ulm, Minnesota. HONU collected baseline survey data on 5,221 individuals in 2009. For this analysis, we included participants who were aged 40-79 years, free of ASCVD at baseline and had adequate data to calculate 10-year ASCVD risk. New Ulm is served by a single healthcare system, allowing surveillance via electronic health records (EHR). EHR data and state death records were used to determine rates of non-fatal myocardial infarction and stroke, and ASCVD death from 2010-2019. ASCVD event rates were compared to estimated 10-year risks calculated using the PCE, and stratified by sex and clinically relevant risk categories. Results: The sample (n=2,819, mean age 56.1 ± 9.9 years, 59.6% female) had a low prevalence of tobacco use (8.1% current smokers), diabetes (6.5%) and higher prevalence of hypertension (44.4%) and hyperlipidemia (56.6%). The median estimated 10-year ASCVD risk for the entire sample was 5.7% (interquartile range 2.3 -13.5%) with an observed 10-year ASCVD event rate of 3.4%. ASCVD rates were lower than predicted across all risk categories in both men and women, especially in those with a 10-year risk ≥7.5% (Table). Conclusion: In a rural sample exposed to ASCVD risk reduction efforts, observed rates of ASCVD were substantially lower compared to estimated ASCVD risk. The uncertainty of current risk models and the potential for significantly lower than predicted ASCVD event rates in certain populations should be included in the clinician-patient risk discussion.

A longitudinal evaluation of cardiovascular risk factors, treatment patterns, and outcomes in patients with documented cardiovascular disease treated with lipid lowering therapy in the United Kingdom

Abstract Background Over time, guidelines for dyslipidemia management in patients at high risk of atherosclerotic cardiovascular disease (CVD) changed with the goal of improving patient outcomes. Guidelines have been released by the European Joint Task Force in 2007, 2012 and 2016, European Society of Cardiology in 2011, 2016 and 2019, Joint British Societies in 2014, and National Institute for Health and Care Excellence in 2014. Purpose Evaluate cardiovascular risk factors, treatment patterns, and cardiovascular outcomes over time related to dyslipidemia management. Methods Ten prevalent cohorts of patients with documented CVD receiving lipid-lowering therapy (LLT) were created using Clinical Research Practice Datalink (CPRD) records as of January 1, each year from 2008 through 2017. For each cohort, we identified CVD risk factors and LLT, and estimated the 1-year composite rate of fatal and nonfatal myocardial infarction (MI), ischemic stroke (IS), or revascularization. Patient follow-up was censored at the earliest of one year, end of data, or the outcome of interest. Patients in each cohort were required to be ≥18 years old, have ≥1 years of available medical history, and have received ≥2 LLT prescriptions in the prior year. Documented CVD was defined as MI, IS, angina, revascularization, transient ischemic attack, carotid stenosis, abdominal aortic aneurysm, or peripheral arterial disease. Patients could be in multiple cohorts. Results Annual patient counts ranged from 170,501 to 179,137 through 2013 and declined to 94,418 by 2017 (due to fewer patients in the overall CPRD data). Comparing 2008, 2011 (when ESC guidelines were revised) and 2017 showed the following for CVD risk factors: mean age was 71.6, 72.3, and 72.5 years; males were 59.9%, 61.1%, and 63.1%; current smoking was 15.1%, 15.2%, and 13.9%; type 2 diabetes was 18.4%, 20.2%, and 22.4%; stage 3–5 chronic kidney disease was 22.4%, 25.1%, and 22.8%; history of MI was 22.5%, 23.9%, and 27.4%; history of IS was 5.5%, 6.6%, and 7.9%; LDL &amp;lt;1.8 mmol/L was 27.8%, 29.2% and 37.2%; and LDL &amp;lt;1.4 mmol/L was 9.9%, 10.1%, and 15.6%. In terms of treatment, high intensity statin use increased from 12.9% to 15.7% to 30.8%; atorvastatin 40–80 mg use increased from 12.9% to 15.5% to 30.5%; while simvastatin 20–40 mg use decreased from 55.4% to 58.8% to 36.7%. The 1-year cardiovascular event rate declined from 2.54 to 2.35 to 1.96 events per 100 person-years (Figure). Conclusions After 2011 in the UK, there was an increased use of high intensity statins, a greater proportion of patients with LDL levels &amp;lt;1.8 and &amp;lt;1.4 mmol/L, and lower 1-year cardiovascular event rates. While improved CVD management likely contributed to the event rate decline, less than 40% of very high-risk patients achieved an LDL &amp;lt;1.8 mmol/L, and the proportion with LDL &amp;lt;1.4 mmol/L, as recommended by the 2019 ESC guidelines, was less than 20%. Clinicians should continue their efforts to reduce LDL in these patients. Figure 1 Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Amgen

Combining minimal risk stratification and prediction of obstructive CAD – clinical utility of a dual pre-test probability model

Abstract Background The recently updated pre-test probability (PTP) model for diagnosing chronic coronary syndrome suggested by the European Society of Cardiology (ESC) was designed to predict the presence of obstructive coronary artery disease (CAD). In addition to this model, identification of non-obstructive CAD and utilization of preventive interventions may also lower rates of death and non-fatal myocardial infarction. Opposite to the ESC PTP, the minimal risk tool (MRT) is a new model developed to identify individuals without CAD but symptoms suggestive of CAD. We explored a combined use of the 2 models to predict the absence or presence of obstructive CAD. Methods This was a sub-study of the Danish study of Non-Invasive testing in Coronary Artery Disease (Dan-NICAD) which included patients with low-intermediate PTP of CAD. Minimal risk was defined as having a coronary calcium score of 0, no evidence of coronary atherosclerosis at coronary computed tomography angiography, and no cardiovascular (CV) events defined as myocardial infarction, death or revascularization in the mean observation period of 3.1 [2.7–3.4] years. Obstructive CAD was defined as a fractional flow reserve &amp;lt;0.80 in a major vessel during invasive coronary angiography (ICA) or a high-grade stenosis by visual assessment (&amp;gt;90% lumen reduction). The risk factors included in the MRT were age, sex, smoking history, diabetes mellitus, dyslipidaemia, family history of premature CAD, hypertension, symptoms related to stress, and high-density lipoprotein concentration. Based on a point-system ranging from 0–5, the MRT and the ESC PTP were combined (dual-PTP) (figure 1). A dual-PTP ≤1 indicated very low risk. Using both minimal risk and obstructive CAD as references, the dual PTP was compared to the MRT and the ESC PTP through tests of model discrimination. Results Of the 1544 eligible patients, 710 (46%) had normal coronary arteries and no CV events. Obstructive CAD was diagnosed in 152 (10%). Equivalent to a dual-PTP &amp;lt;1 point, 209 patients with ESC PTP&amp;lt;5% and MRT&amp;gt;50% or ESC PTP 5–15% and MRT &amp;gt;75% were classified as very low risk. Of these patients, 84% were at true minimal risk (red area figure 1). Furthermore, only 6 patients would have been diagnosed with obstructive CAD at ICA, and 0 events would be missed. The dual-PTP was non-inferior to the MRT and the ESC PTP in identifying patients having minimal risk and obstructive CAD, respectively (minimal risk: c-statistics 0.74 (0.72–0.77) vs. 0.76 (0.73–0.78); obstructive CAD: c-statistics 0.66 (0.62–0.70) vs. (0.67 (0.63–0.72)). The dual-PTP was superior to the ESC PTP in discriminating patients at minimal risk (c-statistics 0.74 (0.72–0.77) vs. 0.69 (0.67–0.71). Conclusions Combining the ESC PTP and the MRT, the dual-PTP seems to enable accurate prediction of both patients with minimal risk and patients with obstructive CAD. Based on the dual-PTP, patients can safely be deferred from or referred for diagnostic testing Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Aarhus University, Health Research Fund of Central Denmark Region

The investigation and prognosis in patients with non-alcoholic fatty liver disease and coronary vulnerable plaque

Objective: To investigate the prevalence and prognosis of non-alcoholic fatty liver disease (NAFLD) complicated with coronary vulnerable plaque (VP). Method: Consecutive patients were included who had undergone coronary artery CT angiography (CCTA) from January 1, 2011 to January 30, 2015 at the First People's Hospital of Neijiang. NAFLD was diagnosed according to the liver imaging findings (liver/spleen CT ratio≤1.0) and clinical data. Baseline data, diagnosis, vulnerable plaque were recorded and followed up. The end points included all-cause death rate, cardiac death rate, non-fatal myocardial infarction rate, and elective coronary revascularization rate. Result: A total of 1 069 patients were eventually recruited in this study, including 316 (29.6%) cases diagnosed as NAFLD. In patients with NAFLD, 130 (41.1%) cases had vulnerable plaque, which was significantly higher than 217 of 753 non-NAFLD patients (28.8%) (P<0.01). The percentages of spotty calcification, low attenuation plaque, positive remodeling and napkin ring sign in NAFLD cohort were 36.5%, 14.2%, 17.6% and 6.8% respectively, while those corresponding in non-NAFLD cohort were 18.4%, 6.3%, 5.8% and 3.2% respectively. The proportion of each vulnerable feature in NAFLD cohort was significantly higher than that in the non-NAFLD cohort, with P values of 0.016, 0.028, 0.019 and 0.042, respectively. The cardiac mortality rate in NAFLD group was significantly higher than and that of non-NAFLD group (7.0% vs. 3.6%, P=0.044). Multivariate Cox analysis suggested that NAFLD was not an independent risk factor for cardiac death. NAFLD subgroup (n=316) was divided into VP positive group (NAFLD+VP+, n=130) and VP negative group (NAFLD+VP-, n=186). The mean follow-up time was 4.6±1.3 years. All-cause mortality rate, cardiac death rate, elective coronary artery reconstruction rate, non-fatal myocardial infarction rate in NAFLD+VP+group were 20.8%, 12.3%, 25.4%, 13.8% respectively, which were significantly higher than those corresponding rates in NAFLD+VP-group (5.9%, 3.2%, 8.6%, 6.5%) (P<0.01, 0.002,<0.01, and 0.032 respectively). Conclusion: The incidences of cardiac mortality, elective coronary revascularization, and non-fatal myocardial infarction are significantly higher in patients with NAFLD than those without. NAFLD combined with vulnerable plaque of coronary arteries predicts worse prognosis.

MO016MYOCARDIAL INFARCTION IN THE PIVOTAL STUDY OF IV IRON IN HAEMODIALYSIS: A PRE-SPECIFIED SECONDARY ANALYSIS

Abstract Background and Aims Coronary artery disease is prevalent in patients with CKD but how often a myocardial infarction (MI) occurs in patients on maintenance haemodialysis, and the prognostic importance of these MIs, is uncertain. The PIVOTAL trial investigated the effects of proactive high-dose versus reactive low-dose intravenous (IV) iron in incident haemodialysis patients. We now report the rates of MI, sub-types of MI, and the prognostic importance of these MIs, as well as the effect of high versus low dose iron on this event. Method This was a pre-specified secondary analysis of 2141 patients enrolled in the PIVOTAL trial. All potential endpoints in the trial, including MIs were adjudicated by a blinded Endpoint Adjudication Committee. The outcomes of time-to-first MI (type 1 or type 2 MI, STEMI or NSTEMI) and the composite outcome of MI and death due to MI were reported. In addition to time-to-first MI, we also analysed recurrent events, to account for the cumulative burden of events over time, as well as case-fatality related to MI. The time-to-event analyses of the primary, secondary and post hoc outcomes were performed in the intention-to-treat population using Cox proportional hazards regression, with treatment group as the only explanatory variable. The Kaplan–Meier method was used to estimate event rates. Recurrent events were analysed using the proportional-means model of Lin et al. and described in the form of mean frequency functions. Results 8.4% of patients experienced a MI over a median of 2.1 years follow-up. Rates of type 1 MIs (3.2/100 patient years) were 2.5 times higher than type 2 MIs (1.3/100 patient years). NSTEMIs (3.3/100 patient years) were 6.6 times more common than STEMIs (0.5/100 patient years). Mortality was high after non-fatal MI (30-day and 1-year mortality were 11.3% and 39.8%, respectively). In time-to-first event analyses, proactive high-dose IV iron reduced the rate of non-fatal MI (HR 0.69, 95% CI 0.51-0.93; p=0.01) and the composite endpoint of non-fatal and fatal MI (HR 0.69, 95% CI 0.52-0.93, p=0.015) (Figure) when compared to low dose reactive IV iron. The benefits of a proactive high-dose IV iron strategy were seen in type 1 MIs but not type 2 MIs. Conclusion Most MIs in patients on HD were type 1 and NTEMIs. Patients randomised to the high-dose group of PIVOTAL had a substantial reduction in fatal and non-fatal MI compared to those in the low-dose group.