Evaluation of deep learning-based reconstruction late gadolinium enhancement images for identifying patients with clinically unrecognized myocardial infarction.

BACKGROUND: The presence of infarction in patients with unrecognized myocardial infarction (UMI) is a critical feature in predicting adverse cardiac events. This study aimed to compare the detection rate of UMI using conventional and deep learning reconstruction (DLR)-based late gadolinium enhancement (LGEO and LGEDL, respectively) and evaluate optimal quantification parameters to enhance diagnosis and management of suspected patients with UMI. METHODS: This prospective study included 98 patients (68 men; mean age: 55.8 ± 8.1 years) with suspected UMI treated at our hospital from April 2022 to August 2023. LGEO and LGEDL images were obtained using conventional and commercially available inline DLR algorithms. The myocardial signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and percentage of enhanced area (Parea) employing the signal threshold versus reference mean (STRM) approach, which correlates the signal intensity (SI) within areas of interest with the average SI of normal regions, were analyzed. Analysis was performed using the standard deviation (SD) threshold approach (2SD-5SD) and full width at half maximum (FWHM) method. The diagnostic efficacies based on LGEDL and LGEO images were calculated. RESULTS: The SNRDL and CNRDL were two times better than the SNRO and CNRO, respectively (P < 0.05). Parea-DL was elevated compared to Parea-O using the threshold methods (P < 0.05); however, no intergroup difference was found based on the FWHM method (P > 0.05). The Parea-DL and Parea-O also differed except between the 2SD and 3SD and the 4SD/5SD and FWHM methods (P < 0.05). The receiver operating characteristic curve analysis revealed that each SD method exhibited good diagnostic efficacy for detecting UMI, with the Parea-DL having the best diagnostic efficacy based on the 5SD method (P < 0.05). Overall, the LGEDL images had better image quality. Strong diagnostic efficacy for UMI identification was achieved when the STRM was ≥ 4SD and ≥ 3SD for the LGEDL and LGEO, respectively. CONCLUSIONS: STRM selection for LGEDL magnetic resonance images helps improve clinical decision-making in patients with UMI. This study underscored the importance of STRM selection for analyzing LGEDL images to enhance diagnostic accuracy and clinical decision-making for patients with UMI, further providing better cardiovascular care.

Detection of unrecognized myocardial infarction by preprocedural transthoracic echocardiography in patients undergoing elective percutaneous coronary intervention.

BACKGROUND: Previous studies showed that unrecognized myocardial infarction (UMI) identified on cardiac magnetic resonance (CMR) was related to worse prognosis. We aimed to investigate the efficacy of preprocedural transthoracic echocardiography (TTE) to detect the presence of UMI in patients undergoing percutaneous coronary intervention (PCI). METHODS: A total of 138 patients with chronic coronary syndrome (CCS) and preserved left ventricular ejection fraction (LVEF) without history of myocardial infarction or revascularization were retrospectively studied. UMI was evaluated with pre-PCI late gadolinium enhancement (LGE)-CMR. TTE and two-dimensional speckle-tracking echocardiography (2D-STE) were performed before PCI. All patients were divided into two groups according to the presence or absence of UMI, and clinical and echocardiographic findings were compared between these two groups. RESULTS: UMI was detected in 43 patients (31.2%). Multivariable logistic regression analysis revealed that higher SYNTAX score, the presence of wall motion abnormalities (WMAs) and lower global longitudinal strain (GLS) were independent predictors of the presence of UMI. Furthermore, GLS provided incremental efficacy for the detection of UMI over abnormal Q waves, SYNTAX score and WMAs. CONCLUSIONS: Preprocedural TTE in combination with 2D-STE could help identify patients with UMI regardless of the presence or absence of ECG findings and WMAs.

Safety and incremental prognostic value of stress cardiovascular magnetic resonance in patients with known chronic kidney disease.

BACKGROUND: Cardiovascular disease (CVD) is the main cause of mortality in patients with chronic kidney disease (CKD). Although several studies have demonstrated the consistently high prognostic value of stress cardiovascular magnetic resonance (CMR), its prognostic value in patients with CKD is not well established. We aimed to assess the safety and the incremental prognostic value of vasodilator stress perfusion CMR in consecutive symptomatic patients with known CKD. METHODS: Between 2008 and 2021, we conducted a retrospective dual center study with all consecutive symptomatic patients with known stage 3 CKD, defined by estimated glomerular filtration rate (eGFR) between 30 and 60 ml/min/1.73 m2, referred for vasodilator stress CMR. All patients with eGFR < 30 ml/min/1.73 m2 (n = 62) were excluded due the risk of nephrogenic systemic fibrosis. All patients were followed for the occurrence of major adverse cardiovascular events (MACE) defined as cardiac death or recurrent nonfatal myocardial infarction (MI). Cox regression analysis was used to determine the prognostic value of stress CMR parameters. RESULTS: Of 825 patients with known CKD (71.4 ± 8.8 years, 70% men), 769 (93%) completed the CMR protocol. Follow-up was available in 702 (91%) (median follow-up 6.4 (4.0-8.2) years). Stress CMR was well tolerated without occurrence of death or severe adverse event related to the injection of gadolinium or cases of nephrogenic systemic fibrosis. The presence of inducible ischemia was associated with the occurrence of MACE (hazard ratio [HR] 12.50; 95% confidence interval [CI] 7.50-20.8; p < 0.001). In multivariable analysis, ischemia and late gadolinium enhancement were independent predictors of MACE (HR 15.5; 95% CI 7.72 to 30.9; and HR 4.67 [95% CI 2.83-7.68]; respectively, both p < 0.001). After adjustment, stress CMR findings showed the best improvement in model discrimination and reclassification above traditional risk factors (C-statistic improvement: 0.13; NRI = 0.477; IDI = 0.049). CONCLUSIONS: In patients with known stage 3 CKD, stress CMR is safe and its findings have an incremental prognostic value to predict MACE over traditional risk factors.

Reassessing the clinical significance of electrocardiographically unrecognized myocardial infarctions: Radionuclide infarct size and its impact on long-term prognosis.

BACKGROUND: Silent or unrecognized myocardial infarction (UMI) diagnosed by surveillance electrocardiography (ECG) carries similarly poor prognosis as recognized MI (RMI) for poorly understood reasons. METHODS: This study included 5430 consecutive patients who presented to the nuclear laboratory and underwent 2-day stress and rest Tc-99m sestamibi and ECG studies between March 1991 and June 1999. UMI was diagnosed if ECG showed Q-wave MI in the absence of a history of RMI. We measured infarct size (% defect size as compared with the entire left ventricular sestamibi uptake), ejection fraction (EF, %), and summed difference score (SDS, sestamibi uptake by myocardium in stress minus sestamibi uptake in rest images as a marker of ischemia). Survival was determined by follow-up survey (median 6 years). RESULTS: We identified 346 UMIs, 628 RMIs, and 4456 subjects without MI (No MI). As compared with RMI, UMI patients had lesser abnormalities on nuclear scans (p < .0001 for all), including smaller infarct size (5.7% vs. 12.2%), higher EF (58% vs. 53%), and lesser ischemia (SDS; 3.9% vs. 2.7%). UMI prognosis was as poor as that of RMI (annual mortality rate 4.7% vs. 4.8% with No MI rate of 2.9%; p < .001 for all comparisons), and this persisted after multivariate analysis. Infarct size quantification successfully risk-stratified ECG-UMI patients, but UMI patients continued to predict mortality even if the infarct size was 0%. CONCLUSIONS: Although UMI patients have lesser abnormalities on nuclear scans, ECG-based UMI continues to independently predict mortality, indicating the continuing relevance of ECG in clinical practice.

Long-term prognostic value of stress perfusion cardiovascular magnetic resonance in patients without known coronary artery disease.

BACKGROUND: To assess the incremental long-term prognostic value of vasodilator stress perfusion cardiovascular magnetic resonance (CMR) in patients without known coronary artery disease (CAD). METHODS: Between 2010 and 2011, consecutive patients with cardiovascular risk factors without known CAD referred for stress CMR were followed for the occurrence of major adverse cardiac events (MACE), defined by cardiovascular mortality or recurrent non-fatal myocardial infarction (MI). Uni- and multivariable Cox regressions were performed to determine the prognostic value of ischemia and unrecognized MI defined by sub-endocardial or transmural late gadolinium enhancement (LGE). RESULTS: Among 2,295 patients without known CAD, 2058 (89.7%) (71.2 ± 12.5 years; 37.5% males) completed the follow-up (median [IQR]: 8.3 [7.3-8.7] years), and 203 had MACE (9.9%). Using Kaplan-Meier analysis, ischemia and unrecognized MI were associated with MACE (hazard ratio, HR: 4.64 95% CI: 3.69-6.17 and HR: 2.88; 95% CI: 2.08-3.99, respectively; both p < 0.001). In multivariable stepwise Cox regression, ischemia and unrecognized MI were independent predictors of MACE (HR = 3.71; 95% CI 2.73-5.05, p < 0.001 and HR = 1.73; 95% CI 1.22-2.45, p = 0.002; respectively) and cardiovascular mortality (HR: 3.13; 95% CI: 2.17-4.51, p < 0.001 and HR = 1.73; 95% CI 1.15-2.62, p = 0.009; respectively). The addition of ischemia and unrecognized MI led to an improved model discrimination for MACE (change in C statistic from 0.61 to 0.72; NRI = 0.431; IDI = 0.053). CONCLUSIONS: Inducible ischemia and unrecognized MI identified by stress CMR have incremental long term prognostic value for the incidence of MACE in patients without known CAD over traditional risk factors and left ventricular ejection fraction.

Long-term prognosis of unrecognized myocardial infarction detected with cardiovascular magnetic resonance in an elderly population.

BACKGROUND: Individuals with unrecognized myocardial infarctions (UMIs) detected with cardiovascular magnetic resonance (CMR) constitute a recently defined group whose prognosis has not been fully evaluated. However, increasing evidence indicate that these individuals may be at considerable cardiovascular risk. The aim of the present study was to investigate the prognostic impact of CMR detected UMIs for major adverse cardiac events (MACE) in community living elderly individuals. METHODS: Late gadolinium enhancement CMR was performed in 248 randomly chosen 70-year-olds. Individuals with myocardial infarction (MI) scars, with or without a hospital diagnosis of MI were classified as recognized MI (RMI) or UMI, respectively. Medical records and death certificates were scrutinized. MACE was defined as cardiac death, non-fatal MI, a new diagnosis of angina pectoris, or symptom-driven coronary artery revascularization. RESULTS: During follow-up (mean 11 years) MACE occurred in 10 % (n = 18/182) of the individuals without MI scars, in 20 % (n = 11/55) of the individuals with UMI, and in 45 % (n = 5/11) of the individuals with RMI, with a significant difference between the UMI group and the group without MI scars (p = 0.045), and between the RMI group and the group without MI scars (p = 0.0004). Cardiac death and/or non-fatal MI occurred in 15, 5, and 3 of the individuals in the NoMI, UMI, and RMI group respectively. Hazards ratios for MACE adjusted for risk factors and sex were 2.55 (95 % CI 1.20-5.42; p = 0.015) for UMI and 3.28 (95 % CI1.16-9.22; p = 0.025) for RMI. CONCLUSIONS: The presence of a CMR detected UMI entailed a more than double risk for MACE in community living 70-year-old individuals.

Sex and ethnic differences in unrecognized myocardial infarctions: Observations on recognition and preventive therapies from the multiethnic population-based HELIUS cohort.

Background: Epidemiological studies suggest sex differences in the prevalence and characteristics of unrecognized and recognized myocardial infarction (uMI, rMI). Despite increasingly diverse populations, observations are limited in multiethnic contexts. Gaining better understanding may inform policy makers and healthcare professionals on populations at risk of uMI who could benefit from preventive measures. Methods: We used baseline data from the multiethnic population-based HELIUS cohort (2011-2015; Amsterdam, the Netherlands). Using logistic regressions, we studied sex differences in the prevalence and proportion of uMIs across ethnic groups. Next, we studied whether symptoms, clinical parameters, and sociocultural factors were associated with uMIs. Finally, we compared secondary preventive therapies in women and men with a uMI or rMI. We relied on pathological Q-waves on a resting electrocardiogram as the electrocardiographic signature for (past) MI. Results: Overall, and in Turkish and Moroccan subgroups, the prevalence of uMIs was higher in men than women. The proportion of uMIs was similar in women (21.0%) and men (18.4%), yet varied by ethnicity. In women and men, symptoms (chest pain, dyspnea) and clinical parameters (hypertension, hypercholesterolemia), and in women also lower educational level and diabetes were associated with lower odds of uMIs. Women (0.0%) and men (3.6%) with uMI were unlikely to receive secondary preventive therapies compared to those with rMI (28.1-40.9%). Conclusions: The prevalence of uMIs was higher in men than women, and sex differences in the proportion of uMIs varied somewhat across ethnic groups. People with uMIs did not receive adequate preventative medications, posing a risk for recurrent events.

Burden of risk factors in women and men with unrecognised myocardial infarction: a systematic review and meta-analysis.

AIMS: Unrecognised myocardial infarction (MI) is a MI that remains undetected in the acute phase and is associated with an unfavourable prognosis. With this systematic review and meta-analysis, we evaluated the burden of cardiovascular risk factors in individuals with unrecognised MI. METHODS AND RESULTS: We searched general population-based cohort studies diagnosing unrecognised MI by electrocardiogram or myocardial imaging up to 24 November 2023. Pooled mean differences (MD) or risk ratios (RR) with 95% confidence intervals (CI) were determined, and random-effects meta-analyses were performed. Fourteen cohort studies were included involving 200,450 individuals (mean age 62.8±9.9 years, 56.0% women), among which 4,322 (2.2%) experienced unrecognised MI (mean age 66.3±8.2 years, 47.8% women) and 4,653 (2.1%) recognised MI (mean age 68.5±7.3 years, 33.8% women). Compared to individuals without MI, those with unrecognised MI had higher body mass index (MD 0.27, 95% CI 0.16-0.39) and systolic blood pressure (MD 4.48, 95% CI 2.81-6.15), and higher prevalence of hypertension (RR 1.27, 95% CI 1.06-1.51) and diabetes mellitus (RR 1.67, 95% CI 1.36-2.06). Furthermore, individuals with unrecognised MI had lower prevalence of hypertension (RR 0.92, 95% CI 0.88-0.97) and diabetes mellitus (RR 0.80, 95% CI 0.70-0.92). CONCLUSION: Individuals with unrecognised MI are characterised by a substantial burden of metabolic risk factors. Our findings suggest insufficient recognition and management of cardiovascular risk factors among individuals with unrecognised MI.

Predictors and prognostic value of coronary computed tomography angiography for unrecognized myocardial infarction in patients with chronic coronary syndrome.

OBJECTIVE: Unrecognized myocardial infarction (UMI) on delayed-enhancement cardiac magnetic resonance imaging (DE-CMR) and coronary computed tomography angiography (CCTA) derived high-risk features provide prognostic information in patients with chronic coronary syndrome (CCS). The study aimed to assess the prognostic value of UMI and predictors of UMI using CCTA in patients with CCS who underwent elective percutaneous coronary intervention (PCI). METHODS: This study enrolled 181 patients with CCS who underwent DE-CMR and CCTA before elective PCI. The CCTA-derived predictors of UMI and the association of baseline clinical characteristics, CCTA findings, and CMR-derived factors, including UMI, with MACEs, defined as death, nonfatal myocardial infarction, unplanned late revascularization, hospitalization for congestive heart failure, and stroke, were investigated. RESULTS: UMI was detected in 57 (31.5%) patients. ROC analysis revealed that the optimal cut-off values of Agatston score and mean peri-coronary fat attenuation index (FAI) for predicting the presence of UMI were 397 and -69.8, respectively. The multivariable logistic regression analysis revealed that left ventricular mass, Agatston score >397, mean FAI >-69.8, positive remodeling of the target lesion, and CCTA-derived stenosis severity were independent predictors of UMI. Kaplan-Meier analysis revealed that patients with UMI were associated with increased risk of MACEs. The Cox proportional hazards analysis showed post-PCI minimum lumen diameter and the presence of UMI were independent predictors of MACEs. The risk of MACEs significantly increased according to the number of four preprocedural CCTA-relevant features of UMI. CONCLUSION: Preprocedural comprehensive CCTA analysis may help predict the presence of UMI and provide prognostic information in patients with CCS who underwent PCI.

Prognostic implications of non-infarct-related territory unrecognized myocardial infarction in patients with non-ST-segment-elevation acute coronary syndrome.

BACKGROUND: Prognostic value of non-infarct-related territory (non-IR) unrecognized myocardial infarction (UMI) in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) remains to be elucidated. We sought to evaluate the prognostic impact of non-IR UMI in patients with first NSTE-ACS presentation. METHODS: This retrospective single-center analysis was conducted in patients with NSTE-ACS without prior history of coronary artery disease, who underwent uncomplicated urgent percutaneous coronary intervention (PCI) within 48 h of admission between August 2014 and January 2018. All patients underwent postprocedural cardiac magnetic resonance imaging (CMR) within 30 days after PCI. Non-IR UMI was defined as the presence of non-IR delayed gadolinium enhancement with an ischemic distribution pattern. We investigated the association of non-IR UMI, other CMR findings and baseline clinical characteristics with major adverse cardiac events (MACE), defined as death, non-fatal myocardial infarction, stroke, late revascularization, and hospitalization for congestive heart failure. RESULTS: A total of 168 NSTE-ACS patients were included [124 men (73.8 %); 66 ±â€¯11 years]. Non-IR UMI was detected in 28 patients (16.7 %). During a median follow-up of 32 (15-58) months, MACE occurred in 10 (35.7 %) patients with non-IR UMI, and 20 (14.3 %) patients without (p = 0.013). Cox's proportional hazards analysis showed that the presence of non-IR UMI was an independent predictor of MACE (hazard ratio [HR], 2.37, 95 % confidence interval [CI], 1.09-5.18, p = 0.030). In patients with NSTE-ACS undergoing urgent PCI, the prevalence of non-IR UMI was 16.7 %. CONCLUSIONS: Non-IR UMI provided prognostic information independent of conventional risk factors and the extent of myocardial injury caused by NSTE-ACS.

Multimodality coronary imaging to predict non-culprit territory unrecognized myocardial infarction in Non-ST-Elevation acute coronary syndrome.

PURPOSE: Unrecognized myocardial infarction (UMI) detected by cardiac magnetic resonance (CMR) imaging is associated with adverse outcomes in patients with acute and chronic coronary syndrome. This study aimed to assess the predictors of optical coherence tomography (OCT) and coronary computed tomography angiography (CCTA) findings for non-infarct-related (non-IR) territory UMI in patients presenting with non-ST-elevation acute coronary syndrome (NSTE-ACS). METHODS: We investigated 69 patients with a first clinical episode of NSTE-ACS who underwent pre-percutaneous coronary intervention (PCI) 320-slice CCTA, uncomplicated urgent PCI with OCT assessment within 24 h of admission, and post-PCI CMR. UMI was assessed using late gadolinium enhancement to identify regions of hyperenhancement with an ischemic distribution pattern in non-IR territories. RESULTS: Non-IR UMI was detected in 11 patients (15.9%). Lower ejection fraction, higher Gensini score, higher Agatston score, high pericoronary adipose tissue attenuation (PCATA), OCT-defined culprit lesion plaque rupture, and OCT-defined culprit lesion cholesterol crystal were significantly associated with the presence of non-IR UMI. On dividing the total cohort was divided into five groups according to the numbers of two OCT-derived risk factors and two CCTA-derived risk factors, the frequency of non-IR UMI frequency significantly increased according to the number of these relevant risk features (p < 0.001). Patients with all of the non-IR UMI risk factors showed 50% prevalence of non-IR UMI, compared with 2.2% of patients with low risk factors (≤ 2). CONCLUSIONS: Integrated CCTA and culprit lesion OCT assessment may help identify the presence of non-IR UMI, potentially providing prognostic information in patients with first NSTE-ACS episode.

Coronary Computed Tomography Angiographic Predictors of Non-culprit Territory Unrecognized Myocardial Infarction Assessed by Cardiac Magnetic Resonance in Non-ST-elevation Acute Coronary Syndrome.

OBJECTIVES: This study sought to assess the predictors of coronary computed tomography angiographic findings for non-infarct-related (non-IR) territory unrecognized myocardial infarction (UMI) in patients with a first episode of non-ST-elevation acute coronary syndrome (NSTE-ACS). BACKGROUND: UMI detected by cardiac magnetic resonance imaging (CMR) is associated with adverse outcomes in patients with both acute coronary syndrome and chronic coronary syndrome. However, the association between the presence of UMI and coronary computed tomography angiographic (CCTA) findings remains unknown. METHODS: We investigated 158 patients with a first clinical episode of NSTE-ACS, who underwent pre-PCI 320-slice CCTA and uncomplicated urgent percutaneous coronary intervention (PCI) within 48 h of admission. In these patients, post-PCI CMR was performed within 30 days from urgent PCI and before non-IR lesion staged PCI. UMI was assessed using late gadolinium enhancement (LGE)-CMR by identifying regions of hyperenhancement with an ischemic distribution pattern in non-IR territories (non-IR UMI). CCTA analysis included qualitative and quantitative assessments of the culprit segment, Agatston score, mean peri-coronary fat attenuation index (FAI), epicardial fat volume (EFV) and epicardial fat attenuation (EFA). RESULTS: Non-IR UMI was detected in 30 vessel territories (9.7%, 30/308 vessels) of 28 patients (17.7%, 28/158 patients). The presence of low-attenuation plaque, spotty calcification, napkin ring sign, and positive remodeling was not significantly different between vessels with and without subtended non-IR UMI. Agatston score >30.0 (OR: 8.39, 95% confidence interval (CI): 2.17 to 32.45, p = 0.002), mean FAI >-64.3 (OR: 3.23, 95% CI: 1.34 to 7.81, p = 0.009), and stenosis severity (OR: 1.04, 95% CI: 1.02 to 1.06, p < 0.001) were independently associated with non-IR UMI. Neither EFV (p = 0.340) nor EFA (p = 0.700) was associated with non-IR UMI. CONCLUSION: The prevalence of non-IR UMI was 17.7 % in patients with first NSTE-ACS presentation. Agatston score, mean FAI, and coronary stenosis severity were independent CCTA predictors of the presence of non-IR UMI. The integrated CCTA assessment may help identify the presence of non-IR UMI before urgent PCI.

Sex-Based Differences in Unrecognized Myocardial Infarction.

Background Myocardial infarction is an important cause of morbidity and mortality in both men and women. Atypical or the absence of symptoms, more prevalent among women, may contribute to unrecognized myocardial infarctions and missed opportunities for preventive therapies. The aim of this research is to investigate sex-based differences of undiagnosed myocardial infarction in the general population. Methods and Results In the Lifelines Cohort Study, all individuals ≥18 years with a normal baseline ECG were followed from baseline visit till first follow-up visit (≈5 years, n=97 203). Individuals with infarct-related changes between baseline and follow-up ECGs were identified. The age- and sex-specific incidence rates were calculated and sex-specific cardiac symptoms and predictors of unrecognized myocardial infarction were determined. Follow-up ECG was available after a median of 3.8 (25th and 75th percentile: 3.0-4.6) years. During follow-up, 198 women experienced myocardial infarction (incidence rate 1.92 per 1000 persons-years) compared with 365 men (incidence rate 3.30; P<0.001 versus women). In 59 (30%) women, myocardial infarction was unrecognized compared with 60 (16%) men (P<0.001 versus women). Individuals with unrecognized myocardial infarction less often reported specific cardiac symptoms compared with individuals with recognized myocardial infarction. Predictors of unrecognized myocardial infarction were mainly hypertension, smoking, and higher blood glucose level. Conclusions A substantial proportion of myocardial infarctions are unrecognized, especially in women. Opportunities for secondary preventive therapies remain underutilized if myocardial infarction is unrecognized.

Imaging of Clinically Unrecognized Myocardial Fibrosis in Patients With Suspected Coronary Artery Disease.

BACKGROUND: Stress cardiac magnetic resonance (CMR) provides accurate assessment of both myocardial infarction (MI) and ischemia. OBJECTIVES: This study aimed to evaluate the incremental prognostic value of unrecognized myocardial infarction (UMI), detected during assessment of coronary artery disease (CAD) by stress CMR, beyond cardiac function and ischemia. METHODS: In the multicenter SPINS (Stress CMR Perfusion Imaging in the United States) study, 2,349 consecutive patients (63 ± 11 years of age, 53% were male) with suspected CAD were assessed by stress CMR and followed over a median of 5.4 years. UMI was defined as the presence of late gadolinium enhancement consistent with MI in the absence of medical history of MI. This study investigated the association of UMI with all-cause mortality and nonfatal MI (death and/or MI), and major adverse cardiac events (MACE). RESULTS: UMI was detected in 347 patients (14.8%) and clinically recognized myocardial infarction (RMI) in 358 patients (15.2%). Compared with patients with RMI, patients with UMI had a similar burden of cardiovascular risk factors, but significantly lower left ventricular ejection fraction (p < 0.001) and lower rates of guideline-directed medical therapies, including aspirin (p < 0.001), statin (p < 0.001), and beta-blockers (p = 0.002). During follow-up, 328 deaths and/or MIs and 528 MACE occurred. In univariate analysis, UMI and RMI were strongly associated with death and/or MI (UMI: hazard ratio [HR]: 2.15; 95% confidence interval [CI]: 1.63 to 2.83; p < 0.001; RMI: HR: 2.45; 95% CI: 1.89 to 3.18) and MACE. Compared with patients with RMI, patients with UMI presented an increased risk for heart failure hospitalization (UMI vs. RMI: HR: 2.60; 95% CI: 1.48 to 4.58; p < 0.001). In a multivariate model including ischemia and left ventricular ejection fraction, UMI and RMI maintained robust prognostic association with death and/or MI (UMI: HR: 1.82; 95% CI: 1.37 to 2.42; p < 0.001; RMI: HR: 1.54; 95% CI: 1.14 to 2.09) and MACE. CONCLUSIONS: In a multicenter cohort of patients with suspected CAD, presence of UMI or RMI portended an equally significant risk for death and/or MI, independently of the presence of ischemia. Compared with RMI patients, those with UMI were less likely to receive guideline-directed medical therapies and presented an increased risk for heart failure hospitalization that warrants further study. (Stress CMR Perfusion Imaging in the United States [SPINS]; NCT03192891).

Silent myocardial infarction and risk of heart failure: Current evidence and gaps in knowledge.

Coronary heart disease (CHD) is the most common underlying risk factor for heart failure (HF); up to one-third of the patients who are hospitalized for HF each year in the United States have a history of myocardial infarction (MI). Although silent MI (SMI) could account for up to one-half of all MIs, only a few studies examined the relationship between SMI and risk of HF. These few studies agreed on their conclusions that SMI is associated with increased risk of HF. However, there was less agreement on the magnitude of risk and the sex differences in the association between SMI and HF, which is probably due to the heterogeneity in how these studies defined SMI. This report summarizes and discusses the current evidence linking SMI to HF, the impact of the methods by which SMI is defined on the reported relationship between SMI and HF, the potential mechanisms for such relationship, the implications of these findings, and the gaps in knowledge that need to be addressed.

Small and large vessel disease in persons with unrecognized compared to recognized myocardial infarction: The Tromsø Study 2007-2008.

BACKGROUND: Unrecognized myocardial infarction (MI) is a frequent condition with unknown underlying reason. We hypothesized the lack of recognition of MI is related to pathophysiology, specifically differences in underlying small and large vessel disease. METHODS: 6128 participants were examined with retinal photography, ultrasound of the carotid artery and a 12­lead electrocardiography (ECG). Small vessel disease was defined as narrower retinal arterioles and/or wider retinal venules measured on retinal photographs. Large vessel disease was defined as carotid artery pathology. We defined unrecognized MI as ECG-evidence of MI without a clinically recognized event. We analyzed the cross-sectional relationship between MI recognition and markers of small and large vessel disease, adjusted for age and sex. RESULTS: Unrecognized MI was present in 502 (8.2%) and recognized MI in 326 (5.3%) of the 6128 participants. Compared to recognized MI, unrecognized MI was associated with small vessel disease indicated by narrower retinal arterioles (OR 1.66, 95% CI 1.05-2.62, highest vs. lowest quartile). Unrecognized MI was less associated with wider retinal venules (OR 0.55, 95% CI 0.35-0.87, lowest vs. highest quartile). Compared to recognized MI, unrecognized MI was less associated with large vessel disease indicated by presence of plaque in the carotid artery (OR for presence of carotid artery plaque in unrecognized MI 0.51, 95% CI 0.37-0.69). No significant sex interaction was present. CONCLUSIONS: Unrecognized MI was more associated with small vessel disease and less associated with large vessel disease compared to recognized MI. These findings suggest that the pathophysiology behind unrecognized and recognized MI may differ.

Long-Term Prognostic Implications of Previous Silent Myocardial Infarction in Patients Presenting With Acute Myocardial Infarction.

OBJECTIVES: This study investigated the prevalence of silent myocardial infarction (MI) in patients presenting with first acute myocardial infarction (AMI), and its relation with mortality and major adverse cardiovascular events (MACE) at long-term follow-up. BACKGROUND: Up to 54% of MI occurs without apparent symptoms. The prevalence and long-term prognostic implications of previous silent MI in patients presenting with seemingly first AMI are unclear. METHODS: A 2-center observational longitudinal study was performed in 392 patients presenting with first AMI between 2003 and 2013, who underwent late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) examination within 14 days post-AMI. Silent MI was assessed on LGE-CMR images by identifying regions of hyperenhancement with an ischemic distribution pattern in other territories than the AMI. Mortality and MACE (all-cause death, reinfarction, coronary artery bypass grafting, and ischemic stroke) were assessed at 6.8 ± 2.9 years follow-up. RESULTS: Thirty-two patients (8.2%) showed silent MI on LGE-CMR. Compared with patients without silent MI, mortality risk was higher in patients with silent MI (hazard ratio: 3.87; 95% confidence interval: 1.21 to 12.38; p = 0.023), as was risk of MACE (hazard ratio: 3.10; 95% confidence interval: 1.22 to 7.86; p = 0.017), both independent from clinical and infarction-related characteristics. CONCLUSIONS: Silent MI occurred in 8.2% of patients presenting with first AMI and was independently related to poorer long-term clinical outcome, with a more than 3-fold risk of mortality and MACE. Silent MI holds prognostic value over important traditional prognosticators in the setting of AMI, indicating that these patients represent a high-risk subgroup warranting clinical awareness.

Prognostic impact of unrecognized myocardial scar in the non-culprit territories by cardiac magnetic resonance imaging in patients with acute myocardial infarction.

Aims: Unrecognized myocardial scar by late gadolinium enhancement (LGE) magnetic resonance imaging (MRI) is strongly associated with cardiac event in patients with stable coronary artery disease. The purpose of this study was to evaluate the prognostic impact of unrecognized non-infarct-related LGE (non-IR-LGE) in patients with acute myocardial infarction (AMI). Methods and results: We studied 269 patients with a first clinical episode of AMI underwent cardiac MRI within 6 weeks after onset (209 men; age, 66 ± 12 years). LGE, cine MRI and T2-weighted imaging were obtained to evaluate the presence and extent of LGE and to evaluate cardiac function. Major adverse cardiac events (MACE) were defined as cardiovascular death, non-fatal AMI, unstable angina requiring revascularization, fatal arrhythmia, and heart failure. Unrecognized non-IR LGE was observed in 13.0% of patients. During follow-up periods (median, 22 months; range, 3-95 months), 8.9% of patients experienced MACE in this study. In addition, 22.9% of patients with unrecognized non-IR LGE and 6.8% of patients without unrecognized non-IR-LGE experienced MACE (P < 0.01). The presence of unrecognized non-IR LGE predicted MACE with a hazard ratio of 3.45 (95% confidential interval, 1.03-11.47; P < 0.01). In addition, unrecognized non-IR LGE was the strongest independent predictors of MACE with a hazard ratio of 3.30 by the Cox proportional hazards model (P < 0.01). In contrast, angiography-proven multi-vessel disease and transmural extent of infarct-related LGE were not independently associated with MACE. Conclusion: Among patients with a first clinical episode of AMI, unrecognized non-IR myocardial scar provides incremental prognostic value for predicting MACE beyond that of common clinical, angiographic and functional variables.

Prevalence of electrocardiographic unrecognized myocardial infarction and its association with mortality.

BACKGROUND: Identifying unrecognized myocardial infarction (MI) is important for secondary prevention. The aim of this study is to determine the prevalence and correlates of unrecognized MI and the association with mortality in the general population. METHODS: All participants ≥18years participating in the Lifelines population, a three-generation Cohort Study and Biobank, were included (n=152,180). Participants with unrecognized MI were matched with controls without MI (1:2) based on age and gender. Unrecognized MI was defined when no history of MI was reported in combination with electrocardiographic (ECG) signs corresponding to MI. A history of MI was defined as a reported history of MI in combination with ECG signs and/or the use of antithrombotic medication. RESULTS: MI was present in 1881(1.2%) of participants and was unrecognized in 431 (22.9%) participants. Under the age of 50years, percentages of unrecognized MI relative to the total amount of MI were 34% and 55% in men and women respectively. Compared to recognized MI, classical cardiovascular risk factors were less prevalent in participants with unrecognized MI. During a median follow- up time of 5, 4 and 4years, 4.4%, 6.4% and 2.2% of participants with unrecognized MI, recognized MI and without MI died, respectively. In a multivariable logistic regression unrecognized MI was an independent predictor of death. CONCLUSIONS: The prevalence of unrecognized MI is substantial and classical cardiovascular risk factors are less prevalent in participants with unrecognized MI. Nevertheless, unrecognized MI is associated with mortality. Risk stratification and early diagnosis is necessary to reduce the morbidity and mortality after MI.

Pain Tolerance in Persons With Recognized and Unrecognized Myocardial Infarction: A Population-Based, Cross-Sectional Study.

BACKGROUND: Unrecognized myocardial infarction (MI) is a prevalent condition associated with a similar risk of death as recognized MI. It is unknown why some persons experience MI with few or no symptoms; however, one possible explanation is attenuated pain sensitivity. To our knowledge, no previous study has examined the association between pain sensitivity and recognition of MI. METHODS AND RESULTS: We conducted a population-based cross-sectional study with 4849 included participants who underwent the cold pressor test (a common experimental pain assay) and ECG. Unrecognized MI was present in 387 (8%) and recognized MI in 227 (4.7%) participants. Participants with unrecognized MI endured the cold pressor test significantly longer than participants with recognized MI (hazard ratio for aborting the cold pressor test, 0.64; CI, 0.47-0.88), adjusted for age and sex. The association was attenuated and borderline significant after multivariable adjustment. The association between unrecognized MI and lower pain sensitivity was stronger in women than in men, and statistically significant in women only, but interaction testing was not statistically significant (P for interaction=0.14). CONCLUSIONS: Our findings suggest that persons who experience unrecognized MI have reduced pain sensitivity compared with persons who experience recognized MI. This may partially explain the lack of symptoms associated with unrecognized MI.