Unrecognized Myocardial Infarction Research Articles

Myocardial Infarction Signs and Symptoms: Females vs. Males.

Cardiovascular disease is the number one killer of females in the United States today, and myocardial infarction (MI) plays a role in many of these deaths. Females also present with more "atypical" symptoms than males and appear to have differences in pathophysiology underlying their MIs. Despite both differences in symptomology and pathophysiology being present in females versus males, a possible link between the two has not been studied extensively. In this systematic review, we analyzed studies examining differences in symptoms and pathophysiology of MI in females and males and evaluated possible links between the two. A search was performed for sex differences in MI in the databases PubMed, CINAHL (Cumulative Index to Nursing and Allied Health Literature) Complete, Biomedical Reference Collection: Comprehensive, Jisc Library Hub Discover, and Web of Science. Seventy-four articles were ultimately included in this systematic review. Typical symptoms for both ST-elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) such as chest, arm, or jaw pain were more common in both sexes, but females presented on average with more atypical symptoms such as nausea, vomiting, and shortness of breath. Females with MI also presented with more prodromal symptoms such as fatigue in days leading up to MI, had longer delays in presentation to the hospital after symptom onset, and were older with more comorbidities than males. Males on the other hand were more likely to have a silent or unrecognized MI, which concurs with their overall higher rate of MI. As they age, females have a decrease in antioxidative metabolites and worsened cardiac autonomic function than male. In addition, at all ages, females have less atherosclerotic burden than mles, have higher rates of MI not related to plaque rupture or erosion, and have increased microvasculature resistance when they have an MI. It has been proposed that this physiological difference is etiologic for the male-female difference in symptoms, but this has not been studied directly and is a promising area of future research. It is also possible that differences in pain tolerance between males and females may play a role in differing symptom recognition, but this has only been studied one time where females with higher pain thresholds were more likely to have unrecognized MI. Again, this is a promising area for future study for the early detection of MI. Finally, differences in symptoms for patients with different atherosclerotic burden and for patients with MI due to a cause other than plaque rupture or erosion has not been studied and are both promising avenues to improve detection and patient care in the future.

Prognostic value of unrecognized myocardial infarction and silent ischemia detected by stress CMR in asymptomatic patients with prior cryptogenic ischemic stroke

Prognostic value of unrecognized myocardial infarction and silent ischemia detected by stress CMR in asymptomatic patients with prior cryptogenic ischemic stroke

Prognostic implications of unrecognized myocardial infarction before elective percutaneous coronary intervention

Unrecognized myocardial infarction (UMI) is associated with adverse outcomes. This prospective, single-center study elucidated the prevalence and prognostic significance of UMI before elective percutaneous coronary intervention (PCI) using delayed-enhancement cardiac magnetic resonance (DE-CMR). We enrolled 236 patients with stable coronary artery disease who underwent DE-CMR before elective PCI. The prevalence of UMI and the association of clinical and CMR-derived variables with major adverse cardiac events (MACE), defined as cardiovascular death, nonfatal MI, hospitalization for congestive heart failure, and unplanned late revascularization, were assessed. Final analysis revealed that 63/213 (29.6%) patients had UMI. Target territory UMI was observed in 38 patients (17.8% of the total cohort, 60.3% of patients with UMI). UMI was significantly associated with sex, diabetes mellitus, left ventricular ejection fraction, SYNTAX score, and fractional flow reserve in the target vessels. During follow-up (median, 23 months), MACE occurred in 17 (27.0%) patients with UMI and 17 (11.3%) without UMI (P = 0.001). Multivariable modeling revealed that UMI (hazard ratio: 2.18, 95%CI, 1.10–4.33, P = 0.001) was an independent predictor of MACE. Kaplan–Meier analysis indicated that the presence of UMI was significantly associated with a higher incidence of MACE. UMI was independently associated with a greater risk of MACE after successful PCI.

Prognostic implications of unrecognized myocardial infarction before elective percutaneous coronary intervention

Abstract Background A non-negligible proportion of myocardial infarction (MI) is not clinically recognized and unrecognized myocardial infarction (UMI) is associated with adverse outcomes. Purpose To determine the prevalence and prognostic significance of UMI by delayed-enhancement cardiac magnetic resonance (DE-CMR) before elective percutaneous coronary intervention (PCI). Methods In this prospective, single-center study, 236 patients with stable coronary artery disease undergoing elective and uncomplicated PCI were studied. All patients underwent DE-CMR before PCI. The prevalence of UMI was evaluated and the association of clinical and CMR-derived variables with primary MACE, defined as cardiovascular death, nonfatal MI, hospitalization for heart failure, unplanned late revascularization, and ischemic stroke was investigated. Results In the final analysis of 213 patients, 63 patients (29.6%) showed UMI. Target territory UMI was observed in 38 (17.8% of total, 60.3% of patients with UMI). UMI was significantly associated with sex, diabetes mellitus, left ventricular ejection fraction, SYNTAX score and fractional flow reserve in target vessels. During follow-up periods (median, 23 months), MACE was observed in 17 (27.0%) of patients with UMI, and 17 (11.3%) without (P=0.001). In a multivariable model, UMI (hazard ratio [HR] 2.18, 95% confidential interval, 1.10–4.33, P=0.001) remained as an independent predictor of MACE. Kaplan–Meier analysis indicated that the presence of UMI was significantly associated with higher incidence of MACE. Conclusions The prevalence of UMI in patients undergoing elective PCI was 29.6%. UMI was independently associated with an increased risk of MACE after successful PCI. Given the non-negligible prevalence and potential clinical significance of UMI, clinical studies comparing PCI and guideline directed medical therapy (GDMT) versus GDMT only strategy might have to take the presence of UMI into consideration. Funding Acknowledgement Type of funding sources: None.

Multimodality coronary imaging to predict non-culprit territory unrecognized myocardial infarction assessed by cardiac magnetic resonance in non-ST-elevation acute coronary syndrome

Abstract Objectives This study sought to assess the predictors of coherence tomography (OCT) and coronary computed tomography angiographic (CCTA) findings for non-infarct-related (non-IR) territory unrecognized myocardial infarction (UMI) in patients with first non-ST-elevation acute coronary syndrome (NSTE-ACS) presentation. Background UMI detected by cardiac magnetic resonance (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 findings of multimodality coronary imaging remains unknown. Methods We investigated 69 patients with a first clinical episode of NSTE-ACS, who underwent pre-PCI 320-slice CCTA, uncomplicated urgent percutaneous coronary intervention (PCI) with OCT assessment within 48 hours of admission, and post-PCI CMR. UMI was assessed on late gadolinium enhancement (LGE-CMR) by identifying regions of hyperenhancement with an ischemic distribution pattern in non-IR territories (non-IR UMI). Results Non-IR UMI was detected in 11 patients (15.9%). ROC analysis revealed the optimal cut-off value of PCATA in culprit vessel for predicting the presence of non-IR UMI were −71.3. Lower ejection fraction, higher Gensini score, high pericoronary inflammation (>−71.3), OCT-defined culprit lesion plaque rupture (OCT-PR), and OCT-defined culprit lesion cholesterol crystal (OCT-CC) were significantly associated with the presence of non-IR UMI (Figure 1A). OCT findings are shown in Figure 1B. Patients with non-IR UMI had a higher prevalence of OCT-PR and OCT-CC than those without. Compared with patients without non-IR UMI, the prevalence of high pericoronary inflammation was higher in patients with non-IR UMI (Figure 1C). When the total cohort was divided into four groups according to the numbers of aforementioned OCT-derived risk factors and PCATA, patients with all of these UMI risk factors showed 46.2% (6/13) prevalence of non-IR UMI, whereas none of 15 patients without these factors showed non-IR UMI (Figure 1D). Conclusions When culprit lesion showed OCT-PR, OCT-CC, and high PCATA, about half of these patients are likely to have non-IR UMI. The integrated CCTA and OCT assessment may help identify the presence of non-IR UMI, potentially providing prognostic information in first NSTE-ACS patients. Funding Acknowledgement Type of funding sources: None.

Incremental prognostic value of stress CMR for cardiovascular risk stratification after a cryptogenic ischemic stroke

Abstract Background One-third of ischemic strokes are “cryptogenic” without clearly identified etiology. Although coronary artery disease (CAD) is the main cause of death after stroke, the interest of CAD screening in patients with cryptogenic stroke is still debated. Purpose The aim of the study was to assess the incremental prognostic value of stress cardiovascular magnetic resonance (CMR) beyond traditional risk factors for predicting cardiovascular events in patients with a prior cryptogenic ischemic stroke. Methods Between 2008 and 2021, consecutive patients with prior cryptogenic strokes referred for stress CMR were included and followed for the occurrence of major adverse cardiovascular events (MACE), defined by cardiovascular death or nonfatal myocardial infarction (MI). Univariable and multivariable Cox regressions were performed to determine the prognostic value of unrecognized MI and silent ischemia. Results Of 542 patients (55.2% male, mean age 71.4±8.8 years) who completed the follow-up (median 5.9 years), 66 (12.2%) experienced MACE. Silent ischemia and unrecognized MI were detected in 18% and 17% of patients, respectively. Using Kaplan-Meier analysis, silent ischemia and unrecognized MI were associated with the occurrence of MACE (hazard ratio, HR: 8.43 [95% CI: 5.11–13.9]; HR: 7.87 [95% CI: 4.80–12.9]; respectively, p<0.001). In multivariable analysis, silent ischemia and unrecognized MI were independent predictors of MACE (HR: 8.08 [95% CI: 4.21–15.5]; HR: 6.65 [95% CI: 3.49–12.7]; respectively, 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=0.428; IDI=0.048). Conclusions In patients with prior cryptogenic stroke, stress CMR findings have an incremental prognostic value to predict MACE over traditional risk factors. Funding Acknowledgement Type of funding sources: None.

Prognostic implication of unrecognized myocardial infarction in patients with non-ST-segment-elevation acute coronary syndrome

Abstract Background Prognostic value of unrecognized non-infarct-related territory (non-IR) myocardial infarction (UMI) in patients with non-ST-segment-elevation acute coronary syndrome (NSTE-ACS) remains to be elucidated. Purpose This study sought to evaluate the prevalence of non-IR UMI and its prognostic value 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 hours 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 all-cause death, non-fatal myocardial infarction, ischemic stroke, late revascularization and hospitalization for congestive heart failure. Results A total of 168 NSTE-ACS patients were included (124 males (73.8%); 66±11 years). Non-IR UMI was detected in 28 patients (16.7%). During a median follow-up of 32 months (15–58), MACE occurred in 10 (35.7%) patients with non-IR UMI, and 20 (14.3%) patients without (P=0.013). Patients with MACE showed higher frequency of non-IR UMI in RCA territory and multi vessel disease, higher level of NT-proBNP at admission, higher Genisini score, and greater extent of UMI. Cox's proportional hazards analysis showed that the presence of non-IR UMI was an independent predictor of MACE (HR 2.34, 95% CI 1.02–5.37, P=0.045), after adjusting confounding factors, such as multi vessel disease and serum levels of NT-proBNP at admission. The discriminant efficacy (IDI and NRI) of predicting MACE was significantly improved when the presence of non-IR UMI added to the reference clinical risk model. Kaplan-Meier analysis revealed that patients with non-IR UMI were significantly associated with poor prognosis. (Figure 1). Conclusions In patients with NSTE-ACS undergoing urgent PCI, the prevalence of non-IR UMI was 16.7%. Non-IR UMI provided prognostic information independent of conventional risk factors. Funding Acknowledgement Type of funding sources: None.

Additional prognostic value of stress cardiovascular magnetic resonance for cardiovascular risk stratification after a cryptogenic ischemic stroke.

BackgroundOne-third of ischemic strokes are “cryptogenic” without clearly identified etiology. Although coronary artery disease (CAD) is the main cause of death after stroke, the interest in CAD screening in patients with cryptogenic stroke is still debated.AimThe aim of the study was to assess the incremental prognostic value of stress cardiovascular magnetic resonance (CMR) beyond traditional risk factors for predicting cardiovascular events in patients with a prior cryptogenic ischemic stroke.Materials and methodsBetween 2008 and 2021, consecutive patients with prior cryptogenic strokes referred for stress CMR were included and followed for the occurrence of major adverse cardiovascular events (MACEs), defined by cardiovascular death or non-fatal myocardial infarction (MI). Univariable and multivariable Cox regressions were performed to determine the prognostic value of unrecognized MI and silent ischemia.ResultsOf 542 patients (55.2% male, mean age 71.4 ± 8.8 years) who completed the follow-up (median 5.9 years), 66 (12.2%) experienced MACE. Silent ischemia and unrecognized MI were detected in 18 and 17% of patients, respectively. Using Kaplan–Meier analysis, silent ischemia and unrecognized MI were associated with the occurrence of MACE [hazard ratio, HR: 8.43 (95% CI: 5.11–13.9); HR: 7.87 (95% CI: 4.80–12.9), respectively, p < 0.001]. In multivariable analysis, silent ischemia and unrecognized MI were independent predictors of MACE [HR: 8.08 (95% CI: 4.21–15.5); HR: 6.65 (95% CI: 3.49–12.7), respectively, 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 = 0.428; IDI = 0.048).ConclusionIn patients with prior cryptogenic stroke, stress CMR findings have an incremental prognostic value to predict MACE over traditional risk factors.

Association of recognized and unrecognized myocardial infarction with depressive and anxiety disorders in 125,988 individuals: A report of the LifeLines cohort study

Association of recognized and unrecognized myocardial infarction with depressive and anxiety disorders in 125,988 individuals: A report of the LifeLines cohort study

Relation of glycemic status with unrecognized MI and the subsequent risk of mortality: The Jackson Heart Study

BackgroundAlmost 1/3 to 1/2 of initial myocardial infarctions (MI) may be silent or unrecognized (UMI), which forecasts future clinical events. Further, limited data exist to describe the potential risk for UMI in African-Americans. The relationship of glucose status with UMI was examined in the Jackson Heart Study: a cohort of African-American individuals. Methods and resultsAt baseline, there were 5,073 participants with an initial 12-lead electrocardiogram (ECG) and fasting glucose measured. Of these participants, 106(2.1%) had a UMI, and 268(4.2%) had a recognized MI. This population consisted of 3,233 (63.7%) participants with normal fasting glucose (NFG), 533 (10.5%) with IFG, and 1,039 (20.4%) with DM. Logistic regression investigated the relationship between glucose status and UMI. Cox proportional hazard models determined the significance of all-cause mortality during follow-up by MI status. The sample was 65% female with a mean age of 55.3 ± 12.9 years. Over a mean follow-up of 10.4 years, there were 795 deaths. Relative to NFG, the crude odds ratio (OR) estimates for UMI at baseline with IFG and DM were 1.00(95% CI:0.48–2.14) and 3.22(2.15–4.81), respectively. With adjustment, DM continued to be significantly associated with UMI [2.30 (1.42–3.71)]. Overall, participants with a baseline UMI had an adjusted Hazard ratio (HR) of 2.00(1.39–2.78) of death compared to no prior MI. Compared to those with no MI, those with a recognizedMI had an adjusted HR of 1.70(1.31–2.17) for mortality. ConclusionsDM is associated with UMI in African-Americans. Further, a UMI carried similar risk of death compared to those with a recognized MI.

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

ObjectivesThis 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).BackgroundUMI 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.MethodsWe 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).ResultsNon-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.ConclusionThe 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.

Prognostic value of stress cardiovascular magnetic resonance in asymptomatic patients without known coronary artery disease.

A few studies suggest a significant prognostic value of silent myocardial ischaemia detected in asymptomatic patients. However, the current guidelines do not recommend stress testing in asymptomatic individuals. To assess the long-term prognostic value of vasodilator stress perfusion cardiovascular magnetic resonance (CMR) in asymptomatic individuals without known coronary artery disease (CAD). Between 2009 and 2011, a retrospective cohort study with a median follow-up of 9.2years (interquartile range: 7.8-9.6) included 1,027 consecutive asymptomatic individuals with ≥ 2 cardiovascular risk factors but without known known CAD referred for stress CMR. Major adverse cardiovascular events (MACE) included cardiovascular mortality and nonfatal myocardial infarction (MI). Among 1,027 asymptomatic subjects, 903 (87.9%) (mean age 70.6 ± 12.4years and 46.2% males) completed the follow-up, and 91 had MACE (10.1%). Using Kaplan-Meier analysis, silent ischaemia and unrecognised MI were associated with MACE (hazard ratio [HR]: 8.70; 95% CI: 5.79-13.10 and HR: 3.40; 95% CI: 2.15-5.38, respectively; both p < 0.001). In multivariable stepwise Cox regression, silent ischaemia and unrecognised MI were independent predictors of MACE (HR: 6.66; 95% CI 4.41-9.23; and HR: 2.42; 95% CI 1.23-3.21, respectively; both p < 0.001). The addition of silent ischaemia and unrecognised MI led to improved model discrimination for MACE (change in C statistic from 0.66 to 0.82; NRI = 0.497; IDI = 0.070). Silent ischaemia and unrecognised MI are good long-term predictors for the incidence of MACE in selected asymptomatic individuals with multiple risk factors and without known CAD. These stress CMR parameters have incremental long-term prognostic value to predict MACE over traditional risk factors. • Silent ischaemia and unrecognised myocardial infarction defined by stress CMR are good long-term predictors of cardiovascular events in asymptomatic individuals without known coronary artery disease. • The addition of stress cardiac MR imaging led to improved model discrimination for cardiovascular events over traditional risk factors in this specific population.

Ischemic Heart Disease: Noninvasive Imaging Techniques and Findings.

Ischemic heart disease is a leading cause of death worldwide and comprises a large proportion of annual health care expenditure. Management of ischemic heart disease is now best guided by the physiologic significance of coronary artery stenosis. Invasive coronary angiography is the standard for diagnosing coronary artery stenosis. However, it is expensive and has risks including vascular access site complications and contrast material–induced nephropathy. Invasive coronary angiography requires fractional flow reserve (FFR) measurement to determine the physiologic significance of a coronary artery stenosis. Multiple noninvasive cardiac imaging modalities can also anatomically delineate or functionally assess for significant coronary artery stenosis, as well as detect the presence of myocardial infarction (MI). While coronary CT angiography can help assess the degree of anatomic stenosis, its inability to assess the physiologic significance of lesions limits its specificity. Physiologic significance of coronary artery stenosis can be determined by cardiac MR vasodilator or dobutamine stress imaging, CT stress perfusion imaging, FFR CT, PET myocardial perfusion imaging (MPI), SPECT MPI, and stress echocardiography. Clinically unrecognized MI, another clear indicator of physiologically significant coronary artery disease, is relatively common and is best evaluated with cardiac MRI. The authors illustrate the spectrum of imaging findings of ischemic heart disease (coronary artery disease, myocardial ischemia, and MI); highlight the advantages and disadvantages of the various noninvasive imaging methods used to assess ischemic heart disease, as illustrated by recent clinical trials; and summarize current indications and contraindications for noninvasive imaging techniques for detection of ischemic heart disease.Online supplemental material is available for this article.Published under a CC BY 4.0 license.

Accuracy of OMI ECG findings versus STEMI criteria for diagnosis of acute coronary occlusion myocardial infarction.

In the STEMI paradigm of Acute Myocardial Infarction (AMI), many NSTEMI patients have unrecognized acute coronary occlusion MI (OMI), may not receive emergent reperfusion, and have higher mortality than NSTEMI patients without occlusion. We have proposed a new OMI vs. Non-Occlusion MI (NOMI) paradigm shift. We sought to compare the diagnostic accuracy of OMI ECG findings vs. formal STEMI criteria for the diagnosis of OMI. We hypothesized that blinded interpretation for predefined OMI ECG findings would be more accurate than STEMI criteria for the diagnosis of OMI. We performed a retrospective case-control study of patients with suspected acute coronary syndrome. The primary definition of OMI was either 1) acute TIMI 0-2 flow culprit or 2) TIMI 3 flow culprit with peak troponin T 1.0ng/mL or I 10.0ng/mL. 808 patients were included, of whom 49% had AMI (33% OMI; 16% NOMI). Sensitivity, specificity, and accuracy of STEMI criteria vs Interpreter 1 using OMI ECG findings among 808 patients were 41% vs 86%, 94% vs 91%, and 77% vs 89%, and for Interpreter 2 among 250 patients were 36% vs 80%, 91% vs 92%, and 76% vs 89%. STEMI(-) OMI patients had similar infarct size and mortality as STEMI(+) OMI patients, but greater delays to angiography. Blinded interpretation using predefined OMI ECG findings was superior to STEMI criteria for the ECG diagnosis of Occlusion MI. These data support further investigation into the OMI vs. NOMI paradigm and suggest that STEMI(-) OMI patients could be identified rapidly and noninvasively for emergent reperfusion using more accurate ECG interpretation.

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

BackgroundTo assess the incremental long-term prognostic value of vasodilator stress perfusion cardiovascular magnetic resonance (CMR) in patients without known coronary artery disease (CAD).MethodsBetween 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).ResultsAmong 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).ConclusionsInducible 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.

Prognostic value of unrecognized myocardial infarction and hyperemic coronary sinus flow in patients undergoing elective percutaneous coronary intervention

Abstract Background Cardiac magnetic resonance (CMR) imaging is a useful instrument for the assessment of pathological and functional conditions without the need for ionizing radiation, radioactive tracers, or intravascular catheterization. Both unrecognized myocardial infarction (UMI) and impaired global myocardial blood flow (g-MBF) have been reported to be strongly associated with worse outcome in patients with cardiovascular disease. However, their combined efficacy remains undetermined. Purpose We sought to assess the prognostic value of the presence of UMI and pre-procedural hyperemic g-MBF evaluated by phase-contrast cine magnetic resonance imaging (PC-CMR) in patients with chronic coronary syndrome who underwent elective percutaneous coronary intervention (PCI). Methods A total of 177 patients with de novo functionally significant stenosis who underwent pre-PCI CMR and PCI between September, 2016 and March, 2019 were retrospectively studied. UMI was defined as a scar detected by late gadolinium enhancement (LGE) without previously diagnosed MI. g-MBF was assessed by quantifying coronary sinus flow using PC-CMR at rest and hyperemic state. The predictors of major adverse cardiac events (MACE; cardiac death, nonfatal myocardial infarction, clinically driven unplanned revascularization, or hospitalization for congestive heart failure) during follow-up were investigated. Results UMI was detected in 40 (27.7%) patients and rest and maximal hyperemic g-MBF evaluated by the coronary sinus flow obtained by PC-CMR were 0.95 ml/min/g and 2.26 ml/min/g, respectively. During the median follow-up of 26 months, cardiovascular death occurred in 1 patient (0.6%), nonfatal myocardial infarction occurred in 4 patients (2.3%), and clinically driven revascularization and hospitalization due to congestive heart failure occurred in 25 patients (14.1%) and 3 patients (1.7%) patients, respectively. In patients with MACE, hyperemic g-MBF was significantly lower and the prevalence of UMI were significantly higher compared with those without MACE (1.94 ml/min/g vs 2.36 ml/min/g P=0.014; 48.3% vs 23.6%, P=0.011). Cox proportional hazards model indicated that impaired hyperemic g-MBF (&amp;lt;2.00 ml/min/g) and the presence of UMI were significant predictors of MACE (HR 2.22, 95% CI 1.060–4.640, P=0.034; HR 2.660, 95% CI 1.290–5.470, P=0.008). During follow-up, cardiac event-free survival was significantly worse in patients with impaired hyperemic g-MBF (&amp;lt;2.00 ml/min/g) and UMI (log-rank χ2=11.0, P=0.010). Conclusion In patients with chronic coronary syndrome undergoing elective PCI, the combined assessment of UMI and hyperemic g-MBF obtained by preprocedural noninvasive CMR may provide significant prognostic information. Funding Acknowledgement Type of funding source: None

Late gadolinium enhancement is a risk factor for major adverse cardiac events in unrecognised myocardial infarction without apparent symptoms: a meta-analysis

To assess the prognostic role of unrecognised myocardial infarction (UMI) detected at late gadolinium enhancement cardiac magnetic resonance imaging (LGE-CMRII). Electronic databases including PubMed, EMBASE, Medline, and Cochrane were searched systematically for studies exploring the predictive value of UMI detected by LGE-CMRI for major adverse cardiac events (MACEs) and all-cause mortality in patients without apparent symptoms. Pooled hazard ratios (HRs) along with their 95% confidence intervals (CIs) were obtained from a random-effects model. Subgroup analyses were performed according to the different participants and outcomes. Eight studies (2,009 participants) were identified comprising 442 patients with UMI detected at LGE-CMRI and 1,567 without UMI. The presence of UMI on LGE was associated with a significantly increased risk for MACEs (HRs: 3.44, 95% CI: 2.06 to 5.75; p<0.001) and all-cause mortality (HRs: 2.43, 95% CI: 1.00 to 5.87; p=0.05). In the subgroup analysis, the presence of UMI on LGE remained significantly associated with the risk of MACEs in patients with suspected coronary artery disease (HRs: 3.82, 95% CI: 2.49 to 5.85; p<0.01) and diabetes mellitus (HRs: 4.97, 95% CI: 3.02 to 8.18; p<0.01). The presence of UMI detected by LGE-CMRI is associated with an increased risk of MACEs and all-cause mortality in patients without symptoms. LGE-CMRI could provide important prognostic information and guide risk stratification in patients with UMI.

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

BackgroundStress cardiac magnetic resonance (CMR) provides accurate assessment of both myocardial infarction (MI) and ischemia. ObjectivesThis 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. MethodsIn 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). ResultsUMI 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. ConclusionsIn 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)

Association of Recognized and Unrecognized Myocardial Infarction With Depressive and Anxiety Disorders in 125,988 Individuals: A Report of the Lifelines Cohort Study.

No previous study has focused on recognition of myocardial infarction (MI) and the presence of both depressive and anxiety disorders in a large population-based sample. The aim of this study was to investigate the association of recognized MI (RMI) and unrecognized MI (UMI) with depressive and anxiety disorders. Analyses included 125,988 individuals enrolled in the Lifelines study. Current mental disorders according to the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) were assessed with the Mini-International Neuropsychiatric Interview. UMI was detected using electrocardiogram in participants who did not report a history of MI. The classification of RMI was based on self-reported MI history together with the use of either antithrombotic medications or electrocardiogram signs of MI. Analyses were adjusted for age, sex, smoking, somatic comorbidities, and physical health-related quality of life as measured by the RAND 36-Item Health Survey in different models. Participants with RMI had significantly higher odds of having any depressive and any anxiety disorder as compared with participants without MI (depressive disorder: odds ratio [OR] = 1.86, 95% confidence interval [CI] = 1.38-2.52; anxiety disorder: OR = 1.60, 95% CI = 1.32-1.94) after adjustment for age and sex. Participants with UMI did not differ from participants without MI (depressive disorder: OR = 1.60, 95% CI = 0.96-2.64; anxiety disorder: OR = 0.73, 95% CI = 0.48-1.11). After additional adjustment for somatic comorbidities and low physical health-related quality of life, the association between RMI with any depressive disorder was no longer statistically significant (OR = 1.18; 95% CI =0.84-1.65), but the association with any anxiety disorder remained (OR = 1.27, 95% CI = 1.03-1.57). Recognition of MI seems to play a major role in the occurrence of anxiety, but not depressive, disorders.

Causes, spectrum, and treatment of the diabetic neuropathy

Half of all diabetics are affected by adiabetic neuropathy. Microangiopathy, dysfunctional Schwann cell interactions, accumulation of toxic metabolites, and inflammatory processes all contribute to nerve damage. Overview and perspectives of the pathophysiology as well as the current and future treatment implications. Literature search (1990-2020). Clinically predominant are sensory and autonomic symptoms; however, muscle weakness can occur as well. Complications such as unrecognized myocardial infarctions and the diabetic foot syndrome are potentially life-threatening and can cause major disability. The pathophysiology of neuropathies in type1 and type 2 diabetes mellitus differs due to additional risk factors of the metabolic syndrome. To reduce the risk of neuropathy, an intensive insulin therapy is superior compared to the conventional insulin therapy. Oral antidiabetic drugs should be chosen based on individual risk profiles. Metformin can cause an iatrogenic vitamin B12 deficiency. In the treatment of neuropathic pain, the calcium channel blocker pregabalin has the highest recommendation level. The tricyclic antidepressant amitriptyline is considered to be equally effective, but it is contraindicated in autonomic dysregulation and cognitive impairment. Alternatively, the serotonin-norepinephrine reuptake inhibitor duloxetine is approved for the symptomatic treatment of diabetic neuropathies. Controversially discussed medications include alpha-lipoic acid, epalrestat, and L‑serine. The diabetic neuropathy is frequent and causes severe complications. Agood understanding of the underlying pathophysiology can contribute to the development of novel treatment strategies in the future.