Is Myocardial Infarction Overdiagnosed?

This Viewpoint examines whether overdiagnosis rather than underdiagnosis may now be the dominant form of myocardial infarction misdiagnosis.

Role of Computed Tomography in Cardiac Electrophysiology.

With the increasing prevalence of arrhythmias, the use of electrophysiology (EP) procedures has increased. Recent advancements in computed tomography (CT) technology have expanded its use in pre-assessments and post-assessments of EP procedures. CT provides high-resolution images, is noninvasive, and is widely available. This article highlights the strengths and weaknesses of cardiac CT in EP.

Classification Algorithm to Distinguish Between Type 1 and Type 2 Myocardial Infarction in Administrative Claims Data.

BACKGROUND: Type 2 myocardial infarction (T2MI) and type 1 myocardial infarction (T1MI) differ with respect to demographics, comorbidities, treatments, and clinical outcomes. Reliable quality and outcomes assessment depends on the ability to distinguish between T1MI and T2MI in administrative claims data. As such, we aimed to develop a classification algorithm to distinguish between T1MI and T2MI that could be applied to claims data. METHODS: Using data for beneficiaries in a Medicare accountable care organization contract in a large health care system in New England, we examined the distribution of MI diagnosis codes between 2018 to 2021 and the patterns of care and coding for beneficiaries with a hospital discharge diagnosis International Classification of Diseases, Tenth Revision code for T2MI, compared with those for T1MI. We then assessed the probability that each hospitalization was for a T2MI versus T1MI and examined care occurring in 2017 before the introduction of the T2MI code. RESULTS: After application of inclusion and exclusion criteria, 7759 hospitalizations for myocardial infarction remained (46.5% T1MI and 53.5% T2MI; mean age, 79±10.3 years; 47% female). In the classification algorithm, female gender (odds ratio, 1.26 [95% CI, 1.11-1.44]), Black race relative to White race (odds ratio, 2.48 [95% CI, 1.76-3.48]), and diagnoses of COVID-19 (odds ratio, 1.74 [95% CI, 1.11-2.71]) or hypertensive emergency (odds ratio, 1.46 [95% CI, 1.00-2.14]) were associated with higher odds of the hospitalization being for T2MI versus T1MI. When applied to the testing sample, the C-statistic of the full model was 0.83. Comparison of classified T2MI and observed T2MI suggest the possibility of substantial misclassification both before and after the T2MI code. CONCLUSIONS: A simple classification algorithm appears to be able to differentiate between hospitalizations for T1MI and T2MI before and after the T2MI code was introduced. This could facilitate more accurate longitudinal assessments of acute myocardial infarction quality and outcomes.

Serial troponin-I and long-term outcomes in subjects with suspected acute coronary syndrome.

AIMS: It is unclear how serial high-sensitivity troponin-I (hsTnI) concentrations affect long-term prognosis in individuals with suspected acute coronary syndrome (ACS). METHODS AND RESULTS: Subjects who underwent two hsTnI measurements (Siemens TnI Flex® Reagent) separated by 1-7 h, during a first-time hospitalization for myocardial infarction, unstable angina, observation for suspected myocardial infarction, or chest pain from 2012 through 2019, were identified through Danish national registries. Individuals were stratified per their hsTnI concentration pattern (normal, rising, persistently elevated, or falling) and the magnitude of hsTnI concentration change (<20%, >20-50%, or >50% in either direction). We calculated absolute and relative mortality risks standardized to the distributions of risk factors for the entire study population. A total of 20 609 individuals were included of whom 2.3% had died at 30 days, and an additional 4.7% had died at 365 days. The standardized risk of death was highest among persons with a persistently elevated hsTnI concentration (0-30 days: 8.0%, 31-365 days: 11.1%) and lowest among those with two normal hsTnI concentrations (0-30 days: 0.5%, 31-365 days: 2.6%). In neither case did relative hsTnI concentration changes between measurements clearly affect mortality risk. Among persons with a rising hsTnI concentration pattern, 30-day mortality was higher in subjects with a >50% rise compared with those with a less pronounced rise (2.2% vs. <0.1%). CONCLUSION: Among individuals with suspected ACS, those with a persistently elevated hsTnI concentration consistently had the highest risk of death. In subjects with two normal hsTnI concentrations, mortality was very low and not affected by the magnitude of change between measurements.

In this Danish study of >20 000 individuals with suspected heart attack, we confirmed the clinical importance of drawing two consecutive blood samples for measurement of high-sensitivity troponin-I concentrations (a marker of damage to the heart): The risk of death was highest in persons with two elevated high-sensitivity troponin-I concentrations and lowest in those with two normal concentrations.Among persons who had a first normal and a subsequently elevated high-sensitivity troponin-I concentration, a >50% relative rise was associated with significantly higher risk of death at 30 days.

Coronary Computed Tomographic Angiography With Fractional Flow Reserve in Patients With Type 2 Myocardial Infarction.

BACKGROUND: Type 2 myocardial infarction (T2MI) related to a supply/demand imbalance of coronary blood flow is common and associated with poor prognosis. Coronary artery disease (CAD) may predispose some individuals to T2MI and contribute to its high rate of recurrent cardiovascular events. Little is known about the presence and extent of CAD in this population. OBJECTIVES: The goal of this study was to evaluate the presence and characteristics of CAD among patients with T2MI. METHODS: In this prospective study, consecutive eligible individuals with Fourth Universal Definition of Myocardial Infarction criteria for T2MI were enrolled. Participants underwent coronary computed tomography angiography (CTA), fractional flow reserve derived with coronary CTA (FFRCT), and plaque volume analyses. RESULTS: Among 50 participants, 25 (50%) were female, and the mean age was 68.0 ± 11.4 years. Atherosclerotic risk factors were common. Coronary CTA revealed coronary plaque in 46 participants (92%). A moderate or greater stenosis (≥50%) was identified in 42% of participants, and obstructive disease (≥50% left main stenosis or ≥70% stenosis in any other epicardial coronary artery) was present in 26%. Prevalence of obstructive CAD did not differ according to T2MI cause (P = 0.54). A hemodynamically significant focal stenosis identified by FFRCT was present in 13 participants (26%). Among participants with a stenosis ≥50% (n = 21), FFRCT excluded lesion-specific hemodynamically significant stenosis in 8 cases (38%). CONCLUSIONS: Among individuals with adjudicated T2MI, CAD was prevalent, but the majority of patients had nonobstructive CAD. Mediators of ischemia are likely multifactorial in this population. (Defining the Prevalence and Characteristics of Coronary Artery Disease Among Patients with Type 2 Myocardial Infarction using CT-FFR [DEFINE TYPE 2 MI]; NCT04864119).

Multiple Biomarkers to Predict Major Adverse Cardiovascular Events in Patients With Coronary Chronic Total Occlusions.

Background: There are limited tools available to predict the long-term prognosis of persons with coronary chronic total occlusions (CTO). Objectives: We evaluated performance of a blood biomarker panel to predict cardiovascular (CV) events in patients with CTO. Methods: From 1251 patients in the CASABLANCA study, 241 participants with a CTO were followed for an average of 4 years for occurrence of major adverse CV events (MACE, CV death, non-fatal myocardial infarction or stroke) and CV death/heart failure (HF) hospitalization. Results of a biomarker panel (kidney injury molecule-1, N-terminal pro-B-type natriuretic peptide, osteopontin, and tissue inhibitor of metalloproteinase-1) from baseline samples were expressed as low-, moderate-, and high-risk. Results: By 4 years, a total of 67 (27.8%) MACE events and 56 (23.2%) CV death/HF hospitalization events occurred. The C-statistic of the panel for MACE through 4 years was 0.79. Considering patients in the low-risk group as a reference, the hazard ratio of MACE by 4 years was 6.65 (95% confidence interval [CI]: 2.98-14.8) and 12.4 (95% CI:5.17-29.6) for the moderate and high-risk groups (both P <0.001). The C-statistic for CVD/HF hospitalization by 4 years was 0.84. Compared to the low-risk score group, the moderate and high-risk groups had hazard ratios of 5.61 (95% CI: 2.33-13.5) and 15.6 (95% CI: 6.18, 39.2; both P value <0.001). Conclusion: A multiple biomarker panel assists in evaluating the risk of adverse outcomes in patients with coronary CTO. These results may have implications for patient care and could have a role for clinical trial enrichment. Clinical Trial: CASABLANCA, ClinicalTrials.gov Identifier: NCT00842868.

Clinical outcomes associated with type II myocardial infarction caused by bleeding.

BACKGROUND: Type ll myocardial infarction (T2MI) is caused by a mismatch between myocardial oxygen supply and demand. One subset of individuals is T2MI caused by acute hemorrhage. Traditional MI treatments including antiplatelets, anticoagulants, and revascularization can worsen bleeding. We aim to report outcomes of T2MI patients due to bleeding, stratified by treatment approach. METHODS: The MGB Research Patient Data Registry followed by manual physician adjudication was used to identify individuals with T2MI caused by bleeding between 2009 and 2022. We defined 3 treatment groups: (1) invasively managed, (2) pharmacologic, and (3) conservatively managed Clinical parameters and outcomes for 30-day, mortality, rebleeding, and readmission were abstracted compared between the treatment groups. RESULTS: We identified 5,712 individuals coded with acute bleeding, of which 1,017 were coded with T2MI during their admission. After manual physician adjudication, 73 individuals met the criteria for T2MI caused by bleeding. 18 patients were managed invasively, 39 received pharmacologic therapy alone, and 16 were managed conservatively. The invasively managed group experienced lower mortality (P = .021) yet higher readmission (P = .045) than the conservatively managed group. The pharmacologic group also experienced lower mortality (P= .017) yet higher readmission (P = .005) than the conservatively managed group. CONCLUSION: Individuals with T2MI associated with acute hemorrhage are a high-risk population. Patients treated with standard procedures experienced higher readmission but lower mortality than conservatively managed patients. These results raise the possibility of testing ischemia-reduction approaches for such high-risk populations. Future clinical trials are required to validate treatment strategies for T2MI caused by bleeding.

Implementation of High-Sensitivity Cardiac Troponin Assays in the United States.

BACKGROUND: Few data exist regarding the implementation of high-sensitivity cardiac troponin (hs-cTn) assays in the United States since their approval. OBJECTIVES: This study sought to explore trends in hs-cTn assay implementation over time and assess the association of their use with in-hospital cardiac testing and outcomes. METHODS: The study examined trends in implementation of hs-cTn assays among participating hospitals in the National Cardiovascular Data Registry Chest Pain-MI [Myocardial Infarction] Registry from January 1, 2019 through September 30, 2021. Associations among hs-cTn use, use of in-hospital diagnostic imaging, and patient outcomes were assessed using generalized estimating equation models with logistic or gamma distributions. RESULTS: Among 550 participating hospitals (N = 251,000), implementation of hs-cTn assays increased from 3.3% in the first quarter of 2019 to 32.6% in the third quarter of 2021 (Ptrend < 0.001). Use of hs-cTn was associated with more echocardiography among persons with non-ST-segment elevation acute coronary syndrome (NSTE-ACS; 82.4% vs 75.0%; adjusted odds ratio: 1.43; 95% CI: 1.19-1.73) but not among low-risk chest pain individuals. Use of hs-cTn was associated with less invasive coronary angiography among low-risk patients (3.7% vs 4.5%; adjusted odds ratio: 0.73; 95% CI: 0.58-0.92) but similar use for patients with NSTE-ACS. There was no association between hs-cTn use and noninvasive stress testing or coronary computed tomography angiography testing. Among individuals with NSTE-ACS, hs-cTn use was not associated with revascularization or in-hospital mortality. Use of hs-cTn was associated with a shorter length of stay (median 47.6 hours vs 48.0 hours; ratio: 0.94; 95% CI: 0.90-0.98). CONCLUSIONS: Implementation of hs-cTn among U.S. hospitals is increasing, but most U.S. hospitals continue to use less sensitive assays. The use of hs-cTn was associated with modestly shorter length of stay, greater use of echocardiography for NSTE-ACS, and less use of invasive angiography among low-risk patients.

Performance of a multi-biomarker panel for prediction of cardiovascular event in patients with chronic kidney disease.

BACKGROUND: Patients with chronic kidney disease (CKD) undergoing coronary catheterization are at increased risk of cardiovascular events (CVE). Measuring biomarkers before the procedure may guide clinicians in identifying patients at higher risk of future cardiovascular events. METHODS: In this sub-study the Catheter Sampled Blood Archive in Cardiovascular Diseases (CASABLANCA), 927 patients underwent coronary catheterization and were followed up for two years. Using machine learning algorithm and targeted proteomics from samples of patients with CKD, 4 biomarkers (kidney injury molecule-1, N-terminal pro B-type natriuretic peptide, osteopontin, and tissue inhibitor of metalloproteinase-1) were integrated into a prognostic algorithm to predict CVE. Results from the panel are expressed in a graded fashion (CVE higher risk and lower risk) using a data-driven cutoff optimized for balanced sensitivity and specificity. RESULTS: During the 2-year follow-up, 74 CVE were ascertained. 51 (rate: 51/378 = 13.5%) events occurred in stage 1-2 CKD and 23 (rate: 23/68 = 33.8%) events occurred in stage 3-5 CKD. The C-statistic for predicting 2-years cardiovascular events in all 446 patients was 0.77 (0.72, 0.82). The model was well-calibrated (Hosmer-Lemeshow test p-value >0.40). Considering patients at CVE lower-risk within each CKD staging group as a reference, the hazard ratio (95% confidence interval) of cardiovascular events was 2.82 (1.53, 5.22) for CKD stage 1-2/CVE higher-risk, and 8.32 (1.12, 61.76) for CKD stage 3-5/CVE higher-risk. CONCLUSION: Measuring biomarker panel prior to coronary catheterization may be useful to individualize CVE risk assessment among patients with CKD.

Management of Patients at Risk for and With Left Ventricular Thrombus: A Scientific Statement From the American Heart Association.

Despite the many advances in cardiovascular medicine, decisions concerning the diagnosis, prevention, and treatment of left ventricular (LV) thrombus often remain challenging. There are only limited organizational guideline recommendations with regard to LV thrombus. Furthermore, management issues in current practice are increasingly complex, including concerns about adding oral anticoagulant therapy to dual antiplatelet therapy, the availability of direct oral anticoagulants as a potential alternative option to traditional vitamin K antagonists, and the use of diagnostic modalities such as cardiac magnetic resonance imaging, which has greater sensitivity for LV thrombus detection than echocardiography. Therefore, this American Heart Association scientific statement was commissioned with the goals of addressing 8 key clinical management questions related to LV thrombus, including the prevention and treatment after myocardial infarction, prevention and treatment in dilated cardiomyopathy, management of mural (laminated) thrombus, imaging of LV thrombus, direct oral anticoagulants as an alternative to warfarin, treatments other than oral anticoagulants for LV thrombus (eg, dual antiplatelet therapy, fibrinolysis, surgical excision), and the approach to persistent LV thrombus despite anticoagulation therapy. Practical management suggestions in the form of text, tables, and flow diagrams based on careful and critical review of actual study data as formulated by this multidisciplinary writing committee are given.

Biomarker prognostication across Universal Definition of Heart Failure stages.

AIM: The Universal Definition of Heart Failure (UDHF) provides a framework for staging risk for HF events. It is not clear whether prognostic biomarkers have different meaning across UDHF stages. We sought to evaluate performance of biomarkers to predict HF events among high-risk patients undergoing coronary and/or peripheral angiography categorized into UDHF stages. METHODS: One thousand two hundred thirty-five individuals underwent coronary and/or peripheral angiography were enrolled. Study participants were categorized into UDHF Stage A (at risk), Stage B (pre-HF), and Stage C or D (HF, including end stage) and grouped into Stage A/B and C/D. Biomarkers and clinical variables were used to develop prognostic models. Other measures examined included total HF hospitalizations. RESULTS: Over a median of 3.67 years of follow-up, 155 cardiovascular (CV) deaths occurred, and 299 patients were hospitalized with acute HF. In patients with Stage A/B, galectin-3 (HR = 1.52, P = 0.03), endothelin-1 (HR = 2.16, P = 0.001), and N-terminal pro-B-type natriuretic peptide (NT-proBNP; HR = 1.43, P < 0.001) were associated with incident CV death/HF hospitalization. In Stage C/D, NT-proBNP (HR = 1.26, P = 0.006), soluble urokinase-type plasminogen activator receptor (suPAR; HR = 1.57, P = 0.007) and high-sensitivity C-reactive protein (hs-CRP; HR = 1.15, P = 0.01) were associated with these outcomes. Higher biomarker concentrations were associated with greater total burden of HF events in Stages A/B and C/D. CONCLUSIONS: Among higher risk individuals undergoing angiographic procedures, different biomarkers improve risk stratification in different UDHF stages of HF. More precise prognostication may offer a window of opportunity to initiate targeted preventive measures.

Cardiovascular Disease Projections in the United States Based on the 2020 Census Estimates.

BACKGROUND: Understanding trends in cardiovascular (CV) risk factors and CV disease according to age, sex, race, and ethnicity is important for policy planning and public health interventions. OBJECTIVES: The goal of this study was to project the number of people with CV risk factors and disease and further explore sex, race, and ethnical disparities. METHODS: The prevalence of CV risk factors (diabetes mellitus, hypertension, dyslipidemia, and obesity) and CV disease (ischemic heart disease, heart failure, myocardial infarction, and stroke) according to age, sex, race, and ethnicity was estimated by using logistic regression models based on 2013-2018 National Health and Nutrition Examination Survey data and further combining them with 2020 U.S. Census projection counts for years 2025-2060. RESULTS: By the year 2060, compared with the year 2025, the number of people with diabetes mellitus will increase by 39.3% (39.2 million [M] to 54.6M), hypertension by 27.2% (127.8M to 162.5M), dyslipidemia by 27.5% (98.6M to 125.7M), and obesity by 18.3% (106.3M to 125.7M). Concurrently, projected prevalence will similarly increase compared with 2025 for ischemic heart disease by 31.1% (21.9M to 28.7M), heart failure by 33.0% (9.7M to 12.9M), myocardial infarction by 30.1% (12.3M to 16.0M), and stroke by 34.3% (10.8M to 14.5M). Among White individuals, the prevalence of CV risk factors and disease is projected to decrease, whereas significant increases are projected in racial and ethnic minorities. CONCLUSIONS: Large future increases in CV risk factors and CV disease prevalence are projected, disproportionately affecting racial and ethnic minorities. Future health policies and public health efforts should take these results into account to provide quality, affordable, and accessible health care.

Inflammatory biomarkers and risk of cardiovascular events in patients undergoing coronary angiography.

BACKGROUND: Inflammation, measured by traditional biomarkers such as C-reactive protein, has been linked to cardiovascular (CV) events. Recent technological advancement has allowed for measuring larger numbers of inflammatory biomarkers. A contemporary evaluation with established and novel biomarkers of inflammation is needed. METHODS: 1,090 individuals who underwent coronary angiography were enrolled. Twenty-four inflammatory biomarkers were collected prior to angiography. Unsupervised machine learning cluster analyses determined unique patterns of inflammatory biomarkers. Cox proportional hazard regression assessed both association of inflammatory biomarker clusters and individual biomarker associations with major adverse cardiovascular events (MACE; non-fatal myocardial infarction or stroke, and CV death) during a median follow-up of 3.67 years. RESULTS: Four distinct clusters were recognized. Incremental increases in inflammatory biomarkers were observed from cluster 1 to cluster 4. During follow-up, 263 MACE were ascertained. Considering cluster 1 as a reference, study participants with inflammatory cluster 2 (Hazard ratio [HR] 1.55, 95% confidence interval [CI]: 1.01-2.37), cluster 3 (HR 1.89, CI: 1.25-2.85), and cluster 4 (HR 2.93, CI: 1.95-4.42) were at increased risk of MACE. Interleukin (IL)-1α IL-6, IL-8, IL-10, IL-12, Adhesion molecule-1 high-sensitivity C-reactive protein, ferritin, myeloperoxidase, macrophage inflammatory protein (MIP)-1a, MIP 3, and macrophage colony-stimulating factor-1 were independently associated with MACE. CONCLUSIONS: Among persons undergoing coronary angiography procedures, distinct clusters of inflammatory biomarker distributions with significant prognostic meaning may be identified. These results may identify unique targets for anti-inflammatory treatments aimed at CV disease.

A Biomarker-Enhanced Model for Prediction of Acute Kidney Injury and Cardiovascular Risk Following Angiographic Procedures: CASABLANCA AKI Prediction Substudy.

Background The 2020 Acute Disease Quality Initiative Consensus provided recommendations on novel acute kidney injury biomarkers. In this study, we sought to assess the added value of novel kidney biomarkers to a clinical score in the CASABLANCA (Catheter Sampled Blood Archive in Cardiovascular Diseases) study. Methods and Results We evaluated individuals undergoing coronary and/or peripheral angiography and added 4 candidate biomarkers for acute kidney injury (kidney injury molecule-1, interleukin-18, osteopontin, and cystatin C) to a previously described contrast-associated acute kidney injury (CA-AKI) risk score. Participants were categorized into integer score groups based on the risk assigned by the biomarker-enhanced CA-AKI model. Risk for incident cardiorenal outcomes during a median 3.7 years of follow-up was assessed. Of 1114 participants studied, 55 (4.94%) developed CA-AKI. In adjusted models, neither kidney injury molecule-1 nor interleukin-18 improved discrimination for CA-AKI; addition of osteopontin and cystatin C to the CA-AKI clinical model significantly increased the c-statistic from 0.69 to 0.73 (P for change <0.001) and resulted in a Net Reclassification Index of 59.4. Considering those with the lowest CA-AKI integer score as a reference, the intermediate, high-risk, and very-high-risk groups were associated with adverse cardiorenal outcomes. The corresponding hazard ratios of the very-high-risk group were 3.39 (95% CI, 2.14-5.38) for nonprocedural acute kidney injury, 5.58 (95% CI, 3.23-9.63) for incident chronic kidney disease, 6.21 (95% CI, 3.67-10.47) for myocardial infarction, and 8.94 (95% CI, 4.83-16.53) for all-cause mortality. Conclusions A biomarker-enhanced risk model significantly improves the prediction of CA-AKI beyond clinical variables alone and may stratify the risk of future cardiorenal outcomes. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00842868.

Relation of High-Sensitivity Cardiac Troponin I and Obstructive Coronary Artery Disease in Patients Without Acute Myocardial Infarction.

The relation of high-sensitivity cardiac troponin I (hs-cTnI) concentration and presence of obstructive coronary artery disease (CAD) in patients without myocardial infarction (MI) is unclear. Study participants selected from patients free of MI who underwent coronary angiography with or without intervention were enrolled, and hs-cTnI measured. A gradient boosting model was implemented to build a model for detection of CAD. Cox proportional hazard regression was used to assess the association of hs-cTnI and adverse cardiovascular (CV) outcome. Among 978 study participants, 607 patients (62%) had CAD. Higher concentrations of hs-cTnI were associated with chronic kidney disease, heart failure, CAD, male gender, current tobacco use, anemia, age, and low-density lipoprotein cholesterol. History of CAD, male gender, type 2 diabetes mellitus, hs-cTnI, anemia, age, and high-density lipoprotein cholesterol were the most influential factors for detection of CAD. The gradient boosting model had an area under the curve of 0.82, accuracy of 75%, sensitivity of 88%, specificity of 52%, positive predictive value of 76%, and negative predictive value of 72% for detection of CAD. Increase in 1 log unit of hs-cTnI was significantly associated with increased risk of incident MI (hazard ratio [HR] 1.34, 95% confidence interval [CI] 1.22 to 1.47, p <0.001), CV mortality (HR 1. 24, 95% CI 1.11 to 1.39, p <0.001), and composite of incident MI or CV mortality (HR 1.29, 95% CI 1.20 to 1.40, p <0.001). In conclusion, among patients without acute MI and CAD, higher concentrations of hs-cTnI were associated with the presence of CAD and linked to increased risk of future CV events. ClinicalTrials.gov Identifier: NCT00842868.