Beyond Coronary Artery Disease: Assessing the Microcirculation.

Ischemic heart disease (IHD) affects more than 20 million adults in the United States. Although classically attributed to atherosclerosis of the epicardial coronary arteries, nearly half of patients with stable angina and IHD who undergo invasive coronary angiography do not have obstructive epicardial coronary artery disease. Ischemia with nonobstructive coronary arteries is frequently caused by microvascular angina with underlying coronary microvascular dysfunction (CMD). Greater understanding the pathophysiology, diagnosis, and treatment of CMD holds promise to improve clinical outcomes of patients with ischemic heart disease.

Ventricular Arrhythmias After Primary Percutaneous Coronary Intervention for STEMI.

Importance: Currently, mortality risk for patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) with an uncomplicated postprocedure course is low. Less is known regarding the risk of in-hospital ventricular tachycardia (VT) and ventricular fibrillation (VF). Objective: To evaluate the risk of late VT and VF after primary PCI for STEMI. Design, Setting, and Participants: This cohort study included adults aged 18 years or older with STEMI treated with primary PCI between January 1, 2015, and December 31, 2018, identified in the US National Cardiovascular Data Registry Chest Pain-MI Registry. Data were analyzed from April to December 2020. Main Outcomes and Measures: Multivariable logistic regression was used to evaluate the risk of late VT (≥7 beat run of VT during STEMI hospitalization ≥1 day after PCI) or VF (any episode of VF≥1 day after PCI) associated with cardiac arrest and associations between late VT or VF and in-hospital mortality in the overall cohort and a cohort with uncomplicated STEMI without prior myocardial infarction or heart failure, systolic blood pressure less than 90 mm Hg, cardiogenic shock, cardiac arrest, reinfarction, or left ventricular ejection fraction (LVEF) less than 40%. Results: A total of 174 126 eligible patients with STEMI were treated with primary PCI at 814 sites in the study; 15 460 (8.9%) had VT or VF after primary PCI, and 4156 (2.4%) had late VT or VF. Among the eligible patients, 99 905 (57.4%) at 807 sites had uncomplicated STEMI. The median age for patients with late VT or VF overall was 63 years (IQR, 55-73 years), and 75.5% were men; the median age for patients with late VT or VF with uncomplicated STEMI was 60 years (IQR, 53-69 years), and 77.7% were men. The median length of stay was 3 days (IQR, 2-7 days) for the overall cohort with late VT or VF and 3 days (IQR, 2-4 days) for the cohort with uncomplicated STEMI with late VT or VF. The risk of late VT or VF was 2.4% (overall) and 1.7% (uncomplicated STEMI). Late VT or VF with cardiac arrest occurred in 674 patients overall (0.4%) and in 117 with uncomplicated STEMI (0.1%). LVEF was the most significant factor associated with late VT or VF with cardiac arrest (adjusted odds ratio [AOR] for every 5-unit decrease ≤40%: 1.67; 95% CI, 1.54-1.85). Late VT or VF events were associated with increased odds of in-hospital mortality in the overall cohort (AOR, 6.40; 95% CI, 5.63-7.29) and the cohort with uncomplicated STEMI (AOR, 8.74; 95% CI, 6.53-11.70). Conclusions and Relevance: In this study, a small proportion of patients with STEMI treated with primary PCI had late VT or VF. However, late VT or VF with cardiac arrest was rare, particularly in the cohort with uncomplicated STEMI. This information may be useful when determining the optimal timing for hospital discharge after STEMI.

Angiographic Coronary Slow Flow Is Not a Valid Surrogate for Invasively Diagnosed Coronary Microvascular Dysfunction.

BACKGROUND: Ischemia with no obstructive coronary arteries is frequently caused by coronary microvascular dysfunction (CMD). Consensus diagnostic criteria for CMD include baseline angiographic slow flow by corrected TIMI (Thrombolysis In Myocardial Infarction) frame count (cTFC), but correlations between slow flow and CMD measured by invasive coronary function testing (CFT) are uncertain. OBJECTIVES: The aim of this study was to investigate relationships between cTFC and invasive CFT for CMD. METHODS: Adults with ischemia with no obstructive coronary arteries underwent invasive CFT with thermodilution-derived baseline coronary blood flow, coronary flow reserve (CFR), and index of microcirculatory resistance (IMR). CMD was defined as abnormal CFR (<2.5) and/or abnormal IMR (≥25). cTFC was measured from baseline angiography; slow flow was defined as cTFC >25. Correlations between cTFC and baseline coronary flow and between CFR and IMR and associations between slow flow and invasive measures of CMD were evaluated, adjusted for covariates. All patients provided consent. RESULTS: Among 508 adults, 49% had coronary slow flow. Patients with slow flow were more likely to have abnormal IMR (36% vs 26%; P = 0.019) but less likely to have abnormal CFR (28% vs 42%; P = 0.001), with no difference in CMD (46% vs 51%). cTFC was weakly correlated with baseline coronary blood flow (r = -0.35; 95% CI: -0.42 to -0.27), CFR (r = 0.20; 95% CI: 0.12 to 0.28), and IMR (r = 0.16; 95% CI: 0.07-0.24). In multivariable models, slow flow was associated with lower odds of abnormal CFR (adjusted OR: 0.53; 95% CI: 0.35 to 0.80). CONCLUSIONS: Coronary slow flow was weakly associated with results of invasive CFT and should not be used as a surrogate for the invasive diagnosis of CMD.

Visual Estimates of Coronary Slow Flow Are Not Associated With Invasive Wire-Based Diagnoses of Coronary Microvascular Dysfunction.

BACKGROUND: Coronary slow flow (CSF) by invasive coronary angiography is frequently understood to be an indicator of coronary microvascular dysfunction (CMD) in patients with ischemia with nonobstructive coronary arteries. However, the relationship between visual estimates of CSF and quantitative wire-based invasive diagnosis of CMD is uncertain. METHODS: We prospectively enrolled adults aged ≥18 years with stable ischemic heart disease who were referred for invasive coronary angiography. Individuals with ≥50% epicardial coronary artery stenosis were excluded. Invasive coronary angiography was reviewed for CSF, defined as ≥3 cardiac cycles to opacify distal vessels with contrast. Coronary function testing was performed in the left anterior descending coronary artery using bolus coronary thermodilution techniques to measure coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR). Invasively determined CMD was defined as abnormal CFR (<2.5), abnormal IMR (≥25), or both. RESULTS: Among 104 participants, the median age was 61.5 years and 79% were female. The median CFR was 3.6 (interquartile range, 2.5-4.7) and the median IMR was 21 (interquartile range, 13.3-28.0). Overall, 24.0% of participants had abnormal CFR, 34.6% had abnormal IMR, and 48.1% had a final diagnosis of invasively determined CMD. CSF was present in 23 participants (22.1%). The proportions of patients with CMD (56.5% versus 45.7%; P=0.36), abnormal CFR (17.4% versus 25.9%; P=0.40), and abnormal IMR (43.5% versus 32.1%; P=0.31) were not different in patients with versus without CSF. CONCLUSIONS: Among patients with ischemia with nonobstructive coronary artery, CSF was not associated with abnormal CFR, IMR, or either abnormal CFR or IMR. CSF is not a reliable angiographic surrogate of abnormal CFR or IMR as determined by invasive, wire-based physiology testing. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03537586.

Development and external validation of a dynamic risk score for early prediction of cardiogenic shock in cardiac intensive care units using machine learning.

AIMS: Myocardial infarction and heart failure are major cardiovascular diseases that affect millions of people in the USA with morbidity and mortality being highest among patients who develop cardiogenic shock. Early recognition of cardiogenic shock allows prompt implementation of treatment measures. Our objective is to develop a new dynamic risk score, called CShock, to improve early detection of cardiogenic shock in the cardiac intensive care unit (ICU). METHODS AND RESULTS: We developed and externally validated a deep learning-based risk stratification tool, called CShock, for patients admitted into the cardiac ICU with acute decompensated heart failure and/or myocardial infarction to predict the onset of cardiogenic shock. We prepared a cardiac ICU dataset using the Medical Information Mart for Intensive Care-III database by annotating with physician-adjudicated outcomes. This dataset which consisted of 1500 patients with 204 having cardiogenic/mixed shock was then used to train CShock. The features used to train the model for CShock included patient demographics, cardiac ICU admission diagnoses, routinely measured laboratory values and vital signs, and relevant features manually extracted from echocardiogram and left heart catheterization reports. We externally validated the risk model on the New York University (NYU) Langone Health cardiac ICU database which was also annotated with physician-adjudicated outcomes. The external validation cohort consisted of 131 patients with 25 patients experiencing cardiogenic/mixed shock. CShock achieved an area under the receiver operator characteristic curve (AUROC) of 0.821 (95% CI 0.792-0.850). CShock was externally validated in the more contemporary NYU cohort and achieved an AUROC of 0.800 (95% CI 0.717-0.884), demonstrating its generalizability in other cardiac ICUs. Having an elevated heart rate is most predictive of cardiogenic shock development based on Shapley values. The other top 10 predictors are having an admission diagnosis of myocardial infarction with ST-segment elevation, having an admission diagnosis of acute decompensated heart failure, Braden Scale, Glasgow Coma Scale, blood urea nitrogen, systolic blood pressure, serum chloride, serum sodium, and arterial blood pH. CONCLUSION: The novel CShock score has the potential to provide automated detection and early warning for cardiogenic shock and improve the outcomes for millions of patients who suffer from myocardial infarction and heart failure.

Beyond Coronary Artery Disease: Assessing the Microcirculation.

Ischemic heart disease (IHD) affects more than 20 million adults in the United States. Although classically attributed to atherosclerosis of the epicardial coronary arteries, nearly half of patients with stable angina and IHD who undergo invasive coronary angiography do not have obstructive epicardial coronary artery disease. Ischemia with nonobstructive coronary arteries is frequently caused by microvascular angina with underlying coronary microvascular dysfunction (CMD). Greater understanding the pathophysiology, diagnosis, and treatment of CMD holds promise to improve clinical outcomes of patients with ischemic heart disease.

Psychosocial Factors of Women Presenting With Myocardial Infarction With or Without Obstructive Coronary Arteries.

BACKGROUND: Women with myocardial infarction (MI) are more likely to have elevated stress levels and depression than men with MI. OBJECTIVES: We investigated psychosocial factors in women with myocardial infarction with nonobstructive coronary arteries (MINOCA) and those with MI and obstructive coronary artery disease (CAD). METHODS: Women with MI enrolled in a multicenter study and completed measures of perceived stress (Perceived Stress Scale-4) and depressive symptoms (Patient Health Questionnaire-2) at the time of MI (baseline) and 2 months later. Stress, depression, and changes over time were compared between MI subtypes. RESULTS: We included 172 MINOCA and 314 MI-CAD patients. Women with MINOCA were younger (age 59.4 years vs 64.2 years; P < 0.001) and more diverse than those with MI-CAD. Women with MINOCA were less likely to have high stress (Perceived Stress Scale-4 ≥6) at the time of MI (51.0% vs 63.0%; P = 0.021) and at 2 months post-MI (32.5% vs 46.3%; P = 0.019) than women with MI-CAD. There was no difference in elevated depressive symptoms (Patient Health Questionnaire-2 ≥2) at the time of MI (36% vs 43%; P = 0.229) or at 2 months post-MI (39% vs 40%; P = 0.999). No differences in the rate of 2-month decline in stress and depression scores were observed between groups. CONCLUSIONS: Stress and depression are common among women at the time of and 2 months after MI. MINOCA patients were less likely to report high stress compared with MI-CAD patients, but the frequency of elevated depressive symptoms did not differ between the 2 groups. Stress and depressive symptoms decreased in both MI-CAD and MINOCA patients over time.

Comprehensive Management of ANOCA, Part 1-Definition, Patient Population, and Diagnosis: JACC State-of-the-Art Review.

Angina with nonobstructive coronary arteries (ANOCA) is increasingly recognized and may affect nearly one-half of patients undergoing invasive coronary angiography for suspected ischemic heart disease. This working diagnosis encompasses coronary microvascular dysfunction, microvascular and epicardial spasm, myocardial bridging, and other occult coronary abnormalities. Patients with ANOCA often face a high burden of symptoms and may experience repeated presentations to multiple medical providers before receiving a diagnosis. Given the challenges of establishing a diagnosis, patients with ANOCA frequently experience invalidation and recidivism, possibly leading to anxiety and depression. Advances in scientific knowledge and diagnostic testing now allow for routine evaluation of ANOCA noninvasively and in the cardiac catheterization laboratory with coronary function testing (CFT). CFT includes diagnostic coronary angiography, assessment of coronary flow reserve and microcirculatory resistance, provocative testing for endothelial dysfunction and coronary vasospasm, and intravascular imaging for identification of myocardial bridging, with hemodynamic assessment as needed.

Comprehensive Management of ANOCA, Part 2-Program Development, Treatment, and Research Initiatives: JACC State-of-the-Art Review.

Centers specializing in coronary function testing are critical to ensure a systematic approach to the diagnosis and treatment of angina with nonobstructive coronary arteries (ANOCA). Management leveraging lifestyle, pharmacology, and device-based therapeutic options for ANOCA can improve angina burden and quality of life in affected patients. Multidisciplinary care teams that can tailor and titrate therapies based on individual patient needs are critical to the success of comprehensive programs. As coronary function testing for ANOCA is more widely adopted, collaborative research initiatives will be fundamental to improve ANOCA care. These efforts will require standardized symptom assessments and data collection, which will propel future large-scale clinical trials.

Effect of therapeutic-dose heparin on severe acute kidney injury and death in noncritically ill patients hospitalized for COVID-19: a prespecified secondary analysis of the ACTIV4a and ATTACC randomized trial.

Background: Acute kidney injury (AKI) in patients with COVID-19 is partly mediated by thromboinflammation. In noncritically ill patients with COVID-19, therapeutic-dose anticoagulation with heparin increased the probability of survival to hospital discharge with reduced use of cardiovascular or respiratory organ support. Objectives: We investigated whether therapeutic-dose heparin reduces the incidence of AKI or death in noncritically ill patients hospitalized for COVID-19. Methods: We report a prespecified secondary analysis of the ACTIV4a and ATTACC open-label, multiplatform randomized trial of therapeutic-dose heparin vs usual-care pharmacologic thromboprophylaxis on the incidence of severe AKI (≥2-fold increase in serum creatinine or initiation of kidney replacement therapy (KDIGO stage 2 or 3) or all-cause mortality in noncritically ill patients hospitalized for COVID-19. Bayesian statistical models were adjusted for age, sex, D-dimer, enrollment period, country, site, and platform. Results: Among 1922 enrolled, 23 were excluded due to pre-existing end stage kidney disease and 205 were missing baseline or follow-up creatinine measurements. Severe AKI or death occurred in 4.4% participants assigned to therapeutic-dose heparin and 5.5% assigned to thromboprophylaxis (adjusted relative risk [aRR]: 0.72; 95% credible interval (CrI): 0.47, 1.10); the posterior probability of superiority for therapeutic-dose heparin (relative risk < 1.0) was 93.6%. Therapeutic-dose heparin was associated with a 97.7% probability of superiority to reduce the composite of stage 3 AKI or death (3.1% vs 4.6%; aRR: 0.64; 95% CrI: 0.40, 0.99) compared to thromboprophylaxis. Conclusion: Therapeutic-dose heparin was associated with a high probability of superiority to reduce the incidence of in-hospital severe AKI or death in patients hospitalized for COVID-19.

Existing Nongated CT Coronary Calcium Predicts Operative Risk in Patients Undergoing Noncardiac Surgeries (ENCORES).

BACKGROUND: Preoperative cardiovascular risk stratification before noncardiac surgery is a common clinical challenge. Coronary artery calcium scores from ECG-gated chest computed tomography (CT) imaging are associated with perioperative events. At the time of preoperative evaluation, many patients will not have had ECG-gated CT imaging, but will have had nongated chest CT studies performed for a variety of noncardiac indications. We evaluated relationships between coronary calcium severity estimated from previous nongated chest CT imaging and perioperative major clinical events (MCE) after noncardiac surgery. METHODS: We retrospectively identified consecutive adults age ≥45 years who underwent in-hospital, major noncardiac surgery from 2016 to 2020 at a large academic health system composed of 4 acute care centers. All patients had nongated (contrast or noncontrast) chest CT imaging performed within 1 year before surgery. Coronary calcium in each vessel was retrospectively graded from absent to severe using a 0 to 3 scale (absent, mild, moderate, severe) by physicians blinded to clinical data. The estimated coronary calcium burden (ECCB) was computed as the sum of scores for each coronary artery (0 to 9 scale). A Revised Cardiac Risk Index was calculated for each patient. Perioperative MCE was defined as all-cause death or myocardial infarction within 30 days of surgery. RESULTS: A total of 2554 patients (median age, 68 years; 49.7% women; median Revised Cardiac Risk Index, 1) were included. The median time interval from nongated chest CT imaging to noncardiac surgery was 15 days (interquartile range, 3-106 days). The median ECCB was 1 (interquartile range, 0-3). Perioperative MCE occurred in 136 (5.2%) patients. Higher ECCB values were associated with stepwise increases in perioperative MCE (0: 2.9%, 1-2: 3.7%, 3-5: 8.0%; 6-9: 12.6%, P<0.001). Addition of ECCB to a model with the Revised Cardiac Risk Index improved the C-statistic for MCE (from 0.675 to 0.712, P=0.018), with a net reclassification improvement of 0.428 (95% CI, 0.254-0.601, P<0.0001). An ECCB ≥3 was associated with 2-fold higher adjusted odds of MCE versus an ECCB <3 (adjusted odds ratio, 2.11 [95% CI, 1.42-3.12]). CONCLUSIONS: Prevalence and severity of coronary calcium obtained from existing nongated chest CT imaging improve preoperative clinical risk stratification before noncardiac surgery.

Major Adverse Cardiovascular Events After Colchicine Administration Before Percutaneous Coronary Intervention: Follow-Up of the Colchicine-PCI Trial.

Periprocedural inflammation is associated with major adverse cardiovascular events in patients who undergo percutaneous coronary intervention (PCI). In the contemporary era, 5% to 10% of patients develop restenosis, and in the acute coronary syndrome cohort, there remains a 20% major adverse cardiovascular events rate at 3 years, half of which are culprit-lesion related. In patients at risk of restenosis, colchicine has been shown to reduce restenosis when started within 24 hours of PCI and continued for 6 months thereafter, compared with placebo. The Colchicine-PCI trial, which randomized patients to a 1-time loading dose of colchicine or placebo 1 to 2 hours before PCI, showed a dampening of the inflammatory response to PCI but no difference in postprocedural myocardial injury. On mean follow-up of 3.3 years, the incidence of major adverse cardiovascular events did not differ between colchicine and placebo groups (32.5% vs 34.9%; hazard ratio 0.95 [0.68 to 1.34]).

Coronary Microvascular Disease in Contemporary Clinical Practice.

Coronary microvascular disease (CMD) causes myocardial ischemia in a variety of clinical scenarios. Clinical practice guidelines support routine testing for CMD in patients with ischemia with nonobstructive coronary artery disease. Invasive testing to identify CMD requires Doppler or thermodilution measures of flow to determine the coronary flow reserve and measures of microvascular resistance. Acetylcholine coronary reactivity testing identifies concomitant endothelial dysfunction, microvascular spasm, or epicardial coronary spasm. Comprehensive testing may improve symptoms, quality of life, and patient satisfaction by establishing a diagnosis and guiding-targeted medical therapy and lifestyle measures. Beyond ischemia with nonobstructive coronary artery disease, testing for CMD may play a role in patients with acute myocardial infarction, angina following coronary revascularization, heart failure with preserved ejection fraction, Takotsubo syndrome, and after heart transplantation. Additional education and provider awareness of CMD and its role in cardiovascular disease is needed to improve patient-centered outcomes of ischemic heart disease.

Role of Resilience in the Psychological Recovery of Women With Acute Myocardial Infarction.

Background Psychological well-being is important among individuals with myocardial infarction (MI) given the clear links between stress, depression, and adverse cardiovascular outcomes. Stress and depressive disorders are more prevalent in women than men after MI. Resilience may protect against stress and depressive disorders after a traumatic event. Longitudinal data are lacking in populations post MI. We examined the role of resilience in the psychological recovery of women post MI, over time. Methods and Results We analyzed a sample from a longitudinal observational multicenter study (United States, Canada) of women post MI, between 2016 and 2020. Perceived stress (Perceived Stress Scale-4 [PSS-4]) and depressive symptoms (Patient Health Questionnaire-2 [PHQ-2]) were assessed at baseline (time of MI) and 2 months post MI. Demographics, clinical characteristics, and resilience (Brief Resilience Scale [BRS]) were collected at baseline. Low and normal/high resilience groups were established as per published cutoffs (BRS scores <3 or ≥3). Mixed-effects modeling was used to examine associations between resilience and psychological recovery over 2 months. The sample included 449 women, mean (SD) age, 62.2 (13.2) years, of whom 61.1% identified as non-Hispanic White, 18.5% as non-Hispanic Black, and 15.4% as Hispanic/Latina. Twenty-three percent had low resilience. The low resilience group had significantly higher PSS-4 and PHQ-2 scores than the normal/high resilience group at all time points. In adjusted models, both groups showed a decrease in PSS-4 scores over time. Conclusions In a diverse cohort of women post MI, higher resilience is associated with better psychological recovery over time. Future work should focus on developing strategies to strengthen resilience and improve psychological well-being for women with MI. Registration URL: https://clinicaltrials.gov/ct2/show/NCT02905357; Unique identifier: NCT02905357.