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Purpose: This study reviewed the contribution of inflammation to atherosclerotic cardiovascular disease (ASCVD), which has gained widespread recognition in recent years., Methods: This critical review evaluated how recent publications and ongoing clinical trials in atherosclerotic inflammation will affect clinical care., Findings: Key trials, including CANTOS (Canakinumab Anti-Inflammatory Thrombosis Outcomes Study) with canakinumab (interleukin-1β inhibition), and COLCOT (Colchicine Cardiovascular Outcomes Trial) and LoDoCo2 (Low Dose Colchicine 2) with colchicine, have shown that suppressing inflammation can improve outcomes in ASCVD. Cholesterol crystals play an important role in activating the NOD-, LRR-, and pyrin domain-containing protein 3 inflammasome and subsequent cytokine cascade. Inflammation contributes to significant residual risk after optimal lipid-lowering therapy. High-sensitivity C-reactive protein is a recognized biomarker of residual risk, and newer biomarkers such as the neutrophil to lymphocyte ratio may add additional information. The role of lipoprotein(a) as a proinflammatory agent or possible inflammatory biomarker is under investigation. The contribution of clonal hematopoiesis of indeterminate potential and trained immunity are in the early stages of investigation. Ongoing clinical trials of suppressing inflammation with NOD-, LRR-, and pyrin domain-containing protein 3 inflammasome inhibition (colchicine) and alternative approaches with downstream interleukin-6 ligand inhibition (ziltivekimab) will expand the evidence base for the use of anti-inflammatory agents in ASCVD., Implications: Based on current evidence and ongoing clinical trials, targeting inflammation alongside optimal lipid lowering is likely to be central to the future treatment of ASCVD. (Clin Ther. 2023;45:XXX-XXX) © 2023 Elsevier HS Journals, Inc., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The aim of this study was to assess the effect of coronary artery bypass grafting (CABG) on myocardial perfusion and left ventricular (LV) contractile reserve in patients with reduced ejection fraction (EF). We studied 57 patients (age 59 +/- 8 years, 46 men and 11 women) with EF < or = 40% referred for CABG with dobutamine (up to 40 microg/kg/min) stress-reinjection thallium-201 single-photon emission computed tomography, and radionuclide ventriculography at rest and at low-dose dobutamine before and 3 months after CABG. An increase in resting EF > or = 5% occurred in 12 patients (group A) after CABG (EF 34% before and 46% after CABG), whereas no increase occurred in the remaining 45 patients (group B) (EF 34% before and 32% after CABG). A significant increase in EF from rest to low-dose dobutamine radionuclide ventriculography occurred before and after CABG. The magnitude of increase was more significant after than before CABG in group A (12% vs 7%) as well as in group B (13% vs 7%, both p <0.001). Patients in both groups had a significant reduction in stress, rest, and ischemic perfusion scores after CABG. However, the percentage of reduction in resting perfusion defect score was more significant in group A than in group B (60% vs 30%, respectively, p <0.01). It is concluded that CABG induces a significant improvement in resting myocardial perfusion and EF response to inotropic stimulation, even in the absence of improved EF at rest. Patients without improvement in resting EF after CABG have mild improvement in resting myocardial perfusion that may be sufficient to increase EF after CABG during inotropic stimulation, but not at rest. We describe the myocardium with these characteristics as "the reactive myocardium."

Low-dose dobutamine echocardiography has a high sensitivity for predicting functional recovery after revascularization. In segments with mild wall motion abnormalities, the specificity of the technique is rather low, suggesting overestimation of functional recovery in these segments.

The aim of this study was to assess the influence of the severity of coronary artery stenosis and the grade of collateral circulation on myocardial viability in patients with chronic left ventricular (LV) dysfunction undergoing coronary artery bypass grafting. Forty patients (age 59 +/- 8 years) with old myocardial infarction were studied by dobutamine stress echocardiography (DSE) before coronary artery bypass grafting. LV function was assessed using a 16-segment, 5-grade score model. Viability and functional recovery were respectively defined as a reduction in wall motion score > or = 1 at low-dose DSE and at follow-up echocardiograms obtained 3 months after surgery. There were 56 stenotic coronary arteries subtending severely dyssynergic myocardial segments, of which 38 were occluded. Among 186 severely dyssynergic segments, functional recovery occurred in 42 (23%). There was no significant difference between myocordial regions with patent or occluded coronary arteries with respect to prevalence of viability or functional recovery and percentage of viable or recovered segments relative to the total number of dyssynergic segments. In patients with total occlusion, these parameters were not different between regions with different collateral grades. Sensitivity, specificity, and accuracy of low-dose DSE for prediction of regional functional recovery were 71%, 90%, and 86%, respectively. It is concluded that in patients with chronic LV dysfunction, the presence of total occlusion of coronary arteries supplying severely dyssynergic regions does not imply a lower prevalence or extent of functional recovery after revascularization, regardless of the grade of angiographically visualized collaterals. Low-dose DSE can identify myocardial regions with a high probability of functional improvement after revascularization regardless of the severity of underlying coronary stenosis or collateralization of the involved coronary vessel.

Dobutamine stress echocardiography is an accurate method for the diagnosis and localization of vascular compromise in patients evaluated after coronary artery bypass graft surgery. The test provides useful data for selection of patients for whom coronary angiography may be indicated.

To evaluate the prognostic value of normal dobutamine-atropine technetium-99m sestamibi single-photon emission computed tomography (SPECT) perfusion imaging in women with chest pain and inability to perform an adequate exercise test, 80 women with a normal scintigram were followed up for 23 +/- 13 months. Mean age of the patients was 61 +/- 12 years. Nine patients (11%) had a low probability (< 10%) of coronary artery disease, 43 (54%) had an intermediate probability (10% to 80%) of disease, and 28 (35%) had a high probability (>80%) of disease (including 19 patients with known coronary artery disease). During follow-up, no major cardiac events (cardiac death or nonfatal myocardial infarction) occurred. One patient with known coronary disease underwent coronary bypass surgery after 3 months, and 1 patient with a 91% pretest likelihood of coronary disease underwent coronary angioplasty after 7 months. Thus, the overall incidence of (soft) cardiac events during the follow-up period was 2 of 80 patients, or 1.3%/year. It is concluded that normal dobutamine-atropine technetium-99m sestamibi SPECT perfusion imaging in women with chest pain implies an excellent prognosis, even in women with high pretest likelihood of coronary disease.

There are no standard criteria for the diagnosis of myocardial ischemia in akinetic segments during dobutamine stress echocardiography (DSE). The aim of the study was to assess the relation between different responses of akinetic segments during DSE and ischemia assessed by thallium-201 single-photon emission computed tomography (SPECT). Dobutamine-atropine stress echocardiography with simultaneous stress-reinjection thallium-201 SPECT was performed in 67 patients with old myocardial infarction significant and coronary artery stenosis. Fourteen myocardial segments were matched for both DSE and SPECT. Ischemia on SPECT was defined as reversible thallium defects. In 257 akinetic segments, 4 patterns during DSE were identified: (1) biphasic response in 41 segments (16%), defined as improvement at low dose (5 to 10 microgram/kg/min) followed by worsening at high dose; (2) persistent akinesia in 155 segments (60%); (3) akinesia becoming dyskinesia in 39 segments (15%); and (4) sustained improvement in 22 segments (9%). Reversible thallium defects were detected in 21 segments (51%) in group 1, in 20 segments (13%) in group 2, none in group 3, and in 2 segments in group 4 (9%). The prevalence of reversible defects in biphasic segments was higher compared with other patterns (p <0.00001 vs groups 2 and 3, p <0.005 vs group 4). The ischemic perfusion defect score was significantly higher in group 1 than group 2. The positive predictive value of biphasic response for reversible thallium defects was similar to that of stress-induced dyssynergia in normal segments at rest (51% vs 58%). It is concluded that of the various responses of akinetic segments to dobutamine infusion, the biphasic response is associated with the highest prevalence and greatest severity of ischemic on thallium SPECT. Observation of contractile response at both low- and high-dose DSE is a valuable approach for the diagnosis of myocardial ischemia in akinetic segments.

ST-segment elevation during exercise testing has been attributed to myocardial ischemia and wall motion abnormalities (WMA). However, the functional significance of ST-segment elevation during dobutamine stress testing (DST) has not been evaluated in patients referred for diagnostic evaluation of myocardial ischemia. DST (up to 40 micrograms/kg/min) with simultaneous echocardiography and technetium-99m sestamibi single-photon emission computed tomography (SPECT) was performed in 229 consecutive patients with suspected myocardial ischemia who were unable to perform an adequate exercise test; 127 (55%) had a previous acute myocardial infarction (AMI). ST elevation was defined as > or = 1 mm new or additional J point elevations with a horizontal or upsloping ST segment lasting 80 ms. Reversible perfusion defects on SPECT and new or worsening WMA during stress on echocardiography were considered diagnostic of ischemia. ST elevation occurred in 40 patients (17%) during the test; 34 of them (85%) had previous AMI. All patients with ST-segment elevation had abnormal scintigrams (fixed or reversible defects, or both) and abnormal wall motion (fixed or transient defect, or both) at peak stress. In patients who had ST elevation and no previous AMI (n = 6), ischemia was detected in all by echocardiography and in 5 (83%) by SPECT. In patients with previous AMI, the prevalence of ischemia was not different with or without ST elevation (53% vs 43% by echocardiography and 53% vs 48% by SPECT, respectively). Baseline regional wall motion score in the infarct zone was higher in patients with ST elevation.(ABSTRACT TRUNCATED AT 250 WORDS)

This study compared the efficacy of dobutamine stress testing using 2-dimensional echocardiography and perfusion tomography for the noninvasive identification of coronary artery disease (CAD) in patients with left bundle branch block (LBBB). Twenty-four patients with permanent, complete LBBB (11 with previous myocardial infarction) were studied prospectively with dobutamine echocardiography and perfusion tomography. The presence of > 50% luminal diameter coronary stenosis was compared with the presence of dobutamine-induced fixed or reversible perfusion defects, and with resting or dobutamine-induced abnormalities of wall thickening. For each test, the left anterior coronary artery territory was compared with the circumflex and/or right coronary artery. Significant CAD was found in the left anterior descending coronary artery in 12 patients; all (100%) were identified by perfusion imaging, and 10 (83%, p = NS) by 2-dimensional stress echocardiography. In the 12 patients without left anterior descending CAD, scintigraphy was also positive in all (specificity: 0%), and echocardiography in only 1 (specificity: 92%, p < 0.01). The diagnostic accuracy was 50% and 87% (p < 0.05), respectively. This low specificity of perfusion tomography was improved by requiring an associated apical defect to indicate left anterior descending CAD and was corrected by restricting the diagnosis of coronary disease to those patients with partially reversible defects. In the circumflex and/or right coronary artery territory, sensitivity and specificity were similar using both techniques. We conclude that dobutamine-stress echocardiography is a specific and accurate test for the noninvasive identification of CAD, even in the left anterior descending artery territory of patients with LBBB.

The extent and severity of dobutamine-induced left ventricular (LV) dysfunction with and without angina were evaluated in 105 consecutive patients with significant coronary artery disease and a positive dobutamine stress echocardiographic test, defined as new or worsening wall motion abnormalities during high-dose dobutamine stress (up to 40 micrograms/kg/min). Wall motion score (WMS) was derived using a 16-segment, 4-grade scoring method. The difference between stress and rest WMS (delta WMS) was derived as a global measure of stress-induced LV dysfunction. Typical angina occurred in 61 patients (58%) during the test. There was no significant difference between patients with or without angina with respect to age, gender, prevalence of previous myocardial infarction, multivessel disease, or number of diseased coronary arteries. Patients with angina had a higher prevalence of a history of angina before the test. Rest, stress, and delta WMS, number and distribution of ischemic segments, and number of segments with an increase in regional WMS of > or = 2 were not significantly different in patients with or without angina. ST-segment depression was more frequent in patients with angina (56% vs 29%, p < 0.05). Patients with (vs those without) ST-segment depression had a significantly higher number of ischemic segments with normal baseline contraction, an equal total number of ischemic segments, and a similar delta WMS. It is concluded that in patients with anatomically and functionally significant coronary artery disease, the amount of stress-induced LV dysfunction evaluated by dobutamine stress echocardiography is similar in patients with or without angina.(ABSTRACT TRUNCATED AT 250 WORDS)

This study was performed to assess the prevalence of spontaneous improvement of regional left ventricular function in patients after acute myocardial infarction, and to evaluate the role of low-dose dobutamine stress echocardiography for its prediction. In 57 patients with a first acute myocardial infarction (thrombolysis, n = 27; Q-wave, n = 49), regional wall motion was evaluated with 2-dimensional echocardiography at rest, during a low-dose dobutamine stress test performed within 1 week after hospital admission, and at 3-month follow-up. Myocardial viability was considered if there was an improvement of > or = 1 grade in dyssynergic segments from rest to low-dose dobutamine infusion; recovery of regional function was defined as an improvement of > or = 1 grade between rest and follow-up echocardiograms. Wall motion score index decreased from rest to low-dose dobutamine echocardiography (1.46 +/- 0.29 to 1.39 +/- 0.30, p < 0.0001), and this change persisted at follow-up study (1.37 +/- 0.30). No differences were found between patients who did and did not undergo thrombolyis, or between those who had Q-wave and non-Q-wave infarction. At baseline echocardiography, 189 of 627 segments were dyssynergic (85 hypokinetic, 104 akinetic). Viability at low-dose dobutamine stress echocardiography was more frequent in hypokinetic than in akinetic segments (30 of 85 vs 12 of 104, odds ratio 4.18, 95% confidence interval [CI] 1.87 to 9.48).(ABSTRACT TRUNCATED AT 250 WORDS)

Purpose: To compare the relative value of clinical variables with dobutamine-atropine stress echocardiography to predict cardiac events during long-term follow-up. Dobutamine stress echocardiography is increasingly used for the detection of coronary artery disease, but little is known of its prognostic value., Patients and Methods: A total of 430 patients (310 men; mean age 61 years, range 22 to 90) were enrolled in the study. Patients were referred for chest pain complaints and were unable to perform an adequate exercise stress test. All patients underwent dobutamine-atropine stress test (incremental dobutamine infusion: 10 to 40 micrograms/kg/minute, continued with atropine 0.25 to 1 mg intravenously if necessary to achieve 85% of the age predicted maximal heart rate, without symptoms or signs of ischemia) and clinical cardiac evaluation. Follow-up was 17 +/- 5 months, with a minimum of 6 months; 3 patients were lost to follow-up. Cardiac events were defined as cardiac death, nonfatal myocardial infarction, and coronary revascularization., Results: Seventy-nine cardiac events occurred in 76 patients: cardiac death (n = 11), nonfatal myocardial infarction (n = 18), and coronary revascularization (n = 50). By multivariate regression analysis, the prognostic value of the stress test in addition to common clinical variables was assessed. (1) Cardiac death was predicted by age greater than 70 years (odds ratio 5.6, 1.5 to 20) or new wall motion abnormalities in a study that is normal at rest (odds ratio 4.1, 1.1 to 15). (2) Death or myocardial infarction was predicted by a history of myocardial infarction (odds ratio 4.8, 1.8 to 13) or age greater than 70 years (odds ratio 2.3, 1.1 to 5.4), and the stress test outcome provided no additional information. (3) If all events were combined, only stress test results were prognostic: new wall motion abnormalities in a study that is normal at rest (odds ratio 3.1, 1.9 to 5.1), wall motion abnormalities at rest (wall motion score at rest > or = 1.12) (odds ratio 2.5, 1.4 to 4.0), or any new wall motion abnormalities during stress (odds ratio 2.0, 1.4 to 3.8). The positive predictive value of any new wall motion abnormality during stress for all late cardiac events was 25% (95% confidence interval [CI] 19 to 31) with a negative predictive value of 87% (95% CI 83 to 91)., Conclusion: In a large cohort of unselected patients with chest pain syndromes, new wall motion abnormalities induced by dobutamine provide additional information for late cardiac events, independent of clinical variables.

The purpose of this study was to establish the safety of high-dose dobutamine-atropine stress echocardiography in patients with suspected or proven coronary artery disease. Six hundred fifty consecutive examinations were completed. Mean age of patients was 61 years; 300 had a previous myocardial infarction. Heart rate increased from 73 to 129 beats/min during stress testing, blood pressure did not change significantly (from 140/81 to 150/80 mm Hg). Atropine was added to dobutamine in 239 patients when no ischemia was induced with dobutamine alone and the peak heart rate was < 85% of the theoretical maximal heart rate. Atropine was more frequently administered to patients taking beta blockers (77 vs 27%, p < 0.001). New wall motion abnormalities developed in 243 patients (37%). Significant or symptomatic cardiac tachyarrhythmias, or both, developed during 24 examinations: 1 patient developed ventricular fibrillation, 3 patients developed sustained ventricular tachycardia, 12 patients experienced nonsustained ventricular tachycardia (< 10 beats) and 8 patients had paroxysmal atrial fibrillation. Cardiac arrhythmias were more frequent in patients with a history of ventricular arrhythmias (ventricular tachycardia and fibrillation) (odds ratio 9.9, 2.0 to 45) or left ventricular dysfunction at rest (wall motion score > 1.12) (odds ratio 2.9, 1.1-7.6), but not associated with atropine addition. No death or myocardial infarction occurred. The full dose was not given to 13 patients despite absence of signs or markers of ischemia for limiting side effect, yielding an overall feasibility of the stress test of 98%.(ABSTRACT TRUNCATED AT 250 WORDS)