Effect of Paroxetine-Mediated G-Protein Receptor Kinase 2 Inhibition vs Placebo in Patients With Anterior Myocardial Infarction: A Randomized Clinical Trial.

Importance: Left ventricular remodeling following acute myocardial infarction results in progressive myocardial dysfunction and adversely affects prognosis. Objective: To investigate the efficacy of paroxetine-mediated G-protein-coupled receptor kinase 2 inhibition to mitigate adverse left ventricular remodeling in patients presenting with acute myocardial infarction. Design, Setting, and Participants: This double-blind, placebo-controlled randomized clinical trial was conducted at Bern University Hospital, Bern, Switzerland. Patients with acute anterior ST-segment elevation myocardial infarction with left ventricular ejection fraction (LVEF) of 45% or less were randomly allocated to 2 study arms between October 26, 2017, and September 21, 2020. Interventions: Patients in the experimental arm received 20 mg of paroxetine daily; patients in the control group received a placebo daily. Both treatments were provided for 12 weeks. Main Outcomes and Measures: The primary end point was the difference in patient-level improvement of LVEF between baseline and 12 weeks as assessed by cardiac magnetic resonance tomography. Secondary end points were changes in left ventricular dimensions and late gadolinium enhancement between baseline and follow-up. Results: Fifty patients (mean [SD] age, 62 [13] years; 41 men [82%]) with acute anterior myocardial infarction were randomly allocated to paroxetine or placebo, of whom 38 patients underwent cardiac magnetic resonance imaging both at baseline and 12 weeks. There was no difference in recovery of LVEF between the experimental group (mean [SD] change, 4.0% [7.0%]) and the control group (mean [SD] change, 6.3% [6.3%]; mean difference, -2.4% [95% CI, -6.8% to 2.1%]; P = .29) or changes in left ventricular end-diastolic volume (mean difference, 13.4 [95% CI, -12.3 to 39.0] mL; P = .30) and end-systolic volume (mean difference, 11.4 [95% CI, -3.6 to 26.4] mL; P = .13). Late gadolinium enhancement as a percentage of the total left ventricular mass decreased to a larger extent in the experimental group (mean [SD], -13.6% [12.9%]) compared with the control group (mean [SD], -4.5% [9.5%]; mean difference, -9.1% [95% CI, -16.6% to -1.6%]; P = .02). Conclusions and Relevance: In this trial, treatment with paroxetine did not improve LVEF after myocardial infarction compared with placebo. Trial Registration: ClinicalTrials.gov Identifier: NCT03274752.

Preservation of Contractile Reserve and Diastolic Function by Inhibiting the NLRP3 Inflammasome with OLT1177® (Dapansutrile) in a Mouse Model of Severe Ischemic Cardiomyopathy Due to Non-Reperfused Anterior Wall Myocardial Infarction.

Interleukin-1ß (IL-1ß), a product of the NLRP3 inflammasome, modulates cardiac contractility and diastolic function. We proposed that OLT1177® (dapansutrile), a novel NLRP3 inhibitor, could preserve contractile reserve and diastolic function after myocardial infarction (MI). We used an experimental murine model of severe ischemic cardiomyopathy through the ligation of the left coronary artery without reperfusion, and after 7 days randomly assigned mice showing large anterior MI (>4 akinetic segments), increased left ventricular (LV) dimensions ([LVEDD] > 4.4 mm), and reduced function (LV ejection fraction < 40%) to a diet that was enriched with OLT1177® admixed with the chow in the diet at 3.75 g/kg (Group 1 [n = 10]) or 7.5 g/kg (Group 2 [n = 9]), or a standard diet as the no-treatment control group (Group 3 [n = 10]) for 9 weeks. We measured the cardiac function and contractile reserve with an isoproterenol challenge, and the diastolic function with cardiac catheterization at 10 weeks following the MI surgery. When compared with the control (Group 3), the mice treated with OLT1177 (Group 1 and 2) showed significantly greater preservation of their contractile reserve (the percent increase in the left ventricular ejection fraction [LVEF] after the isoproterenol challenge was +33 ± 11% and +40 ± 6% vs. +9 ± 7% in the standard diet; p < 0.05 and p < 0.005 for Group 1 and 2, respectively) and of diastolic function measured as the lower left ventricular end-diastolic pressure (3.2 ± 0.5 mmHg or 4.5 ± 0.5 mmHg vs. 10.0 ± 1.6 mmHg; p < 0.005 and p < 0.009 respectively). No differences were noted between the resting LVEF of the MI groups. These effects were independent of the effects on the ventricular remodeling after MI. NLRP3 inflammasome inhibition with OLT1177® can preserve ß-adrenergic responsiveness and prevent left ventricular diastolic dysfunction in a large non-reperfused anterior MI mouse model. OLT1177® could therefore be used to prevent the development of heart failure in patients with ischemic cardiomyopathy.

Type 2 myocardial infarction and myocardial injury: eligibility for novel medical therapy to derisk clinical trials.

BACKGROUND: Patients with type 2 myocardial infarction (T2MI) and other mechanisms of nonthrombotic myocardial injury have an unmet therapeutic need. Eligibility for novel medical therapy is generally uncertain. METHODS: We predefined colchicine, eplerenone and ticagrelor as candidates for repurposing towards novel therapy for T2MI or myocardial injury. Considering eligibility for randomisation in a clinical trial, each drug was classified according to indications and contraindications for therapy and survival for at least 24 hours following admission. Eligibility criteria for prescription were evaluated against the Summary of Medical Product Characteristics. Consecutive hospital admissions were screened to identify patients with ≥1 high-sensitivity troponin-I value >99th percentile. Endotypes of myocardial injury were adjudicated according to the Fourth Universal Definition of MI. Patients' characteristics and medication were prospectively evaluated. RESULTS: During 1 March to 15 April 2020, 390 patients had a troponin I>URL. Reasons for exclusion: type 1 MI n=115, indeterminate diagnosis n=42, lack of capacity n=14, death <24 hours n=7, duplicates n=2. Therefore, 210 patients with T2MI/myocardial injury and 174 (82.8%) who survived to discharge were adjudicated for treatment eligibility. Patients who fulfilled eligibility criteria initially on admission and then at discharge were colchicine 25/210 (11.9%) and 23/174 (13.2%); eplerenone 57/210 (27.1%) and 45/174 (25.9%); ticagrelor 122/210 (58.1%) and 98/174 (56.3%). Forty-six (21.9%) and 38 (21.8%) patients were potentially eligible for all three drugs on admission and discharge, respectively. CONCLUSION: A reasonably high proportion of patients may be considered eligible for repurposing novel medical therapy in secondary prevention trials of type 2 MI/myocardial injury.

Low dose combined oral contraceptives induced thrombotic anterior wall myocardial infarction: a case report.

BACKGROUND: Combined oral contraceptive pills are associated with an established risk for venous thrombosis; however, their risk for arterial thrombosis remains uncertain, especially with the development of low dose new generations of combined oral contraceptive. Arterial thrombosis is less likely to occur with the use of oral contraceptive pills in the absence of cardiovascular risk factors. CASE PRESENTATION: We report a 35-year old female with no cardiovascular risk factors who presented with thrombotic anterior wall myocardial infarction 6 months after using a third generation low dose combined oral contraceptive pills (Marvelon; ethinylestradiol 30 mcg and desogestrel 150 mcg). CONCLUSION: Third generation low dose combined oral contraceptives may lead to myocardial infarction in young women, even in the absence of other cardiovascular risk factors.

Relationship between fragmented QRS complexes and ejection fraction recovery in anterior ST-segment elevation myocardial infarction patients undergoing thrombolytic treatment.

BACKGROUND: Acute anterior ST-segment elevation myocardial infarction (STEMI) is a life-threatening disease. Adverse cardiac events of acute anterior STEMI include cardiovascular death or worsening congestive heart failure. This study investigated the role of fragmented QRS complex (fQRS) in predicting insufficient ejection fraction (EF) recovery in acute anterior STEMI. METHODS: Patients with acute anterior STEMI who received thrombolytic therapy were prospectively enrolled in this study. Twelve-lead electrocardiography (ECG) was obtained from all patients during admission and 24 and 48 h after admission. We divided the patients into two groups according to the presence of fQRS appearance within 48 h: absence of fQRS in any lead (fQRS-), and its presence in two or more contiguous leads (fQRS+). All patients were evaluated with transthoracic echocardiography at admission, and at follow-up 6 and 12 months later. RESULTS: A total of 138 consecutive patients were included in the study. Seventy-three patients (52.9%) had fQRS in the ECG. EF recovery in the fQRS(+) group was significantly lower than that of the fQRS(-) group (39% vs. 43.9%, P < 0.001). Multiple logistic regression analysis showed that the fQRS (odds ratio: 4.147, 95% confidence interval: 1.607-10.697, P = 0.003) were an independent predictor of poor EF recovery. CONCLUSION: The presence of fQRS is an independent predictor for inadequate EF recovery in acute anterior STEMI patients undergoing thrombolytic treatment. Assessment of fQRS on surface ECG may be used in determining high-risk patients for poor EF recovery after acute anterior STEMI.

The effect of ticagrelor based dual antiplatelet therapy on development of late left ventricular thrombus after acute anterior ST elevation myocardial infarction.

AIM: The aim of this study is to investigate the impact of ticagrelor as compared to clopidogrel based dual antiplatelet therapy (DAPT) during post-discharge management on the incidence of left ventricular (LV) thrombus in patients with first acute anterior ST elevation myocardial infarction (STEMI). METHOD: 641 patients who met the inclusion criteria were divided into two groups based on the receipt of either ticagrelor or clopidogrel based DAPT. RESULT: Left ventricular thrombus was detected in 73 (11.4%) patients at the first month echocardiographic examination. Ticagrelor based DAPT was associated with significantly less incidence of LV thrombus when compared to clopidogrel [20 (7.4%) vs 53 (14.0%) OR: 0.50 (0.29-0.86)]. Penalized maximum likelihood estimation (PMLE) logistic regression analyses were performed to fourteen candidate variables for identifying the independent predictors of LV thrombus, ticagrelor (compared with clopidogrel) [OR: 0.53 (0.28-0.96), p = 0.039], body mass index (BMI) [OR: 0.58 (0.44-0.77), p < 0.001], KILLIP class (I vs II-IV) [OR: 0.35 (0.14-0.83), p = 0.017], age [OR: 1.22 (1.08-1.40), p < 0.001], poor postprocedural myocardial blush grade (MBG) [OR: 3.35 (1.32-8.15), p = 0.012] and LVEF predischarge [OR: 0.79 (0.72-0.86), p < 0.001] were found to be associated with LV thrombus. CONCLUSION: Our study demonstrated that the incidence of LV trombus was significantly lower with ticagrelor than clopidogrel-based DAPT during postdischarge treatment for anterior STEMI patients.

Atrial fibrillation, intra-ventricular thrombus, and other anticoagulant indications relationship with adverse outcomes in acute anterior myocardial infarction patients.

BACKGROUND: The aim of this study was to assess the predictive value of atrial fibrillation (AF), left ventricular thrombus (LVT), and other oral anticoagulant (OAC) indications on 1-year major adverse cardio-cerebrovascular events (MACCE) and bleeding in acute anterior ST-elevated myocardial infarction (STEMI) patients treated by primary percutaneous coronary intervention (PPCI). METHODS: Our study population included 969 anterior STEMI patients referred for PPCI from the prospective multicenter CIRCUS trial. Patients with a formal indication of OAC within the first year were compared to those without indication. RESULTS: A total of 161 (16.6%) patients were eligible for OAC after anterior STEMI mainly for AF (51.5%) and LVT (39.7%). This group had a higher morbidity profile despite similar reperfusion settings - 67% of them were treated with OAC. At 1 year, OAC indication was associated with a significant increase in MACCE rate [OR 3.37 95% CI (2.36;4.82) p<0.001] as well as bleeding [OR=1.96 95% CI (1.09;3.50) p=0.02]. After adjustment for principal confounders, OAC indication remained strongly associated with MACCE [HR 3.40 (1.26;9.14) p=0.016]. CONCLUSIONS: In a prospective cohort of anterior STEMI, AF, LVT, and other OAC indications were present upon discharge in 1 patient out of 6 and only two thirds were treated with OAC. OAC indication was independently associated with an increased risk of MACCE and bleeding at one year.

Recurrent unexpected myocardial infarction in a young woman: Insights on spontaneous coronary artery dissection and multimodality imaging.

A 45-year-old female was admitted for a transient anterior ST-segment elevation myocardial infarction (STEMI). Coronary angiogram showed a diffuse severe stenosis of the distal left anterior descending (LAD) coronary artery, which was managed medically. Three years later, a recurrent transient anterior STEMI led to a second coronary angiography showing a tubular stenosis of the mid-LAD with normal distal coronary bed. An optical coherence tomography (OCT) revealed a spontaneous coronary artery dissection (SCAD) with an extensive compressive mural hematoma without any intimal tear. Conservative treatment was continued. A repeat systematic angiogram 3months later suggested spontaneous healing but the OCT revealed several focal residual hematomas. This case illustrates the different possible angiographic appearances of SCAD and the contribution of the OCT in doubtful situations.

[Ischemic stroke related to spontaneous]. / Accident vasculaire cérébral ischémique en rapport avec hématome coronaire spontané.

Cardiovascular disease in women is a particularly complex pathology especially in the youngest population. The clinical presentation of acute coronary syndromes is sometimes misleading and does not necessarily point to the potential presence of cardiac disease given the frequent absence of cardiovascular risks. Such complexity results in delayed diagnosis, which worsens the outcome of myocardial infarction and generates complications related to the absence of coronary revascularization. We report the case of a patient who suffered an (undiagnosed) apical myocardial infarction that went undetected and was complicated by a voluminous intraventricular thrombus with embolus migration in the cerebral circulation resulting in an ischemic accident. The combination of these two pathologies make their therapeutic management particularly difficult. As widely reported in the literature, the outcome of myocardial infarction in women is poorer than in their male counterparts for a number of reasons. We can assume that in the youngest patients, another physiopathological mechanism is often involved, namely, the occurrence of hematoma and spontaneous coronary dissection. Diagnosis is often difficult even with coronary angiography diagnosis. As shown in the case reported here, initial examination results, if not thoroughly analyzed, may be erroneously interpreted as normal. It is also likely that the presence of hematoma or coronary wall dissection without any plaque rupture may negatively influence the outcome owing to the implementation of inappropriate treatments. In conclusion, in patients presenting with an ischemic cerebral accident, meticulous cardiac examination must be performed even in young women with no cardiovascular risk factors given that the occurrence of hematoma or coronary dissection may contribute to the formation of mural thrombi in the setting of myocardial infarction. Cardiac MRI seems to be particularly effective in the diagnosis of myocardial infarction complicated by the presence of intracavitary thrombi.

Outcomes and Prognostic Impact of Prophylactic Oral Anticoagulation in Anterior ST-Segment Elevation Myocardial Infarction Patients With Left Ventricular Dysfunction.

BACKGROUND: The contemporary role of prophylactic anticoagulation following extensive anterior wall ST-segment myocardial infarction (STEMI) is unclear. METHODS AND RESULTS: We evaluated anterior STEMI patients with left ventricle dysfunction (left ventricular ejection fraction ≤40%) ("high risk"), categorized by prophylactic warfarin use, within a regional STEMI. Patients with pre-existing atrial fibrillation were excluded. The primary outcome was an adjusted (for Global Registry of Acute Coronary Events risk score) 1-year composite of recurrent ischemia, stroke/transient ischemic attack/systemic embolism, or all-cause death. Of the 2032 STEMI admissions, 436 (21.5%) were high risk. After excluding 19 (4.4%) patients with definite left ventricle thrombus and 21 (4.8%) in-hospital deaths (2 had left ventricle thrombus), prophylactic warfarin was utilized in 236/398 (59.3%) high-risk survivors. Prescriptions were comparable across sex, but recipients were on average younger (58.5 years versus 64.0 years, P<0.001) and lower risk (Global Registry of Acute Coronary Events risk: 163 versus 181, P<0.001). No association on the adjusted ischemic composite (23.3% versus 25.3%, odds ratio 0.96, 95% CI 0.60-1.55) or thromboembolic events (2.1% versus 1.2%, odds ratio 1.99, 95% CI 0.38-10.51) was observed, but reduced 1-year all-cause mortality was noted (2.5% versus 8.6%, odds ratio 0.30, 95% CI 0.11-0.81); numerically higher major bleeding was observed at 1 year (2.5% versus 1.2%, odds ratio 2.17, 95% CI 0.43-10.96). CONCLUSIONS: A high utilization of prophylactic warfarin occurs in anterior STEMI patients with left ventricle dysfunction, yet appears to provide no additional benefit on the ischemic composite. The association with lower all-cause mortality, but higher bleeding, calls for an improved understanding of its role in high-risk STEMI.

Effects of Low-Dose Recombinant Human Brain Natriuretic Peptide on Anterior Myocardial Infarction Complicated by Cardiogenic Shock.

INTRODUCTION:: The mortality due to cardiogenic shock complicating acute myocardial infarction (AMI) is high even in patients with early revascularization. Infusion of low dose recombinant human brain natriuretic peptide (rhBNP) at the time of AMI is well tolerated and could improve cardiac function. OBJECTIVE:: The objective of this study was to evaluate the hemodynamic effects of rhBNP in AMI patients revascularized by emergency percutaneous coronary intervention (PCI) who developed cardiogenic shock. METHODS:: A total of 48 patients with acute ST segment elevation myocardial infarction (STEMI) complicated by cardiogenic shock and whose hemodynamic status was improved following emergency PCI were enrolled. Patients were randomly assigned to rhBNP (n=25) and control (n=23) groups. In addition to standard therapy, study group individuals received rhBNP by continuous infusion at 0.005 µg kg-1 min-1 for 72 hours. RESULTS:: Baseline characteristics, medications, and peak of cardiac troponin I (cTnI) were similar between both groups. rhBNP treatment resulted in consistently improved pulmonary capillary wedge pressure (PCWP) compared to the control group. Respectively, 7 and 9 patients died in experimental and control groups. No drug-related serious adverse events occurred in either group. CONCLUSION:: When added to standard care in stable patients with cardiogenic shock complicating anterior STEMI, low dose rhBNP improves PCWP and is well tolerated.

Effects of low-dose recombinant human brain natriuretic peptide on anterior myocardial infarction complicated by cardiogenic shock

Abstract INTRODUCTION: The mortality due to cardiogenic shock complicating acute myocardial infarction (AMI) is high even in patients with early revascularization. Infusion of low dose recombinant human brain natriuretic peptide (rhBNP) at the time of AMI is well tolerated and could improve cardiac function. OBJECTIVE: The objective of this study was to evaluate the hemodynamic effects of rhBNP in AMI patients revascularized by emergency percutaneous coronary intervention (PCI) who developed cardiogenic shock. METHODS: A total of 48 patients with acute ST segment elevation myocardial infarction (STEMI) complicated by cardiogenic shock and whose hemodynamic status was improved following emergency PCI were enrolled. Patients were randomly assigned to rhBNP (n=25) and control (n=23) groups. In addition to standard therapy, study group individuals received rhBNP by continuous infusion at 0.005 µg kg−1 min−1 for 72 hours. RESULTS: Baseline characteristics, medications, and peak of cardiac troponin I (cTnI) were similar between both groups. rhBNP treatment resulted in consistently improved pulmonary capillary wedge pressure (PCWP) compared to the control group. Respectively, 7 and 9 patients died in experimental and control groups. No drug-related serious adverse events occurred in either group. CONCLUSION: When added to standard care in stable patients with cardiogenic shock complicating anterior STEMI, low dose rhBNP improves PCWP and is well tolerated.

Relation of Left Ventricular Mass and Infarct Size in Anterior Wall ST-Segment Elevation Acute Myocardial Infarction (from the EMBRACE STEMI Clinical Trial).

Biomarker measures of infarct size and myocardial salvage index (MSI) are important surrogate measures of clinical outcomes after a myocardial infarction. However, there is variability in infarct size unaccounted for by conventional adjustment factors. This post hoc analysis of Evaluation of Myocardial Effects of Bendavia for Reducing Reperfusion Injury in Patients With Acute Coronary Events (EMBRACE) ST-Segment Elevation Myocardial Infarction (STEMI) trial evaluates the association between left ventricular (LV) mass and infarct size as assessed by areas under the curve for creatine kinase-MB (CK-MB) and troponin I release over the first 72 hours (CK-MB area under the curve [AUC] and troponin I [TnI] AUC) and the MSI. Patients with first anterior STEMI, occluded left anterior descending artery, and available LV mass measurement in EMBRACE STEMI trial were included (n = 100) (ClinicalTrials.govNCT01572909). MSI, end-diastolic LV mass on day 4 cardiac magnetic resonance, and CK-MB and troponin I concentrations were evaluated by a core laboratory. After saturated multivariate analysis, dominance analysis was performed to estimate the contribution of each independent variable to the predicted variance of each outcome. In multivariate models that included age, gender, body surface area, lesion location, smoking, and ischemia time, LV mass remained independently associated with biomarker measures of infarct size (CK-MB AUC p = 0.02, TnI AUC p = 0.03) and MSI (p = 0.003). Dominance analysis demonstrated that LV mass accounted for 58%, 47%, and 60% of the predicted variances for CK-MB AUC, TnI AUC, and MSI, respectively. In conclusion, LV mass accounts for approximately half of the predicted variance in biomarker measures of infarct size. It should be considered as an adjustment variable in studies evaluating infarct size.

Value of human brain natriuretic peptide in treatment of acute anterior myocardial infarction evaluated via three-dimensional speckle tracking imaging.

Three-dimensional ultrasound speckle tracking imaging was used to evaluate the effects of recombinant human brain natriuretic peptide (rhBNP) in acute anterior and extensive anterior myocardial infarction. Ninety patients with acute anterior or extensive myocardial infarction were randomly divided into 3 groups: Group A [emergency percutaneous coronary intervention (PCI)], Group B (emergency PCI + rhBNP early treatment), and Group C (emergency PCI + late rhBNP treatment). Within 6 h of admission and at 1 week and 3 and 6 months after PCI, patients underwent routine transthoracic echocardiography and real-time three-dimensional echocardiography. At 1 week, 1 month, 3 months, 6 months, and 12 months, ejection fraction values in groups B and C were significantly greater than those in group A (P < 0.05), and left ventricular end-diastolic volume and left ventricular end-systolic volume values in groups B and C were less than those in group A (P < 0.05). Within 6 h of admission in each group, long-axis, radial, circumferential, and area variables corresponding to anterior descending artery segments showed no significant difference (all P > 0.05). However, at 1 week, 1 month, 3 months, 6 months, and 12 months, long-axis, radial, circumferential and area variables in groups B and C were significantly less than those in group A (P < 0.05). Intervention with rhBNP can im-prove resilience of the local myocardium, left ventricular mechanical function, and cardiac remodeling. Within 6 h of admission or after PCI, rhBNP application showed no significant difference in heart function improvement or myocardial remodeling inhibition.

Takotsubo cardiomyopathy and thrombotic thrombocytopenic purpura preceding a lupus diagnosis: a case report.

Takotsubo cardiomyopathy, a rare stress-related cardiomyopathy, has been observed in a few cases secondary to systemic lupus erythematosus (SLE). Herein, we report an unusual case where a postmenopausal woman presented initially with Takotsubo syndrome, later developed thrombotic thrombocytopenic purpura and cerebrovascular events, initially without clinical or laboratory features of SLE. During the course of her illness, she was found to satisfy four of the Systemic Lupus International Collaborating Clinics classification criteria for a SLE diagnosis. This unique presentation of our patient, initially with Takotsubo cardiomyopathy, the development of thrombotic thrombocytopenic purpura and cerebrovascular events preceding the diagnosis of SLE illustrates the importance of clinical observation and follow-up.

Individualised dual antiplatelet therapy in a patient with short bowel syndrome after acute myocardial infarction with coronary artery stenting.

Short bowel syndrome after extensive surgical resection of the intestine is characterised by inadequate digestion and absorption of nutrients. Additional clinical problems include impaired absorption and metabolism of diverse drugs requiring individualised medical therapy or alternative treatments. We report a case of individualised dual antiplatelet therapy in a patient who underwent an extensive intestinal resection complicated by acute myocardial infarction requiring percutaneous coronary intervention and stent implantation. Genetic testing of CYP2C19 gene polymorphisms and platelet aggregation testing were used to assess responses to aspirin, clopidogrel, prasugrel and ticagrelor. Given its unique pharmacokinetics with good absorption and without need of metabolism to an active substance, ticagrelor appears to be the best for patients with short bowel syndrome who require dual antiplatelet therapy after coronary stent implantation.