Randomized, Placebo-Controlled Phase 2b Study to Evaluate the Safety and Efficacy of Recombinant Human Lecithin Cholesterol Acyltransferase in Acute ST-Segment-Elevation Myocardial Infarction: Results of REAL-TIMI 63B.

BACKGROUND: High-density lipoprotein plays a key role in reverse cholesterol transport. In addition, high-density lipoprotein particles may be cardioprotective and reduce infarct size in the setting of myocardial injury. Lecithin-cholesterol acyltransferase is a rate-limiting enzyme in reverse cholesterol transport. MEDI6012 is a recombinant human lecithin-cholesterol acyltransferase that increases high-density lipoprotein cholesterol. Administration of lecithin-cholesterol acyltransferase has the potential to reduce infarct size and regress coronary plaque in acute ST-segment-elevation myocardial infarction. METHODS: REAL-TIMI 63B (A Randomized, Placebo­controlled Phase 2b Study to Evaluate the Safety and Efficacy of MEDI6012 in Acute ST Elevation Myocardial Infarction) was a phase 2B multinational, placebo-controlled, randomized trial. Patients with ST-segment-elevation myocardial infarction within 6 hours of symptom onset and planned for percutaneous intervention were randomly assigned 2:1 to MEDI6012 (2- or 6-dose regimen) or placebo and followed for 12 weeks. The primary outcome was infarct size as a percentage of left ventricular mass by cardiac MRI at 10 to 12 weeks, with the primary analysis in patients with TIMI Flow Grade 0 to 1 before percutaneous intervention who received at least 2 doses of MEDI6012. The secondary outcome was change in noncalcified plaque volume on coronary computed tomographic angiography from baseline to 10 to 12 weeks with the primary analysis in patients who received all 6 doses of MEDI6012. RESULTS: A total of 593 patients were randomly assigned. Patients were a median of 62 years old, 77.9% male, and 95.8% statin naive. Median time from symptom onset to randomization was 146 (interquartile range [IQR], 103-221) minutes and from hospitalization to randomization was 12.7 (IQR, 6.6-24.0) minutes, and the first dose of drug was administered a median of 8 (IQR, 3-13) minutes before percutaneous intervention. The index myocardial infarction was anterior in 69.6% and TIMI Flow Grade 0 to 1 in 65.1% of patients. At 12 weeks, infarct size did not differ between treatment groups (MEDI6012: 9.71%, IQR 4.79-16.38; placebo: 10.48%, [IQR, 4.92-16.61], 1-sided P=0.79. There was also no difference in noncalcified plaque volume (geometric mean ratio, 0.96 [95% CI, NA-1.10], 1-sided P=0.30). There was no significant difference in treatment emergent serious adverse events. CONCLUSIONS: Administration of MEDI6012 in patients with acute ST-segment-elevation myocardial infarction did not result in a significant reduction in infarct size or noncalcified plaque volume at 12 weeks. MEDI6012 was well tolerated with no excess in overall serious adverse events. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03578809.

Identification of an epicardial slow conduction channel using ripple mapping in ablation of postinfarct ventricular tachycardia.

An 82-year-old man underwent redo catheter ablation of ventricular tachycardia (VT) after anterior infarction. A ripple mapping conducting channel (RMCC) was identified within the anterior scar in the left ventricular epicardium during sinus rhythm. Along the RMCC, delayed potentials during sinus rhythm, a good pace map with a long stimulus to the QRS interval, and mid-diastolic potentials during VT were recorded, and epicardial ablation at this site eliminated the VT. These findings suggested that the RMCC in the epicardial scar served as a critical isthmus of the postinfarct VT, and ablation targeting the RMCC was effective.

[Effects of telmisartan on inflammation and fibrosis after acute myocardial infarction in rats].

OBJECTIVE: To explore the protection mechanisms of telmisartan on inflammation and fibrosis after myocardial infarction in rats. METHODS: The model of acute myocardial infarction (AMI) was established by ligating left anterior descending coronary artery. The surviving rats were divided into AMI (AMI) and telmisartan treatment (telmisartan) groups. And another sham operation group (sham) was designated (n = 8). At the end of study, total heart weight (THW), left ventricular weight (LVW) and weight index were measured; myocardial infarction and inflammatory reactions detected by hematoxylin and eosin and Masson staining; the serum levels of C-reactive protein (CRP), tumor necrosis factor-alpha (TNFα), monocyte chemotactic protein-1 (MCP-1), interleukin-6 (IL-6) and interleukin-1 beta (IL-1ß) by enzyme-linked immunosorbent assay (ELISA); the levels of transforming growth factor 1 (TGFß1), collagen I, collagen III and MMP9 mRNA in myocardial tissue by reverse transcription-polymerase chain reaction (RT-PCR); the expressions of TGFß1, collagen I, collagen III, matrix metallopeptidase 9 (MMP9) and nuclear factor-kappa B (NF-κB) by Western blot. RESULTS: Compared with sham group, significant pathological changes of myocardium occurred in AMI group. The serum levels of CRP [(472 ± 132) vs (104 ± 28) ng/ml], TNFα [(229 ± 41) vs (18 ± 5) pg/ml], MCP-1[(558 ± 116) vs (158 ± 20) pg/ml], IL-6 [(404 ± 63) vs (21 ± 4) pg/ml] and IL-1ß [(625 ± 145) vs (189 ± 34) pg/ml] increased (P < 0.05). RT-PCR analysis showed that the expression levels of TGFß1, collagen I, collagen III and MMP9 increased significantly. The results of Western blot were consistent and NF-κB was activated significantly (P < 0.05). Compared with AMI group, the above-mentioned indicators decreased obviously in telmisartan group (P < 0.05). CONCLUSION: Telmisartan may regulate inflammation and myocardial fibrosis after acute myocardial infarction by signaling pathways of NF-κB and TGFß in rats.

Intracoronary electrocardiogram ST-segment elevation in patients with non-ST-segment elevation myocardial infarction and its association with culprit lesion location and myocardial injury.

AIMS: An intracoronary electrocardiogram (IC-ECG) is a sensitive method to detect local myocardial ischaemia. We investigated the prevalence of IC-ECG ST-segment elevation (STE) with respect to culprit lesion location in patients with non-ST-segment elevation myocardial infarction (NSTEMI) and its relationship with elevated levels of cardiac biomarkers. METHODS AND RESULTS: We examined 87 NSTEMI patients who underwent IC-ECG recording by locating the insulated polymer-coated guidewire distal to the culprit lesion before percutaneous coronary intervention (PCI). Cardiac biomarkers were serially examined. IC-ECG STE was observed in 24 patients (27.6%) before PCI, and was significantly more frequent in patients with LCx culprit lesions (LAD vs. LCx vs. RCA, 12.1% vs. 53.3% vs. 16.7%; p<0.001). Peak cardiac troponin I (cTnI) values were associated with IC-ECG STE, ejection fraction (EF), cTnI values on admission, and type B2/C lesions. In multivariate analysis, IC-ECG STE (odds ratio [OR], 5.04; 95% confidence intervals [CI]: 1.51-16.85; p=0.009), and EF (OR, 0.95; 95% CI: 0.90-1.00; p=0.043) were predictors of greater peak cTnI values. CONCLUSIONS: IC-ECG STE was not uncommon in NSTEMI patients, particularly those with LCx culprit lesions. IC-ECG monitoring before PCI may help identify NSTEMI patients with high risk of greater myocardial injury.

Focal myocardial infarction induces global remodeling of cardiac sympathetic innervation: neural remodeling in a spatial context.

Myocardial infarction (MI) induces neural and electrical remodeling at scar border zones. The impact of focal MI on global functional neural remodeling is not well understood. Sympathetic stimulation was performed in swine with anteroapical infarcts (MI; n = 9) and control swine (n = 9). A 56-electrode sock was placed over both ventricles to record electrograms at baseline and during left, right, and bilateral stellate ganglion stimulation. Activation recovery intervals (ARIs) were measured from electrograms. Global and regional ARI shortening, dispersion of repolarization, and activation propagation were assessed before and during sympathetic stimulation. At baseline, mean ARI was shorter in MI hearts than control hearts (365 ± 8 vs. 436 ± 9 ms, P < 0.0001), dispersion of repolarization was greater in MI versus control hearts (734 ± 123 vs. 362 ± 32 ms(2), P = 0.02), and the infarcted region in MI hearts showed longer ARIs than noninfarcted regions (406 ± 14 vs. 365 ± 8 ms, P = 0.027). In control animals, percent ARI shortening was greater on anterior than posterior walls during right stellate ganglion stimulation (P = 0.0001), whereas left stellate ganglion stimulation showed the reverse (P = 0.0003). In infarcted animals, this pattern was completely lost. In 50% of the animals studied, sympathetic stimulation, compared with baseline, significantly altered the direction of activation propagation emanating from the intramyocardial scar during pacing. In conclusion, focal distal anterior MI alters regional and global pattern of sympathetic innervation, resulting in shorter ARIs in infarcted hearts, greater repolarization dispersion, and altered activation propagation. These conditions may underlie the mechanisms by which arrhythmias are initiated when sympathetic tone is enhanced.

[Acute anterior myocardial infarction presented with cardiogenic shock in a patient on herbal medication]. / Bitkisel ilaç tedavisi alan ve akut anterior miyokart enfarktüsüne bagli kardiyojenik sok gelisen olgu.

Uncontrolled usage of herbal medications may cause problems that can lead to serious complications, including death. Panax is thought to have hypocholesterolemic, anticarcinogenic, antiinflammatory, and antimicrobial effects via its saponin ingredient and positive inotropic effects via its panax ginseng effect. However, clinical studies have shown that it can increase the low-density lipoprotein (LDL) levels secondary to its hypocholesterolemic effect, have a hypertensive effect in chronic users via ginseng abuse syndrome, and also have hypotensive effects. Here, we present a case with typical angina pectoris in which coronary angiography was suggested but refused. The male patient initiated panax therapy and presented to our emergency department with diffuse anterior myocardial infarction and cardiogenic shock, and was discharged after appropriate therapy.

Intralipid, a clinically safe compound, protects the heart against ischemia-reperfusion injury more efficiently than cyclosporine-A.

BACKGROUND: We have recently shown that postischemic administration of intralipid protects the heart against ischemia-reperfusion injury. Here we compared the cardioprotective effects of intralipid with cyclosporine-A, a potent inhibitor of the mitochondrial permeability transition pore opening. METHODS: In vivo rat hearts or isolated Langendorff-perfused mouse hearts were subjected to ischemia followed by reperfusion with intralipid (0.5%, 1% and 2% ex-vivo, and 20% in vivo), cyclosporine-A (0.2 µM, 0.8 µM, and 1.5 µM ex- vivo and 10 mg/kg in vivo), or vehicle. The hemodynamic function, infarct size, calcium retention capacity, mitochondrial superoxide production, and phosphorylation levels of protein kinase B (Akt)/glycogen synthase kinase-3ß (GSK-3ß) were measured. The values are mean ± SEM. RESULTS: Administration of intralipid at reperfusion significantly reduced myocardial infarct size compared with cyclosporine-A in vivo (infarct size/area at risk)%: 22.9 ± 2.5% vs. 35.2 ± 3.5%; P = 0.030, n = 7/group). Postischemic administration of intralipid at its optimal dose (1%) was more effective than cyclosporine-A (0.8 µM) in protecting the ex vivo heart against ischemia-reperfusion injury, as the rate pressure product at the end of reperfusion was significantly higher (mmHg · beats/min: 12,740 ± 675 [n = 7] vs. 9,203 ± 10,781 [n = 5], P = 0.024), and the infarct size was markedly smaller (17.3 ± 2.9 [n = 7] vs. 29.2 ± 2.7 [n = 5], P = 0.014). Intralipid was as efficient as cyclosporine-A in inhibiting the mitochondrial permeability transition pore opening (calcium retention capacity = 280 ± 8.2 vs. 260.3 ± 2.9 nmol/mg mitochondria protein in cyclosporine-A, P = 0.454, n = 6) and in reducing cardiac mitochondrial superoxide production. Unlike intralipid, which increased phosphorylation of Akt (6-fold) and GSK-3ß (5-fold), cyclosporine-A had no effect on the activation of these prosurvival kinases. CONCLUSIONS: Although intralipid inhibits the opening of the mitochondrial permeability transition pore as efficiently as cyclosporine-A, intralipid is more effective in reducing the infarct size and improving the cardiac functional recovery.

Recurrent polymorphic ventricular tachycardia treated by ablation of Purkinje arborization within an infarct border-zone.

A 70-year-old patient with 3-vessel coronary artery disease and a left ventricular aneurysm underwent coronary artery bypass grafting, together with a surgical anterior ventricular endocardial restoration (SAVER) procedure. Four days later, he suddenly developed recurrent sustained and nonsustained polymorphic ventricular tachycardia, preceded by monomorphic ventricular premature contractions, and did not respond to any antiarrhythmic drug, including lidocaine, esmolol, or amiodarone. Repeated electrical cardioversion procedures were performed (28 in total). Mapping was performed to target the earliest site of activation in the left ventricle during the ventricular premature contractions, a site where the premature beats were preceded by Purkinje potentials. That site was located along a scar border-zone. Ablation at that site resulted in the disappearance of the monomorphic ventricular premature contractions and in the complete suppression of the electrical storm. These findings appear to indicate that the area in which the Purkinje potentials were recorded along the scar border-zone played an important role in the mechanism of the polymorphic ventricular tachycardia after myocardial infarction.

Current pacemaker and defibrillator therapy.

BACKGROUND: Pacemakers have been available for 50 years, and implantable cardiac defibrillators for 25. Clear indications for each have been established on the basis of data from randomized clinical trials (RCTs). METHODS: This review article is the product of a collaborative effort by a cardiologist and a cardiac surgeon. The authors arrived at a consensus through a selective review of the literature, with special attention to randomized controlled trials and registry data. RESULTS: Atrioventricular (AV) block only rarely necessitates permanent pacemaker stimulation after inferior myocardial infarction, of which it is a rare (12% to 20%) and often transient accompaniment. AV block is more common, however, in anterior wall infarction (frequency ca. 5%), and often necessitates permanent pacemaker therapy in such cases. Pacemaker complications are rare; they include oversensing (the detection of impulse noise) (0.7%), undersensing (the failure to detect impulses) (3.8%), electrode fractures (3.8%), isolation defects (3.4%), perforation (<1%), dislocation (<1%), and infection (<1% to 12%). Many RCTs have confirmed that defibrillators are effective in the prevention of sudden cardiac death (SCD): they lower the risk of SCD by 20% to 30% in primary prevention and by 20% to 40% in secondary prevention. Cardiac resynchronization therapy improves the clinical manifestations and outcome of patients with congestive heart failure, with a relative risk reduction (RR) of 20% to 40%, even among patients in NYHA classes I and II (RR ca. 40%). Implantable defibrillators only rarely cause problems or complications in either the short or the long term. Emotional disturbances, including anxiety, are a rare side effect, occurring in less than 1% of cases. CONCLUSION: Pacemakers and implantable defibrillators are well-established electrotherapeutic devices that are highly effective and have only rare complications.