Late coronary artery reperfusion has additive beneficial effects on infarct expansion when combined with early angiotensin converting enzyme inhibitor therapy post myocardial infarction

Background: Individually, late coronary artery reperfusion and early angiotensin converting enzyme (ACE) inhibitor therapy prevent infarct expansion post myocardial infarction (MI). Objectives: To examine the effect of late reperfusion on infarct expansion when added to early ACE inhibitor therapy post MI. Methods: Rats were randomized into two groups: Reperfusion group: rats underwent coronary artery occlusion followed by reperfusion 2 hours after MI, a time too late to reduce infarct size. A control group: rats underwent permanent coronary artery occlusion followed by a sham operation 2 hours after MI. All rats received enalapril (2.0 ± 0.2 mg/kg) daily in drinking water, started immediately after the second operation. Rats were sacrificed 2 weeks after coronary occlusion. Hearts were arrested and fixed at a constant pressure, then sectioned and photographed for morphometric analysis. Results: Infarct size was similar in the reperfusion and control groups (23 ± 2 vs 26 ± 2%, p = NS). Septal thickness was also similar in both groups (1.8 ± 0.1 vs 1.8 ± 0.1 mm, p = NS). There was a trend towards thicker infarcts in the reperfusion group compared to the control group (0.84 ± 0.06 vs 0.72 ± 0.05 mm, p = 0.1). Compared to early ACE inhibition alone, late reperfusion combined with early ACE inhibition limited infarct expansion (expansion index, 1.13 ± 0.12 vs 1.44 ± 0.14, p < 0.05), prevented left ventricular (LV) dilation (LV volume, 0.30 ± 0.02 vs 0.39 ± 0.03 ml, p < 0.01) and prevented LV hypertrophy (LV weight, 0.71 ± 0.18 vs 0.77 ± 0.20 gm, p < 0.05). Conclusions: Late coronary artery reperfusion prevents infarct expansion, LV dilation and hypertrophy even when added to early ACE inhibitor therapy post MI. This suggests that late reperfusion may be beneficial in patients with acute MI treated with early ACE inhibitor therapy.     

Stem‐cell therapy in ST‐segment elevation myocardial infarction with reduced ejection fraction: A multicenter,double‐blind randomized trial

Background

Left ventricular ejection fraction (LVEF) is a major determinant of long‐term prognosis after ST‐segment elevation myocardial infarction (STEMI). STEMI patients with reduced LVEF have a poor prognosis, despite successful reperfusion and the use of renin‐angiotensin‐aldosterone inhibitors.

Hypothesis

Intracoronary infusion of bone marrow–derived mononuclear cells (BMMC) may improve LVEF in STEMI patients successfully reperfused.

Methods

The main inclusion criteria for this double‐blind, randomized, multicenter study were patient age 30 to 80 years, LVEF ≤50%, successful angioplasty of infarct‐related artery, and regional dysfunction in the infarct‐related area analyzed before cell injection. Cardiac magnetic resonance imaging was used to assess LVEF, left ventricular volumes, and infarct size at 7 to 9 days and 6 months post–myocardial infarction.

Results

One hundred and twenty‐one patients were included (66 patients in the BMMC group and 55 patients in the placebo group). The primary endpoint, mean LVEF, was similar between both groups at baseline (44.63% ± 10.74% vs 42.23% ± 10.33%; P = 0.21) and at 6 months (44.74% ± 12.95 % vs 43.50 ± 12.43%; P = 0.59). The groups were also similar regarding the difference between baseline and 6 months (0.11% ± 8.5% vs 1.27% ± 8.93%; P = 0.46). Other parameters of left ventricular remodeling, such as systolic and diastolic volumes, as well as infarct size, were also similar between groups.

Conclusions

In this randomized, multicenter, double‐blind trial, BMMC intracoronary infusion did not improve left ventricular remodeling or decrease infarct size.     

Role of aldosterone in mid- and long-term left ventricular remodelling after acute myocardial infarction: The REMI study

Aims

Whether aldosterone levels after myocardial infarction (MI) are associated with mid- and long-term left ventricular (LV) remodelling in the era of systematic use of renin–angiotensin system inhibitors is uncertain. We prospectively investigated the relationship between aldosterone levels and mid- and long-term LV remodelling in patients with acute MI.

Methods and results

Plasma aldosterone was measured in 119 patients successfully treated by primary percutaneous coronary angioplasty for a first acute ST-elevation MI (STEMI) 2–4 days after the acute event. LV volumes were assessed by cardiac magnetic resonance (CMR) and transthoracic echocardiography (TTE) in the same timeframe and 6 months later. LV assessment was repeated by TTE 3–9 years after MI (n = 80). The median aldosterone level at baseline was 23.1 [16.8; 33.1] pg/ml. In the multivariable model, higher post-MI aldosterone concentration was significantly associated with more pronounced increase in LV end-diastolic volume index (TTE: β ± standard error [SE]: 0.113 ± 0.046, p = 0.015; CMR: β ± SE: 0.098 ± 0.040, p = 0.015) and LV end-systolic volume index (TTE: β ± SE: 0.083 ± 0.030, p = 0.008; CMR: β ± SE: 0.064 ± 0.032, p = 0.048) at 6-month follow-up, regardless of the method of assessment. This result was consistent also in patients with a LV ejection fraction (LVEF) >40%. The association between baseline plasma aldosterone and adverse LV remodelling did not persist at the 3–9-year follow-up evaluation.

Conclusion

Aldosterone concentration in the acute phase was associated with adverse LV remodelling in the medium term, even in the subgroup of patients with LVEF >40%, suggesting a potential role of the mineralocorticoid system in post-MI adverse remodelling. Plasma aldosterone was no longer associated with LV remodelling in the long term (NCT01109225).     

Intracoronary infusion of autologous mononuclear bone marrow cells in patients with acute myocardial infarction treated with primary PCI: Pilot study of the multicenter HEBE trial

Objective : This study was a pilot trial to determine safety and feasibility of intracoronary infusion of mononuclear bone marrow cells (MBMC) in patients with acute myocardial infarction (MI). Background : Studies reporting the effect of MBMC therapy on improvement of left ventricular (LV) function have shown variable results. The HEBE trial is a large multicenter, randomized trial that currently enrolls patients. Prior to this trial we performed a pilot study. Methods : Twenty‐six patients with a first acute MI were prospectively enrolled in eight centers. Bone marrow aspiration was performed at a median of 6 days after primary PCI (interquartile range, 5–7 days). MBMC were isolated by gradient centrifugation and were infused intracoronary the same day. All patients underwent magnetic resonance imaging before cell infusion and after 4 months. Clinical events were assessed up to 12 months. Results : Within 10 hr after bone marrow aspiration, 246 ± 133 × 10⁶ MBMC were infused, of which 3.9 ± 2.3 × 10⁶ cells were CD34⁺. In one patient, this procedure was complicated by local dissection. LV ejection fraction significantly increased from 45.0 ± 6.3% to 47.2 ± 6.5% (P = 0.03). Systolic wall thickening in dysfunctional segments at baseline improved with 0.9 ± 0.7 mm (P < 0.001). Infarct size decreased 37% from 17.8 ± 8.2 to 11.2 ± 4.2 gram (P < 0.001). During 12‐month follow‐up, 3 additional revascularizations were performed and an ICD was implanted in one patient, 3 weeks after PCI. Conclusion : In patients with acute MI, intracoronary infusion of MBMC is safe in a multicenter setting. At 4‐month follow‐up, a modest increase in global and regional LV function was observed, with a concomitant decrease in infarct size. © 2008 Wiley‐Liss, Inc.     

Time dependence of left ventricular recovery after delayed recanalization of an occluded infarct-related coronary artery: findings of a pilot study

Objectives. We sought to test the hypothesis that late recanalization of infarct-related coronary arteries (IRAs) improves long-term left ventricular (LV) function.Background. Reperfusion within 24 h of an acute myocardial infarction (MI) has been shown to improve myocardial healing and to reduce infarct expansion. Uncontrolled data suggest that there may be a time window of several weeks for such an effect.Methods. Sixteen asymptomatic patients 10 ± 4 days after a first Q wave anterior wall MI with persistent left anterior descending coronary artery occlusion and infarct-zone akinesia were randomized to immediate (2 weeks) or delayed (3 months) angioplasty. Repeat catheterization and cardiac magnetic resonance imaging (MRI) were performed after 3 and 12 months.Results. Angiography 3 months after MI revealed that LV ejection fraction (LVEF) had increased ([mean ± SD] 54.4 ± 4.3% vs. 63.9 ± 7.4%, p < 0.01) as a result of improved regional function (p < 0.01) and LV end-systolic volume had decreased (p < 0.002), whereas LV end-diastolic volume remained unchanged. With delayed angioplasty, LVEF, infarct zone wall motion and LV volumes did not improve. Cardiac MRI at baseline and at 3 and 12 months confirmed these findings and extended them up to 1 year, indicating that delayed angioplasty could no longer improve LV function because of marked LV dilation (p < 0.01). Immediate angioplasty had a high success rate, but restenosis (50%) was accompanied by new severe angina as a clinical indicator of salvaged myocardium, which did not occur after delayed angioplasty.Conclusions. This pilot study in selected patients supports the hypothesis that myocardial viability persists (“hibernation”) for 2 to 3 weeks but not for 3 months after MI, during which time it may be worthwhile to restore blood flow to a large myocardial territory, even in asymptomatic patients, to improve long-term LV function.     

Diannexin reduces no-reflow after reperfusion in rabbits with large ischemic myocardial risk zones

Introduction and Aims : In patients with ST‐segment elevation myocardial infarction who receive percutaneous coronary intervention and stenting, a large zone with no‐reflow is associated with adverse outcomes. During myocardial ischemia/reperfusion, phosphatidylserine (PS) translocates to the surface of endothelial cells triggering attachment of platelets and leukocytes, thus impairing microvascular blood flow. Diannexin, a recombinant dimer of the endogenous human annexin V protein, binds PS and thus inhibits the adverse effects of PS. It has been shown to attenuate postischemic reperfusion injury in several experimental models. We speculated that Diannexin would reduce no‐reflow in the heart after coronary artery occlusion (CAO) and reperfusion. Rabbits received: (1) Diannexin 5 min pre‐CAO (diannexin pre ischemia [DPI], 400 μg/kg, n = 17), or (2) Diannexin 5 min pre‐coronary reperfusion (diannexin pre reperfusion [DPR], 400 μg/kg, n = 20), or (3) saline (Cont, n = 18), with 30 min CAO and 3 h reperfusion. In a secondary analysis, rabbits were divided into two groups based on the overall average risk zone size of 29% of the left ventricle (LV): small (<29% of LV) and large (>29% of LV). Results: Overall, risk zones and infarct size, and the no‐reflow zone were similar in all groups. In hearts with large risk zones the no‐reflow area was significantly smaller in both drug‐treated groups (DPI, 22 ± 5% and DPR, 22 ± 3% vs. control 40 ± 3%, P < 0.006), the hemorrhagic areas were significantly smaller, and infarct size was reduced at the P < 0.06 level compared with control. In animals with small risk zones there were no significant differences. Diannexin treatment did not affect hemodynamics or LV function. Conclusion: Diannexin was cardioprotective in rabbits with a severe ischemic insult. This is important, because large infarcts accompanied by no‐reflow in humans are associated with increased complications. In animals with small risk zones, no significant drug effect was observed.     

Feasibility of primary clot extraction prior to percutaneous coronary intervention in acute myocardial infarction

Objectives : To test the feasibility, safety, and in‐hospital outcomes of utilizing the FilterWire EZ to extract clot prior to percutaneous coronary intervention (PCI) in patients presenting with acute myocardial infarction (MI). Background : PCI in patients with acute MI is associated with a higher incidence of distal embolization, no‐reflow, or slow flow partly due to the presence of clot burden. Methods : The authors describe the feasibility, safety, and outcomes of using a FilterWire EZ distal protection device as a clot extraction device in patients who presented with acute MI and documented clot on coronary angiography. Results : Fifteen consecutive male patients with a mean age of 54 ± 8 years presented with acute MI (60% ST elevation MI). MI involved left anterior descending artery (n = 4), circumflex artery (n = 3), and right coronary artery (n = 8). Clot extraction followed by PCI reduced the percent diameter stenosis from 94 ± 12 to 65 ± 11 (P < 0.001) and restored TIMI 3 flow in all patients without distal embolization. The angiographic, procedural, and clinical success rates were 100%. The mean left ventricular ejection fraction (LVEF) was 52 ± 8% (range 30–62%) with only three patients (15%) who had an LVEF <50% and five patients (33%) without apparent wall motion abnormalities on echocardiography. Conclusions : Clot extraction before PCI during acute MI in native coronaries is feasible, safe, and effective in restoring TIMI 3 flow without distal embolization. Whether this approach results in better outcomes and improved LV function compared with standard therapy alone requires further investigation. © 2008 Wiley‐Liss, Inc.     

Decreased level of melatonin in serum predicts left ventricular remodelling after acute myocardial infarction

Abstract: As experimental studies suggest that melatonin is cardioprotective after myocardial infarction (MI), this study sought to investigate the relationships between circulating levels of melatonin and left ventricular (LV) remodelling in patients after acute MI. This prospective study included 161 patients (age 61 ± 3 yr; 78% men) undergoing primary percutaneous coronary intervention who were assessed echocardiographically at hospital discharge (day 3–7) and at 12 months. LV remodelling was defined as >20% increase in LV end‐diastolic volume at 12‐month follow‐up compared with baseline. Serum melatonin concentrations were measured at admission, during the light period. Twenty‐four patients showed LV remodelling, and 137 had no evidence of LV remodelling. Patients with LV remodelling had lower levels of melatonin at study entry [9.96 (8.28–11.03) versus 16.74 (13.77–19.59) pg/mL, respectively; P < 0.0001]. Multivariate analysis showed that melatonin levels (OR = 2.10, CI 95% 1.547–2.870, P < 0.001) were an independent predictor of LV remodelling at 12‐month follow‐up. Receiver operating characteristic (ROC) analysis showed an area under the curve of 0.959 (CI 95% 0.93–0.98; P < 0.0001). To our knowledge, this is the first study to show the relationship between melatonin and LV remodelling during the chronic phase post‐MI.     

First‐in‐Man Study of Dedicated Bifurcation Sirolimus‐eluting Stent: 12‐month Results of BiOSS LIM® Registry

Objectives

The aim was to assess the effectiveness and safety profile of a new dedicated bifurcation stent ‐ sirolimus‐eluting BiOSS LIM® (Balton, Poland) in 12‐month Registry.

Background

The optimal approach to coronary bifurcations treatment by percutaneous coronary intervention (PCI) has been still a subject of debate. Dedicated bifurcation stents are one of the proposed solutions.

Methods

This was the international, 3‐center registry, which enrolled patients with non‐ST‐elevation acute coronary syndrome (NSTE‐ACS) and stable angina. Provisional T‐stenting was the obligatory strategy of the treatment. Angiographic control was planned at 12 months. The primary endpoint was cumulative rate of death, myocardial infarction (MI) and target lesion revascularization (TLR) at 12 months.

Results

A total of 60 patients with coronary bifurcations were enrolled (mean age 66.4 ± 11 years, 28.3% of female). There were 21.7% of patients with NSTE‐ACS, 78.3% with hypertension, 38.3% with diabetes, 28.3% had previous MI, and 46.7% and 10% underwent prior revascularization, respectively, PCI and coronary artery bypass graft. The device success rate was 100%. Side branch was treated with an additional classical drug‐eluting stent implantation in 23.3% of cases. At 12 months, the cumulative major adverse cardiovascular events rate was 11.7%. During follow‐up (11 ± 1 months) there was 1 non‐cardiac death (1.7%), 1 non‐ST‐elevated myocardial infarction (1.7%) due to restenosis and no case of stroke or in‐stent thrombosis. Overall TLR was 8.3% (clinically driven TLR – 1.7%, angiographically driven – 6.6%). Mean late lumen loss was as follows: In main vessel – 0.35 ± 0.33 mm, in main branch – 0.34 ± 0.27 mm and in side branch – 0.18 ± 0.38 mm.

Conclusion

Dedicated bifurcation stent BiOSS® LIM proved to be feasible device, with promising safety and long‐term clinical effectiveness in the treatment of coronary bifurcation lesions, including distal left main stem stenosis. (J Interven Cardiol 2015;28:51–60)

     

Infarct Size Reduction and Attenuation of Global Left Ventricular Remodeling with the CorCap<Superscript>TM</Superscript> Cardiac Support Device Following Acute Myocardial Infarction in Sheep

Background:Whether mechanical restraint of the left ventricle (LV) can influence remodeling following myocardial infarction (MI) remains poorly understood. The following discussion details three studies examining the effects of surgically placing a cardiac support device (CSD) over the entire epicardial surface, on infarct expansion, global cardiac function and myocyte geometry and function post-MI. Methods: The effects of passive constraint on infarct expansion and global cardiac function/myocardial energetics were investigated in 10 sheep (5 MI only; 5 MI + CSD) using pressure-volume analysis and magnetic resonance imaging (MRI). Additionally, 11 sheep (5 MI only; 6 MI + CSD) were used to study the effects of passive restraint on myocyte geometry and function post-MI, with 10 additional uninstrumented sheep serving as controls. Baseline data was collected followed by the creation of an anterior infarct. 1 week post-infarct the animals underwent a second set of data collection studies followed by placement of the CSD in the experimental groups. Additional data was collected at 2 and 3 months post-MI. The animals in the myocyte function group underwent additional studies immediately following the 3 month time point. Results: Infarct expansion was diminished as a result of the CSD. At 1 week post-MI the akinetic area was similar in both groups. At the terminal time-point, the akinetic area in the control group was similar to the 1-week time-point whereas, in the CSD group, the area of akinesis decreased (P = 0.001). A comparison of the two groups at the terminal time-point demonstrates a significantly diminished area of akinesis in the CSD group (P = 0.004). The relative area of akinesis followed a similar pattern. The CSD group also exhibited a decrease in end-diastolic volume (control 110.3 ± 19.8 mL vs. CSD 67.6 ± 4.7 mL, P = .006) and an improved ejection fraction (control 15.5% ± 5.7% vs. CSD 29.46% ± 4.42%, P = .008) relative to the control group. Myocardial energetics were also enhanced in the CSD group as evidenced by significant improvements in potential energy (control 2015 ± 503 mL ⋅ mm Hg/beat vs. CSD 885 ± 220 mL ⋅ Hg/beat, P = .006), efficiency (control 39.4% ± 13.6% vs. CSD 59.8% ± 8.5%, P = .044), and oxygen consumption (control 0.072 ± 0.013 mL O₂/beat vs. CSD 0.052 ± 0.007 mL O₂/beat, P = .034). Isolated LV myocyte shortening velocity was reduced by 35% from control values (P < 0.05) in both MI groups. LV myocyte β-adrenergic response was reduced with MI, but normalized in the MI + CSD group. Relative collagen content was increased and matrix metalloproteinase-9 was decreased within the MI border region of the CSD group. Conclusions:The CorCap cardiac support device retarded infarct expansion, improved global and regional cardiac function and beneficially modified LV and myocyte remodeling post-MI. These findings provide evidence that non-pharmacological strategies can interrupt adverse LV remodeling post-MI.     

Myocardial Inflammation Predicts Remodeling and Neuroinflammation After Myocardial Infarction

Background

The local inflammatory tissue response after acute myocardial infarction (MI) determines subsequent healing. Systemic interaction may induce neuroinflammation as a precursor to neurodegeneration.

Hypercholesterolemia exacerbates ventricular remodeling in the rat model of myocardial infarction

BackgroundDetrimental left ventricular (LV) remodeling is exacerbated in hypercholesterolemic patients with myocardial infarction; however, this could result from either larger infarcts or more extensive remodeling itself in this population. Therefore, we sought to investigate whether high cholesterol feeding exacerbates LV remodeling and heart failure in rats with myocardial infarction independently from its influence on infarct size.Methods and ResultsMyocardial infarction was induced by permanent ligation of left coronary artery in rats fed normal and high-cholesterol diet and the animals were followed for 8 weeks. Hypercholesterolemic rats were matched with normocholesterolemic animals for infarct size 24 hours after infarction and exhibited more pronounced LV dilation at 8 weeks after infarction (LV systolic/diastolic diameter 8.1 ± 0.2/10.2 ± 0.3 versus 6.7 ± 0.2/8.9 ± 0.2, respectively, measured by echocardiography, P < .05 each). Pressure-volume curves obtained in isolated Langendorff-perfused hearts revealed higher diastolic LV volumes (1677 ± 102 versus 1385 ± 46 μL/kg body weight, P < .05) and hemodynamic examination demonstrated higher LV end-diastolic pressure (21.8 ± 0.7 versus 18.7 ± 1.0 mm Hg, P < .05) in hypercholesterolemic rats compared with normocholesterolemic animals.ConclusionIn a rat model of myocardial infarction, LV remodeling and heart failure are more pronounced in rats fed high-cholesterol diet in comparison to animals fed normal chow. This effect is independent from effect of hypercholesterolemia on infarct size.     

Effects of long-term renal sympathetic denervation on heart failure after myocardial infarction in rats

The purpose of the present study was to investigate the effects of long-term renal denervation (RD) on heart failure due to myocardial infarction (MI). Wistar rats were anesthetized and the bilateral renal nerves were surgically denervated 2 days before MI was induced by coronary artery ligation. Four weeks later, left ventricular (LV) function and sodium excretion were determined. In MI rats, RD improved the reduced sodium excretion. MI + RD rats revealed lower LV end-diastolic pressure and greater maximum dP/dt as compared with those of MI+ innervation (INN) rats. LV end-diastolic and end-systolic dimensions were significantly smaller and LV fractional shortening was greater in MI + RD rats than in MI + INN rats (20.9% ± 3.2% vs 14.9% ± 3.0%). In rats without MI, RD did not affect either sodium excretion or LV function and dimensions. The present results suggest that the long-term RD reduces LV filling pressure and improves LV function after MI, probably due to a restoration of impaired natriuresis. Increased renal sympathetic nerve activity might contribute to the progression of heart failure after MI. Received: June 11, 2001 / Accepted: September 22, 2001     

No Cardioprotective Benefit of Ischemic Postconditioning in Patients With ST‐Segment Elevation Myocardial Infarction

Background

Postconditioning is a potential cardioprotective strategy that has demonstrated conflicting and variable reductions in infarct size in human trials.

Objectives

To determine whether postconditioning could increase the extent of myocardial salvage in patients with acute ST‐segment elevation myocardial infarction undergoing primary percutaneous coronary intervention (PPCI).

Methods

One hundred two patients (aged 57 ± 11 years; 88% male) were randomly assigned to a postconditioning or standard protocol. Cardiovascular magnetic resonance imaging was performed 3 days after PPCI to measure the volumetric extent of myocardial necrosis and the area at risk.

Results

With similar time‐to‐reperfusion (170 ± 84 minutes in the postconditioning group vs. 150 ± 70 minutes in the standard group, P = 0.22), the myocardial salvage index was not significantly different between the postconditioned group and the control group, averaging 42 ± 22% vs. 33 ± 21%, respectively (P = 0.08). Furthermore, postconditioning was not associated with a smaller infarct size compared to controls (13 ± 7 g/m² vs. 15 ± 8 g/m², respectively, P = 0.18).

Conclusions

Postconditioning does not significantly increase myocardial salvage or reduce infarct size in patients with STEMI undergoing PPCI. However, the possibility of a more modest impact of postconditioning cannot be excluded with our sample size. (J Interven Cardiol 2013;26:482‐490)

     

Cardiac Thyrotropin-releasing Hormone Inhibition Improves Ventricular Function and Reduces Hypertrophy and Fibrosis After Myocardial Infarction in Rats

BackgroundCardiac thyrotropin-releasing hormone (TRH) is a tripeptide with still unknown functions. We demonstrated that the left ventricle (LV) TRH system is hyperactivated in spontaneously hypertensive rats and its inhibition prevented cardiac hypertrophy and fibrosis. Therefore, we evaluated whether in vivo cardiac TRH inhibition could improve myocardial function and attenuate ventricular remodeling in a rat model of myocardial infarction (MI).Methods and ResultsIn Wistar rats, MI was induced by a permanent left anterior descending coronary artery ligation. A coronary injection of a specific small interfering RNA against TRH was applied simultaneously. The control group received a scrambled small interfering RNA. Cardiac remodeling variables were evaluated one week later. In MI rats, TRH inhibition decreased LV end-diastolic (1.049 ± 0.102 mL vs 1.339 ± 0.102 mL, P < .05), and end-systolic volumes (0.282 ± 0.043 mL vs 0.515 ± 0.037 mL, P < .001), and increased LV ejection fraction (71.89 ± 2.80% vs 65.69 ± 2.85%, P < .05). Although both MI groups presented similar infarct size, small interfering RNA against TRH treatment attenuated the cardiac hypertrophy index and myocardial interstitial collagen deposition in the peri-infarct myocardium. These effects were accompanied by attenuation in the rise of transforming growth factor-β, collagen I, and collagen III, as well as the fetal genes (atrial natriuretic peptide, B-type natriuretic peptide, and beta myosin heavy chain) expression in the peri-infarct region. In addition, the expression of Hif1α and vascular endothelial growth factor significantly increased compared with all groups.ConclusionsCardiac TRH inhibition improves LV systolic function and attenuates ventricular remodeling after MI. These novel findings support the idea that TRH inhibition may serve as a new therapeutic strategy against the progression of heart failure.     

Reduction of "no-reflow" phenomenon by intra-aortic balloon counterpulsation in a randomized magnetic resonance imaging experimental study

OBJECTIVES: Intra-aortic balloon counterpulsation (IABC) can improve post-myocardial infarction (MI) outcomes, but the mechanisms of such effect remain unclear. We hypothesized that IABC augmentation reduces the extent of microvascular obstruction after acute infarction. BACKGROUND: Microvascular obstruction or "no-reflow" (MO) has been shown to negatively influence left ventricular (LV) remodeling after myocardial infarction (MI). METHODS: Seventeen dogs underwent 90 min of coronary artery occlusion followed by reperfusion. Animals were then randomized to either IABC (n = 9) or control (n = 8); IABC augmentation was performed for 24 h after MI. Microvascular obstruction and infarct size by first-pass and delayed contrast-enhanced magnetic resonance imaging (MRI) were measured at 1 and 24 h after reperfusion and compared with postmortem infarct size and MO by microspheres. RESULTS: Microvascular obstruction by MRI, expressed as percent LV mass, decreased significantly in IABC (4.9 +/- 2.2% to 3.6 +/- 1.5%) and increased in controls (3.4 +/- 0.5% to 4.9 +/- 1.1% from 1 to 24 h, respectively; p < 0.001). Similar results were found for MO defined by microspheres. In the control group, MO increased significantly, during 24 h of study (from 8.8 +/- 1.7% to 43.2 +/- 11.1% of infarcted myocardium; p < 0.05), whereas not important change was observed in the IABC group (from 21.3 +/- 7.1% to 25.8 +/- 14.7%; p < 0.05 vs. control at 24 h). Infarct size, measured by MRI, increased in both groups (13.2 +/- 1.8 to 15.5 +/- 2.1 from 1 to 24 h, respectively; p < 0.05). CONCLUSIONS: Intra-aortic balloon counterpulsation augmentation performed after reperfusion improves myocardial perfusion at the tissue level, and reduces the extent of no-reflow caused by microvascular obstruction.     

The impact of right ventricular function assessed by 2‐dimensional speckle tracking echocardiography on early mortality in patients with inferior myocardial infarction

Background

Right ventricular (RV) involvement in inferior myocardial infarction (MI) increases in‐hospital morbidity and mortality.

Hypothesis

RV systolic dysfunction assessed by 2‐dimensional speckle tracking echocardiography (STE) might be a predictor of early mortality in patients with acute inferior MI.

Methods

Eighty‐one consecutive patients with acute inferior MI (mean age, 60.8 ± 12.7 years; 18 females) were included. RV myocardial involvement was defined as an elevation >1 mm in V₁ or V₄R within 12 hours of symptom onset. RV function was assessed by STE. Patients were followed for 30 days for all‐cause mortality.

Results

Thirty‐eight patients had RV myocardial involvement, and they had significantly lower tricuspid annular plane systolic excursion (TAPSE), tricuspid annular systolic velocity (RVS), and left ventricular (LV) and RV global longitudinal strain (GLS). Nine patients (11%) died within 30 days. The mean age of mortality group was higher with more female frequency. They had significantly higher pro‐BNP, hs‐troponin T, and creatinine levels, but lower hemoglobin levels. TIMI 3 flow was significantly less achieved in mortality group. RV myocardial involvement was more frequent in the mortality group, and they had significantly lower TAPSE, RVS, and LV and RV GLS. Multivariate analysis revealed that age and RV GLS were independent predictors of early mortality. RV GLS ≤ –14% predicted early mortality in patients with acute inferior MI with a sensitivity of 88.9% and a specificity of 62.5% (AUC: 0.817, P = 0.002).

Conclusions

RV GLS may be useful in predicting early mortality in patients with acute inferior MI.     

Longitudinal study of cardiac remodelling in rabbits following infarction

Background

Cardiac remodelling following myocardial infarction (MI) is a complex, dynamic process. There have been few longitudinal studies of these changes.

Methods

A 2-dimensional transthoracic echocardiography was performed on 20 rabbits, before and 1, 2, 4, 8, and 12 weeks after MI (n = 14) and twice for controls (n = 6). Chronic left ventricular (LV) infarct size was histologically characterized and correlated with mechanical function. A linear mixed model was used to analyze longitudinal and infarct size-related changes in LV end-systolic volume (ESV), end-diastolic volume (EDV), ejection fraction (EF), sphericity, circumferential strain, and wall motion score index.

Results

Mean LV infarct size was 28.9% ± 9.3%. After MI, rapid remodelling occurred in LVESV, LVEF, and sphericity for 2 weeks and LVEDV for 4 weeks, with slower changes afterwards. LV infarct size correlated with LVESV (r = 0.76), LVEDV (r = 0.71), and LVEF (r = 0.69). Larger infarcts resulted in greater LVESV dilation (P = 0.04) and faster LVEDV (P < 0.01), LVEF (P < 0.01), and sphericity (P < 0.01) remodelling. Apical global circumferential strain and wall motion score index increased for 1 week, then stabilized, regardless of infarct size, and apical global circumferential strain was correlated with apical infarction (r = 0.58). Additionally, regional circumferential strain decreased in segments with severe (> 80%) infarction more quickly (P < 0.01) and by a greater degree (P = 0.04) compared with segments with minor (< 20%) infarction.

Conclusions

The most dynamic remodelling of cardiac function in this model occurred during the first 4 weeks, stabilizing thereafter, with changes maintained up to 12 weeks. Infarct size affected both the early rate and long-term extent of mechanical remodelling.     

Outcome of Early Revascularization Surgery in Patients with ST‐Elevation Myocardial Infarction

Objectives

To compare morbidity and mortality of patients with ST‐elevation myocardial infarction (MI) undergoing coronary artery bypass graft (CABG) surgery within 24 hours with those who had surgery delayed >24 hours.

Background

Patients with ST‐elevation MI are currently managed by emergency percutaneous coronary intervention (PCI). If PCI is unsuccessful, or if there is severe coronary artery disease not amenable to PCI, CABG is considered. If the patient is clinically stable, surgeons wait several days before performing surgery, as very early surgery carries a prohibitive risk.

Methods

One hundred and eighty‐four patients with acute ST elevation MI (STEMI) who had undergone CABG were divided into two groups based on their surgery timing (<24 hours vs. >24 hours). Mortality and complication rates were studied between the two groups by Fischer test. Time‐to‐event analyses were performed for five primary variables: all‐cause mortality, cardiac events, congestive heart failure, stroke, and renal failure.

Results

At one month post‐CABC, all‐cause mortality was noted in 10.6% of patients who had CABG within 24 hours of STEMI diagnosis, compared with 8.9% in patients who had CABG after 24 hours (P = 0.3). Cardiac events including re‐exploration, atrial fibrillation, graft occlusion, and arrhythmias requiring shock occurred in 17.1% versus 13.9% between the two groups, respectively (P = 0.68). One year post‐coronary artery bypass surgery, there was no difference in individual or combined events between the two groups.

Conclusions

In patients with ST‐elevation myocardial infarction who required emergency coronary artery bypass surgery, there was no difference in procedure complications or mortality between early (within 24 hours) or later (more than 24 hours). That was noted at one month and one year after the index myocardial infarction. (J Interven Cardiol 2015;28:14–23)