Fragmented QRS complexes after acute myocardial infarction are independently associated with unfavorable left ventricular remodeling

Background

Recovery of left ventricular ejection fraction (LVEF) after acute myocardial infarction (MI) is not universal and is difficult to predict. Fragmented QRS (fQRS) complexes are thought to be markers of myocardial scar. We hypothesized that fQRS complexes on 12?lead surface ECGs during the initial post-MI period would be associated with adverse LV remodeling over the following year.

Effect of vericiguat on left ventricular structure and function in patients with heart failure with reduced ejection fraction: The VICTORIA echocardiographic substudy

Aim

Vericiguat significantly reduced the primary composite outcome of heart failure (HF) hospitalization or cardiovascular death in the VICTORIA trial. It is unknown if these outcome benefits are related to reverse left ventricular (LV) remodelling with vericiguat in patients with HF with reduced ejection fraction (HFrEF). The aim of this study was to compare the effects of vericiguat versus placebo on LV structure and function after 8 months of therapy in patients with HFrEF.

Methods and results

Standardized transthoracic echocardiography (TTE) was performed at baseline and after 8 months of therapy in a subset of HFrEF patients in VICTORIA. The co-primary endpoints were changes in LV end-systolic volume index (LVESVI) and LV ejection fraction (LVEF). Quality assurance and central reading were performed by an echocardiographic core laboratory blinded to treatment assignment. A total of 419 patients (208 vericiguat, 211 placebo) with high-quality paired TTE at baseline and 8 months were included. Baseline clinical characteristics were well balanced between treatment groups and echocardiographic characteristics were representative of patients with HFrEF. LVESVI significantly declined (60.7 ± 26.8 to 56.8 ± 30.4 ml/m²; p < 0.01) and LVEF significantly increased (33.0 ± 9.4% to 36.1 ± 10.2%; p < 0.01) in the vericiguat group, but similarly in the placebo group (absolute changes for vericiguat vs. placebo: LVESVI −3.8 ± 15.4 vs. −7.1 ± 20.5 ml/m²; p = 0.07 and LVEF +3.2 ± 8.0% vs. +2.4 ± 7.6%; p = 0.31). The absolute rate per 100 patient-years of the primary composite endpoint at 8 months tended to be lower in the vericiguat group (19.8) than the placebo group (29.6) (p = 0.07).

Conclusions

In this pre-specified echocardiographic study, significant improvements in LV structure and function occurred over 8 months in both vericiguat and placebo in a high-risk HFrEF population with recent worsening HF. Further studies are warranted to define the mechanisms of vericiguat's benefit in HFrEF.     

Influence of Myocardial Hemorrhage on Staging of Reperfused Myocardial Infarctions With T2 Cardiac Magnetic Resonance Imaging: Insights Into the Dependence on Infarction Type With Ex Vivo Validation

Objectives

This study sought to determine whether T₂ cardiac magnetic resonance (CMR) can stage both hemorrhagic and nonhemorrhagic myocardial infarctions (MIs).

The impact of age on ablation outcomes in AF-mediated cardiomyopathy

Introduction

The absence of ventricular scar in patients with atrial fibrillation (AF) and systolic heart failure (HF) predicts left ventricular (LV) recovery following AF ablation. It is unknown whether age impacts the degree of LV recovery, reverse remodeling, or AF recurrence following catheter ablation (CA) among this population.

Objectives

To evaluate the impact of age on LV recovery and AF recurrence in a population with AF and systolic HF without fibrosis (termed AF-mediated cardiomyopathy) following CA.

Methods

Consecutive patients undergoing CA between 2013 and 2021 with LV ejection fraction (LVEF) < 45% and absence of cardiac magnetic resonance imaging (CMR) detected LV myocardial fibrosis were stratified by age (<65 vs. ≥65 years). Following CA, participants underwent remote rhythm monitoring for 12 months with repeat CMR for HF surveillance.

Results

The study population consisted of 70 patients (10% female, mean LVEF 33 ± 9%), stratified into younger (age < 65 years, 63%) and older (age ≥ 65 years, 37%) cohorts. Baseline comorbidities, LVEF (34 ± 9 vs. 33 ± 8 ≥65 years, p = .686), atrial and ventricular dimensions (left atrial volume index: 55 ± 21 vs. 56 ± 14 mL/m² age ≥ 65, p = .834; indexed left ventricular end-diastolic volume: 108 ± 40 vs. 104 ± 28 mL/m² age ≥ 65, p = .681), pharmacotherapy and ablation strategy (pulmonary vein isolation in all; posterior wall isolation in 27% vs. 19% age ≥ 65, p = .448; cavotricuspid isthmus in 9% vs. 11.5% age ≥ 65) were comparable (all p > .05) albeit a higher CHADS₂VASc score in the older cohort (2.7 ± 0.9 vs. 1.6 ± 0.6 age < 65, p < .001).   Freedom from AF was comparable (hazard ratio: 0.65, 95% confidence interval: 0.38–1.48, LogRank p = .283) as was AF burden [0% (interquartile range, IQR: 0.0–2.1) vs. age ≥ 65: [0% (IQR 0.0–1.7), p = .516], irrespective of age. There was a significant improvement in LV systolic function in both groups (ΔLVEF + 21 ± 14% vs. +21 ± 12% age ≥ 65, p = .913), with LV recovery in the vast majority (73% vs. 69%, respectively, p = .759) at 13 (IQR: 12–16) months. This was accompanied by comparable improvements in functional status (New York Heart Association class p = .851; 6-min walk distance 50 ± 61 vs. 93 ± 134 m in age ≥ 65, p = .066), biomarkers (ΔN-terminal-pro brain natriuretic peptide −139 ± 246 vs. −168 ± 181 age ≥ 65,p = .629) and HF symptoms (Short Form-36 survey Δphysical component summary p = .483/Δmental component summary, p = .841).

Conclusion

In patients undergoing CA for AF with systolic HF in the absence of ventricular scar, comparable improvements in ventricular function, symptoms, and freedom from AF are achieved irrespective of age.     

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.     

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.     

Vasopeptidase Inhibition Peri- and Post-MI in Zucker Insulin Resistant Rats: Effect on MI Size,Arrhythmias, Remodeling,Function and Fetal Gene Expression

Summary Mortality peri-myocardial infarction (MI) is increased with insulin resistance. As the vasopeptidase inhibitor (VPI) omapatrilat improves insulin sensitivity, it may be beneficial peri-MI in Zucker Insulin Resistant rats (ZIR). ZIR rats (n = 228) received omapatrilat 10 mg/kg/day, 7 days pre-MI, to 38 days post-MI, or control. Twenty-four protocol (n = 72): a subgroup of rats received the kinin receptor antagonist icatibant. Ambulatory ECG recordings, and MI size were evaluated. Thirty-eight-day protocol (n = 156): left ventricular (LV) remodeling, cardiac hemodynamics, morphology, infarct size, and RT-PCR for GLUT-4 and fetal genes were measured. Omapatrilat improved post-MI survival 24 h (62% vs 38%, P = 0.0007) which was maintained 38 days. There was a kinin-induced reduction of ventricular arrhythmias and there appeared to be a kinin-independent reduction in MI size (23.5 ± 2.4% vs 17.0 ± 2.2%, P = 0.053) for 24-h post-MI. Omapatrilat reduced but did not prevent LV dilatation, dysfunction, and fetal gene expression 38 days post-MI. Omapatrilat did not prevent reduced cardiac GLUT-4 expression. In ZIR rats, mortality post-MI is reduced by omapatrilat, due and a kinin-dependent reduction in ventricular arrhythmias and possibly a kinin-independent reduction in MI size. Ventricular dilatation, dysfunction, and fetal gene expression are variably attenuated but not prevented.     

ACE-Inhibition plus Mineralocorticoid Antagonism versus ACE-inhibition alone in Patients with Anterior Myocardial Infarction

Background. Aldosterone exerts pro-fibrotic effects, acting via mineralo-corticoid reeptors in cardiovascular tissues. Aldosterone antagonism in combination with ACE inhibition may better protect against untoward effects of aldosterone than ACE inhibition alone. Methods. In a double blind, randomised study the tolerability and efficacy of canreonate (25 mg/day) plus captopril versus captopril alone were evaluated in 187 patients with an acute anterior myocardial infarction (MI) and a serum creatinine concentration <2.0 mg/dL and a serum K concentration <5.0 mmol/L. Ninety-four patients received captopril and 25 mg canreonate (group A). Group B (93 patients) received captopril and placebo. At baseline and at 10 and 90 days after admission Doppler echocardiography was performed. Results. Clinical and demographic aspects were similar in both groups. Also, baseline cardiac enzyme levels, left ventricular (LV) function and incidence of surgical interventions and angioplasty were comparable. Overall, creatinine, blood urea and serum K did not show significant differences between groups. However, in 9 patients in group A increases in serum K > 5.5 mmol/dL and creatinine >2.0 mg/L were observed after 10 days of treatment. At 90 days, the mitral E/A ratio was higher (p = 0.001) and LV end systolic volume smaller (p = 0.021) in patients treated with canreonate than in those receiving placebo. No further side effects were observed during the study period. Conclusions. Our data suggest that the combination of captopril plus canreonate is well tolerated following an acute myocardial infarction and has a beneficial effect on diastolic and systolic LV parameters and may decrease post-MI remodelling.     

Transcoronary Infusion of Bone Marrow Derived Multipotent Stem Cells to Preserve Left Ventricular Geometry and Function After Myocardial Infarction

Background

Myocardial damage after myocardial infarction (MI) was deemed irreversible after late reperfusion. Administration of multipotent stem cell (MSC) into such infarct may regenerate the myocardium and capillary network.

Hypothesis

Transcoronary infusion of bone marrow derived multipotent stem cells into infarcted related artery after acute myocardial infarction is feasible, safe and improve left ventricular function.

Methods

We conducted a pilot study in patients who survived ST‐elevation MI with late reperfusion therapy and remained hemodynamically stable. Bone marrow derived MSC was infused into a patent infarct‐related coronary artery during brief low pressure (2 atm) balloon inflation. A 3‐T gadolinium‐based MRI was performed at baseline and 8 weeks later to evaluate infarct area and LV function.

Results

We enrolled 10 patients, age 63.8 ± 2.8 years 5.2 ± 4.12 × 10⁶ MSC were infused via coronary artery 24.8 ± 16 days after infarction. The procedures were successful in all patients without any in‐hospital event. Infarct size by MRI decreased by 5.84% (P = .018) over 8 weeks. Mean baseline left ventricular ejection fraction (LVEF) was 44.1% ± 9% and was 46.3% ± 9% at 8 weeks (P = .34). A trend of smaller LV end‐systolic volume with 65.02 ± 18.2 ml vs 63.04 ± 21.89 ml (P = .09) with no change of LV end‐diastolic volume observed.

Conclusion

MSC infusion into coronary circulation was feasible and safe after myocardial infarction. Infarct size was reduced with preservation of LV geometry. Copyright © 2010 Wiley Periodicals, Inc.     

Myocardial Partition Coefficient of Gadolinium: A Pilot Study in Patients With Acute Myocarditis,Chronic Myocardial Infarction,and in Healthy Volunteers

Background

The tissue-blood partition coefficient (PC) of gadolinium, derived from T1 measurements, reflects myocardial connective tissue fraction and tissue injury, increasing in proportion with edema or fibrosis. We determined the myocardial PC of gadolinium in patients with acute myocarditis, chronic myocardial infarction (MI), and healthy volunteers. We hypothesized that the characteristics of the injured myocardium in patients with MI and myocarditis may differ and that the PC will be higher in chronically injured myocardium (MI) compared with acutely injured myocardium (myocarditis).

Continuous multi-day tracking of post-myocardial infarction recovery of cardiac electrical stability and autonomic tone using electrocardiogram patch monitors

Background

Sudden cardiac death (SCD) risk is elevated following acute myocardial infarction (MI). The time course of SCD susceptibility post-MI requires further investigation.

Methods

In this observational cohort study, we employed state-of-the-art noninvasive ECG techniques to track the daily time course of cardiac electrical instability and autonomic function following ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI). Preventice BodyGuardian MINI-EL Holters continuously recorded ECGs for 7 days at hospital discharge and at 40 days for STEMI (N = 5) or at 90 days for NSTEMI patients (N = 5). Cardiac electrical instability was assessed by T-wave alternans (TWA) and T-wave heterogeneity (TWH); autonomic tone was determined by rMSSD-heart rate variability (HRV).

Results

TWA was severely elevated (≥60 μV) in STEMI patients (80 ± 10.3 μV) at discharge and throughout the first recording period but declined by 50% to 40 ± 2.3 μV (p = .03) by Day 40 and remained in the normal range (<47 μV). TWH, a related phenomenon analyzed from 12-lead ECGs, was reduced by 63% in the five STEMI patients from discharge to normal (<80 μV) at follow-up (105 ± 27.3 to 39 ± 3.3 μV, p < .04) but increased by 65% in a STEMI case (89 to 147 μV), who received a wearable defibrillator vest and later implantable cardioverter defibrillator. In NSTEMI patients, TWA was borderline abnormal (47 ± 3.3 μV) at discharge and declined by 19% to normal (38 ± 1.2 μV) by Day 90 (p = .05). An overall reciprocal increase in rMSSD-HRV suggested recovery of vagal tone.

Conclusions

This study provides proof-of-principle for tracking post-MI SCD risk in individual patients with implications for personalized therapy.     

Cardiovascular magnetic resonance assessment of 1st generation CoreValve and 2nd generation Lotus valves

Objectives

We sought to compare using serial CMR, the quantity of AR and associated valve hemodynamics, following the first‐generation CoreValve (Medtronic, Minneapolis, MN) and the second‐generation Lotus valve (Boston Scientific, Natick, MA).

Background

Aortic regurgitation (AR) following Transcatheter Aortic Valve Replacement (TAVR) confers a worse prognosis and can be accurately quantified using cardiovascular magnetic resonance (CMR). Second generation valves have been specifically designed to reduce paravalvular AR and improve clinical outcomes.

Methods

Fifty‐one patients (79.0 ± 7.7 years, 57% male) were recruited and imaged at three time points: immediately pre‐ and post‐TAVR, and at 6 months.

Results

CMR‐derived AR fraction immediately post‐TAVR was greater in the CoreValve compared to Lotus group (11.7 ± 8.4 vs. 4.3 ± 3.4%, P = 0.001), as was the frequency of ≥moderate AR (9/24 (37.5%) versus 0/27, P < 0.001). However, at 6 months AR fraction had improved significantly in the CoreValve group such that the two valve designs were comparable (6.4 ± 5.0 vs 5.6 ± 5.3%, P = 0.623), with no patient in either group having ≥moderate AR. The residual peak pressure gradient immediately following TAVR was significantly lower with CoreValve compared to Lotus (14.1 ± 5.6 vs 25.4 ± 11.6 mmHg, P = 0.001), but again by 6 months the two valve designs were comparable (16.5 ± 9.4 vs 19.7 ± 10.5 mmHg, P = 0.332). There was no difference in the degree of LV reverse remodeling between the two valves at 6 months.

Conclusion

Immediately post‐TAVR, there was significantly less AR but a higher residual peak pressure gradient with the Lotus valve compared to CoreValve. However, at 6 months both devices had comparable valve hemodynamics and LV reverse remodeling.

     

Risk assessment of post-myocardial infarction patients with preserved ejection fraction using 45-min short resting Holter electrocardiographic recordings

Background

Risk stratification for sudden cardiac death in post-myocardial infarction (post-MI) patients remains a challenging task. Several electrocardiographic noninvasive risk factors (NIRFs) have been associated with adverse outcomes and were used to refine risk assessment. This study aimed to evaluate the performance of NIRFs extracted from 45-min short resting Holter ECG recordings (SHR), in predicting ventricular tachycardia inducibility with programmed ventricular stimulation (PVS) in post-MI patients with preserved left ventricular ejection fraction (LVEF).

Methods

We studied 99 post-MI ischemia-free patients (mean age: 60.5 ± 9.5 years, 86.9% men) with LVEF ≥40%, at least 40 days after revascularization. All the patients underwent PVS and a high-resolution SHR. The following parameters were evaluated: mean heart rate, ventricular arrhythmias (premature ventricular complexes, couplets, tachycardias), QTc duration, heart rate variability (HRV), deceleration capacity, heart rate turbulence, late potentials, and T-wave alternans.

Results

PVS was positive in 24 patients (24.2%). HRV, assessed by the standard deviation of normal-to-normal R–R intervals (SDNN), was significantly decreased in the positive PVS group (42 ms vs. 51 ms, p = .039). SDNN values <50 ms were also associated with PVS inducibility (OR 3.081, p = .032 in univariate analysis, and 4.588, p = .013 in multivariate analysis). No significant differences were identified for the other NIRFs. The presence of diabetes, history of ST-elevation MI (STEMI) and LVEF <50% were also important predictors of positive PVS.

Conclusions

HRV assessed from SHR, combined with other noninvasive clinical and echocardiographic variables (diabetes, STEMI history, LVEF), can provide an initial, practical, and rapid screening tool for arrhythmic risk assessment in post-MI patients with preserved LVEF.     

Fatty liver disease,heart rate and cardiac remodelling: Evidence from the UK Biobank

Background and Aims

Growing evidence supports an association between fatty liver disease (FLD) and cardiac dysfunction and remodelling, leading to cardiovascular disease and heart failure. Herein, we investigated the independent contribution of FLD to cardiac dysfunction and remodelling in participants from the UK Biobank with cardiac magnetic resonance (CMR) data available.

Methods

A total of 18 848 Europeans without chronic viral hepatitis and valvular heart diseases, with liver magnetic resonance imaging and CMR data were included in the analyses. Clinical, laboratory and imaging data were collected using standardized procedures. Multivariable regression models were used to test the association between FLD and CMR endpoints, after adjusting for several cardiometabolic risk factors. Linear regression models with regularization (Least Absolute Shrinkage and Selection Operator [LASSO], Ridge and Elastic Net) were used to generate predictive models for heart-related endpoints.

Results

FLD was independently associated with higher average heart rate, higher cardiac remodelling (higher eccentricity ratio and lower remodelling index), lower left and right ventricular volumes (end-systolic, end-diastolic and stroke volumes) as well as with lower left and right atrial maximal volumes (p < 0.001). FLD was the strongest positive predictor for average heart rate, followed by age, hypertension and type 2 diabetes. Male sex was the strongest positive predictor for eccentricity ratio followed by FLD, age, hypertension and BMI. For LV volumes, FLD was the strongest negative predictor along with age.

Conclusions

FLD is an independent predictor of higher heart rate and early cardiac remodelling associated with reduced ventricular volumes.     

Cytokine Combination Therapy with Erythropoietin and Granulocyte Colony Stimulating Factor in a Porcine Model of Acute Myocardial Infarction

Purpose

Erythropoietin (EPO) and granulocyte colony stimulating factor (GCSF) have generated interest as novel therapies after myocardial infarction (MI), but the effect of combination therapy has not been studied in the large animal model. We investigated the impact of prolonged combination therapy with EPO and GCSF on cardiac function, infarct size, and vascular density after MI in a porcine model.

Methods

MI was induced in pigs by a 90 min balloon occlusion of the left anterior descending coronary artery. 16 animals were treated with EPO+GCSF, or saline (control group). Cardiac function was assessed by echocardiography and pressure-volume measurements at baseline, 1 and 6 weeks post-MI. Histopathology was performed 6 weeks post-MI.

Results

At week 6, EPO+GCSF therapy stabilized left ventricular ejection fraction, (41?±?1% vs. 33?±?1%, p?<?0.01) and improved diastolic function compared to the control group. Histopathology revealed increased areas of viable myocardium and vascular density in the EPO+GCSF therapy, compared to the control. Despite these encouraging results, in a historical analysis comparing combination therapy with monotherapy with EPO or GCSF, there were no significant additive benefits in the LVEF and volumes overtime using the combination therapy.

Conclusion

Our findings indicate that EPO+GCSF combination therapy promotes stabilization of cardiac function after acute MI. However, combination therapy does not seem to be superior to monotherapy with either EPO or GCSF.     

Cardioprotection by Recombinant Human Erythropoietin Following Acute Experimental Myocardial Infarction: Dose Response and Therapeutic Window

Summary Background: Recombinant human erythropoietin (rhEPO) protects tissue from ischemic damage, but translation of this finding into useful guidelines with respect to human trials for myocardial infarction (MI) requires a determination of the minimum effective rhEPO dose and the therapeutic window following MI. Method and Results: Serial echocardiography revealed that during four weeks following MI, induced by a permanent coronary ligation in rats, the LV end-diastolic and end-systolic volumes in untreated rats expanded from 0.35 ± 0.01 and 0.14 ± 0.01 ml to 0.84 ± 0.04 and 0.61 ± 0.06 ml, respectively, and ejection fraction (EF) reduced by 50%. A single i.v. injection of rhEPO immediately following MI in a dose of 150 IU/kg was as effective as 3000 IU/kg in causing a 2-fold reduction of the number of apoptotic nuclei in the AAR 24-h later, a 2-fold reduction of the MI size measured 4 weeks later, attenuation of progressive LV dilatation and fall in EF. A 3000 IU/kg dose had similar therapeutic effects when delayed by 4, 8, or 12 h following MI, but was not effective after a 24-h delay. A single dose of 150 IU/kg was effective within 4 h post-MI, but was without effect if administered after an 8-h delay. Conclusion: Cell death, final MI size, myocardial remodeling and functional decline are significantly reduced in rats by a single injection of rhEPO in a dose as low as 150 IU/kg if administered during the first 4 h after the ischemic event. Higher doses extend the therapeutic window up to 12 h.     

Plasma MMP-2, MMP-9 and N-BNP in long-term survivors following complicated myocardial infarction: relation to cardiac magnetic resonance imaging measures of left ventricular structure and function

BackgroundAltered activity of the matrix metalloproteinases (MMP-2 and -9), has been implicated in the left ventricular (LV) remodeling process occurring after myocardial infarction (MI). In the acute phase, a relation between plasma MMP-9 levels and parameters of LV dysfunction has been demonstrated. The relationship in long-term survivors has not been investigated. We studied the relationships of these biochemical markers, and N-terminal pro-B-type natriuretic peptide (N-BNP), with measures of long-term LV remodeling.Methods and ResultsPlasma levels of N-BNP, MMP-2, and MMP-9 were measured at randomization, 1 month, 1 year, and >4 years after complicated AMI. Contrast-enhanced cardiac magnetic resonance (CMR) was performed at 4.4 (±0.4) years in 52 clinically stable long-term survivors of the index AMI. We assessed the relationships of plasma N-BNP, MMP-2, and MMP-9 with myocardial scarring, and measures of long-term LV remodeling. Compared with a reference population, N-BNP and MMP-9 levels were increased at all time points from the acute phase until >4 years after MI. Plasma N-BNP and MMP-9 correlated only in the subacute phase (randomization, mean 3.3 days after MI) days after acute MI (r = 0.38, P = .006). At CMR assessment ≥4 years, log MMP-9 level was inversely related to LV ejection fraction (P = .002) and nonscarred myocardial mass (P = .008). This relationship was independent of MMP-2. Log N-BNP was related to end diastolic volume index (P = .0002). There was no correlation between log MMP-9 and LV volumes.ConclusionThere is a time-dependent relationship between plasma N-BNP and MMP-9 levels, these peptides correlating only in the acute phase after MI. In long-term follow-up, plasma MMP-9 and N-BNP levels were related to different parameters of LV remodeling. These findings suggest that in long-term survivors of complicated MI, different mechanisms modulate plasma levels of MMP-9 and N-BNP.     

Effect of scar and His–Purkinje and myocardium conduction on response to conduction system pacing

Introduction

Conduction system pacing (CSP), in the form of His bundle pacing (HBP) or left bundle branch pacing (LBBP), is emerging as a valuable cardiac resynchronization therapy (CRT) delivery method. However, patient selection and therapy personalization for CSP delivery remain poorly characterized. We aim to compare pacing-induced electrical synchrony during CRT, HBP, LBBP, HBP with left ventricular (LV) epicardial lead (His-optimized CRT [HOT-CRT]), and LBBP with LV epicardial lead (LBBP-optimized CRT [LOT-CRT]) in patients with different conduction disease presentations using computational modeling.

Methods

We simulated ventricular activation on 24 four-chamber heart geometries, including His–Purkinje systems with proximal left bundle branch block (LBBB). We simulated septal scar, LV lateral wall scar, and mild and severe myocardium and LV His–Purkinje system conduction disease by decreasing the conduction velocity (CV) down to 70% and 35% of the healthy CV. Electrical synchrony was measured by the shortest interval to activate 90% of the ventricles (90% of biventricular activation time [BIVAT-90]).

Results

Severe LV His–Purkinje conduction disease favored CRT (BIVAT-90: HBP 101.5 ± 7.8 ms vs. CRT 93.0 ± 8.9 ms, p < .05), with additional electrical synchrony induced by HOT-CRT (87.6 ± 6.7 ms, p < .05) and LOT-CRT (73.9 ± 7.6 ms, p < .05). Patients with slow myocardium CV benefit more from CSP compared to CRT (BIVAT-90: CRT 134.5 ± 24.1 ms; HBP 97.1 ± 9.9 ms, p < .01; LBBP: 101.5 ± 10.7 ms, p < .01). Septal but not lateral wall scar made CSP ineffective, while CRT was able to resynchronize the ventricles in the presence of septal scar (BIVAT-90: baseline 119.1 ± 10.8 ms vs. CRT 85.1 ± 14.9 ms, p < .01).

Conclusion

Severe LV His–Purkinje conduction disease attenuates the benefits of CSP, with additional improvements achieved with HOT-CRT and LOT-CRT. Septal but not lateral wall scars make CSP ineffective.     

Impacts of nicorandil on infarct myocardium in comparison with nitrate: assessed by cardiac magnetic resonance imaging

In this pilot study, we compared the infarct and edema size in acute myocardial infarction (MI) patients treated by nicorandil with those treated by nitrate, using cardiac magnetic resonance (CMR) imaging. Fifty-two acute MI patients who underwent emergency percutaneous coronary intervention (PCI) were enrolled, and were assigned to receive nicorandil or nitrate at random just before reperfusion. For the assessment of infarct and edema areas, short-axis delayed enhancement (DE) and T2-weight (T2w) CMR images were acquired 6.1 ± 2.4 days after the onset of MI. A significant correlation was observed between the peak creatinine kinase (CK) level and the infarct size on DE CMR (r = 0.62, p < 0.05), as well as the edema size on T2w CMR (r = 0.70, p < 0.05) in patients treated by nicorandil (28 patients). A similar correlation was seen between the peak CK level and the infarct size on DE CMR (r = 0.84, p < 0.05), as well as the edema size on T2w CMR (r = 0.84, p < 0.05) in patients treated by nitrate (24 patients). The maximum CK level was significantly lower in patients treated by nicorandil rather than nitrate (1991 ± 1402, 2785 ± 2121 IU/L, respectively, p = 0.03). Both the edema size on T2w CMR and the infarct size on DE CMR were significantly smaller in patients treated by nicorandil rather than nitrate (17.7 ± 9.9, 21.9 ± 13.7 %; p = 0.03, 10.3 ± 6.0, 12.7 ± 6.9 %, p = 0.03, respectively). The presence and amount of microvascular obstruction were significantly smaller in patients treated by nicorandil rather than nitrate (39.2, 64.7 %; p = 0.03; 2.2 ± 1.3, 3.4 ± 1.5 cm²; p = 0.02, respectively). Using CMR imaging, we demonstrated that the complementary use of intravenously and intracoronary administered nicorandil during PCI favorably acts more on the damaged myocardium after MI than nitrate. We need a further powered prospective study on the use of nicorandil.     

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.