Late Left Ventricular Remodeling Research Articles

Predictive value of early left ventricular end-diastolic volume changes for late left ventricular remodeling after ST-elevation myocardial infarction.

Left ventricular remodeling (LVR) is a major predictor of adverse outcomes in patients with acute ST-elevation myocardial infarction (STEMI). This study aimed to prospectively evaluate LVR in patients with STEMI who were successfully treated with primary percutaneous coronary intervention (PCI) and examine the relationship between early left ventricular dilation and late LVR. Overall 301 consecutive patients with STEMI who underwent primary PCI were included. Serial echocardiography was performed on the first day after PCI, on the day of discharge, at 1 month, and 6 months after discharge. Left ventricular remodeling occurred in 57 (18.9%) patients during follow-up. Left ventricular end-diastolic volume (LVEDV) reduced from day 1 postoperative to discharge in the LVR group compared with that in the non-LVR (n-LVR) group. The rates of change in LVEDV (ΔLVEDV%) were -5.24 ± 16.02% and 5.05 ± 16.92%, respectively (p < 0.001). LVEDV increased in patients with LVR compared with n-LVR at 1-month and 6-month follow-ups (ΔLVEDV% 13.05 ± 14.89% vs. -1.9 ± 12.03%; 26.46 ± 14.05% vs. -3.42 ± 10.77%, p < 0.001). Receiver operating characteristic analysis showed that early changes in LVEDV, including ΔLVEDV% at discharge and 1-month postoperative, predicted late LVR with an area under the curve value of 0.80 (95% confidence interval 0.74-0.87, p < 0.0001). Decreased LVEDV at discharge and increased LVEDV at 1-month follow-up were both associated with late LVR at 6-month. Comprehensive and early monitoring of LVEDV changes may help to predict LVR.

Elevated LDL Cholesterol Increases Microvascular Endothelial VWF and Thromboinflammation After Myocardial Infarction.

In reperfused myocardial infarction, VWF (von Willebrand factor)-mediated platelet adhesion contributes to impaired microvascular reflow and possibly also to postmyocardial infarction inflammation. We hypothesized that postischemic thromboinflammatory processes are worsened by elevated LDL (low-density lipoprotein) cholesterol. Myocardial ischemia-reperfusion or sham procedure was performed in wild-type mice and hyperlipidemic mice deficient for the LDL receptor and Apobec-1 (apolipoprotein-B mRNA editing enzyme catalytic polypeptide-1; DKO [double knockout]). DKO subgroups were treated with N-acetylcysteine, which inhibits pro-adhesive VWF multimers or with recombinant ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin motifs-13), which enzymatically cleaves endothelial surface-associated VWF. Myocardial contrast echocardiography perfusion imaging and molecular imaging for VWF, platelet glycoprotein Ibα, and leukocyte CD18 (cluster of differentiation) were performed 30 minutes post-reperfusion. Histology, infarct sizing, and echocardiography were performed at 1.5 or 72 hours; late echocardiography was performed at day 21. After ischemia-reperfusion, DKO compared with wild-type mice had ≈2-fold higher (P<0.05) risk area signal for microvascular platelet adhesion, VWF, and CD18; greater impairment in microvascular reflow, and 2-fold larger infarct size. Treatment of DKO mice with N-acetylcysteine and ADAMTS13 reduced molecular imaging signal for microvascular platelet adhesion, VWF, and CD18; improved early microvascular reflow; and reduced eventual infarct size. ADAMTS13 suppressed the postmyocardial infarction neutrophil and monocyte infiltration, enhanced the time-dependent recovery of left ventricular systolic function, and prevented late left ventricular remodeling. In reperfused myocardial infarction, elevated LDL cholesterol promotes thromboinflammation through excess microvascular endothelial VWF and platelet adhesion, resulting in less microvascular reflow and larger infarct size. In the presence of elevated LDL cholesterol, therapies that suppress endothelial-associated VWF can promote recovery of left ventricular function and protect against remodeling.

68Ga]Ga-DOTA-FAPI-04 PET/MR in patients with acute myocardial infarction: potential role of predicting left ventricular remodeling

PurposeTo assess predictive value of 68Ga-labeled fibroblast activation protein inhibitor-04 ([68Ga]Ga-DOTA-FAPI-04) PET/MR for late left ventricular (LV) remodeling in patients with ST-segment elevated myocardial infarction (STEMI).MethodsTwenty-six patients with STEMI were included in the study. [68Ga]Ga-DOTA-FAPI-04 PET/MR was performed at baseline and at average 12 months after STEMI. LV remodeling was defined as >10% increase in LV end-systolic volume (LVESV) from baseline to 12 months.ResultsThe LV remodeling group demonstrated higher [68Ga]Ga-DOTA-FAPI-04 uptake volume (UV) at baseline than the non-LV remodeling group (p < 0.001). [68Ga]Ga-DOTA-FAPI-04 UV at baseline was a significant predictor (OR = 1.048, p = 0.011) for LV remodeling at 12 months after STEMI. Compared to clinical information, MR imaging and cardiac function parameters at baseline, [68Ga]Ga-DOTA-FAPI-04 UV demonstrated better predictive ability (AUC = 0.938, p < 0.001) for late LV remodeling, with sensitivity of 100.0% and specificity of 81.3%.Conclusions[68Ga]Ga-DOTA-FAPI-04 PET/MR is an effective tool to non-invasively quantify myocardial fibroblasts activation, and baseline [68Ga]Ga-DOTA-FAPI-04 UV may have potential predictive value for late LV remodeling.

Evaluation of different late left ventricular remodeling definitions for predicting long-term outcomes in acute myocardial infarction patients undergoing percutaneous coronary intervention

Abstract Background Late left ventricular remodeling (LLVR) after the index acute myocardial infarction (AMI) is a common complication, and is associated with poor outcome. However, the optimal definition of LLVR has been debated because of its different incidence and influence on prognosis. At present, there are limited data regarding the influence of different LLVR definitions on long-term outcomes in AMI patients undergoing percutaneous coronary intervention (PCI). Purpose To explore the impact of different definitions of LLVR on long-term mortality, re-hospitalization or an urgent visit for heart failure, and identify which definition was more suitable for predicting long-term outcomes in AMI patients undergoing PCI. Methods We prospectively observed 460 consenting first-time AMI patients undergoing PCI from January 2012 to December 2018. LLVR was defined as a ≥20% increase in left ventricular end-diastolic volume (LVEDV), or a &amp;gt;15% increase in left ventricular end-systolic volume (LVESV) from the initial presentation to the 3–12 months follow-up, or left ventricular ejection fraction (LVEF) &amp;lt;50% at follow up. These parameters of the cardiac structure and function were measuring through the thoracic echocardiography. The association of LLVR with long-term prognosis was investigated by Cox regression analysis. Results The incidence rate of LLVR was 38.1% (n=171). The occurrence of LLVR according to LVESV, LVEDV and LVEF definition were 26.6% (n=117), 31.9% (n=142) and 11.5% (n=51), respectively. During a median follow-up of 2 years, after adjusting other potential risk factors, multivariable Cox regression analysis revealed LLVR of LVESV definition [hazard ratio (HR): 2.50, 95% confidence interval (CI): 1.19–5.22, P=0.015], LLVR of LVEF definition (HR: 16.46, 95% CI: 6.96–38.92, P&amp;lt;0.001) and LLVR of Mix definition (HR: 5.86, 95% CI: 2.45–14.04, P&amp;lt;0.001) were risk factors for long-term mortality, re-hospitalization or an urgent visit for heart failure. But only LLVR of LVEF definition was a risk predictor for long-term mortality (HR: 6.84, 95% CI: 1.98–23.65, P=0.002). Conclusions LLVR defined by LVESV or LVEF may be more suitable for predicting long-term mortality, re-hospitalization or an urgent visit for heart failure in AMI patients undergoing PCI. However, only LLVR defined by LVEF could be used for predicting long-term mortality. Funding Acknowledgement Type of funding sources: None. Association Between LLVR and outcomesKaplan-Meier Estimates of the Mortality

P3490Intravenous administration of atorvastatin early after cardiac ischemia attenuates adverse left ventricular remodeling, ameliorates cardiac function and limits the deleterious effects of reinfarction

Abstract Background Statins have shown to attenuate reperfusion-induced myocardial injury. However, whether statins directly target ischemia-related cardiac damage attenuating adverse left ventricular (LV) remodeling and post-myocardial infarction (MI) complications remains unknown. Purpose We examined the impact of a single intravenous administration of IV-STATIN early after ischemia onset on LV remodeling and reinfarction in a dyslipidemic pig model by serial CMR. Methods Diet-induced hypercholesterolemic pigs (N=14; cholesterol: 394±61mg/dL) were subjected to 90min of ischemia (MI-induction by LAD-coronary balloon occlusion) and further reperfusion. One group of pigs received an intravenous bolus of IV-STATIN (a modified preparation of atorvastatin; 0.3mg/kg) at 15min of ischemia (IV-STATIN-ISCH; n=7) whereas the other was orally treated with atorvastatin shortly post-MI (ATORVA-POST-MI; n=7). 40 days thereafter animals underwent a second MI-induction (reinfarction) and were sacrificed at day43. All animals remained post-MI and until sacrifice on p.o. atorvastatin treatment and a high-cholesterol diet. Serial CMR analysis was performed at day3 (early LV remodeling), prior-reinfarction (late LV remodeling; day40) and post-reinfarction (day43) for the assessment of global anatomical and functional parameters and segmental motility. Myocardial tissue was collected for molecular and histological analyses of cell death-, inflammatory-, and angiogenic-related markers. Results CMR revealed 3 days post-MI an absolute 6% reduction on infarct size in IV-STATIN-ISCH pigs as compared to ATORVA-POST-MI pigs (18.0±0.8% LV vs. 23.9±1.9% LV; p&lt;0.05) with the resultant 25% increase in myocardial salvage (p&lt;0.05). These infarct size-limiting effects remained up to day40 and lead to 30% smaller scars vs. ATORVA-POST-MI pigs (9.9±0.8% LV vs. 13.9±1.9% LV; respectively; p=0.06). Interestingly, reinfarction did not expand the damage produced by MI in IV-STATIN-ISCH animals whereas it increased by 13% the scar size of ATORVA-POST-MI pigs (p&lt;0.05). These IV-STATIN-ISCH- related benefits detected throughout the study were associated with a significant global improvement in stroke volume and LVEF as well and less regional wall motion abnormalities and dysfunctional segments in the jeopardized region (p&lt;0.05 vs. ATORVA-POST-MI). The scar of reinfarcted IV-STATIN-ISCH pigs showed lower apoptosis execution and MCP-1 expression and higher vessel density vs. ATORVA-POST-MI (p&lt;0.05). Lipids levels and liver/renal parameters remained unchanged in all animals throughout the study. Conclusions This is the first study to prove that intravenous administration of IV-STATIN early after MI improves structural and functional cardiac remodeling and limits the worsening effects of reinfarction. The potential cardiac benefits afforded by CardioshieldTM infusion early after MI-diagnosis (i.e., out-of-hospital and/or cath lab setting) deserves to be clinically investigated. Acknowledgement/Funding Fundaciό Investigaciό Marato TV3 #20154310; PNS 2015-71653-R and PNS SAF2016-76819-R MINECO, ISCIII; CIBERCV CN16/11/00411

P6603The predictive role of T786C single nucleotide polymorphism in endothelial no-synthase gene in late left ventricular remodeling after ST-segment elevation myocardial infarction

Abstract Introduction Endothelial NO-synthase (eNOS) is constitutive enzyme, which is expressed in mature endothelial cells and promotes direct vascular dilatation. Single nucleotide polymorphism (SNP) of T786C in eNOS gene may influence on adverse cardiac remodeling after ST-elevation myocardial infarction (STEMI). Purpose To investigate possible associations between SNP T786C in eNOS gene and adverse cardiac remodeling after STEMI Methods 177 acute STEMI patients treated with primary and facilitate percutaneous coronary intervention that were admitted to intensive care unit of a Therapy National Institute were enrolled in the study. Anthropometry, cardiovascular risk assay, coronary angiography, echocardiography and biomarkers' measure were performed at baseline. The DNA extraction was performed with a commercial kit using real-time polymerase chain reaction PCR. All procedures performed in the study involving human participants were in accordance with the ethical standards and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards and approved by the local ethics committee (Protocol No. 8, 29.08.2016). Written informed consent was obtained from each patient. Results There were correlations between 786CC polymorphism in eNOs gene and adverse cardiac remodeling (r=0.48; p=0.001), LDL cholesterol (r=0.32; p=0.012), type 2 diabetes mellitus (r=0.30; p=0.042), diastolic BP (r=−0.26; p=0.048), unstable angina prior to STEMI (r=0.25; p=0.047) and total quantity of complicated STEMI (r=0.23; p=0.042). Additionally, there were not significant relations between 786CC polymorphism in eNOs gene and multiple coronary vessel injury, STEMI localization, levels of circulating biomarkers of myocardial injury, and amount of damaged coronary arteries. Using univariate and multivariate regressive logistic analysis we found that 786CC genotype of eNOS was independent predictor for late adverse LV remodeling (β-coefficient = 1.57342; odds ratio = 4.8231; 95% confidence interval = 1.5349–15.1552; p=0.0071). Conclusions The polymorphism 786CC in eNOs gene was found as an independent predictor for late adverse cardiac remodeling after STEMI. Acknowledgement/Funding None

Prognostic significance of soluble ST2 as predictor of late left ventricular remodeling after ST-segment elevation myocardial infarction

The aim — to study the prognostic value of soluble ST2 regarding the development of pathological left ventricular remodeling (LVR) 6 months after acute ST‑ segment elevation myocardial infarction (STEMI)Materials and methods. The study included 65 retrospectively selected patients with STEMI who were hospitalized in the intensive care unit of L. T. Malaya National Institute of Therapy of National Academy of Medical Sciences of Ukraine for the period from January 2016 to June 2018 after myocardial revascularization. All patients had a recovery in TIMI III blood flow. Among the patients, men with a middle age 58.71 ± 11.04 years (83.1 %) prevailed. Ultrasound diagnosis with the determination of the longitudinal strain was conducted. The level of sST2 and N‑terminal cerebral natriuretic peptide was determined by ELISA. Patients were monitored for 6 months. According to the results of the re‑examination, two subgroups were identified, depending on the development of pathological LVR: in the first group, the increase in the endodiastolic LV volume was more than 10 % (n = 29), in the second — less than 10 % (n = 36).Results and discussion. Using ROC‑analysis, it was established that sST2 level &gt; 35 ng/ml during the hospitalization period of STEMI is a predictor of pathological LVR 6 months after successful percutaneous coronary intervention (AUC = 0.672; 95 % confidence interval — 0.523 — 0.799, p = 0.0344, sensitivity — 46.7 %, specificity — 85.7 %). A single and multivariate log‑regression analysis revealed that sST2 &gt; 35 ng/ml was an independent predictor of the development of late LVR.Conclusions. The serum sST2 level of more than 35 ng/ml in patients with STEMI after successful percutaneous coronary intervention with the bloodstream in the infarct‑dependent artery TIMI III is associated with abnormal LVR, which can be used to stratify its risk in this cohort of patients.

ST2 as a predictor of late ventricular remodeling after myocardial infarction

ST2 is known to be heightened in the early phase after myocardial infarction, and associated with left ventricular remodeling (LVR). Explore the potential role of ST2 as a predictor for late LVR. Patients with a reperfused ST-segment elevation myocardial infarction (STEMI) were included in a prospective cohort. They underwent cardiac magnetic resonance (CMR) at 3 days (baseline), 3 and 12 months. Among 163 patients, 33 presented LVR as defined as a 10% change in LV end-systolic volume during follow-up. All patients were matched to 33 STEMI patients without LVR (non-remodelers) in term of age, gender, anterior infarction, baseline LV ejection fraction (LVEF) and infarct size. Early LVR ( n = 15) was defined as LVR occurring between baseline and 3 months, and Late LVR ( n = 18) as LVR occurring between 3 and 12 months. Usual CMR parameters were measured, so as global systolic wall stress (SWS). A biomarker analysis was performed at baseline and 3 months. Patients were 57 ± 10 years old, 85% were male. Early LVR patients presented with mean LVEF and infarct size of 48 ± 10.4% and 28 ± 15.6% LV; and Late LVR with 51 ± 11% and 16 ± 14.5% LV, respectively. At baseline, ST2 (46 ± 54.1 ng/mL), NT-proBNP (869 ± 1702 ng/L) and SWS (16.2 ± 7.1 10 3 N·m −2 ) were not different among the groups. At 3 months, Early LVR patients presented higher ST2, NT-proBNP and SWS (26 ± 12.7 ng/mL, 652 ± 1069 ng/L, 23 ± 9.7 10 3 N·m −2 for Early LVR, versus 21 ± 8.6 ng/mL, 354 ± 272.8 ng/L, 18 ± 7.3 10 3 N·m −2 for the corresponding non-remodelers, with P = 0.017, 0.040, and 0.036, respectively). Late LVR patients presented higher ST2 at 3 months than non-remodelers (34.4 ± 15.9 versus 22.1 ± 8.7 ng/mL, P = 0.046), while NT-proBNP and SWS were not different between groups at both time points ( Fig. 1 ). ST2 can be useful to predict LVR after STEMI.

Cyclosporin A in left ventricular remodeling after myocardial infarction

Recent studies suggest that an increase in apoptosis within the myocardium may be a contributing factor for the progression of late adverse left ventricular (LV) remodeling following myocardial infarction (MI). Given that apoptosis is often triggered by induction of the mitochondrial permeability transition (MPT) pore, the goal of this study was to evaluate the therapeutic efficacy of cyclosporin A (CsA), an MPT blocker, to prevent cells from undergoing apoptosis and consequently attenuate late LV remodeling post-MI. MI was induced in C57BL/6 mice and then randomized to either vehicle or CsA groups. Beginning 48 h after surgery after infarction had already occurred, mice were gavaged with CsA (2 mg/kg) or vehicle once daily. LV end-diastolic volume and LV ejection fraction were assessed by echocardiography before MI induction and terminally at either 7 days (n = 7) or 28 days (n = 8) post-MI. LV end-diastolic volume increased and LV ejection fraction decreased in all MI groups with no difference between the CsA-treated and untreated groups. After vehicle and CsA, areas of necrosis were present at 7 and 28 days post-MI with no difference between treatment groups. Caspase-3 activity and terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling in distal nonnecrotic LV both increased after MI but were lower in CsA-treated mice compared with vehicle (P < 0.05). In conclusion, CsA decreased apoptosis occurring late after MI, confirming involvement of a CsA-sensitive MPT in the cell death. However, CsA-mediated reduction in apoptosis in non-MI myocardium was not beneficial against late pump dysfunction occurring during post-MI remodeling.

The influence of thrombolytic therapy on clinical and instrumental parameters of left ventricular remodeling in the late post-infarction period of myocardial infarction with Q-wave

Aim. To evaluate clinical and instrumental parameters of late left ventricular remodeling in patients with myocardial infarction with Q-wave depending on use of thrombolysis. Methods. 87 patients with myocardial infarction with Q-wave on electrocardiography (ECG) were included. First group consisted of 34 patients in whom thrombolytic therapy was performed, second group consisted of 53 patients in whom thrombolysis was not used due to late referral (over 12 hours from initial symptom onset, 88,7%), concomitant hemorrhagic stroke (3,8%), previously reported uncontrolled arterial hypertension (7,6%). All patients were followed up at 3-4 weeks, 60 and 120 months after the onset of myocardial infarction, examination included ECG, echocardiography, clinical examination. Results. In patients of both groups increase of total R-wave amplitude on repetitive ECGs was associated with relative left ventricle wall thickening, increase of left ventricular mass index, decrease of systolic and diastolic wall stresses caused by compensatory hypertrophy of intact cardiomyocytes according to results of correlation analysis. Increase of total amplitude of QS-waves on repetitive ECGs was associated with left ventricular cavity dilatation and spherification with wall thickening, increase of systolic and diastolic wall stresses. Patients in whom thrombolysis was not used had significantly higher rates of angina at post-infarction period. No statistically significant differences of ECG and echocardiography parameters between two groups of patients were found during the whole follow-up period. Non-significant increase of total R-wave amplitude and QS-waves amplitude was registered in patients in whom thrombolysis was started not later than 90 minutes from initial symptom onset compared to patients in whom thrombolysis was started later. Conclusion. Comparison of ECG and echocardiography parameters over time did not reveal any statistically significant differences between the groups with and without thrombolysis.

Serial Assessment of Left Ventricular Remodeling by Measurement of Left Ventricular Torsion Using Speckle Tracking Echocardiography in Patients With Acute Myocardial Infarction

The relation between remodeling and left ventricular (LV) torsion has not yet been fully investigated. The aim of this study was to determine whether LV torsion assessed by speckle tracking imaging can predict progressive LV dilation after acute myocardial infarction (AMI). From January 2006 through June 2008, 91 patients with AMI who were successfully treated with primary coronary intervention underwent conventional and speckle tracking echocardiographies at initial presentation and 3 days and 6 months after first AMI. Patients were divided into 2 groups based on presence of LV remodeling (increase of LV end-diastolic volume >20%) at 6-month follow-up. LV remodeling developed in 23 patients. At initial presentation, LV end-diastolic volume was not significantly different between the no-remodeling and remodeling groups (91.27 ± 35.68 vs 85.74 ± 28.89 ml, p = 0.51), but LV torsion (2.23 ± 0.67 vs 1.70 ± 0.58°/cm, p <0.05) was significantly decreased in the remodeling group. At 6-month follow-up speckle tracking echocardiography, apical rotation and global torsion in patients with remodeling were 6.7 ± 2.6 (p <0.05) and 1.7 ± 0.7°/cm (p = 0.76 from baseline), respectively, and in patients without remodeling, 8.8 ± 3.4 (p <0.01) and 2.5 ± 0.7°/cm (p <0.01 from baseline), respectively. According to receiver operating characteristic analysis, LV torsion of 1.9°/cm (area under curve 0.79, sensitivity 75%, specificity 78%) at initial presentation was selected as a significant predictor of remodeling. In conclusion, decreased LV torsion assessed by speckle tracking echocardiography may predict late LV remodeling after reperfusion therapy after AMI.

Myocardial performance index: prediction and monitoring of remodeling and functioning of the left ventricle after first myocardial infarction

Dynamic changing of left ventricular geometry and contractile state after acute myocardial infarction is responsible for various aspects of left ventricular remodeling and dysfunction. A number of studies have shown that myocardial performance index allows prediction of acute myocardial infarction complications. The objective of our study was to determine the power of myocardial performance index to predict and assess the severity of left ventricular remodeling, systolic and diastolic dysfunction after acute myocardial infarction over the long term. Echocardiography was performed within the first week of hospitalization, after one, three and six months in 77 patients with first acute myocardial infarction. At the end of the study the patients were divided into group A and B with mild and severe left ventricular remodeling, respectively. Myocardial performance index was significantly lower in group A compared to B, at the beginning (0.62 vs. 0.75; p = 0.002), and at the end of study (0, 60 vs. 0, 69; p = 0.004). After six months, 31% of study patients developed LV systolic dysfunction with prevalence in group B (56% vs. 19%, p = 0.002). Myocardial performance index > or = 0.70 at first week after acute myocardial infarction is a strong predictive parameter for extensive early and late left ventricular remodeling and systolic dysfunction (p < 0.05), but it is not a valuable predictor of diastolic failure. MPI obtained at first week of acute myocardial infarction was predictive for early and long term left ventricular remodeling and systolic dysfunction. Myocardial performance index had doubtful clinical use in assessing dynamics of remodeling and it was without clinical value in predicting diastolic function deterioration.

Elevation of Plasma Granzyme B Levels After Acute Myocardial Infarction

Apoptosis is reported to play an important role in left ventricular (LV) remodeling after acute myocardial infarction (AMI). Granzyme B is a member of the serine esterase family, which has an important role in cellular apoptosis and extracellular matrix degradation. Peripheral blood samples were obtained from 33 patients with a first-onset AMI treated by percutaneous coronary intervention (mean age: 61.4+/-8.7 years old) on days 1, 7 and 14 after onset. Plasma levels of tumor necrosis factor (TNF)-alpha, a soluble form of the Fas ligand (sFasL), and granzyme B were measured. TIMI grade 3 recanalization was accomplished in all patients within 12 h after onset. The LV end-diastolic volume index (LVEDVI) was calculated on day 1 and at 6 months after onset. Plasma levels of TNF-alpha, sFasL and granzyme B increased significantly on days 7 and 14 after onset of AMI. Stepwise multivariate regression analysis showed that the plasma granzyme B level on day 14 is a significant explanatory variable for changes in the LVEDVI. Plasma levels of granzyme B increased after AMI, which might be an important factor in the progression of late LV remodeling after AMI.

Stentless and stented aortic valve replacement in elderly patients: factors affecting midterm clinical and hemodynamical outcome

To report on the midterm results of aortic valve replacement (AVR) with stented and stentless bioprosthesis in an elderly population by analyzing the factors affecting survival and hemodynamical performance. In a retrospective study, 145 patients with a Toronto stentless prosthesis are compared with 110 patients with a stented Carpentier-Edwards valve. The 5- to 10-year clinical outcome, transprosthetic gradients, and early and late left ventricular mass (LVM) regression are analyzed in view of specific prosthesis- and patient-related factors. Actuarial survival at 5 years is 82% after stentless AVR versus 68% after stented AVR (p < 0.001) in elderly patients. However, there was no difference in survival at 8 years, being 55.9% and 59.5%, respectively. Univariate analysis revealed that advanced age at the time of operation, NYHA class IV, use of a stented xenograft, presence of patient-prosthesis mismatch (PPM) (IEOA < or = 0.85 cm2/m2), and severe preoperative left ventricular (LV) hypertrophy (LVMI > 180 g/m2) affected survival adversely. But multivariate analysis determined only age, NYHA class IV and excessive LV hypertrophy as independent predictors of late mortality. Stented and stentless xenografts were equally effective in terms of transprosthetic gradients and LVMI regression. The use of a stentless valve significantly reduced the occurrence of PPM (18% vs 41%, p < 0.01). Early LVMI regression at 1 year was optimized by the avoidance of PPM, indicated by a higher absolute (43.7+/-28.3 g/m2 vs 58.6+/-33.8 g/m2, p = 0.003) and relative (25.0+/-12.7% vs 31.4+/-14.9%, p=0.004) mass regression. However, late LV remodeling was predominantly affected by systemic hypertension and severe preoperative LV hypertrophy, resulting in the incomplete LVMI resolution in 61.3% and 66.7% of these patients, respectively. In elderly patients, aortic valve replacement appears to be equally effective with a stentless or stented bioprosthesis. Midterm clinical outcome is mainly determined by patient-related factors such as age, advanced NYHA class, and severity of preoperative LV hypertrophy. Regarding post-AVR left ventricular remodeling, patient-prosthesis mismatch influences the early phase, whereas arterial hypertension affects the late regression more. However, the left ventricular remodeling is continuously compromised by the preoperative presence of excessive hypertrophy, despite the efficacy of the aortic valve replacement.

Pressure-derived collateral flow index: a strong predictor of late left ventricular remodeling after thrombolysis for acute myocardial infarction

Despite proved efficacy of pressure-derived collateral flow index in determining microvascular dysfunction in patients with acute myocardial infarction, its role in prediction of left ventricular remodeling at long term has yet to be demonstrated. In this study, we investigated the relationship between quantitatively assessed microvascular dysfunction by using intracoronary pressure wire and late left ventricular remodeling. The study population consisted of 28 patients with first acute myocardial infarction. They were treated with fibrinolytic therapy. The inclusion criteria were thrombolysis in myocardial infarction grade II-III flow in infarct-related artery and all destined for stent implantation. Cardiac catheterization and stent implantation were performed in mean of 3.3 days after acute myocardial infarction. During the stent implantation procedure, the pressure-derived collateral flow index was measured by using intracoronary pressure wire. Control angiograms were performed at 6+/-2 months. Echocardiographic left ventricular volume indexes were measured at discharge, at 6 months and at 1 year. Changes in left ventricular volumes from baseline to 1 year were followed. Left ventricular end-diastolic volume index at 1 year correlated significantly with the pressure-derived collateral flow index (r=0.69, P<0.01). A significant correlation was also observed between the change in left ventricular end-diastolic volume index from baseline to 1 year and the pressure-derived collateral flow index (r=0.65, P<0.01). The most important predictor of 1-year left ventricular remodeling was the pressure-derived collateral flow index (P<0.0001), and collateral circulation (P=0.03). The pressure-derived collateral flow index is a powerful independent predictor of 1-year left ventricular dilatation. Given its simplicity of measurement, and correlation with microvascular obstruction and left ventricular outcome at long term, the pressure-derived collateral flow index may provide useful and valuable estimates of clinical outcomes after acute myocardial infarction.

N-Terminal Pro–B-Type Natriuretic Peptide and Matrix Metalloproteinases in Early and Late Left Ventricular Remodeling After Acute Myocardial Infarction

N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) is a predictor of left ventricular remodeling. Matrix metalloproteinases (MMPs) contribute to collagen breakdown that is associated with ventricular remodeling after acute myocardial infarction (AMI). We assessed the association between circulating levels of NT-pro-BNP, MMP-2, and MMP-9 and their inhibitor (tissue inhibitor of metalloproteinase-1) early (24 and 72 hours) and late (7 and 30 days) after AMI in 108 patients who had ST-elevation AMI (90 men; mean age 60 years). Serum MMP-2 levels measured 24 and 72 hours after AMI were inversely associated with NT-pro-BNP levels, whereas MMP-9 serum levels were positively related. During late-stage remodeling after AMI, circulating concentrations of tissue inhibitor of metalloproteinase-1 were independently associated with NT-pro-BNP levels 7 and 30 days after AMI. This study shows that, in patients who have ST-elevation AMI, circulating levels of NT-pro-BNP are associated with MMPs in a species-specific and time-dependent manner.

Cardioprotective potential of intermittent fasting in rats

Background: Intermittent Food Deprivation (IF), i.e., the feeding regimen when ad lib food is available only every other day, increases the life span and reduces the incidence of age-associated diseases including cancer, diabetes and kidney disease. We have reported the neuroprotective effects of IF against ischemic injury of the brain (Yu and Mattson, J. Neurosci. Res. 57:830–9; 1999). The mechanisms of neuroprotection of IF is not clear, but diminishing free-radical production, a mild cellular stress response, and attenuated inflammatory response are implicated. Here we investigated the cardioprotective effect of IF in rats. Method: After three months of IF or regular, daily, feeding ad libitum (AF), 5-mo old rats were subjected to coronary ligation or sham operation. A subset of rats was sacrificed 24 hours later to measure the size of myocardial infarction (MI) and the extent of apoptosis. The remaining animals were continued for 10 weeks on the same food regimen, during which time the progression of left ventricular (LV) remodeling was assessed by serial echocardiography. After ten weeks LV function was measured by pressure-volume loops analyses, and hearts were evaluated histologically. Results: 24 hrs following coronary ligation the ischemic area of myocardium, i.e., the area at risk (AAR), was similar in both groups, but in IF rats MI size, expressed as a percent of AAR, was more than 2-fold smaller, apoptosis in the AAR was reduced by more than 4-fold (Fig.1), and the inflammatory response was significantly reduced. At 10-wks late LV remodeling and MI expansion occurred in AF rats but did not occur in IF rats, and LV pump function and arterio-ventricular coupling were superior in IF vs AF rats. The myocyte hypertrophy in areas remote from the MI was also absent in IF rats. Conclusion: Intermittent Food Deprivation protects the heart from ischemic injury in part, at least, via an anti-apoptotic mechanism.

Early assessment of coronary flow reserve by transthoracic Doppler echocardiography predicts late remodeling in reperfused anterior myocardial infarction

Background Microvascular integrity is an essential determinant of favorable late outcome in reperfused myocardial infarction. Coronary flow reserve (CFR) can be assessed by transthoracic Doppler echocardiography and provides a functional estimate of microvascular integrity downstream from the patent infarct-related vessel. Objective We sought to assess the effects of CFR in predicting late left ventricular (LV) remodeling in patients with reperfused acute anterior myocardial infarction treated with primary angioplasty. Methods In all, 31 patients admitted with acute anterior myocardial infarction underwent primary angioplasty of the infarct-related vessel. After angioplasty, angiographic thrombosis in myocardial infarction (TIMI) grade and myocardial blush were scored. On the first day, all underwent stress echocardiography and CFR evaluation of left anterior descending coronary artery by transthoracic Doppler. All patients had resting 2-dimensional echocardiography at 1, 3, and 6 months for assessment of LV function. Results CFR could be successfully assessed in 31 patients. After 6 months 5 patients showed LV dilatation (group I), whereas 26 patients did not show significant variation (group II). On day 1, CFR was higher (group I = 1.43 ± 0.11 vs group II = 1.67 ± 0.26, P = .005) and the deceleration time of diastolic left anterior descending coronary artery flow velocity was longer (group I = 212 ± 41.4 milliseconds vs group II = 286 ± 106.7 milliseconds, P < .02) in patients without, compared with those with LV remodeling, whereas there was no difference in angiographic parameters. Conclusion Early assessment of CFR and the pattern of baseline diastolic coronary flow velocity by transthoracic Doppler echocardiography is feasible, safe, and more useful than angiographic indices in identifying patients at high risk of remodeling in spite of successful primary angioplasty.

Myocardial Echocardiography With Intracoronary Injection of Contrast in Post-Infarction Patients. Implications and Comparison With Angiography and Magnetic Resonance Imaging

We analyzed the safety and feasibility of myocardial echocardiography with intracoronary injection of contrast, its effect on left ventricular remodeling and systolic function, and its relationship with angiography and magnetic resonance imaging (MRI) for the evaluation of post-infarction coronary microcirculation. Thirty patients with a first ST-elevation myocardial infarction and a patent infarct-related artery were studied. Mean perfusion score of the infarcted area was analyzed with myocardial echocardiography. TIMI and Blush grades (angiography) were determined. Mean perfusion score (MRI-perfusion), end-diastolic volume index and ejection fraction were determined with MRI. At 6 months all studies were repeated in the first 17 patients. Forty-seven perfusion studies (30 in the first week and 17 after 6 months) were done without complications (6 [2] min per myocardial echocardiography study). Normal perfusion (myocardial echocardiography 0.75) was detected in 67% of the patients. Myocardial echocardiography was the best predictor of end-diastolic volume (r=-0.69; P =.002) and ejection fraction (r=0.72; P=.001) after 6 months. Normal perfusion was observed in 80% of the patients with TIMI grade 3, and in 14% of those with TIMI grade 2. Of the 40 studies in patients with TIMI grade 3, normal perfusion was seen in 85% of the patients with Blush grade 2-3 and in 50% of those with Blush 0-1. Perfusion was also normal in 90% of the patients with MRI-perfusion =1 and in 62% of those with MRI-perfusion < 1. Myocardial echocardiography is a feasible and relatively rapid technique with no side effects. This technique provided the most reliable perfusion index for predicting late left ventricular remodeling and systolic function. To achieve normal perfusion, TIMI grade 3 is necessary but does not guarantee success. In patients with TIMI grade 3, a normal Blush score or a normal MRI-perfusion study suggests good reperfusion.

Targeted deletion of MMP-2 attenuates early LV rupture and late remodeling after experimental myocardial infarction.

Matrix metalloproteinase-2 (MMP-2) is prominently overexpressed both after myocardial infarction (MI) and in heart failure. However, its pathophysiological significance in these conditions is still unclear. We thus examined the effects of targeted deletion of MMP-2 on post-MI left ventricular (LV) remodeling and failure. Anterior MI was produced in 10- to 12-wk-old male MMP-2 knockout (KO) and sibling wild-type (WT) mice by ligating the left coronary artery. By day 28, MI resulted in a significant increase in mortality in association with LV cavity dilatation and dysfunction. The MMP-2 KO mice had a significantly better survival rate than WT mice (56% vs. 85%, P < 0.05), despite a comparable infarct size (50 +/- 3% vs. 51 +/- 3%, P = not significant), heart rate, and arterial blood pressure. The KO mice had a significantly lower incidence of LV rupture (10% vs. 39%, P < 0.05), which occurred within 7 days of MI. The KO mice exerted less LV cavity dilatation and improved fractional shortening after MI by echocardiography. The LV zymographic MMP-2 level significantly increased in WT mice after coronary artery ligation; however, this was completely prevented in KO mice. In contrast, the increase in the LV zymographic MMP-9 level after MI was similar between KO and WT mice. MMP-2 activation is therefore considered to contribute to an early cardiac rupture as well as late LV remodeling after MI. The inhibition of MMP-2 activation may therefore be a potentially useful therapeutic strategy to manage post-MI hearts.