Comparative Effect of Ticagrelor and Clopidogrel on Left Ventricular Remodeling in Acute Coronary Syndrome Patients: A Retrospective Cohort Study.

Administration of Pigment Epithelium-Derived Factor Inhibits Left Ventricular Remodeling and Improves Cardiac Function in Rats with Acute Myocardial Infarction

Diagnostic cardiac testing is commonplace following the 1.4 million percutaneous coronary intervention (PCI) procedures performed annually in the United States, but limited data exist on current patterns of post-PCI testing. Therefore, this study examined patterns of stress testing and invasive coronary angiography in a large, contemporary cohort of 250 350 elderly PCI patients using a unique data set combining longitudinal Medicare inpatient and outpatient claims with baseline clinical data from the National Cardiovascular Data Registry CathPCI Registry. Between 60 days post-PCI and end of follow-up (median, 24 months), 49% of patients received stress testing first, 10% underwent invasive coronary angiography first, and 41% had no testing. These testing rates are significantly higher than reported rates of recurrent angina after PCI in large registry studies. Paradoxically, several clinical risk factors at time of index PCI were associated with lower, rather than higher, likelihood of downstream testing, including older age, male sex, heart failure, diabetes mellitus, smoking, and renal failure. Fifteen percent of patients with stress testing first after PCI proceeded to subsequent invasive coronary angiography within 90 days of testing; of these, 48% underwent revascularization, compared with 53% of patients referred to catheterization first after PCI. Overall, the revascularization yield was low on patients referred for stress testing after PCI, with only 9% undergoing revascularization within 90 days. In aggregate, these results shed light on patterns of cardiac testing after PCI, and suggest further examination of these data incorporating reason for stress test referral and more insights into patient characteristics, particularly symptoms, after recent PCI.

Background: Lipoprotein (a) (Lp[a]) is associated with an increased risk of cardiovascular disease and mortality, as well as heart failure and myocardial fibrosis. However, the link between Lp(a) and cardiac remodeling as a pathway to adverse cardiac outcomes remains unknown. Objectives: This study investigated the relationship between Lp(a) levels and longitudinal changes in the left ventricular (LV) remodeling over a decade among individuals without a previous history of cardiovascular disease. Methods: 2,366 Multi-Ethnic Study of Atherosclerosis (MESA) participants who underwent cardiac MRI at Visit 1 (2000-02) and Visit 5 (2010-12) and had available Lp(a) at baseline were examined. Lp(a) was analyzed as a continuous and a categorical variable based on quartiles (Q1[<7.6 mg/dL], Q2[7.6-16.7 mg/dL], Q3[16.8-38.8 mg/dL], Q4[>38.8 mg/dL]). Multivariable linear regression analysis was used to examine the association of Lp(a) with changes in cardiac MRI measures of LV remodeling (Table). Results: Participants had a mean age 60±9 years and 53% were women. Over 10-year follow-up, LV indexed volumes decreased, while LV indexed mass and mass to volume ratio increased across all the Lp(a) quartiles. However, LV ejection fraction only decreased in the third and fourth Lp(a) quartiles. Lp(a) examined as a continuous variable was associated with an increase in LV end-systolic indexed volume (per log-unit Lp[a]; β 0.32 mL/m2; P = 0.01), LV indexed mass (per log-unit Lp[a]; β 0.38 g/m2; P = 0.02), and a decrease in LV ejection fraction (per log-unit Lp[a]; β -0.29 %; P = 0.02) over 10 years after adjusting for sociodemographic and traditional cardiovascular risk factors (Table). Similarly, the fourth Lp(a) quartile was associated with an increase in LV end-systolic indexed volume (β 1.07 mL/m2; P = 0.01), LV indexed mass (β 1.17 g/m2; P = 0.02) and a decrease in LV ejection fraction (β -1.01 %; P = 0.01) compared to the first Lp(a) quartile after controlling for risk factors. The observed associations remained significant after further adjusting for aortic valve calcium score at Visit 1 (Table - Model 3), and baseline coronary artery calcium score and interim myocardial infarction (Table - Model 4). Conclusions: In a multi-ethnic cohort of participants free of cardiovascular disease at baseline, higher Lp(a) levels were independently associated with an increase in LV end-systolic volume and LV mass as well as a decrease in LV ejection fraction over the span of a decade.

Background: There is a paucity of information on the time-dependent relationship of cardiac biomarkers to infarct size and left ventricular (LV) remodeling after myocardial infarction (MI). We sought to investigate the relationship between levels high-sensitivity C-reactive protein (hs-CRP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) and indices of infarct size and LV volume after acute MI. Methods: A total of 86 patients with ST-elevation MI within 12 hours after the symptom onset underwent delayed enhancement multi-detector computed tomography (DE MDCT) immediately after percutaneous coronary intervention (PCI) to determine infarct size. LV function and remodeling were assessed by echocardiography. Hs-CRP and NT-proBNP were serially measured at admission, 24 hours, and 2 months. DE MDCT and echocardiography were repeated at 2 months after PCI. Results: Levels of both hs-CRP and NT-proBNP at 24 hours showed positive correlation with infarct size at baseline and at 2 months, and negative correlation with LV ejection fraction at baseline and at 2 months. NT-proBNP at 2 months correlated with infarct size (r=0.561, p=0.007), LV ejection fraction (r= - 0.539, p=0.010), and LV end diastolic and systolic volume indices at 2 months (r=0.796, p=0.032 and r=0.831, p=0.021, respectively). NT-proBNP was higher in patients who developed LV remodeling at 2 months: 929 pg/mL vs. 134 pg/mL, p = 0.002. In contrast, hs-CRP at 2 months showed no relationship to infarct size, LV function, or LV volumes at 2 months. Conclusions: Elevated hs-CRP during active myocardial necrosis was associated with infarct size and LV dysfunction, whereas elevated levels of NT-proBNP early and late after the onset of acute MI were both correlated with infarct size, LV dysfunction, and LV remodeling.

Predictive Value of Left Ventricular Remodeling by Area Strain Based on Three-Dimensional Wall-Motion Tracking After PCI in Patients with Recent NSTEMI

Background and ObjectivesLeft ventricular (LV) remodeling (LVR) after an acute myocardial infarction (AMI) has important clinical implications. We have investigated the prognostic relevance of ventricular systolic dyssnchrony as an indicator of LVR after an AMI.Subjects and MethodsWe enrolled 92 patients (males, 72.8%; mean age, 61.0±13.0 years) with an AMI who underwent successful percutaneous coronary intervention. We analyzed the baseline characteristics, the laboratory and echocardiographic findings, and we performed follow-up echocardiography 6 months after the AMI. The patients were divided into two groups: 1) the presence of LVR, which was defined as an increment of LV end systolic volume (LVESV) >20% compared with the baseline examination; and 2) the absence of LVR.ResultsTwenty-seven patients (29.3%) developed LVR after a 6 month follow-up. There was no statistically significant difference in the clinical and angiographic findings between the two groups. With respect to the laboratory findings, the LVR group had a higher peak creatine kinase MB (CK-MB) (149.9±155.0 vs. 74.6±69.7 U/L, p=0.001) and troponin-I (70.2±73.3 vs. 43.2±39.5 ng/mL, p=0.024) level than the group without LVR. With respect to echocardiographic findings, the baseline LV ejection fraction (EF) and LVESV were not significantly different (LVESV, 73.0±37.3 vs. 91.3±52.0 mL, p=0.013; and EF, 58.3±13.3 vs. 55.6±11.8%, p=0.329) between the groups with and without LVR, respectively. The degree of LV dyssynchrony, which was assessed by tissue Doppler imaging, was significantly higher in the LVR group than the group without LVR (75.2±43.4 vs. 38.3±32.5 ms), and the degree of LV dyssynchrony was an independent predictor for LVR based on multivariate analysis {hazard ratio (HR)=0.097, p<0.001}. In receiver operating characteristics (ROC) curve analysis, the area under the curve (AUC) was 0.754 and a cutoff value of 45.9 predicted the development of LVR with 74.1% sensitivity and 72.3% specificity.ConclusionThe presence of LV dyssynchroncy immediately after a myocardial infarction is an important predictive factor for development LVR.

Background Prediction of left ventricular (LV) remodeling post-acute myocardial infarction (AMI) remains challenging. Several circulating biomarkers have been associated with post-AMI LV remodeling, however, there is no biomarker available to distinguish adverse versus reverse LV remodeling. Purpose In this study, we aimed to assess the association of extracellular vesicles (EVs) associated proteins with LV remodeling post-AMI. Methods Plasma EVs were isolated via precipitation with dextran sulphate as we previously reported. The protein levels of EV associated von Willebrand factor (VWF), SerpinC1 (antithrombin-III), plasminogen and SerpinF2 (alpha 2-antiplasmin) were determined in the citrate-anticoagulated plasma from 57 healthy subjects and 200 patients recruited in the Post-AMI Left Ventricular Remodeling Biomarker Analysis (PAMILA) study. Patients were categorized into two groups: adverse LV remodeling (n=100) characterized by an increase or reverse LV remodeling (n=100) characterized by a decrease, in LV end systolic volume by ≥15% over 6 months. Patients' plasma was collected at baseline (within 3 days after percutaneous coronary intervention), 1 month and 6 months post-AMI. Log transformation of EV protein levels was performed for assessment in a multiple multi-level longitudinal data analysis with structural equation model (with level of significance fixed at 0.05). Results Compared to healthy subjects, baseline protein levels of EV associated VWF and SerpinF2 were significantly higher in post-AMI patients, whereas no difference was observed in SerpinC1 and plasminogen. Among the patients, those on statins (196 out of 200 patients) showed lower protein levels of EV associated VWF (p&lt;0.001) and plasminogen (p=0.003), whereas patients treated with P2Y12 platelet inhibitors (195 out of 200 patients) showed higher protein levels of EV associated VWF (p=0.003) and plasminogen (p=0.035). Multiple multi-level longitudinal data analysis with structural equation model showed that protein levels of EV associated VWF (p&lt;0.001) and SerpinC1 (p=0.021) were lower in patients with adverse LV remodeling than that in patients with reverse LV remodeling during the 6-month follow-up post-AMI. In contrast, protein levels of EV associated plasminogen (p=0.002) and SerpinF2 (p=0.002) were higher in patients with adverse LV remodeling. The differences in the four EV associated proteins between patients with adverse versus reverse LV remodeling remain significant after adjusting for age, gender, ethnicity, medications, lipid profile and risk factors (diabetes, hypertension, dyslipidemia and smoking). Conclusions Lower levels of EV associated coagulation proteins (VWF and SerpinC1) and higher levels of EV associated fibrinolytic proteins (plasminogen and SerpinF2) were presented in patients with adverse LV remodeling compared to those with reverse LV remodeling post-AMI. Acknowledgement/Funding National University Health System Singapore (NUHS O-CRG 2016 Oct-23) to JW Wang

Commentary: Elucidating the mechanisms underlying left ventricular function recovery in patients with ischemic heart failure undergoing surgical remodeling: Physiology versus Empiricism

Ventricular remodeling, the geometric adaptation to injury after acute myocardial infarction, affects the function of both non-infarcted and infarcted muscle, as well as prognosis. Ventricular dilatation bodes especially poorly for late survival.1 It has long been recognized that early infarct expansion is the result of lengthening of the noncontractile region undergoing a stress response with secondary volume overload hypertrophy, a process which maybe progressive over time.2–4⇓⇓ The extent of the initial myocardial damage is linked both to the magnitude and, to a lesser degree, the timing of left ventricular (LV) dilatation and ultimately survival.5 Moreover, ventricular remodeling (enlargement) is influenced not only by infarct size but also the type of infarct healing and coexistent LV wall stresses.5 See p 2351 The most effective interventions to limit or prevent ventricular dilatation after infarction are those addressing the initial myocardial insult through the earliest and most sustained reperfusion therapies.6 The re-establishment of coronary blood flow to the infarcted region, even if delayed in some circumstances, is thought to attenuate ventricular remodeling. Modification of those biochemical and physiological factors that deform the compromised ventricle also influences late ventricular adaptive responses and prognosis. It is now common knowledge that instituting afterload reduction improves ventricular remodeling, attenuates infarct expansion, and provides long-term clinical improvement.1 However, of the three major factors involved in the acute infarct remodeling sequence, cardiologists can exert the most influence only at the onset through the timeliness and …

We sought to examine the impact of coronary chronic total occlusion (CTO) percutaneous coronary intervention (PCI) on left ventricular (LV) function. We performed a systematic review and meta-analysis of studies published between January 1980 and November 2017 on the impact of successful CTO PCI on LV function. A total of 34 observational studies including 2735 patients were included in the meta-analysis. Over a weighted mean follow-up of 7.9 months, successful CTO PCI was associated with an increase in LV ejection fraction by 3.8% (95%CI 3.0-4.7, P < 0.0001, I2 = 45%). In secondary analysis of 15 studies (1248 patients) that defined CTOs as occlusions of at least 3-month duration and reported follow-up of at least 3-months after the procedure, successful CTO PCI was associated with improvement in LV ejection fraction by 4.3% (95%CI [3.1, 5.6], P < 0.0001). In the 10 studies (502 patients) that reported LV end-systolic volume, successful CTO PCI was associated with a decrease in LV end-systolic volume by 4 mL, (95%CI -6.0 to -2.1, P < 0.0001, I2 = 0%). LV end-diastolic volume was reported in 9 studies with 403 patients and did not significantly change after successful CTO PCI (-2.3 mL, 95%CI -5.7 to 1.2 mL, P = 0.19, I2 = 0%). Successful CTO PCI is associated with a statistically significant improvement in LV ejection fraction and decrease in LV end-systolic volume, that may reflect a beneficial effect of CTO recanalization on LV remodeling. The clinical implications of these findings warrant further investigation.

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Objective — to determine the most important markers for predicting of the development of prediction of adverse left ventricular (LV) remodeling in patients within 1 year after acute ST‑segment elevation myocardial infarction (STEMI).&#x0D; Materials and methods. The study involved 134 patients with acute STEMI, 95 (70.9 %) men and 39 (29.1 %) women, who satisfied inclusion criteria and had no exclusion criteria. All of them were hospitalized in the emergency department of L.T. Mala National Therapy Institute of NAMS of Ukraine from January 2018 to February 2021. All patients underwent myocardial revascularization by percutaneous coronary intervention (PCI) within 2 — 12 hours after the event in the V. T. Zaytsev Institute of General and Emergency Surgery. TIMI — 3 flow was restored in all 134 patients. Within 1 — 3 days after revascularization patients were transferred to the research center.&#x0D; Late adverse LV remodeling was defined as elevated LV end diastolic volume (LVEDV) &gt; 10 % and/or LV end systolic volume (LVESV) &gt; 10 % within 1 year after the index event. Serum soluble tumor suppressor‑2 (sST2) levels were determined by enzyme‑linked immunosorbent assay (Presage ST2 Assay, Critical Diagnostics, USA), N‑Terminal Pro‑Brain Natriuretic Peptide (NT‑proBNP) was detected by R&amp;D Systems GmbH, Wiesbaden‑Nordenstadt, Germany), macrophage inhibitory factor (MIF) in blood serum serum was determined by enzyme‑linked immunosorbent assay RayBio®Human MIF ELISA KIT, USA). Statistical analysis was performed using Statistica 8.0 (Stat Soft Inc, USA).&#x0D; Results. Patients were divided into two groups: group 1 included 48 patients with adverse LV remodeling and group 2 consisted of 86 patients without LV remodeling. Uni‑ and multivariate log‑regression analysis demonstrated that LV ejection fraction (EF), MIF, number of damaged coronary vessels, sST2, longitudinal strain were independent predictors of adverse LV remodeling. Analysis of ROC curves showed that the cumulative value of markers such as MIF, ST2, longitudinal strain, number of damaged vessels, LV ejection fraction (AUC = 0.718; p &lt; 0.0001, 95 %, CI 0.634 — 0.792) allows to identify patients with high risk of the development of adverse LV remodeling in patients within 1 year after acute STEMI. The formula with these markers was found out, that can be used to predict adverse LV remodeling: the prognosis of positive effect at Y ≥ 0.5, negative — at Y &lt; 0.5.&#x0D; Conclusions. The study results demonstrated that LV ejection fraction, MIF, number of damaged coronary arteries, sST2, and global longitudinal strain can be used as predictors of adverse LV remodeling.&#x0D;

The identification of patients with a high likelihood of left ventricular (LV) remodeling with a high-risk prognosis has critical implications for risk stratification after acute ST-segment elevation myocardial infarction (STEMI). This study aimed to evaluate the relationship between circulating miR-1 and 6-month post-infarct LV remodeling based on cardiac magnetic resonance (CMR) imaging. A total of 80 patients with a first STEMI treated with primary percutaneous coronary intervention (PCI) who underwent CMR imaging 1 week and 6 months after STEMI were evaluated. The percentage changes of LV ejection fraction (LVEF), LV end-diastolic volume (LVEDV), LV end-systolic volume index (LVESV) at 1 week and 6 months after PCI (%ΔLVEF, %ΔLVEDV and %ΔLVESV) were calculated. miR-1 was measured using polymerase chain reaction (PCR)-based technologies in plasma samples that were collected at admission. The study group was divided into two groups based on a 10% cutoff value for the percentage of change in the LV end-diastolic volume (%ΔLVEDV): remodeling at high risk of major adverse cardiac events (MACEs) (%ΔLVEDV ≥10%, termed the LV remodeling group) and remodeling at lower risk of MACEs (%ΔLVEDV <10%, termed the non-LV remodeling group). The associations of miR-1 expression with the %ΔLVEDV, percentage change in the LV end-systolic volume (%ΔLVESV), and percentage change in the LV ejection fraction at follow-up were estimated. Twenty-two patients (27.5%) showed adverse LV remodeling, and 58 patients (72.5%) did not show adverse LV remodeling at the 6-month follow-up of CMR. The mean LVEF, LVEDV index, and LVESV index values at 1 week were 50.6%±8.2%, 74.6±12.8 mL/m2, and 37.2±10.2 mL/m2, respectively. Mean LVEF at follow-up (53.5%±10.6%) was increased compared with baseline (P<0.001). There were significant decreases in LVEDV index and LVESV index values at follow-up (72.0±14.9 mL/m2 and 33.7±11.0 mL/m2, respectively; P=0.009 and P<0.001, respectively). The expression of miR-1 at admission was positively correlated with the %ΔLVEDV (r=0.611, P<0.001) and %ΔLVESV (r=0.268, P=0.016). Receiver operating characteristic (ROC) analysis showed that miR-1 expression predicted LV remodeling with an area under the curve (AUC) value of 0.68 (95% CI: 0.56-0.78). Compared with the clinical factors of peak creatine kinase-myocardial band (CK-MB) and peak troponin T level, peak logNT-proBNP showed the highest predictive power, with an AUC value of 0.75 (95% CI: 0.64-0.84). A model including the clinical, CMR, and miR-1 factors showed greater predictive power (P=0.034) than a model including only clinical and CMR factors, with AUCs of 0.89 (95% CI: 0.80-0.95) and 0.81 (95% CI: 0.71-0.89), respectively. Circulating miR-1 at admission is an independent predictor of LV remodeling 6 months after STEMI. miR-1 showed incremental value in predicting LV remodeling compared with the clinical and CMR measurements.

Objective To study the relation between white blood cell (WBC) count and left ventricular (LV) remodeling after emergency percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI).Methods A total of 117 ST segment elevation AMI patients having underwent emergency PCI were enrolled.WBC count,cardiac troponin Ⅰ (cTnI),high-sensitivity C-reactive protein (hs-CRP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were obtained at admission before PCI.According to the WBC count level,patients were divided into normal WBC group (WBC count ≤ 10 ×109/L,60 cases) and elevated WBC group (WBC count ＞ 10 × 109/L,57 cases).Two-dimensional echocardiography was applied after PCI.The relation between WBC count and LV remodeling prognosis including LV ejection fraction (LVEF),LV end diastolic diameter (LVEDD) and LV aneurysm were compared after AMI.Results Admission NT-proBNP,hs-CRP and cTnI peak in elevated WBC group were higher than those in normal WBC group [ (2408.83 ± 3173.39) pg/L vs.(713.11 ± 636.82) pg/L,(39.64 ± 59.51) mg/L vs.(11.23 ± 14.14) mg/L,(107.76 ± 107.71) pg/L vs.(62.23 ± 87.79) pg/L,P ＜0.05].Admission WBC count was positively correlated with LVEDD and negatively correlated with LVEF (P ＜0.01 ).Patients with LV aneurysm had higher WBC count than those without LV aneurysm[ ( 12.59 ± 5.22) × 109/L vs. (9.27 ± 2.60) × 109/L,P =0.001 ].Multivariate analyses showed that admission WBC count ≥ 10.5 × 109/L was an independent determinant of LV aneurysm(OR =22.5,95％ CI:2.69-187.83,P ＜ 0.01 ),and this cut-off value yielded sensitivity of 76.9％ and specificity of 69.7％ respectively.Conclusion Admission WBC count may be considered as a prognostic biological tag in the prediction of the development of LV remodeling after emergency PCI in patients with AMI. Key words: Myocardial infarction; Leukocytes; Ventricular remodeling

Objective To investigate the effect of time from myocardial infarction (MI) onset to percutaneous coronary intervention (PCI) on plasma matrix metalloproteinases (MMPs) level and left ventricle (LV) remodeling in patients with acute ST-segment elevation myocardial infarction of anterior wall, and the relationship between MMPs and left ventricular remodeling. Methods All patients with anterior wall STEMI undergoing PCI were divided into early PCI group (PCI within 18 h after MI onset) and delayed PCI group (PCI between 2 and 3 weeks after MI onset). Plasma MMP-2 and MMP-9 activities were assayed on admission, and at 2 days, 1 week after admission. One-year follow-up was finished after PCI. Left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV) and left ventricle ejection fraction (LVEF) were measured by echocardiography at baseline and one year later to elucidate the effects of time from onset to PCI on LV remodeling and the relationship between MMP-2, -9 levels and LV remodeling. Results The MMP-9 activity at 2 days after myocardial infarction was lower in early PCI group than in delayed PCI group〔(46±26)μg/L vs. (66±40) μg/L, P=0.000〕. The changes in LVEDV and LVESV (ΔLVEDV and ΔLVESV) were lower and the change in LVEF (ΔLVEF) was higher in early PCI group than in delayed PCI group〔(10.9±6.2) ml vs. (15.0±6.0) ml, (–1.1±5.7) ml vs. (2.9±4.6) ml, (5.5±4.0) % vs. (3.8±3.4) %, P=0.000, 0.000 and 0.015〕. MMP-9 had positive correlations with ΔLVEDV and ΔLVESV, and a negative correlation with ΔLVEF at admission and after 1-year follow-up (r=0.32, 0.36 and–0.29, respectively, P=0.000, 0.000 and 0.001). Conclusions MMP-9 activity at admission is correlated with LV remodeling and LV function. Early PCI can reduce MMP-9 activity and improve LV remodeling after myocardial infarction. Key words: Myocardial infarction; Ventricle remodeling; Matrix metalloproteinases