Markers Of Left Ventricular Remodeling Research Articles

MMP - 9 is a potential prognostic marker of left ventricular remodeling in patients with coronary artery atherosclerosis

MMP - 9 is a potential prognostic marker of left ventricular remodeling in patients with coronary artery atherosclerosis

The impact of a viable myocardium on markers of left ventricular remodeling after an acute myocardial infarction

Patients with AMI were investigated to determine the impact of a viable myocardial on LV remodeling characteristics. Study participants included 93 patients with an ST-segment elevation in acute coronary syndrome. Stress echocardiograms using dobutamine were performed on each subject.All patients had echocardiography and coronary angiography one and six months following coronary angioplasty. Patients with and without viable areas were split into two groups based on the outcomes of dobutamine stress echocardiography: group I had viable areas, while group II did not. Wall-motion score index, endsystolic volume index (ESVI), end-diastolic volume index (EDVI), and left ventricular ejection fraction (LVEF) were the metrics used to compare the two groups. Therefore, individuals with increasing left ventricular dilatation following reperfusion are distinguished from those with normal left ventricular geometry

MMP-9 is a Potential Prognostic Marker of Left Ventricular Remodeling in Patients with Coronary Artery Disease

MMP-9 is a Potential Prognostic Marker of Left Ventricular Remodeling in Patients with Coronary Artery Disease

How Effective Is a Late-Onset Antihypertensive Treatment? Studies with Captopril as Monotherapy and in Combination with Nifedipine in Old Spontaneously Hypertensive Rats.

Background: A major problem in the treatment of human hypertension is the late diagnosis of hypertension and, hence, the delayed start of treatment. Very often, hypertension has existed for a long time and cardiac damage has already developed. Therefore, we tested whether late-onset antihypertensive treatment is effective in lowering blood pressure (BP) and in reducing or even preventing left ventricular hypertrophy and fibrosis. Methods: Twenty-one male 60-week-old spontaneously hypertensive rats (SHR) were included. Fourteen rats received oral treatment with captopril (CAP) either as monotherapy or combined with nifedipine (CAP + NIF) over 22 weeks. Seven untreated SHR served as controls. We examined the therapeutic effects on BP, heart weight and histological and biochemical markers of left ventricular remodeling and fibrosis. Results: At 82 weeks of age, BP was reduced in the CAP and CAP + NIF groups by 44 and 51 mmHg, respectively (p < 0.001), but not in untreated controls. Despite the late therapy start, cardiac hypertrophy and fibrosis were attenuated compared to controls. Both treatments reduced heart weight by 1.2 mg/g (25%, p = 0.001) and collagens I and III by 66% and 60%, respectively (p < 0.001), thus proving nearly equivalent cardioprotective efficacy. Conclusion: These data clearly emphasize the benefit of antihypertensive treatment in reducing BP and mitigating the development of cardiac damage even when treatment is started late in life.

Impact of First-Phase Ejection Fraction on Clinical Outcomes in Patients Undergoing Transcatheter Aortic Valve Implantation

BackgroundFirst-phase left ventricular ejection fraction (LVEF1) is an early marker of left ventricular remodeling. Reduced LVEF1 has been associated with adverse prognosis in patients with aortic stenosis (AS) and preserved left ventricular ejection fraction (LVEF). It remains to be determined, whether reduced LVEF1 differentiates clinical outcomes after aortic valve replacement. ObjectivesWe investigated the impact of LVEF1 on clinical outcomes in patients undergoing transcatheter aortic valve implantation (TAVI) for symptomatic severe AS with preserved LVEF (≥ 50%). MethodsIn the prospective Bern TAVI registry, we retrospectively categorized patients according to LVEF1 as assessed by transthoracic echocardiography. Clinical outcomes of interest were all-cause mortality and residual heart failure symptoms (New York Heart Association (NYHA) functional class III or IV) at 1 year after TAVI. ResultsA total of 644 patients undergoing TAVI between January 2014 and December 2019 were included in the present analysis. Patients with low LVEF1 had a lower LVEF (62.0 ± 6.89% vs. 64.3 ± 7.82%, P < 0.001) and a higher left ventricular mass index (129.3 ± 39.1 g/m2 vs. 121.5 ± 38.0 g/m2; P = 0.027) compared to patients with high LVEF1. At 1 year, the incidence of all-cause/cardiovascular death, and NYHA III or IV were comparable between patients with low and high LVEF1 (8.3% vs. 9.2%; P = 0.773, 3.9% vs. 6.0%; P = 0.276, 12.9% vs. 12.2%; P = 0.892, respectively). ConclusionsReduced LVEF1 was not associated with adverse clinical outcomes following TAVI in patients with symptomatic severe AS with preserved LVEF. Clinical trial registrationhttps://www.clinicaltrials.gov. NCT01368250.

Abstract 14646: Left Ventricular Global Longitudinal Strain and CT Derived Extracellular Volume Predicts Outcomes in Patients With Low-flow, Low-gradient Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement

Introduction: Low-flow, low-gradient aortic stenosis (LFLG-AS) is associated with impaired left ventricular (LV) function and afterload mismatch. Indications and timing for transcatheter aortic valve replacement (TAVR) in LFLG-AS do not account for the presence of subclinical LV remodeling. We evaluated whether combining LV global longitudinal strain (GLS) and CT-derived extracellular volume (ECV), both markers of LV remodeling, provides incremental prediction of adverse outcomes in patients with LFLG-AS undergoing TAVR. Methods: We retrospectively evaluated patients with LFLG-AS undergoing TAVR in whom pre-TAVR CT-based ECV measurements were available. GLS was measured in pre-TAVR echocardiograms using speckle tracking. Cox regression analysis was performed with a primary outcome of heart failure hospitalization (HFH) or death. Four sub-groups were identified for analysis based on optimal cutoff points: Group 1 (n=64): ECV&lt; 33 + GLS≥

Can left ventricular global function index be a novel marker of unfavorable outcome in patients with acute coronary syndrome

Abstract Left ventricular (LV) global function index (LVGFI) is a MRI marker of left ventricular remodeling. LVGFI has high predictive significance in young healthy individuals. The aim of the study was to assess prognostic significance in patients with acute coronary syndrome (ACS). We include into this analysis 2169 patients with ACS (1340 (61.8%) men and 829 (38.2%) women), mean age 64.08±12.601 years. All patients were observed in 2 Russian multicenter observational studies: ORACLE I (ObseRvation after Acute Coronary syndrome for deveLopment of trEatment options) (2004–2007 years) and ORACLE II (NCT04068909) (2014–2019 years). 1886 (87.0%) pts had arterial hypertension, 1539 (71.0%) – history of coronary artery disease, 647 (29.8%) – history of myocardial infarction, 444 (20.5%) - diabetes mellitus. Duration of the follow-up was 1 years after the hospital discharge. Cases of death from any cause, coronary deaths, repeated coronary events (fatal and non-fatal) were recorded. An echocardiographic study was conducted 5–7 days from the time of hospitalization. The LVGFI was defined as LV stroke volume/LV global volume × 100, where LV global volume was the sum of the LV mean cavity volume ((LV end-diastolic volume + LV end-systolic volume)/2) and myocardial volume (LV mass/density). During the follow-up, 193 deaths were recorded (8.9%), 122 deaths (5.6%) were coronary. In total, repeated coronary events were recorded in 253 (11.7%) patients. Mean LVGFI was 22.64±8.121%. Patients who died during the follow-up were older (73.03±10.936 years and 63.15±12.429 years, p=0.001), had a higher blood glucose level at the admission to the hospital (8.12±3.887 mmol/L and 7.17±3.355 mmol/L, p=0.041), serum creatinine (110.86±53.954 μmol/L and 99.25±30.273 μmol/L, p=0.007), maximum systolic blood pressure (196.3±25.17 mm Hg and 190.3±27.83 mm Hg, p=0.042). Those who died had a lower LVGFI value (19.75±6.77% and 23.01±8.243%, p&amp;lt;0.001). Myocardial mass index, ejection fraction and other left ventricular parameters did not significantly differ between died and alive patients. Among the patients who died, there were higher rate of women, pts with a history of myocardial infarction, heart failure, diabetes. In a multivariate analysis, diabetes mellitus OR1.67 95% CI [1.12–2.51] p=0.012, history of heart failure (1.78 [1.2.-2.59], p=0.003), a history of myocardial infarction (1.47 [1.05–2.05], p=0024), age (1.06 [1.05–1.08], p=0.001) and LVGFI &amp;lt;22% (1.53 [1.08–2.17], p=0.015) were independent predictors of death from any cause. The LVGFI was also independently associated with the risk of coronary death, but not with the risk of all recurring coronary events. Thus, LVGFI may be useful the marker to assess risk in patients who have experienced an ACS episode. Funding Acknowledgement Type of funding source: None

Serum Levels of Bone Morphogenetic Proteins 2 and 4 in Patients with Acute Myocardial Infarction.

Background: Bone morphogenetic proteins-2 and -4 (BMPs) have been implicated in left ventricular remodeling (LVR) processes such as an inflammation and fibrogenesis. We hypothesized that this knowledge could be translated into clinics. Methods: We studied the dynamics of serum levels of BMPs, its correlation with markers of LVR and with parameters of echocardiography in patients (n = 31) during the six-month follow-up period after myocardial infarction (MI). Results: Elevated serum levels of BMPs decreased by the six-month follow-up period. BMP-2 decreased from the first day after MI, and BMP-4 decreased from the Day 14. The elevated level of BMP-2 at Day 1 was associated with a lower level of troponin I, reperfusion time and better left ventricular ejection fraction (LV EF) at the six-month follow-up. Elevated serum level of BMP-4 at Day 1 was associated with a lower level of a soluble isoform of suppression of tumorigenicity 2 (sST2), age and reperfusion time. An elevated level of BMP-2 at the six-month follow-up was associated with higher levels of BMP-4, high-sensitivity C-reactive protein (hCRP) and sST2. High serum level of BMP-2 correlated with high levels of hCRP and matrix metalloproteinase (MMP)-9 on Day 7. High serum level of BMP-4 correlated with low levels of hCRP, MMP-9 at Day 3, sST2 at Day 1 and with decreased LV EF on Day 7. The findings of multivariate analysis support the involvement of BMP-2 in the development of post-infarction LVR. Conclusions: Our research translates experimental data about the BMPs in the development of adverse LVR into the clinic. Elevated serum levels of BMPs decreased by the end of the six-month period after MI. BMP-2 decreased from the first day and BMP-4 decreased from Day 14. BMP-2 and BMP-4 were associated with the development of LVR. Their correlations with markers of inflammation, degradation of the extracellular matrix, hemodynamic stress and markers of myocardial damage further support our hypothesis. Diagnostic and predictive values of these BMPs at the development of post-infarction LVR in vivo should be investigated further.

Multiparametric PET and MRI of myocardial damage after myocardial infarction: correlation of integrin \u03b1v\u03b23 expression and myocardial blood flow

PurposeIncreased angiogenesis after myocardial infarction is considered an important favorable prognostic parameter. The αvβ3 integrin is a key mediator of cell-cell and cell-matrix interactions and an important molecular target for imaging of neovasculature and repair processes after MI. Thus, imaging of αvβ3 expression might provide a novel biomarker for assessment of myocardial angiogenesis as a prognostic marker of left ventricular remodeling after MI. Currently, there is limited data available regarding the association of myocardial blood flow and αvβ3 integrin expression after myocardial infarction in humans.MethodsTwelve patients were examined 31 ± 14 days after MI with PET/CT using [18F]Galacto-RGD and [13N]NH3 and with cardiac MRI including late enhancement on the same day. Normal myocardium (remote) and areas of infarction (lesion) were identified on the [18F]Galacto-RGD PET/CT images by correlation with [13N]NH3 PET and cardiac MRI. Lesion/liver-, lesion/blood-, and lesion/remote ratios were calculated. Blood flow and [18F]Galacto-RGD uptake were quantified and correlated for each myocardial segment (AHA 17-segment model).ResultsIn 5 patients, increased [18F]Galacto-RGD uptake was notable within or adjacent to the infarction areas with a lesion/remote ratio of 46% (26–83%; lesion/blood 1.15 ± 0.06; lesion/liver 0.61 ± 0.18). [18F]Galacto-RGD uptake correlated significantly with infarct size (R = 0.73; p = 0.016). Moreover, it correlated significantly with restricted blood flow for all myocardial segments (R = − 0.39; p < 0.0001) and even stronger in severely hypoperfused areas (R = − 0.75; p < 0.0001).Conclusion[18F]Galacto-RGD PET/CT allows the visualization and quantification of myocardial αvβ3 expression as a key player in angiogenesis in a subset of patients after MI. αvβ3 expression was more pronounced in patients with larger infarcts and was generally more intense but not restricted to areas with more impaired blood flow, proving that tracer uptake was largely independent of unspecific perfusion effects. Based on these promising results, larger prospective studies are warranted to evaluate the potential of αvβ3 imaging for assessment of myocardial angiogenesis and prediction of ventricular remodeling.

Cardiac MRI measurements of pericardial adipose tissue volumes in patients on in-centre nocturnal hemodialysis.

Conversion from conventional hemodialysis (CHD) to in-centre nocturnal hemodialysis (INHD) is associated with left ventricular (LV) mass regression, but the underlying mechanisms are not fully understood. Using cardiac MRI (CMR), we examined the effects of INHD on epicardial adipose tissue (EAT) and paracardial adipose tissue (PAT), and the relationships between EAT, PAT and LV remodeling, biomarkers of nutrition, myocardial injury, fibrosis and volume. We conducted a prospective multicenter cohort study of 37 patients transitioned from CHD to INHD and 30 patients on CHD (control). Biochemical markers and CMR were performed at baseline and 52weeks. CMR images were analyzed by independent readers, blinded to order and treatment group. Among 64 participants with complete CMR studies at baseline (mean age 54; 43% women), there were no significant differences in EAT index(60.6 ± 4.3mL/m2 vs 64.2 ± 5.1mL/m2, p = 0.99) or PATindex (60.0 ± 5.4mL/m2 vs 53.2 ± 5.9mL/m2, p = 0.42) between INHD and CHD groups. Over 52weeks, EATindex and PAT indexdid not change significantly in INHD and CHD groups (p = 0.21 and 0.14, respectively), and the changes in EATindex and PATindex did not differ significantly between INHD and CHD groups (p = 0.30 and 0.16, respectively). Overall, changes in EAT indexinversely correlated with changes in LV end-systolic volume index (LVESVI) but not LV end-diastolic volume index (LVEDVI), LV mass index (LVMI), and LV ejection fraction (LVEF). Changes in PATindex inversely correlated with changes in LVESVI, LVMI and positively correlated with changes in LVEF. There were no correlations between changes in EAT indexor PAT indexwith changes in albumin, LDL, triglycerides, troponin-I, FGF-23, or NT-proBNP levels over 52weeks (all p > 0.30). INHD was not associated with any changes in EATindex and PATindex over 12months. Changes in EATindex were not significantly associated with changes in markers of LV remodeling, nutrition, myocardial injury, fibrosis, volume status. In contrast, changes in PATindex, which paradoxically is expected to exert less paracrine effect on the myocardium, were correlated with changes in LVESVI, LVMI and LVEF. Larger and longer-term studies may clarify the role of PAT in cardiac remodeling with intensified hemodialysis. CLINICALTRIALS. NCT00718848.

Abstract P138: Asthma and Left Ventricular Mass in Young Adults: the Bogalusa Heart Study

Background: A history of asthma from childhood has been related to various risk factors affecting left ventricular (LV) remodeling; however, no prospective study has analyzed the impact of asthma on markers of LV remodeling. Methods: Prospective analyses were performed among 1177 Bogalusa Heart Study participants (average age at follow-up: 36.3±8.3), with a baseline history of self-reported asthma collected since childhood (mean first diagnosed age: 25.2±10.3). LV mass was assessed using 2-dimensional guided M-mode echocardiography, and indexed for body height (m 2.7 ) as LV mass index (LVMI, g/m 2.7 ). A multivariate linear mixed model was fitted for the repeated measures. Results: After an average of 9.1 years follow-up, participants with a history of asthma showed significantly greater LV mass (166.9 vs. 156.3, p=0.007) and LVMI (40.1 vs. 37.1, p=0.002) than those without asthma, with adjustment for age, gender, race, smoking status, antihypertensive medicine, heart rate and systolic blood pressure (SBP) at follow-up. Also, we found significant interactions between SBP and asthma on LV mass and LVMI (p for interaction= 0.008 and 0.006). The associations between asthma and LV measures appeared to be stronger among prehypertensive participants (SBP≥130 mm/Hg) compared with those with normal SBP (&lt;130 mm/Hg) [regression coefficient: 26.12 vs. -0.79 for LV mass; and 6.75 vs. 0.29 for LVMI]. Conclusions: Our findings indicate that a history of asthma is associated with higher LV mass, and such association is stronger among individuals with prehypertension.

Abstract 15545: Incremental Prognostic Value of Echocardiographic Markers of Left Ventricular Remodeling and Diastolic Function in the Surgical Treatment for Ischemic Heart Failure Trial

Introduction: Whether echocardiographic (echo) markers of left ventricular (LV) remodeling and diastolic dysfunction contribute incremental and independent prognostic information to clinical risk markers in patients (Pts) with coronary artery disease and severe LV systolic dysfunction is unclear. We sought to determine which echo variables provide the greatest prognostic value in the Surgical Treatment for Ischemic Heart Failure (STICH) population. Methods: Pts enrolled in STICH for whom transmitral Doppler (E/A ratio) was available on a baseline echo interpreted by an echo core laboratory blinded to treatment and outcomes formed the analysis cohort. Comprehensive datasets to account for missing echo data were created by multiple imputation and the impact on all-cause mortality was determined with the Cox’s regression model. Results: E/A ratio could be measured in 1511 of the 2136 Pts enrolled in STICH. Amongst markers of diastolic dysfunction, E/A ratio was the most significant predictor of mortality (χ 2 41.05, p &lt;0.001) with a non-linear, u-shaped, relationship. Mortality was lowest with E/A ratio = 1.0, and increased for E/A ratio &lt;0.6 and &gt;1.0 up to 2.3, beyond which there was no further increase in risk. The combination of larger LV end-systolic volume index (LVESVI), low or high E/A ratio, and mitral regurgitation severity grade, had highly significant incremental negative effects on mortality (χ 2 69.65, p&lt;0.001) when added to a multivariable model with clinical risk markers. Overall, creatinine (χ 2 30.00, p &lt;0.001), followed by LVESVI (χ 2 27.26, p&lt;0.001), age, and E/A ratio (χ 2 12.46, p&lt;0.001) were among the most significant predictors of mortality and accounted for 74% of the total prognostic information. LVESVI and E/A ratio were stronger predictors of poor prognosis than New York Heart Association (NYHA) functional class, hemoglobin, diabetes, stroke, or atrial fibrillation. Conclusions: Echo markers of advanced LV remodeling and diastolic dysfunction add incremental prognostic value to clinical risk markers and are more predictive of poor prognosis than advanced NYHA functional class or anemia. LVESVI and E/A ratio outperformed other echo markers and should be considered standard in assessing risk in Pts with ischemic LV dysfunction.

Relation of Thoracic Aortic Distensibility to Left Ventricular Area (from the Multi-Ethnic Study of Atherosclerosis [MESA

Decreased arterial compliance is an early manifestation of adverse structural and functional changes within the vessel wall. Its correlation with left ventricular (LV) area on computed tomography, a marker of LV remodeling, has not been well demonstrated. The aim of this study was to test the hypothesis that decreasing aortic compliance and increasing arterial stiffness are independently associated with increased LV area. The study population consisted of 3,540 patients (mean age 61 ± 10 years, 46% men) from the Multi-Ethnic Study of Atherosclerosis (MESA) who underwent aortic distensibility (AD) assessment on magnetic resonance imaging and LV area measurement on computed tomography (adjusted to body surface area). Multivariate logistic regression was performed to assess the association between body surface area-normalized LV area >75th percentile and AD after adjusting for baseline clinical, historical, and imaging covariates. Mean LV area index was 2,153 cm(2), and mean AD was 1.84 × 10(3) mm Hg(-1). Subjects in the lowest AD quartile were older, with higher prevalence rates of hypertension, diabetes, and hypercholesterolemia (p <0.05 for all comparisons). Using multivariate linear regression adjusting for demographics, traditional risk factors, coronary artery calcium, and C-reactive protein, each SD decrease was associated with an 18-cm(2) increase in LV area. In addition, decreasing AD quartiles were independently associated with increasing LV area index, defined as >75th percentile. In conclusion, in this multiethnic cohort, reduced AD was associated with increased LV area. Longitudinal studies are needed to determine if decreased distensibility precedes and directly influences increased LV area.

Effects of Frequent Hemodialysis on Ventricular Volumes and Left Ventricular Remodeling

Higher left ventricular volume is associated with death in patients with ESRD. This work investigated the effects of frequent hemodialysis on ventricular volumes and left ventricular remodeling. The Frequent Hemodialysis Network daily trial randomized 245 patients to 12 months of six times per week versus three times per week in-center hemodialysis; the Frequent Hemodialysis Network nocturnal trial randomized 87 patients to 12 months of six times per week nocturnal hemodialysis versus three times per week predominantly home-based hemodialysis. Left and right ventricular end systolic and diastolic volumes, left ventricular mass, and ejection fraction at baseline and end of the study were ascertained by cardiac magnetic resonance imaging. The ratio of left ventricular mass/left ventricular end diastolic volume was used as a surrogate marker of left ventricular remodeling. In each trial, the effect of frequent dialysis on left or right ventricular end diastolic volume was tested between predefined subgroups. In the daily trial, frequent hemodialysis resulted in significant reductions in left ventricular end diastolic volume (-11.0% [95% confidence interval, -16.1% to -5.5%]), left ventricular end systolic volume (-14.8% [-22.7% to -6.2%]), right ventricular end diastolic volume (-11.6% [-19.0% to -3.6%]), and a trend for right ventricular end systolic volume (-11.3% [-21.4% to 0.1%]) compared with conventional therapy. The magnitude of reduction in left and right ventricular end diastolic volumes with frequent hemodialysis was accentuated among patients with residual urine output<100 ml/d (P value [interaction]=0.02). In the nocturnal trial, there were no significant changes in left or right ventricular volumes. The frequent dialysis interventions had no substantial effect on the ratio of left ventricular mass/left ventricular end diastolic volume in either trial. Frequent in-center hemodialysis reduces left and right ventricular end systolic and diastolic ventricular volumes as well as left ventricular mass, but it does not affect left ventricular remodeling.

Effects of telmisartan on markers of ventricular remodeling in patients with acute myocardial infarction: comparison with enalapril

Enalapril is effective in the suppression of left ventricular remodeling after acute myocardial infarction (AMI), but the effect of telmisartan is unclear. The consecutive 163 AMI patients underwent primary percutaneous coronary intervention and were randomized to telmisartan (n=82) or enalapril (n=81). Left ventriculography was performed in the acute and chronic (6months) phases. Matrix metalloproteinase (MMP)-2 and MMP-9 activities were measured by zymography in the acute (days 1, 7, and 14) and chronic (6months) phases. Plasma pentraxin3 (PTX3), a marker of vascular inflammation, was also measured. There were no adverse effects in the telmisartan group. The analysis of the left ventriculograms in the acute and chronic phases revealed no difference between the two groups. MMP-9 activities at days 7 and 14 and in the chronic phase were decreased compared to that at day 1 in both groups. MMP-2 activity was also decreased in the acute phase, but increased in the chronic phase in both groups. There was no difference in the plasma PTX3 level in the acute phase, but in the chronic phase, PTX3 was significantly lower in telmisartan than in enalapril group (2.6±1.4 vs. 3.2±1.6ng/ml, p=0.04). Telmisartan is well tolerated, shows similar effects on the markers of left ventricular remodeling to those of enalapril, and suppresses vascular inflammation more effectively than enalapril in AMI patients. Telmisartan can be an alternative to angiotensin converting enzyme inhibitor in patients with AMI.

Carvedilol administration in acute myocardial infarction results in stronger inhibition of early markers of left ventricular remodeling than metoprolol

Background The structural secuelae of acute myocardial infarction (AMI) is mostly dictated by left ventricular (LV) remodelling, leading to heart failure. Monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play a critical role in LV remodelling. β-blockers are first line therapy for AMI and heart failure; however, the mechanisms responsible for their benefits remain poorly understood. Different β-blocker agents have been shown to exert beneficial activities both in AMI and heart failure, however, their role in early remodelling after ischemia/reperfusion is to be fully elucidated. We sought to compare the effect of 2 of the most prescribed β-blocker agents in early markers of LV remodelling after AMI. Methods A reperfused AMI was induced in Yorshire pigs, being randomized to early intravenous carvedilol, metoprolol or placebo. Twenty-four hours after reperfusion markers of early remodelling were addressed in the LV. Results The early administration of both β-blockers is able to significantly reduce macrophage infiltration as well as the expression and activity of MCP-1 and MMP-2 compared to placebo. The effects of carvedilol were much stronger than those of metoprolol. Conversely, carvedilol upregulated the expression TIMP-2 to a greater extent than metoprolol. Conclusions In an AMI model closely mimicking human pathophysiology, the early administration of carvedilol reduced the expression of markers associated with early LV remodelling to greater extent than metoprolol. These findings may explain the superior clinical benefits exerted by carvedilol in heart failure.

Association of angiographic perfusion score following percutaneous coronary intervention for ST-elevation myocardial infarction with left ventricular remodeling at 6 weeks in GRACIA-2

Higher angiographic perfusion score (APS) following percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) has been shown to be associated with improved clinical outcomes. The association between APS after STEMI and left ventricular remodeling as assessed by volumetric parameters derived from left ventriculography has not been assessed. The APS (the arithmetic sum of the TIMI Flow Grade (TFG) and TIMI Myocardial Perfusion grade (TMPG) before and after percutaneous coronary intervention (PCI), range of 0-12) was assessed in 168 patients from the GRACIA-2 trial. Left ventriculograms performed in the 30 degrees right anterior oblique projection were obtained among 148 patients at initial angiography (prior to PCI) and at 6 weeks. The association of APS with markers of left ventricular remodeling at 6-weeks was examined using left ventricular ejection fraction, delta end systolic volume, delta stroke volume and wall motion index. Full perfusion (APS 10-12), as compared to partial perfusion (APS 4-9) or failed perfusion (APS 0-3), was associated with a greater left ventricular ejection fraction (61.6% +/- 10.0 vs. 56.9% +/- 12.5 vs. 49.8% +/- 16.9, P = 0.015), a decrease in left ventricular end systolic volume indicating favorable remodeling (mean -4.1 cc +/- 17.3 vs. +2.0 cc +/- 17.3 vs. +9.8 cc +/- 16.1, P = 0.015), a greater improvement in left ventricular stroke volume (mean +13.7 cc +/- 17.1 vs. +6.7 cc +/- 15.5 vs. +1.2 cc +/- 13.4, P = 0.009) and a decreased wall motion index (number of chords in the hypokinetic region) (mean 15.1 +/- 16.4 vs. 21.4 +/- 20.5 vs. 32.9 +/- 22.1, P = 0.026) at 6 weeks. In conclusion, among patients treated with combined reperfusion and revascularization strategies for STEMI, higher APS is associated with more favorable markers of left ventricular remodeling and improved 6-week left ventricular function.

Prohormone brain natriuretic peptide (proBNP), BNP and N-terminal-proBNP circulating levels in chronic hemodialysis patients. Correlation with ventricular function, fluid removal and effect of hemodiafiltration

Brain natriuretic peptide (BNP), N-terminal proBNP (NT-proBNP) and to a lesser extent prohormone proBNP are recognized as biochemical markers of left ventricular dysfunction. In renal failure, interpretation of natriuretic peptide remains unclear, as natriuretic peptide levels may be not only be dependent on cardiac function and dimensions but also on renal function, fluid volume and removal by dialysis procedure including hemodiafiltration (HDF). The purpose of this study was (i) to assess BNP, NT-proBNP and proBNP levels and their correlation with clinical and echocardiographic data in chronic hemodialysis patients, and (ii) to investigate basal level alteration following HDF. Baseline clinical and echocardiographic parameters were collected in 31 dialysis patients without evidence of cardiac failure. Pre- and post-HDF BNP, NT-proBNP and proBNP concentrations were measured. Correlations between echocardiographic measurements and basal circulating peptides, between changes in peptide values and changes in fluid volume after HDF were investigated. Baseline plasmatic levels were elevated (BNP=517+/-840 pg/mL, NT-proBNP=5340+/-6132 pg/mL and proBNP=3569+/-4683 pg/mL) and correlated with left auricular diameter and left ventricular mass index. HDF session induced a significant decrease of 39%, 59% and 36% for BNP, NT-proBNP and proBNP levels, respectively. This decrease was not correlated to post-HDF fluid removal or weight decrease. Correlation between BNP and proBNP was stronger (r(2)=0.88) than between NT-proBNP and proBNP (r(2)=0.54). Despite their elimination, BNP, NT-proBNP and proBNP could be potential markers of left ventricular remodeling in chronic renal failure patients on hemodialysis. According to these results, their cut-off values, however, need to be re-evaluated.

Significance of 8-Hydroxy-2′-Deoxyguanosine Levels in Patients With Idiopathic Dilated Cardiomyopathy

Background Although oxidative stress mediated by reactive oxygen species plays an important role in the pathogenesis of heart failure (HF), good clinical markers for reactive oxygen species in patients with HF have not been established. 8-hydroxy-2′-deoxyguanosine (8-OHdG) is formed from deoxyguanosine in DNA by hydroxyl free radicals and might serve as a sensitive biomarker of intracellular oxidative stress in vivo. Thioredoxin (TRX) is known to be induced in cells as a radical scavenger against oxidative stress. The aim of this study is to evaluate the clinical significance of the serum 8-OHdG and TRX of patients with chronic HF with idiopathic dilated cardiomyopathy (DCM). Methods and Results We estimated serum 8-OHdG and TRX levels using enzyme-linked immunosorbent assay in 32 patients with DCM and investigated the impact of these markers to the clinical characteristics of these patients. Serum levels of 8-OHdG, but not TRX were significantly correlated with New York Heart Association functional class, left atrial diameters, left ventricular end-diastolic diameters, left ventricular end-systolic diameters, and plasma levels of brain natriuretic peptide. Conclusion These data suggest oxidative DNA damage is increased in patients with DCM according to the severity of HF. Serum levels of 8-OHdG may represent clinically useful markers of left ventricular remodeling.

Echocardiography as a Noninvasive Swan-Ganz Catheter

Diwan and co-investigators report in this issue of Circulation that the interval between onset of mitral E and annular early diastolic velocity (Ea) by tissue Doppler, TE−Ea, can be used to estimate left ventricular (LV) filling pressure in patients with mitral valve disease.1 Garcia and colleagues were the first to report that the onset of Ea occurred 7.5±3.5 ms after peak mitral inflow velocity in 7 patients with restrictive cardiomyopathy, whereas Ea started 22±19 ms earlier than did E in the normal group.2 Subsequently, TE−Ea has been shown to correlate with the time constant of LV relaxation (τ) demonstrated by Hasegawa and associates in their elegant animal experiment.3 With worsening of heart failure by rapid pacing, Ea progressively decreased in velocity and delayed in onset. Mitral E occurred coincidently with the termination of the early diastolic left arterial (LA) and LV pressure gradient at baseline and all stages of heart failure. In contrast, with increasing heart failure, Ea was progressively delayed after LA to LV pressure crossover, and TE−Ea was related to τ. Rivas-Gotz, Nagueh, and their associates also demonstrated that TE−Ea was prolonged after constriction of the circumflex coronary artery in dogs.4 In patients with heart failure, LV myocardial relaxation and compliance are decreased. See p 3281 Although LV filling is initiated and enhanced by augmentable myocardial relaxation in healthy individuals, it is driven by high filling pressure in patients with heart failure because myocardial relaxation remains reduced, not being sensitive to preload. Myocardial relaxation also affects the isovolumic relaxation time (IVRT). As relaxation becomes abnormal, LV pressure falls more slowly and the opening of the mitral valve is delayed, resulting in a longer IVRT. IVRT, however, becomes shorter as LA pressure increases; hence, IVRT∝τ/LA pressure. Because TE−Ea∝τ, …