Tracey Steedman

Serum soluble ST2: a potential novel mediator in left ventricular and infarct remodeling after acute myocardial infarction.

OBJECTIVES This study sought to assess, for the first time, the relationship between serum concentrations of the soluble interleukin-1 receptor family member ST2 (sST2) and serial change in left ventricular (LV) function after acute myocardial infarction (AMI). BACKGROUND Serum sST2 levels are elevated early after AMI and are associated with lower pre-discharge LV ejection fraction and adverse cardiovascular outcomes. METHODS The sST2 levels were measured in 100 patients (mean age 58.9 +/- 12.0 years; 77% male), admitted with AMI with resultant LV systolic dysfunction, at baseline and at 12 and 24 weeks. Patients underwent cardiac magnetic resonance imaging and measurement of N-terminal pro-brain natriuretic peptide, norepinephrine, and aldosterone at each time point. RESULTS Median sST2 decreased from 263.3 pg/ml at baseline to 140.0 pg/ml at 24 weeks (p < 0.001). Serum sST2 correlated significantly with LV ejection fraction at baseline (r = -0.30, p = 0.002) and 24 weeks (r = -0.23, p = 0.026); change in sST2 correlated with change in LV end-diastolic volume index (r = -0.24, p = 0.023). Level of sST2 was positively associated with infarct volume index at baseline (r = 0.26, p = 0.005) and 24 weeks (r = 0.22, p = 0.037), and with change in infarct volume index (r = -0.28, p = 0.001). Level of sST2 was significantly higher in patients with greater infarct transmurality and endocardial extent, and in the presence of microvascular obstruction. Level of sST2 correlated significantly with norepinephrine and aldosterone, but not with N-terminal pro-brain natriuretic peptide. CONCLUSIONS Measurement of sST2 early after AMI assists in the prediction of medium-term LV functional recovery. Novel relationships were observed between sST2, infarct magnitude/evolution, and aldosterone. Serum sST2 may be of pathophysiological importance in ventricular and infarct remodeling after AMI. (Effects of Eplerenone on Left Ventricular Remodelling Following Heart Attack; NCT00132093).

Validation of Magnetic Resonance Myocardial Perfusion Imaging With Fractional Flow Reserve for the Detection of Significant Coronary Heart Disease

Background— Magnetic resonance myocardial perfusion imaging (MRMPI) has a number of advantages over the other noninvasive tests used to detect reversible myocardial ischemia. The majority of previous studies have generally used quantitative coronary angiography as the gold standard to assess the accuracy of MRMPI; however, only an approximate relationship exists between stenosis severity and functional significance. Pressure wire–derived fractional flow reserve (FFR) values <0.75 correlate closely with objective evidence of reversible ischemia. Accordingly, we have compared MRMPI with FFR. Methods and Results— One hundred three patients referred for investigation of suspected angina underwent MRMPI with a 1.5-T scanner. The stress agent was intravenous adenosine (140 &mgr;g · kg−1 · min−1), and the first-pass bolus contained 0.1 mmol/kg gadolinium. In the following week, coronary angiography with pressure wire studies was performed. FFR was recorded in all patent major epicardial coronary arteries, with a value <0.75 denoting significant stenosis. MRMPI scans, analyzed by 2 blinded observers, identified perfusion defects in 121 of 300 coronary artery segments (40%), of which 110 had an FFR <0.75. We also found that 168 of 179 normally perfused segments had an FFR ≥0.75. The sensitivity and specificity of MRMPI for the detection of functionally significant coronary heart disease were 91% and 94%, respectively, with positive and negative predictive values of 91% and 94%. Conclusion— MRMPI can detect functionally significant coronary heart disease with excellent sensitivity, specificity, and positive and negative predictive values compared with FFR.

Radiofrequency ablation for persistent atrial fibrillation in patients with advanced heart failure and severe left ventricular systolic dysfunction: a randomised controlled trial

Objective To determine whether or not radiofrequency ablation (RFA) for persistent atrial fibrillation in patients with advanced heart failure leads to improvements in cardiac function. Setting Patients were recruited from heart failure outpatient clinics in Scotland. Design and intervention Patients with advanced heart failure and severe left ventricular dysfunction were randomised to RFA (rhythm control) or continued medical treatment (rate control). Patients were followed up for a minimum of 6 months. Main outcome measure Change in left ventricular ejection fraction (LVEF) measured by cardiovascular MRI. Results 22 patients were randomised to RFA and 19 to medical treatment. In the RFA group, 50% of patients were in sinus rhythm at the end of the study (compared with none in the medical treatment group). The increase in cardiovascular magnetic resonance (CMR) LVEF in the RFA group was 4.5±11.1% compared with 2.8±6.7% in the medical treatment group (p=0.6). The RFA group had a greater increase in radionuclide LVEF (a prespecified secondary end point) than patients in the medical treatment group (+8.2±12.0% vs +1.4±5.9%; p=0.032). RFA did not improve N-terminal pro-B-type natriuretic peptide, 6 min walk distance or quality of life. The rate of serious complications related to RFA was 15%. Conclusions RFA resulted in long-term restoration of sinus rhythm in only 50% of patients. RFA did not improve CMR LVEF compared with a strategy of rate control. RFA did improve radionuclide LVEF but did not improve other secondary outcomes and was associated with a significant rate of serious complications. Clinical trials registration number NCT00292162.

The index of microcirculatory resistance measured acutely predicts the extent and severity of myocardial infarction in patients with ST-segment elevation myocardial infarction.

OBJECTIVES This study investigated the relationship between the index of microcirculatory resistance (IMR) with myocardial injury and microvascular obstruction (MVO) assessed by contrast-enhanced cardiac magnetic resonance (ceCMR) imaging in a broad range of ST-segment elevation myocardial infarction (STEMI) patients undergoing emergency percutaneous coronary intervention (PCI). BACKGROUND Contrast-enhanced cardiac magnetic resonance imaging is the gold standard for assessment of microvascular obstruction (MVO), left ventricular (LV) ejection fraction, and infarct volumes in ST-segment elevation myocardial infarction (STEMI). However, ceCMR is not available acutely. The index of microcirculatory resistance is a simple invasive measure of microvascular function available at the time of emergency PCI. We investigated the relationship between IMR with myocardial injury and MVO assessed by ceCMR in STEMI patients undergoing emergency PCI. METHODS Fifty-seven patients with STEMI were included and 53 (93%) and 47 (82%) patients had complete ceCMR scans 2 days and 3 months following MI, respectively. Microvascular obstruction was defined as a dark core of hypoenhancement within the area of hyperenhanced infarct tissue 10 to 15 min following intravenous gadolinium (0.1 mmol/kg). RESULTS The median IMR (interquartile range [IQR]) was 35 (24 to 63) U. Twenty-seven patients (46%) had MVO. We found that IMR (median [IQR]) was higher in patients with MVO (38 [29 to 55] U) than in patients without MVO (27 [18 to 36] U); p = 0.003). The index of microcirculatory resistance was a negative multivariable predictor of LV ejection fraction, (p < or = 0.001) and infarct volume (p = 0.01) on the ceCMR scan 2 days after MI, and IMR was a multivariable predictor of LV ejection fraction (p = 0.028) and infarct volume (p = 0.048) at 3 months. CONCLUSIONS The index of microcirculatory resistance measured acutely was higher in patients with MVO on ceCMR, and IMR independently predicted LV function and infarct volume. This easily measured physiological parameter provides important prognostic information at the time of emergency PCI.

NT-proBNP can be used to detect right ventricular systolic dysfunction in pulmonary hypertension.

Right ventricular systolic dysfunction (RVSD) at baseline (pre-treatment) predicts early death in patients with pulmonary hypertension (PH). However, RVSD can only be detected reliably by prohibitively invasive or expensive techniques. N-terminal B-type natriuretic peptide concentration ([NT-proBNP]) correlates with RV function in PH; however, an [NT-proBNP] threshold that indicates RVSD in individual patients has not previously been determined. Twenty-five patients with PH (pulmonary arterial hypertension (n = 19) or chronic thromboembolic PH (n = 6)) underwent cardiovascular magnetic resonance (CMR) imaging and NT-proBNP measurement at baseline. [NT-proBNP] was correlated against RV dimensions and ejection fraction (RVEF) measured directly by CMR imaging. The ability of NT-proBNP to detect RVSD (defined as a CMR-derived RVEF >2 sds below control values) was tested and predictors of [NT-proBNP] identified. [NT-proBNP] correlated negatively with RVEF. RVSD was present in nine out of 25 patients. An [NT-proBNP] threshold of 1,685 pg·mL−1 was sensitive (100%) and specific (94%) in detecting RVSD. RVEF and RV mass index independently predicted [NT-proBNP]. In pulmonary hypertension, a baseline N-terminal B-type natriuretic peptide concentration of >1,685 ng·L−1 suggests right ventricular systolic dysfunction, and thus an increased risk of early death. N-terminal B-type natriuretic peptide could prove useful as an objective, noninvasive means of identifying patients with pulmonary hypertension who have right ventricular systolic dysfunction at presentation.

Plasma apelin concentration is depressed following acute myocardial infarction in man.

Apelin, a novel peptide with a putative role in cardiovascular homeostasis, has gained interest as an endogenous inotrope, but has yet to be described following acute myocardial infarction (AMI) in man. We aimed to characterize plasma apelin concentrations following AMI and to examine its relationship with clinical and prognostic biomarkers.

Galectin-3 and Cardiac Function in Survivors of Acute Myocardial Infarction

Background—Galectin-3 is a biomarker associated with inflammation and fibrosis that predicts adverse outcome and relates to biomarkers of extracellular matrix turnover in patients with heart failure, particularly when left ventricular (LV) systolic function is preserved. Whether galectin-3 is related to LV remodeling after acute myocardial infarction is unknown. Methods and Results—Circulating galectin-3 and various extracellular matrix biomarkers were measured in 100 patients (age, 58.9±12.0 years; 77% men) admitted with acute myocardial infarction and LV dysfunction, at baseline (mean 46 hours) and at 24 weeks, with cardiac MRI at each time-point. LV remodeling was defined as change in LV end-systolic volume index. Relationships among galectin-3, biomarkers, and LV remodeling were analyzed across the entire cohort, then according to median baseline LV ejection fraction. Galectin-3 levels were elevated in 22 patients (22%) at baseline and increased significantly over time from 14.7±5.5 to 16.3±6.6 ng/mL (P=0.007). Baseline galectin-3 did not correlate with any LV parameters at baseline or change in any parameter over time. Galectin-3 was positively associated with remodeling in patients with supramedian baseline LV ejection fraction (ie, >49.2%; r=0.40; P=0.01) but not when LV ejection fraction was ⩽49.2%. Galectin-3 correlated significantly with matrix metalloproteinase-3 and monocyte chemoattractant protein-1 at baseline, biomarkers that have been shown to relate to LV remodeling in this cohort. Conclusions—Galectin-3 correlated significantly with certain biomarkers involved in extracellular matrix turnover, although no definite relationship was identified with LV remodeling. Whether galectin-3 plays a pathological role in remodeling remains unclear but merits further study. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00132093.

Association of Left Atrial Volume With Mortality Among ESRD Patients With Left Ventricular Hypertrophy Referred for Kidney Transplantation

Background Left ventricular hypertrophy (LVH) is common in patients with end-stage renal disease (ESRD) and an independent risk factor for premature cardiovascular death. Left atrial volume (LAV), measured using echocardiography, predicts death in patients with ESRD. Cardiovascular magnetic resonance (CMR) imaging is a volume-independent method of accurately assessing cardiac structure and function in patients with ESRD. Study Design Single-center prospective observational study to assess the determinants of all-cause mortality, particularly LAV, in a cohort of ESRD patients with LVH, defined using CMR imaging. Setting & Participants 201 consecutive ESRD patients with LVH (72.1% men; mean age, 51.6 ± 11.7 years) who had undergone pretransplant cardiovascular assessment were identified using CMR imaging between 2002-2008. LVH was defined as left ventricular mass index >84.1 g/m2 (men) or >74.6 g/m2 (women) based on published normal left ventricle dimensions for CMR imaging. Maximal LAV was calculated using the biplane area-length method at the end of left ventricle systole and corrected for body surface area. Predictors CMR abnormalities, including LAV. Outcome All-cause mortality. Results 54 patients died (11 after transplant) during a median follow-up of 3.62 years. Median LAV was 30.4 mL/m2 (interquartile range, 26.2-58.1). Patients were grouped into high (median or higher) or low (less than median) LAV. There were no significant differences in heart rate and mitral valve Doppler early to late atrial peak velocity ratio. Increased LAV was associated with higher mortality. Kaplan-Meier survival analysis showed poorer survival in patients with higher LAV (log rank P = 0.01). High LAV and left ventricular systolic dysfunction conferred similar risk and were independent predictors of death using multivariate analysis. Limitations Only patients undergoing pretransplant cardiac assessment are included. Limited assessment of left ventricular diastolic function. Conclusions Higher LAV and left ventricular systolic dysfunction are independent predictors of death in ESRD patients with LVH.

Microvascular Obstruction Remains a Portent of Adverse Remodeling in Optimally Treated Patients With Left Ventricular Systolic Dysfunction After Acute Myocardial Infarction

Background—Microvascular obstruction (MO) is associated with large acute myocardial infarction and lower left ventricular (LV) ejection fraction and predicts greater remodeling, but whether this effect is abolished by contemporary antiremodeling therapies is subject to debate. We examined the influence of several infarct characteristics, including MO, on LV remodeling in an optimally treated post–acute myocardial infarction cohort, using contrast-enhanced cardiac magnetic resonance. Methods and Results—One hundred patients (mean age, 58.9±12 years, 77% men) underwent contrast-enhanced cardiac magnetic resonance at baseline (≈4 days) and at 12 and 24 weeks. The effects on LV remodeling (ie, change in LV end-systolic volume index [&Dgr;LVESVi]) of infarct site, transmurality, endocardial extent, and the presence of early and late MO were analyzed. Mean baseline infarct volume index decreased from 34.0 (21.2) mL/m2 to 20.9 (12.9) mL/m2 at 24 weeks (P<0.001). Infarct site had no influence on remodeling, but greater baseline infarct transmurality (r=0.47, P<0.001) and endocardial extent (r=0.26, P<0.01) were associated with higher &Dgr;LVESVi. Early MO was seen in 69 patients (69%) and persisted as late MO in 56 patients (56%). Patients with late MO underwent significantly greater remodeling than those without MO (&Dgr;LVESVi, +4.1 [13.4] versus −7.0 [12.7] mL/m2, respectively, P=0.001); those with early MO only displayed an intermediate &Dgr;LVESVi (−4.9 [13.0] mL/m2). Importantly, late MO was seen frequently despite optimal coronary blood flow having been restored at angiography. Conclusions—Late MO on predischarge contrast-enhanced cardiac magnetic resonance remains an ominous predictor of adverse LV remodeling despite powerful antiremodeling therapy and may be useful in the risk stratification of survivors of acute myocardial infarction. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00132093.

Vascular stiffness is related to superoxide generation in the vessel wall

Objectives Oxidative stress causes endothelial dysfunction and plays a major role in the pathogenesis of cardiovascular disease. Increased vascular stiffness is an intermediate phenotype in the development of cardiovascular disease. We hypothesized that vascular stiffness is partially determined by oxidative stress. Methods We examined 163 participants out of whom 80 had coronary artery disease. Vascular stiffness was assessed by pulse wave analysis, pulse wave velocity and measurement of aortic compliance by cardiac MRI. Circulating markers of oxidative stress and vascular superoxide generation in saphenous vein were measured. Results After adjustment for age, sex, BMI, heart rate, blood pressure and lipids only carotid-femoral pulse wave velocity and aortic compliance were different between patients and control group. Aortic compliance was reduced (11.4 ± 6.3 vs. 13.9 ± 7.3 ml × 10−3 per mmHg; P = 0.035) and vascular superoxide generation increased (1.01 ± 0.45 vs. 0.76 ± 0.44 nmol/mg per min; P = 0.035) in patients with coronary artery disease compared with those without. In a multiple stepwise regression analysis, aortic compliance was determined by age (P < 0.001) and vascular superoxide production (P = 0.033). CYBA C242T and NOS3 G894T polymorphisms had additive effects on vascular superoxide generation (P = 0.026) and xanthine oxidase activity was increased in patients with CAD (P = 0.043). Genetic factors (P = 0.033) and xanthine oxidase activity (P < 0.001) were also related to aortic compliance. Conclusion By measuring vascular superoxide generation and aortic compliance using cardiac MRI, we demonstrated a functional relationship between oxidative stress and vascular stiffness. Patients identified with high levels of vascular stiffness are most likely to benefit from strategies to reduce vascular oxidative stress.