Colin J. Petrie

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.

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.

Comparison of serial measurements of infarct size and left ventricular ejection fraction by contrast-enhanced cardiac magnetic resonance imaging and electrocardiographic QRS scoring in reperfused anterior ST-elevation myocardial infarction

BACKGROUND Left ventricular ejection fraction (LVEF) is a powerful prognostic marker after acute myocardial infarction and is dependent on infarct magnitude. Contrast-enhanced cardiac magnetic resonance (ceCMR) represents the current criterion standard means of LVEF and infarct size measurement. Infarct size and LVEF can be estimated from the 12-lead electrocardiogram (ECG) using the Selvester QRS score. We examined for the first time the relationship between serial measures of LVEF and infarct size by ceCMR and ECG in patients with reperfused anterior ST-elevation myocardial infarction (STEMI) and depressed LVEF. METHODS Thirty-four patients (mean +/- SD age, 59 +/- 11.8 years; 70.6% male) underwent ceCMR and simultaneous ECG at mean 93 hours after admission and at 12 and 24 weeks. The QRS score was calculated on each ECG, from which infarct size and LVEF were estimated and compared with the equivalent ceCMR measurements. RESULTS Infarct size on ceCMR was higher than that by QRS score at each time-point (P < .001) with modest correlation (r = 0.56-0.78, P < .001). Left ventricular ejection fraction was consistently significantly higher on CMR than on ECG, with weak correlation (r = 0.37-0.51, P < .05). We derived a novel equation relating QRS score to CMR-measured LVEF in the subacute phase of infarction: LVEF = 61 - (1.7 x QRS score) (%). CONCLUSIONS In patients with reperfused anterior ST-elevation myocardial infarction and depressed LVEF, ceCMR is moderately correlated with the QRS in the serial measurement of infarct size and LVEF. Infarct size (measured by ceCMR) and LVEF are consistently higher than those calculated on the QRS score in the acute and subacute phases of infarction.

Monocyte chemoattractant protein-1: A dichotomous role in cardiac remodeling following acute myocardial infarction in man?

INTRODUCTION Monocyte chemoattractant protein-1 (MCP-1) is elevated after acute myocardial infarction (AMI), and potentiates left ventricular (LV) remodeling in murine models of AMI. We examined the relationships between serum MCP-1, change in LV function and biomarkers related to remodeling in a cohort of AMI patients. METHODS Serum MCP-1 concentrations were measured in 100 patients (age 58.9+/-12.0 years, 77% male) admitted with AMI and LV dysfunction, at baseline (mean 46 h), 12 and 24 weeks; cardiac magnetic resonance imaging and measurement of matrix metalloproteinase-2 (MMP-2), MMP-3 and MMP-9 occurred at each time-point. RESULTS MCP-1 increased significantly from 697 [483, 997]pg/mL at baseline to 878 [678, 1130]pg/mL at 24 weeks (p<0.001). MMP-3 concentration increased while MMP-9 decreased significantly over time; MMP-2 concentration did not change significantly. BASELINE MCP-1 correlated with change in (Delta) LV end-systolic volume index (DeltaLVESVI; r= -0.48, p=0.01) and with DeltaLV ejection fraction (DeltaLVEF; r=0.50, p=0.02). However, DeltaMCP-1 correlated positively with DeltaLVESVI (r=0.40, p=0.006) and negatively with DeltaLVEF (r= -0.36, p=0.004). MCP-1 had no relationship with any MMP. CONCLUSIONS MCP-1 may have a dichotomous role following AMI, aiding early infarct healing but potentiating later remodeling, which merits further study before any therapeutic trials of MCP-1 modulation in humans.

Diagnostic, prognostic, and therapeutic implications of brain natriuretic peptide in dialysis and nondialysis-dependent chronic renal failure.

Premature cardiovascular disease is the leading cause of morbidity and mortality in patients with end‐stage renal failure. Natriuretic peptides, specifically brain natriuretic peptide, are released from the heart in response to chamber distension and thus increased in the presence of volume expansion and cardiac overload. Their physiological role is to cause vasodilatation and promote natriuresis to maintain volume homeostasis. Increasingly serum levels of brain natriuretic peptide are used to both diagnose and manage cardiovascular disorders. Furthermore, augmenting the beneficial hemodynamic actions of brain natriuretic peptide may have a therapeutic role in decompensated heart failure. However, the diagnostic role of serum brain natriuretic peptide levels in patients with advanced renal dysfunction remains to be defined. These patients have a high prevalence of left ventricular disorders, specifically left ventricular hypertrophy, which may reduce the diagnostic utility of brain natriuretic peptide. In addition, ventricular stretch may be determined by intravascular volume status rather than by cardiac dysfunction. Nonetheless, as the prognosis of patients with end‐stage renal failure and co‐existing heart failure is so poor, the availability of a further marker of cardiac ‘‘distress’’ may in the future become a useful diagnostic tool and in due course may become a primary goal for titration and tailoring of therapy.

Cardiomyopathy in Becker Muscular Dystrophy—Does Regional Fibrosis Mimic Infarction?

We present a case of a 39-year-old man with Becker muscular dystrophy and severe congestive cardiac failure. Cardiac magnetic resonance imaging revealed subendocardial late gadolinium enhancement, similar to that seen in myocardial infarction. He had no risk factors for atherosclerotic coronary artery disease and coronary angiography was normal. We propose that regional subendocardial myocardial fibrosis which has been described histologically in the cardiomyopathy associated with Becker muscular dystrophy may resemble previous infarction at contrast enhanced cardiac magnetic resonance imaging.

Cardiac and extracardiac abnormalities detected by cardiac magnetic resonance in a post-myocardial infarction cohort.

Objectives: All patients should undergo formal assessment of ventricular function following acute myocardial infarction (AMI). Cardiac magnetic resonance (CMR) is not widely used as a test before discharge in AMI patients. This study sought to determine the impact of contrast-enhanced CMR (ceCMR) scanning before discharge in addition to standard transthoracic echocardiography (TTE) on patient care following AMI. Methods: 100 patients admitted with AMI, all of whom had a left ventricular ejection fraction (LVEF) <40% on TTE, underwent ceCMR imaging before discharge. Abnormalities of clinical relevance detected on ceCMR, which influenced patient management, are reported. Results: Each patient (77% male, mean age 58.9 years, SD 12) underwent TTE and ceCMR at a mean 1.4 (range 0.8–3.2) and 4.2 days (range 2–11), respectively, following admission. ceCMR significantly influenced the management of 24/100 (24%) of the patient cohort, through detection of LV thrombus, right ventricular infarction, intracardiac neoplasia, and a variety of intrathoracic and intra-abdominal pathology. There were no issues regarding safety in this high-risk group of patients. Conclusion: In a cohort of AMI patients with reduced LVEF, ceCMR scanning before discharge improved the management of 24% of the cohort. ceCMR is a useful and safe adjunct to standard care after AMI.

Interleukin-21--a biomarker of importance in predicting myocardial function following acute infarction?

INTRODUCTION Following acute myocardial infarction (AMI), the acute inflammatory response contributes to wound healing but also to progressive myocardial injury. Interleukin-21 (IL-21) plays a key role in immunoregulation; whether IL-21 is associated with left ventricular (LV) remodelling after AMI is unknown. METHODS Plasma IL-21 concentrations were measured in 100 patients (age 58.9 ± 12.0 years, 77% male) admitted with AMI and LV dysfunction, at baseline (mean 46 h) and again at 24 weeks; cardiac magnetic resonance and measurement of B-type natriuretic peptide, monocyte chemoattractant protein-1, matrix metalloproteinase (MMP)-2, -3, -9, and tissue inhibitor of metalloproteinase (TIMP)-1, -2, -4 occurred at both time-points. Remodelling was defined as change in LV end-systolic volume index (ΔLVESVI). RESULTS Plasma IL-21 concentration was unchanged over time (48.1 [SD 35.4]pg/mL at baseline vs. 48.8 [61.3]pg/mL at 24 weeks, p=0.92). Baseline IL-21 correlated significantly with ΔLVESVI (r=0.30, p=0.005) and change in LV end-diastolic volume index (r=0.33, p=0.003). On multivariate analysis, plasma IL-21 was an independent predictor of remodelling. IL-21 was also significantly associated with higher TIMP-4 concentrations and lower MMP-9 concentrations at baseline. CONCLUSIONS IL-21 predicts adverse remodelling following AMI in patients with LV dysfunction. Whether it plays a direct pathophysiological role in remodelling merits further study.

Low pulse pressure as a poor-man's indicator of a low cardiac index in patients with severe cardiac dysfunction

Aims A low pulse pressure (PP) may reflect poor cardiac output (CO), but has not been well characterized by invasive haemodynamic studies. Methods We investigated the relationship between PP and cardiac index (CI) in patients with cardiovascular disease including those with normal and impaired cardiac function. Cardiac catheterization data from 1897 patients was analysed. Results Mean age was 59 years; 57% were men, mean (SD) PP was 65 (25) mmHg and mean (SD) CI was 2.9 (0.8) l/min/m2. Correlation between CI and PP was absent if the CI was more than 3 l/min/m2, with a weak correlation if CI was between 2 and 3 l/min/m2 (r = 0.161; P < 0.001). For those with a CI of less than 2 l/min/m2, the correlation was much stronger (r = 0.414; P < 0.001). In a multivariable regression analysis, a low PP predicted a low CI, at cardiac indices of less than 3 l/min/m2. This was independent of potential confounders, including age, sex, presence of hypertension, presence of heart failure, presence of aortic stenosis, diabetes, renal function, heart rate, systemic vascular resistance, left ventricular end diastolic pressure and mean arterial pressure. Conclusion In patients with a CI of less than 3 l/min/m2, a low PP is a marker of a low CI. In patients with severe heart failure and a low CO, PP pressure might be useful as a ‘poor-mans’ surrogate of CO.