Evidence Of Cardiac Remodeling Research Articles

#2167 Polyclonal immunoglobulin free light chains: an evidence of cardiac remodeling in patients with glomerular diseases

Abstract Background and Aims It was previously shown, that polyclonal immunoglobulin free light chains (FLC) are the independent predictor of mortality in patients with decompensated heart failure, chronic kidney disease (CKD) and also in general population. Mechanisms of this phenomenon are still unknown. The aim of our study is to reveal the possible relationships between FLC and cardiac remodeling in patients with glomerular diseases. Method We included 97 patients with biopsy-proven diagnosis of different immune-mediated glomerular diseases, 53% were men, mean age was 48 ± 14.6 years. Serum Freelite FLC levels were measured as well as standard clinical and laboratory investigation. At the time of biopsy transthoracic echocardiography was also performed. Glomerular filtration rate (eGFR) was estimated by “2021 CKD-EPI Creatinine” equation. Results Median of eGFR was 46.8 ml/min/1.73 m² (28.7-80.0), FLC-kappa level was 27.4 mg/l (16.8- 48.4), FLC-lambda level was 28.2 mg/l (20.8-43.3). FLC-kappa levels were above reference range in 65%, FLC-lambda levels – in 54%. LV diastolic dysfunction (DD) was present in 68%. Comparison in groups showed that the elevation of FLC-kappa more than 19.4 mg/l was associated with bigger LV mass index (LVMI) – 138.3 ± 30.2 g/m² vs 99.9 ± 31.2 g/m² р = 0.022, the parallel correlation was found between LVMI and levels of FLC-lambda higher than 26.3 mg/l (136.2 ± 64.8 g/m² vs 104.0 ± 36.6 g/m², р = 0.023). Spearman analysis has shown statistically significant correlations between FLC levels and E/e’- Rs = 0.501 p = 0.0001 for FLC-kappa, Rs = 0.343 p = 0.012 for FLC-lambda. Combined FLC level higher than 52.9 mg/l was a significant predictor of DD with area under the ROC curve (AUC) 0.703 (sensitivity 76.5%, specificity 62.5%). Conclusion Elevation of serum pFLC level could be a promising marker of cardiac remodeling, especially, of DD in patients with glomerular diseases. Possible pathogenic role of FLC in cardiorenal relationships may be revealed in further studies.

Longitudinal Changes in Cardiac Structure and Function in Severe Obesity: 11-Year Follow-Up in the Utah Obesity Study.

BackgroundProgressive cardiac remodeling and worsening myocardial function over time have been proposed as potential mediators of heart failure in obesity.Methods and ResultsWe serially assessed cardiac structure and function in 254 subjects participating in a longitudinal study of obesity. Demographic, clinical, laboratory, and echocardiographic features were determined at baseline and 2‐, 6‐, and 11‐year follow‐up. We measured body mass index (BMI) exposure as the area under the curve of the BMI at each of the 4 visits. At enrollment, mean age of the subjects was 47 years, 79% were women, mean BMI was 44 kg/m2, 26% had diabetes mellitus, 48% had hypertension, and 53% had hyperlipidemia. Between baseline and 11 years, BMI increased by 1.1 and 0.3 kg/m2 in men and women, respectively. There were modest increases in left ventricular (LV) end‐diastolic volume, LV mass, and left atrial volume, and significant decreases in early/late mitral diastolic flow velocity ratio and E wave deceleration time. However, there were no significant changes in LV ejection fraction or ratio of early mitral diastolic flow velocity/early mitral annular velocity, whereas right ventricular fractional area change increased. Significant predictors of the change in LV mass were male sex, baseline BMI, BMI area under the curve, and change in LV stroke volume, but not smoking, hypertension, or diabetes mellitus.ConclusionsIn long‐standing, persistent severe obesity, there was evidence of cardiac remodeling over a period of 11 years, but no clear worsening of systolic or diastolic function. Measures of remodeling were most strongly related to BMI. The observed changes might predispose to heart failure with preserved ejection fraction, but are not classic for an evolving dilated cardiomyopathy.

SUN-076 2D ECHOCARDIOGRAPHY ASSESSMENT OF LEFT VENTRICULAR DYSFUNCTION IN PEDIATRIC CHRONIC KIDNEY DISEASE PATIENTS IN TIKUR ANBESSA SPECIALIZED HOSPITAL, A CROSS SECTIONAL STUDY, ADDIS ABABA, ETHIOPIA

In 2012 KDIGO defines CKD as abnormalities of kidney structure or function, present for > 3 months, with implication for health. In children, the majority of CKD stems from congenital anomalies of the kidney and urinary tract (CAKUT). Left ventricular (LV) hypertrophy, LV systolic and diastolic dysfunction that are the most common CV abnormalities in adult and pediatric patients with end stage renal disease (ESRD) develop during early stages of CKD and progress as renal function deteriorates. The complications that develop from CKD, such as anemia, hypertension, electrolyte abnormality, can lead to the CV abnormality. Objective: To assess the prevalence of left ventricular dysfunction by 2D echocardiography in pediatric patients with chronic kidney disease attending Renal follow up Clinic in Tikur Anbessa Specialized hospital. A hospital based cross sectional study was conducted among 95 CKD children <18 years of age attending follow up at renal clinic in TASH from May – September 2018. A structured checklist was used to collect data on the socio- demographic characteristics; health (CKD) related characteristics of participant children. Echocardiography examination was performed in pediatric cardiology department. The study included a total of 95 CKD patients. Fifty three (55.8%) were male, and 42 (44.2%) were female. Congenital anomaly of the kidney and urinary tract (CAKUT) accounted for 65 (68.4%) of CKD cause. Forty (42.1%) of the CKD were at stage2 and stage3 accounted for 38(40%) of the total CKD. Systolic hypertension was present among 22(23.2%) of the children. Thirty (31.6%) had diastolic hypertension. 74.5% had cardiac remodeling as evidenced by abnormal cardiac geometry. 63.8% had concentric remodeling and 10.6% had concentric hypertrophy. Diastolic dysfunction was seen among 20.4% of the children. Low ejection fraction was detected in only 3.2% of the children. The variable, which was significantly associated with LVMI, was the presence of anemia (p value 0.018). The mean RWT was lower among those who had anemia, with statistically significant difference between the two groups with p value 0.043. Among the factors tested for possible association with cardiac dysfunction anemia was the only factor, which had statistically significant association with cardiac dysfunction in this study. Among the echocardiographic parameters the parameter, which had strongest correlation with diastolic dysfunction, was LVMI with Pearson correlation coefficient of 0.764. Majority of the children (74.5%) with CKD had evidence of cardiac remodeling. Diastolic dysfunction was the commonest type of functional cardiac impairment as opposed to systolic dysfunction. Anemia was associated with higher relative incidence of diastolic dysfunction. LVMI was the echocardiography parameter that was strongly correlated with diastolic dysfunction.

Impairments in left ventricular mitochondrial bioenergetics precede overt cardiac dysfunction and remodelling in Duchenne muscular dystrophy.

Ninety-eight per cent of patients with Duchenne muscular dystrophy (DMD) develop cardiomyopathy, with 40% developing heart failure. While increased propensity for mitochondrial induction of cell death has been observed in left ventricle, it remains unknown whether this is linked to impaired mitochondrial respiratory control and elevated H2 O2 emission prior to the onset of cardiomyopathy. Classic mouse models of DMD demonstrate hyper-regeneration in skeletal muscle which may mask mitochondrial abnormalities. Using a model with less regenerative capacity that is more akin to DMD patients, we observed elevated left ventricular mitochondrial H2 O2 and impaired oxidative phosphorylation in the absence of cardiac remodelling or overt cardiac dysfunction at 4weeks. These impairments were associated with dysfunctions at complex I, governance by ADP and creatine-dependent phosphate shuttling, which results in a less efficient response to energy demands. Mitochondria may be a therapeutic target for the treatment of cardiomyopathy in DMD. In Duchenne muscular dystrophy (DMD), mitochondrial dysfunction is predicted as a response to numerous cellular stressors, yet the contribution of mitochondria to the onset of cardiomyopathy remains unknown. To resolve this uncertainty, we designed in vitro assessments of mitochondrial bioenergetics to model mitochondrial control parameters that influence cardiac function. Both left ventricular mitochondrial responsiveness to the central bioenergetic controller ADP and the ability of creatine to facilitate mitochondrial-cytoplasmic phosphate shuttling were assessed. These measurements were performed in D2.B10-DMDmdx /2J mice - a model that demonstrates skeletal muscle atrophy and weakness due to limited regenerative capacities and cardiomyopathy more akin to people with DMD than classic models. At 4weeks of age, there was no evidence of cardiac remodelling or cardiac dysfunction despite impairments in ADP-stimulated respiration and ADP attenuation of H2 O2 emission. These impairments were seen at both submaximal and maximal ADP concentrations despite no reductions in mitochondrial content markers. The ability of creatine to enhance ADP's control of mitochondrial bioenergetics was also impaired, suggesting an impairment in mitochondrial creatine kinase-dependent phosphate shuttling. Susceptibly to permeability transition pore opening and the subsequent activation of cell death pathways remained unchanged. Mitochondrial H2 O2 emission was elevated despite no change in markers of irreversible oxidative damage, suggesting alternative redox signalling mechanisms should be explored. These findings demonstrate that selective mitochondrial dysfunction precedes the onset of overt cardiomyopathy in D2.mdx mice, suggesting that improving mitochondrial bioenergetics by restoring ADP, creatine-dependent phosphate shuttling and complex I should be considered for treating DMD patients.

Cobalt Administration Causes Reduced Contractility with Parallel Increases in TRPC6 and TRPM7 Transporter Protein Expression in Adult Rat Hearts

Exposure to circulating cobalt (Co2+) in patients with metal-on-metal orthopaedic hip implants has been linked to cardiotoxicity but the underlying mechanism(s) remain undefined. The aim of the current study was to examine the effects of Co2+ on the heart in vivo and specifically on cardiac fibroblasts in vitro. Adult male rats were treated with CoCl2 (1 mg/kg) for either 7 days or 28 days. Inductively coupled plasma mass spectrometry (ICP-MS) was used to measure Co2+ uptake into various organs of the body. Co2+ accumulated in the heart over time with significant levels evident after only 7 days of treatment. There was no evidence of cardiac remodelling following Co2+ treatment as assessed by heart weight:body weight and left ventricular weight:body weight. However, a decrease in fractional shortening, as measured using echocardiography, was observed after 28 days of Co2+ treatment. This was accompanied by increased protein expression of the ion transient receptor potential (TRP) channels TRPC6 and TRPM7 as assessed by quantitative immunoblotting of whole cardiac homogenates. Uptake of Co2+ specifically into rat cardiac fibroblasts was measured over 72 h and was shown to dramatically increase with increasing concentrations of applied CoCl2. Expression levels of TRPC6 and TRPM7 proteins were both significantly elevated in these cells following Co2+ treatment. In conclusion, Co2+ rapidly accumulates to significant levels in the heart causing compromised contractility in the absence of any overt cardiac remodelling. TRPC6 and TRPM7 expression levels are significantly altered in the heart following Co2+ treatment and this may contribute to the Co2+-induced cardiotoxicity observed over time.

Perinatal outcomes associated with abnormal cardiac remodeling in women with treated chronic hypertension

Adverse maternal outcomes associated with chronic hypertension include accelerated hypertension and resultant target organ damage. One example is long-standing hypertension leading to maternal cardiac dysfunction. Our group has previously identified that features of such injury manifest as cardiac remodeling with left ventricular hypertrophy. Moreover, these features of cardiac remodeling identified in women with chronic hypertension during pregnancy were associated with adverse perinatal outcomes. Recent definitions of maternal cardiac remodeling using echocardiography have been expanded to include measurements of wall thickness. We hypothesized that these new features characterizing cardiac remodeling in women with chronic hypertension may also be associated with adverse perinatal outcomes. There were 3 aims in this study of women with treated chronic hypertension during pregnancy: to (1) apply the updated definitions of maternal cardiac remodeling; (2) elucidate whether these features of cardiac remodeling were associated with adverse perinatal outcomes; and (3) determine which, if any, of the newly defined cardiac remodeling strata were most damaging when compared to women with normal cardiac geometry. This was a retrospective study of women with treated chronic hypertension during pregnancy delivered from January 2009 through January 2016. Cardiac remodeling was categorized by left ventricular mass index and relative wall thickness into 4 groups determined using the 2015 American Society of Echocardiography guidelines: normal geometry, concentric remodeling, eccentric hypertrophy, and concentric hypertrophy. Perinatal outcomes were analyzed according to each category of cardiac remodeling compared with outcomes in women with normal geometry. A total of 314 women with treated chronic hypertension underwent echocardiography at a mean gestational age of 17.9 weeks. There were no differences between maternal age (P= .896), habitus (P=.36), or duration of chronic hypertension (P= .212) among the 4 groups. Abnormal cardiac remodeling was found in 51% and was significantly associated with increased rates of superimposed preeclampsia (P= .015), preterm birth (P < .001), and neonatal intensive care admission (P= .003). These outcomes reached the greatest significance when comparisons were made between eccentric hypertrophy and normal geometry. Using current American Society of Echocardiography guidelines, 51% of women with treated chronic hypertension during pregnancy have some degree of abnormal cardiac remodeling. Any suggestion of maternal cardiac remodeling, regardless of subtype, was associated with increased risks for superimposed preeclampsia and preterm birth with its resultant perinatal sequelae. Eccentric ventricular hypertrophy, previously thought to mimic exercise physiology, appears to be the most associated with adverse perinatal outcomes. Despite evidence of cardiac remodeling, ejection fraction was preserved.

Cardiac remodeling and dysfunction in childhood obesity: a cardiovascular magnetic resonance study.

BackgroundObesity affects nearly one in five children and is associated with increased risk of premature death. Obesity-related heart disease contributes to premature death. We aimed to use cardiovascular magnetic resonance (CMR) to comprehensively characterize the changes in cardiac geometry and function in obese children.Methods and resultsForty-one obese/overweight (age 12 ± 3 years, 56 % female) and 29 healthy weight children (age 14 ± 3 years, 41 % female) underwent CMR, including both standard cine imaging and displacement encoded imaging, for a complete assessment of left ventricular (LV) structure and function. After adjusting for age, LV mass index was 23 % greater (27 ± 4 g/m2.7 vs 22 ± 3 g/m2.7, p <0.001) and the LV myocardium was 10 % thicker (5.6 ± 0.8 mm vs 5.1 ± 0.8 mm, p <0.001) in the obese/overweight children. This evidence of cardiac remodeling was present in obese children as young as age 8. Twenty four percent of obese/overweight children had concentric hypertrophy, 59 % had normal geometry and 17 % had either eccentric hypertrophy or concentric remodeling. LV mass index, thickness, ejection fraction and peak longitudinal and circumferential strains all correlated with epicardial adipose tissue after adjusting for height and gender (all p <0.05). Peak longitudinal and circumferential strains showed a significant relationship with the type of LV remodeling, and were most impaired in children with concentric hypertrophy (p <0.001 and p = 0.003, respectively).ConclusionsObese children show evidence of significant cardiac remodeling and dysfunction, which begins as young as age 8. Obese children with concentric hypertrophy and impaired strain may represent a particularly high risk subgroup that demands further investigation.Electronic supplementary materialThe online version of this article (doi:10.1186/s12968-016-0247-0) contains supplementary material, which is available to authorized users.

Abstract 15439: Obese Children With Concentric Hypertrophy and Impaired Cardiac Strain: A Potentially High-risk Subgroup Identified With Cardiac Magnetic Resonance

Objectives: Obesity affects nearly one in five children and is associated with increased risk of premature death. Heart disease may contribute to this premature death. We aimed to use cardiac magnetic resonance (CMR) to comprehensively assess the prevalence and severity of heart disease in obese children, with the hypothesis that obese children have cardiac remodeling and impaired cardiac function compared to healthy weight children. Methods and Results: Twenty obese (age 12 ± 3 years, 60% female) and 20 healthy weight children (age 13 ± 3 years, 50% female) underwent CMR, including both standard cine imaging and displacement encoded imaging, for a complete assessment of left ventricular (LV) structure and function. After adjusting for age, obese children had a 27% increase in LV mass (p &lt;0.001, Figure 1A) and a 12% increase in LV thickness (obese = 5.5 ± 0.7 mm, healthy = 5.0 ± 0.7 mm, p = 0.01). This evidence of cardiac remodeling was present in obese children as young as age 8. Forty percent of obese children had concentric hypertrophy, 40% had normal geometry and 20% had either eccentric hypertrophy or concentric remodeling. LV ejection fraction and peak strains were not different between the healthy weight and obese groups. However, peak longitudinal strain showed a significant relationship with the type of LV remodeling, and was most impaired in obese children with concentric hypertrophy (Figure 1B). Conclusions: Obese children show evidence of significant heart disease, which begins as young as age 8. The presence of concentric hypertrophy in 40% of obese children along with the association with impaired cardiac strain in these children may represent a high-risk subgroup. Given the associations between pediatric obesity and early mortality, these early signs of heart disease in obese children demand further investigation.

106 Echocardiographic Evaluation Of Post-partum Ventricular Remodelling – Implications For The Detection Of Cardiac Disease

BackgroundPeripartum cardiomyopathy (PPCM) is a potentially life-threatening cause of heart failure that often presents soon after delivery. Diagnosis of the condition may be difficult due to the physiological changes in...

253 IMPACT OF LOW BIRTH WEIGHT ON THE EXPRESSION OF THE RENIN-ANGIOTENSIN SYSTEM, FACTORS WHICH REGULATE AUTOPHAGY, FIBROSIS AND CAPILLARY DENSITY IN THE HEART DURING EARLY POSTNATAL LIFE

Background: Low birth weight (LBW) is associated with increased hypertension in offspring. RAS is important in hypertension but is also implicated in cardiac angiogenesis, remodelling and autophagy. We aimed to investigate the effects of LBW on the cardiac RAS and these cardiac processes. Methods: Plasma renin activity and ANGII in average birth weight (ABW) and LBW lambs at d20 were determined using radioimmunoassay. Left ventricle samples were collected from the lambs at d21 for the analysis of gene and protein expression. Results: There was increased plasma renin activity and ANGII concentrations in LBW compared to ABW lambs. There was increased ACE2 mRNA and decreased abundance of ATR1 but no changes in abundance of ACE or ATR2 in LBW compared to ABW lambs. There was increased phospho-Akt protein and decreased capillary density in the heart of LBW lambs compared to ABW lambs. There was decreased collagen I and II mRNA expression but no evidence of cardiac remodelling or fibrosis in the LBW lambs. There was decreased FoxO1 and FoxO3a protein in the LBW lambs compared to ABW lambs, but no changes in autophagy proteins: phospho-FoxO1, phospho-FoxO3a, Beclin1, LC3B and LAMP1 was not altered in LBW lambs. Conclusion: Although circulating and local cardiac RAS components were altered in LBW lambs there was no increase in fibrosis or autophagy in the heart of the LBW lamb. LBW resulted in decreased capillary density during early postnatal life and this may result in an increased risk of impaired heart function in later life.

Mitochondrial DNA Variant for Complex I Reveals a Role in Diabetic Cardiac Remodeling

Myocardial remodeling and dysfunction are serious complications of type 2 diabetes mellitus (T2DM). Factors controlling their development are not well established. To specifically address the role of the mitochondrial genome, we developed novel conplastic rat strains, i.e. strains with the same nuclear genome but a different mitochondrial genome. The new animals were named T2DN(mtFHH) and T2DN(mtWistar), where the acronym T2DN denotes their common nuclear genome (type 2 diabetic nephropathy (T2DN) rats) and mtFHH or mtWistar the origin of their mitochondria, Fawn Hooded Hypertensive (FHH) or Wistar rats, respectively. The T2DN(mtFHH) and T2DN(mtWistar) showed a similar progression of diabetes as determined by HbA1c, cholesterol, and triglycerides with normal blood pressure, thus enabling investigation of the specific role of the mitochondrial genome in cardiac function without the confounding effects of obesity or hypertension found in other models of diabetes. Echocardiographic analysis of 12-week-old animals showed no abnormalities, but at 12 months of age the T2DN(mtFHH) showed left ventricular remodeling that was verified by histology. Decreased complex I and complex IV but not complex II activity within the electron transport chain was found only in T2DN(mtFHH), which was not explained by differences in protein content. Decreased cardiac ATP levels in T2DN(mtFHH) were in agreement with a lower ATP synthetic capacity by isolated mitochondria. Together, our data provide experimental evidence that mtDNA sequence variations have an additional role in energetic heart deficiency. The mitochondrial DNA background may explain the increased susceptibility of certain T2DM patients to develop myocardial dysfunction.

Pulmonary Oxidative Stress Is Increased in Cyclooxygenase-2 Knockdown Mice with Mild Pulmonary Hypertension Induced by Monocrotaline

The aim of this study was to examine the role of cyclooxygenase-2 (COX-2) and downstream signaling of prostanoids in the pathogenesis of pulmonary hypertension (PH) using mice with genetically manipulated COX-2 expression. COX-2 knockdown (KD) mice, characterized by 80–90% suppression of COX-2, and wild-type (WT) control mice were treated weekly with monocrotaline (MCT) over 10 weeks. Mice were examined for cardiac hypertrophy/function and right ventricular pressure. Lung histopathological analysis was performed and various assays were carried out to examine oxidative stress, as well as gene, protein, cytokine and prostanoid expression. We found that MCT increased right ventricular systolic and pulmonary arterial pressures in comparison to saline-treated mice, with no evidence of cardiac remodeling. Gene expression of endothelin receptor A and thromboxane synthesis, regulators of vasoconstriction, were increased in MCT-treated lungs. Bronchoalveolar lavage fluid and lung sections demonstrated mild inflammation and perivascular edema but activation of inflammatory cells was not predominant under the experimental conditions. Heme oxygenase-1 (HO-1) expression and indicators of oxidative stress in lungs were significantly increased, especially in COX-2 KD MCT-treated mice. Gene expression of NOX-4, but not NOX-2, two NADPH oxidase subunits crucial for superoxide generation, was induced by ∼4-fold in both groups of mice by MCT. Vasodilatory and anti-aggregatory prostacyclin was reduced by ∼85% only in MCT-treated COX-2 KD mice. This study suggests that increased oxidative stress-derived endothelial dysfunction, vasoconstriction and mild inflammation, exacerbated by the lack of COX-2, contribute to the pathogenesis of early stages of PH when mild hemodynamic changes are evident and not yet accompanied by vascular and cardiac remodeling.

Chronic SR Ca2+-ATPase inhibition causes adaptive changes in cellular Ca2+ transport.

Phospholamban, the critical regulator of the cardiac SERCA2a Ca2+ affinity, is phosphorylated at Ser16 and Thr17 during beta-adrenergic stimulation (eg, isoproterenol). To assess the impact of nonphosphorylatable phospholamban, a S16A, T17A double-mutant (DM) was introduced into phospholamban knockout mouse hearts. Transgenic lines expressing DM phospholamban at levels similar to wild types (WT) were identified. In vitro phosphorylation confirmed that DM phospholamban could not be phosphorylated, but produced the same shift in EC50 of SERCA2a for Ca2+ as unphosphorylated WT phospholamban. Rates of basal twitch [Ca2+]i decline were not different in DM versus WT cardiomyocytes. Isoproterenol increased the rates of twitch [Ca2+]i decline in WT, but not DM myocytes, confirming the prominent role of phospholamban phosphorylation in this response. Increased L-type Ca2+ current (ICa) density, with unaltered characteristics, was the major compensation in DM myocytes. Consequently, the normal beta-adrenergic-induced increase in ICa caused larger dynamic changes in absolute ICa density. Isoproterenol increased Ca2+ transients to a comparable amplitude in DM and WT. There were no changes in myofilament Ca2+ sensitivity, or the expression levels and Ca2+ removal activities of other Ca2+-handling proteins. Nor was there evidence of cardiac remodeling up to 10 months of age. Thus, chronic inhibition of SERCA2a by ablation of phospholamban phosphorylation (abolishing its adrenergic regulation) results in a unique cellular adaptation involving greater dynamic ICa modulation. This ICa modulation may partly compensate for the loss in SERCA2a responsiveness and thereby partially normalize beta-adrenergic inotropy in DM phospholamban mice.

Cardiac Remodelling and Failure after Myocardial Infarction

Acute myocardial infarction, particularly when it produces large transmural infarcts, can initiate complex changes in the structural and functional architecture of both infarcted and non-infarcted regions of the left ventricle, known as ventricular remodelling; these changes can profoundly affect left ventricular function and, consequently, clinical outcome and prognosis. Ventricular remodelling is a dynamic process with regional and global effects on wall thickness and composition and on chamber size, shape and function; it can include infarct extension, infarct expansion, regional and global distortion and ventricular dilatation. A systematic strategy for the [primary] prevention of cardiac remodeling should probably be applied as early as possible to all patients suffering acute myocardial infarction. A [secondary] prevention strategy should focus on the early identification and treatment of subsets of patients with evidence of cardiac remodeling, because later treatments have already been shown to be beneficial. Cardiologists must choose the strategy most appropriate for each individual patient.