Severe Left Ventricular Remodeling Research Articles

Predictive Value of Two-Dimensional Speckle-Tracking Echocardiography in Patients Undergoing Surgical Ventricular Restoration

ObjectivesParameters of left ventricular (LV) mechanics, obtained from speckle-tracking echocardiography (STE), were found to be of prognostic value in patients with heart failure and those who underwent cardiac surgery. This study aimed to assess the value of STE in patients scheduled to undergo surgical ventricular restoration (SVR).MethodsA total of 158 consecutive patients with baseline STE who underwent SVR due to an LV anteroapical aneurysm were included in the analysis. Preoperative longitudinal STE parameters were evaluated for their association with an outcome, defined as all-cause mortality, LV assist device implantation, or heart transplantation. The echocardiographic follow-up to assess the change in the regional function of the segments remote from the aneurysm was performed in 43 patients at a median of 10 months [interquartile range (IQR): 6–12.7 months] after SVR.ResultsDuring a median follow-up of 5.1 years (IQR: 1.6–8.7 years), events occurred in 68 patients (48%). Less impaired mean basal end-systolic longitudinal strain (BLS) with a cutoff value ≤ −10.1 % demonstrated a strong association with event-free survival, also in patients with an LV shape corresponding to an intermediate shape between aneurysmal and globally akinetic. Initially hypo- or akinetic basal segments with preoperative end-systolic strain ≤ −7.8% showed a greater improvement in wall motion at the short-term follow up.ConclusionPatients with less impaired preoperative BLS exhibited a better event-free survival after SVR, also those with severe LV remodeling. The preserved preoperative segmental longitudinal strain was associated with a greater improvement in regional wall motion after SVR. BLS assessment may play a predictive role in patients with an LV anteroapical aneurysm who are scheduled to undergo SVR.

Machine-learning–based exploration to identify remodeling patterns associated with death or heart-transplant in pediatric-dilated cardiomyopathy

We investigated left ventricular (LV) remodeling, mechanics, systolic and diastolic function, combined with clinical characteristics and heart-failure treatment in association to death or heart-transplant (DoT) in pediatric idiopathic, genetic or familial dilated cardiomyopathy (DCM), using interpretable machine-learning. Echocardiographic and clinical data from pediatric DCM and healthy controls were retrospectively analyzed. Machine-learning included whole cardiac-cycle regional longitudinal strain, aortic, mitral and pulmonary vein Doppler velocity traces, age and body surface area. We used unsupervised multiple kernel learning for data dimensionality reduction, positioning patients based on complex conglomerate information similarity. Subsequently, k-means identified groups with similar phenotypes. The proportion experiencing DoT was evaluated. Pheno-grouping identified 5 clinically distinct groups that were associated with differing proportions of DoT. All healthy controls clustered in groups 1 to 2, while all, but one, DCM subjects, clustered in groups 3 to 5; internally validating the algorithm. Cluster-5 comprised the oldest, most medicated patients, with combined systolic and diastolic heart-failure and highest proportion of DoT. Cluster-4 included the youngest patients characterized by severe LV remodeling and systolic dysfunction, but mild diastolic dysfunction and the second-highest proportion of DoT. Cluster-3 comprised young patients with moderate remodeling and systolic dysfunction, preserved apical strain, pronounced diastolic dysfunction and lowest proportion of DoT. Interpretable machine-learning, using full cardiac-cycle systolic and diastolic data, mechanics and clinical parameters, can potentially identify pediatric DCM patients at high-risk for DoT, and delineate mechanisms associated with risk. This may facilitate more precise prognostication and treatment of pediatric DCM.

Left ventricular blood flow energetics after acute ST-segment elevation myocardial infarction associate with left ventricular remodeling

Abstract Background Myocardial infarction (MI) leads to complex changes in left ventricular (LV) haemodynamics. It remains unknown how four-dimensional (4D) acute changes in LV blood flow kinetic energy (KE) affect LV remodeling. We hypothesized that LV blood flow energetics are independently associated with adverse LV-remodeling. Methods In total, 69 revascularised ST-segment elevation MI patients were enrolled. All patients underwent cardiovascular magnetic resonance (CMR) examination within 2 days of the index event and at 3-month. CMR examination included cine, late gadolinium enhancement, and whole-heart 4D flow acquisitions. CMR analysis included: LV volumes, function, infarct size (indexed to body surface area), microvascular obstruction (MVO), two-dimensional, retrospective valve tracking derived mitral inflow metrics, and 4D blood flow KE components (Fig. 1). Adverse LV-remodeling was defined and categorized according to increase in LV end-diastolic volume: 10% (mild), 15% (moderate), and 20% (severe). Results Twenty-four patients (35%) developed mild, 17 patients (25%) moderate, 11 patients (16%) severe LV remodeling. Demographics and clinical history were comparable between patients with/without LV remodeling. In univariable logistic regression analysis, A-wave KE was associated with mild, moderate, and severe LV remodeling (p=0.03, p=0.02, p=0.02, respectively), whereas infarct size was associated with only mild LV remodeling (p=0.02). In multivariable logistic regression analysis, whilst the infarct size and A-wave KE were identified as independent markers for mild LV remodeling (p=0.03, p=0.09, respectively), A-wave KE was the only independent marker regarding moderate and severe LV remodeling (both, p<0.01). In ROC analysis for A-wave KE to be associated with the presence of adverse LV remodeling, the area under the curve was 0.67 for mild (p=0.02), 0.70 for moderate (p=0.01), 0.71 for severe (p=0.03) LV remodeling. Conclusion In patients with STEMI, LV hemodynamics assessment by LV blood flow KE demonstrated an incremental value to predict adverse LV-remodeling. A-wave KE early after acute MI had an independent effect on adverse LV remodeling. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): This work was supported by the British Heart Foundation [FS/10/62/28409 to S.P.] and Dutch Technology Foundation (STW), project number 11626 (JW, ME).

T-tubule disruption is a prominent feature of HFrEF but not HFpEF

Heart failure comprises two main entities; heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF), which both results from severe left ventricular remodeling. Whereas HFpEF is commonly caused by concentric hypertrophy and stiffening of the ventricular wall, HFrEF results from chamber dilation, wall thinning and reduced pump capacity.

Epicardial fat amount is associated with the magnitude of left ventricular remodeling in aortic stenosis.

Both genetic and environmental factors interact to control left ventricular (LV) remodeling in the context of aortic stenosis (AS). Epicardial adipose tissue (EAT) is a specific visceral adipose tissue with paracrine properties in close contact with the myocardium. We sought to assess determinants of EAT amount and its association with the magnitude and pattern of LV remodeling in patients suffering from severe AS. Between January 2014 and September 2017, we prospectively explored consecutive patients referred to our Heart Valve Center for SAVR presenting with severe AS and normal left ventricular ejection fraction (> 50%). Comprehensive transthoracic echocardiography (TTE) including assessment of LV remodeling and EAT amount were performed. 202 patients were included. EAT was significantly larger in elderly, diabetic and obese patients. EAT thickness was correlated positively with indexed LV mass in AS (r2 = 0.21; p < 0.0001) as well as severe LV remodeling pattern. Importantly, this observation persisted after adjustment for other factors associated with LV remodeling (β ± SE = 1.74 ± 0.34; p < 0.0001). Large amounts of EAT are positively and independently associated with more pronounced and severe LV remodeling in severe AS. Further exploration regarding the impact of functional properties of EAT on LV remodeling is required.

Interaction of Left Ventricular Remodeling and Regional Dyssynchrony on Long-Term Prognosis after Cardiac Resynchronization Therapy

Left ventricular (LV) remodeling in heart failure (HF) manifested by chamber dilatation is associated with worse clinical outcomes. However, the impact of LV dilatation on the association of measures of dyssynchrony with long-term prognosis and resynchronization potential after cardiac resynchronization therapy (CRT) remains unclear. Two hundred sixty CRT patients in New York Heart Association classes II to IV, with ejection fractions≤35% and QRS intervals≥120msec, were prospectively studied. Quantitative echocardiographic assessment of LV volumes and mechanical dyssynchrony by radial strain was conducted at both baseline and 6-month follow-up. Primary outcome events were predefined as death or HF hospitalization, and secondary outcome events were defined as all-cause death over the 4years after CRT. Patients were divided into two groups using the median of the baseline indexed LV end-diastolic volume (EDVI). Patients with less dilated left ventricles (EDVI<90mL/m2) had improved prognosis compared to those with severely dilated left ventricles (EDVI≥90mL/m2) for both primary (adjusted hazard ratio [HR], 2.20; 95% CI, 1.44-3.38; P<.01) and secondary (adjusted HR, 1.94; 95% CI, 1.21-3.11; P<.01) events. Similarly, reduction in baseline dyssynchrony was associated with good prognosis for both the primary (HR, 0.39; 95% CI, 0.23-0.68; P=.001) and secondary (HR, 0.41; 95% CI, 0.22-0.75; P=.004) events. A linear association was found between each 10% reduction in dyssynchrony and events (P<.01). Notably, patients with less dilated left ventricles had nearly fourfold more frequent improvement in dyssynchrony compared to those with severely dilated left ventricles (odds ratio, 4.10; 95% CI, 1.81-9.28; P<.01). No other baseline prognostic marker was associated with the resynchronization ability of CRT. Patients with severe LV remodeling (EDVI≥90mL/m2) have a poor prognosis following CRT device implantation. This is most likely due to impaired resynchronization efficacy.

Rola krążącego receptora dla IL-33 (sST2) w monitorowaniu terapii niewydolności serca

Heart failure (HF) is currently one of the major health problems in Poland and in other European countries. Despite the progress that has been made in the treatment of HF, mortality and the incidence of re-hospitalization for HF are still very high. One of the reasons is the lack of proper heart failure treatment optimization. Among the currently studied new biomarkers of heart failure, one of the special interest is circulating receptor for IL-33 (sST2). It has been shown that IL-33 plays cardioprotective role. Its molecular mechanisms of action are based mainly on the activation of the transmembrane form of ST2 receptor (ST2L). Availability of IL-33 for ST2L is limited by binding to the soluble fraction of the ST2 (sST2) — called a „decoy receptor”. The presence of elevated levels of sST2 in the population of patients with heart failure is associated with more severe left ventricular remodeling, impaired diastolic function and right ventricle function. Patients with both HF and high and/or rising levels sST2 are at high risk of adverse cardiovascular events. The standard treatment for heart failure leads to reduction in sST2 concentration. Among the drugs used in the heart failure treatment, two with the largest impact on reducing concentration of sST2 are beta-blockers in high doses, and aldosterone.

GENDER DIFFERENCES OF CORONARY HEART DISEASE PATIENTS WITH POSTINFARCTION CARDIOSCLEROSIS AND CHRONIC MITRAL REGURGITATION BY THE DATA OF CORONARY ANGIOGRAPHY REGISTRY

Aim. To reveal gender differences of clinical and functional parameters in postmyocardial infarction patients with chronic mitral regurgitation by data of coronary angiography Registry.Material and methods. Among 15283 patients of Coronary angiography Registry© evaluated from 1991 to 2012 we selected end assessed clinical and functional parameters of 350 men and 53 women with Q-wave myocardial infarction and moderate or severe mitral regurgitation and signs of scars detected by echocardiography.Results. Comparing to the men, women had lower hemoglobin level (135,5±11,3 vs 148,3±14,2 g/l, р&lt;0,001) and rate of smokers (9,8 vs 62,6%, р&lt;0,001). The prevalence of hypothyroidism (29,7 vs 9,6%, р=0,001) and severe MR (17,0 vs 9,1%, р=0,038) were higher in women. They had higher indexes of left atrium size (25,1±2,9 vs 23,7±3,2 mm/m2, р=0,008), left ventricular (LV) posterior wall thickness (6.0±0.7 vs 5,2±0,8 mm/m2, р&lt;0,001), lower extent of LV wall motion abnormalities (28,7±14,7 vs 33,5±14,9%, р=0,036) and higher LV ejection fraction (47,3±8,2 vs 43,9±9,2%, р=0,013). The localization of myocardial scars and coronary stenosis did not differ between men and women. According to the results of multivariate analysis, female gender was independently associated with greater index of LV posterior wall thickness (OR 3,215; CI 1,781–5,804; р&lt;0,001), hypothyroidism (OR 3,070; CI 0,994–9,483; р=0,050), greater body mass index (OR 1,17; CI 1,042–1,317; р=0,008), smoking (ОR 0,056; CI 0,013–0,244; р&lt;0,001) and lower hemoglobin level (OR 0,927; CI 0,890–0,966; р&lt;0,001).Conclusion. There are gender differences in clinical and functional parameters of postmyocardial infarction patients with chronic mitral regurgitation: more severe LV remodeling in women.

Imaging Challenges in Secondary Mitral Regurgitation

Chronic secondary mitral regurgitation (SMR) is a complex entity that is often clinically underappreciated.1 It complicates either ischemic heart disease or dilated cardiomyopathy; its prevalence varies among series but may reach ≤50% in patients with heart failure.2 When present, SMR may exhibit a broad range of severity and confers an adverse prognosis, which is worse with increasing severity of mitral regurgitation (MR).3,4 The management of SMR poses a unique set of challenges, based partly on the complexity of the valve disorder and the still-evolving adoption of the optimal therapeutic approach.5 Noninvasive imaging and, in particular, echocardiography, plays a critical role for the initial and longitudinal assessment, for individual risk stratification and outcome prediction, and for guiding intervention in patients with chronic SMR.6 SMR develops because of a combination of mitral leaflet tethering secondary to left ventricular (LV) dilatation/deformation with papillary displacement/discoordination, annular dilatation/dysfunction, insufficient LV-generated closing forces attributable to reduction of LV contractility, and global LV/papillary muscle dyssynchrony.1,5 Tethering of the mitral leaflets is the principal lesion of SMR and results in restriction of systolic leaflet motion, namely type IIIb of Carpentier’s classification. SMR does not typically occur in global LV dysfunction without tethering. However, once tethering occurs, leaflet closure is further impaired by LV dysfunction because there is decreased force opposing tethering.6–9 The key event in the pathogenesis of SMR is the distortion of normal LV geometry—regional and global LV remodeling—with subsequent apical and lateral displacement of papillary muscles, which, in turn, draws the chordae tendineae away from the line of coaptation.7,8 The extent of LV systolic dysfunction and dilatation is weakly correlated to the degree of SMR unless accompanied by geometric distortion in the region of the papillary muscles.1,9 …

Establishing New Porcine Ischemic Cardiomyopathy Model by Transcatheter Ischemia-Reperfusion of the Entire Left Coronary Artery System for Preclinical Experimental Studies

Heart failure associated with ischemic cardiomyopathy (ICM) as a result of myocardial infarction (MI) is an increasing health concern (1). Although a variety of new potential therapies have been reported to have the potential of fundamental therapeutic effects in preclinical animal experimental stud

Clinical significance of papillary muscle late enhancement detected via cardiac magnetic resonance imaging in patients with single old myocardial infarction

Contrast-enhanced cardiac magnetic resonance imaging (MRI) can depict papillary muscle (PM) necrosis or fibrosis by late enhancement (LE) of PM, but its clinical significance in old myocardial infarction (OMI) has been little understood. Myocardial LE and PM-LE were detected with contrast imaging in 60 patients with OMI caused by a single culprit coronary artery lesion. Left ventricular (LV) morphology and function, mitral valve geometry, and severity of mitral regurgitation were also evaluated by cine imaging. Sphericity index was calculated for the assessment of LV remodeling. PM-LE was detected in 32 of 60 (53.3%) OMI patients. Unilateral PM-LE was detected in 22 patients and bilateral PM-LE in 10 patients. Patients with bilateral PM-LE demonstrated more severe LV remodeling and functional mitral regurgitation than those with unilateral or no PM-LE (sphericity index; bilateral PM-LE, 1.60±0.15, unilateral PM-LE, 1.71±0.29, no PM-LE, 1.85±0.27, p≤0.05) (mitral regurgitation; bilateral PM-LE, 1.10±0.57, unilateral PM-LE, 0.41±0.73, no PM-LE, 0.54±0.84, p≤0.05). In cases of unilateral PM-LE, posteromedial PM-LE resulting from right coronary artery-related OMI was accompanied by less severe mitral regurgitation, while anterolateral PM-LE resulting from left coronary artery-related OMI was not associated with severity of mitral regurgitation. More than half of patients with OMI showed unilateral or bilateral PM-LE, and bilateral PM-LE was closely related to more severe LV remodeling and functional mitral regurgitation.

Remodeled left ventricular myocardium remote to infarction sites is the arrhythmogenic substrate for sudden cardiac death

Ventricular tachyarrhythmias are life threatening cardiac arrhythmias and are the most common causes of sudden cardiac death. Greater post-infarction left ventricular remodeling has been shown to have a greater preponderance of ventricular arrhythmias. The hypothesis herein is that adverse structural and electrophysiological remodeling at non-infarcted regions after myocardial infarction constitutes the arrhythmogenic substrate responsible for clinically occurring ventricular arrhythmias leading to sudden cardiac death. Post-infarction patients with more severe left ventricular remodeling (regional hypertrophy) at sites remote to infarction scar might have the highest risk for sudden cardiac death due to lethal ventricular arrhythmias. In the hypertrophic non-infarcted zone, larger action potential duration and repolarization heterogeneity is not in self arrhythmogenic, but can predispose towards arrhythmia development under certain condition, such as transient myocardial ischemia. We should draw more attention to apparently "normal" non-infarction region for further understanding the mechanism of sudden cardiac death.

Myocardial performance index: prediction and monitoring of remodeling and functioning of the left ventricle after first myocardial infarction

Dynamic changing of left ventricular geometry and contractile state after acute myocardial infarction is responsible for various aspects of left ventricular remodeling and dysfunction. A number of studies have shown that myocardial performance index allows prediction of acute myocardial infarction complications. The objective of our study was to determine the power of myocardial performance index to predict and assess the severity of left ventricular remodeling, systolic and diastolic dysfunction after acute myocardial infarction over the long term. Echocardiography was performed within the first week of hospitalization, after one, three and six months in 77 patients with first acute myocardial infarction. At the end of the study the patients were divided into group A and B with mild and severe left ventricular remodeling, respectively. Myocardial performance index was significantly lower in group A compared to B, at the beginning (0.62 vs. 0.75; p = 0.002), and at the end of study (0, 60 vs. 0, 69; p = 0.004). After six months, 31% of study patients developed LV systolic dysfunction with prevalence in group B (56% vs. 19%, p = 0.002). Myocardial performance index > or = 0.70 at first week after acute myocardial infarction is a strong predictive parameter for extensive early and late left ventricular remodeling and systolic dysfunction (p < 0.05), but it is not a valuable predictor of diastolic failure. MPI obtained at first week of acute myocardial infarction was predictive for early and long term left ventricular remodeling and systolic dysfunction. Myocardial performance index had doubtful clinical use in assessing dynamics of remodeling and it was without clinical value in predicting diastolic function deterioration.

Effects of Various Diuretics on Cardiac Function in Rats with Heart Failure

Torasemide is a long-acting loop diuretic that combines the effects of both furosemide and spironolactone. It has been reported that torasemide but not furosemide might attenuate myocardial remodeling accompanied by left ventricular (LV) dysfunction. However, nothing is known about the effect of torasemide, long-acting loop diuretic and spironolactone, an aldosterone receptor antagonist in a rat model of chronic heart failure (CHF). Therefore, we compared the therapeutic effects of torasemide, furosemide and spironolactone on the progression of LV remodeling in a rat model of CHF after experimental autoimmune myocarditis (EAM). EAM was elicited in Lewis rats by immunization with porcine cardiac myosin. Twenty-eight days after immunization, rats were treated for 28 days with torasemide, furosemide and spironolactone. Diuretic actions, heart weight/body weight, heart rate, mean blood pressure, myocardial function by echocardiography, cardiac fibrosis, myocyte diameter and cardiac aldosterone synthetase (CYP11B2) were evaluated. Increased cardiac CYP11B2, severe LV remodeling and resultant cardiac dysfunction was found in CHF rats, whereas decreased cardiac CYP11B2, less remodeling and improvement of cardiac function were found in torasemide- and spironolactone-treated CHF rats. Our results indicate that torasemide and spironolactone treatment significantly improved cardiac function and LV remodeling compared with furosemide treatment.

Abstract 5422: Effect of Age on Expression of AT 1 and AT 2 Receptors and ACE-2, Angiotensin (1–7), Ac-SDKP and Smad-2 Proteins After Acute Reperfused ST-Segment Elevation Myocardial Infarction

Recent evidence suggests that aging alters the expression of inflammatory cytokines, impairs healing and promotes adverse left ventricular (LV) remodeling after chronic reperfused ST-segment elevation myocardial infarction (RSTEMI). Whether aging alters the expression of angiotensin II type 1 (AT 1 ) and type 2 (AT 2 ) receptors, and angiotensin-converting-enzyme-2 (ACE-2), angiotensin (Ang) (1–7), N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) and Smad-2 proteins early after acute RSTEMI is not known. AT 2 receptors have been implicated in cardioprotection, ACE-2 and Ang (1–7) in the counter-regulatory arm of the renin-angiotensin-system (RAS) and Ac-SDKP in inflammation and collagen synthesis. We hypothesized that aging is associated with downregulation of AT 2 receptors and ACE-2, Ang (1–7), Ac-SDKP and Smad-2 proteins. We compared in-vivo LV remodeling and function (echocardiography/Doppler) and the ex-vivo molecular expression of AT 1 and AT 2 receptors, ACE-2, Ang (1–7) and Ac-SDKP after acute RSTEMI (90 min no-flow ischemia and 120 min reperfusion) in young (group 1, n=12) and old (group 2, n=12) dogs. Compared to group 1 controls, group 2 hearts showed more severe echocardiographic LV remodeling and dysfunction (with lower ejection fraction, larger volumes and more diastolic dysfunction, infarct expansion and thinning). In addition, group 2 hearts showed no change in AT 1 receptor protein and decrease in AT 2 receptor protein and ACE-2, Ang (1–7), Ac-SDKP and Smad-2 proteins in the reperfused ischemic zone. The findings suggest that aging is associated with changes in proteins in the regulatory as well as the counter-regulatory arm of the RAS during acute RSTEMI. The age-related downregulation of AT 2 receptors, ACE-2, Ang (1–7), Ac-SDKP and Smad-2 may contribute to the more severe LV remodeling and dysfunction after acute RSTEMI. Targeting these proteins early during reperfusion may improve outcome in acute RSTEMI.

Age-related differences in postinfarct left ventricular rupture and remodeling

Cardiac rupture is more prevalent in elderly patients with first onset of acute myocardial infarct (MI), but the mechanism remains unexplored. We investigated the differences in the incidence of cardiac rupture and early left ventricular (LV) remodeling following coronary artery ligation between old (12-mo) and young (3-mo) C57Bl/6 male mice and explored responsible mechanisms. The incidence of rupture within 1 wk after MI was significantly higher in old than in young mice (40.7 vs. 18.3%, P = 0.013) despite a similar infarct size in both age groups. Old mice dying of rupture had more severe infarct expansion than young counterparts. Echocardiography and catheterization at day 7 revealed more profound LV chamber dilatation and dysfunction as well as higher blood pressures in aged mice. At day 3 after MI immediately before the peak of rupture occurrence, we observed significantly higher content of type I and III collagen, a greater density of macrophage and neutrophil, and markedly enhanced mRNA expression of inflammatory cytokines in the infarcted myocardium in old than in young mice. Furthermore, a more dramatic increment of matrix metalloproteinase (MMP)-9 activity was found in old than in young infarcted hearts, in keeping with enhanced inflammatory response. Collectively, these results revealed that old mice had a higher risk of post-MI cardiac rupture despite a higher level of collagen content and cross-linking. Enhanced inflammatory response and subsequent increase in MMP-9 activity together with higher blood pressure are important factors responsible for the higher risk of cardiac rupture and more severe LV remodeling in the aged heart following acute MI.

Persistent Cardiac Aldosterone Synthesis in Angiotensin II Type 1A Receptor–Knockout Mice After Myocardial Infarction

The renin-angiotensin-aldosterone system is implicated in the pathogenesis of heart failure. Pharmacological blockade of angiotensin II (Ang II)-dependent signaling is clinically effective in reducing cardiovascular events after myocardial infarction (MI) but still fails to completely prevent remodeling. The molecular basis underlying this Ang II-independent remodeling is unclear. Acute MI was induced by coronary ligation in wild-type (WT) and angiotensin II type IA receptor-knockout (AT1A-KO) mice. Left ventricular (LV) geometry, hemodynamics, and cardiac gene expression were evaluated on day 28. Severe LV remodeling and resultant cardiac dysfunction were observed in WT mice, whereas less marked, but still significant, LV remodeling and cardiac dysfunction were induced in AT1A-KO mice. Gene expression levels of aldosterone synthase and the cardiac aldosterone content were both elevated in the MI hearts, even in AT1A-KO mice. In AT1A-KO mice treated with spironolactone (20 mg/kg per day), LV remodeling, cardiac dysfunction, and cardiac gene expression of collagens and natriuretic peptides were almost normalized. Our results indicate that genetic blockade of AT1A signaling fails to arrest aldosterone production in cardiac tissues and that cardiac aldosterone plays a critical role in post-MI LV remodeling. The results suggest that spironolactone could be potentially effective in patients with MI, when used in combination with renin-angiotensin system blockade, by blocking the actions of aldosterone produced by Ang II-independent mechanisms.

The dog model of left ventricular remodeling after myocardial infarction

Background: For over a century, the dog model has been used widely in research studying cardiovascular physiology pertinent to humans. It has been specially applied, over the past 2 decades, in research on the pathophysiology and treatment of left ventricular (LV) remodeling and heart failure. Methods and Results: Because progressive LV remodeling and the march to heart failure are major problems facing myocardial infarction (MI) survivors, the dog model of acute MI was modified for the study of LV structural remodeling and dysfunction during post-MI healing (especially anterior MI). The dog model of post-MI LV remodeling, as the other models, has contributed to our understanding of the pathophysiology of LV remodeling and underlying mechanisms, and to the development of improved therapeutic strategies. Recent increase in costs and public concern over their use in research should be considered when using this model Conclusions: This is an important model for studying strategies to prevent severe LV remodeling in humans.

Cardiac troponin I and T alterations in hearts with severe left ventricular remodeling

Cardiac troponin T (cTnT) and troponin I (cTnI) have been suggested as new, more specific markers of myocardial cellular damage. The objective of this study was to examine how the distributions of cTnI and cTnT were affected in postinfarction left ventricular remodeled (LVR) myocardium. At 2 months postinfarct in a porcine heart failure model, both Western blot and biochemical assay analyses were performed on left ventricular myocardium remote from the infarct zone in ligation animals (n = 8). Results were compared with data from the left ventricular myocardium from similar sized healthy (control) pigs (n = 7). Autoradiograms from Western blot analysis showed that the protein mass for cTnI and cTnT in LVR hearts decreased 80% (P < 0.001) and 40% (P < 0.02), respectively, when compared with nondiseased tissue. Similarly, the concentrations for cTnI and cTnT in LVR hearts decreased 42% (P < 0.05) and 70% (P < 0.001), respectively, compared with nondiseased normal tissue. The clinical assumption is that the appearance of cTnI and cTnT in the blood is proportional to chronic loss of cTnI and cTnT from injured myocardium associated with left ventricular remodeling.