Differences In Ventricular Remodeling Research Articles

Cardiac magnetic resonance shows increased adverse ventricular remodeling in younger patients after ST-segment elevation myocardial infarction

ObjectivesYoung patients account for about half of ST-segment elevation myocardial infarction (STEMI) patients and display a unique risk profile compared with old patients. Whether these differences are related to disparities in ventricular remodeling remains unknown. This study aimed to evaluate age-related differences in ventricular remodeling after primary percutaneous coronary intervention (PPCI) for STEMI.MethodsIn this observational study, consecutive STEMI patients between October 2019 and March 2021 who underwent serial cardiovascular magnetic resonance at index admission (3 to 7 days) and 3 months after PPCI were enrolled. Adverse remodeling was defined as ≥ 10% enlargement in left ventricular end-diastolic volume index (LVEDVi), while reverse remodeling was defined as a decrease in left ventricular end-systolic volume index (LVESVi) of more than 10%.ResultsA total of 123 patients were included and grouped into young (< 60 years, n = 71) and old (≥ 60 years, n = 52) patients. Despite generally similar baseline structural and infarct characteristics, LVESVi significantly decreased only in old patients during follow-up (p = 0.034). The incidence of adverse remodeling was higher (49.3% vs 30.8%, p = 0.039), while the incidence of reverse remodeling was lower (31.0% vs 53.8%, p = 0.011) in young compared with old patients. Younger age (< 60 years) was associated with a significantly higher risk of adverse remodeling (adjusted OR 3.51, 95% CI 1.41–8.74, p = 0.007) and lower incidence of reverse remodeling (adjusted OR 0.42, 95% CI 0.18–0.97, p = 0.046).ConclusionsIn STEMI patients undergoing PPCI, young patients are at a higher risk of adverse remodeling and less probably develop reverse remodeling than old patients. Equal or more attention should be paid to young patients with STEMI compared with their older counterparts.Key Points• In STEMI patients undergoing PPCI, young patients displayed unfavorable remodeling compared with old patients.• Young patients are at a higher risk of adverse remodeling and less probably develop reverse remodeling than old patients.• Equal or more attention should be paid to young patients compared with their older counterparts.

Abstract 10282: Biventricular Shape Markers in Repaired Tetralogy of Fallot Associate with Pulmonary Valve Replacement Better Than Standard Clinical Indices

Introduction: Current indications for pulmonary valve replacement (PVR) in repaired tetralogy of Fallot (rTOF) rely on global ventricular measurements but are inconsistently applied, lead to mixed outcomes, and are widely debated. Hypothesis: We aimed to test the hypothesis that specific regional markers of biventricular shape can discriminate differences in ventricular remodeling between rTOF patients that were and were not designated for follow-up PVR better than standard clinical indices. Methods: In this cross-sectional retrospective study, biventricular shape models were fit to CMR images from 84 rTOF patients. A statistical atlas of end-diastolic shape was constructed using principal component analysis. Multivariate regression was used to quantify shape marker and clinical index associations with subsequent intervention status (PVR, n=48 vs. No-PVR, n=36) while accounting for confounders. Clustering analysis was then used to test the ability of statistically significant shape markers and clinical indices to discriminate PVR status as evaluated by Matthews correlation coefficient (MCC). Geometric strain analysis was also conducted to assess shape marker associations with systolic function. Results: PVR status correlated with shape markers associated with RV apical dilation and LV dilation (p&lt;0.001), RV basal bulging and LV conicity (p&lt;0.02), and pulmonary valve dilation (p&lt;0.002). PVR status also correlated with RV EF (p&lt;0.03) and non-significantly correlated with LV ESVi (p&lt;0.06). Clustering analysis revealed that shape markers discriminated PVR status better than clinical indices (MCC=0.49 and MCC=0.28, respectively). These shape markers were also significantly associated with RV and LV radial strain. Conclusions: Biventricular shape markers discriminated PVR status better than standard and current use clinical indices for PVR. These specific, regional features of cardiac morphology can provide mechanistic insight into adaptive vs. maladaptive types of ventricular remodeling that provide the foundation for clinical decision-making but may be overlooked when relying solely on global ventricular measurements.

Sex-related differences in ventricular remodeling after myocardial infarction

The epidemiology, clinical features and outcome of myocardial infarction (MI) display significant differences between men and women. Prominent sex differences have also been suggested in left ventricular (LV) remodeling after MI. Ventricular remodeling refers to a deterioration of LV geometry and function often leading to heart failure (HF) development and an increased risk of adverse cardiovascular events. Women have a lower propensity to the acquisition of a spherical geometry and LV dysfunction. These differences can be attributed at least partially to a lower frequency of transmural infarction and smaller areas of microvascular obstruction in women, as well as to a less prominent activation of neuroendocrine systems and apoptotic, inflammatory and profibrotic pathways in women. Estrogens might play a role in this difference, which could partially persist even after the menopause because of a persisting intramyocardial synthesis of estrogens in women. Conversely, androgens may exert a detrimental influence. Future studies should better clarify sex differences in the predictors, clinical correlates, prognostic impact and disease mechanisms of remodeling, as well as the existence of sex-specific therapeutic targets. This research effort should hopefully allow to optimize the treatment of MI during the acute and post-acute phase, possibly through different therapeutic strategies in men and women, with the goal of reducing the risk of HF development and improving patient outcome.

Sex differences in ventricular remodeling and long-term heart failure outcomes following acute coronary syndrome

Abstract Background Compared with men, women are at increased risk of heart failure hospitalization following acute coronary syndrome (ACS). Purpose We sought to determine whether this increased hazard was associated with differing patterns in left ventricular (LV) remodeling over the first 12 months after ACS. Methods In a prospective multi-centre observational cohort study, 2,140 patients with ACS underwent echocardiography at 1, 4, and 12 months following the index event. Heart failure hospitalisation events were captured over a median 4.8 (IQR 3.4–6.5) years and relative risk compared between women and men using a multivariable Cox model adjusted for baseline demographics (age and systolic blood pressure) and echocardiographic variables (LV end diastolic and end systolic volumes, LV ejection fraction, interventricular septal wall thickness, and E/e') captured at baseline and 12 months. Results The 609 (28.5%) women were older (mean [SD] age 70 [12] versus 65 [12] years), had higher systolic blood pressure, demonstrated smaller increases in peak myocardial biomarkers, and were less likely to undergo coronary revascularization during the index admission (41.9% versus 62.0%; p&amp;lt;0.001 for all). After indexing for body surface area, women had smaller LV end diastolic and end systolic volumes, greater LV ejection fractions, and greater septal wall thickness and diastolic filling pressure estimates (E/e' 14 versus 11; p&amp;lt;0.001 for all). Diastolic volumes further diverged at 12 months (p=0.05) and septal wall thickness increased compared with men (p=0.016). In unadjusted and adjusted analyses women were at increased risk of future heart failure hospitalization (unadjusted HR 1.5, 95% CI 1.2–1.9, adjusted HR 1.6, 95% CI 1.1–2.4). Conclusions Women experience a more concentric remodeling pattern over the 12 months following ACS. Women remain at increased risk of long-term heart failure hospitalization after accounting for clinical and echocardiographic characteristics. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): National Heart Foundation of New Zealand, New Zealand Health Research Council

Age-related differences in ventricular remodeling and long-term heart failure outcomes following acute coronary syndrome

Abstract Background Older patients are at increased risk of heart failure hospitalization following acute coronary syndrome (ACS). Purpose We sought to determine whether this increased hazard was related to differing patterns in left ventricular (LV) remodeling over the first 12 months after ACS. Methods In a prospective multi-centre observational cohort study, 2,140 patients with ACS underwent echocardiography at 1, 4, and 12 months following the index event. Long-term heart failure hospitalisation events were captured for a median 4.8 (IQR 3.4–6.5) years and the relative risk compared between individuals ≤65 years and those &amp;gt;65 years using a multivariable Cox model adjusted for baseline clinical (sex, blood pressure, coronary revascularisation) and echocardiographic (LV end diastolic and end systolic volumes, LV ejection fraction, interventricular septal wall thickness, and E/e') variables recorded at baseline and 12 months. Results The 1177 (55%) participants who were &amp;gt;65 years were more likely to be women (34% versus 22%), had higher blood pressure, were more likely to present with non-ST elevation ACS, demonstrated smaller increases in peak myocardial biomarkers and were less likely to undergo coronary revascularization during the index admission (43.2% versus 72.3%; p&amp;lt;0.001 for all comparisons). At the 1 month visit, after indexing for body surface area, older patients had similar LV end diastolic but larger end systolic volumes (p=0.029), lower LV ejection fractions, and greater left ventricular mass and diastolic filling pressure estimates (E/e' 14 versus 10; p&amp;lt;0.001 for all) compared with the young. Systolic volumes appeared to further diverge at 12 months (p=0.064) however LV mass did not change in either group. In unadjusted analysis older patients were at increased risk of future heart failure hospitalization (HR 4.1, 95% CI 3.2–5.3). This increased risk persisted after adjustment for differences in baseline clinical and echocardiography data, and LV remodeling (adjusted HR 2.4, 95% CI 1.5–3.9). Conclusions Older patients experience a more eccentric remodeling pattern over the 12 months following ACS. Older individuals remain at increased risk of long-term heart failure hospitalization after accounting for clinical and echocardiographic characteristics. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): New Zealand Heart Foundation, New Zealand Health Research Council

A055 Sex Differences in Ventricular Remodeling and Long-Term Heart Failure Outcomes Following Acute Coronary Syndrome

Compared with men, women are at increased risk of heart failure hospitalisation following acute coronary syndrome (ACS). We investigated whether this increased hazard was associated with differing left ventricular (LV) remodelling patterns over the first 12 months after ACS. In a prospective multi-centre observational cohort study, 2,140 patients with ACS underwent echocardiography at 1, 4, and 12 months. Heart failure events were captured over a median 4.8 (IQR 3.4-6.5) years and relative risk compared between women and men using a multivariable Cox model adjusted for baseline demographics (age and systolic blood pressure) and echocardiographic variables (LV end-diastolic and end-systolic volumes, LV ejection fraction, septal wall thickness, and E/e') captured at 1 and 12 months. The 609 (28.5%) women were older, had higher blood pressure, demonstrated smaller increases in cardiac biomarkers, and were less likely to undergo revascularisation during the index admission (41.9% versus 62.0%; p<0.001 for all). After indexing, women had smaller LV end-diastolic and end-systolic volumes, greater LV ejection fractions, and greater septal wall thickness and diastolic filling pressure estimates (E/e' 14 versus 11; p<0.001 for all). Diastolic volumes further diverged at 12 months (p=0.05) and septal wall thickness increased compared with men (p=0.016). In unadjusted and adjusted analyses women were at increased risk of heart failure hospitalisation (unadjusted HR 1.5, 95%CI 1.2-1.9, adjusted HR 1.6, 95%CI 1.1-2.4). Women experience a more concentric remodeling pattern following ACS. Women remain at increased risk of long-term heart failure hospitalisation after accounting for clinical and echocardiographic characteristics.Tabled 1≤65 years (n=963)>65 years (n=1177)pSex, men755 (78.4)776 (65.9)<0.001Systolic BP, mmHg124.22 (20.08)132.69 (22.42)<0.001LV end diastolic volume, indexed to BSA65.86 (19.27)65.87 (22.20)0.997% change from 1 to 12 months1.81 (26.47)3.59 (24.55)0.220LV end systolic volume, indexed to BSA28.64 (15.57)30.62 (19.23)0.029% change from 1 to 12 months2.60 (35.36)6.70 (41.09)0.064 Open table in a new tab

A054 Age-Related Differences in Ventricular Remodeling and Long-Term Heart Failure Outcomes Following Acute Coronary Syndrome

Older patients are at increased risk of heart failure following acute coronary syndrome (ACS). We investigated whether this hazard related to differing patterns in left ventricular (LV) remodeling. In a prospective multi-centre observational study, 2,140 patients with ACS underwent echocardiography at 1, 4, and 12 months following the index event with long-term heart failure hospitalisations captured for a median 4.8 (IQR 3.4-6.5) years. Individuals ≤65 years and those >65 years were compared using multivariable Cox models adjusted for baseline clinical (sex, blood pressure, revascularisation) and echocardiographic (LV end-diastolic/end-systolic volumes, LV ejection fraction, septal wall thickness, and E/e') variables recorded at 1 and 12 months. The 1177 (55%) participants who were >65 years were more likely to be women, had higher blood pressure, demonstrated smaller increases in cardiac biomarkers and were less likely to undergo coronary revascularisation (p<0.001 for all). At the 1-month visit, after indexing, older patients had similar LV end-diastolic but larger end-systolic volumes (p=0.029), lower LV ejection fractions, and greater LV mass and diastolic filling pressure estimates (E/e' 14 versus 10; p<0.001 for all). Systolic volumes appeared to further diverge at 12 months (p=0.064) however LV mass did not change in either group. In both unadjusted and adjusted analyses older patients were at increased risk of future heart failure hospitalisation (unadjusted HR 4.1, 95%CI 3.2-5.3; adjusted HR 2.4, 95%CI 1.5-3.9). Older patients experience more eccentric remodeling following ACS although remain at increased risk of heart failure hospitalisation after accounting for clinical and echocardiographic characteristics.Tabled 1≤65 years (n=963)>65 years (n=1177)p-valueLV end systolic volume, indexed to BSA28.64 (15.57)30.62 (19.23)0.029% change from 1 to 12 months2.60 (35.36)6.70 (41.09)0.064 Open table in a new tab

Gender Differences in Ventricular Remodeling and Function in College Athletes, Insights from Lean Body Mass Scaling and Deformation Imaging

Several studies suggest gender differences in ventricular dimensions in athletes. Few studies have, however, made comparisons of data indexed for lean body mass (LBM) using allometry. Ninety Caucasian college athletes (mixed sports) who were matched for age, ethnicity, and sport total cardiovascular demands underwent dual-energy x-ray absorptiometry scan for quantification of LBM. Athletes underwent comprehensive assessment of left and right ventricular and atrial structure and function using 2-dimensional echocardiography and deformation imaging using the TomTec analysis system. The mean age of the study population was 18.9 ± 1.9 years. Female athletes (n = 45) had a greater fat free percentage (19.4 ± 3.7%) compared to male athletes (11.5 ± 3.7%). When scaled to body surface area, male had on average 19 ± 3% (p <0.001) greater left ventricular (LV) mass; in contrast, when scaled to LBM, there was no significant difference in indexed LV mass -1.4 ± 3.0% (p = 0.63). Similarly, when allometrically scaled to LBM, there was no significant gender-based difference in LV or left atrial volumes. Although female athletes had mildly higher LV ejection fraction and LV global longitudinal strain in absolute value, systolic strain rate and allometrically indexed stroke volume were not different between genders (1.5 ± 3.6% [p = 0.63] and 0.0 ± 3.7% [p = 0.93], respectively). There were no differences in any of the functional atrial indexes including strain or strain rate parameters. In conclusion, gender-related differences in ventricular dimensions or function (stroke volume) appear less marked, if not absent, when indexing using LBM allometrically.

Heart failure in women.

Heart failure (HF) is increasing in incidence globally, and approximately half of all HF patients are women. When women and men with HF are compared, there are significant differences in disease etiology, expression, outcomes, and perhaps, response to therapy. Hypertension rather than coronary artery disease is a more important etiology of HF in women, and HF with preserved left ventricular ejection fraction (HFPEF) is more common in women. Regardless of its etiology, women have better survival and less sudden cardiac death, but poorer quality of life with equivalent degrees of left ventricular dysfunction. Animal studies of myocardial response to stressors resulting in heart failure corroborate sex differences in ventricular remodeling, cellular morphology, and function. Despite the fact that women make up nearly 50 % of HF patients, their inclusion in randomized clinical trials has remained at about 20 %, with no trials including women as a prespecified subgroup for statistical analysis. Thus, the evidence base for treatment of HF in women is not robustly supported by sex-specific data.

Race Differences in Ventricular Remodeling and Function Among College Football Players

Athletic training is associated with increases in ventricular mass and volume. Recent studies have shown that left ventricular mass increases proportionally in white athletes with a mass/volume ratio approaching unity. The objective of this study was to compare the proportionality in ventricular remodeling and ventricular function in black versus white National Collegiate Athletic Association Division I football players. From 2008 to 2011, football players at Stanford University underwent cardiovascular screening with a 12-point history and physical examination, electrocardiography, and focused echocardiography. Compared with white players, black players had on average higher left ventricular mass indexes (77 ± 11 vs 71 ± 11 g/m(2), p = 0.009), higher mass/volume ratios (1.18 ± 0.16 vs 1.06 ± 0.09 g/ml, p <0.001), and higher QRS vector magnitudes (3.2 ± 0.7 vs 2.7 ± 0.8, p = 0.002). Black race had an odds ratio of 14 (95% confidence interval 5 to 42, p <0.001) for a mass/volume ratio >1.2. Mass/volume ratio was inversely related to early diastolic tissue Doppler velocity e' (r = -0.50, p <0.001) but not to QRS vector magnitude (r = 0.065, p = 0.034). With regard to systolic indexes, there was no significant difference in the left ventricular ejection fraction, velocity of circumferential shortening, and isovolumic acceleration. In conclusion, black college football players exhibit more concentric ventricular remodeling, lower early diastolic annular velocities, and increased ventricular voltage compared with white players. Ventricular mass increases proportionally to volume in white players but not in black players.

Abstract 9254: Race Differences in Ventricular Remodeling Among College Football Players: Implications for a Cardiovascular Screening Program

Objective: Intensive athletic training is associated with increased cardiac ventricular mass and volume. We sought to investigate the hypothesis that African American (AA) football players remodel with a greater mass-to-volume (M:V) ratio than their Caucasian counterparts. We also sought to compare diastolic and systolic function between the two groups. We finally examined the correlation between precordial ECG voltage and M:V ratio. Methods: All entering Stanford Division I football players (81 Caucasian and 39 AA) over a 5 year period underwent cardiovascular screening with history, physical exam, ECG and focused echocardiogram. Comparison of remodeling and functional indices plus ECG voltage parameters was performed using Student’s t-test and multivariable logistic regression analysis adjusted for body size, resting blood pressure and field position. Results: Compared with their Caucasian counterparts, AA football players had on average higher LV mass index (77 ± 11 vs. 71±11 g/m 2 , p=0.009), higher relative wall thickness (0.31 ± 0.04 vs. 0.24 ± 0.20, p&lt;0.001) and higher mass to volume ratio (1.18 ± 0.16 vs. 1.06 ± 0.09 g/mL, p&lt; 0.001). AA football players had lower early diastolic tissue Doppler velocity (18 ± 2 vs. 19 ± 2 cm/s, p=0.043). There were no significant differences in systolic indices of LV ejection fraction or velocity of circumferential shortening. AA players showed significantly greater precordial voltage on QRS spatial vector magnitude score consisting of |V2-S| + |V5-R| (31.9 vs. 27.0 mV, p = 0.002). There were no significant relationships between M:V and net voltage. Conclusion: College footballers of African ancestry exhibit more physiologic concentric ventricular remodeling, lower early diastolic annular velocities and increased ventricular voltage when compared to Caucasian FP. These findings may be important in deriving race specific indices of ventricular remodeling for use in screening college athletes.

Abstract P248: The DCM-Causing D230N Tropomyosin Mutation Produces an Age-Dependent Phenotype in Mice that Is Influenced by Transgene Dosage

A recent study in two large multigenerational families demonstrated a novel mutation in tropomyosin (Tm), Asp230Asn (D230N) that caused DCM with a unique natural history resulting in a striking bimodal disease distribution. Infants and young children with the D230N Tm mutation presented with a severe, often fatal DCM while adults developed a mild to moderate clinical phenotype. Position 230 in tropomyosin is proximal to the C-terminal unwinding of tropomyosin that is essential for the Tm-Tm overlap and for the Tm-cardiac troponin T (cTnT) interaction. We hypothesized that the age-dependent remodeling is a result of temporal isoform switches in the closely linked Tm-binding partner cTnT. To directly address this hypothesis, we used the regulated in vitro motility assay to determine the biophysical effects of the D230N Tm mutation as well as the effects of cTnT isoform changes on the regulatory function of thin filaments. We have found that both wild type and D230N Tm filaments inhibit filament sliding at low calcium indicating that the D230N mutation does not completely disrupt regulation. However in the presence of high calcium the D230N Tm mutation significantly decreases the maximal velocity of filament sliding (3.790 ± 0.1333 microns/sec, n=98) as compared to the wild type filaments (4.900 ± 0.1044, microns/sec n=76). These findings support an altered Tm-cTnT interaction because at maximal calcium concentrations, the myofilament activation at the level of cardiac troponin is not properly transmitted to tropomyosin thus decreasing the activity of myosin-ATPase. In order to extend our biophysical observations and to provide translational insight, we generated a D230N Tm transgenic mouse model. In preliminary studies we demonstrate that at two months the D230N transgenic mice have evidence for early dilatation. In addition, the differences in ventricular remodeling were highly dependent on transgene dose. At six months, we observed dilatation of the ventricle and thinning of the walls compared to non-transgenic siblings. However, the differences were not as marked as those at the two-month time point. Collectively, these findings support an age-dependent DCM phenotype that is modulated by transgene dosage.

Cardiac Resynchronization Therapy Reduces the Risk of Cardiac Events in Patients With Diabetes Enrolled in the Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT)

Data are limited regarding whether the presence of diabetes mellitus (DM) influences the benefit of cardiac resynchronization with defibrillator therapy (CRT-D) in heart failure (HF) patients. The effect of CRT-D was evaluated in 1817 patients who were enrolled in the Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT). Patients were minimally symptomatic (New York Heart Association class I or II), with ejection fraction ≤0.30 and QRS ≥130 ms. We used Cox regression to determine hazard ratio (HR) of CRT-D versus implantable cardioverter-defibrillator (ICD) therapy for the risk of HF event or death, whichever came first (MADIT-CRT primary end point), in DM (n=552) and non-DM (n=1265) patients. Compared with the non-DM patients, those with DM had more coronary risk factors. During an average follow-up of 2.4 years, DM patients had significantly more primary end point events than non-DM patients (26.6% versus 18%, P<0.001). CRT-D was associated with a significant reduction in risk of primary end point in both DM (HR=0.56, P<0.001) and non-DM patients (HR=0.67, P=0.003). Compared with non-DM patients, CRT-D:ICD HRs in DM patients were lower in the total population, and in subgroups with ischemic cardiomyopathy (0.63 versus 0.64), nonischemic cardiomyopathy (0.39 versus 0.73), and left bundle-branch block (0.36 versus 0.50). There were no significant differences in ventricular remodeling, arrhythmia events, or device-related complications between DM and non-DM patients. Patients with diabetes, left ventricular dysfunction, mildly symptomatic HF, and wide QRS complex derive similar benefit from CRT-D compared with patients without diabetes. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00180271.

Relation of Arterial Properties to Left Ventricular Hypertrophy in Hypertensive Adults: Focus on Gender-Related Differences

Although gender-related differences in ventricular remodeling and arterial stiffness have been described, the impact of gender on the association between vascular compliance and left ventricular hypertrophy (LVH) has not been investigated. The current study was designed to determine the gender-related differences in the association between echographically determined LVH measures and arterial stiffness in hypertensive men and women. In the current study, 104 hypertensive participants (61 men and 43 women) were enrolled. Large artery elasticity index (LAEI) and small artery elasticity index (SAEI) were determined using pulse wave contour analysis (HDI CR 2000, Eagan, Minnesota). Left ventricular hypertrophy parameters including intraventricular septum thickness (IVST), posterior wall thickness (PWT), and left ventricular mass index (LVMI) were assessed echographically. Hypertensive male versus female were similar in terms of age, body mass index (BMI), blood pressure, concomitant medications, and cardiovascular risk factors. Left ventricular mass index was significantly, inversely associated with IVST (r = -.32, P = .01), PWT (r = -.32, P = .01), and LVMI (r = -.28, P = .03) in men and significantly, inversely associated with IVST (r = -39, P = .01), PWT (r = -.42, P = .005), LVMI (r = -.54, P < .0001) in women. Small artery elasticity index was significantly, inversely associated with LVMI (r = -0.36, P = .02) in women only. In regression analysis, LAEI explained more variability than SAEI and was an independent predictor of LVH parameters in hypertensive men and women. Compliance of large arteries is potentially an independent predictor of LVH in hypertensive men and women. Therefore, arterial compliance is being considered an important tool in predicting LVH in hypertensive participants.

Estrogen attenuates chronic volume overload induced structural and functional remodeling in male rat hearts

We have previously reported gender differences in ventricular remodeling and development of heart failure using the aortocaval fistula model of chronic volume overload in rats. In contrast to males, female rats exhibited no adverse ventricular remodeling and less mortality in response to volume overload. This gender-specific cardioprotection was lost following ovariectomy and was partially restored using estrogen replacement. However, it is not known if estrogen treatment would be as effective in males. The purpose of this study was to evaluate the structural and functional effects of estrogen in male rats subjected to chronic volume overload. Four groups of male rats were studied at 3 days and 8 wk postsurgery as follows: fistula and sham-operated controls, with and without estrogen treatment. Biochemical and histological studies were performed at 3 days postsurgery, with chronic structural and functional effects studied at 8 wk. Measurement of systolic and diastolic pressure-volume relationships was obtained using a blood-perfused isolated heart preparation. Both fistula groups developed significant ventricular hypertrophy after 8 wk of volume overload. Untreated rats with fistula exhibited extensive ventricular dilatation, which was coupled with a loss of systolic function. Estrogen attenuated left ventricular dilatation and maintained function in treated rats. Estrogen treatment was also associated with a reduction in oxidative stress and circulating endothelin-1 levels, as well as prevention of matrix metalloproteinase-2 and -9 activation and breakdown of ventricular collagen in the early stage of remodeling. These data demonstrate that estrogen attenuates ventricular remodeling and disease progression in male rats subjected to chronic volume overload.

Racial differences in ventricular remodeling in hypertensive heart disease: an autopsy study

Racial differences in ventricular remodeling in hypertensive heart disease: an autopsy study