Left Ventricular Dilatation Hypertrophy Research Articles

Association of a favorable cardiovascular health profile (Life"s Simple 7 and Fuster-BEWAT scores) with the presence of a newly proposed 4-tiered left ventricular hypertrophy

Abstract Funding Acknowledgements Type of funding sources: None. Background AHA"s Life"s Simple 7 cardiovascular health score is recommended for use in primary prevention. Simpler tools not requiring laboratory tests, such as the Fuster-BEWAT score (FBS) (blood pressure [B], exercise [E], weight [W], alimentation [A], and tobacco [T]), are also available. Purpose This study sought to compare the effectiveness of Life"s Simple 7 and FBS in predicting the newly proposed 4-tiered left ventricular hypertrophy (LVH) classification based on LV dilatation (high LV end-diastolic volume [EDV] index) and concentricity (mass/end-diastolic volume [M/EDV]0.67) in the general Chinese population. Methods Participants from Northeast China Rural Cardiovascular Health study who underwent cardiac echocardiography (n = 11,261) were enrolled. Patients with LVH were divided into 4 groups—eccentric nondilated (normal M/EDV and EDV), eccentric dilated (increased EDV, normal M/EDV), concentric nondilated (increased M/EDV, normal EDV), and concentric dilated (increased M/EDV and EDV)—and compared with patients with normal LVM. Results With poor Life"s Simple 7 and FBS as references, individuals with ideal Life"s Simple 7 and FBS showed lower adjusted odds of having eccentric nondilated (Life"s Simple 7, odds ratio [OR]: 0.26; 95% confidence interval [CI]: 0.20 to 0.34 vs. FBS, OR: 0.28; 95% CI: 0.20 to 0.38), eccentric dilated (OR: 0.73 [0.57-0.94] vs. OR: 0.57 [0.43-0.76]), concentric nondilated (OR: 0.12 [0.04-0.38] vs. OR: 0.19 [0.07-0.52]), and concentric dilated LVH (OR: 0.12 [0.03-0.37] vs. OR: 0.26 [0.10-0.72]). Taken together, the odds for these 4 LV geometric phenotypes decreased in a graded manner in subjects with intermediate and ideal ICHS and FBS compared with subjects with poor ICHS and FBS (p for trend <0.01). For the total ICHS and FBS on a continuous scale from 0 (all 7 poor) to 7 (all 7 ideal), risk reductions of the 4 distinct LVH patterns were of comparable magnitude for each 1-point increment of ICHS and FBS. Similar levels of significantly discriminating accuracy were found for Life"s Simple 7 and FBS with respect to the eccentric nondilated (C-statistic: 0.737; 95% CI: 0.725 to 0.750 vs. 0.731; 95% CI: 0.718 to 0.744, respectively), eccentric dilated (0.684 [0.670-0.699] vs. 0.686 [0.671-0.701]), concentric nondilated (0.658 [0.624-0.692] vs. 0.650 [0.615-0.684]), and concentric dilated LVH (0.711 [0.678-0.744] vs. 0.698 [0.663-0.733]). Conclusions Our findings demonstrate that the FBS appears capable of performing just as well as does the Life"s Simple 7 in predicting the novel 4-group classification of LVH, making the FBS particularly suited as a reliable low-cost indicator of CV health in settings where access to laboratory analysis is limited and health care resources are constrained. Abstract Figure.

FREQUENCY AND RISK FACTORS OF LEFT VENTRICULAR GEOMETRIC ABNORMALITIES IN HYPERTENSIVE PATIENTS: A STUDY BASED ON THE UPDATED CLASSIFICATION SYSTEM OF LEFT VENTRICULAR GEOMETRY

Objective: To determine the association between cardiovascular risk factors and the abnormalities of left ventricular geometric abnormalities.
 Study Design: Prospective cross-sectional, single centered study.
 Place and Duration of Study: Armed Forces Institute of Cardiology, Rawalpindi, from Jun 2018 to Dec 2018.
 Methodology: This study permission was sought from hospital ethics committee. Written informed consent was taken from participants of study. Particulars of all the patients who meet the inclusion were included i.e., 351 hypertensive.
 Results: Left ventricular geometric abnormalities were detected in 321 subjects (91%), wherein concentric non dilated left ventricular hypertrophy is the most common left ventricular geometric abnormality (39%). Elevated systolic blood pressure and diabetes mellitus were positively associated with concentric left ventricular remodeling, whereas body mass index and chronic kidney disease were inversely associated with concentric abnormalities. systolic blood pressure and diabetes mellitus, chronic kidney disease, large WC were positively associated with eccentric dilated left ventricular hypertrophy, while body mass index, duration of hypertension, MS were inversely associated with eccentric dilated left ventricular hypertrophy. Elevated systolic blood pressure was the strongest risk factor for eccentric dilated left ventricular hypertrophy. Large WC, systolic blood pressure and diabetes mellitus were positively associated with concentric left ventricular hypertrophy, whereas body mass index was negatively associated with concentric left ventricular hypertrophy.
 Conclusion: Appropriate risk factor management and compliance can prevent left ventricular geometric abnormalities hence poorer outcomes in our population

P1612The ablation of VEGFR-1 signaling promotes angiotensin II induced cardiac dysfunction and sudden death

Abstract Introduction Concentric left ventricular hypertrophy (LVH) and diastolic dysfunction develops as an adaptive response to pressure overload. Eventually this may lead to decompensated hypertrophy characterised by interstitial fibrosis, contractile dysfunction as well as changes in metabolism and electrophysiology, consequentially triggering heart failure. The molecular mechanisms involved in cardiac remodelling are not fully understood but maladaptive angiogenesis could promote the transition from adaptive LVH to decompensated heart failure. Angiogenesis is mediated by vascular endothelial growth factors but their role in LVH has remained unresolved. Purpose In this study, we wanted to investigate whether vascular endothelial growth factor receptor 1 (VEGFR-1) signaling has a role in the progression of LVH and development of heart failure. Methods We used wild type littermate controls and domain specific knock out mouse lacking the intracellular VEGFR-1 tyrosine kinase domain (VEGFR-1 TK−/−) and induced pathological hypertrophy with subcutaneous angiotensin II infusion. We examined the cardiac function with echocardiography and acquired surface ECG signal during the development of LVH. Mice were followed up for 14 days before sacrification and sample collection. Cross-sectional cardiac samples were stained with Masson's trichrome to assess the level of fibrosis and immunostained for lectin to determine capillary area. Additionally, we performed a CD31 whole mount staining to visualise capillary 3D network. To analyse changes in gene expression levels, we performed RT qPCR measurements. Results VEGFR-1 TK deficiency led to increased mortality (33.3%) and lack of adaptive LVH. Whereas wild type mice responded to angiotensin II infusion with a significant increase in ejection fraction (55.5% to 69.9%) within the first 6 days, VEGFR-1 TK−/− mice displayed a 5.2% decrease and without adaptive thickening of the LV anterior wall. The most striking difference was seen in LV volume, where wild type mice displayed a 63.3% reduction but in VEGFR-1 TK−/− mice it remained unaltered after angiotensin II infusion. Histological analyses showed that VEGFR-1 TK−/− mice displayed significant cardiomyocyte hypertrophy combined with ventricular dilatation but without changes in fibrosis or angiogenesis. ECG analysis revealed that VEGFR-1 TK−/− mice exhibited widening of the QRS complex, similar to human LVH, and this was accompanied by increased ANP/BNP levels. Conclusions In this study, we show that the ablation of VEGFR-1 TK signaling has an unexpected role in pressure overload inducing mortality. VEGFR-1 TK−/− mice displayed dilated LVH and a protracted response to angiotensin II infusion, suggesting that VEGFR-1 signaling is required for the adaptive response and concentric hypertrophy of the myocardium.

THE EFFECT OF DEGREE AND TYPE OF LEFT VENTRICULAR HYPERTROPHY ON VENTRICULAR ARRHYTHMIAS IN HYPERTENSION

Finding the arrythmogenic potential in patients with arterial hypertension as well as its correlation with left ventricular hypertrophy (LVH), and its type and degree. The research included 109 hypertensive patients (pts) (54 male and 55 female), 54.2 ± 7.9 years old without symptomatic coronary disease, myocardial infarction and systolic dysfunction. All the pts had a clinical examination, ECG, 24 h Holter monitoring with Lown classification of ventricular arrhythmias, an echocardiogram with left ventricular mass index (LVMI) and a specific type of LVH. QT interval dispersion (QTd) was calculated on 12 leads standard ECG. 75 pts had LVH (LVMI: 172.6 ± 42.95 g/m2) while 35 pts were without LVH (109.3 ± 15.9 g/m2). Non sustained ventricular tachycardia was registered in 13 pts (17.6%) with LVH and 1 female patient without LVH (2.9%). Patients with VT had a considerably higher ILVM (214.9 ± 6.8 vs. 151.9 ± 47.2 g/m2) than the average and higher QTd (73.7 ± 19.1 vs. 55.2 ± 20.2). VT was registered in 3/19 (15.8%) with eccentric nedilated type LVH, 6/38 (15.8%) with concentric LVH, 1/11 (9.1) (disproportional septal LVH) and 3/5 ( 60%) with dilated LVH. Univariate analysis showed a considerable correlation between the degree of arrhythmias and ILVM (p<0.001) and QTd (p=0.012). Ventricular arrhythmias in patients with arterial hypertension are considerably correlated to the degree of LVH expressed in ILVM and QTd.

Prevalence and determinants of left ventricular geometric abnormalities in hypertensive patients: A study based on the updated classification system of left ventricular geometry

ObjectiveThis study was to determine whether different risk factors were associated with different type of left ventricular (LV) geometric abnormalities. MethodsThis retrospective analysis included 2290 hypertensive participants without other cardiovascular disease, valve disease and with ejection fraction ≥50%. The type of LV geometric abnormality was defined on the basis of the new classification system. ResultsLV geometric abnormalities were detected in 1479 subjects (64.6%), wherein concentric LV remodeling is the most common LV geometric abnormality (40.3%). Large waist circumference (WC) and neck circumference (NC) were positively associated with concentric LV remodeling, whereas body mass index (BMI) [odds ratio (OR) 0.89, 95% CI 0.85∼0.92, P ＜ 0.001] and systolic blood pressure (SBP) (OR 0.99, 95% CI 0.98∼0.99, P = 0.018) were inversely associated with concentric abnormalities. SBP and age were positively associated with eccentric dilated LVH, while male was inversely associated with eccentric dilated left ventricular hypertrophy (LVH). Age was the strongest risk factor for eccentric dilated LVH (OR 1.05, 95% CI 1.03∼1.07, P ＜ 0.001). Age, NC, SBP, hyperuricemia, and alcohol use were positively associated with concentric LVH, whereas BMI (OR 0.95, 95% CI 0.90∼0.99, P = 0.033) and male (OR 0.12, 95% CI 0.07∼0.18, P ＜ 0.001) were negatively associated with concentric LVH. ConclusionThe prevalence of hypertensive LV geometric abnormality in rural area of Southern China was obvious higher. Compared with eccentric LV geometric abnormalities, there were more risk factors, including large WC and NC, age, NC, SBP, hyperuricemia, alcohol use, BMI and gender, which were associated with concentric LV geometric abnormalities.

OP.5C.07] DO COMBINED ELECTROCARDIOGRAPHIC AND ECHOCARDIOGRAPHIC MARKERS OF LEFT VENTRICULAR HYPERTROPHY IMPROVE CARDIOVASCULAR RISK ESTIMATION?

Objective: We estimated the risk of cardiovascular mortality associated with echocardiographic (ECHO) sub-types of left ventricular hypertrophy (LVH), as defined by an up-dated classification, in subjects with and without electrocardiographic (ECG) LVH. To this purpose 1,691 representatives of the general population of Monza, enrolled in the Pressioni Monitorate e Loro Associazioni (PAMELA) study, were included in the present analysis. Design and method: Cut-points for ECHO-LVH and abnormal LV geometry were derived from reference values of the healthy fraction of the PAMELA population by combining LV mass index, LV diameter and relative wall thickness, ECG-LVH was defined according to Cornell voltage index. Death certificates were collected over an average 211 months follow-up period. Results: A total of 89 fatal cardiovascular events were recorded during follow-up. Compared to individuals with neither ECHO-LVH nor ECG-LVH, fully adjusted risk of cardiovascular mortality increased (HR 3.36, 95% CI: 1.51-7.47, p = 0.003) in subjects with both ECHO- and ECG-LVH, whereas the risk entailed by ECHO-LVH alone was of borderline statistical significance (p = 0.04). Combined concentric LVH and ECG-LVH, but not concentric LVH alone, predicted the long-term incidence and risk of fatal cardiovascular events (HR = 3.78, 95% CI: 1.25–11.38, p = 0.01). Similar findings were observed for eccentric non dilated LVH. Conclusions: The present analysis underlines the value of combining ECG and ECHO in the assessment of cardiovascular prognosis related to LVH. The advantage of combining both noninvasive techniques in refining risk prediction persists also when echo-LVH is categorized according to concentric or eccentric LV patterns.

Prevalence and correlates of new-onset left ventricular geometric abnormalities in a general population: the PAMELA study.

We sought to evaluate new-onset abnormal LV (left ventricle) patterns and their correlates over a 10-year period in members of the general population enrolled in the Pressioni Arteriose Monitorate e Loro Associazioni study. The study included 817 patients with normal LV geometry at baseline evaluation having a readable echocardiogram at the end of follow-up. Cut-points for abnormal LV geometric patterns were derived from reference values of the healthy fraction of the Pressioni Arteriose Monitorate e Loro Associazioni population. Over a 10-year period 39% of participants progressed to abnormal LV geometric patterns as follows: LV concentric remodelling (15.2%), eccentric dilated left ventricular hypertrophy (LVH) (8.4%), concentric LVH (7.9%), eccentric nondilated LVH (6.8%), and concentric dilated LVH (0.7%). Age [odds ratio (OR): 1.039; 95% confidence interval (CI) 1.023-1.056, P < 0.0001], LV mass index (OR: 1.039; 95% CI 1.026-1.052, P < 0.0001), night-time SBP (OR: 1.024; 95% CI 1.005-1.043, P = 0.01), office SBP changes during follow-up (OR: 1.017 95% CI 1.007-1028, P = 0.001), and BMI (OR: 1.067; 95% CI 1.017-1.120, P = 0.009) emerged as key correlates of new-onset abnormal LV geometry. Age and LV mass index turned out to be strong determinants of all sub-types of LVH; whereas blood pressure, BMI, and sex exhibited a different predictive value across the various LV geometric patterns. Our study provides the first evidence that long-term changes from normal cardiac morphology toward abnormal LV geometry represent a clinically relevant phenomenon at the community level. From a practical perspective this finding reinforces the concept that life-style changes and pharmacologic treatment aimed to reduce over-weight/obesity and optimize blood pressure are of paramount importance for prevention of subclinical cardiac damage.

Right ventricular remodeling and updated left ventricular geometry classification: is there any relationship?

Objective: We sought to evaluate right ventricular (RV) structure and function in hypertensive patients with various left ventricular (LV) geometric patterns using an updated classification for LV geometry.Methods: This cross-sectional study included 232 hypertensive subjects. All the subjects underwent complete two-dimensional (2D) and three-dimensional (3D) echocardiographic examination. Using LV mass index, LV end-diastolic diameter and relative wall thickness, according to the updated classification, all subjects were divided into six different groups: normal LV geometry, concentric remodeling, eccentric LV hypertrophy (LVH), concentric, dilated, and concentric-dilated LVH.Results: RV wall thickness was increased in concentric and concentric-dilated LVH compared with normal LV geometry and LV concentric remodeling. RV longitudinal function was reduced in concentric and concentric-dilated patients compared with other hypertensive groups. 3D RV volumes were significantly higher in eccentric, dilated, and concentric-dilated LVH hypertensive subjects. Conversely, 3D RV ejection fraction was lower in these groups.Conclusion: RV longitudinal myocardial function and 3D RV function are significantly influenced by LV geometry in hypertensive patients. RV remodeling is the most pronounced in the patients with concentric, dilated, and concentric-dilated LVH geometric patterns.

Does Left Ventricular Geometric Patterns Impact Right Atrial Phasic Function? Findings from the Hypertensive Population.

The aim of the study was to evaluate right atrial (RA) phasic function in hypertensive patients with different left ventricular (LV) geometric patterns by using two-dimensional (2DE) and three-dimensional (3DE) echocardiography. This cross-sectional study involved 177 hypertensive patients who underwent 2DE and 3DE examination. The updated criteria of LV geometry that included LV mass index, LV end-diastolic diameter, and relative wall thickness were applied. Using this classification, patients were separated into six groups: normal geometry, concentric remodeling, eccentric nondilated LV hypertrophy (LVH), concentric LVH, dilated LVH, and concentric-dilated LVH. Two-dimensional echocardiography and 3DE RA volumes were significantly higher in concentric and dilated LVH than in other LV geometric types. RA reservoir function, estimated by total 2DE and 3DE RA emptying fraction (EF), was decreased in subjects with dilated LVH compared with normal geometric and concentric LV remodeling patterns. RA conduit function assessed with 2DE and 3DE RA passive EF, gradually reduced from normal LV geometry to dilated LVH. RA pump function was increased in patients with concentric and dilated LVH than in subjects with normal LV geometry and concentric remodeling. 2DE strain analysis confirmed these findings about RA phasic function. Concentric LVH and dilated LVH were associated with RA enlargement and dysfunction irrespectively of main demographic and clinical parameters. Left ventricular geometric patterns have significant impact on RA phasic function in hypertensive patients. Concentric and dilated LVH patterns have the most prominent negative effect on RA morphological and functional remodeling.

Risk of mortality in relation to an updated classification of left ventricular geometric abnormalities in a general population: the Pamela study.

We estimated the risk of cardiovascular and all-cause mortality associated with left ventricular geometric patterns, as defined by a new classification system proposed by the Dallas Heart Study, in 1716 representatives of the general population of Monza enrolled in the Pressioni Monitorate e Loro Associazioni (PAMELA) study. Cut-points for abnormal left ventricular geometric patterns were derived from reference values of the healthy fraction of the PAMELA population by combining left ventricular mass (LVM) index, left ventricular diameter and relative wall thickness. Death certificates were collected over an average 211 months follow-up period. During follow-up, 89 fatal cardiovascular events and 264 all-cause deaths were recorded. Concentric remodelling was the most common left ventricular geometric abnormality (9.4%) followed by eccentric nondilated left ventricular hypertrophy (LVH) (6.3%), concentric LVH (4.6%) and eccentric dilated LVH (3.5%). Compared with normal left ventricular geometry, concentric LVH [hazard ratio 2.20, 95% confidence interval (95% CI) 1.44-3.37, P < 0.0003], eccentric dilated LVH (hazard ratio 1.90, 95% CI 1.17-3.08, P = 0.009) and eccentric nondilated LVH (hazard ratio 1.57, 95% CI 1.07-2.31, P = 0.02) predicted the risk of cardiovascular mortality, after adjustment for baseline covariates, including ambulatory blood pressure. Similar findings were observed for all-cause mortality. Only concentric LVH maintained a significant prognostic value for both outcomes after adjustment for baseline differences in LVM index. The new classification system of left ventricular geometric patterns may improve mortality risk stratification in a general population. The risk is markedly dependent on LVM values; only concentric LVH provides a prognostic information beyond that conveyed by cardiac mass.

The relationship between left ventricular deformation and different geometric patterns according to the updated classification: findings from the hypertensive population.

We sought to investigate left ventricular mechanics in hypertensive patients with different geometric patterns by using two-dimensional (2DE) and three-dimensional (3DE) strain analysis. This cross-sectional study included 197 hypertensive individuals who underwent a complete 2DE and 3DE examination. We applied the new updated criteria of left ventricular geometry that considered left ventricular mass index, left ventricular end-diastolic diameter and relative wall thickness. According to this classification the individuals were divided into six groups: normal geometry, concentric remodelling, eccentric nondilated left ventricular hypertrophy (LVH), concentric LVH, dilated LVH and concentric-dilated LVH. Multidirectional 2DE and 3DE left ventricular strain decreased from the hypertensive patients with normal geometry, across the individuals with left ventricular concentric remodelling, eccentric nondilated LVH, to the patients with concentric LVH and dilated LVH patterns. The reduction of left ventricular systolic and early diastolic strain rates was noticed to be heading in the same direction, as well as the elevation of late diastolic strain rates. Left ventricular twist and torsion were increased in the participants with concentric and dilated LVH patterns. Reduced 2DE and 3DE strains were associated with concentric and dilated LVH patterns independent of demographic and clinical parameters. Left ventricular deformation in hypertensive patients is significantly impacted by left ventricular geometry. Concentric and dilated LVH patterns have the greatest unfavourable effect on 2DE and 3DE left ventricular mechanics. The updated classification of left ventricular geometry provides valuable and comprehensive information about left ventricular mechanical deformation and function in hypertensive population.

The influence of left ventricular geometry on left atrial phasic function in hypertensive patients

Objective. We aimed to investigate left atrial (LA) phasic function in hypertensive patients with different geometric patterns using two-dimensional (2DE) and three-dimensional (3DE) echocardiography. Methods. This cross-sectional study included 213 hypertensive subjects who underwent a complete 2DE and 3DE examination. The new updated criteria for left ventricular (LV) geometry, which consider LV mass index, LV end-diastolic diameter and relative wall thickness, were applied. According to this classification, the subjects were divided into six groups: normal geometry, concentric remodeling, eccentric non-dilated left ventricular hypertrophy (LVH), concentric LVH, dilated LVH and concentric-dilated LVH. Results. 2DE and 3DE LA volumes gradually increased from normal LV geometry to concentric and concentric-dilated LVH. LA reservoir and conduit functions, estimated by 2DE and 3DE LA total and passive emptying fractions, were decreased in subjects with concentric and concentric-dilated LVH. LA booster pump function was increased in patients with concentric, dilated and concentric-dilated LVH compared to subjects with normal LV geometry. The same results regarding LA phasic function were provided by 2DE strain analysis. Concentric, dilated and non-concentric dilated LVH were associated with LA enlargement independently of main demographic and clinical features. Conclusion. LV geometric patterns significantly influence LA phasic function. Concentric and dilated LVH patterns have the most prominent negative effect on LA enlargement assessed by both 2DE and 3DE.

Cardiovascular risk in relation to a new classification of hypertensive left ventricular geometric abnormalities.

In 2010, the Dallas Heart Study proposed an upgrade of the left ventricular geometric classification proposed in 1991, by using left ventricular mass combined with end diastolic volumes, and introducing the new categories of dilated left ventricular hypertrophy (LVH). We adopted the new method to test the prognostic impact of the left ventricular geometric patterns from the new classification. We evaluated baseline anthropometric, laboratory and echocardiographic parameters of 8848 hypertensive patients from the Campania Salute Network (53 ± 12 years, 56% male), free of prevalent cardiovascular disease, valve disease and with ejection fraction ≥50%. Cut points for left ventricular mass index, relative wall thickness and left ventricular end-diastolic dimension (cm/m) were derived from our historical normal reference population. Composite cardiovascular end-points were cardiac death, fatal and nonfatal myocardial infarction and stroke. Independent of confounders, eccentric dilated LVH, concentric nondilated LVH and concentric dilated LVH were associated with higher cardiovascular risk (hazard ratios between 2 and 9, all P < 0.01), mostly depending on the magnitude of LVM index. A volume load was present especially in dilated forms of LVH, the extent of which was important in the determination of harmful types of left ventricular geometry. Consideration of left ventricular dilatation in the evaluation of risk related to hypertensive left ventricular geometry reveals the importance of the extent of the volume load coexisting with the typical hypertensive pressure overload. At a given normal ejection fraction, the balance between the two hemodynamic components influences the shape of left ventricular geometric adaptation, the amount of left ventricular mass and the impact on prognosis.

Left ventricular dilatation and subclinical renal damage in primary hypertension.

A new classification of left ventricular geometry based on left ventricular dilatation and concentricity has recently been developed. This classification identifies subgroups differing with regard to systemic haemodynamics, left ventricular function and cardiovascular prognosis. We investigated the relationship between the new classification of left ventricular geometry and subclinical renal damage, namely urine albumin excretion and early intrarenal vascular changes in primary hypertensive patients. A total of 449 untreated hypertensive patients were studied. Four different patterns of left ventricular hypertrophy (eccentric nondilated, eccentric dilated, concentric nondilated and concentric dilated hypertrophy) were identified by echocardiography. Albuminuria was measured as the albumin-to-creatinine ratio. Early intrarenal vascular changes, expressed as the renal volume to resistive index ratio, were evaluated by ultrasound and Doppler scan. Patients with concentric dilated left ventricular hypertrophy had higher albumin excretion rates (P = 0.0258) and prevalence of microalbuminuria (P < 0.0001) and lower renal volume to resistive index ratio than patients with concentric nondilated hypertrophy (P = 0.0093). Patients with eccentric dilated hypertrophy showed a higher prevalence of microalbuminuria than patients with eccentric nondilated hypertrophy (P < 0.0001). Moreover, patients with chamber dilatation showed a higher prevalence of microalbuminuria (P = 0.0002) and lower renal volume to resistive index ratio (P = 0.0107) than patients without chamber dilatation. After adjusting for potentially confounding variables, left ventricular chamber dilatation was an independent predictor of subclinical renal damage. Left ventricular dilatation is associated with subclinical renal damage in hypertension. These findings extend previous reports and provide a pathophysiological rationale for the observed unfavourable prognosis in patients with left ventricular dilatation.

Subclassification of left ventricular hypertrophy based on dilation stratifies coronary artery disease patients with distinct risk.

A new 4-tired classification of left ventricular hypertrophy (LVH) based on LV concentricity and dilation has been proposed; however, the association between the new categorization of LV geometry and outcomes in patients with coronary artery disease (CAD) is still unknown. All the 2297 patients with CAD included underwent echocardiographic examination prior to discharge. Left ventricular mass (LVM) was calculated, and left ventricular end-diastolic volume (EDV) was indexed by body surface area (BSA). Study cohort was divided into five groups according to LV geometry: (i) eccentric nondilated LVH (normal LVM/EDV((2/3)) and EDV/BSA) (n=129); (ii) eccentric dilated LVH (normal LVM/EDV((2/3)) with increased EDV/BSA) (n=222); (iii) concentric nondilated LVH (increased LVM/EDV((2/3)) with normal EDV/BSA) (n=441); (iv) concentric dilated LVH (increased LVM/EDV((2/3)) and EDV/BSA) (n=118); and (v) normal LV mass (n=1387). Dilated LVH was associated with a higher event rates of all-cause death (eccentric 13·1% vs. 3·1%; concentric 13·6% vs. 8·4%) and composite events (eccentric: 17·6% vs. 5·4%; concentric: 18·6% vs. 12·7%) compared with nondilated LVH. While eccentric nondilated LVH had comparable risk for adverse outcomes compared with normal LV mass (all-cause death: relative risk (RR) 0·68, 95% confidential interval (CI) 0·25-1·85; composite events: RR 0·75, 95% CI 0·36-1·58). Cox regression analyses showed that eccentric dilated LVH had the highest propensity to all-cause death (adjusted hazard ratio [aHR] 2·752 [95% CI 1·749-4·328], P<0·001) and composite events (aHR 2·462 [95% CI 1·688-3·592], P<0·001). In patients with CAD, dilated LVH and nondilated LVH provide distinct prognostic information. Eccentric nondilated LVH does not predict adverse outcomes.

Abstract 260: Time Course Observation of Left Ventricular Hypertrophy and Regression Induced by an Improved Technique

In order to study the left ventricular hypertrophy (LVH) and its regression, we improved the surgical technique for producing LV pressure overload and its reversing mouse model using the titanium clip placement for transverse aortic banding (AB) and removal for debanding (DB). A time course study on heart function and histology proved the importance of the regression time. Materials and methods: The technique was applying titanium clip for AB and removing for DB with minimal invasion. A total of 95 male C57BL6 mice weighing 20-30 g were used in this study. Experimental groups included: control (n=11), AB 3 (11), 4 (12), and 6 (12) wks, DB at 3 (12), 4 (11), and 6 (12) wks of AB for 1 wk. Carotid arteries velocity were measured to evaluate the constrictive level. Heart/body weight ratio, cardiac wall thickness from echocardiography, LV pressure from catheterization and heart histology studies were used to evaluate the pressure overload and hypertrophy. Results: The echocardiographic and histology results indicated that AB induce significent LVH which was a concentric hypertrophy at AB 3 wks and then progressively become a dilated hypertrophy at AB 6 wks. The cardiac function also indicated a stable ejection fraction before 3 wks of AB and then gradually declined at AB 6 wks. After 6 wks AB, the enlargement in LV dimensions becomes significant. When deband at 3 and 4 wks for one week, there were significant regression of hypertrophy but the regression is limited after AB 6 wks and the evidences of lung congestion were apparent. In catheterizaiton, the LV systolic pressure were markedly elevated in AB mice but these pressure elevations became less at AB 6 wks and the LV end-diastolic pressure (LVEDP) at AB 6 wks was elevated significantly. After DB at AB 3 and 4 wks, the pressure parameters retriced close to normal but LVEPD elevation retreat is limited in the DB 6 wks group. Conclusion: With applying and removing titanium clip to induce pressure overload and reversing can provide a relatively simple, effecive, consistent and minimal invasive methods to establish the mouse model for studying LVH and its regression. Our data indicate that AB induced mouse LVH could be retriced close to normal when remove the constriction at the concentric LVH phase but the regression is limited in dilated LVH.

Phosphorylation of phospholamban at threonine-17 reduces cardiac adrenergic contractile responsiveness in chronic pressure overload-induced hypertrophy

Physiological hemodynamic stress, such as aerobic exercise, is intermittent and requires an increase in Ca2+ -dependent contractility through sympathetic nervous system activation. Pathological hemodynamic stress, such as hypertension, is persistent and requires sustained increases in cardiac function. Over time, this causes left ventricular hypertrophy (LVH)-reduced responsiveness to sympathetic stimulation. In this study, we examined the hypothesis that blunted in vivo adrenergic contractile responsiveness in pressure overload (PO)-induced cardiac hypertrophy is caused by abnormalities in the abundance and/or basal phosphorylation state of Ca2+ regulatory proteins. PO, induced by aortic constriction, caused concentric LVH or dilated LVH. Only animals with dilation exhibited a decrease in baseline left ventricle function [fractional area change (FAC); measured with echocardiography]. All PO animals had a reduced contractile response to adrenergic agonists (increase in FAC with 40 microg.kg(-1).min(-1) dobutamine, control 0.30 +/- 0.04, n = 5 vs. banded 0.10 +/- 0.03, n = 10; P < 0.01). PO animals had reduced phospholamban (PLB) protein abundance (P = 0.07, not significant) and increased PLB phosphorylation at the calmodulin-dependent kinase II (CaMKII)-specific site (PLB-Thr17, P < 0.05) but not at the protein kinase A-specific site (PLB-Ser16). PLB-Thr17 phosphorylation was inversely correlated with dobutamine-induced increases in contractility in PO animals (r2 = 0.81, P < 0.05). Continuous induction of Ca2+ transients in isolated ventricular myocytes for 24 h increased phosphorylation at PLB-Thr17 and diminished inotropic responsiveness and PLB-Ser16 phosphorylation after exposure to isoproterenol (P < 0.05). These data show that reduced adrenergic responsiveness in feline PO hypertrophy and failure involves increases in basal PLB-Thr17 phosphorylation, suggesting that activation of CaMKII in PO hypertrophy contributes to defective adrenergic reserve in compensated LVH and early heart failure.