Endocardial Fractional Shortening Research Articles

Metformin Prevents Low-dose Isoproterenol-induced Cardiac Dilatation and Systolic Dysfunction in Male Sprague Dawley Rats.

Myocardial metabolic abnormalities are well-recognized alterations in chronic heart failure, effects that may contribute to progressive cardiac dysfunction. However, whether metabolic alterations in-part mediate their deleterious effects by modifying the chronic impact of excess low-dose sympathetic stimulation on cardiac chamber dilatation is uncertain. We therefore aimed to determine the effect of metformin administration on cardiac function and mitochondrial architectural changes in a rat model of chronic sympathetic-induced left ventricular (LV) remodeling and systolic dysfunction [daily subcutaneous isoproterenol (ISO) injection at a low dose of 0.02 mg/kg for 7 months]. Echocardiography was used to assess in vivo LV dimensions and function, and mitochondrial and myofibril arrangement was assessed using transmission electron microscopy. Seven months of low-dose ISO administration increased LV diastolic diameter (in mm) [control (CONT): 7.29 ± 0.19 vs. ISO: 8.76 ± 0.21; P = 0.001], an effect that was attenuated by metformin (ISO + MET: 7.63 ± 0.29 vs. ISO: P = 0.001) administration. Similarly, ISO increased LV end-systolic diameter (CONT: 4.43 ± 0.16 vs. ISO: 5.49 ± 0.16: P < 0.0001), an effect prevented by metformin (ISO + MET: 4.04 ± 0.25 vs. ISO: P < 0.0001). Moreover, chronic ISO administration reduced LV endocardial fractional shortening (P = 0.0001), midwall fractional shortening (P = 0.0001), and ejection fraction (P = 0.0001), effects similarly prevented by metformin administration. Furthermore, changes in mitochondrial arrangement and relative mitochondrial area (CONT: 37.7 ± 2.2 vs. ISO: 28.1 ± 2.9; P = 0.05) were produced by ISO administration, effects prevented by metformin. In conclusion, metformin offers cardiac protection against chronic sympathetic-induced LV dilatation and systolic dysfunction. These data support a role for myocardial metabolic changes in mediating LV dilatation and LV dysfunction produced by chronic neurohumoral activation in cardiac disease.

Global longitudinal strain as a marker for systolic function in patients with pheochromocytomas.

Cardiomyopathy is a frequent complication of pheochromocytoma, and echocardiography is the most accessible method for its evaluation. The objective of this study was to assess the clinical significance of classical and novel echocardiographic parameters of cardiac function in 24 patients with pheochromocytomas (PPGL) compared to 24 subjects with essential hypertension (EH). Fourteen PPGL patients were reassessed after successful surgery. Left ventricular hypertrophy was four times more prevalent in patients with PPGL vs EH (75% vs 17%; P = 0.00005). Left ventricular mass index (LVMi) significantly correlated with urine metanephrine (MN) (rs = 0.452, P = 0.00127) and normetanephrine (NMN) (rs = 0.484, P = 0.00049). Ejection fraction (EF) and endocardial fractional shortening (EFS) were normal in all participants and did not correlate with urine metanephrines. Global longitudinal strain (GLS) was significantly lower in PPGL compared to EH group (-16.54 ± 1.83 vs -19.43 ± 2.19; P < 0.00001) and revealed a moderate significant positive correlations with age (rs = 0.489; P = 0.015), LVMi (rs = 0.576, P < 0.0001), MN (rs = 0.502, P = 0.00028) and NMN (rs = 0.580, P < 0.0001). Relative wall thickness (RWT) showed a strong positive correlation with urine MN (rs = 0.559, P < 0.0001) and NMN (rs = 0.689, P < 0.00001). Markedly decreased LVMi (118.2 ± 26.9 vs 102.9 ± 22.3; P = 0.007) and significant improvement in GLS (-16.64 ± 1.49 vs -19.57 ± 1.28; P < 0.001) was observed after surgery. ΔGLS depended significantly on the follow-up duration. In conclusion, classical echocardiographic parameters usually used for assessment of systolic cardiac function are not reliable tests in pheochromocytoma patients. Instead, GLS seems to be a better predictor for the severity and the reversibility of catecholamine-induced myocardial function damage in these subjects. RWT should be measured routinely as an early indicator of cardiac remodeling.

Associations of inflammatory markers with impaired left ventricular diastolic and systolic function in collagen-induced arthritis.

BackgroundHigh-grade inflammation may play a pivotal role in the pathogenesis of left ventricular (LV) dysfunction. Evidence to support a role of systemic inflammation in mediating impaired LV function in experimental models of rheumatoid arthritis (RA) remains limited. The aim of the present study was to determine the effects of high-grade systemic inflammation on LV diastolic and systolic function in collagen-induced arthritis (CIA).MethodsTo induce CIA, bovine type-II collagen emulsified in incomplete Freund’s adjuvant was injected at the base of the tail into 21 three-month old Sprague Dawley rats. Nine-weeks after the first immunisation, LV function was assessed by pulsed Doppler, tissue Doppler imaging and Speckle tracking echocardiography. Cardiac collagen content was determined by picrosirius red staining; circulating inflammatory markers were measured using ELISA.ResultsCompared to controls (n = 12), CIA rats had reduced myocardial relaxation as indexed by lateral e’ (early diastolic mitral annular velocity) and e’/a’ (early-to-late diastolic mitral annular velocity) and increased filling pressures as indexed by E/e’. No differences in ejection fraction and LV endocardial fractional shortening between the groups were recorded. LV global radial and circumferential strain and strain rate were reduced in CIA rats compared to controls. Higher concentrations of circulating inflammatory markers were associated with reduced lateral e’, e’/a’, radial and circumferential strain and strain rate. Greater collagen content was associated with increased concentrations of circulating inflammatory markers and E/e’.ConclusionHigh-grade inflammation is associated with impaired LV diastolic function and greater myocardial deformation independent of haemodynamic load in CIA rats.

Temporal Measures in Cardiac Structure and Function During the Development of Obesity Induced by Different Types of Western Diet in a Rat Model.

Obesity is recognized worldwide as a complex metabolic disorder that has reached epidemic proportions and is often associated with a high incidence of cardiovascular diseases. To study this pathology and evaluate cardiac function, several models of diet-induced obesity (DIO) have been developed. The Western diet (WD) is one of the most widely used models; however, variations in diet composition and time period of the experimental protocol make comparisons challenging. Thus, this study aimed to evaluate the effects of two different types of Western diet on cardiac remodeling in obese rats with sequential analyses during a long-term follow-up. Male Wistar rats were distributed into three groups fed with control diet (CD), Western diet fat (WDF), and Western diet sugar (WDS) for 41 weeks. The animal nutritional profile and cardiac histology were assessed at the 41st week. Cardiac structure and function were evaluated by echocardiogram at four different moments: 17, 25, 33, and 41 weeks. A noninvasive method was performed to assess systolic blood pressure at the 33rd and 41st week. The animals fed with WD (WDF and WDS) developed pronounced obesity with an average increase of 86.5% in adiposity index at the end of the experiment. WDF and WDS groups also presented hypertension. The echocardiographic data showed no structural differences among the three groups, but WDF animals presented decreased endocardial fractional shortening and ejection fraction at the 33rd and 41st week, suggesting altered systolic function. Moreover, WDF and WFS animals did not present hypertrophy and interstitial collagen accumulation in the left ventricle. In conclusion, both WD were effective in triggering severe obesity in rats; however, only the WDF induced mild cardiac dysfunction after long-term diet exposure. Further studies are needed to search for an appropriate DIO model with relevant cardiac remodeling.

Impact of Blunted Nocturnal Blood Pressure Dipping on Cardiac Systolic Function in Community Participants Not Receiving Antihypertensive Therapy.

Blunted nocturnal blood pressure (BP) dipping (nondipping) predicts cardiovascular morbidity and mortality, and is associated with heart failure (HF) independent of office BP. Whether nondipping is independently associated with cardiac systolic function prior to the development of HF is uncertain. We assessed whether nocturnal BP dipping pattern and nocturnal BP were associated with indexes of cardiac systolic function [endocardial fractional shortening (endFS), midwall FS (mFS), ejection fraction (EF)] independent of left ventricular mass index (LVMI) and relative wall thickness (RWT) in 491 randomly selected community participants not receiving antihypertensive therapy. Nocturnal BP and dipping pattern were determined from 24-hour BP monitoring where nighttime was defined from fixed-clock time intervals. BP dipping was defined as night-to-day BP ratio. Pulse wave velocity (PWV) was determined using SphygmoCor, and total peripheral resistance (TPR) was calculated from echocardiographic data. On bivariate analyses, nocturnal BP and BP dipping but not day BP were correlated with indexes of cardiac systolic function (P < 0.005). After adjustments for potential confounders including age, LVMI (or RWT) and 24 hour (or day) BP, endFS (P < 0.01), mFS (P < 0.05), and EF (P < 0.01) were associated with nocturnal BP and BP dipping. These relationships survived further adjustments for PWV, and the homeostasis model of insulin resistance. The decreased mFS in reverse dippers was in-part explained by an increased TPR. In an untreated community sample, blunted nocturnal BP dipping is independently and inversely associated with cardiac systolic function. Hence, nondipping is related to a reduced cardiac systolic function prior to the development of HF.

Comparison of Efficacy of Amlodipine and Cilnidipine on Left Ventricular Hypertrophy amongst Hypertensive Patients

Left ventricular hypertrophy is one of the commonest cardiac sign seen in hypertensive patients. According to American Heart Association and Joint National Committee VIII calcium channel blockers are first line drug in treatment of hypertension. Previous meta-analysis shows Calcium channel blocker can reduce left ventricular hypertrophy by 9-11%. The study was undertaken to evaluate and compare the efficacy of Amlodipine and Cilnidipine on Left ventricular hypertrophy and Systolic function. Total 48 patients were selected and enrolled as study participants. The patients were then divided as (1) Hypertensive group (n=22) and (2) Diabetic hypertensive group (n=26) - selected patients received either Amlodipine (2.5 to 10 mg) or cilnidipine (5 to 20 mg) with or without Angiotensin receptor blockade along with antidiabetic medication. Echocardiography report done to all selected patients at baseline and 12 months. Amlodipine and Cilnidipine, both can reduce left ventricular mass, left ventricular mass index, and relative wall thickness with statistical significance but without any clinical relevance when compared with the baseline. The total mean reduction in percentage of above parameters was more with Cilnidipine treated arm than Amlodipine. Both drugs have no effect on cardiac systolic function i.e., ejection fraction and endocardial fractional shortening. From this study it can be concluded that Cilnidipine is better in reducing left ventricular hypertrophy than Amlodipine in hypertensive patients without any deleterious action on systolic function.

Left Ventricular Function Assessed by One-Point Carotid Wave Intensity in Newly Diagnosed Untreated Hypertensive Patients.

To investigate whether newly diagnosed untreated hypertensive patients show higher left ventricular (LV) contractility, as assessed by traditional echocardiographic indices and carotid wave intensity (WI) parameters, including amplitude of the peak during early (W1 ) and late systole (W2 ). A total of 145 untreated hypertensive patients were compared with 145 age- and sex-matched normotensive subjects. They underwent comprehensive echocardiography and WI analysis. WI analysis was performed at the level of the common carotid artery. The diameter changes were the difference between the displacement of the anterior and posterior walls, with the cursors set to track the media-adventitia boundaries 2 cm proximal to the carotid bulb and calibrated by systolic and diastolic BP. Peak acceleration was derived from blood flow velocity measured by Doppler sonography with the range-gate positioned at the center of the vessel diameter. WI was based on the calculation of (dP/dt)×(dU/dt), where dP/dt and dU/dt were the derivatives of BP (P) and velocity (U) with respect to time. One-point pulse wave velocity (PWVβ) and the interval between the R wave on ECG and the first peak of WI (R-W1 ), using a high definition echo-tracking system implemented in the ultrasound machine (Aloka), were also derived. After adjustment for body weight, heart rate, and physical activity, the two groups had similar general characteristics and diastolic function. However, hypertensives showed significantly higher LV mass, LV ejection fraction (LVEF), circumferential and LV end-systolic stress, and one-point PWV as well as W1 (13.646 ± 7.368 vs 9.308 ± 4.675 mmHg m/s3 , P =.001) and W2 (4.289 ± 2.017 vs 2.995 ± 1.868 mmHg m/s3 , P =.001). Hypertensives were divided into tertiles according to LVEF: W1 (11.934 ± 5.836 vs 11.576 ± 5.857 vs 17.227 ± 8.889 mmHg m/s3 , P <.0001) was higher in the highest LVEF tertile along with relative wall thickness, midwall fractional shortening, endocardial fractional shortening, and R-W1 . Newly diagnosed hypertensives show increased LVM and LV contractility, including carotid WI parameters and R-W1 values, as compared with normotensive subjects, but no differences in LV diastolic function.

Ethanol-Associated Cardiomyocyte Apoptosis and Left Ventricular Dilation Are Unrelated to Changes in Myocardial Telomere Length in Rats

AimThe aim of this work was to determine whether ethanol-associated myocardial apoptosis and cardiac dilation are related to myocardial telomere shortening in rats. Methods and ResultsSprague-Dawley (SD) rats received either drinking water with (ethanol: n = 19) or without (control: n = 19) 5% (v/v) ethanol ad libitum, for 4 months. Left ventricular (LV) dimensions and function (echocardiography and isolated perfused heart preparations), cardiomyocyte apoptosis (terminal deoxynucleotide transferase–mediated dUTP nick-end labeling), and leukocyte and myocardial telomere length (real-time polymerase chain reaction) were determined at the end of the study. Ethanol administration resulted in a marked increase in cardiomyocyte apoptosis (ethanol 0.85 ± 0.13% vs control 0.36 ± 0.06%; P = .0021) and LV dilation (LV end-diastolic diameter: ethanol 8.20 ± 0.14 mm vs control 7.56 ± 0.11 mm [P = .0014]; volume intercept at 0 mm Hg (V0) of the LV end-diastolic pressure-volume relationship: ethanol 0.40 ± 0.03 mL vs control 0.31 ± 0.02 mL [P = .020]). However, there were no changes in systolic chamber function as indexed by LV endocardial fractional shortening or the slope of the LV systolic pressure-volume relationship (end systolic elastance). The percentage of myocardial apoptosis was correlated with the degree of LV dilation (% apoptosis vs LV EDD: r = 0.39; n = 38; P = .021; vs V0: r = 0.44; n = 19; P = .046). No differences in leukocyte or cardiac telomere length were noted between the ethanol and control groups. Furthermore, cardiac telomere length was not associated with indexes of LV dilation (LVEDD and V0) or cardiomyocyte apoptosis. ConclusionsChronic ethanol-associated myocardial apoptosis and adverse remodeling occurs independently from changes in cardiac telomere length. Telomere shortening may not be a critical mechanism responsible for cardiomyocyte apoptosis and adverse cardiac remodeling.

Long-Term Low Intensity Physical Exercise Attenuates Heart Failure Development in Aging Spontaneously Hypertensive Rats

Background: Physical exercise is a strategy to control hypertension and attenuate pressure overload-induced cardiac remodeling. The influence of exercise on cardiac remodeling during uncontrolled hypertension is not established. We evaluated the effects of a long-term low intensity aerobic exercise protocol on heart failure (HF) development and cardiac remodeling in aging spontaneously hypertensive rats (SHR). Methods: Sixteen month old SHR (n=50) and normotensive Wistar-Kyoto (WKY, n=35) rats were divided into sedentary (SED) and exercised (EX) groups. Rats exercised in treadmill at 12 m/min, 30 min/day, 5 days/week, for four months. The frequency of HF features was evaluated at euthanasia. Statistical analyses: ANOVA and Tukey or Mann-Whitney, and Goodman test. Results: Despite slightly higher systolic blood pressure, SHR-EX had better functional capacity and lower HF frequency than SHR-SED. Echocardiography and tissue Doppler imaging showed no differences between SHR groups. In SHR-EX, however, left ventricular (LV) systolic diameter, larger in SHR-SED than WKY-SED, and endocardial fractional shortening, lower in SHR-SED than WKY-SED, had values between those in WKY-EX and SHR-SED not differing from either group. Myocardial function, assessed in LV papillary muscles, showed improvement in SHR-EX over SHR-SED and WKY-EX. LV myocardial collagen fraction and type I and III collagen gene expression were increased in SHR groups. Myocardial hydroxyproline concentration was lower in SHR-EX than SHR-SED. Lysyl oxidase gene expression was higher in SHR-SED than WKY-SED. Conclusion: Exercise improves functional capacity and reduces decompensated HF in aging SHR independent of elevated arterial pressure. Improvement in functional status is combined with attenuation of LV and myocardial dysfunction and fibrosis.

Impact of Castration on Changes in Left Ventricular Diastolic Pressure–Volume Relations Induced by Chronic Adrenergic Stimulation in Rats

A reduced testosterone concentration characterizes heart failure and independently predicts outcomes. Although testosterone replacement therapy may have non cardiac-related therapeutic benefits in heart failure, whether reduced testosterone concentrations protect against adverse left ventricular remodeling (LV dilatation) is uncertain. We therefore evaluated whether surgical castration modifies LV dilatation after 6 months of daily injections of the β-adrenergic receptor (AR) agonist, isoproterenol (ISO) (0.015 mg·kg(-1)·d(-1)), to rats. The extent of LV dilatation and LV systolic chamber dysfunction were determined using both echocardiography and isolated perfused heart procedures. The extent of LV dilatation was determined from LV diastolic pressure-volume (P-V) relationships. As compared with the saline vehicle-treated group, after 6 months of β-AR activation in sham-castrated rats, a marked right shift in the LV diastolic P-V relationship was noted with an increased LV volume intercept at 0 mm Hg diastolic pressure (LV V(0) in milliliters) (ISO = 0.38 ± 0.02, saline vehicle = 0.30 ± 0.02, P < 0.05). However, chronic β-AR activation did not alter LV systolic chamber function either in vivo (LV endocardial fractional shortening, echocardiography) or ex vivo (LV end systolic elastance). Although castration decreased body weight, castration failed to modify the impact of ISO on the LV diastolic P-V relationships or the LV volume intercept at 0 mm Hg diastolic pressure (LV V(0) in milliliters) (castration ISO = 0.35 ± 0.02, castration saline vehicle = 0.27 ± 0.03, P < 0.05). In conclusion, castration does not influence the extent of LV dilatation induced by chronic adrenergic activation in an animal model, where adverse LV remodeling precedes LV systolic chamber dysfunction.

Physiological hemodynamical reactions to road-traffic noise in an experimental setting

Left ventricular hypertrophy (LVH) is more frequently associated with LV dilatation and systolic chamber dysfunction in males than in females. The mechanisms of this effect are uncertain. As excessive adrenergic stimulation may be responsible for LV dilatation and systolic chamber dysfunction in hypertension, we aimed to assess whether gender determines the adverse effects on LV chamber remodeling following 6 months of daily b-adrenergic receptor (AR) stimulation (isoproterenol [ISO] at 0.04 mg/ kg.day) in spontaneously hypertensive rats (SHR). LV dilatation was assessed in vivo from LV end diastolic diameter (EDD) (echocardiography) and ex vivo from the volume intercept at 0 mm Hg pressure (V0) of the LV diastolic pressure-volume relationship (isolated, perfused heart technique). LV systolic function was determined in vivo from LV endocardial fractional shortening (FSend) and ex vivo from the slope (LV end systolic elastance [LV Ees]) of the LV end systolic pressure-volume relationship (isolated, perfused heart technique). As compared to saline-treated male SHR, male SHR receiving ISO for 6 months developed an increased LV EDD and LV V0, and a decreased LV Ees (Table). In contrast, ISO administration failed to modify LV EDD, LV V0 or LV Ees in female SHR (Table). In conclusion, as compared to female SHR, male SHR are more susceptible to the adverse effects of chronic b-AR activation on LV cavity dimensions and systolic chamber function. These results suggest that the higher prevalence of LV dilatation and systolic chamber dysfunction in males than in females with LVH may be attributed to an increased susceptibility to the adverse effects of adrenergic stimulation.

Telomere length and adrenergic-induced left ventricular dilatation and systolic chamber dysfunction in rats

The mechanisms responsible for telomere shortening in heart failure are uncertain. We evaluated whether left ventricular (LV) dilatation and systolic chamber dysfunction produced by chronic β-adrenergic receptor (β-AR) activation is associated with leukocyte or cardiac telomere shortening. Following 6 months of daily injections of the β-AR agonist, isoproterenol (0.02 mg/kg/day) or the saline vehicle to rats, the extent of LV dilatation and LV systolic chamber dysfunction were determined using echocardiography and isolated perfused heart procedures, and relative telomere length of leukocyte (LTL) and cardiac (CTL) deoxyribonucleic acid were determined using a quantitative real-time polymerase chain reaction assay. β-AR activation resulted in LV dilatation as indexed by increased LV diastolic diameters (9.2 ± 0.6 vs. 8.4 ± 0.9 mm, P = 0.01) and increased diastolic volume intercepts at zero pressure of the LV diastolic pressure-volume relationship (isolated, perfused heart preparation) (0.40 ± 0.06 vs. 0.37 ± 0.08 ml, P = 0.03). Moreover, β-AR activation resulted in LV systolic chamber dysfunction as indexed by reductions in LV endocardial fractional shortening (0.40 ± 0.05 vs. 0.45 ± 0.06, P = 0.01) and the slope of the LV systolic pressure-volume relation (609 ± 176 vs. 901 ± 230, P = 0.01). Although LTL decreased with age in rats receiving either the β-AR agonist or the saline vehicle (P < 0.05), neither CTL (-0.10 ± 0.14 vs. -0.15 ± 0.12, P = 0.3) nor LTL (-0.11 ± 0.19 vs. -0.15 ± 0.18, P = 0.5) were modified by β-AR activation. In conclusion, chronic β-AR activation sufficient to produce LV dilatation and systolic chamber dysfunction is not associated with alterations in leukocyte or cardiac telomere length. Telomere shortening in chronic heart failure is unlikely to be attributed to chronic β-AR activation.

Evaluation of Left Ventricular Function by Bedside Ultrasound in Acute Toxic Myocarditis

BackgroundMyocarditis can be difficult to diagnose in the Emergency Department (ED) due to the lack of classic symptoms and the wide variation in presentations. Poor cardiac contractility is a common finding in myocarditis and can be evaluated by bedside ultrasound. ObjectiveTo demonstrate the utility of fractional shortening measurements as an estimation of left ventricular function during bedside cardiac ultrasound evaluation in the ED. Case ReportA 54-year-old man presented to the ED complaining of 3 days of chest tightness, palpitations, and dyspnea, as well as persistent abdominal pain and vomiting. An electrocardiogram (ECG) showed sinus tachycardia with presumably new ST-segment elevation and signs of an incomplete right bundle branch block. A bedside echocardiogram was performed by the emergency physician that showed poor left ventricular function by endocardial fractional shortening measurements. On further questioning, the patient revealed that for the past 2 weeks he had been regularly huffing a commercially available compressed air duster. Based on these history and examination findings, the patient was given a presumptive diagnosis of toxic myocarditis. A follow-up echocardiogram approximately 7 weeks later demonstrated resolution of the left ventricular systolic dysfunction and his ECG findings normalized. ConclusionCardiac ultrasound findings of severely reduced global function measured by endocardial fractional shortening were seen in this patient and supported the diagnosis of myocarditis. Endocardial fractional shortening is a useful means of easily evaluating and documenting left ventricular function and can be performed at the bedside in the ED.

Tolerância ao esforço em ratos com estenose aórtica e disfunção ventricular diastólica e/ou sistólica

Physical stress tolerance (ST) is a measurement of cardiorespiratory fitness. Aerobic capacity is reduced in heart failure (HF) although there is no data available on this parameter in animals with ventricular dysfunction and no signs of HF.Evaluate ST in rats with ventricular diastolic dysfunction isolated or associated with systolic dysfunction induced by ascending aortic stenosis (AoS).Young male Wistar rats (20-30 days old), divided in: control group (CG, n=11) and AoSG group, (n=12). Animals were assessed at 6 and 18 weeks after AoS surgery. Treadmill exercise test was until exhaustion and evaluated treadmill speed and lactate concentration [LAC] at lactate threshold, treadmill speed and [LAC] at exhaustion, and total testing time.Echocardiography data revealed remodeling of the left atrium and left ventricular concentric hypertrophy at 6 and 18 weeks. Endocardial fractional shortening was greater in AoSG than CG at 6 and 18 weeks. Midwall fractional shortening was greater in AoSG than in CG only 6 week. Cardiac index was similar in CG and AoSG at 6 and 18 weeks and decreased between from 6 to 18 weeks in both groups. The E wave to A wave ratio was greater in CG than in AoSG at both periods and did not change in both groups between week 6 and 18. Treadmill stress testing parameters were similar in both groups at 6 or 18 weeks.Although AoS promotes isolated diastolic dysfunction or associated with systolic dysfunction at 6 or 18 weeks, it is not sufficient to modify physical stress tolerance.

Reverse chamber remodelling following adrenergic-induced advanced cardiac dilatation and pump dysfunction

As adrenergic-induced cardiac dilatation is associated with cardiomyocyte cell death, whether cessation of excessive adrenergic effects can achieve complete reverse chamber remodelling in established cardiac dilatation and pump dysfunction has been questioned. We assessed whether following the development of cardiac dilatation and pump dysfunction subsequent to 6 months of daily β-adrenergic receptor agonist administration (isoproterenol [ISO] at 0.01 mg/kg daily) to rats, withdrawal of ISO administration for a further 4 months (ISO + recovery) reverses the adverse effects on the heart. Chronic ISO administration and the withdrawal of ISO administration were associated with changes in cardiomyocyte apoptosis, but not myocardial necrosis (pathological score). After 6 months of ISO administration, left ventricular (LV) end diastolic and systolic diameters, and the volume intercept of the LV diastolic pressure-volume relationship (LV V (0)), were markedly increased and LV endocardial fractional shortening (FS(end)), LV end systolic chamber (slope of the systolic pressure-volume relationship-Ees) and myocardial (slope of the systolic stress-strain relationship-En) contractility were substantially decreased. Chronic ISO administration produced a 2.5 times increase in LV V (0) (ISO = 0.40 ± 0.04 vs. saline = 0.16 ± 0.01, P < 0.001). Following a 6-month period of ISO administration and a subsequent withdrawal period for a further 4 months, LV chamber diameters, LV V (0) (ISO + recovery = 0.21 ± 0.02 vs. saline = 0.23 ± 0.02, P < 0.001), FS(end), LV Ees and LV En were all noted to be similar to control rats. The proportion of ISO + recovery rats with LV chamber diameters, LV V (0), FS(end), LV Ees and LV En values above or below the 95% confidence interval for the saline + recovery rats was similar to the proportion of saline + recovery rats above or below their own 95% confidence intervals. In conclusion, even in the presence of adrenergic-induced cardiomyocyte apoptosis, marked cardiac dilatation and pump dysfunction produced by chronic β-adrenergic receptor activation can be completely reversed by withdrawal of the excessive adrenergic stimulus.

In-treatment midwall and endocardial fractional shortening predict cardiovascular outcome in hypertensive patients with preserved baseline systolic ventricular function: the Losartan Intervention For Endpoint reduction study

Endocardial fractional shortening (EFS) and midwall shortening (MWS) are impaired in patients with left ventricular hypertrophy. However, it remains unknown whether improvement of left ventricular systolic function during treatment reduces cardiovascular morbidity and mortality in hypertensive patients with preserved left ventricular function. Echocardiograms were performed yearly in 840 hypertensive patients with electrocardiographic left ventricular hypertrophy and baseline left ventricular ejection fraction more and equal to 50%. Baseline and annual in-treatment levels of EFS, MWS and blood pressure (BP) were related to occurrence of a composite endpoint (cardiovascular death, myocardial infarction or stroke) and the component endpoints during 3914 patient-years of follow-up. Adjusting for in-treatment BP, left ventricular mass, relative wall thickness and randomized treatments, higher in-treatment EFS was associated with lower risk of myocardial infarction (by 35% per standard deviation [4.5%], P = 0.004) and heart failure (49%, P < 0.001), but in-treatment stress-corrected EFS predicted only incident heart failure (41%, P = 0.014) but not other endpoints. Higher in-treatment MWS tended to be associated with lower risk of composite endpoints (16% per standard deviation [1.8%], P = 0.07) and was significantly associated with myocardial infarction (33%, P = 0.004) and heart failure (43%, P < 0.001). Higher in-treatment stress-corrected MWS was associated with lower rates of myocardial infarction (35%, P = 0.021) and heart failure (50%, P = 0.001). These results support a prognostic role for left ventricular myocardial function, as estimated by stress-corrected MWS, during aggressive BP lowering in hypertensive patients with preserved ejection fraction at baseline evaluation.

Assessment of longitudinal left ventricular systolic function by different echocardiographic modalities in patients with newly diagnosed mild-to-moderate hypertension

Standard echocardiographic methods reflect chamber dynamics and do not provide a direct measure of myocardial fiber shortening. Therefore we evaluated longitudinal left ventricular myocardial function by tissue Doppler echocardiography; strain (S), strain rate (SR), tissue Doppler velocity (TDV) in newly diagnosed mild to moderate hypertensive patients. Our cross-sectional and observational study population consisted of 57 patients and 48 normotensive control subjects. Patients with obesity, diabetes mellitus, regional wall motion abnormality, secondary hypertension and a history or clinical evidence of cardiovascular disease, arrhythmias or conduction abnormalities were excluded from the study. Ejection fraction, endocardial fractional shortening (eFS), meridional end-systolic stress (mESS), stress-adjusted eFS (observed /predicted eFS) were measured by M-mode echocardiography. Relationship between the left ventricular mass index and mESS was assessed by Pearson's linear regression model. Hypertensive patients had significantly decreased longitudinal myocardial function compared to control subjects determined by septal (-1.25+/-0.30 vs. -1.02+/-0.33, p<0.001) and lateral (-1.20+/-0.28 vs. 1.02+/-0.41, p<0.01) SR (1/s) measurements. However, there was no significant correlation between the mESS and strain-strain rate measurements in both normal and hypertensive subjects. Early impairment in longitudinal left ventricular systolic function can be expected despite normal endocardial left ventricular function indicated by M-mode echocardiography in patients with newly diagnosed and never treated mild to moderate hypertension.

Normal Ranges and Physiological Changes of Midwall Fractional Shortening in Healthy Korean Population

Background and ObjectivesLeft ventricular (LV) midwall fractional shortening (FSmw) reflects systolic function more accurately than LV endocardial fractional shortening (eFS) in patients with increased LV wall thickness. Although the normal reference ranges of LV-FSmw have been suggested in Western population studies, its reference values and age-related physiological changes in Eastern populations remain unknown.Subjects and MethodsConventional echocardiographic parameters, LV-FSmw, and stress-corrected LV-FSmw were assessed in 160 healthy and clinically normal subjects with a mean age of 45 (range, 11-72 years; 104 males, 56 women), all of whom were confirmed to be free of disease, based on laboratory investigations, clinical and physical examination findings and computed tomographic coronary angiographic examinations.ResultsLV-FSmw was higher in women compared to men. However, the differences were without statistical significance (18.2±1.5% for male gender and 19.4±2.5% for female gender, p=0.07). In contrast to LV-eFS that progressively increased with age (p=0.001), LV-FSmw and stress-corrected LV-FSmw was not influenced by changes in age (p=0.88 and 0.29, respectively). The results remained unchanged when analyses were performed adjusting for gender.ConclusionThe results of this study provide normal reference values for LV-FSmw and stress-corrected LV-FSmw and their natural physiological changes with advancing age. These measures can be used as reference standards for research on LV systolic function in the setting of pressure or volume overload.

Assessment of cardiac involvement in sarcoidosis by echocardiography

The main objective of this study is to determine the prevalence of left ventricular systolic and diastolic dysfunction in patients with chronic sarcoidosis without clinical evidence of heart disease. The study includes 69 chronic sarcoidosis patients, 30 diagnosed by organ biopsy and 39 by clinical history, chest X-ray, high resolution computerized tomography (HRCT) and bronchoalveolar lavage (BAL), without suspected cardiac involvement. The control group consisted of 26 subjects selected from a population of hospital workers. The examination includes 12-lead ECG and echocardiographic examination. The results show that there were no differences in atrial size, left ventricular diameters, wall thickness, left ventricular ejection fraction or endocardial fractional shortening between the sarcoid group and controls. Signs of diastolic dysfunction were found in 33 (55%) patients, however, this group was significantly older than the others and had marginally higher blood pressure. Sarcoid patients had lower midwall fractional shortening (mFS) than controls; patients with diastolic dysfunction also had lower mFS but the difference was not significant. In conclusion, the results demonstrated an absence of left ventricular systolic dysfunction, evaluated by traditional echocardiographic methods, in our chronic sarcoidosis patients and an apparent absence of any relation between left ventricular diastolic dysfunction and sarcoidosis. Lower mFS was found among patients, particularly those with a long history of sarcoidosis. Further analysis is required to evaluate the significance of this index as a potential marker of heart involvement in chronic sarcoidosis.

Abstract 5882: Myocardial Contractile Dysfunction in Heart Failure with Preserved Ejection Fraction

Background Patients with heart failure and preserved ejection fraction (HFpEF) have diastolic dysfunction, but are traditionally considered to have normal left ventricular (LV) systolic function. However, ventricular remodeling can result in preservation of EF despite abnormal myocardial contractility. Methods We performed echo-Doppler characterization of LV chamber and myocardial systolic properties in a population-based study, comparing patients with HFpEF (N=244) to healthy controls (CON, N=617), and hypertensives without HF (HTN, N=719), then examined long term outcome. Results All subjects had a normal EF (&gt;50%). However, systolic chamber function, measured by wall stress-corrected endocardial fractional shortening (sc-eFS), was impaired in HFpEF (96±12%) compared to both CON (100±8%, p&lt;0.0001) and HTN (108±11%, p&lt;0.0001). Myocardial contractility, assessed by wall stress-corrected midwall shortening (sc-mFS), was also reduced in HFpEF (91±13%) compared to CON (100±10%, p&lt;0.0001) and HTN (105±12%, p&lt;0.0001). HTN had increased sc-eFS and sc-mFS compared with both HFpEF and CON (p&lt;0.0001). In HFpEF, impaired sc-mFS was associated with increased mortality, independent of age (Figure ), while EF and sc- eFS were not. Conclusions Despite preservation of EF, unselected HFpEF patients from the community have significantly impaired systolic chamber function and depressed myocardial contractility. Abnormal myocardial contractility in HFpEF is associated with increased mortality. These data suggest that myocardial systolic dysfunction contributes to the pathophysiology of HFpEF and may represent a potential therapeutic target.