Lower Fractional Shortening Research Articles

Abstract 13276: DHA but not Etanercept Expedites Resolution of Inflammation leading to Improved Survival Following Myocardial Infarction in Aging Mice

Dietary intake of n-3 polyunsaturated fatty acids (PUFA) has been touted for cardioprotective benefits. n-3 PUFA contains docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) but their individual effects on left ventricle (LV) remodeling remains unclear compared to anti-inflammatory molecule. We assessed the individual component of n-3 PUFA and their therapeutic potential on LV remodeling post-MI in aging mice (n=150). Male C57BL/6J mice were fed chow diet for first 12 months and then placed on safflower oil (SO; 10% w/w) enriched diet (n-6 PUFA) for 3 months to induce obesity. Then mice were randomized into 5 isocaloric groups: SO or DHA or EPA or DHA+EPA (D+E) or Etanercept (ETAN; 5mg/kg/day) (n=26-30 mice/group) for 2 months. At 17 months of age, mice were subjected to permanent coronary artery ligation resulting in MI and monitored for d1 and d5 survival; maintaining no-MI as d0 naïve controls. Post-MI survival was highest in DHA fed mice compared with ETAN and all other groups (p<0.05). Mice in all groups had lower fractional shortening and extensive ventricular remodeling post-MI compared to d0 control. DHA and D+E mice reduced neutrophil infiltration at d1 compared to SO (p<0.05). The DHA and EPA fed mice showed increased ccr2 and cxcl2 expression at d1 indicating the higher monocyte density, expediting the clearance of dead LV tissues. DHA and EPA groups (both p<0.05) showed early induction of resolving enzyme HO-1 (hemeoxygenase) at d1 which peaked at d5 facilitating resolution of inflammation post-MI. LV immunohistochemistry of DHA fed mice showed enhanced expression of COX-2 (cyclooxygenase-2) at d1 and 5-LOX (5-lipoxygenase) at d5 post-MI compared to d0, and other 4 groups (all p<0.05). Further, DHA fed mice showed the higher expression of timp-1, timp-2 and timp-3 with decrease in MMP-9 levels at d5 stabilizing the matrix maturation within the infarcted LV and thus promoting resolution. In summary, our results suggest that DHA but not ETAN improved post-MI survival in aging and obese mice by reducing neutrophil density, via coordination of COX, LOX and HO-1, leading to enhanced resolution of inflammation post-MI.

Indications for intervention in asymptomatic children with chronic mitral regurgitation.

Based on outcome data, surgery is recommended for asymptomatic adults with chronic mitral regurgitation (MR) and systolic dysfunction, marked left ventricular (LV) dilation, pulmonary hypertension, atrial fibrillation, or high likelihood of successful repair; but indications for children are poorly defined. We sought to determine predictors of postoperative LV dysfunction in asymptomatic children with chronic MR. The surgical database was searched for all children who underwent mitral valve surgery for chronic MR (2000-2012). Exclusion criteria were preoperative symptoms, acute MR, cardiomyopathy, or other defects affecting LV size. Preoperative and latest follow-up clinical and echocardiographic data were obtained. LV dysfunction was defined as ejection fraction (EF) ≤55% or shortening fraction (SF) ≤28%. Associations between preoperative factors and late LV dysfunction were determined using univariate Poisson regression. For the 25 children who met criteria, preoperative median LV end systolic Z score (LVESZ) was 5.3, EF was 65%, and SF was 34%. At follow-up (median 3.9 years), nine patients (36%) had LV dysfunction. Lower preoperative SF (OR 0.6, p < 0.001) and higher LVESZ (OR 1.7, p < 0.01) were associated with late LV dysfunction. LVESZ ≥ 5 combined with SF ≤ 33% had a sensitivity of 89%, specificity of 88%, and negative predictive value of 93% for late LV dysfunction. Only 1/14 patients with preoperative SF > 33% had late LV dysfunction. For asymptomatic children with chronic MR, surgery should be considered before LVESZ exceeds five and SF falls below 33%. Patients with SF > 33% may be followed with serial echocardiographic measurements.

Prevalence of myocarditis in pediatric intensive care unit cases presenting with other system involvement

ObjectiveTo assess children with myocarditis, the frequency of various presenting symptoms, and the accuracy of different investigations in the diagnosis. MethodsThis was an observational study of 63 patients admitted to PICU with non-cardiac diagnosis. Cardiac enzymes, chest-X ray, echocardiography, and electrocardiogram were performed to diagnose myocarditis among those patients. ResultsThere were 16 cases of definite myocarditis. The age distribution was non-normal, with median of 5.5 months (3.25–21). Of the 16 patients who were diagnosed with myocarditis, 62.5% were originally diagnosed as having respiratory problems, and there were more females than males. Among the present cases, the accuracy of cardiac enzymes (cardiac troponin T [cTn] and creatine phosphokinase MB [CKMB]) in the diagnosis of myocarditis was only 63.5%, while the accuracy of low fractional shortening and of chest-X ray cardiomegaly was 85.7 and 80.9%; respectively. Cardiac troponin folds 2.02 had positive predictive value of 100%, negative predictive value of 88.7%, specificity of 100%, sensitivity of 62.5%, and accuracy of 90.5%. ConclusionsChildren with myocarditis present with symptoms that can be mistaken for other types of illnesses. When clinical suspicion of myocarditis exists, chest-X ray and echocardiography are sufficient as screening tests. Cardiac troponins confirm the diagnosis in screened cases, with specificity of 100%.

P720Notch3 is an important mediator of cardiac adaptation to pressure overload

Notch3, a receptor expressed in vascular smooth muscle cells (VSMC) and pericytes, has a key role in the integrity of resistance arteries by controlling the maturation of VSMC and the arterial differentiation. The goal of the study was to decipher the role of Notch3 in the normal heart and in the response to pressure overload. To reach our objectives, we used adult male C57Bl/6J mice lacking expression of the Notch3 gene (N3-/-). Hypertension was induced by continuous infusion of Angiotensin II (AngII) for 28 days (1μg/kg/min) in WT and N3-/- mice (n>13). The analysis combined with echocardiography analysis, mRNA quantification, western-blot, immuno- and/or histo-morphometry. In basal conditions, N3-/- mice exhibited cardiac hypertrophy (+20%, p<0.001 vs Wild Type, WT) combined with defects at the structure of coronary artery as evidenced by decreased F-actin content in the media (-20%, p<0.05) and decreased density of arterioles (p<0.05). The AngII -induced Hypertension is lower inN3-/- mice (-20%, p<0.05 vs WT +AngII). Despite this blunted systemic effect, N3-/- mice developed a more severe heart failure (HF) compared to WT+AngII mice with lower shortening fraction (-20%, p<0.01), higher cardiac hypertrophy (+35%, p<0.05), and enhanced markers of fibrosis and inflammation [induction of galectin-3 (x3.5, p<0.01)]. The results in N3-/- +AngII mice, which combined the induction of Angiopoietin 2 mRNA (+70%, p<0.05) and the repression of VEGFa (p<0.05) are in favour of coronary artery destabilization. Interestingly, coronary vessels did not show medial hypertrophy and this lack of adaptive response to hypertension was accompanied by a decreased expression of F-actin and SM actin mRNA (-50%, p<0.01). Moreover a treatment by Notch3 antisens oligonucleotides (ON) of WT +AngII mice impair coronary artery network as suggested by Angiopoietin 2 induction (p<0.05 vs WT+AngII+ scrambled ON). Altogether, we provide lines of evidence that alterations of Notch3 signaling pathway in the coronary arteries might play a role in the occurrence of HF in response to chronic increase in blood pressure.

Left Ventricular Function in Long-Term Survivors of Childhood Lymphoma

Survivors of childhood lymphoma (CL) have markedly increased risk of developing heart failure. Echocardiographic studies after cardiotoxic treatment have primarily demonstrated left ventricular (LV) systolic dysfunction. In the present study, we hypothesized that longer follow-up and a more comprehensive echocardiographic examination would reveal more cardiac abnormalities. We conducted a cross-sectional study with echocardiography 20.4 ± 8.6years after diagnosis in 125 survivors of CL, grouped according to treatment methods, and compared with matched controls. Treatment included mediastinal radiotherapy (median 40.0Gy) in 66 and anthracyclines (median dose 160mg/m(2)) in 92 survivors of CL. Abnormal LV function, left-sided valve dysfunction, or both occurred in 62 patients (50%). Diastolic dysfunction occurred in 29%. Compared with control subjects, mitral annular early diastolic velocities (e') were reduced in patients (septal e' 0.09 ± 0.03 vs 0.12 ± 0.03m/s, p <0.001), and the E/e' ratio was increased, particularly after mediastinal radiotherapy (10.6 ± 6.4 vs 5.6 ± 1.3, p <0.001). Survivors of CL had lower fractional shortening than control subjects (32 ± 6 vs 36 ± 7, p <0.001), but mean ejection fraction was equal and overt systolic dysfunction was infrequent. After mediastinal radiotherapy alone, global longitudinal myocardial strain was lower (p <0.05) compared with other treatment groups. Left-sided valvular dysfunction occurred in 55% of patients after mediastinal radiotherapy. In conclusion, survivors of CL had reduced LV diastolic function assessed by tissue Doppler imaging. This was more pronounced after mediastinal radiotherapy, which also frequently led to valvular disease. Systolic function was normal in most survivors of CL.

Long‐Term Outcome in Dogs with Patent Ductus Arteriosus: 520 Cases (1994–2009)

BackgroundPublished information regarding survival and long‐term cardiac remodeling after patent ductus arteriosus (PDA) closure in dogs is limited.ObjectivesTo report outcome and identify prognostic variables in dogs with PDA, and to identify risk factors for persistent remodeling in dogs with a minimum of 12 months of follow‐up after closure.AnimalsFive hundred and twenty client‐owned dogs.MethodsRetrospective review of medical records of 520 dogs with PDA. Outcome was determined by contacting owners and veterinarians. Dogs with PDA closure and ≥ 12 months of follow‐up were asked to return for a re‐evaluation.ResultsIn multivariable analysis of 506 dogs not euthanized at the time of diagnosis, not having a PDA closure procedure negatively affected survival (HzR = 16.9, P < .001). In 444 dogs undergoing successful PDA closure, clinical signs at presentation (HzR = 17, P = .02), concurrent congenital heart disease (HD) (HzR = 4.8, P = .038), and severe mitral regurgitation (MR) documented within 24 hours of closure (HzR = 4.5, P = .028) negatively affected survival. Seventy‐one dogs with ≥ 12 months follow‐up demonstrated a significant reduction in radiographic and echocardiographic measures of heart size (P = 0) and increased incidence of acquired HD (P = .001) at re‐evaluation. Dogs with increased left ventricular size and low fractional shortening at baseline were more likely to have persistent remodeling at re‐evaluation.Conclusions and Clinical ImportancePatent ductus arteriosus closure confers important survival benefits and results in long‐term reverse remodeling in most dogs. Clinical signs at presentation, concurrent congenital HD, and severe MR negatively affect survival. Increased left ventricular systolic dimensions and systolic dysfunction at baseline correlated significantly with persistent remodeling.

Cardiac function of the naked mole-rat: ecophysiological responses to working underground.

The naked mole-rat (NMR) is a strictly subterranean rodent with a low resting metabolic rate. Nevertheless, it can greatly increase its metabolic activity to meet the high energetic demands associated with digging through compacted soils in its xeric natural habitat where food is patchily distributed. We hypothesized that the NMR heart would naturally have low basal function and exhibit a large cardiac reserve, thereby mirroring the species' low basal metabolism and large metabolic scope. Echocardiography showed that young (2-4 yr old) healthy NMRs have low fractional shortening (28 ± 2%), ejection fraction (43 ± 2%), and cardiac output (6.5 ± 0.4 ml/min), indicating low basal cardiac function. Histology revealed large NMR cardiomyocyte cross-sectional area (216 ± 10 μm(2)) and cardiac collagen deposition of 2.2 ± 0.4%. Neither of these histomorphometric traits was considered pathological, since biaxial tensile testing showed no increase in passive ventricular stiffness. NMR cardiomyocyte fibers showed a low degree of rotation, contributing to the observed low NMR cardiac contractility. Interestingly, when the exercise mimetic dobutamine (3 μg/g ip) was administered, NMRs showed pronounced increases in fractional shortening, ejection fraction, cardiac output, and stroke volume, indicating an increased cardiac reserve. The relatively low basal cardiac function and enhanced cardiac reserve of NMRs are likely to be ecophysiological adaptations to life in an energetically taxing environment.

Impact of the Length of Vitamin D Deficiency on Cardiac Remodeling

This study was aimed to evaluate the influence of vitamin D (VD) deficiency on cardiac metabolism, morphology, and function. Thus, we investigated the relationship of these changes with the length of the nutrient restriction. Male weanling Wistar rats were allocated into 4 groups: C2 (n=24), animals were fed an AIN-93G diet with 1000 IU VD/kg of chow and were kept under fluorescent light for 2 months; D2 (n=22), animals were fed a VD-deficient AIN-93G diet and were kept under incandescent light for 2 months; C4 (n=21) animals were kept in the same conditions of C2 for 4 months; and D4 (n=23) animals were kept in the same conditions of D2 for 4 months. Biochemical analyses showed lower β-hydroxyacyl coenzyme-A dehydrogenase activity and higher lactate dehydrogenase activity in VD-deficient animals. Furthermore, VD deficiency was related to increased cytokines release, oxidative stress, apoptosis, and fibrosis. Echocardiographic data showed left ventricular hypertrophy and lower fractional shortening and ejection fraction in VD-deficient animals. Difference became evident in the lactate dehydrogenase activity, left ventricular weight, right ventricle weight, and left ventricular mass after 4 months of VD deficiency. Our data indicate that VD deficiency is associated with energetic metabolic changes, cardiac inflammation, oxidative stress, fibrosis and apoptosis, cardiac hypertrophy, left chambers alterations, and systolic dysfunction. Furthermore, length of the restriction influenced these cardiac changes.

Cardiac ventricular dimensions predict cognitive decline and cerebral blood flow abnormalities in aging men.

BackgroundThe aims of this study are to examine possible associations between left cardiac ventricular measures in sixth decade and cognitive performance, both cross sectionally and longitudinally, and to examine if left cardiac ventricular measures could predict future changes in cerebral blood flow (CBF).Methods211 elderly men from a cohort of the population study “Men born in 1914” completed M-mode echocardiography and a cognitive test battery at age 68. The cognitive test battery was repeated at age 81. CBF was estimated with 99mTc-HMPAO SPECT in 72 survivors at age 83. Cognitive performance at baseline and at 1st follow up and CBF at 1st follow up were analysed in relation to left ventricular internal dimension in diastole (LVIDd mm/m2) and fractional shortening (FS).ResultsSubjects with enlarged LVIDd at age 68 had poorer results on verbal and speed-performance tests at baseline and on verbal and visuo-spatial tests 14 years later on. Low FS was associated with decreased results on visuo-spatial tests at baseline. There was an inverse relationship between LVIDd and both verbal and spatial ability at the baseline and after 14 years of follow-up. Normotensive men with lower FS had also decreased CBF in a majority of brain areas 14 years later.ConclusionsMild echocardiographic abnormalities in 68 ys.-old men, as increased LVIDd and lower FS, are associated with lower cognitive test results and may predict cognitive decline and silent cerebral perfusion abnormalities 14 years later.

An echocardiographic study of healthy Border Collies with normal reference ranges for the breed

ObjectivesThe objectives of this study were to obtain standard echocardiographic measurements from healthy Border Collies and to compare these measurements to those previously reported for a general population of dogs. AnimalsStandard echocardiographic data were obtained from twenty apparently healthy Border Collie dogs. These data (n = 20) were compared to data obtained from a general population of healthy dogs (n = 69). MethodsBorder Collies were deemed healthy based on normal history, physical examination, complete blood count, serum biochemical profile, electrocardiogram, and blood pressure, with no evidence of congenital or acquired heart disease on echocardiographic examination. Standard two dimensional, M-mode, and Doppler echocardiographic measurements were obtained and normal ranges determined. The data were compared to data previously obtained at our hospital from a general population of normal dogs. ResultsTwo dimensional, M-mode, and Doppler reference ranges for healthy Border Collies are presented in tabular form. Comparison of the weight adjusted M-mode echocardiographic means from Border Collies to those from the general population of dogs showed Border Collies to have larger left ventricular systolic and diastolic dimensions, smaller interventricular septal thickness, and lower fractional shortening. ConclusionsThere are differences in some echocardiographic parameters between healthy Border Collies and the general dog population, and the echocardiographic reference ranges provided in this study should be used as breed specific reference values for Border Collies.

Abstract MP13: Circulating Long-chain Monounsaturated Fatty Acids and Cardiac Structure and Function

Background: We previously observed a prospective association of higher levels of plasma phospholipid long-chain monounsaturated fatty acids (LCMUFA, 22:1 and 24:1 fatty acids) with higher risk of incident congestive heart failure (CHF) in two independent cohorts: the Cardiovascular Health Study (CHS) and Atherosclerosis Risk in Communities Study. This is consistent with decades-old animal experiments demonstrating cardiotoxicity of LCMUFA, including cardiac lipid accumulation and dysfunction. However, relationships of LCMUFA to cardiac structure and function in humans are unknown. Aim: to evaluate associations of circulating LCMUFA with indices of cardiac structure and function including left-ventricular mass (LVM), LV hypertrophy (LVH), LV wall thickness, and systolic and diastolic function. Methods: We evaluated 2,220 CHS participants (age=74.6±5.0) in whom plasma phospholipid LCMUFA were measured in 1992 and M-mode echocardiography was performed in 1996. Primary outcomes were LVM index (LVM / height to the 2.7th power), LVH (LVM / height, &gt;143 g/m for men and &gt;102 g/m for women), LV wall thickness (average of posterior and septal wall thickness), systolic function (% fractional shortening), and diastolic function (ratio of early to atrial ventricular filling velocities, E/A ratio). Adjusting for sociodemographics, lifestyle factors, dietary factors, and prevalent cardiovascular diseases, we performed linear regression analyses to examine associations of 22:1 and 24:1 levels with each continuous outcome. For LVH (a common binary outcome), Poisson regression analysis was performed. Results: Mean±SD plasma phospholipid levels of 22:1 and 24:1 were 0.03±0.01 and 1.96±0.44 percent of total fatty acids. Across the interdecile range, higher levels of 22:1 and 24:1 were each associated with lower fractional shortening by 1.2% (95% confidence interval=0.1-2.3%, p=0.03) and 1.4% (0.2-2.7%, p=0.02), respectively. Higher levels of 22:1 and 24:1 were also associated with higher risk of LVH by 27% (0-62%, p=0.05) and 40% (5-86%, p=0.02), respectively. LCMUFA were not associated with LVM index, LV wall thickness, or E/A ratio (p&gt;0.1 each). Findings were similar after excluding 410 adults with prevalent coronary heart disease or CHF. Conclusions: Higher circulating levels of plasma phospholipid 22:1 and 24:1 were associated with two indices of lower systolic function and greater risk of LVH, but not with other indices. These findings, if replicated, suggest mechanistic pathways whereby LCMFUA exposure may increase CHF risk and potentially inform future prevention efforts.

The importance of early bedside echocardiography in children with scorpion envenomation

Scorpion sting may cause myocardial injury and heart failure (HF). Clinical signs of failure may develop several hours or even days after the sting, while electrocardiography (ECG) and blood examination soon after the sting may be normal. We sought to examine whether normal echocardiographic (echo) examination performed shortly after hospital arrival would exclude subsequent HF. We also sought to check if blood troponin and natriuretic peptide values measured shortly after arrival may predict or exclude subsequent HF. Natriuretic peptide activities have not been measured in scorpion sting victims. We also wanted to check if HF occurs in envenomated young infants. In a 3-year prospective study we looked at the demographic, clinical, laboratory, ECG, and echo data of all patients with general envenomation who arrived at the emergency department (ED) after scorpion sting. Clinical, laboratory, ECG, and echo results on arrival and 24 h after arrival were checked and compared between groups of patients with normal and abnormal echo on arrival. We then looked for differences in clinical course, therapy, and outcome between groups. The study included 98 children aged 80 days to 19 years (median 53.1 months), 25 were below the age of 2 years. Envenomation by the “yellow scorpion”Leiurus quinquestriatus was suspected in 74 cases. Median time between sting and ED arrival was 80 min. Echo was performed on arrival in 93 of the 98 patients, (in 5 occasions it was not performed or not recorded) 74 were normal and 19 were abnormal. Abnormal echo included hypokinesia and low fractional shortening and ejection fraction of the left ventricle. Clinical signs, abnormal ECG, and laboratory results were not discriminative between groups on arrival. Mean troponin T was higher in patients with abnormal echo, but within normal range in 13 of the 19 patients with abnormal echo and above normal in 2 of the 74 patients with normal echo – missing sensitivity and specificity. Mean N-terminal pro B-type natriuretic peptide was above normal in both groups but within normal range in 5 patients with abnormal echo and above normal range in 24 patients with normal echo – missing sensitivity and specificity. None of the patients with normal echo had subsequent HF and none of the children younger than 2 years of age had HF. All patients survived the intoxication and were discharged home without sequel. We conclude that early echo examination is an important procedure. In our study, normal examination excluded subsequent HF. Abnormal examination accelerated cardiac therapy which might have contributed to our favorable outcome. HF did not occur in infants younger than two years of age.

The second member of transient receptor potential-melastatin channel family protects hearts from ischemia-reperfusion injury

The second member of the transient receptor potential-melastatin channel family (TRPM2) is expressed in the heart and vasculature. TRPM2 channels were expressed in the sarcolemma and transverse tubules of adult left ventricular (LV) myocytes. Cardiac TRPM2 channels were functional since activation with H2O2 resulted in Ca(2+) influx that was dependent on extracellular Ca(2+), was significantly higher in wild-type (WT) myocytes compared with TRPM2 knockout (KO) myocytes, and inhibited by clotrimazole in WT myocytes. At rest, there were no differences in LV mass, heart rate, fractional shortening, and +dP/dt between WT and KO hearts. At 2-3 days after ischemia-reperfusion (I/R), despite similar areas at risk and infarct sizes, KO hearts had lower fractional shortening and +dP/dt compared with WT hearts. Compared with WT I/R myocytes, expression of the Na(+)/Ca(2+) exchanger (NCX1) and NCX1 current were increased, expression of the α1-subunit of Na(+)-K(+)-ATPase and Na(+) pump current were decreased, and action potential duration was prolonged in KO I/R myocytes. Post-I/R, intracellular Ca(2+) concentration transients and contraction amplitudes were equally depressed in WT and KO myocytes. After 2 h of hypoxia followed by 30 min of reoxygenation, levels of ROS were significantly higher in KO compared with WT LV myocytes. Compared with WT I/R hearts, oxygen radical scavenging enzymes (SODs) and their upstream regulators (forkhead box transcription factors and hypoxia-inducible factor) were lower, whereas NADPH oxidase was higher, in KO I/R hearts. We conclude that TRPM2 channels protected hearts from I/R injury by decreasing generation and enhancing scavenging of ROS, thereby reducing I/R-induced oxidative stress.

TRPM2 Channels Protect Hearts from Ischemia-Reperfusion Injury

TRPM2 channels are expressed in the heart and vasculature. To elucidate the function of TRPM2, we generated a global TRPM2-KO mouse. To evaluate whether TRPM2 channels were functional in the heart, we activated TRPM2 channels with H2O2 and demonstrated that Ca2+ influx was dependent on extracellular Ca2+ and significantly higher in WT compared to TRPM2-KO myocytes. We then examined the effects of TRPM2 channels on cardiac function, both at rest and after ischemia-reperfusion (I/R) injury. At rest, there were no differences in LV mass, heart rate, fractional shortening (FS) and +dP/dt between WT and TRPM2-KO hearts. At 2-3 days post-I/R injury, despite similar areas-at-risk and infarct sizes, TRPM2-KO hearts had lower FS and +dP/dt when compared to WT hearts. Compared to WT I/R myocytes, expression of Na+/Ca2+ exchanger (NCX1) and NCX1 current were increased, and action potential duration was prolonged in TRPM2-KO I/R myocytes. After 2 h of hypoxia followed by 30 min of reoxygenation to simulate I/R in vitro, levels of reactive oxygen species (ROS) were significantly higher in TRPM2-KO when compared to WT myocytes. Oxygen radical scavenging enzymes (SOD1 and SOD2) and their upstream regulators (FoxO1, FoxO3a and HIF-1α) were lower while NADPH oxidase (Nox2) was higher in TRPM2-KO I/R hearts. We conclude that TRPM2 channels protected hearts from I/R injury by enhancing expression of oxygen radical scavenging enzymes, thereby reducing oxidative stress associated with ischemia-reperfusion.

The significance of mild renal dysfunction in chronic heart failure.

Heart failure is a major public health concern. Prediction models in heart failure have employed echo-cardiography and other advanced laboratory parameters in predicting the risk of mortality. However, most of the patients in the resource poor economies still do not have easy access to these advanced technology. To determine the clinical and echocardiographic correlates of patients with chronic heart failure (CHF) in the presence or mild renal disease (MRD). One hundred CHF patients were categorized based on their estimated glomerular filtration rates into either normal renal function or MRD. The clinical and echocardiographic variables of both groups were compared. There were 38 females and 62 males with an overall mean age of 54 years. A significantly greater proportion of patients with mild renal disease presented in New York Heart Association classes 3 and 4 (82.9% vs 27.1%). Patients with MRD had echocardiographic findings of a significantly larger left atrial dimension, lower ejection fraction and fractional shortening and shorter deceleration time. A significantly greater proportion of patients with mild renal disease also had moderate-severe mitral and tricuspid regurgitation and grades 2-3 diastolic dysfunction compared to patients without mild renal disease. Patients with MRD also exhibited a significantly greater degree of deterioration in the fractional shortening and ejection fraction compared to non-MRD patients. Multivariate regression analysis indicated that a low ejection fraction and a low fractional shortening were significantly associated with MRD. Identification of MRD in chronic heart failure patients using the estimated glomerular filtration rate is valuable in resource poor countries. The presence of MRD in CHF is associated with poor left ventricular function and increased deterioration of ventricular function.

Comparison of Prevalence, Clinical Course, and Pathological Findings of Left Ventricular Systolic Impairment Versus Normal Systolic Function in Patients With Hypertrophic Cardiomyopathy

Impaired left ventricular systolic function (ILVSF) in hypertrophic cardiomyopathy (HC) is a risk factor for sudden death and a determinant of high mortality. We determined its prevalence, clinical parameters, long-term outcome, and pathologic findings of explanted hearts. We retrospectively analyzed 382 patients with HC; ILVSF was characterized by LV ejection fraction <50% at rest and was identified in 24 patients (6.3%). Patients with ILVSF were younger than patients with normal SF (43.5 ± 14.1 vs 55.3 ± 20.4 years, p = 0.001) and had larger LV end-diastolic cavity diameter (53.2 ± 12.2 vs 43.8 ± 6.2 mm, p = 0.001), larger left atrium (51.2 ± 6.5 vs 44.3 ± 8 mm, p <0.001), and lower fractional shortening (30.7 ± 11.1% vs 45.5% ± 10.3%, p <0.001). A combined end point (heart failure death or heart transplantation) was considered. Median follow-up was 3 years (1.2 to 6.3). Fourteen patients with ILVSF (58.3%) had the end point compared to 3 (0.8%) with normal SF (p <0.001). In explanted hearts, fibrosis represented 30.5 ± 12.5% of the left ventricle; we observed a direct correlation between fibrosis and ventricular dilation (r = 0.794, p = 0.001) and an inverse correlation between fibrosis and ejection fraction (r = -0.623, p = 0.023). Number and length density of small arterioles (<50 μm in diameter) were significantly decreased. In conclusion, ILVSF in HC has a poor prognosis and is associated with fibrosis and selective decreased development of small arterioles.

Dialysis-associated morbidity, ultrafiltration, and cardiovascular variables in children with HIV infection

Children infected with HIV on maintenance hemodialysis (HD) have increased mortality with adequate single pool Kt/V, as compared to non-HIV children on HD. It is unclear if HIV subjects on HD have similar dialysis-associated morbidity (DAM) and blood volume changes (dBV) as non-HIV subjects. It is also unclear how those variables are related to left ventricular mass index (LVMI), shortening fraction (SF), pre- and postdialysis blood pressure and mortality. We investigated the relationship between LVMI, SF and dBV and DAM using noninvasive monitoring of hematocrit in HIV vs. non-HIV subjects and their association with mortality. We used a cross-sectional study design and analyzed 18 pediatric subjects (9 had vertically transmitted HIV) on HD over a 17-month period. HIV subjects tolerated fluid removal during HD treatments as well as non-HIV subjects. In our study we confirmed an association of LVMI with DAM in subjects on HD. We found that HIV subjects who did not survive had a significantly lower SF and similar viral load as compared to subjects who survived. Noninvasive monitoring of hematocrit in HIV subjects with compromised heart function allows effective ultrafiltration. Routine echocardiography should be periodically performed in all HIV-infected children on renal replacement therapy because subclinical abnormalities, i.e. increased LVMI or reduced SF in this population can be predictors of mortality.

The antioxidant edaravone attenuates ER-stress-mediated cardiac apoptosis and dysfunction in rats with autoimmune myocarditis

Experimental autoimmune myocarditis (EAM) is mediated by myocardial infiltration by myosin-specific T-cells secreting inflammatory cytokines. In this study, rat models of EAM were prepared by injection with porcine cardiac myosin. One week after immunization, edaravone was administered intraperitoneally at 3 or 10 mg/kg/day to rats for 2 weeks. Cardiac function was measured by haemodynamic and echocardiographic studies and TUNEL assay was performed. Left ventricular (LV) expression of NADPH oxidase sub-units (p47phox and p67phox), pro-inflammatory cytokines (TNF-α), endoplasmic reticulum (ER) stress signalling proteins (GRP78, caspase-12 and GADD153) and mitogen-activated protein kinase (MAPK) family proteins (phospho-p38 MAPK and phospho-JNK) were measured by western blotting. Edaravone improved LV function in a dose-dependent manner. Central venous pressure was significantly low and LV ejection fraction and fractional shortening was significantly high in edaravone groups compared with those in the vehicle group. In addition, edaravone treatment down-regulated LV expressions of p47phox, TNF-α, GADD153, phospho-p38 MAPK and phospho-JNK. Furthermore, the LV expressions of p67phox, GRP78, caspase-12 and TUNEL-positive cells of rats with EAM treated with edaravone were significantly low compared with those of the vehicle group. These findings suggest that edaravone ameliorated the progression of EAM by inhibiting oxidative and ER stress and, subsequently, cardiac apoptosis.

Patent ductus arteriosus ligation is associated with impaired left ventricular systolic performance in premature infants weighing less than 1000 g

Patent ductus arteriosus ligation is often complicated by systemic hypotension and oxygenation failure. The ability of the immature myocardium to compensate for altered afterload is poorly understood. The aim of this study was to characterize the effects of patent ductus arteriosus ligation on myocardial performance in preterm infants. Serial echocardiographic analysis was performed before and after patent ductus arteriosus ligation. Characteristics of the patent ductus arteriosus, myocardial performance (fractional shortening, mean velocity of circumferential fiber shortening, and left ventricular output) and left ventricular afterload (end-systolic wall stress) were assessed. The stress-velocity relationship was measured as a preload-independent, afterload-adjusted measure of myocardial contractility. Forty-six preterm infants were assessed at 28.5 +/- 11.3 days and a weight of 1058 +/- 272 g. Patent ductus arteriosus ligation was followed by increased left ventricular exposed vascular resistance temporally coinciding with reduced left ventricular preload, decreased left ventricular contractility, and low left ventricular output. Neonates weighing 1000 g or less had a higher rate of low fractional shortening (<25%) or low left ventricular output (<170 mL x kg(-1) x h(-1)) and increased need for cardiotropes and demonstrated a trend toward an impaired stress-velocity relationship. Neonates with impaired left ventricular systolic performance were more likely to require cardiotropes and have low systolic arterial pressure, increased heart rate, and abnormal base deficit. Patent ductus arteriosus ligation is sometimes associated with impaired left ventricular systolic performance, which is most likely attributable to altered loading conditions. Neonates weighing 1000 g or less are at increased risk of impaired left ventricular systolic performance, which might relate to maturational differences and decreased tolerance to altered loading conditions.

Cardiac Function During Exercise in Obese Prepubertal Boys: Effect of Degree of Obesity

The purpose of the study was to evaluate the dynamics of diastolic and systolic function from rest to maximal exercise using conventional echocardiography and tissue Doppler imaging (TDI) in obese prepubertal boys compared to age-matched lean controls. Eighteen obese (10 with first degree obesity and 8 with second degree obesity according to French curves, BMI: 23.3+/-1.8 and 29.0+/-2.0 kg/m2, respectively) and 17 lean controls (BMI=17.6+/-0.6 kg/m2, P<0.001), aged 10-12 years were recruited. After resting echocardiography, all children performed a maximal exercise test. Regional diastolic and systolic myocardial velocities were acquired at rest and each workload. Stroke volume and cardiac output were calculated. At rest, obese boys had greater left ventricular (LV) diameters and LV mass. Boys in the first degree group showed no diastolic or systolic dysfunction, whereas boys with second degree obesity showed subtle diastolic dysfunction. During exercise, both obese groups showed greater stroke volume and cardiac output. First degree obese boys exhibited greater systolic and diastolic tissue Doppler velocities than controls, whereas second degree obese boys had lower diastolic tissue velocities irrespective of exercise intensity and lower fractional shortening at high exercise intensities than controls. In conclusion, no impairment in diastolic or systolic function is noticed in prepubertal boys with first degree of obesity. Enhanced regional myocardial function response to exercise was also demonstrated in this population, suggesting adaptive compensatory cardiac changes in mild obesity. However, when obesity becomes more severe, impaired global and regional cardiac function at rest and during exercise can be observed.