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Background: Around 20-40% of heart transplant patients experience moderate to severe rejection within the first year after heart transplantation. Endomyocardial biopsy (EMB) is a gold standard for diagnosing heart transplant rejection. There is a need for non-invasive alternatives that allow for early, safe and reliable diagnosis of acute graft rejection prior to the onset of clinical symptoms., Aims: Our aim was to investigate the potential of speckle tracking derived strain analysis in the diagnosis of acute graft rejection., Methods: Patients indicated for EMB consented to a trans-thoracic echocardiography examination (TTE) within 2 hours of the EMB. Of this cohort, those with at least 2 EMBs separated ≥ 1 week, and whose TTE could be analyzed for strain, were included. The relationship between strain and EMB results was evaluated., Results: Of the 43 patients included (mean age 51.33±1.79, 67% male), 23 had findings of rejection identified on at least one EMB and at least one EMB without rejection for comparison. A significant deterioration in the longitudinal strain during rejection compared to non-rejection was found on apical 4-chamber views (-11.51±0.91 vs -13.48±0.96, P=0.025) and apical 2-chamber views (-11.84±0.78 vs -14.43±0.83, P=0.002). In the patients in whom no rejection was identified on either EBM, there was no significant change in longitudinal strain values at two different time points., Conclusion: Worsening of longitudinal strain was associated with acute cellular rejection. Routine TTE-based strain analysis could help in early detection of cardiac rejection and timing of EMB.

Impaired cerebrovascular reactivity (CVR), an important risk factor for future stroke, is affected by a presence carotid stenosis. However, in some cases CVR can be impaired in the absence of carotid stenosis due to several poorly characterized mechanisms. We hypothesized that arterial stiffening as observed in coronary heart disease (CHD) could be associated with alteration in CVR in CHD patients without carotid stenosis. The study population consisted of patients referred for coronary angiography without significant carotid stenosis (<50 %). CVR was evaluated by breath holding index (BHI) measured with transcranial color code duplex ultrasound. Arterial stiffness was assessed by pulse wave velocity (PWV) measured by the oscillometric method. The extent of coronary atherosclerosis was quantified by Gensini score (GS). Out of 186 subjects, sixty-two patients fulfilled the inclusion and exclusion criteria. BHI decreased with increasing PWV (r = -0.47, p<0.001). Decrease in BHI was significantly inversely associated with GS (r = -0.61, p<0.001). GS was associated with PWV (p<0.001). In conclusion, impaired CVR was associated with increased arterial stiffening in CHD patients in the absence of significant carotid stenosis. Thus, we speculate that increased arterial stiffness may at least partially contribute to the pathophysiology of CVR alteration in coronary artery disease.

Background: Betablockade has been shown to have cardioprotective effects in patients under perioperative stress. Besides animal model of septic shock and a small cohort of septic patients, these benefits have not been studied in septic shock patients who require norepinephrine administration., Methods: After correction of preload, an esmolol bolus (0.2-0.5 mg/kg) followed by continuous 24 h infusion was administered in septic patients with sinus or supraventricular tachycardia (HR > 120/min). Exclusion criteria were severe LV systolic dysfunction, atrioventricular blockade and norepinephrine infusion at rates over 0.5 mg/kg/min. Monitoring with echocardiography and pulmonary artery catheter before, at 2, 6, 12, 24 h following the start and 6 h after ceasing of the esmolol drip. Patients were maintained normovolemic throughout the study and adjustments of concomitant norepinephrine infusion rates were made as required., Results: Ten septic patients (mean age 54.4 ± 18.7), APACHE II 21.5 ± 6.2, CRP 275 ± 78 mg/l, procalcitonin 14.5 ± 10.1 mg/l, were given esmolol drip of 212.5 ± 63.5 mg/h at start to 272.5 ± 89.5 mg/h at 24 h. Heart rate decreased from mean 142 ± 11/min to 112 ± 9/min (p < 0.001) with parallel insignificant reduction of cardiac index (4.94 ± 0.76 to 4.35 ± 0.72 l/min/m(2)). Stroke volume insignificantly increased from 67.1 ± 16.3 ml to 72.9 ± 15.3 ml. No parallel change of pulmonary artery wedge pressure was observed (15.9 ± 3.2 to 15.0 ±  2.4 mmHg) as well as no significant changes of norepinephrine infusion (0.13 ±  0.17 to 0.17 ± 0.19 mg/kg/min), DO(2), VO(2), OER or arterial lactate., Conclusions: Saving the heart 30 beats/min did not demonstrate adverse impact on global haemodynamics in rates above 110/min. Using well titratable betablocker seems to be safe and cardioprotective in septic shock patients with high cardiac output.

Background: In mice, transverse aortic constriction (TAC) is variably characterized as a model of pressure overload-induced hypertrophy (left ventricular [LV] hypertrophy, or LVH) or heart failure (HF). While commonly used, variability in the TAC model is poorly defined. The objectives of this study were to characterize the variability in the TAC model and to define a simple, noninvasive method of prospectively identifying mice with HF versus compensated LVH after TAC., Methods: Eight-week-old male C57BL/6J mice underwent TAC or sham and then echocardiography at 3 weeks post-TAC. A group of sham and TAC mice were euthanized after the 3-week echocardiogram, while the remainder underwent repeat echocardiography and were euthanized at 9 weeks post-TAC. The presence of TAC was assessed with two-dimensional echocardiography, anatomic aortic m-mode and color flow, and pulsed-wave Doppler examination of the transverse aorta (TA) and by LV systolic pressure (LVP). Trans-TAC pressure gradient was assessed invasively in a subset of mice. HF was defined as lung/body weight>upper limit in sham-operated mice., Results: As compared with sham, TAC mice had higher TA velocity, LVP and LV weight, and lower ejection fraction (EF) at 3 or 9 weeks post-TAC. Only a subset of TAC mice (28%) developed HF. As compared with compensated LVH, HF mice were characterized by similar TA velocity and higher percent TA stenosis, but lower LVP, higher LV weight, larger LV cavity, lower EF and stress-corrected midwall fiber shortening, and more fibrosis. Both EF and LV mass measured by echocardiography at 3 weeks post-TAC were predictive of the presence of HF at 3 or 9 weeks post-TAC., Conclusions: In wild-type mice, TAC produces a variable cardiac phenotype. Marked abnormalities in LV mass and EF at echocardiography 3 weeks post-TAC identify mice with HF at autopsy. These data are relevant to appropriate design and interpretation of murine studies., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Impaired renal function with loss of nephron number in chronic renal disease (CKD) is associated with increased cardiovascular morbidity and mortality. However, the structural and functional cardiac response to early and mild reduction in renal mass is poorly defined. We hypothesized that mild renal impairment produced by unilateral nephrectomy (UNX) would result in early cardiac fibrosis and impaired diastolic function, which would progress to a more global left ventricular (LV) dysfunction. Cardiorenal function and structure were assessed in rats at 4 and 16 wk following UNX or sham operation (Sham); (n = 10 per group). At 4 wk, blood pressure (BP), aldosterone, glomerular filtration rate (GFR), proteinuria, and plasma B-type natriuretic peptide (BNP) were not altered by UNX, representing a model of mild early CKD. However, UNX was associated with significantly greater LV myocardial fibrosis compared with Sham. Importantly, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining revealed increased apoptosis in the LV myocardium. Further, diastolic dysfunction, assessed by strain echocardiography, but with preserved LVEF, was observed. Changes in genes related to the TGF-β and apoptosis pathways in the LV myocardium were also observed. At 16 wk post-UNX, we observed persistent LV fibrosis and impairment in LV diastolic function. In addition, LV mass significantly increased, as did LVEDd, while there was a reduction in LVEF. Aldosterone, BNP, and proteinuria were increased, while GFR was decreased. The myocardial, structural, and functional alterations were associated with persistent changes in the TGF-β pathway and even more widespread changes in the LV apoptotic pathway. These studies demonstrate that mild renal insufficiency in the rat results in early cardiac fibrosis and impaired diastolic function, which progresses to more global LV remodeling and dysfunction. Thus, these studies importantly advance the concept of a kidney-heart connection in the control of myocardial structure and function.

Natriuretic peptides (NPs) are cardioprotective through the activation of guanylyl cyclase (GC) receptors A and B. CD-NP, also known as cenderitide, is a novel engineered NP that was designed to uniquely serve as a first-in-class dual GC receptor agonist. Recognizing the aldosterone suppressing actions of GC-A activation and the potent inhibitory actions on collagen synthesis and fibroblast proliferation through GC-B activation, the current study was designed to establish the anti-fibrotic actions of CD-NP, administered subcutaneously, in an experimental rat model of early cardiac fibrosis induced by unilateral nephrectomy (UNX). Our results demonstrate that a two week subcutaneous infusion of CD-NP significantly suppresses left ventricular fibrosis and circulating aldosterone, while preserving both systolic and diastolic function, in UNX rats compared to vehicle treated UNX rats. Additionally we also confirmed, in vitro, that CD-NP significantly generates the second messenger, cGMP, through both the GC-A and GC-B receptors. Taken together, this novel dual GC receptor activator may represent an innovative anti-fibrotic therapeutic agent.

Objective: Standard blood flow rates for cardiopulmonary bypass have been assumed to be the same for awake cardiac surgery with thoracic epidural anesthesia (TEA) as for general anesthesia. However, compared with general anesthesia, awake cardiac surgery with epidural anesthesia may be associated with higher oxygen consumption and may result in lactic acidosis when standard blood flow rates were used. The aim of our study was to investigate if standard blood flow rates are adequate in awake cardiac surgery., Methods: Forty-five patients undergoing elective on-pump cardiac surgery were assigned to receive either epidural (Group TEA, n=15), combined (Group TEA-GA, n=15) or general (Group GA, n=15) anesthesia. To monitor the adequacy of standard blood flow rates, arterial lactate, acid base parameters, and central venous and jugular bulb saturation were measured at six time points (before, during, and after the surgery) in all groups. Blood flow rates were adjusted when needed., Results: No lactic acidosis has developed in any group (p=NS). TEA as compared with TEA-GA and GA groups had lower central venous (67±4%, 75±11%, and 72±13%, respectively, p<0.05) and jugular bulb oxygen saturations during cardiopulmonary bypass (60±7%, 68±9%, and 75±12%, respectively, p<0.05) during the post-cardiopulmonary bypass period. The TEA group as compared with the TEA-GA and GA groups also had mild hypercapnic respiratory acidosis (56±10, 42±8, and 37±4 mmHg, respectively, p<0.05) and mild decrease of arterial oxygen saturation (93±4%, 97±2%, and 96±1%, respectively, p<0.05) at the end of surgery without any clinical consequences. Thus, no additional blood flow rates adjustments in any study group and no ventilatory support in TEA group were required., Conclusions: Under careful monitoring, the use of standard blood flow rates is adequate for patients undergoing awake on-pump normothermic cardiac surgery., (Copyright © 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.)

Aims: the ratio of early diastolic transmitral flow velocity (E) to early diastolic mitral annular velocity (E(a)) is frequently used to predict an increase in left ventricular filling pressure (LVFP). However, this approach has several limitations. The aim of this study was to test whether additional information is gained by new echocardiographic indexes utilizing strain and strain rate (SR) derived from 2-dimensional speckle tracking echocardiography (2D-STE) for the estimation of LVFP., Methods and Results: fifty-one patients with idiopathic dilated cardiomyopathy (IDC) underwent pulsed-wave tissue Doppler echocardiography and 2D-STE performed simultaneously with right heart catheterization. Receiver operating characteristic analysis showed that circumferential strain and the SR during late diastolic LV filling (0.956 and 0.951, both P = 0.001), E/circumferential SR at early diastolic LV filling (0.949, P = 0.001), and E/circumferential strain at the time of peak E-wave (0.948, P = 0.001) had greater area under the curve than the E/E(a) ratio (0.911, P = 0.001) for the prediction of pulmonary capillary wedge pressure > 12 mmHg., Conclusion: when compared with the E/E(a) ratio, several 2D-STE-derived parameters better estimated the increase in LVFP in patients with IDC.

Background: Reductions in numbers of circulating progenitor cells (CD34+ cell subsets) have been demonstrated in patients at risk for, or in the presence of, cardiovascular disease. The mediators of these reductions remain undefined. To determine whether neurohumoral factors might regulate circulating CD34+ cell subsets in vivo, we studied complementary canine models of left ventricular (LV) dysfunction., Methods and Results: A pacing model of severe LV dysfunction and a hypertensive renal wrap model in which dogs were randomized to receive deoxycorticosterone acetate (DOCA) were studied. Circulating CD34+ cell subsets including hematopoietic precursor cells (HPCs: CD34+/CD45(dim)/VEGFR2-) and endothelial progenitor cells (EPCs: CD34+/CD45-/VEGFR2+) were quantified. Additionally, the effect of mineralocorticoid excess on circulating progenitor cells in normal dogs was studied. The majority of circulating CD34+ cells expressed CD45dimly and did not express VEGFR2, consistent with an HPC phenotype. HPCs were decreased in response to pacing, and this decrease correlated with plasma aldosterone levels (Spearman rank correlation=-0.67, P=0.03). In the hypertensive renal wrap model, administration of DOCA resulted in decreased HPCs. No changes were seen in EPCs in either model. Normal dogs treated with DOCA exhibited a decrease in HPCs in peripheral blood but not bone marrow associated with decreased telomerase activity., Conclusions: This is the first study to demonstrate that mineralocorticoid excess, either endogenous or exogenous, results in reduction in HPCs. These data suggest that mineralocorticoids may induce accelerated senescence of progenitor cells, leading to their reduced survival and decline in numbers.

Background: Mechanisms promoting the transition from hypertensive heart disease to heart failure with preserved ejection fraction are poorly understood. When inappropriate for salt status, mineralocorticoid (deoxycorticosterone acetate) excess causes hypertrophy, fibrosis, and diastolic dysfunction. Because cardiac mineralocorticoid receptors are protected from mineralocorticoid binding by the absence of 11-beta hydroxysteroid dehydrogenase, salt-mineralocorticoid-induced inflammation is postulated to cause oxidative stress and to mediate cardiac effects. Although previous studies have focused on salt/nephrectomy in accelerating mineralocorticoid-induced cardiac effects, we hypothesized that hypertensive heart disease is associated with oxidative stress and sensitizes the heart to mineralocorticoid, accelerating hypertrophy, fibrosis, and diastolic dysfunction., Methods and Results: Cardiac structure and function, oxidative stress, and mineralocorticoid receptor-dependent gene transcription were measured in sham-operated and transverse aortic constriction (studied 2 weeks later) mice without and with deoxycorticosterone acetate administration, all in the setting of normal-salt diet. Compared with sham mice, sham plus deoxycorticosterone acetate mice had mild hypertrophy without fibrosis or diastolic dysfunction. Transverse aortic constriction mice displayed compensated hypertensive heart disease with hypertrophy, increased oxidative stress (osteopontin and NOX4 gene expression), and normal systolic function, filling pressures, and diastolic stiffness. Compared with transverse aortic constriction mice, transverse aortic constriction plus deoxycorticosterone acetate mice had similar left ventricular systolic pressure and fractional shortening but more hypertrophy, fibrosis, and diastolic dysfunction with increased lung weights, consistent with heart failure with preserved ejection fraction. There was progressive activation of markers of oxidative stress across the groups but no evidence of classic mineralocorticoid receptor-dependent gene transcription., Conclusions: Pressure-overload hypertrophy sensitizes the heart to mineralocorticoid excess, which promotes the transition to heart failure with preserved ejection fraction independently of classic mineralocorticoid receptor-dependent gene transcription.

Aims: We hypothesized that subjects with a normal body mass index (BMI), but high body fat (BF) content [normal weight obesity (NWO)], have a higher prevalence of cardiometabolic dysregulation and are at higher risk for cardiovascular (CV) mortality., Methods and Results: We analysed 6171 subjects >20 years of age from the Third National Health and Nutrition Examination Survey (NHANES III) and the NHANES III mortality study, whose BMI was within the normal range (18.5-24.9 kg/m(2)), and who underwent a complete evaluation that included body composition assessment, blood measurements, and assessment of CV risk factors. Survival information was available for >99% of the subjects after a median follow-up of 8.8 years. We divided our sample using sex-specific tertiles of BF%. The highest tertile of BF (>23.1% in men and >33.3% in women) was labelled as NWO. When compared with the low BF group, the prevalence of metabolic syndrome in subjects with NWO was four-fold higher (16.6 vs. 4.8%, P < 0.0001). Subjects with NWO also had higher prevalence of dyslipidaemia, hypertension (men), and CV disease (women). After adjustment, women with NWO showed a significant 2.2-fold increased risk for CV mortality (HR = 2.2; 95% CI, 1.03-4.67) in comparison to the low BF group., Conclusion: Normal weight obesity, defined as the combination of normal BMI and high BF content, is associated with a high prevalence of cardiometabolic dysregulation, metabolic syndrome, and CV risk factors. In women, NWO is independently associated with increased risk for CV mortality.

Background: In idiopathic dilated cardiomyopathy (IDC), myocardial deformational parameters and their mutual relationships remain incompletely characterized., Methods: Thirty-seven patients with IDC underwent two-dimensional speckle-tracking echocardiography (2D-STE) to assess left ventricular rotation, torsion, and longitudinal, circumferential, and radial systolic and diastolic strains and strain rates. Additionally, 2D-STE was performed in 14 controls., Results: All deformational parameters on 2D-STE were significantly lower in patients with IDC compared with controls. Seven patients exhibited opposite basal (positive, counterclockwise) and 11 patients exhibited opposite apical (negative, clockwise) rotation at end-systole. Circumferential, radial, and longitudinal early diastolic strain rates were correlated most strongly with the corresponding spatial components of systolic deformation., Conclusion: In patients IDC, all torsional, systolic, and diastolic deformational parameters were decreased. Corresponding three-dimensional components of systolic and diastolic deformations were closely coupled. Considerable variation in the direction of basal and apical rotation exists in a subset of patients with IDC.

Using the Mueller maneuver (MM) to simulate obstructive sleep apnea (OSA), our aim was to investigate acute changes in left-sided cardiac morphologic characteristics and function which might develop with apneas occurring during sleep. Strong evidence supports a relation between OSA and both atrial fibrillation and heart failure. However, acute effects of airway obstruction on cardiac structure and function have not been well defined. In addition, it is unclear how OSA might contribute to the development of atrial fibrillation and heart failure. Echocardiography was used in healthy young adults to measure various parameters of cardiac structure and function. Subjects were studied at baseline, during, and immediately after performance of the MM and after a 10-minute recovery. Continuous heart rate, blood pressure, and pulse oximetry measurements were made. During the MM, left atrial (LA) volume index markedly decreased. Left ventricular (LV) end-systolic dimension increased in association with a decrease in LV ejection fraction. On release of the maneuver, there was a compensatory increase in blood flow to the left side of the heart, with stroke volume, ejection fraction, and cardiac output exceeding baseline. After 10 minutes of recovery, all parameters returned to baseline. In conclusion, sudden imposition of severe negative intrathoracic pressure led to an abrupt decrease in LA volume and a decrease in LV systolic performance. These changes reflected an increase in LV afterload. Repeated swings in afterload burden and chamber volumes may have implications for the future development of atrial fibrillation and heart failure.

Brain (B-type) natriuretic peptide (BNP) and tissue Doppler imaging may distinguish restrictive cardiomyopathy (RCMP) from idiopathic constrictive pericardial disease (CP). However, their comparative efficacy is unknown for patients with CP from secondary causes (e.g., surgery or radiotherapy). We compared the efficacy of tissue Doppler imaging and BNP for differentiation of RCMP (n = 15) and CP (n = 16) were compared. BNP was higher in patients with RCMP than CP (p = 0.008), but the groups overlapped, particularly for BNP <400 pg/ml. BNP was lower with idiopathic CP than secondary CP (139 +/- 50 vs 293 +/- 69 pg/ml; p <0.001) or RCMP (139 +/- 50 vs 595 +/- 499 pg/ml; p <0.001), but not significantly different between those with secondary CP and RCMP (293 +/- 69 vs 595 +/- 499 pg/ml; p = 0.1). Patients with CP and RCMP had less overlap in early diastolic and isovolumic contraction tissue Doppler imaging velocities compared with BNP, with clear separation of groups evident with mean early diastolic annular velocities (averaged from 4 walls). Early diastolic tissue Doppler imaging velocity was superior to BNP for differentiation of CP and RCMP (area under the curve 0.97 vs 0.76, respectively; p = 0.01). In conclusion, mean early diastolic mitral annular velocity correctly distinguished CP from RCMP even when there was a large overlap of BNP between the 2 groups.

Background: Capitalizing on mechanoenergetic coupling, we investigated whether strain echocardiography can noninvasively estimate the ratio of adenosine triphosphate (ATP) to adenosine diphosphate (ADP), a marker of energetic status during acute myocardial ischemia and reperfusion., Methods: Twenty-eight pigs were divided into 7 groups (1 baseline, 4 ischemic, and 2 reperfusion). Ischemia was induced by left anterior descending coronary artery occlusion. Longitudinal systolic lengthening (SL) and postsystolic shortening (PSS) strain were measured by echocardiography. The ATP/ADP ratio was obtained from myocardial biopsies in the ischemic and control regions., Results: SL and PSS strain and the ATP/ADP ratio progressively decreased (P < .05) with increased duration (12, 40, 120, and 200 minutes) of ischemia. A mathematical formula (ATP/ADP = -0.97 + 0.25 x PSS strain + 0.20 x SL strain) estimated best the ATP/ADP ratio (r = 0.94, P < .05). Reperfusion after 12 but not after 120 minutes of ischemia significantly improved the ATP/ADP ratio and decreased SL and PSS strain., Conclusions: Strain echocardiography closely reflected changes and enabled the noninvasive estimation of the ATP/ADP ratio. A higher ATP/ADP ratio is associated with functional improvement after reperfusion.

Background: Leptin could be a key regulator of C-reactive protein (CRP) levels, which serve as a marker of systemic inflammation. Both leptin and CRP are predictors of cardiovascular disease (CVD). However, the interactions between leptin and CRP, and their association with CVD, remain unclear. We therefore studied them in a large, multiethnic population., Methods: We analyzed leptin and CRP levels, anthropometric variables and cardiovascular risk factor data from 6,251 participants from the Third National Health and Nutrition Examination Survey (NHANES III). Logistic regression was used to estimate the association between leptin, CRP and CVD (defined as history of myocardial infarction or stroke). Receiver operating characteristic curves were created to study the additional value of leptin and CRP for the association with CVD., Results: The mean age was 44.4 +/- 0.21 years (52.5% women). After adjustment for age, race, dyslipidemia, hypertension, diabetes, smoking, obesity and CRP, high levels of leptin were significantly associated with CVD in men (odds ratio 2.47, 95% CI 1.19-5.19) and in women (odds ratio 3.30, 95% CI 1.47-7.99). After adjustment for leptin, CRP was not associated with CVD. There was a significant correlation between levels of leptin and CRP (Spearman correlation rho = 0.22 in men and rho = 0.32 in women, both P < 0.0001). The area under the curve, representing the association between cardiovascular risk factors and CVD, increased after the addition of high levels of both leptin and CRP together., Conclusion: High leptin levels are independently associated with CVD even after adjustment for CRP; elevated CRP levels are not associated with CVD after adjustment for leptin. However, increased concentrations of both leptin and CRP confer the highest risk for CVD.

Acute decompensated heart failure (ADHF) is a growing public health problem with high mortality and costs. ADHF often, if not usually, occurs in the setting of cardiovascular and noncardiovascular comorbidities as well as advanced age. New insights provide support for the concept of heart failure as a state of deficiency of and/or resistance to endogenous B-type natriuretic peptide. The primary goals of ADHF therapy are to relieve symptoms and optimize volume status with minimal side effects. Few therapies are proven to effectively do so. Nesiritide is a balanced vasodilator with favorable neurohumoral effects and is superior to placebo in providing rapid symptom relief and to nitroglycerin in reducing filling pressures. Recent trials confirm a lack of renal toxicity at recommended doses. An adequately powered multinational mortality trial is underway. Nesiritide represents a proven therapy for normotensive/hypertensive ADHF patients with severe symptoms at rest.

Natriuretic peptides (NPs) secreted by the heart in response to volume overload are pleiotropic molecules with vasodilating, diuretic, natriuretic, antiproliferative, and antifibrotic actions. Functioning of the NP system is altered in congestive heart failure (CHF), suggesting that support of the NP system might be beneficial in treatment of acute and chronic CHF. Several approaches alone or in combination with other pharmacologic therapies have been shown to enhance function of the NP system: direct administration of native and designer NPs, inhibition of degradation of NPs and their second messenger (cyclic guanosine monophosphate ), and stimulation of cGMP generation. Despite increasing numbers of studies using NPs in therapy of acute and chronic CHF, several controversies regarding safety, efficacy, and dosing of NPs need to be addressed. Moreover, further research is warranted to identify the stages and etiologies of CHF that may profit from NP therapy.

Background: Body mass index (BMI) is the most widely used measure to diagnose obesity. However, the accuracy of BMI in detecting excess body adiposity in the adult general population is largely unknown., Methods: A cross-sectional design of 13 601 subjects (age 20-79.9 years; 49% men) from the Third National Health and Nutrition Examination Survey. Bioelectrical impedance analysis was used to estimate body fat percent (BF%). We assessed the diagnostic performance of BMI using the World Health Organization reference standard for obesity of BF%>25% in men and>35% in women. We tested the correlation between BMI and both BF% and lean mass by sex and age groups adjusted for race., Results: BMI-defined obesity (> or =30 kg m(-2)) was present in 19.1% of men and 24.7% of women, while BF%-defined obesity was present in 43.9% of men and 52.3% of women. A BMI> or =30 had a high specificity (men=95%, 95% confidence interval (CI), 94-96 and women=99%, 95% CI, 98-100), but a poor sensitivity (men=36%, 95% CI, 35-37 and women=49%, 95% CI, 48-50) to detect BF%-defined obesity. The diagnostic performance of BMI diminished as age increased. In men, BMI had a better correlation with lean mass than with BF%, while in women BMI correlated better with BF% than with lean mass. However, in the intermediate range of BMI (25-29.9 kg m(-2)), BMI failed to discriminate between BF% and lean mass in both sexes., Conclusions: The accuracy of BMI in diagnosing obesity is limited, particularly for individuals in the intermediate BMI ranges, in men and in the elderly. A BMI cutoff of> or =30 kg m(-2) has good specificity but misses more than half of people with excess fat. These results may help to explain the unexpected better survival in overweight/mild obese patients.

We report an unusual source of intra-operative bleeding in a patient undergoing cardiosurgical reoperation. After sternotomy, hematocrit dropped significantly. Only intra-thoracic bleeding from adhesions was considered to be responsible for the anemia. During reperfusion, abdominal wall was distended with a bluish bulge in the right hemidiaphragm. Immediate laparotomy revealed bleeding from a tear in the right hepatic lobe without any diaphragm injury. The tear was likely caused by blunt trauma from an oscillating saw. We emphasize cautious use of an oscillating saw in patients with hepatic congestion undergoing a repeat sternotomy. We propose that lifting the sternum in redo procedures might prevent the hepatic tear.

Echocardiographic strain waveforms are highly variable, so their interpretation is experience-dependent and subjective. We tested whether an artificial neural network (ANN) can distinguish between strain waveforms obtained at baseline and during experimentally induced acute ischemia. An open-chest model of coronary occlusion and acute ischemia was used in 14 adult pigs. Strain waveforms were obtained using a GE Vivid 7 ultrasound system. An ANN design was implemented in MATLAB, and backpropagation and "leave-one-out" processes were used to train and test it. Specificity of 86% and sensitivity of 87% suggest that ANNs could aid in diagnostic prescreening of echocardiographic strain waveforms.

Objectives: The purpose of this study was to compare the longitudinal, circumferential, and radial mechanics of the left ventricle (LV) in patients with constrictive pericarditis (CP) and restrictive cardiomyopathy (RCM)., Background: Diastolic dysfunction in CP is related to epicardial tethering and pericardial constraint, whereas in RCM it is predominantly characterized by subendocardial dysfunction. Assessment of variations in longitudinal and circumferential deformation of LV might be useful to distinguish these 2 conditions., Methods: Longitudinal, radial, and circumferential mechanics of the LV were quantified by 2-dimensional speckle tracking of B-mode cardiac ultrasound images in 26 patients with CP, 19 patients with RCM, and 21 control subjects., Results: In comparison with control subjects, patients with CP had significantly reduced circumferential strain (base; -16 +/- 6% vs. -9 +/- 6%; p < 0.016), torsion (3 +/- 1 degrees /cm vs. 1 +/- 1 degrees /cm; p < 0.016), and early diastolic apical untwisting velocities (E(r); 116 +/- 62 degrees /s vs. -36 +/- 50 degrees /s; p < 0.016), whereas longitudinal strains, displacement, and early diastolic velocities at the LV base (E(m)) were similar to control subjects. In contrast, patients with RCM showed significantly reduced longitudinal displacement (base; 14.7 +/- 2.5 cm vs. 9.8 +/- 2.8 cm; p < 0.016) and E(m) (-8.7 +/- 1.3 cm/s vs. -4.4 +/- 1.1 cm/s; p < 0.016), whereas circumferential strain and E(r) were similar to those of control subjects. For differentiation of CP from RCM, the area under the curve was significantly higher for E(m) in comparison with E(r) (0.97 vs. 0.76, respectively; p = 0.01). After pericardiectomy, there was a significant decrease in longitudinal early diastolic LV basal myocardial velocities (7.4 cm/s vs. 6.8 cm/s; p = 0.023). Circumferential strain, torsion, and E(r), however, remained unchanged., Conclusions: Deformation of the LV is constrained in the circumferential direction in CP and in the longitudinal direction in RCM. Subsequent early diastolic recoil of LV is also attenuated in each of the 2 directions, respectively, uniquely differentiating the abnormal diastolic restoration mechanics of the LV seen in CP and RCM.

Background: Obstructive sleep apnea (OSA) may predispose patients to congestive heart failure (CHF), suggesting a deleterious effect of OSA on myocardial contractility., Methods: A cross-sectional study of 85 subjects with suspected OSA who had undergone their first overnight polysomnogram, accompanied by an echocardiographic study. Patients were divided according to the apnea-hypopnea index as follows: < 5 (control subjects); 5 to 14 (mild OSA); and >or= 15 (moderate-to-severe OSA). Right and left ventricular function was evaluated using the myocardial performance index (MPI) and other echocardiographic parameters. For the right ventricle analyses, we excluded patients with a Doppler pulmonary systolic pressure of >or= 45 mm Hg, while for the left ventricle we excluded patients with an ejection fraction of

Background: Sonomicrometry is a gold standard in experimental studies on myocardial motion. However, limited information exists regarding mechanical and biochemical changes produced by sonomicrometry crystal (SC) insertion into the myocardial wall., Methods: In 10 open-chest pigs, we implanted SCs into the inner half of apical anterior and midposterior regions. Longitudinal strains (systolic lengthening, end-systolic, peak shortening, and postsystolic shortening strains) and strain rate (SR) measurements (peak systolic ejection and early and late diastolic SRs) were obtained by Doppler SR echocardiography along with troponin I levels measured from peripheral blood before and after SC insertion., Results: SR and strain parameters did not change significantly after SC implantation. Troponin I levels increased significantly from less than 0.010 to 0.129 +/- 0.138 microg/L (P < .005) after SC implantation., Conclusions: Our study demonstrates that despite biochemical evidence of myocardial injury, carefully implanted SCs do not alter systolic or diastolic regional myocardial function assessed by Doppler echocardiography.

Background: Emerging evidence suggests that a mildly elevated body mass index (BMI), is related to improved survival and fewer cardiovascular events in patients with coronary artery disease (CAD). We hypothesize that these results are related to the poor diagnostic performance of BMI to detect adiposity, especially in the intermediate BMI ranges., Methods and Results: A cross-sectional study of 95 patients with CAD referred to phase II cardiac rehabilitation. Body fat (BF)% was estimated by air displacement plethysmography. Height, weight, BMI and waist circumference were measured the same day. We calculated the correlation between BMI and both, BF% and lean mass and assessed the diagnostic performance of BMI to detect obesity defined as a BF% > 25% in men and > 35% in women. Although BMI had a good correlation with BF% (rho = 0.66, P < 0.0001), it also had a good correlation with lean mass (rho = 0.41, P < 0.0001), and BMI failed to discriminate between both (P-value = 0.72). A BMI >or= 30 kg/m2 had a good specificity (95%; 95% CI, 83-100) but a poor sensitivity (43%; 95% CI, 32-54) while a BMI >or= 25 kg/m2 had a good sensitivity (91%; 95% CI, 84-97) but a poor specificity (65%; 95% CI, 42-88) to detect BF%-obesity., Conclusions: In patients with CAD, BMI does not discriminate between BF% and lean mass, and a BMI < 30 kg/m(2) is a poor index to diagnose obesity. These findings may explain the controversial findings that link mild elevations of BMI to better survival and fewer cardiovascular events in patients with CAD. Body composition techniques to accurately diagnose obesity in patients with CAD might be necessary.

Objective: Attenuation of radio frequency (RF) signals limits the use of contrast echocardiography. The harmonic-to-fundamental ratio (HFR) of the RF signals compensates for attenuation. We tested whether HFR analysis measures the left ventricular nonperfused area under simulated experimental attenuation., Methods: Radio frequency image data from short axis systolic projections were obtained from 11 open-chest dogs with left anterior descending or left circumflex coronary artery occlusion followed by left atrial bolus injection of a perflutren microbubble contrast agent. Clinical attenuation was simulated by calibrated silicone pads interposed between the epicardial surface and the transducer to induce mild (7-dB) and severe (14-dB) reduction of the backscattered RF signals. Harmonic-to-fundamental ratio values were calculated for each image pixel for 0-, 7-, and 14-dB attenuation conditions and reproducibly showed a "perfused area" and a "nonperfused area." A reference nonperfused area was obtained by manual delineation in high-quality contrast scans., Results: Correlations of the HFR-detected and manually outlined perfusion defect areas were R = 0.92 for 0 dB, R = 0.94 for 7 dB, and R = 0.90 for 14 dB; the mean difference was less than 0.36 cm(2) (negligible) in all 3 attenuation settings. Conclusions. Attenuation compensation by our HFR method allows precise measurement of myocardial perfusion defect areas in contrast scans with simulated high level of attenuation.

Doppler tissue imaging (DTI) and DTI-derived strain imaging are robust physiologic tools used for the noninvasive assessment of regional myocardial function. As a result of high temporal and spatial resolution, regional function can be assessed for each phase of the cardiac cycle and within the transmural layers of the myocardial wall. Newer techniques that measure myocardial motion by speckle tracking in gray-scale images have overcome the angle dependence of DTI strain, allowing for measurement of 2-dimensional strain and cardiac rotation. DTI, DTI strain, and speckle tracking may provide unique information that deciphers the deformation sequence of complexly oriented myofibers in the left ventricular wall. The data are, however, limited. This review examines the structure and function of the left ventricle relative to the potential clinical application of DTI and speckle tracking in assessing the global mechanical sequence of the left ventricle in vivo.

Objectives: We introduced a harmonic-to-fundamental ratio (HFR) of the radiofrequency (RF) signals that reduces confounding effects of attenuation. We studied whether HFR analysis of RF signals received from contrast microbubbles allows accurate measurement of the left ventricular (LV) cavity area under varying levels of attenuation., Background: Attenuation is a fundamental problem in ultrasound imaging and limits the use of clinical echocardiography., Methods: RF data from short axis systolic and diastolic scans were obtained from 14 open-chest dogs following left-atrial bolus of Optison. Attenuation was induced by interposed silicone pads calibrated to induce 7dB or 14dB reductions of the backscattered RF signal. RF images were reconstructed from the RF signals, HFR values calculated for each image pixel for 0dB, 7dB and 14dB attenuation conditions, and LV area obtained by summation of "LV cavity pixels". A reference LV cavity area was obtained from endocardial border tracings in enhanced scans by experts., Results: Correlation of the HFR-defined and reference areas at systole was R=0.95, R=0.94, and R=0.91 for 0dB, 7dB and 14dB levels of attenuation, respectively, and at diastole was R=0.95 for 0dB, 7dB and 14dB levels of attenuation. The mean difference from both systolic and diastolic values was <1.45 cm(2) (i.e. negligible) in all attenuation settings., Conclusion: Our novel HFR method supports precise measurement of the LV cavity area in contrast images with simulated high attenuation of ultrasound signals.

Objectives: We sought to clarify the role of isovolumic intervals during a cardiac cycle by in vivo visualization of left ventricular (LV) intracavitary flow dynamics., Background: Asynchronous LV deformation during isovolumic contraction (IVC) and isovolumic relaxation (IVR) might represent a transient feature of myocardial wall mechanics that reverses the direction of blood flow., Methods: In 10 beating porcine hearts, the changes in LV intracavitary flow were recorded at baseline and after LV epicardial and right atrial pacing with high-resolution Doppler and contrast echocardiography. Two-dimensional vector flow fields were generated offline from B-mode contrast images with particle imaging velocimetry., Results: During IVC, flow from the LV apex accelerated toward the base, whereas blood from the base was redirected toward the outflow through formation of an anterior vortex. Conversely, during IVR, flow was initially directed toward the apex and then briefly reversed toward the base. Epicardial pacing from the LV base altered the stages of flow redirection during the pre-ejection period and delayed mitral valve closure (28 +/- 14 ms vs. 61 +/- 13 ms, p < 0.001) and aortic valve opening (77 +/- 18 ms vs. 111 +/- 18 ms, p = 0.004)., Conclusions: Isovolumic intervals are not periods of hemodynamic stasis but, rather, phases with dynamic changes in intracavitary flow. Experimentally induced aberrant epicardial electrical activation alters stages of flow redirection and prolongs the pre-ejection period. Normal electromechanical activation through the His-Purkinje system in mammalian hearts maintains an inherent synchrony with the sequence of intracavitary flow redirection.

Background: We previously found that a 2-dimensional (2D) strain echocardiography method had some limitations in the assessment of low magnitudes and rates of deformation. Here, we study whether a recently introduced high spatial resolution speckle tracking (HRT) method improves accuracy of 2D strain measurements., Methods: A gelatin block was cyclically compressed by a hydraulic piston. Regional deformations measured by 2D-HRT were compared with reference strains obtained from an embedded pair of sonomicrometry crystals. Global deformations (along the gelatin block) were compared to strains calculated from tracings of piston motion. We tested a wide range of strains (5.4%-21.5%) and combined each measurement with simulated heart rates (24-196/min)., Results: Regional deformations measured by 2D-HRT demonstrated excellent correlation (r = 0.99, P < .0001) and agreement (bias +/- 2SD = -0.3 +/- 1.3%) with sonomicrometry. Close correlation (r = 0.99, P < .0001) and agreement (bias +/- 2SD = 0.5 +/- 1.2%) was observed also for global strains measured by 2D-HRT and compared with tracings of piston motion. There was good reproducibility of all tests: interobserver and intraobserver variabilities were 3.2% and 3.4% for regional strains and 3.1% and 3.5% for global strains, respectively., Conclusion: In our in vitro setting, the 2D-HRT method produced precise and accurate measurements of strains for clinically relevant ranges of deformation magnitudes and ranges.

Dilated cardiomyopathy (DCM) is a leading cause of end-stage heart failure and cardiac transplantation. Anticardiac antibodies are common and removal of these through immunoadsorption (IA) is associated with improvement in global cardiac function. The effect of IA on regional function and quality of life (QOL) without intravenous immunoglobulin (IVIG) substitution has not been described. We performed a pilot trial using Immunosorba columns in four patients with chronic DCM and NYHA Class II-III congestive heart failure. Subjects were followed for 6 months with serial echocardiograms and validated QOL assessments. Regional and global left ventricular (LV) end-systolic deformations were assessed by two-dimensional strain echocardiography. Total IgG decreased 95% (from 1,210 +/- 274 mg/dl to 57 +/- 16 mg/dl, P = 0.003) and IgG3 decreased 61% (from 33 +/- 16 mg/dl to 13 +/- 7 mg/dl, P = 0.024). QOL improved from baseline to 6 months as assessed by the Living with Heart Failure questionnaire (from 54 +/- 18 to 19 +/- 7, P = 0.029). Mean LV ejection fraction improved from 35 to 40% at Day 5 and to 44% at 6 months (P = NS). The LV end diastolic and end systolic volumes decreased (220-202 ml, 159-130 ml, P = NS) at 6 months. Global end-systolic strain improved from -7.3% at baseline to -8.5% at Day 5 and -8.8% at 6 months (P = NS). Regional LV function and response to IA was not uniform. Even without IVIG substitution, IA for the treatment of chronic DCM is associated with improved QOL up to 6 months after treatment. A randomized, sham-controlled trial is required to confirm the benefits of IA for DCM., ((c) 2007 Wiley-Liss, Inc.)

The myofiber geometry of the left ventricle (LV) changes gradually from a right-handed helix in the subendocardium to a left-handed helix in the subepicardium. In this review, we associate the LV myofiber architecture with emerging concepts of the electromechanical sequence in a beating heart. We discuss: 1) the morphogenesis and anatomical arrangement of muscle fibers in the adult LV; 2) the sequence of depolarization and repolarization; 3) the physiological inhomogeneity of transmural myocardial mechanics and the apex-to-base sequence of longitudinal and circumferential deformation; 4) the sequence of LV rotation; and 5) the link between LV deformation and the intracavitary flow direction observed during each phase of the cardiac cycle. Integrating the LV structure with electrical activation and motion sequences observed in vivo provides an understanding about the spatiotemporal sequence of regional myocardial performance that is essential for noninvasive cardiac imaging.

The effect of phalloidin, an agent detaching nebulin from actin in skeletal muscle, on the isometric force in lamprey skinned cardiac muscle, which has nebulin in amounts comparable to that in skeletal muscle, has been studied. We found that, unlike mammalian cardiac muscle expressing nebulin less abundantly and responding to phalloidin by a force increase, lamprey cardiac muscle responds to phalloidin by a force decrease (approximately 50% decrease), thereby resembling the response of skeletal muscle. These results support our hypothesis that nebulin detachment from actin underlies phalloidin-induced force loss and suggest a role of actin-nebulin interaction in contractile function.

Background: Myocardial function is transmurally heterogeneous. Postsystolic work may functionally reflect ischemic but viable myocardium. We calculated systolic and postsystolic regional myocardial work index (RMWi) in subendocardial and subepicardial layers of myocardium supplied by a slowly occluding coronary artery., Methods: Progressive stenosis of the left anterior descending coronary artery lasting 11 +/- 5 days (end point) was induced in 10 dogs, and pressure-strain loops were obtained from subendocardial and subepicardial layers of apical and middle anterior segments by intracardiac ultrasound., Results: At baseline, the RMWi was significantly higher (P < .05) in the subendocardial layer. At the end point, there was no significant change in the RMWi in ischemic myocardium; however, the postsystolic RMWi was higher (P < .05) in the subendocardial layer and accompanied a decrease in subendocardial myocardial blood flow, although viability was largely maintained., Conclusion: A significant subendocardial postsystolic RMWi at rest suggests an impending ischemic injury in coronary artery disease when segmental function is still preserved.

Background: Studies of the association between obesity, and total mortality and cardiovascular events in patients with coronary artery disease (CAD) have shown contradictory results. We undertook a systematic review to determine the extent and nature of this association., Methods: We selected cohort studies that provided risk estimates for total mortality, with or without cardiovascular events, on the basis of bodyweight or obesity measures in patients with CAD, and with at least 6 months' follow-up. CAD was defined as history of percutaneous coronary intervention, coronary artery bypass graft, or myocardial infarction. We obtained risk estimates for five predetermined bodyweight groups: low, normal weight (reference), overweight, obese, and severely obese., Findings: We found 40 studies with 250,152 patients that had a mean follow-up of 3.8 years. Patients with a low body-mass index (BMI) (ie, <20) had an increased relative risk (RR) for total mortality (RR=1.37 [95% CI 1.32-1.43), and cardiovascular mortality (1.45 [1.16-1.81]), overweight (BMI 25-29.9) had the lowest risk for total mortality (0.87 [0.81-0.94]) and cardiovascular mortality (0.88 [0.75-1.02]) compared with those for people with a normal BMI. Obese patients (BMI 30-35) had no increased risk for total mortality (0.93 [0.85-1.03]) or cardiovascular mortality (0.97 [0.82-1.15]). Patients with severe obesity (> or =35) did not have increased total mortality (1.10 [0.87-1.41]) but they had the highest risk for cardiovascular mortality (1.88 [1.05-3.34])., Interpretation: The better outcomes for cardiovascular and total mortality seen in the overweight and mildly obese groups could not be explained by adjustment for confounding factors. These findings could be explained by the lack of discriminatory power of BMI to differentiate between body fat and lean mass.

Cardiovascular disease (CVD) remains as the first cause of death worldwide. Scientific community works everyday trying to ameliorate this burden. Only in the year 2004 around 2,790 publications about the therapeutic use of antihypertensive agents can be found in MEDLINE. Despite this overwhelming effort and information, only a relatively short number of manuscripts have a real impact in clinical practice. For the busy clinician, it becomes almost impossible to screen and be updated with the landmark publications. The purpose of this article is to provide concise information related to prevention of CVD. We reviewed publications in the past 5 years regarding cardiovascular risk factors with special attention to dyslipidemia, hypertension, diabetes, smoking cessation and obesity, discussing some new findings and treatments. We also discuss obstructive sleep apnea (OSA) as a recently identified cardiovascular risk factor, and provide a general overview about its pathophysiology and treatment.

Introduction: Doppler tissue imaging is a new technology for quantitative evaluation of myocardial motion and contractility, and is available in several ultrasound systems. This study evaluates the comparability, accuracy, and reproducibility of measurements of velocity, strain rate, and strain by two high-end ultrasound systems., Methods: Accuracy was assessed by imaging a tissue-mimicking gelatin phantom, and the comparability of measurements in the right ventricular free wall and interventricular septum was assessed in 20 healthy participants. Reproducibility was evaluated by repeated recordings in vitro and in a random subset of patients., Results: In vitro, a high degree of accuracy was found in both systems, with one system measuring slightly lower values than the reference values (mean difference 0.35 +/- 0.18 cm/s, P < .001). Values higher than the reference values were measured by both systems for strain and strain rate. In vivo, no systematic differences in measured velocities, strain rate, and strain were found; however, wide limits of agreement were seen for strain and strain rate. Measurements of tissue velocity, strain, and strain rate were well reproducible, nevertheless wide variation was found in both systems (coefficient of variation = 9%-19%)., Conclusion: For clinical purposes, both systems have sufficient accuracy for measurements of tissue velocity. The variation in measurements of strain rate and strain by Doppler tissue imaging should be taken into account when designing studies using this new technology. Approaches to potentially reduce this variation should be addressed in future studies.

Objectives: We investigated whether the onset and progression of regional left ventricular (LV) shortening and lengthening parallel the apex-to-base differences in depolarization and repolarization., Background: Limited information exists regarding apex-to-base differences in longitudinal and circumferential deformation sequence of the LV., Methods: The apex-to-base differences in electric activation and the progression of longitudinal and circumferential shortening and lengthening sequences were determined in 8 porcine beating hearts in situ by implanting bipolar electrodes and an array of 14 sonomicrometry crystals in the LV free wall., Results: Electric activation started at the apical subendocardium and showed significant delay in reaching the LV base. The onsets of mechanical activation and subsequent 20%, 40%, and 80% peak longitudinal shortenings required longer time to occur at base compared to the apex. The repolarization sequence propagated in reverse, with the base repolarizing before the apex. Subendocardial longitudinal shortening at base and subepicardial circumferential shortening at apex continued beyond the period of LV ejection, resulting in an apex-to-base gradient in the onset of lengthening. This gradient correlated with the duration of isovolumic relaxation (r = 0.85, p = 0.004) and the time required for reaching the lowest LV diastolic pressure (r = 0.70, p = 0.04)., Conclusions: Apex-to-base delay in mechanical shortening of LV parallels the apex-to-base direction of the electric activation sequence. Basal subendocardial and apical subepicardial regions deform through a characteristic phase of postsystolic shortening. Short-lived apex-to-base and subendocardial-to-subepicardial relaxation gradients at the onset of diastole may have a physiologic significance in facilitating active restoration of the LV cavity in diastole.

Background: A new 2-dimensional strain echocardiography (2DSE) method has been introduced that measures myocardial deformations by tracking localized acoustic markers. We compared strains measured in vitro and in vivo by 2DSE with those obtained by sonomicrometry., Methods: For the in vitro study, a tissue-mimicking gelatin block was cyclically compressed and longitudinal strains obtained by 2DSE and sonomicrometry crystals. For the in vivo study, arrays of crystals were implanted into the apical anteroseptal (test region) and midposterior (control region) in 16 open-chest pigs and strains measured by 2DSE and crystals at baseline and after acute ischemia., Results: In vitro, pooled data demonstrated good correlation (r = 0.99, P < .0001) and close agreement (bias +/- 2SD = 0.7 +/- 2.2%) of 2DSE and sonomicrometry. For a combination of low testing strains (5.4%) and strain rates (0.8 and 1.2 Hz), 2DSE overestimated strains by sonomicrometry. In vivo, linear regression analysis of pooled measurements demonstrated again a good correlation (r = 0.94, P < .0001) and agreement (1.1 +/- 7.5%) of 2DSE with sonomicrometry with a trend toward lower absolute values of strains by 2DSE., Conclusion: The 2DSE demonstrated good overall correlation and agreement with sonomicrometry for the tested in vitro and in vivo values. Some caution with 2DSE measurements is needed for combinations of low strains and strain rates.

Subendocardial and subepicardial layers of the left ventricle (LV) are characterized with right- and left-handed helical orientations of myocardial fibers. We investigated the origin of biphasic deformations of the LV wall during isovolumic contraction (IVC) and relaxation (IVR). In eight open-chest adult pigs, strain rates were measured along the right- and left-handed helical directions in the LV anterior wall by implanting 16 sonomicrometry crystals. Sonomicrometry strain rates were compared with the longitudinal subendocardial strain rates obtained by tissue Doppler imaging. During ejection and diastolic filling, shortening and lengthening occurred synchronously along the right- and left-handed helical directions. However, during IVC and IVR, the deformations were dissimilar in the two directions. Transmural shortening during IVC occurred along the right-handed helical direction and was accompanied with transient lengthening in the left-handed helical direction. Conversely, during IVR, the LV lengthened along the left-handed helical direction and shortened in the right-handed helical direction. Peak subendocardial strain rates obtained by tissue Doppler imaging during IVC and IVR correlated with corresponding sonomicrometry strain rate values obtained along the right- and left-handed helical directions (r = 0.81, P < 0.001 and r = 0.70, P = 0.001, respectively). Our data suggest that brief counterdirectional movements occur within the LV wall during IVC and IVR. Shortening along the right-handed helical direction is accompanied with reciprocal lengthening in the left-handed helical direction during IVC and vice versa during IVR. The results support an association between asynchronous deformation of subendocardial and subepicardial muscle fibers and the biphasic isovolumic movements observed with high-resolution tissue Doppler imaging.

Background: We aimed to assess whether myocardial postsystolic thickening (PST) can be induced by an acute increase in right ventricular (RV) afterload and, thus, demonstrate that PST may have a nonischemic cause., Methods: In 8 anesthetized open-chest pigs, radial strains of the interventricular septum (IVS) and left ventricular inferolateral wall were obtained by Doppler tissue echocardiography before and during constriction of the pulmonary artery., Results: After each constriction, RV peak systolic pressure increased from 30 +/- 5 to 57 +/- 8 mm Hg (P < .001). Peak systolic radial strain of the IVS decreased from 20.8% +/- 5.3% to 9.5% +/- 4.1% (P = .003), and PST of the IVS increased from 0.3% +/- 0.5% to 6.1% +/- 4.8% (P = .01). The onset of PST started 41 +/- 20 milliseconds after peak negative dP/dt of RV pressure. The inferolateral wall did not show PST., Conclusion: An acute increase in RV pressure causes a significant reduction in peak systolic strain of the IVS associated with the nonischemic appearance of PST.

Background: Onset of myocardial relaxation is highly energy dependent. Perfusion and therefore energy substrate delivery are predominantly reduced in the subendocardial myocardium in the early stages of progressive ischemia. We hypothesized that delayed onset of subendocardial diastolic thinning will functionally identify regionally hypoperfused resting myocardium., Methods and Results: Progressive left anterior descending coronary artery stenosis was induced by an ameroid occluder and maintained for 1 or 2 weeks (end point) in 12 dogs. M-mode tissue Doppler images of the anterior apical and middle segments (testing region) and middle inferior segment (control region) were acquired selectively in the subendocardium and subepicardium. The time to the onset of thinning was measured with the use of tissue Doppler velocity (TOTv) and a thickness function (TOTt). At the end point in the testing region, myocardial flow was significantly lower in the subendocardial layer (P<0.05) in all animals, whereas viability staining showed preserved transmural viability in 10 dogs and thin subendocardial necrosis in 2 dogs. Both TOTv and TOTt were significantly (P<0.01) prolonged in the testing region. The mean difference between subendocardial and subepicardial TOTv values versus that in the control region identified the ischemic region, even when only dogs with hypoperfused but transmurally viable myocardium were considered (P<0.05). Systolic and diastolic myocardial velocities did not identify subendocardial hypoperfusion., Conclusions: In resting myocardium subtended to progressive coronary stenosis, a delayed onset of subendocardial thinning suggests an early stage of hypoperfusion, before the development of local wall motion abnormalities.

Background: Ischemia is primarily a metabolic event. However, regional functional changes can be affected by structural alterations. We developed an experimental model of sole myocardial energy metabolism inhibition and characterized the resulting regional dysfunction., Methods: In 12 pigs, we regionally inhibited creatine kinase (CK) and, consequently, myocyte high-energy phosphate transfer by intracoronary administration of iodoacetamide. Myocardial biopsies for CK activity and structural analyses and strain rate (SR) echocardiography scans were obtained at baseline and 60 minutes after iodoacetamide administration. Plasma levels of the CK isoenzyme MB and troponin I were assessed to determine possible myocardial damage., Results: CK activity in the iodoacetamide-perfused myocardium decreased to 0.5% of the original value and was accompanied by a reduction in peak systolic SR ( P < .0001), end-systolic strain ( P < .0001), and peak SRs of myocardial early and late filling waves ( P < .0001). Microscopy showed contracture without sarcomere disruption. Plasma levels of CK isoenzyme MB and troponin I did not change., Conclusions: Regional inhibition of myocyte energetics leads to both systolic and diastolic dysfunction by SR echocardiography, but the presence of a residual phosphotransfer protects microstructural integrity.

Takayasu's arteritis is a non-specific form of vasculitis involving the aorta, its main branches and pulmonary arteries. It is a rare disease in our country, contrasting with the high prevalence in Southeast Asia, Africa and South America. We discuss the course of the disease in our patient who was a young women who developed Takayasu's arteritis associated with autoimmune thyroiditis and malabsorption syndrome due to celiac sprue. Long-term immunosuppressive therapy contributed to stabilizing the associated diseases, but did not stop the progression of the vascular lesions. The main adverse outcome in our patient was the development of severe renovascular hypertension. Bilateral renal artery stenosis was treated by angioplasty with stent implantation. Based on literature reports, the association of Takayasu's disease with multiple autoimmune disorders is a rare event. However, it would appear that the arteritis was the limiting disease for prognosis in our patient.

Acivicin, an amino acid antibiotic, was administered to 36 adult patients with previously treated metastatic colorectal cancer. The starting dose for good-risk patients was 15 mg/m2/day day given as a short intravenous infusion on 5 consecutive days every 3 weeks. Patients previously treated with radiation therapy, mitomycin, or nitrosoureas and those with inadequate bone marrow reserve received 12 mg/m2 on the same schedule. In 33 evaluable patients, one partial response occurred. Sixteen patients had stable disease with a median time to disease progression of 15 weeks (range 9-27) and a median survival of 8 months. The median survival of the whole group was, however, less than 6 months. Myelotoxicity was mild and resulted in no significant complications. Nonhematological toxicity primarily consisted of nausea, vomiting, drowsiness, depression, and altered mentation. Acivicin given by this schedule is inactive at these dose levels in previously treated patients with colorectal carcinoma.

Thirty patients with measurable metastatic colorectal cancer refractory to 5-fluorouracil-containing regimens, received AZQ (1,4-cyclohexadiene-1,4-dicarbamic acid, 2,5-bis(1-aziridinyl)3,6,dioxo,diethylester, NSC 182986) on a 5-day intravenous schedule administered every 4 weeks. Good risk patients received AZQ at the starting daily dose of 8 mg/m2, while patients who had had therapy with radiation or myelosuppressive drugs such as mitomycin C or a nitrosourea compound received an initial daily dose of 6 mg/m2. There were no complete or partial remissions. Only one of 27 evaluable patients had objective tumor regression. Five additional patients had disease stabilization. The dose-limiting toxicity was myelosuppression, with thrombocytopenia being more severe than neutropenia. The myelosuppression occurred late in the treatment cycle (day 20), was more severe with repeated treatments, and was more severe in patients who had poor bone marrow reserves. AZQ administered by the 5-day dose schedule as used in this study is not effective against colorectal cancer.

Thirty-two patients with measurable metastatic colorectal cancer refractory to 5-fluorouracil-containing regimens received aclacinomycin A (ACM-A) on a single-dose I.V. schedule administered over 4 hours every 3 weeks. Good-risk patients received ACM-A at the starting daily dose of 100 mg/m2 while patients who had had therapy with radiation or myelosuppressive drugs such as mitomycin C or a nitrosourea compound received an initial daily dose of 80 mg/m2. There were no complete or partial remissions in this study. Twelve of 30 evaluable patients had disease stabilization. Nausea and vomiting were the dose-limiting toxic effects; myelosuppression was moderate, with neutropenia more severe than thrombocytopenia. Other toxic effects included diarrhea (in 53% of the treatment courses), phlebitis (36%), and mucositis (27%). Alopecia was rare and occurred in 3% of treatment courses, while none of the patients developed clinical manifestation of cardiac toxicity. Aclacinomycin-A administered by the single-dose schedule as used in this study is not effective against colorectal cancer.