Left-ventricular function has been shown to be an important prognostic factor in estimating operative risk in cardiac surgery. As such, left-ventricular ejection fraction (LVEF) is included in the EuroSCORE. However, left-ventricular... more
Left-ventricular function has been shown to be an important prognostic factor in estimating operative risk in cardiac surgery. As such, left-ventricular ejection fraction (LVEF) is included in the EuroSCORE. However, left-ventricular function is more comprehensively assessed by measures of both systolic and diastolic dysfunction. We hypothesised that end-diastolic dysfunction is an additional independent indicator for predicting outcome following coronary artery bypass grafting (CABG). We retrospectively assessed all patients undergoing isolated off-pump CABG between October 2000 and September 2004 by two surgeons. Left-ventricular end-diastolic pressure (LVEDP), measured during cardiac catheterisation, was used as a measure of left-ventricular diastolic dysfunction. Logistic regression was used to assess the association between LVEDP (a continuous and dichotomous variable) and mortality, while adjusting for EuroSCORE. A total of 925 patients with complete LVEDP data were identified...
left ventricular (LV) mechanical dyssynchrony (LVMD) has emerged as a therapeutic target using cardiac resynchronization therapy (CRT) in chronic heart failure patients. Current methods used to evaluate LVMD are technically challenging... more
left ventricular (LV) mechanical dyssynchrony (LVMD) has emerged as a therapeutic target using cardiac resynchronization therapy (CRT) in chronic heart failure patients. Current methods used to evaluate LVMD are technically challenging and do not assess all the components of LVMD simultaneously. We analysed real-time 3D speckle tracking (3DST) echocardiography as a novel method to assess LVMD. three-dimensional ST was performed in 60 unselected patients (71 ± 9 years old; 39% with ischaemic cardiomyopathy) who were referred to optimize and to control of a CRT device; implanted according to current guidelines (9 added to be excluded from the protocol). Two standardized conditions [right ventricular (RV) versus an optimized biventricular (BiV) pacing modality] were tested. These two pacing modalities lead to two distinct electrical activation patterns. We sought to test the capability of 3DST to distinguish these two patterns. The LV ejection fraction was 24 ± 9 in the RV mode and 29 ...
Doppler echocardiographic measurement of time-velocity integral of blood flow across the aortic annulus ("stroke distance") or of stroke volume (SV) have been proposed as noninvasive measures of cardiac pump performance that... more
Doppler echocardiographic measurement of time-velocity integral of blood flow across the aortic annulus ("stroke distance") or of stroke volume (SV) have been proposed as noninvasive measures of cardiac pump performance that could elucidate the hemodynamics of hypertension. To evaluate the performance of these measures of hemodynamic volume load in a population with a wide range of body build and other characteristics, we obtained technically adequate imaging and Doppler echocardiograms in 1,935 of 2,212 (87%) American Indian Strong Heart Study participants, without mitral regurgitation or segmental left ventricular (LV) dysfunction, in Arizona, Oklahoma, and South/North Dakota. The subjects ranged widely in age (48 to 81 years) and body mass index (17.0 to 62.6 kg/m2); 65% were women; 1,161 were normotensive and 774 were hypertensive. As a reference standard, LV and stroke volumes were calculated from LV internal dimensions by the Teichholz method. Doppler SVs were modera...
UNLABELLED Anthracyclines are widely used in chemotherapy regimens for several malignancies, with cardiotoxicity being the major limiting factor in high-dose schedules. Recently, it was reported that doxorubicin induces apoptosis in... more
UNLABELLED Anthracyclines are widely used in chemotherapy regimens for several malignancies, with cardiotoxicity being the major limiting factor in high-dose schedules. Recently, it was reported that doxorubicin induces apoptosis in cardiac muscle cells in vivo and, as such, is expected to be involved in the genesis of doxorubicin-induced cardiomyopathy. The aim of this study was to validate an animal model for in vivo monitoring of doxorubicin cardiotoxicity by means of scintigraphic detection of apoptosis. METHODS Three groups of 5 male Wistar rats each were treated for 3, 4, and 5 times with a weekly intraperitoneal injection of doxorubicin at 2.5 mg/kg. At 24 h before and 24 h after the final treatment, (99m)Tc-annexin pinhole scintigraphy was performed. A control group of 5 rats was scanned without doxorubicin treatment. A cardiac uptake ratio was calculated from planar scintigraphy results with the following formula: (mediastinum - fat)/fat. After scintigraphy, the rats were s...
The cardiovascular risk in patients with hypothyroidism is related to an increased risk of functional cardiovascular abnormalities and to an increased risk of atherosclerosis. The pattern of cardiovascular abnormalities is similar in... more
The cardiovascular risk in patients with hypothyroidism is related to an increased risk of functional cardiovascular abnormalities and to an increased risk of atherosclerosis. The pattern of cardiovascular abnormalities is similar in subclinical and overt hypothyroidism, suggesting that a lesser degree of thyroid hormone deficiency may also affect the cardiovascular system. Hypothyroid patients, even those with subclinical hypothyroidism, have impaired endothelial function, normal/depressed systolic function, left ventricular diastolic dysfunction at rest, and systolic and diastolic dysfunction on effort, which may result in poor physical exercise capacity. There is also a tendency to increase diastolic blood pressure as a result of increased systemic vascular resistance. All these abnormalities regress with L-T4 replacement therapy. An increased risk for atherosclerosis is supported by autopsy and epidemiological studies in patients with thyroid hormone deficiency. The "tradit...
Comparative cardiac ultrastructure, morphometry, and electrocardiography after dietary copper and selenium restriction were examined. Male weanling Long-Evans rats were fed diets that were either adequate in both copper and selenium... more
Comparative cardiac ultrastructure, morphometry, and electrocardiography after dietary copper and selenium restriction were examined. Male weanling Long-Evans rats were fed diets that were either adequate in both copper and selenium (Cu+/Se+) or restricted in either Cu (Cu-) or Se (Se-) for 8 wk. At wk 8, electrocardiograms (ECG) and dP/dts were obtained and heart tissue was utilized for electron microscopy. Upon examination, Cu- rats were anemic, exhibited a greater heart: body weight ratio, and developed concentric hypertrophy characterized by an enhanced thickening of the left and right ventricular free walls, and interventricular septum. ECG recordings from lead aVF in the Cu- group showed a greater R wave amplitude in comparison to the Cu+/Se+ group. Se- rats recorded a greater left ventricular +dP/dtmax than both the Cu+/Se+ and Cu- groups. Cardiac myofibril volume densities were decreased in both Cu- and Se- rats in comparison to the Cu+/Se+ rats. In addition Cu- rats showed ...
We reported that left ventricular (LV) dilatation after 4 weeks of isolated mitral regurgitation (MR) in the dogs is marked by extracellular matrix loss and an increase in adrenergic drive. Given that extracellular matrix proteins and... more
We reported that left ventricular (LV) dilatation after 4 weeks of isolated mitral regurgitation (MR) in the dogs is marked by extracellular matrix loss and an increase in adrenergic drive. Given that extracellular matrix proteins and their receptor integrins influence β-adrenergic receptor (β-AR) responses in vitro, we tested whether β1-AR activation modulates focal adhesion (FA) signaling and LV remodeling in these same dogs with isolated MR. Normal dogs were compared with dogs with MR of a 4-week duration and with MR dogs treated with β 1 -AR blockade (β 1 -RB) (extended-release metoprolol succinate, 100 mg QD) that was started 24 hours after MR induction. In MR LVs, a decrease in collagen accumulation compared with normal dogs was associated with a decrease in FA kinase tyrosine phosphorylation, along with FA kinase interaction with adapter and cytoskeletal proteins, p130 Cas and paxillin, respectively, as determined by immunoprecipitation assays. There was increased phosphoryla...
Am. J. Respir. Cell Mol. Biol. Vol. 23, pp. 762–771, 2000 Internet address: www.atsjournals.org Chronic hypoxic pulmonary hypertension (PH) is associated with vasoconstriction and structural remodeling of pulmonary vessels including... more
Am. J. Respir. Cell Mol. Biol. Vol. 23, pp. 762–771, 2000 Internet address: www.atsjournals.org Chronic hypoxic pulmonary hypertension (PH) is associated with vasoconstriction and structural remodeling of pulmonary vessels including narrowing of the arterial lumen and loss of distal functional arteries. To test whether lung overexpression of the angiogenic factor vascular endothelial growth factor (VEGF) is beneficial in hypoxic PH, recombinant adenovirus encoding the human VEGF 165 gene under the control of a cytomegalovirus promoter (Ad.VEGF) or control vector containing no gene in the expression cassette (Ad.Null) was administered intratracheally to rats. With Ad.VEGF (108 plaque-forming units [pfu]), VEGF protein was present in bronchoalveolar lavage fluid as early as 2 d and until 17 d after gene transfer, but was not detected in serum. Only small patchy areas of
Patients with advanced heart failure have a high mortality and morbidity despite medical therapy. Depending on the underlying heart disease and severity of heart failure, 3.7 to 52.8% of patients have a QRS complex > or =120 ms who may... more
Patients with advanced heart failure have a high mortality and morbidity despite medical therapy. Depending on the underlying heart disease and severity of heart failure, 3.7 to 52.8% of patients have a QRS complex > or =120 ms who may have interventricular and intraventricular dyssynchrony correctible by cardiac resynchronization therapy (CRT). The latter is usually achieved with biventricular pacing, with the left ventricular lead placed in a tributary of the coronary sinus (CS), with a reported success rate between 88-92%. The technical advances for implantation include preformed guide sheaths to cannulate the CS, over the wire leads with passive fixation mechanism, and surgical placement methods. Device-specific CRT features include optimizing heart failure through insurance of a high percentage of pacing, heart failure monitoring, atrioventricular and interventricular timing, and avoiding double ventricular sensing. Furthermore, arrhythmic co-morbidities of heart failure suc...
Background— Pressure overload is accompanied by cardiac myocyte apoptosis, hypertrophy, and inflammatory/fibrogenic responses that lead to ventricular remodeling and heart failure. Despite incomplete understanding of how this process is... more
Background— Pressure overload is accompanied by cardiac myocyte apoptosis, hypertrophy, and inflammatory/fibrogenic responses that lead to ventricular remodeling and heart failure. Despite incomplete understanding of how this process is regulated, the upregulation of tumor necrosis factor (TNF)-α after aortic banding in the myocardium is known. In the present study, we tested our hypothesis that TNF-α regulates the cardiac inflammatory response, extracellular matrix homeostasis, and ventricular hypertrophy in response to mechanical overload and contributes to ventricular dysfunction. Methods and Results— C57/BL wild-type mice and TNF-knockout (TNF −/− ) mice underwent descending aortic banding or sham operation. Compared with sham-operated mice, wild-type mice with aortic banding showed a significant increase in cardiac TNF-α levels, which coincided with myocyte apoptosis, inflammatory response, and cardiac hypertrophy in week 2 and a significant elevation in matrix metalloproteinas...
Background: Activity of the renin-angiotensin-aldosterone system is thought to play a major role in determining blood pressure (BP) and target organ damage such as left ventricular hypertrophy. In Afro-Caribbean subjects, however,... more
Background: Activity of the renin-angiotensin-aldosterone system is thought to play a major role in determining blood pressure (BP) and target organ damage such as left ventricular hypertrophy. In Afro-Caribbean subjects, however, hypertension tends to be more severe despite lower plasma renin activity. We investigated whether this might be due to a different relation between aldosterone and renin in Afro-Caribbean compared to white subjects.Methods: Plasma aldosterone and renin activity were assessed in the morning after 15 min seated in 383 hypertensive subjects of Afro-Caribbean or white ethnicity (61% Afro-Caribbean, 83% on treatment) attending a hypertension clinic in London, UK. Left ventricular mass index (LVMI) was assessed by echocardiography in 276 subjects.Results: Plasma renin activity was lower in Afro-Caribbean compared to white subjects (0.4 [0.3–1.0] v 1.4 [0.5–3.4] ng/mL/h, medians [interquartile range], P < .0001). Despite this, aldosterone was higher in Afro-Ca...