Biomedical subjects

Lisa de las Fuentes

Publications and source records attributed to Lisa de las Fuentes.

14 recordsLinked to original sources

PubMed2006

Relation of left ventricular lead placement in cardiac resynchronization therapy to left ventricular reverse remodeling and to diastolic dyssynchrony.

The effects of left ventricular (LV) lead placement for cardiac resynchronization therapy (CRT) on LV remodeling and dyssynchrony are not well defined. Sixty-one patients (age 60 +/- 11 years, 76% men) were evaluated by echocardiography before and 4 +/- 2 months after CRT and grouped by the LV lead placement (lateral, posterolateral, or anterolateral). Echocardiographic measurements included LV volumes and LV ejection fraction. Tissue Doppler imaging was used to assess for inter- and intraventricular systolic and diastolic dyssynchrony. Analysis of variance was used to determine the effect of the LV lead placement on echocardiographic variables after CRT. The LV lead was placed in a lateral cardiac vein in 33 patients (54%), posterolateral in 15 (25%), and anterior in 13 (21%). Lateral LV lead placement was associated with significantly smaller LV volumes compared with the posterolateral lead placement (p <0.01). Diastolic dyssynchrony improved significantly with lateral lead placement compared with the anterior lead location (p <0.05). Improvement in LV ejection fraction and inter- and intraventricular systolic dyssynchrony was similar among the 3 groups. In conclusion, in patients undergoing CRT, a lateral lead location resulted in greater reverse LV remodeling and improved diastolic dyssynchrony compared with other lead placement locations.

Diastole↗

PubMed2006

Clinical outcomes after cardiac resynchronization therapy: importance of left ventricular diastolic function and origin of heart failure.

BACKGROUND: Cardiac resynchronization therapy (CRT) improves functional outcomes in patients with severe systolic heart failure. Whether the effects of CRT on left ventricular (LV) diastolic function and clinical outcomes are influenced by the cause as either ischemic or nonischemic cardiomyopathy (CM) has not been well established. METHODS: A total of 57 patients (age 60 +/- 11 years; 25% women; LV ejection fraction 25 +/- 5%) were studied before and 4 +/- 2 months after CRT by echocardiography. Heart failure cause was ischemic CM in 19 and nonischemic CM in 38. Measurements of LV systolic and diastolic function were determined by 2-dimensional and Doppler echocardiography with Doppler tissue imaging of regional myocardial velocities. Clinical outcome events were assessed at long-term follow-up and included hospitalization for heart failure exacerbation, heart transplantation, or cardiac-related death. RESULTS: There were significant increases in LV ejection fraction, reductions in end-systolic volumes, and improved LV systolic dyssynchrony in both groups. However, significant improvements in LV diastolic function were observed only in the patients with nonischemic CM. Clinical events occurred in 53% of the ischemic group versus 26% of the nonischemic group (P < .05) after 20 +/- 11 months of CRT. Univariate and multivariate analysis revealed that Doppler-estimated LV filling pressures were predictors of clinical outcome events. CONCLUSIONS: After CRT patients with ischemic CM exhibit lack of improvement in LV diastolic function despite favorable effects on LV systolic performance. The Doppler-derived LV filling indices may be an important predictor of long-term clinical outcomes after CRT.

Cardiac Pacing, Artificial↗

PubMed2006

Alterations in left ventricular structure and function in type-1 diabetics: a focus on left atrial contribution to function.

This study was designed to determine the effects of type 1 diabetes mellitus (T1DM) on left ventricular (LV) and particularly left atrial (LA) structure and function. We evaluated 88 non-obese subjects: 44 with T1DM, 44 age- and gender-matched normal controls (age 39 +/- 11 years). LV and LA structure and function were quantified using two-dimensional echocardiography, pulse-wave Doppler, and tissue Doppler imaging, including early and late diastolic myocardial velocities (Em global and Am global, respectively). The T1DM subjects averaged higher heart rate, relative wall thickness, and ejection fraction, and lower indexed end-systolic volume than normal controls (P < .001, P < .05, P = .01, and P < .05, respectively). T1DM was related to A wave velocity, Am global, A wave integral, LA ejection fraction, and LA systolic ejection fraction (P < .01, P < .05, P < .0005, P < .001, and P < .0005, respectively). In multivariate analyses, T1DM was an independent predictor of the A wave integral, LA ejection fraction, and LA systolic ejection fraction (P < .01, P < .01, and P < .005, respectively). Thus, despite increased relative wall thickness, LV systolic function is increased and early diastolic filling is normal in T1DM subjects; however, they possess changes in LA transport function suggesting increased reliance on LA contribution to LV filling.

Adolescent↗

PubMed2006

Characterization of left ventricular diastolic function in hypertension by use of Doppler tissue imaging and color M-mode techniques.

BACKGROUND: Abnormalities in left ventricular (LV) relaxation and/or increased filling pressures are indicators of LV diastolic dysfunction in patients with hypertension (HTN). The purpose of this study was to assess clinical use of pulsed wave Doppler, Doppler tissue imaging (DTI), and color M-mode (CMM) indices for determination of diastolic function in patients with HTN. METHODS: In all, 278 ambulatory patients with normal LV systolic function were grouped according to the presence of HTN with and without LV hypertrophy (LVH) (determined by the 2-dimensional area-length method) as follows: healthy control subjects (NC, n = 122), HTN without LVH (HTN, n = 70), and HTN with LVH (HTN+LVH, n = 86). Pulsed wave Doppler-derived measurements included transmitral E- and A-wave velocities, E/A ratio, and deceleration and isovolumic relaxation time intervals; DTI-derived early diastolic (Em) velocities were obtained at 4 LV annular sites. CMM-derived flow propagation velocity and the intraventricular pressure gradient were also calculated. Analysis of covariance adjusted for age and sex of diastolic indices was performed to compare the differences among groups. RESULTS: Only DTI-derived filling pressures demonstrated progressive statistically significant differences among all 3 groups (ie, HTN vs NC, HTN+LVH vs NC, and HTN vs HTN+LVH). However, CMM-derived flow propagation velocity and intraventricular pressure gradient indices were similar among the groups. CONCLUSION: DTI is a robust method compared with pulsed wave Doppler- and CMM-derived indices for the quantitative assessment of LV relaxation and filling pressures in patients with HTN.

Echocardiography, Doppler, Color↗

PubMed2006

N-terminal pro B-type natriuretic peptide levels: correlation with echocardiographically determined left ventricular diastolic function in an ambulatory cohort.

OBJECTIVES: To investigate the correlations of plasma N-terminal pro B-type natriuretic peptide (NT-proBNP) levels with echocardiographic measurements of left ventricular (LV) systolic and/or diastolic function. BACKGROUND: Plasma levels of NT-proBNP are increased in heart failure. The extent to which NT-proBNP levels increase in LV diastolic dysfunction has not been well characterized. METHODS: Plasma NT-proBNP levels were measured in 191 consecutive, clinically stable, ambulatory patients. Echocardiography was used to determine LV systolic (LV ejection fraction [LVEF]) and diastolic function by mitral E wave to Doppler tissue early diastolic lateral annulus velocity ratio (E/Em). Patients with a history, physical findings, and/or echocardiographic evidence of cardiovascular disease (n = 148) were grouped as: (1) normal LV systolic function (LVEF > or = 55%, n = 81); and (2) LV systolic dysfunction (LVEF < 55%, n = 67). They were compared to a group of healthy control subjects (n = 43). Multivariate regression analyses were used to determine significant correlations with plasma NT-proBNP levels. RESULTS: NT-proBNP levels correlated negatively with LVEF (P < .001) and positively with E/Em (P = .001). Multivariate regression analysis demonstrated a significant correlation of NT-proBNP levels with LVEF (P < .001) and E/Em (P = .03). CONCLUSIONS: In this clinically stable, ambulatory cohort of patients with cardiovascular disease and healthy control subjects, plasma NT-proBNP levels were significantly higher in those with LV systolic dysfunction and/or elevated filling pressures, independent of the effects of LV mass, renal function, and age. These results suggest that NT-proBNP levels may be a useful adjunct in the characterization of patients presenting with history and/or symptoms compatible with LV systolic and/or diastolic dysfunction.

Ambulatory Care↗

PubMed2005

Improvements in left ventricular diastolic function after cardiac resynchronization therapy are coupled to response in systolic performance.

OBJECTIVES: To determine the short-term effects of cardiac resynchronization therapy (CRT) on measurements of left ventricular (LV) diastolic function in patients with severe heart failure. BACKGROUND: Cardiac resynchronization therapy improves systolic performance; however, the effects on diastolic function by load-dependent pulsed-wave Doppler transmitral indices has been variable. METHODS: Fifty patients with severe heart failure were evaluated by two-dimensional Doppler echocardiography immediately prior to and 4 +/- 1 month after CRT. Measurements included LV volumes and ejection fraction (EF), pulsed-wave Doppler (PWD)-derived transmitral filling indices (E- and A-wave velocities, E/A ratio, deceleration time [DT], diastolic filling time [DFT], and isovolumic relaxation time). Tissue Doppler imaging was used for measurements of systolic and diastolic (Em) velocities at four mitral annular sites; mitral E-wave/Em ratio was calculated to estimate LV filling pressure. Color M-mode flow propagation velocities were also obtained. RESULTS: After CRT, LV volumes decreased significantly (p < 0.001) and LVEF increased >5% in 28 of 50 patients (56%) and were accompanied by reduction in PWD mitral E-wave velocity and E/A ratio (both p < 0.01), increased DT and DFT (both p < 0.01), and lower filling pressures (i.e., E-wave/Em septal; p < 0.01). Patients with LVEF response < or =5% after CRT had no significant changes in measurements of diastolic function; LV relaxation (i.e., Em velocities) worsened in this group. CONCLUSIONS: In heart failure patients receiving CRT, improvement in LV diastolic function is coupled to the improvement in LV systolic function.

Aged↗

PubMed2005

Cardiac resynchronization therapy acutely improves diastolic function.

BACKGROUND: Invasive studies have shown that cardiac resynchronization therapy (CRT) acutely improves left ventricular (LV) systolic performance and lowers filling pressures in a majority of patients with medically-refractory severe heart failure. Measurements included LV volume, ejection fraction, PWD early (E-wave) and atrial (A-wave) velocities, diastolic filling time (DFT), and DTI early diastolic mitral annular velocity (Em) at the lateral and septal annulus; PWD mitral E-wave/Em and E/FP were calculated to estimate LV filling pressures. RESULTS: Immediately after CRT, LV volumes decreased and LVEF increased significantly. PWD mitral E-wave velocity decreased and E-wave duration and DFT increased significantly; mitral E/FP ratio also decreased significantly, consistent with a decrease in LV filling pressure. Patients with a pre-CRT mitral E/A ratio >1 (n = 20), demonstrated improvements in LV diastolic filling and lower filling pressures whereas those with an E/A ratio < or =1 (n = 21) did not show significant changes in diastolic indices. CONCLUSIONS: The acute effects of CRT include echocardiographic evidence of reduced LV volumes and increased LVEF with improved diastolic filling and lower filling pressures; LV relaxation is not significantly altered. The benefits in diastolic function are dependent on the PWD-determined LV filling characteristics prior to CRT.

Cardiac Pacing, Artificial↗

PubMed2005

Plasma triglyceride level is an independent predictor of altered left ventricular relaxation.

BACKGROUND: Diastolic dysfunction, manifested by impaired left ventricular (LV) relaxation, is prevalent among individuals with metabolic disorders. The objective of this study was to evaluate the extent to which plasma triglyceride (TG) levels are related to LV diastolic function. METHODS: A total of 424 subjects (age 49 +/- 12 years) had fasting plasma TG levels measured and underwent echocardiography for assessment of LV structure and function: LV ejection fraction and LV mass indexed to height (LVM/Ht(2.7)); transmitral inflow early diastolic peak velocity (E wave) and late diastolic peak velocity (A wave), and E wave to A wave ratio (E/A); deceleration time; and Doppler tissue imaging early diastolic myocardial velocity (EM), an index of LV relaxation. RESULTS: All subjects had normal LV ejection fraction, 48% had hypertension, 16% had increased LVM/Ht(2.7), 11% had type 2 diabetes mellitus, 37% were obese, and 27% had hypertriglyceridemia (TG > 150 mg/dL). Univariate analysis showed significant relationships between TG level and E/A, deceleration time, and Em (P < or = .001 for all). After adjustment for potential confounders in multivariate models (eg, age, systolic blood pressure, and LVM/Ht(2.7)), TG levels remained predictive of E/A, deceleration time, and Em (P < or = .05, <.001, and < or =.0001, respectively). Stepwise multivariate analysis showed that after age and body mass index, the TG level was the next most predictive variable of Em. CONCLUSIONS: Plasma TG levels show a strong relationship with impaired LV relaxation, an early marker of diastolic dysfunction in human beings. These findings support a hypothesis whereby elevated TG levels favor myocyte intracellular lipid accumulation, possibly leading to lipotoxic diastolic dysfunction.

Female↗

PubMed2004

Genes for left ventricular hypertrophy.

Left ventricular (LV) hypertrophy is very common, particularly among hypertensives. The presence of LV hypertrophy profoundly affects morbidity and mortality from cardiovascular diseases and stroke, and is now recognized as the most important predictor of chronic heart failure. Hypertension, obesity, and diabetes are important determinants of LV hypertrophy, but they fail to identify many individuals with the condition, suggesting that other factors, likely genetic in origin, play a role. Although much research has been undertaken to understand the causes of hypertrophy and the medical treatments that can lead to its regression, much remains unknown about its genetic basis. LV hypertrophy is considered a complex genetic disease, likely representing an interaction of several genes with the environment. The heritability of LV mass, measured as a quantitative trait, falls between 0.3 and 0.7 in different populations, suggesting it has a familial component. Genes encoding proteins involved in LV structure, as well as genes encoding cell signal transduction, hormones, growth factors, calcium homeostasis, substrate metabolism, and blood pressure are likely candidates for the development of common forms of LV hypertrophy. An overview of the pathophysiology of LV hypertrophy and dysfunction is provided, in addition to evidence of the genetic basis for LV hypertrophy in humans and animal models.

Genetic Predisposition to Disease↗

PubMed2003

Timing of cardiac transplantation in patients with heart failure receiving beta-adrenergic blockers.

BACKGROUND: Previous work shows that patients with heart failure patients who have peak oxygen consumption (VO2 peak) >14 ml/kg/min do not derive a survival benefit from cardiac transplantation. However, this was shown before beta-blocker therapy for patients with systolic heart failure became common, and beta-blockers improve survival in patients with heart failure without changing VO(2) peak. Our purpose was to re-evaluate the utility of VO(2) peak >14 ml/kg/min as an indicator of the need for cardiac transplantation in patients with heart failure who are taking beta-blockers. METHODS: Actuarial, hemodynamic, and exercise ventilatory data were collected from 540 patients with heart failure, 256 of whom were taking beta-blockers. We tracked death and cardiac transplantation. We stratified the percentage of patients event-free 1 and 3 years after VO(2) peak study by their VO(2) peak and beta-blocker status, and compared 1- and 3-year post-transplant survival (United Network of Organ Sharing [UNOS] data). We also compared total mortality for the patients with heart failure as stratified by beta-blocker stats and VO(2) peak (excluding the 42 who underwent transplantation) with UNOS post-transplant survival. RESULTS: Patients with heart failure who were receiving beta-blockers and whose VO(2) peak was > or =12 ml/kg/min had greater 1- and 3-year event-free survival rates (95% confidence intervals, 92.6%-96.6% and 85.8%-96.0%) than did post-transplant patients (83.9%-86.3% and 75.4%-76.6%). However, in patients with heart failure not taking beta-blockers, VO(2) peak <14 ml/kg/min was associated with worse 3-year survival (38.9 - 62.1%) than that for post-transplant patients. Excluding the 42 patients with heart failure in our study who underwent transplantation and then evaluating survival of the remaining patients with heart failure (not event-free survival) did not substantially change these results. CONCLUSIONS: Patients with heart failure who are receiving beta-blockers do not derive a survival advantage at 1 and 3 years after cardiac transplantation if VO(2) peak is > or =12 ml/kg/min. Patients not taking beta-blockers whose VO(2) peak is <14 ml/kg/min have superior survival with cardiac transplantation.

Adrenergic beta-Antagonists↗

PubMed2003

Myocardial fatty acid metabolism: independent predictor of left ventricular mass in hypertensive heart disease.

The expression of myocardial fatty acid beta-oxidation enzymes is downregulated at the gene transcriptional level in animal models of left ventricular hypertrophy and of heart failure. Humans with idiopathic dilated cardiomyopathy have decreased myocardial fatty acid oxidation. The extent to which molecular mechanisms, such as a reduction in myocardial fatty acid oxidation, regulate the cardiac hypertrophic response in humans in vivo is unknown. Positron emission tomography was used to measure myocardial blood flow, oxygen consumption, fatty acid utilization, and oxidation in two groups of patients: (1) hypertensive left ventricular hypertrophy (n=19; left ventricular mass, 211+/-39 g; left ventricular ejection fraction, 67+/-4%) and (2) left ventricular dysfunction (n=9; left ventricular mass, 210+/-36 g; left ventricular ejection fraction, 31+/-10%); these were compared with a normal control group (n=36; left ventricular mass, 139+/-25 g; left ventricular ejection fraction, 66+/-6%). Left ventricular mass showed significant correlation with gender, diastolic and systolic blood pressure, myocardial fatty acid uptake, utilization and oxidation, myocardial blood flow, body mass index, and left ventricular ejection fraction (all P<0.02). Independent predictors of increased left ventricular mass were male gender (r=0.38, P<0.001), myocardial fatty acid oxidation (r=-0.24, P<0.018), systolic blood pressure (r=0.41, P<0.001), and left ventricular ejection fraction (r=-0.29, P=0.005). Thus, myocardial fatty acid metabolism is an independent predictor of left ventricular mass in hypertension and in left ventricular dysfunction. The extent to which reduced myocardial fatty acid metabolism affects cardiovascular morbidity and mortality and whether pharmacologic modulation results in improved outcomes remains to be determined.

Adult↗

PubMed2002

Altered myocardial fatty acid and glucose metabolism in idiopathic dilated cardiomyopathy.

OBJECTIVES: The purpose of this study was to determine whether patients with idiopathic dilated cardiomyopathy (IDCM) exhibit alterations in myocardial fatty acid and glucose metabolism. BACKGROUND: Alterations in myocardial metabolism have been implicated in the pathogenesis of heart failure (HF); however, studies of myocardial metabolic function in human HF have yielded conflicting results. Animal models of HF have shown a downregulation of the expression of enzymes of fatty acid beta-oxidation that recapitulates the fetal energy metabolic program, in which fatty acid metabolism is decreased and glucose metabolism is increased. METHODS: Seven patients with IDCM (mean left ventricular ejection fraction 27 +/- 8%) and 12 normal controls underwent positron emission tomography for measurements of myocardial blood flow (MBF), myocardial oxygen consumption (MVO(2)), myocardial glucose utilization (MGU), myocardial fatty acid utilization (MFAU) and myocardial fatty acid oxidation (MFAO). RESULTS: The systolic and diastolic blood pressures, plasma substrates and insulin levels, MBF and MVO(2), were similar between groups. The rates of MFAU and MFAO were significantly lower in IDCM than in the normal control group (MFAU: 134 +/- 44 vs. 213 +/- 49 nmol/g/min, p = 0.003; and MFAO: 113 +/- 50 vs. 205 +/- 49 nmol/g/min, p = 0.001) and the rates of MGU were significantly higher in IDCM than the normal control group (MGU: 247 +/- 63 vs. 125 +/- 64 nmol/g/min, p < 0.001). CONCLUSIONS: Patients with IDCM exhibit alterations in myocardial metabolism characterized by decreased fatty acid metabolism and increased myocardial glucose metabolism, a pattern similar to that shown in animal models of HF. Whether alterations in myocardial metabolism constitute an adaptive response or mediate the development of HF remains to be determined.

Adult↗

PubMed1993

Insulin-like growth factor binding proteins in sera of pregnant nonhuman primates.

Insulin-like growth factors (IGFs) are mitogenic peptides that are important for fetal and maternal tissue growth during pregnancy. They circulate complexed primarily with a serum binding protein, IGFBP-3, which regulates the availability of the IGFs to their target tissues. We previously reported that in pregnant women, serum IGFBP-3 levels, assessed by Western ligand blotting, decline markedly beginning at 6 weeks gestation due to a circulating protease that cleaves IGFBP-3 into a 29-kilodalton (kDa) protein and lower mol wt (M(r)) fragments. In the current study, we compared IGFBP profiles, IGFBP-3 and IGFBP-1 levels, and IGFBP protease activities in sera from pregnant and nonpregnant women, baboons, and rhesus monkeys, using Western ligand blotting, IGFBP-specific immunoassays, IGFBP-3 protease assay, and zymographic gel electrophoresis. Serum IGFBP profiles in nonpregnant human and nonhuman primates were similar and were not cycle-dependent. IGFBP-3 (37-43 kDa), IGFBP-2 (31 kDa), and IGFBP-1 (28 kDa) were identified in all three species using IGFBP-specific human antisera. A 24-kDa IGFBP was also present and is believed to be IGFBP-4. Serum IGFBP-1 levels increased throughout gestation in human and nonhuman primates. Serum IGFBP-2 and putative IGFBP-4 were barely detectable in all three species from midgestation to term, but increased several days postpartum. In contrast, serum IGFBP-3 profiles differed markedly between species during gestation. Rather than the decrease seen in human pregnancy serum, there was an increase in circulating IGFBP-3 levels in nonhuman primates. Furthermore, for both baboon and rhesus monkey, the M(r) of serum IGFBP-3 was about 2 kDa greater in pregnant than in nonpregnant animals, and deglycosylation studies suggested that the higher M(r) forms may be alternatively glycosylated or may have a unique primary structure. As in nonpregnant women, serum IGFBP-3 protease activity was absent in nonpregnant and pregnant baboons. However, rhesus monkey serum contained a calcium-dependent protease that cleaved recombinant human IGFBP-3 into unique fragments, compared to the human pregnancy enzyme. Unlike human pregnancy serum, which proteolyzes IGFBP-3, in human nonpregnancy serum, rhesus serum incubated under similar conditions did not result in proteolysis of rhesus IGFBP-3, suggesting that the IGFBP-3 protease in human pregnancy serum is not present in the circulation of the rhesus monkey. To assess proteolytic activity in these sera, zymographic polyacrylamide gel analysis, using gelatin as a substrate, was performed. A minor band of proteolytic activity (72 kDa) was observed in all three species throughout gestation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMedDate not supplied

Hypertensive left ventricular hypertrophy is associated with abnormal myocardial fatty acid metabolism and myocardial efficiency.

BACKGROUND: Hypertension-induced left ventricular hypertrophy (LVH) is associated with an increased risk of cardiovascular morbidity and death by mechanisms not well characterized. METHODS AND RESULTS: Myocardial fatty acid (FA) metabolism and left ventricular (LV) mass were evaluated in 13 patients with hypertensive LVH with normal LV ejection fraction and 42 normal control subjects (primary cohort). Contractile performance was also evaluated in 5 hypertensive LVH patients and 5 matched normal control subjects (magnetic resonance [MR] substudy). Myocardial FA utilization (MFAU) and myocardial FA oxidation (MFAO) were assessed by positron emission tomography by use of 1-carbon-11 palmitate. Myocardial contractile function (strain and stress) was determined by cardiac MR imaging with tissue tagging and calibrated arterial pressure traces; myocardial external minute work and efficiency were derived. In the primary cohort decreased MFAO was predictive of increased LV mass (model r(2) = 0.61, P = .03). In the MR substudy decreased MFAO (corrected for myocardial oxygen consumption [MVO(2)]) in the hypertensive LVH group compared with the normal group (MFAU/MVO(2), 26 +/- 5 vs 37 +/- 8; MFAO/MVO(2), 24 +/- 6 vs 35 +/- 7; both P = .03) was paralleled by decreased myocardial external minute work (0.13 +/- 0.03 J x g(-1) x min(-1) vs 0.17 +/- 0.04 J x g(-1) x min(-1), P = .07) and decreased myocardial efficiency (5.2% +/- 1.4% vs 7.1% +/- 1.0%, P = .03). CONCLUSIONS: Abnormalities in myocardial FA metabolism are apparent in hypertensive LVH, and these abnormalities may be responsible, at least in part, for a reduction in myocardial efficiency.

Aged↗