Abstract Objectives Heart failure (HF) is associated with changes in myocardial metabolism that lead to impairment of contractile function. Trimetazidine (TMZ) modulates cardiac energetic efficiency ...and improves outcomes in ischemic heart disease. We evaluated the effects of TMZ on left ventricular ejection fraction (LVEF), cardiac metabolism, exercise capacity, O2 uptake, and quality of life in patients with nonischemic HF. Methods and Results Sixty patients with stable nonischemic HF under optimal medical therapy were included in this randomized double-blind study. Patients were randomized to TMZ (35 mg orally twice a day) or placebo for 6 months. LVEF, 6-minute walk test (6MWT), maximum O2 uptake in cardiopulmonary exercise test, different markers of metabolism, oxidative stress, and endothelial function, and quality of life were assessed at baseline and after TMZ treatment. Left ventricular peak glucose uptake was evaluated with the use of the maximum standardized uptake value (SUV) by 18-fluorodeoxyglucose positron emission tomography (18 FDG-PET). Etiology was idiopathic in 85% and hypertensive in 15%. Both groups were similar in age, functional class, LVEF, and levels of N-terminal pro–B-type natriuretic peptide at baseline. After 6 months of TMZ treatment, no changes were observed in LVEF (31 ± 10% vs 34 ± 8%; P = .8), 6MWT (443 ± 25 m vs 506 ± 79 m; P = .03), maximum O2 uptake (19.1 ± 5.0 mL kg−1 min−1 vs 23.0 ± 7.2 mL kg−1 min−1 ; P = .11), functional class (percentages of patients in functional classes I/II/III/IV 10/3753/0 vs 7/40/50/3; P = .14), or quality of life (32 ± 26 points vs 24 ± 18 points; P = .25) in TMZ versus placebo, respectively. In the subgroup of patients evaluated with18 FDG-PET, no significant differences were observed in SUV between both groups (7.0 ± 3.6 vs 8.2 ± 3.4 respectively; P = .47). Conclusions In patients with nonischemic HF, the addition of TMZ to optimal medical treatment does not result in significant changes of LVEF, exercise capacity, O2 uptake, or quality of life.
The development of the semilunar valves takes place in association with septation of the outflow tract in the embryonic heart. Although numerous studies have focused on this process, the causal ...mechanisms of valvular development remain obscure. This paper reports an immunohistochemical analysis of tenascin and type-I collagen distribution in developing chick heart valves. Tenascin is a glycoprotein that is present on some embryonic extracellular matrices. It plays several significant roles in tissue differentiation, cell growth, and tissue interactions; it is also important for the formation of specific zones of connective tissue that fulfill mechanical functions. Our results show that tenascin is present during valvular morphogenesis and histogenesis, and that its distribution is associated with zones specialized in bearing mechanical loads.
9-Aminoacridine is the parent compound of a family of pharmacologically active model substances that bind to DNA through intercalation between base pairs. In the present study we show that ...9-aminoacridine inhibits the B-to-Z isomerization of poly(dA-dT) in conditions that otherwise cause it to occur (5 M NaCl and 123 mM Ni(ClO4)2). Higher concentrations of Ni(ClO4)2 (155 mM) are able to induce the Z-form due to the disruption of the drug-polynucleotide interaction by the metal ion. Additionally, the dye reverses the Z-form in certain conditions. Thus, the data from this study indicate that 9-aminoacridine binds preferentially to the B-form of poly(dA-dT).
To identify variables related to time spent on a waiting list for cataract extraction and the effect of waiting time on some outcomes.
Twelve ophthalmology units throughout Spain.
Cohort study.
This ...study included consecutive patients scheduled to have cataract removal by phacoemulsification. Sociodemographic and clinical data, including visual acuity, and Visual Function Index 14 (VF-14) results were collected before and after cataract extraction. Univariate and multivariate linear regression was performed to identify variables related to time on the waiting list for cataract extraction and the influence of waiting time on postoperative visual acuity, visual function, and complications.
The study comprised 3787 patients. Patients with social support spent significantly more time (1.04 times) on the waiting list (P = .0188), while those with contralateral visual acuity better than 0.5 and those with vision-related daily living difficulties spent less time on the waiting list. Patients who waited longer than 5 months for cataract extraction had smaller gains in visual acuity than those who waited fewer than 3 months (P = .0348). Time on the waiting list did not significantly influence changes in the VF-14 results or complications from surgery.
The finding that some contradictory sociodemographic factors influence time spent on a waiting list for cataract extraction suggests that rational, explicit, and homogeneous appropriateness and priority criteria are not being applied to these patients. Use of such criteria could improve waiting times and order waiting lists so patients who need cataract extraction the most would receive it soonest.
No author has a financial or proprietary interest in any material or method mentioned.
To examine the relation between Visual Function Index-14 (VF-14) scores and VA by accounting for concurrent ocular comorbidities, effect of the better seeing eye (BSE), and VA before and after ...cataract surgery.
Prospective cohort study.
A total of 4335 patients with cataract who completed the VF-14 before and after cataract surgery.
Collaborating clinicians provided demographic and clinical data before and after cataract surgery. Lowess curves, general linear models, and Spearman correlation coefficients were used to study the relation between the VF-14 and the VA.
Scores in the VF-14 preintervention, change in VF-14 after surgery, VA before surgery, and VA change after surgery.
General linear models and Spearman correlation coefficients showed a significant (P < 0.0001) association between VF-14 score and VA (measured in decimal fraction) when the preoperative VA was ≤0.5 (20/40) and no association (P > 0.4020) when the VA was >0.5 (20/40). Small VA gains (≤0.5) after surgery only led to significant gains (P < 0.0001) in functionality in patients with other ocular pathologies and whose BSE was the surgical eye. Gains in VA >0.5 had a significant (P < 0.02) effect on VF-14 change scores in most patients.
The VF-14 seems to be more sensitive when the preoperative VA is <0.5 (20/40), especially in patients whose BSE is the surgical eye. The VF-14 seems responsive to increases in VA if the gains exceed 0.5. For gains <0.5, the VF-14 seems unresponsive, except for patients with other ocular pathologies in whom the BSE before and after surgery is the surgical eye.
Ventricular dyssynchrony is a common finding in patients with heart failure (HF), especially in the presence of conduction delays. The loss of ventricular synchrony leads to progressive impairment of ...contractile function, which may be explained in part by segmental abnormalities of myocardial metabolism. However, the association of these metabolic disarrangements with parameters of ventricular dyssynchrony and electrocardiography (ECG) findings has not yet been studied.
Our aim was to determine the correlation between the presence of left bundle branch block (LBBB) with left ventricular (LV) mechanical synchrony assessed by multiple-gated acquisition scan (MUGA) and with patterns of 18-fluorodeoxyglucose (18FDG) uptake in patients with non-ischemic heart failure. Twenty-two patients with non-ischemic cardiomyopathy, LV ejection fraction (LVEF) ≤45% and New York Heart Association (NYHA) Functional Class II or III symptoms under standard medical therapy were included, along with 10 healthy controls matched for age and gender. A 12-lead ECG was obtained to measure the length of the QRS. Mechanical LV synchrony was assessed by MUGA using phase analysis. All patients and controls underwent positron emission tomography with 18FDG to determine the distribution of myocardial glucose uptake. The standard deviation of peak (18)FDG uptake was used as an index of metabolic heterogeneity. Student's t-test and Pearson's correlation were used for statistical analysis.
The mean age of the patients with HF was 54 ± 12 years and 72% were male. The length of the QRS was 129 ± 31 milliseconds and LBBB was present in 9 patients. Patients with HF had decreased LV 18FDG uptake compared with controls (7.56 ± 3.36 vs. 11.63 ± 4.55 standard uptake value; p = 0.03). The length of the QRS interval correlated significantly with glucose uptake heterogeneity (r = 0.62; p = 0.002) and mechanical dyssynchrony (r = 0.63; p = 0.006). HF patients with LBBB showed marked glucose uptake heterogeneity compared with HF patients without LBBB (41.4 ± 10 vs 34.7 ± 4.9 ml/100 g/min, respectively; p = 0.01).
Patients with non-ischemic heart failure exhibit a global decrease in myocardial glucose uptake. Within this group, subjects who also have LBBB exhibit a marked heterogeneity in segmental glucose uptake, which directly correlates with QRS duration.
The present study analyzes the composition and organization of the extracellular matrix (ECM) and its changes in the course of development of the chick embryo semilunar heart valves. In the present ...work we have employed chick embryos from stage 29 until hatching, using silver and picrosirius red staining, lectin probes and light and transmission electron microscopy. Our results show that during semilunar valve development a series of elements arise and are organized in the ECM which seem to be more closely related to the maintenance of the structural and biomechanical properties of the valvular leaflets than with morphogenetic processes per se.
Inhaled nitric oxide (iNO) is a potent pulmonary vasodilator, but therapeutic experience in patients with severe pulmonary hypertension is scarce.
Eleven patients with severe pulmonary hypertension, ...6 due to pulmonary arterial hypertension and 4 due to chronic thromboembolic disease, were selected for iNO therapy. A phosphodiesterase type 5 inhibitor (PDE5i) was added in cases of clinical worsening. In this study we evaluate the clinical effectiveness and safety of long-term treatment with iNO either alone or combined with a PDE5i.
After 1 month of iNO administration, improvements were observed in World Health Organization functional class, Borg scale (p = 0.003), brain natriuretic peptide levels (p = 0.002) and 6-minute walk test (p = 0.003). After 6 months of treatment, 7 patients had clinical deterioration that was reversed upon adding a PDE5i. One of these patients died in Month 8 and another underwent pulmonary transplantation in Month 9. The clinical condition of the remaining 9 patients was unchanged after 1 year. A second right catheterization showed improvement in mean pulmonary arterial pressure (66 +/- 15 mm Hg to 56 +/- 18 mm Hg; p = 0.01), pulmonary vascular resistance (1,234 +/- 380 dyn/s/cm(5) to 911 +/- 410 dyn/s/cm(5); p = 0.008) and cardiac index (2.0 +/- 0.4 liters/min/m(2) to 2.5 +/- 0.4 liters/min/m(2); p = 0.04). There was no significant increase in methemoglobin, no worsening of pulmonary function and no sudden withdrawal syndrome.
We suggest that iNO therapy alone or in combination with a PDE5i could be a therapeutic alternative for severe pulmonary hypertension.
