Concentric left ventricular remodelling is associated with subclinical systolic dysfunction in patients with psoriatic arthritis.

Objectives: Subclinical left ventricular (LV) abnormalities have been reported in echocardiographic studies of patients with psoriatic arthritis (PsA). Left ventricular systolic dysfunction (LVSD) often coexists with concentric LV remodelling, an unfavourable prognostic factor that is commonly found in patients at high cardiovascular risk. However, it is unclear whether PsA is associated with concentric LV remodelling. This cross-sectional study assesses the prevalence of and factors associated with concentric LV remodelling in a cohort of patients with PsA, and tests the hypothesis that concentric LV remodelling is a major determinant of LVSD in PsA. Method: We evaluated 101 adults attending an outpatient clinic with PsA diagnosed according to the ClASsification criteria for Psoriatic ARthritis (CASPAR). All patients were free of cardiovascular disease. Patients with PsA were compared with 101 controls matched for age, gender, body mass index, hypertension, and diabetes. Echocardiography was performed: concentric LV remodelling was defined if the relative wall thickness was > 0.43; stress-corrected mid-wall shortening was used as an index of LVSD and considered impaired if < 86.5%. Results: Concentric LV remodelling was found in 58% of patients with PsA and 18% of controls (p < 0.001). LVSD was found in a significantly higher proportion of patients with PsA (56%, p < 0.001) than controls. The presence of PsA yielded a 10-fold higher probability of having LVSD [odds ratio (OR) 9.6, 95% confidence interval (CI) 4.2-21.9, p < 0.0001]. In patients with PsA, concentric LV remodelling increased the risk of LVSD four-fold (OR 3.7, 95% CI 1.3-10.2, p = 0.013). Conclusion: Most asymptomatic patients with PsA have concentric LV remodelling, which is closely associated with subclinical LVSD.

Traditional cardiovascular risk factors or inflammation: Which factors accelerate atherosclerosis in arthritis patients?

Patients with chronic inflammatory arthritis experience an increased incidence of cardiovascular (CV) events. In addition to visualizing atherosclerotic plaques, ultrasound examinations (USs) of the carotid arteries permit the measurement of subclinical markers of atherosclerosis, such as intima-media thickness (cIMT) and carotid segmental distensibility (cDC). The aims of the study were to identify the determinants of atherosclerosis acceleration (plaques, cIMT and cDC) in a sample of patients suffering from chronic arthritis and to compare these patients with a control group of people with ≤1 traditional risk factor (TRF) for CV disease. METHODS: We recruited 137 patients with rheumatoid arthritis (RA), 43 patients with psoriatic arthritis (PsA), 28 patients with ankylosing spondylitis (AS) and 48 healthy volunteers without histories of previous CV events. These patients underwent carotid artery US examinations using dedicated hardware. RESULTS: Regression and multivariate analyses demonstrated that only age (p<0.001) was consistently associated with cDC, cIMT and atherosclerotic plaques, both in the entire sample of patients with arthritis and in the subgroup of patients with RA. Among modifiable TRFs for cardiovascular disease, only hypertension, diabetes mellitus and smoking exhibited associations with some carotid phenotypes, with borderline significance. When patients with RA carrying ≤1 TRF were compared with control subjects carrying ≤1 TRF, only cDC was slightly lower in the RA group than in the control group. CONCLUSIONS: Age is the major determinant of subclinical atherosclerosis in patients with different types of arthritis, as the contributions of other TRFs and disease activity and duration indices to the disease seem to be limited.

The worrisome liaison between left ventricular systolic dysfunction and mitral annulus calcification in type 2 diabetes without coronary artery disease: data from the SHORTWAVE study.

BACKGROUND AND AIM: Mitral annulus calcification (MAC) is a marker for coronary artery disease (CAD) and predicts poor outcome in the general population. No data are available on MAC in patients with type 2 diabetes. In these patients we assessed prevalence of MAC and the relation between MAC and left ventricular (LV) systolic function. METHODS AND RESULTS: As many as 386 patients with type 2 diabetes without CAD were studied with Doppler echocardiography. LV systolic dysfunction was defined by analyzing 120 healthy subjects. Stress-corrected midwall shortening (sc-MS) and mitral annular peak systolic velocity (peak S') were considered as indexes of LV circumferential and longitudinal shortening and classified low if <89% and <8.5 cm/s, respectively (10th percentiles of controls). Patients who had MAC (107 = 28%) were older with longer duration of DM and were receiving more anti-hypertension medications than those who had not. At echocardiographic evaluation patients with MAC showed higher LV mass, larger left atrial volume (LAV), reduced sc-MS (88.4 ± 14.9 vs 92.6 ± 14.3%; p = 0.01) and peak S' (8.9 ± 2.2 vs 10.0 ± 2.0 cm/s; p < 0.001) than patients without MAC. Multiple logistic regression demonstrated older age (OR 1.03 [IC 1.01-1.06], p = 0.009), larger LAV (OR 1.19 [IC 1.11-1.28], p < 0.001) and combined reduction in sc-MS and peak S' (OR 3.00 [IC 1.57-5.72], p = 0.001) as independent factors associated with MAC. CONCLUSIONS: MAC is detectable in one fourth of patients with type 2 diabetes without CAD and is mostly related to LV systolic dysfunction expressed as combined impairment of LV circumferential and longitudinal fibers, independent of age and LAV.

Adjuvant trastuzumab cardiotoxicity in patients over 60 years of age with early breast cancer: a multicenter cohort analysis.

BACKGROUND: Adjuvant Trastuzumab with chemotherapy is the gold standard for human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (HER2+ EBC). Older patients have been largely under-represented in clinical trials, and few data on Trastuzumab cardiotoxicity have been reported in this subgroup. PATIENTS AND METHODS: Four hundred and ninety-nine consecutive HER2+ EBC patients were treated with adjuvant trastuzumab and chemotherapy (aTrastC) at 10 Italian institutions. We evaluated disease prevalence and patient characteristics in the patients older than 60 years of age (over-60), prevalence of aTrastC cardiotoxicity and risk factors. RESULTS: There were 160 'over-60' patients (32%), in whom a higher prevalence of hypertension, diabetes, renal dysfunction, dyslipidemia and treatment with ACEi (40 versus 8%) and beta blockers (20 versus 8%) was found than in the younger patients (339 = 68%). Clinical heart failure occurred in 6% of the 'over-60' and in 2% of the younger patients. A reduction in left ventricular ejection fraction of >10 points was detected in 33% of the 'over-60' and in 23% of the younger patients (all P < 0.05). aTrastC was discontinued in 10% of the 'over-60' and in 4% of the younger patients (P = 0.003), restarted in 44% of the 'over-60' and in 58% of the younger women (P = ns). CONCLUSION: In clinical practice, 32% of HER2+ EBC patients treated with aTrastC are 'over-60'. These patients have an increased cardiovascular risk profile and develop aTrastC cardiotoxicity commonly.

Retinal proteomic changes following unilateral optic nerve transection and early experimental glaucoma in non-human primate eyes.

In this work we compared proteomic changes in non-human primate (NHP) retinas at the onset of early experimental glaucoma (EEG) and 3 weeks after optic nerve transection (ONT), as a means to identify regulators in the retina's response to EEG and ONT. Both eyes of 7 NHPs with either unilateral EEG (n = 4) or ONT (n = 3) were enucleated. Proteins were analyzed by a label-free quantitative mass spectrometry system and the abundance of identified retinal proteins was compared between the treated eye and its contralateral control for each NHP. Cellular processes associated with regulated proteins were identified using the MetaCore program. As a result, a total of 209 and 200 proteins were identified in EEG and ONT retinas, respectively. The EEG eyes exhibited two distinguishable levels of maximum IOP: the highest IOP <27 mmHg (n = 2) and >45 mmHg (n = 2), termed mild IOP EEG and high IOP EEG eyes, respectively. A limited overlap of proteins regulated in the same direction was seen between the high IOP EEG and either the mild IOP EEG eyes or ONT eyes. Most of the proteins that were up regulated in the high IOP EEG eyes were down regulated in the mild IOP EEG eyes; the latter showed an overall down regulation that was not seen in the other two conditions. An association with cytoskeleton regulation was recognized for up-regulated proteins in the high IOP EEG eyes. We conclude that mild IOP EEG, high IOP EEG and ONT retinas exhibited condition-specific proteomic changes with little overlap between conditions. Cytoarchitecture regulation appears to be a component of the early retinal response to chronic experimental IOP elevation.

Baseline characteristics of the transient pattern electroretinogram in non-human primates: inter-ocular and inter-session variability.

This study assessed the inter-ocular and inter-session variability of the transient pattern electroretinogram (PERG) in a group of non-human primates. The transient PERG was measured both eyes of 29 non-human primates, and again after three months in 23 eyes of 23 of these animals. Signals were elicited using a contrast (90%, 75 cdm(-2)) reversing (5 reversals sec(-1)) checkerboard pattern (0.56 cpd). PERGs were also measured for stimuli of varied spatial frequency (n=8, 0.07-2.22 cpd), contrast (n=4, 20-100%), mean luminance (n=4, 4.7-75 cdm(-2)) and defocus (n=5, +1, +2, +3 diopters). The inter-eye and inter-session limits-of-agreement (LOA; 95%) were determined for each PERG parameter. Variability was also compared with previous studies using the coefficient-of-variability (COV). Pharmacological blockade of the inner retinal contributions to the PERG measured under these conditions was conducted in one animal using intravitreal injection of tetrodotoxin (approximately 6 microM) and N-methyl-D-aspartic acid (approximately 6 microM). The N95 component of the primate transient PERG showed spatial tuning, with a peak between 0.14 and 0.28cpd. This spatial tuning was not as apparent for the P50 component. A linear relationship between P50 and N95 amplitude was found with contrast and mean luminance. Both components were attenuated with the introduction of +2 diopters or more of defocus. The inter-session COV for the P50 and N95 components were 23.8 and 19.2%, respectively, while the LOA were 58 and 46%, respectively. The N95:P50 ratio had smaller inter-session variability, was robust to changes in contrast, mean luminance and defocus, and was effective for characterization of inner-retinal dysfunction after pharmacologic block.

Depth of penetration of scanning laser Doppler flowmetry in the primate optic nerve.

OBJECTIVES: To estimate the measuring depth of the blood flow and to establish the vascular contributions to these measurements with scanning laser Doppler flowmetry (SLDF) of the primate anterior optic nerve. METHODS: Optic nerve blood flow in each eye of 8 monkeys was measured using SLDF before and following surgical occlusion of the central retinal artery (n = 4) or posterior ciliary arteries (n = 4). The regional blood flow in both eyes was determined using a nonradioactive microsphere method. RESULTS: The blood flow in the nerve fiber layer (NFL), including the prelaminar region, was measured with microspheres after central retinal artery occlusion; it was significantly reduced (-83%) with no significant change in the combined laminar and retrolaminar regions. The blood flow measured with SLDF had a 51% reduction. After posterior ciliary artery occlusion, the blood flow in the NFL was measured with microspheres and was not significantly affected (+2%); neither was that measured with SLDF (-12%). However, there was a 51% reduction in the laminar and retrolaminar regions when microspheres were used. The mean +/- SD tissue thickness of the NFL was 359 +/- 16 microm and 353 +/- 54 microm in each group. CONCLUSIONS: Scanning laser Doppler flowmetry measures blood flow principally in the NFL of the anterior optic nerve, which is primarily supplied by the central retinal artery. Blood flow in the laminar and retrolaminar regions makes a small contribution to the SLDF measurement, with an NFL thickness between 300 and 400 microm. CLINICAL RELEVANCE: Scanning laser Doppler flowmetry is used for the noninvasive evaluation of ocular microcirculation in diseases such as glaucoma. Because of the dual blood flow supply in the optic nerve and the limited penetration power of the laser, the instrument primarily measures the microcirculation on the surface of the optic nerve, which is largely supplied by the central retinal artery rather than the ciliary arteries.

Two new sesquiterpene lactones from Montanoa tomentosa ssp. microcephala.

Two new sesquiterpene lactones: 8alpha-(4'-acetoxymethacryloyloxy)-3alpha,9beta-dihydroxy-1(10)E,4Z,11(13)-germacratrien-12,6alpha-olide (1) and 8alpha-(2'E)-(2'-acetoxymethyl-2'-butenoyloxy)-3alpha,9beta-dihydroxy-1(10)E,4Z,11(13)-germacratrien-12,6alphaolide (2), together with the known zoapatanolide A were isolated from the aerial parts of Montanoa tomentosa Cerv. in La Llave et Lex ssp. microcephala (Sch. Bip. In K. Koch) V.A. Funk (Asteraceae). The structures of all compounds were established on the basis of 1D, 2D NMR, and EIMS analysis.

Predictive value of a 1-day, 1-eye trial on the 1-month ocular hypotensive response of latanoprost 0.005%.

PURPOSE: To determine if a 1-day, 1-eye trial of latanoprost 0.005% was predictive of the 1-month intraocular pressure response in patients with uncontrolled open-angle glaucoma on maximally tolerated medical therapy without latanoprost. METHODS: One eye of 39 consecutive patients was enrolled in prospective trial of latanoprost 0.005%. An investigator masked to treatment eye and intraocular pressure result measured intraocular pressure at 1 day and 1 month after treatment. The diagnostic precision of the 1-day, 1-eye trial for the 1-month result was determined at a 10%, 20%, and 30% reduction from baseline intraocular pressure. RESULTS: Treatment produced a mean +/- SD (range) decrease in intraocular pressure from 20.9 +/- 4.6 (14 to 35) mm Hg to 16.6 +/- 3.6 (9 to 26) mm Hg at 24 hours (P <.0001, paired t test). This reduction in intraocular pressure was similar at 1 month with mean +/- SD (range) intraocular pressure of 16.1 +/- 3.1 (9 to 22) mm Hg (P <.0001, paired t test). The accuracy of the 1-day, 1-eye trial for the 1-month response at a 10%, 20%, and 30% reduction of intraocular pressure from baseline intraocular pressure was 96% (chi square = 29.5, P <.001), 74% (chi square = 8.4, P =.004), and 80% (chi square = 10.2, P =.001), respectively. CONCLUSION: A 1-day, 1-eye trial of latanoprost 0.005% is predictive of the 1-month intraocular pressure response in patients with uncontrolled open-angle glaucoma.

Characterization of post-discharge atrial fibrillation following open-heart surgery in uncomplicated patients referred to an early rehabilitation program.

BACKGROUND: Atrial fibrillation (AF) is frequently observed after open-heart surgery, following discharge from the cardiac surgery clinic. Compared to those usually reported in the early postoperative period, this arrhythmia is delayed in onset and is often a cause of re-hospitalization. Post-discharge AF has never been characterized in the literature. METHODS: We retrospectively analyzed post-discharge AF occurring within 30 days of coronary artery bypass graft or of valvular procedures in 376 patients referred to an early postoperative rehabilitation program. To investigate the probability of the persistence of post-discharge AF, we prospectively examined 232 patients who had undergone valvular procedures. RESULTS: An arrhythmia was recognized in 61/376 patients (16%), resulted in worsening of the NYHA functional class in 27 (44%) and in life-threatening hemodynamic effects requiring urgent cardioversion in 5 (8%). Events were predicted by the occurrence of postoperative AF (6-fold higher risk), left ventricular hypertrophy, an enlarged left atrium and valvular pathology (3-fold) and by the lack of beta-blocker protection (5-fold). AF persisted in 20/232 (9% of the study population, 18% of patients who had post-discharge AF) and had a relevant impact on the patient's clinical status. Predictors of events were older age, an enlarged left atrium and a lower left ventricular ejection fraction. CONCLUSIONS: Post-discharge AF following open-heart surgery is frequent in patients undergoing valvular procedures and often persists over time. The clinical impact of the arrhythmia is relevant, it might cause re-hospitalizations in many circumstances and, consequently, may have an impact on hospital resources. Events are much less frequent in patients taking beta-blockers than in those who do not, and they can be predicted by simple variables observed in the early stages after surgery.

[Reversibility of left ventricular dysfunction in elderly patients with dilated cardiomyopathy undergoing treatment with carvedilol. Report of a case]. / Reversibilità della disfunzione ventricolare sinistra nell'anziano affetto da cardiomiopatia dilatativa sottoposto a trattamento con carvedilolo. Descrizione di un caso.

Owing to recurrent episodes of congestive heart failure, an 88-year-old man with moderate aortic stenosis and dilated cardiomyopathy was treated with carvedilol and closely followed up. At the beginning of the treatment the patient was in NYHA functional class IV and presented with severe global left ventricular hypokinesia with an ejection fraction of 15%. Carvedilol was started at a dose of 3.125 mg twice daily and progressively increased to 12.5 mg twice daily. Six months later the left ventricular volumes had become almost normal, wall motion abnormalities had completely reversed and the ejection fraction was markedly increased (62%). The patient was classified in NYHA functional class II. This case shows the recovery of left ventricular systolic function during the administration of carvedilol in an old patient with dilated cardiomyopathy and chronic congestive heart failure.

Triterpene saponins from Tupidanthus calyptratus.

Five new bisdesmosidic saponins (1--5) were isolated from the aerial parts of Tupidanthus calyptratus. Their structures were determined by (1)H--(1)H correlation spectroscopy (COSY, TOCSY, ROESY) and (1)H--(13)C correlation (HSQC, HMBC) NMR experiments, FABMS, and chemical data.

The topographic relationship between multifocal electroretinographic and behavioral perimetric measures of function in glaucoma.

PURPOSE: To study the spatial relationship between local functional abnormalities found using multifocal electroretinography (MERG) and those measured using standard automated perimetry (SAP) in a group of glaucoma patients with well-defined, localized visual field loss. METHODS: MERG's were measured for 15 patients with longstanding, stable, localized SAP visual field loss and for 27 normal controls using VERIS Science (EDI, San Mateo, CA). Most glaucoma patients had substantial asymmetry of visual field defects across the horizontal midline so that within-eye comparisons of MERG changes could be made in addition to comparisons between glaucoma and healthy, aged-matched controls. RESULTS: For the glaucoma patient group as a whole, conventional measurements of MERG responses, such as peak-to-trough amplitude, peak implicit time, and scalar-product density, did not reveal abnormalities that spatially corresponded to local sensitivity losses determined by SAP visual field thresholds. Some of the patients had MERG abnormalities (e.g., reduced amplitudes) in areas of advanced SAP visual field loss that indicated local retinal dysfunction. On average, glaucoma patients were missing a MERG component that resembled the optic nerve head component as described by Sutter and Bearse. CONCLUSIONS: Different MERG components may be affected at different stages of glaucoma, perhaps reflecting a diversity of pathophysiologic mechanisms. This may complicate spatial and temporal relationships between abnormalities found using the MERG and behavioral perimetry, particularly when conventional measurements of MERG responses are used to characterize a diverse patient group/disease.

Three common assumptions about ocular blood flow and glaucoma.

Although substantial indirect evidence exists to link altered ocular blood flow to glaucoma, it must be remembered that the validity of investigations in this area depends on acceptance of three basic assumptions: 1) ischemia directly causes or increases the susceptibility of the optic nerve to glaucomatous damage; 2) optic nerve vascular anatomy and physiology allows identification of the critical vascular beds in optic nerve disease; and 3) current measurement techniques provide the ability to monitor important vascular beds. The hypotheses underlying these assumptions are examined.

Measurement of ocular blood flow.

Many of these techniques have been adapted to investigate hemodynamic alterations, not only in glaucoma, but in diverse disorders such as diabetic retinopathy, macular degeneration, retinal dystrophies, and nonglaucomatous optic neuropathies. However, each of these techniques has limitations and there is not a single methods that provides comprehensive measurements for all the ocular tissues. Our enhanced understanding of ocular vascular anatomy has helped to direct our hemodynamic investigations of the various vascular beds within the eye. However, many of the techniques have lacked validation (reproducibility and accuracy) prior to clinical implementation. Understanding the limitations and the theoretical assumptions of each of these techniques will allow more prudent application in the clinical arena in the future.