The acute effect of an echo-contrast agent on right ventricular dimensions and contractility in pigs

BACKGROUND:: The aim of the present study was to examine the effect of the second-generation ultrasound contrast agent (2nd GUCA) SonoVue on right ventricular (RV) dimensions and contractility and to investigate whether a dose-related interaction exists between the contrast agent and RV function. METHODS:: Twenty-eight pigs were randomly assigned to 3 groups for intravenous administration: a low-dose group (0.5 cc of SonoVue), a high-dose group (1 cc of SonoVue), and a control group (2 cc of normal saline). RV end-diastolic (EDD) and end-systolic dimension (ESD) and pulmonary pressure (PP) were measured, and the fractional shortening (FS%) was calculated before the administration of SonoVue or normal saline and after the return of the RV-EDD or PP to the baseline value. The time to reach maximal RV-EDD or PP value and the time until the return of RV-EDD or PP to the baseline value were also measured. RESULTS:: Contrast agent infusion was followed by an acute transient increase of RV-EDD, RV-ESD, FS, and PP in both the low-dose and high-dose groups, but the increase was greater in the high-dose group. FS and PP did not change significantly in the control group. A dose-dependent delay in the time from baseline to maximum RV-EDD and PP was detected in the high-dose group (P < 0.001 for both) as well as a delay in the return from maximum to the baseline values (P < 0.001 for both). CONCLUSIONS:: Administration of the 2nd GUCA SonoVue is associated with an acute, transient, dose-dependent RV dilatation and an increase in pulmonary pressure with a consequent impact on RV contractility.     

Impact of the proton pump inhibitors and CYP2C19*2 polymorphism on platelet response to clopidogrel as assessed by four platelet function assays

Background

Previous studies suggested a possible negative interference of proton pump inhibitors (PPIs) on clopidogrel’s antiplatelet effect because of the competitive inhibition of the CYP 2C19 isoenzyme. Moreover, carriers of the loss-of-function allele of CYP2C19 polymorphism (CYP2C19*2) display significantly lower responses to clopidogrel. In this study, we investigated the association between CYP2C19*2 genotype, PPI intake and clopidogrel resistance in patients with coronary artery disease (CAD) and their effect on clinical outcome.

Methods

We recruited 95 patients with CAD receiving chronic clopidogrel therapy in combination with aspirin. Platelet reactivity was simultaneously assessed by INNOVANCE PFA-100 P2Y, ADP-induced light transmission aggregometry (LTA), flow-cytometric vasodilator-stimulated phosphoprotein (VASP)-phosphorylation assay and multiple electrode aggregometry (Multiplate). Cardiovascular outcomes were recorded during 1-year follow-up period.

Results

Only platelet reactivity assessed by measuring platelet phosphorylated-VASP demonstrated a significant higher platelet reactivity in carriers of CYP2C19*2 (p = 0.023). The other methods displayed higher - but not statistically significant - platelet reactivity in patients carrying the CYP2C19*2 variant as compared with non-carriers. Patients on PPIs demonstrated almost similar suppression of platelet reactivity in comparison with those not treated with PPIs by all platelet function assays. In logistic regression analysis none of the platelet function assays measurements were related with clinical outcomes. Similarly neither CYP2C19*2 genetic variant nor PPI treatment were associated with adverse clinical events.

Conclusions

PPI co-administration did not influence clopidogrel’s antiplatelet effect on laboratory testing by all platelet function assays used. On the contrary, patients carrying CYP2C19*2 genotype had significantly higher residual platelet reactivity as estimated by VASP-phosphorylation assay.     

Clinical characteristics and predictors of in-hospital mortality in acute heart failure with preserved left ventricular ejection fraction

Acute heart failure (AHF) with preserved left ventricular ejection fraction (PLVEF) represents a significant part of AHF syndromes featuring particular characteristics. We sought to determine the clinical profile and predictors of in-hospital mortality in patients with AHF and PLVEF in the Acute Heart Failure Global Survey of Standard Treatment (ALARM-HF). This survey is an international observational study of 4,953 patients admitted for AHF in 9 countries (6 European countries, Mexico, and Australia) from October 2006 to March 2007. Patients with PLVEF were defined by an LVEF ≥ 45%. Of the total cohort, 25% of patients had PLVEF. In-hospital mortality was significantly lower in this subgroup (7% vs 11% in patients with decreased LVEF, p = 0.013). Candidate variables included demographics, baseline clinical findings, and treatment. Multivariate logistic regression analysis showed that the variables independently associated with in-hospital mortality included systolic blood pressure at admission (p <0.001), serum sodium (p = 0.041), positive troponin result (p = 0.023), serum creatinine >2 mg/dl (p = 0.042), history of peripheral vascular disease and anemia (p = 0.004 and p = 0.015, respectively), secondary (hospitalization for other reason) versus primary AHF diagnosis (p = 0.043), and previous treatment with diuretics (p = 0.023) and angiotensin-converting enzyme inhibitors (p = 0.021). In conclusion, patients with AHF and PLVEF have lower in-hospital mortality than those with decreased LVEF. Low systolic blood pressure, low serum sodium, renal dysfunction, positive markers of myocardial injury, presence of co-morbidities such as peripheral vascular disease and anemia, secondary versus primary AHF diagnosis, and absence of treatment with diuretics and angiotensin-converting enzyme inhibitors at admission may identify high-risk patients with AHF and PLVEF.     

Influence of breathing movements and Valsalva maneuver on vena caval dynamics

AIM: To study changes produced within the inferior vena cava (IVC) during respiratory movements and identify their possible clinical implications.METHODS: This study included 100 patients (46 women; 54 men) over 18 years of age who required an abdominal computed tomography (CT) and central venous access. IVC cross-sectional areas were measured on CT scans at three levels, suprarenal (SR), juxtarenal (JR) and infrarenal (IR), during neutral breathing and again during the Valsalva maneuver. All patients were instructed on how to perform a correct Valsalva maneuver. In order to reduce the total radiation dose in our patients, low-dose CT protocols were used in all patients. The venous blood pressure (systolic, diastolic and mean) was invasively measured at the same three levels with neutral breathing and the Valsalva maneuver during venous port implantation. From CT scans, three-dimensional models of the IVC were constructed and a collapsibility index was calculated for each patient. These data were then correlated with venous pressures and cross-sectional areas.RESULTS: The mean patient age was 51.64 ± 12.01 years. The areas of the ellipse in neutral breathing were 394.49 ± 85.83 (SR), 380.10 ± 74.55 (JR), and 342.72 ± 49.77 mm² (IR), and 87.46 ± 18.35 (SR), 92.64 ± 15.36 (JR) and 70.05 ± 9.64 mm² (IR) during the Valsalva (Ps < 0.001). There was a correlation between areas in neutral breathing and in the Valsalva maneuver (P < 0.05 in all areas). Large areas decreased more than smaller areas. The collapsibility indices were 0.49 ± 0.06 (SR), 0.50 ± 0.04 (JR) and 0.50 ± 0.04 (IR), with no significant differences in any region. Reconstructed three-dimensional models showed a flattening of the IVC during Valsalva, adopting an ellipsoid cross-sectional shape. The mean pressures with neutral breathing were 9.44 ± 1.78 (SR), 9.40 ± 1.44 (JR) and 8.84 ± 1.03 mmHg (IR), and 81.08 ± 21.82 (SR), 79.88 ± 19.01 (JR) and 74.04 ± 16.56 mmHg (IR) during Valsalva (Ps < 0.001). There was a negative correlation between cross-sectional caval area and venous blood pressure, but this was not statistically significant in any of the cases. There was a significant correlation between diastolic and mean pressures measured during neutral breathing and in Valsalva.CONCLUSION: Respiratory movements have a major influence on IVC dynamics. The increase in intracaval pressure during Valsalva results in a significant decrease in the IVC cross-sectional area.