Potentials and limitations of the Valsalva maneuver as a method of differentiating between normal and pseudonormal left ventricular filling patterns.

Pseudonormalization of the left ventricular (LV) filling pattern complicates the Doppler echocardiographic assessment of LV diastolic function in patients with heart failure. The Valsalva maneuver is recommended as a method of differentiating between normal and pseudonormal LV filling patterns. However, neither a standardized Valsalva maneuver nor a healthy control population has been studied so far. Therefore, we studied changes in mitral flow velocities in response to a standardized Valsolva maneuver in 55 heart failure patients with LV systolic dysfunction and 35 control subjects. The study subjects were instructed to elevate their intrathoracic airway pressure to 40 mm Hg for 10 seconds. Doppler mitral flow velocities were recorded at rest and during the Valsalva maneuver. All study subjects had comparable decreases in early mitral flow velocity, but mitral flow velocity at atrial contraction increased rather than decreased in patients with a restrictive LV filling pattern. This markedly abnormal response might be useful in detecting elevated filling pressures and pseudonormal filling patterns. Furthermore, in all but 2 patients and all control subjects with an E/A ratio between 1 and 2, inversion of the E/A ratio occurred. This proves that, in contrast to previous beliefs, inversion of the E/A ratio does not differentiate between normal and pseudonormal LV filling patterns.     

Indication of long-term endothelial dysfunction after sirolimus-eluting stent implantation.

AIMS: Endothelial dysfunction has been related both to progression of atherosclerotic disease and to future cardiovascular events. We assessed local epicardial endothelial function 6 months after sirolimus-eluting stent (SES) or bare metal stent (BS) implantation. METHODS AND RESULTS: In 12 patients (seven SES, five BS), endothelium-dependent vasomotion of a coronary segment 15 mm in length, starting 2 mm distal to the stent, was assessed with quantitative coronary angiography immediately after the procedure and at 6 months follow-up, after intracoronary infusion of acetylcholine. Intravascular ultrasound (IVUS) was performed and coronary flow reserve (CFR) assessed in all patients. At follow-up significant vasoconstriction was seen in SES (median 32% diameter reduction from baseline) but not in BS (median 2% reduction) patients after acetylcholine infusion (P=0.03 for SES vs. BS); endothelium-independent vasodilatation to nitrates did not differ significantly between groups (20% SES, 5% BS, P=0.14). IVUS revealed no late unhealed dissections and CFR was comparable between groups (SES 3.1 vs. BS 3.2, n.s.). CONCLUSION: SES implantation may have an adverse effect on local endothelium-dependent vasomotor responses compared with BS implantation at 6 months. Long-term clinical consequences of this observation are still unknown.     

Initial observation regarding changes in vessel dimensions after balloon angioplasty and stenting followed by catheter-based beta-radiation. Is stenting necessary in the setting of catheter-based radiotherapy?

AIMS: We sought to compare the effect of intracoronary beta-radiation on the vessel dimensions in de novo lesions using three-dimensional intravascular ultrasound quantification after balloon angioplasty and stenting. METHODS AND RESULTS: Forty patients (44 vessels; 28 balloon angioplasty and 16 stenting) treated with catheter-based beta-radiation and 18 non-irradiated control patients (18 vessels; 10 balloon angioplasty and 8 stenting) were investigated by means of three-dimensional volumetric intravascular ultrasound analysis post-procedure and at 6-8 months follow-up. Total vessel (EEM) volume enlarged after both balloon angioplasty and stenting (+37 mm(3) vs +42 mm(3), P=ns), but vessel wall volume (plaque plus media) also increased similarly (+33 mm(3) vs +49 mm(3), P=ns) in the irradiated patients. Lumen volume remained unchanged in both groups (+3 mm(3) vs -7 mm(3), P=ns). In the stent-covered segments, neointima at follow-up was significantly smaller in the irradiated group than the control group (8 mm(3) vs 27 mm(3), P=0.001, respectively), but the total amount of tissue growth was similar in both groups (33 mm(3) vs 29 mm(3), P=ns). CONCLUSIONS: Intracoronary beta-radiation induces vessel enlargement after balloon angioplasty and/or stenting, accommodating tissue growth. Additional stenting may not play an important role in the prevention of constrictive remodelling in the setting of catheter-based intracoronary beta-radiotherapy.     

Sirolimus-eluting versus paclitaxel-eluting stent implantation for the percutaneous treatment of left main coronary artery disease: a combined RESEARCH and T-SEARCH long-term analysis.

OBJECTIVES: The purpose of this study was to investigate the long-term clinical and angiographic profile of sirolimus-eluting stent (SES) versus paclitaxel-eluting stent (PES) in patients undergoing percutaneous intervention for left main (LM) coronary disease. BACKGROUND: The long-term clinical and angiographic impact of SES as opposed to PES implantation in this subset of patients is unknown. METHODS: From April 2002 to March 2004, 110 patients underwent percutaneous intervention for LM stenosis at our institution; 55 patients were treated with SES and 55 with PES. The two groups were well balanced for all baseline characteristics. RESULTS: At a median follow-up of 660 days (range 428 to 885), the cumulative incidence of major adverse cardiovascular events was similar (25% in the SES group vs. 29%, in the PES group; hazard ratio 0.88 [95% confidence interval 0.43 to 1.82]; p = 0.74), reflecting similarities in both the composite death/myocardial infarction (16% in the SES group and 18% in the PES group) and target vessel revascularization (9% in the SES group and 11% in the PES group). Angiographic in-stent late loss (mm), evaluated in 73% of the SES group and in 77% of the PES group, was 0.32 +/- 74 in the main and 0.36 +/- 0.59 in the side branch in the SES group vs. 0.46 +/- 0.57 (p = 0.36) and 0.52 +/- 0.42 (p = 0.41) in the PES group, respectively. CONCLUSIONS: In consecutive patients undergoing percutaneous LM intervention, PES may perform closely to SES both in terms of angiographic and long-term clinical outcome.     

Low anti‐RhD IgG‐Fc‐fucosylation in pregnancy: a new variable predicting severity in haemolytic disease of the fetus and newborn

Haemolytic disease of the fetus and newborn (HDFN) may occur when maternal IgG antibodies against red blood cells (RBCs), often anti‐RhD (anti‐D) antibodies, cross the placenta and mediate the destruction of RBCs via phagocytic IgG‐Fc‐receptors (FcγR). Clinical severity is not strictly related to titre and is more accurately predicted by the diagnostically‐applied monocyte‐based antibody‐dependent cellular cytotoxicity (ADCC), a sensitive test with relatively low specificity. This suggests that other factors are involved in the pathogenesis of HDFN. Binding of IgG to FcγR requires the N‐linked glycan at position 297 in the IgG‐Fc‐region, consisting of several different glycoforms. We therefore systematically analysed IgG‐derived glycopeptides by mass spectrometry from 70 anti‐D IgG1 antibodies purified from the plasma of alloimmunized pregnant women. This revealed a variable decrease in Fc‐fucosylation in the majority of anti‐D IgG1 (even down to 12%), whereas the total IgG of these patients remained highly fucosylated, like in healthy individuals (>90%). The degree of anti‐D fucosylation correlated significantly with CD16 (FcγRIIIa)‐mediated ADCC, in agreement with increased affinity of defucosylated IgG to human FcγRIIIa. Additionally, low anti‐D fucosylation correlated significantly with low fetal‐neonatal haemoglobin levels, thus with increased haemolysis, suggesting IgG‐fucosylation to be an important pathological feature in HDFN with diagnostic potential.