Percutaneous Implantation of Aortic Valve Prosthesis in Patients with Calcific Aortic Stenosis: Technical Advances, Clinical Results and Future Strategies

To date, one third of patients with symptomatic aortic stenosis are not operated on because of advanced age, depressed left ventricular function, or comorbidities. Whereas balloon aortic valvuloplasty can be used as a palliative treatment in this population, the hemodynamic and clinical benefits of the procedure are only temporary. With the goal of offering to this subset of patients a nonsurgical therapeutic option with improved results and longer term positive outcomes, we developed a percutaneous implantable bioprosthetic heart valve able to be inserted within the native diseased aortic valve using cardiac catheterization techniques. The first human implant was performed by our group in April 2002 using the antegrade transeptal approach. Since then, we have implanted the valve on compassionate basis in a series of nonsurgical elderly patients with end-stage aortic stenosis and multiple comorbidities, all declined by cardiac surgeons for valve replacement. This article describes the technical improvements of the device and implantation protocols, provides clinical results of the first series of patients, and outlines strategies for future development of the percutaneous heart valve.     

Genetic and Biological Aspects of the HL-A System of Human Histocompatibility

The HL-A system of leukocyte group antigens is a system of great complexity and polymorphism, governed by an autosomal region which includesa number of subunits or subloci. It constitutes the principal system of histo-compatibility in man.

Extensive population and family studies have resulted in the identificationof two HL-A subloci. The first sublocus determines antigens HL-A 1, 2, 3, 9,Da 15 and Da 17 as alternative alleles. Antigens HL-A 5, 7, 8, Da 4, Da 6, HN,and probably Da 9 and Da 18 are determined in similar fashion at a secondsublocus. The products of 20 per cent of the genes of the first sublocus, and of29 per cent of the genes of the second sublocus are still unknown.

Study of 113 families has documented 226 human HL-A genotypes and 452haplotypes. The observed gene and haplotype frequencies were in close agreement with the anticipated values calculated on the basis of Mendelian laws.This result supports the concept that the HL-A system is in equilibrium.

Although the HL-A system plays a major role as a determinant of humanallograft responses, its primordial function may be of relevance to other fundamental biological problems, with particular reference to host defenses againstmicroorganisms, viruses and neoplastic cells.

     

Epstein-Barr virus in familial Hodgkin's disease

Summary Hodgkin's disease (HD) has been found to be linked to Epstein-Barr virus (EBV). Familial HD (FHD) may be related to a possible unknown agent. We have determined whether EBV small RNAs (EBERs) were found in Reed-Sternberg cells from FHD. Five families were studied for histological subtype and EBER presence. There was a striking similarity in FHD subtypes of each family and 3/11 (27%) of the cases were EBER positive. In conclusion, EBV EBERs are only infrequently found in FHD and other factors including viruses different from EBV should be further investigated in FHD.     

Interatrial Conduction in Patients Undergoing AV Stimulation: Effects of Increasing Right Atrial Stimulation Rate

To evaluate the frequency of spontaneous or rate dependent interatrial blocks, the interatrial conduction time (IACT) was studied on 100 consecutive patients (mean age 78.3 ±7.8 years) during a transvenous dual chamber pacemaker implant. The spontaneous interatrial conduction time (SIACT) was measured from the intrinsic deflection (ID) of the unipolar right atrial signal to the ID of the left atrial signal recorded in a bipoiar way by an esophageal lead. The paced interatrial conduction time (PIACT) was measured from the stimulus artifact to the left atrial ID, when the atrium was paced at a slightly higher rate than the spontaneous rate and during incremental atrial pacing. From these measurements, the maximum increase ofPIACT (MIPIACT) was deduced. In this elderly population, the PIACT was similar (117 ± 26.9 msec) to the data in the literature. However, there were large interindividual variations that were also found in SIACT. We found a close correlation between SIACT and PIACT (P < 0.0001). PIACT was on average 50 msec longer than SIACT. SIACT increased with age (P < 0.03). The MIPIACT was 15.3 ± 15.2 msec. In the majority of patients, the MIPIACT was > 10 msec, and even reached 90 msec in one patient. MIPIACT was longer in patients with a PIACT exceeding 110 msec (P < 0.004). Based on IACT alone, the AV interval must be lengthened on average by 50 msec when changing from atrial tracking-ventricular pacing to atrial pacing-ventricular pacing, but large individual differences must be kept in mind. Elderly people should probably have a longer AV delay.     

Attention modulates auditory pattern memory as indexed by event-related brain potentials

The role of selective attention on auditory pattern processing was investigated using the mismatch negativity, an event-related brain potential component associated with sensory memory. Participants responded to changes in an alternating tone pattern in a designated ear while a similar auditory pattern was presented in the opposite ear. Participants were also presented with the same sequences while reading a book (no response required). In all conditions, changes in the pattern elicited a mismatch negativity (MMN) that peaked at 160–220 ms poststimulus. MMN amplitude varied with attention: the amplitude was higher in response to deviant stimuli presented in the attended ear than to the deviant stimuli presented in the unattended ear or during reading. The results show that selective attention modulates auditory pattern memory.     

Iloprost: Intracellular Ca2+-dependent Contractile Effect on Isolated Smooth Muscle Cells from Guinea-pig Ileum

Prostaglandin E₂ (PGE₂) and iloprost induced a concentration-dependent contraction of smooth muscle cells isolated from the circular layer of guinea-pig ileum. PGE₂- and iloprost-induced contractions were inhibited by the selective EP₁-receptor antagonist, SCI9220 (1-acetyl-2-(8-chloro-10, 11-dihydrodibenz (b,f) (1,4) oxazepine-10-carbonyl)-hydrazine), indicating the involvement of the EP₁ subtype of the PGE₂ receptor. When cells were incubated for 10 min in the presence of strontium (4 mm L^?1), an inhibitor of the release of Ca²⁺ from intracellular store, the contractile effect of PGE₂ and iloprost was inhibited. In contrast, incubation of cells in Ca²⁺-free medium, Ca²⁺-free medium plus EGTA, or in the presence of nifedipine, an organic Ca²⁺-channel blocker, did not alter the PGE₂- and iloprost-induced contraction. These observations suggest that the myogenic effect of PGE₂ and iloprost on intestinal smooth muscle is dependent on the release of intracellular calcium.     

Comparative haemodynamic effects of intravenous flecainide in patients with and without heart failure and with and without beta-blocker therapy

The haemodynamic effects of flecainide were compared in threedifferent subsets of patients with documented coronary disease.Ten patients (A) had no heart failure, 5 patients were on betablockers (B) and 5 patients had overt heart failure (C). Flecainidewas associated with negative inotropic effects that were relativelymore pronounced in patients with left ventricular dysfunction:pulmonary wedge pressure increased by 27% in A, by 31% in Band by 42% in C; left ventricular stroke volume and stroke workdecreased respectively by 10 and 12% in A, 21 and 19% in B,26 and 28% in C. Ejection fraction decreased by 9% in A, 13%in B and 20% in C, in relation with an increase in end systolicvolume ( + 9% in A, +10% in Band + 5%inC). Absolute changes, however, were not significantly differentfrom one group to another except for the increase of systemicvascular resistance which was more pronounced in C as comparedwith the other groups. The myocardial depression was also confirmedby the fall in dPjdt that was maximal at the end of injection;dP/dt remained depressed 15 min later despite some improvement.Flecainide thus exerts negative inotropic effects that are maximalat the end of infusion and may be of importance in patientswith established left ventricular dysfunction.