Safety, Feasibility, and Hemodynamic Effects of Mild Hypothermia in Transcatheter Aortic Valve Replacement: The TAVR-CHILL Trial.

The safety, feasibility, and hemodynamic effects of mild hypothermia (MH) induced by transnasal cooling were studied in transcatheter aortic valve replacement (TAVR). MH is a common therapy following cardiac arrest and seems to have favorable effects in myocardial infarction and on hemodynamic stability. In TAVR, hemodynamic instability is common during rapid pacing. Twenty subjects undergoing TAVR were randomized 1:1 to hypothermia or normothermia. Hemodynamic endpoints were mean arterial blood pressure and required dosage of vasoactive and inotropic drugs. Patients were followed up at 6 months. All patients in the MH group (n=10) reached the target temperature of 34°C before first rapid pacing. Tympanic and urinary bladder temperature remained significantly lower in the MH group during the procedure. No adverse effects of cooling were observed. Mean arterial pressure was higher in the MH group (90±20 mm Hg) than in the control group (71±13 mm Hg) at the start of the procedure, at first rapid pacing (94±19 vs. 80±16 mm Hg), and at balloon aortic valvuloplasty (90±17 vs. 73±14 mm Hg). Less norepinephrine was administered to the hypothermia group. Transnasal cooling during TAVR was safe and well tolerated. We observed a more stable hemodynamic profile in the MH group, indicated by higher blood pressure and lower levels of vasoactive drugs required. A larger study of patients with severe ventricular dysfunction is required to more comprehensively investigate the hemodynamic effects of transnasal cooling in TAVR.

Impact of pressure recovery on echocardiographic assessment of asymptomatic aortic stenosis: a SEAS substudy.

OBJECTIVES: The aim of this analysis was to assess the diagnostic importance of pressure recovery in evaluation of aortic stenosis (AS) severity. BACKGROUND: Although pressure recovery has previously been demonstrated to be particularly important in assessment of AS severity in groups of patients with moderate AS or small aortic roots, it has never been evaluated in a large clinical patient cohort. METHODS: Data from 1,563 patients in the SEAS (Simvastatin and Ezetimibe in Aortic Stenosis) study was used. Inner aortic diameter was measured at annulus, sinus, sinotubular junction, and supracoronary level. Aortic valve area index (AVAI) was calculated by continuity equation and pressure recovery and pressure recovery adjusted AVAI (energy loss index [ELI]), by validated equations. Primarily, sinotubular junction diameter was used to calculate pressure recovery and ELI, but pressure recovery and ELI calculated at different aortic root levels were compared. Severe AS was identified as AVAI and ELI < or =0.6 cm(2)/m(2). Patients were grouped into tertiles of peak transaortic velocity. RESULTS: Pressure recovery increased with increasing peak transaortic velocity. Overestimation of AS severity by unadjusted AVAI was largest in the lowest tertile and if pressure recovery was assessed at the sinotubular junction. In multivariate analysis, a larger difference between AVAI and ELI was associated with lower peak transaortic velocity (beta = 0.35) independent of higher left ventricular ejection fraction (beta = -0.049), male sex (beta = -0.075), younger age (beta = 0.093), and smaller aortic sinus diameter (beta = 0.233) (multiple R(2) = 0.18, p < 0.001). Overall, 47.5% of patients classified as having severe AS by AVAI were reclassified to nonsevere AS when pressure recovery was taken into account. CONCLUSIONS: For accurate assessment of AS severity, pressure recovery adjustment of AVA must be routinely performed. Estimation of pressure recovery at the sinotubular junction is suggested.

The use of collagenase III for the isolation of porcine aortic valvular interstitial cells: rationale and optimization.

BACKGROUND AND AIM OF THE STUDY: Substantial heart valve research relies on the isolation of valvular interstitial cells (VICs). While a wide variety of conditions have been reported for VIC isolation, the effectiveness of these methods has rarely been compared. It is also likely that valve donor age will influence these valvular tissue dissociation conditions. The study aim was to increase the efficiency and cost-effectiveness of VIC isolation, while taking into account possible differences due to valve donor age. METHODS: Aortic valves were obtained from six-month-old (n = 24) and six-week-old (suckling) pigs (n = 45) within 24 h of death. After removal of endothelial cells, the tissues were minced and subjected to a variety of enzymatic digestions for variable lengths of time. RESULTS: The optimal concentration of collagenase III was determined as 1 mg/ml for six-week-old pigs, and 2 mg/ml for six-month-old pigs. The optimal duration of digestion was 4 h for both ages. The addition of neutral protease (2 mg/ml) further increased yield, while additional DNAse and hyaluronidase had no effect. Yield was not influenced by the volume of enzyme solution, nor the use of previously frozen enzyme solution. CONCLUSION: These findings provide age-specific conditions for improving the yield of VIC isolation, which should be of value in experimental studies of valvular cell biology and tissue engineering investigations.

Assessment of the severity of aortic stenosis: comparison of gradient and valve area.

Hemodynamic data, including simultaneously measured left ventricular pressure, aortic pressure, and cardiac output, were obtained in 17 patients with isolated valvar aortic stenosis, before and during infusion of dobutamine, isoprenaline, dopamine, and pacing. Infusion of sympathomimetic drugs resulted in a significant increase of both mean and peak systolic aortic valve gradient, cardiac output, heart rate, and systolic aortic valve flow per second. On the other hand, the calculated aortic valve area did not change significantly in spite of variable alterations of all values used for calculating aortic valve area and different causes of hemodynamic changes induced. Aortic valve area is considered a better indicator of the severity of aortic stenosis than is the aortic valve gradient and thus a more suitable indicator for operation.

Histological assessment of orthotopic aortic valve leaflet allografts: its role in selecting graft pre-treatment.

Histopathological studies of human cardiac valve grafts recovered at autopsy or re-operation, together with long-term clinical follow-up of valve graft recipients, have indicated that the success of grafts is largely dependent upon the extent to which they are replaced by host fibrous connective tissue. To find the valve preparation technique with least inhibitory effect on tissue ingrowth after grafting, various sterilizing and storage procedures were evaluated using a series of aortic valve leaflet allografts in dogs. To facilitate evaluation, a method for rapidly assaying relative degrees of colonization of grafts was first devised. Application of this method has unequivocally identified a newly-formulated antibiotic solution as the pre-treatment most compatible with host tissue ingrowth.