Aortic root volume is associated with contained rupture of the aortic annulus in balloon-expandable transcatheter aortic valve replacement.

BACKGROUND: Aortic annulus rupture is a rare, but potentially fatal complication of transcatheter aortic valve replacement (TAVR), especially when it occurs by balloon-expandable devices. In order to improve the predictability of procedures and avoid ruptures we investigated whether or not the aortic root volume measures is a useful indicator of risk, and if it could be useful for the prosthesis size selection. METHODS AND RESULTS: From a retrospective series of 172 TAVR patients, seven experienced contained aortic annulus ruptures. The receiver operating curves were used to illustrate sensitivity and specificity of the different aortic annulus size and aortic root volume measures. The annulus area oversizing of ≥20% resulted in a sensitivity of 100%, specificity of 55.76%, and positive predictive value (PPV) of 8.75%. In patients receiving 26 mm prostheses, the aortic root volume (ARV <13600 mm(3)) provided a better specificity and PPV (79.63 and 18.52%, respectively). A two-step testing procedure considering the area derived average annulus diameter (Darea <23 mm) as a first separating parameter and then the ARV (<13,600 mm(3)) as a further indicator showed the most promising results with the PPV of 31.25%. Regardless of the procedure steps no false negative results were predicted. CONCLUSIONS: Our data show that the ARV provides a better predictive value for correct prosthesis sizing than established annulus measurements, especially in 'borderline' annuli. We suggest a two-step testing procedure for prostheses size selection, considering Darea and ARV to minimize the risk of annulus rupture. Prospective studies and examination of larger datasets are warranted to confirm these findings.

Quality of life among elderly patients undergoing transcatheter or surgical aortic valve replacement- a model-based longitudinal data analysis.

BACKGROUND: Quality of life (QoL) measurements reported in observational studies are often biased, since patients who failed to improve are more likely to be unable to respond due to death or impairment. In order to observe the development of QoL in patients close to death, we analyzed a set of monthly QoL measurements for a cohort of elderly patients treated for aortic valve stenosis (AS) with special consideration of the effect of distance to death. METHODS: QoL in 169 elderly patients (age ≥ 75 years), treated either with transcatheter aortic valve replacement (TAVR; n = 92), surgical aortic-valve replacement (n = 70), or drug-based therapy (n = 7), was evaluated using the standardized EQ-5D questionnaire. Over a two-year period, patients were consulted using monthly telephone interviews or outpatient visits, leading to a total of 2463 time points at which QoL values, New York Heart Association (NYHA) Functional Classification and their status of assistance were assessed. Furthermore, post-procedural clinical events and complications were monitored. Linear and ordered logistic regression analyses with random intercept were carried out, taking into account overall trends and distance to death. RESULTS: QoL measures decreased slightly over time, were temporarily impaired at month 1 after the initial episode of hospitalization and decreased substantially at the end of life with a measurable effect starting at the sixth from last follow-up (month) before death. Many clinical complications (bleeding complications, stroke, acute kidney injury) showed an impairment of QoL measurements, but the inclusion of lagged variables demonstrated medium term (three months) QoL impairments for access site bleeding only. All other complications are associated with event-related impairments that decreased dramatically at the second and third follow-up interviews (month) after event. CONCLUSIONS: Distance to death shows clear effects on QoL and should be taken into account when analyzing QoL measures in the elderly patients treated for aortic valve stenosis. TRIAL REGISTRATION: German Clinical Trial Register Nr. DRKS00000797.

In-hospital resource utilization in surgical and transcatheter aortic valve replacement.

BACKGROUND: Little is known about preoperative predictors of resource utilization in the treatment of high-risk patients with severe symptomatic aortic valve stenosis. We report results from the prospective, medical-economic "TAVI Calculation of Costs Trial". METHODS: In-hospital resource utilization was evaluated in 110 elderly patients (age ≥ 75 years) treated either with transfemoral (TF) or transapical (TA) transcatheter aortic valve implantation (TAVI, N = 83), or surgical aortic valve replacement (AVR, N = 27). Overall, 22 patient-specific baseline parameters were tested for within-group prediction of resource use. RESULTS: Baseline characteristics differed between groups and reflected the non-randomized, real-world allocation of treatment options. Overall procedural times were shortest for TAVI, intensive care unit (ICU) length of stay (LoS) was lowest for AVR. Length of total hospitalization since procedure (THsP) was lowest for TF-TAVI; 13.4 ± 11.4 days as compared to 15.7 ± 10.5 and 21.2 ± 15.4 days for AVR and TA-TAVI, respectively. For TAVI and AVR, EuroScore I remained the main predictor for prolonged THsP (p <0.01). Within the TAVI group, multivariate regression analyses showed that TA-TAVI was associated with a substantial increase in THsP (55 to 61 %, p <0.01). Additionally, preoperative aortic valve area (AVA) was identified as an independent predictor of prolonged THsP in TAVI patients, irrespective of risk scores (p <0.05). CONCLUSIONS: Our results demonstrate significant heterogeneity in patients baseline characteristics dependent on treatment and corresponding differences in resource utilization. Prolonged ThsP is not only predicted by risk scores but also by baseline AVA, which might be useful in stratifying TAVI patients. TRIAL REGISTRATION: German Clinical Trial Register Nr. DRKS00000797.

Transfemoral aortic valve implantation: bleeding events, related costs and outcomes.

Although less invasive then SAVR, TAVI is associated with a significant rate of access site and non-access site bleeding. These complications are major determinants of therapy outcome, however, the economic consequences are not well defined. The purpose of this study was to determine the relationship between bleeding, in-hospital resource utilization and costs among patients undergoing transfemoral aortic valve implantation (TF-AVI) at a representative university hospital in Germany. Between February 2010 and December 2011, we prospectively enrolled 60 consecutive patients undergoing TAVI using a 18F transfemoral approach at our institution. The relationship between overt bleeding (OVB), defined according to the definitions provided by the Valve Academic Research Consortium, in-hospital resource utilization and in-hospital costs was investigated. The mean age was 82 (±6) years, 53% were female and the mean EuroScore was 17.2% (±8, 7). Thirty-eight percent (23/60) of the patients had an OVB following TF-AVI procedure. In-hospital mortality was 8.7% in the OVB patients (2/23) and 2.7% among patients without any OVB (1/37; NOVB), which was not statistically significant (p = 0.3). The total length of stay (LOS) of patients with and without bleeding complication were 15.0 ± 6.4 and 10.4 ± 5.1 days, respectively (p < 0.01). Time spent on ICU in the OVB group was twice as long as compared to the NOVB group (120.5 ± 98.5 min vs. 63.6 ± 26.5 min, p < 0.01). Consequently, in-hospital costs were statistically significant higher in OVB patients (40.051 ± 9.293 vs. 33.625 ± 4.368, p < 0.01). Bleeding is associated with increased resource use and in-hospital costs among TF-AVI patients. Our data indicates that strategies reducing bleeding risk may have the potential to generate important in-hospital costs reductions in TF-AVI patients.

Elevated endogenous expression of the dominant negative basic helix-loop-helix protein ID1 correlates with significant centrosome abnormalities in human tumor cells.

BACKGROUND: ID proteins are dominant negative inhibitors of basic helix-loop-helix transcription factors that have multiple functions during development and cellular differentiation. Ectopic (over-)expression of ID1 extends the lifespan of primary human epithelial cells. High expression levels of ID1 have been detected in multiple human malignancies, and in some have been correlated with unfavorable clinical prognosis. ID1 protein is localized at the centrosomes and forced (over-)expression of ID1 results in errors during centrosome duplication. RESULTS: Here we analyzed the steady state expression levels of the four ID-proteins in 18 tumor cell lines and assessed the number of centrosome abnormalities. While expression of ID1, ID2, and ID3 was detected, we failed to detect protein expression of ID4. Expression of ID1 correlated with increased supernumerary centrosomes in most cell lines analyzed. CONCLUSIONS: This is the first report that shows that not only ectopic expression in tissue culture but endogenous levels of ID1 modulate centrosome numbers. Thus, our findings support the hypothesis that ID1 interferes with centrosome homeostasis, most likely contributing to genomic instability and associated tumor aggressiveness.

Impact of pulmonary hypertension on in-hospital outcome after surgical or transcatheter aortic valve replacement.

AIMS: We aimed to analyse the impact of pulmonary hypertension (PH) on the in-hospital outcome of either surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR). METHODS AND RESULTS: Data from all 107,057 patients undergoing isolated SAVR or TAVR in Germany between 2007 and 2014 were provided by the German Federal Bureau of Statistics. About 18% of patients with aortic valve stenosis suffered from PH. Patients with PH had more comorbidities with consequently increased EuroSCORE (TAVR without PH: 12.3%; with PH: 24%). The presence of PH led to an increase of in-hospital strokes, bleedings, acute kidney injuries, and pacemaker implantations in both treatment groups (TAVR and SAVR), but the PH-associated increase of complications and mortality was less pronounced among patients receiving TAVR (mortality after TAVR without PH: 5.4%; with PH: 7.2%). After baseline risk adjustment, the TAVR procedure was associated with a reduced risk of in-hospital stroke (OR 0.81, p=0.011), bleeding (OR 0.22, p<0.001), and mortality (OR 0.70, p=0.005) among PH patients, and in comparison to surgical treatment. CONCLUSIONS: PH is a risk factor for worse outcome of SAVR and TAVR. This fact is less pronounced among TAVR patients. Our data suggest a shift towards the transcatheter approach in patients suffering from PH.

"Heart Team" decision making in elderly patients with symptomatic aortic valve stenosis who underwent AVR or TAVI - a look behind the curtain. Results of the prospective TAVI Calculation of Costs Trial (TCCT).

AIMS: Little is known about how "Heart Team" treatment decisions among patients suitable for either surgical aortic valve replacement (AVR) or transcatheter aortic valve implantation (TAVI) are made under routine conditions. METHODS AND RESULTS: The "Heart Team" decision-making process was analysed with respect to124 patients of a non-randomised prospective clinical trial that included patients aged ≥75 years: 41 patients underwent AVR and 83 underwent TAVI. By use of the non-parametric classification and regression tree (CART) methodology, 21 baseline parameters were tested to reconstruct the decision process retrospectively. Next, multivariate logistic and Cox regression models were fitted to evaluate the decision and outcome relevance (two-year survival) of the parameters as identified in the CART procedure. For patients with a baseline EuroSCORE I ≥13.48%, no further cut-off points were identified and the majority of these patients underwent TAVI. Among patients with a baseline EuroSCORE I <13.48%, age and left ventricular ejection fraction (LVEF) were identified as further relevant decision parameters. The decision relevance of EuroSCORE I (p=0.003), age (p=0.024) and LVEF (p=0.047) were confirmed by multivariate analysis; however, outcome relevance can be confirmed for EuroSCORE I (p=0.015) only, while treatment decision (TAVI or AVR) was not a significant predictor of mortality (p=0.655). CONCLUSIONS: Despite or even because of the systematic risk selection according to EuroSCORE I values, we observed two-year survival rates of about 75% regardless of whether the patient received TAVI or AVR, suggesting that the decisions made by the "Heart Team" were appropriate.

Analysis of the additional costs of clinical complications in patients undergoing transcatheter aortic valve replacement in the German Health Care System.

BACKGROUND: This study aims at analyzing complication-induced additional costs of patients undergoing transcatheter aortic valve replacement (TAVR). METHODS: In a prospective observational study, a total of 163 consecutive patients received either transfemoral (TF-, n=97) or transapical (TA-) TAVR (n=66) between February 2009 and December 2012. Clinical endpoints were categorized according to VARC-2 definitions and in-hospital costs were determined from the hospital perspective. Finally, the additional costs of complications were estimated using multiple linear regression models. RESULTS: TF-TAVR patients experienced significantly more minor access site bleeding, major non-access site bleeding, minor vascular complications, stage 2 acute kidney injury (AKI) and permanent pacemaker implantation. Total in-hospital costs did not differ between groups and were on average €40,348 (SD 15,851) per patient. The average incremental cost component of a single complication was €3438 (p<0.01) and the estimated cost of a TF-TAVR without complications was €34,351. The complications associated with the highest additional costs were life-threatening non-access site bleeding (€47,494; p<0.05), stage 3 AKI (€20,468; p<0.01), implantation of a second valve (€16,767; p<0.01) and other severe cardiac dysrhythmia (€10,611 p<0.05). Overall, the presence of complication-related in-hospital mortality increased costs. CONCLUSIONS: Bleeding complications, severe kidney failure, and implantation of a second valve were the most important cost drivers in our TAVR patients. Strategies and advances in device design aimed at reducing these complications have the potential to generate significant in-hospital cost reductions for the German Health Care System.