Guy Witberg

Mortality prediction following transcatheter aortic valve replacement: A quantitative comparison of risk scores derived from populations treated with either surgical or percutaneous aortic valve replacement. The Israeli TAVR Registry Risk Model Accuracy Assessment (IRRMA) study

BACKGROUND Accurate risk stratification is pivotal for appropriate selection of patients with severe symptomatic aortic stenosis for either surgical or transcatheter aortic valve replacement (TAVR). We sought to determine whether recent risk prediction models developed specifically in TAVR patients enhance prognostication in comparison with previous surgical scores used in clinical practice (EuroScore I, EuroScore II, STS). METHODS The Israeli TAVR Registry Risk Model Accuracy Assessment (IRRMA) study utilized a multicenter prospective TAVR database (n=1327) to perform a quantitative comparison between previous risk scores developed in either surgical or TAVR populations, with the present registry serving as an independent external validation set. RESULTS In the IRRMA population, 4 variables (NYHA functional class IV, chronic obstructive pulmonary disease, systolic pulmonary artery pressure ≥60mmHg, vascular access other than by the femoral route) identified by cross-validation and leave-one-out analyses provided the most discriminative model (C-statistic=0.63) for predicting 30-day mortality. Previous scores developed in surgical (EuroScores I and II, STS), TAVR (FRANCE-2, OBSERVANT), or mixed (German AV score) populations were applied to the IRRMA cohort. Resultant C-statistics ranged between 0.52-0.71 (for the German AV and FRANCE-2 scores, respectively) and did not differ significantly (p=0.07 for the comparison between the lowest and highest C-statistics). The observed C-statistic for 5 of these 6 scores was lower than originally reported when applied to the IRRMA population. CONCLUSION Available TAVR risk scores showed limited accuracy when applied to an independent validation set and did not enhance prognostication in comparison to previous surgical scores.

Real-World Use of Novel P2Y12 Inhibitors in Patients with Acute Myocardial Infarction: A Treatment Paradox

Objective: To assess the real-world use, clinical outcomes, and adherence to novel P2Y12 inhibitors. Methods: We evaluated 1,093 consecutive acute myocardial infarction patients undergoing a percutaneous intervention. Patients were derived from a prospective, multicenter, nationwide registry and were followed for 30 days; 381 patients (35%) received clopidogrel, 468 (43%) received prasugrel, and 244 (22%) received ticagrelor. Patients treated with clopidogrel were older and more likely to suffer from chronic renal failure and stroke and/or present with non-ST-elevation myocardial infarction (NSTEMI) (p < 0.01 for all). Independent predictors of undertreatment with novel P2Y12 inhibitors included: older age (OR 0.17; 95% CI 0.1-0.27, p < 0.0001), a prior stroke (OR 0.41; 95% CI 0.2-0.68, p = 0.008), and NSTEMI (OR 0.37; 95% CI 0.26-0.54, p < 0.0001). Results: Novel P2Y12 inhibitors were associated with a lower incidence of cardiovascular events, major bleeding, and/or death (7.6 vs.11%, HR 0.67; 95% CI 0.43-1, p = 0.05). However, after a multivariate analysis this trend was not statistically significant. Patients discharged with ticagrelor versus thienopyridines demonstrated a higher rate of crossover to other P2Y12 inhibitors (11 vs. 5%, p = 0.03). Conclusions: In a real-world cohort, there was an underutilization of novel P2Y12 inhibitors which was more pronounced in higher-risk subsets that might benefit from novel P2Y12 inhibitors at least as much as other patients.

Effect of coronary artery disease severity and revascularization completeness on 2-year clinical outcomes in patients undergoing transcatether aortic valve replacement.

AimsTo evaluate the effect of coronary artery disease (CAD) severity and completeness of revascularization on clinical outcomes following transcatheter aortic valve replacement (TAVR) using the SYNTAX score (SS), clinical SYNTAX score (cSS), and residual SYNTAX score (rSS). Methods and resultsWe studied 287 consecutive patients undergoing TAVR at our institution. Patients were classified as having CAD or no CAD and coronary patients were stratified according to SS and cSS. The completeness of revascularization was stratified using the rSS. We compared the 2-year outcomes according to SS/cSS/rSS. Forty-nine patients (17.1%) had CAD and sustained a higher rate of the primary endpoint at 2 years (28.3 vs. 16.1%, P=0.026). Stratified by CAD severity, the difference was driven by the high-severity groups (75.0 vs. 16.1%, P=0.002 for SS>22 and 41.2 vs. 16.1%, P=0.001 for cSS>63). Low-severity CAD patients did not have worse outcomes versus no CAD. When evaluating the effect of revascularization, patients with a rSS less than 8 did not have worse outcomes versus patients who did not have CAD. ConclusionIn patients undergoing TAVR, it is the severity of CAD (as assessed by the SS/cSS) that is associated with worse prognosis and not the mere presence of CAD. More complete revascularization attenuates the effect of CAD on clinical outcomes.

Impact of Coronary Artery Revascularization Completeness on Outcomes of Patients With Coronary Artery Disease Undergoing Transcatheter Aortic Valve Replacement: A Meta-Analysis of Studies Using the Residual SYNTAX Score (Synergy Between PCI With Taxus and Cardiac Surgery)

Background— Coronary artery disease (CAD) is highly prevalent in patients undergoing transcatheter aortic valve replacement. In the overall CAD population, complete revascularization or reasonable incomplete revascularization (ICR) is associated with improved outcomes; whether the same applies for the transcatheter aortic valve replacement population is still a matter of debate. Methods and Results— We conducted a systematic review and meta-analysis of studies that examined the prognostic effect of revascularization completeness in patients undergoing transcatheter aortic valve replacement using the residual SYNTAX score (Synergy Between PCI With Taxus and Cardiac Surgery) to separate between reasonable ICR and ICR (using the individual threshold used by each study). Six studies with a total of 3107 patients were included. The duration of follow-up ranged from 0.7 to 3 years. Overall, ICR was associated with an increased risk for mortality. This was true when comparing ICR patients to those with no CAD (odds ratio, 1.85; 95% confidence interval, 1.42–2.40; P<0.01), to those with reasonable ICR (odds ratio, 1.69; 95% confidence interval, 1.26–2.28; P<0.001), or to both groups combined (odds ratio, 1.71; 95% confidence interval, 1.36–2.16; P<0.001). On the contrary, patients in the reasonable ICR category did not show an increased risk for mortality when compared with those with no CAD (odds ratio, 1.11; 95% confidence interval, 0.89–1.39; P=0.33). Conclusions— Our results suggest that for patients with CAD undergoing transcatheter aortic valve replacement, a residual SYNTAX score–guided revascularization strategy may carry significant benefits in terms of mortality. Adequate revascularization may offer a unique and valuable opportunity to improve the prognosis of these patients.

Transcatheter versus surgical aortic valve replacement in patients at low surgical risk: A meta-analysis of randomized trials and propensity score matched observational studies

Although transcatheter aortic valve replacement (TAVR) is officially indicated for high risk aortic stenosis (AS) patients, the procedure is increasingly being performed in patients who are not at high surgical risk, including a substantial number of low risk patients. However, data on the benefit of TAVR in this patient population is limited.

Prognostic significance of aortic valve gradient in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement

To evaluate the effect of baseline aortic valve gradient (AVG) both as a continuous and a categorical variable on mortality in patients undergoing transcatheter aortic valve replacement (TAVR), focusing on the high‐gradient severe aortic stenosis (AS) patients.

Aortic Valve Gradient and Clinical Outcome in Patients Undergoing Transcatheter Aortic Valve Implantation for Severe Aortic Stenosis

Objectives: To explore the relation between the baseline aortic valve gradient (AVG) as a continuous variable and clinical outcomes following transcatheter aortic valve implantation (TAVI) in general and specifically in patients with high-gradient aortic stenosis (AS). Methods: We reviewed 317 consecutive patients who underwent TAVI at our institution. We investigated the relation between AVG as a continuous/categorical variable and outcome among all patients and in patients without low-flow low-gradient AS, using the Cox proportional hazard model adjusting for multiple prognostic variables. Results: Patients had a peak AVG of 79.9 ± 22.8 mm Hg (mean 50.5 ±15.7). During a mean follow-up of 2.7 years, AVG was inversely associated with mortality and mortality or cardiac hospitalization. Every 10-mm-Hg increase in peak AVG was associated with 18% reduction in mortality (p = 0.003) and 19% reduction in mortality/cardiac hospitalization (p < 0.001). Every 10-mm-Hg increase in mean AVG was associated with a 24% reduction in both outcomes (p = 0.005 and p < 0.001). Subgroup analysis of patients with left-ventricular ejection fraction >40% or peak AVG >64 mm Hg yielded similar results. Conclusions: Mean and peak baseline AVGs are directly associated with improved outcomes after TAVI; AVG can be used to select the patients most likely to benefit from TAVI.

Long-term outcomes of patients with complex coronary artery disease according to agreement between the SYNTAX score and revascularization procedure in contemporary practice.

AimsThe SYNTAX score (SS) has been shown to identify subgroups of patients with left main or triple-vessel coronary artery disease (LM/3VCAD) that can be treated with a percutaneous coronary intervention (PCI) with equal clinical outcomes as coronary artery bypass surgery (CABG).We sought to assess the adequacy of referral to PCI/CABG of patients with LM/3VCAD at our institution. Patients and methodsWe retrospectively matched all patients with LM/3VCAD referred to CABG (n=145) to patients referred to PCI in our institution during 2009–2010. We calculated the SS and clinical SS (cSS) according to the European Society of Cardiology guidelines and compared the agreement rates between the revascularization modality and the SS as well as clinical outcomes at the 3-year follow-up. ResultsThe overall agreement rates between the revascularization procedure and the SS was 67%, for example the rate was higher in patients referred to PCI compared with CABG (78 vs. 49%) and patients with 3VCAD compared with patients with LMCAD (68 vs. 51%). Patients without agreement between the revascularization modality and the SS had higher rates of combined adverse cardiac events (42.6 vs. 27% P=0.008). Similar results were observed when using the cSS at different cutoff levels. ConclusionAt our institution, there was considerable disagreement between a clinical judgment-based coronary revascularization and the SS/cSS-based allocation process as to the preferred revascularization modality for patients with complex CAD. Our results suggest that integrating the SS/cSS into the decision-making process for assigning patients to revascularization would yield better clinical outcomes.

Iliofemoral artery lumen volume assessment with three dimensional multi-detector computed tomography and vascular complication risk in transfemoral transcatheter aortic valve replacement

BACKGROUND Transfemoral Transcatheter Aortic Valve Replacement (TAVR) carries a risk of Vascular Complications (VCs) at the access site. The currently used measures for assessing the risk for VCs are not accurate enough, and sometimes fail to predict them. We therefore aimed to examine whether Iliofemoral artery lumen volume (IFV) assessment with 3-dimensional computed tomography (CT) predicts VCs after transfemoral TAVR. METHODS We identified 45/560 trans-femoral TAVR patients with VC, then performed nearest neighbor 1:1 matching for patients with no VC, matching for age, sex, TAVR year, valve size and type, closure-device, sheath size and peripheral vascular disease. IFV, minimal diameter, tortuosity, and calcification were measured, and their diagnostic performance assessed. RESULTS The final analysis included 45 patients with and 45 patients without VCs. The two groups were well balanced. For all patients, median IFV was 8.65 ml (IQR 6.5-11.95). IFV was lower in patients with VC compared to patients without VC: 7.10 ml (IQR 5.4-9.0) vs. 10.10 ml (IQR 8.3-13.3), p < 0.001. VC risk had marginal association with iliofemoral artery minimal diameter (p = 0.06) and no association with tortuosity or calcification. Compared with other measurements, IFV had the most favorable receiver operating curve for the prediction of VC, with an area under the curve (AUC) of 0.78. CONCLUSION IFV measurement using 3-dimensional CT is significantly associated with VCs in transfemoral TAVR patients and might be superior to currently accepted parameters. IFV should be further studied among extended cohorts of TAVR treated patients as a novel tool for VC risk assessment prior to transfemoral TAVR.

Calculated Risk for Sudden Cardiac Death in Patients with Apical Versus Nonobstructive Nonapical Hypertrophic Cardiomyopathy

There are limited and conflicting data regarding the prognosis of patients with apical hypertrophic cardiomyopathy (HC) and their risk for sudden cardiac death (SCD). We used data from a single tertiary center for comparing the clinical course and the calculated risk for SCD in patients with nonobstructive apical HC (apical HC) versus patients with nonobstructive, nonapical HC (NONA HC). The 5-year SCD risk was calculated based on the HC risk-SCD tool. A total of 109 patients were included in the cohort of whom 44 (40%) patients were diagnosed with apical HC. The majority of patients were males with a median age at diagnosis of 40 years (interquartile range 26, 59 years). Patients with apical HC had a significant lower calculated 5-year risk for SCD compared with patients with NONA HC (2.65 ± 2.2% vs 4.00 ± 3.5%, respectively, p = 0.017), primarily due to a lower incidence of familial SCD (20% vs 43% respectively, p = 0.014). Only 9% of patients with apical HC had a calculated risk of >6% (implantable cardioverter-defibrillator recommended), as compared with 23% of patients with NONA HC. During a median follow-up of 1,018 days (interquartile range 546, 1449 days), apical HC patients tended to develop less malignant ventricular arrhythmia episodes compared with NONA HC patients (0% vs 7.7%, respectively, p = 0.060). In conclusion, apical HC patients have a lower calculated risk of SCD compared with NONA HC patients, mainly due to a lower incidence of family history of SCD. Thus, apical HC should be considered a form of HC less prone to SCD.