Prospective Assessment of the Diagnostic Accuracy of Instantaneous Wave-Free Ratio to Assess Coronary Stenosis Relevance: Results of ADVISE II International, Multicenter Study (ADenosine Vasodilator Independent Stenosis Evaluation II).

OBJECTIVES: The purpose of this study was to assess the diagnostic accuracy of the instantaneous wave-free ratio (iFR) to characterize, outside of a pre-specified range of values, stenosis severity, as defined by fractional flow reserve (FFR) ≤0.80, in a prospective, independent, controlled, core laboratory-based environment. BACKGROUND: Studies with methodological heterogeneity have reported some discrepancies in the classification agreement between iFR and FFR. The ADVISE II (ADenosine Vasodilator Independent Stenosis Evaluation II) study was designed to overcome limitations of previous iFR versus FFR comparisons. METHODS: A total of 919 intermediate coronary stenoses were investigated during baseline and hyperemia. From these, 690 pressure recordings (n = 598 patients) met core laboratory physiology criteria and are included in this report. RESULTS: The pre-specified iFR cut-off of 0.89 was optimal for the study and correctly classified 82.5% of the stenoses, with a sensitivity of 73.0% and specificity of 87.8% (C statistic: 0.90 [95% confidence interval (CI): 0.88 to 0.92, p < 0.001]). The proportion of stenoses properly classified by iFR outside of the pre-specified treatment (≤0.85) and deferral (≥0.94) values was 91.6% (95% CI: 88.8% to 93.9%). When combined with FFR use within these cut-offs, the percent of stenoses properly classified by such a pre-specified hybrid iFR-FFR approach was 94.2% (95% CI: 92.2% to 95.8%). The hybrid iFR-FFR approach obviated vasodilators from 65.1% (95% CI: 61.1% to 68.9%) of patients and 69.1% (95% CI: 65.5% to 72.6%) of stenoses. CONCLUSIONS: The ADVISE II study supports, on the basis rigorous methodology, the diagnostic value of iFR in establishing the functional significance of coronary stenoses, and highlights its complementariness with FFR when used in a hybrid iFR-FFR approach. (ADenosine Vasodilator Independent Stenosis Evaluation II-ADVISE II; NCT01740895).

Electrical characteristics of a split cathodal pacing configuration.

Several electrical configurations can be used for biventricular pacing to achieve cardiac resynchronization. Commercially approved biventricular pacing systems stimulate the RV with an endocardial lead and the LV with a unipolar lead positioned in the cardiac venous circulation using the tip electrodes of both leads linked as a common cathode. The distribution of current with this parallel circuit, split cathodal configuration is dependent on the separate impedances of the two leads. A total of 19 patients with left bundle branch block and congestive heart failure underwent implantation of a cardiac venous lead and standard bipolar right atrial and RV pacing leads. Stimulation thresholds and impedances were measured for the RV and LV in five electrical configurations: (1) unipolar LV from the cardiac venous lead; (2) bipolar LV using the tip electrode in the cardiac vein as the cathode and the ring electrode of the RV lead as the anode; (3) bipolar RV from the RV lead; (4) unipolar split cathodal stimulation of the cardiac venous and RV leads; and (5) bipolar split cathodal stimulation of the cardiac venous and RV leads. Repeat measurements of RV and LV thresholds were made from the pulse generator at 1-year follow-up. The LV stimulation threshold increased from 0.7 +/- 0.5 V in the unipolar configuration to 1.0 +/- 0.8 V in the unipolar split cathodal configuration (P = 0.01) and from 1.0 +/- 0.7 V in the bipolar configuration to 1.3 +/- 0.9 V in the bipolar split cathodal configuration (P < 0.001). The RV stimulation threshold increased from 0.3 +/- 0.2 V in the bipolar configuration to 0.5 +/- 0.2 V in the bipolar split cathodal configuration (P = 0.005). The bipolar impedance measured 874 +/- 299 Omega for the coronary venous lead, 705 +/- 152 for the RV lead, 442 +/- 87 in the split unipolar cathodal configuration, and 516 +/- 64 in the bipolar split cathodal configuration. At 1-year follow-up, the LV stimulation threshold was 1.8 +/- 1.6 in the unipolar split cathodal configuration and 2.4 +/- 1.6 in the bipolar split cathodal configuration (P = 0.003). The RV stimulation threshold at 1 year was 0.7 +/- 0.3 in the unipolar split cathodal configuration and 0.8 +/- 0.3 in the bipolar split cathodal configuration (P = 0.02). The split cathodal configuration significantly increases the apparent stimulation threshold for both the LV and the RV as compared with individual stimulation of either chamber alone. Programming to the bipolar split cathodal configuration further increases the apparent stimulation threshold. These observations support the development of pacing systems with separate LV and RV output circuits for resynchronization therapy.