Comprehensive Angiography-Derived Functional Assessment of Epicardial and Microvascular Coronary Disease. Correlation With Non-invasive Myocardial Stress Imaging.

Coronary angiography (CA) is poorly correlated with non-invasive myocardial stress imaging (NSI) and myocardial ischemia is often observed in patients with unobstructed coronary arteries. Moreover, the diagnostic performance of combined epicardial and microcirculatory angiography-derived physiological assessment and its correlation with NSI remains unknown. A total of 917 coronary vessels in 319 patients who underwent both CA and NSI were included in this multicenter observational retrospective analysis. Quantitative flow ratio (QFR) and angiography-derived index of microcirculatory resistance (IMRangio) analyses were performed to estimate coronary epicardial and microcirculatory function respectively. NSI demonstrated evidence of myocardial ischemia in 76% of the cases. IMRangio (36 [22 to 50] vs 29 [21 to 41], p <0.001) was significantly higher and QFR (0.92 [0.78 to 0.99] vs 0.97 [0.91 to 0.99], p <0.001) was significantly lower in vessels subtending ischemic territories. Overall, the diagnostic accuracy of QFR was moderate (area under the curve of receiver operating characteristic [AUCROC] 0.632 [95% confidence interval [CI] 0.589 to 0.674], p <0.0001) but it was higher in patients with normal microcirculatory function (AUCROC = 0.726 [95% CI 0.669 to 0.784], p <0.0001, p Value for AUCROC comparison = 0.009). Combined QFR/IMRangio assessment provided incremental diagnostic performance compared with the evaluation of epicardial or microcirculatory districts in isolation (p Value for AUC comparison <0.0001) and it was able to identify the predominant mechanism of myocardial ischemia in 77% of the patients with positive NSI. Our study suggests the value of a combined angiography-derived assessment of epicardial and microvascular function for the definition of the predominant mechanism of myocardial ischemia in patients with suspected coronary artery disease.

Integrated Assessment of Computational Coronary Physiology From a Single Angiographic View in Patients Undergoing TAVI.

BACKGROUND: Angiography-derived computational physiology is an appealing alternative to pressure-wire coronary physiology assessment. However, little is known about its reliability in the setting of severe aortic stenosis. This study sought to provide an integrated assessment of epicardial and microvascular coronary circulation by means of single-view angiography-derived physiology in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI). METHODS: Pre-TAVI angiographic projections of 198 stenotic coronary arteries (123 patients) were analyzed by means of Murray's law-based quantitative flow ratio and angiography microvascular resistance. Wire-based reference measurements were available for comparison: fractional flow reserve (FFR) in all cases, instantaneous wave-free ratio in 148, and index of microvascular resistance in 42 arteries. RESULTS: No difference in terms of the number of ischemia-causing stenoses was detected between FFR ≤0.80 and Murray's law-based quantitative flow ratio ≤0.80 (19.7% versus 19.2%; P=0.899), while this was significantly higher when instantaneous wave-free ratio ≤0.89 (44.6%; P=0.001) was used. The accuracy of Murray's law-based quantitative flow ratio ≤0.80 in predicting pre-TAVI FFR ≤0.80 was significantly higher than the accuracy of instantaneous wave-free ratio ≤0.89 (93.4% versus 77.0%; P=0.001), driven by a higher positive predictive value (86.9% versus 50%). Similar findings were observed when considering post-TAVI FFR ≤0.80 as reference. In 82 cases with post-TAVI angiographic projections, Murray's law-based quantitative flow ratio values remained stable, with a low rate of reclassification of stenosis significance (9.9%), similar to FFR and instantaneous wave-free ratio. Angiography microvascular resistance demonstrated a significant correlation (Rho=0.458; P=0.002) with index of microvascular resistance, showing an area under the curve of 0.887 (95% CI, 0.752-0.964) in predicting index of microvascular resistance ≥25. CONCLUSIONS: Angiography-derived physiology provides a valid, reliable, and systematic assessment of the coronary circulation in a complex scenario, such as severe aortic stenosis.

Cost-effectiveness of transcatheter aortic valve implantation versus surgical aortic valve replacement in low surgical risk aortic stenosis patients.

BACKGROUND: The PARTNER 3 trial demonstrated clinical benefits of transcatheter aortic valve implantation (TAVI) with the SAPIEN 3 device, over surgical aortic valve replacement (SAVR) in patients with severe symptomatic aortic stenosis (sSAS) at low risk of surgical mortality. Using PARTNER 3 outcomes and Italy-specific costs data, this cost-utility analysis from the perspective of the Italian National Health System aimed to determine the cost-effectiveness of SAPIEN 3 TAVI versus SAVR in low risk sSAS patients in Italy. METHODS: A two-stage cost-utility model was developed to estimate changes in both direct healthcare costs and health-related quality of life using TAVI with SAPIEN 3 compared with SAVR. Early adverse events associated with TAVI were captured utilising the PARTNER 3 dataset. These data fed into a Markov model that captured longer-term outcomes of patients, following TAVI or SAVR intervention. RESULTS: Analysis findings estimated that TAVI with SAPIEN 3 offers benefits over SAVR in terms of increased quality-adjusted life years (QALYs) with only a small increase in costs, representing an incremental cost-effectiveness ratio/QALY gained of €2989 per patient. The results were robust, with TAVI with SAPIEN 3 remaining cost-effective across several scenarios and in probabilistic sensitivity analyses. CONCLUSIONS: This model demonstrated that TAVI with SAPIEN 3 is likely to be cost effective compared with SAVR for the treatment of patients with sSAS who are at low risk of surgical mortality. These findings can inform policy makers to facilitate policy development in Italy on intervention selection for this patient population.

Significant Drop in Right Atrial Pressure Does Not Influence Fractional Flow Reserve Coronary Assessment.

The effect of a highly elevated level of right atrial filling pressure on fractional flow reserve (FFR) measurement remains unclear. Transcatheter tricuspid valve intervention, a recently introduced option for inoperable or high-risk patients, represents a unique model of in-vivo physiology to investigate the eventual influence of central venous pressure on coronary FFR measurements. The case is reported of a patient with a degenerated tricuspid surgical bioprosthesis who underwent transcatheter tricuspid valve-in-valve replacement and concomitant coronary functional assessment with FFR. In an experimental model, the significant fall in right atrial pressure did not influence FFR measurements in the presence of angiographically proven mild coronary artery disease.

Functional Assessment of Coronary Artery Disease in Patients Undergoing Transcatheter Aortic Valve Implantation: Influence of Pressure Overload on the Evaluation of Lesions Severity.

BACKGROUND: Aortic valve stenosis may influence fractional flow reserve (FFR) of concomitant coronary artery disease by causing hypertrophy and reducing the vasodilatory reserve of the coronary circulation. We sought to investigate whether FFR values might change after valve replacement. METHODS AND RESULTS: The functional relevance of 133 coronary lesions was assessed by FFR in 54 patients with severe aortic valve stenosis before and after transcatheter aortic valve implantation (TAVI) during the same procedure. A linear mixed model was used to verify the interaction of TAVI effect with the FFR values. No significant overall change in FFR values was found before and after the aortic valve stenosis removal (0.89±0.10 versus 0.89±0.13; P=0.73). A different trend in FFR groups (positive if ≤0.8; negative if >0.8) was found after TAVI (P for interaction <0.001). Positive FFR values worsened after TAVI (0.71±0.11 versus 0.66±0.14). Conversely, negative FFR values improved after TAVI (0.92±0.06 versus 0.93±0.07). Similarly, FFR values in coronary arteries with lesions presenting percent diameter stenosis >50 worsened after TAVI (0.84±0.12 versus 0.82±0.16; P=0.02), whereas FFR values in arteries with mild lesions (percent diameter stenosis <50) tended toward improvement after TAVI (0.90±0.07 versus 0.91±0.09; P=0.69). Functional FFR variations after TAVI changed the indication to treat the coronary stenosis in 8 of 133 (6%) lesions. CONCLUSIONS: Coronary hemodynamics are influenced by aortic valve stenosis removal. Nevertheless, FFR variations after TAVI are minor and crossed the diagnostic cutoff of 0.8 in a small number of patients after valve replacement. Borderline coronary lesions might become functionally significant after valve replacement, although FFR-guided interventions were infrequent even in patients with angiographically significant lesions.

iFR-FFR comparison in daily practice: a single-center, prospective, online assessment.

AIMS: To compare the performance of instantaneous wave-free ratio (iFR) with fractional flow reserve (FFR) in a real-life, prospective, single-center, and independent study. METHODS AND RESULTS: Fifty-four patients were included and 89 angiographic intermediate lesions underwent functional evaluation with both iFR and FFR. FFR was used as the gold standard, and the patients having FFR values 0.80 or less only underwent percutaneous coronary intervention. Linear regression demonstrated close agreement between the two techniques (R = 0.83, P < 0.0001). Receiver operator characteristic analysis confirmed the strong correlation, with an area under the curve approximately equal to unity. iFR detected ischemia with a sensitivity and specificity of 100 and 87%, respectively, thus revealing a positive predictive value of 78% and a negative predictive value of 100%. In addition, according to FFR assessment, percutaneous coronary intervention was performed on 39 lesions (43.8%) in 27 patients (50%), whereas positive iFR values were found in 52 lesions (+14.6% compared with FFR). At clinical follow-up (ranging from 6 to 16 months), all patients remained asymptomatic and none of them experienced major adverse cardiovascular events. CONCLUSIONS: In this independent, online, comparison of iFR-FFR values in patients with angiographic intermediate lesions, results are consistent with those derived from previous offline controlled trials, and support the correlation between iFR and FFR in daily clinical practice.

A multicenter, randomized study to test immunosuppressive therapy with oral prednisone for the prevention of restenosis after percutaneous coronary interventions: cortisone plus BMS or DES versus BMS alone to eliminate restenosis (CEREA-DES) - study design and rationale.

BACKGROUND: Several randomized trials and registries have shown a reduction of restenosis after coronary angioplasty with drug-eluting stents (DESs) compared with bare metal stents (BMSs). However, cost-efficacy analysis and long-term outcome of DESs compared to BMSs deserve further assessment. Moreover, concern has been raised regarding adverse clinical events occurring late after DES implantation, in particular, late stent thrombosis related to the suspension of dual antiplatelet therapy. The use of a short-cycle oral treatment with prednisone at immunosuppressive dose after BMS implantation has shown remarkable efficacy in reducing restenosis in nondiabetic patients, with very low additional cost and without the need for long-term dual antiplatelet therapy. Such results are however limited by small sample size. STUDY DESIGN: Cortisone plus BMS or DES versus BMS alone to Eliminate Restenosis is an independent, prospective, multicenter, randomized study. It will randomize 375 nondiabetic patients with coronary artery disease in three different arms to BMS (control group), DES (DES group) or BMS followed by a 40-day prednisone treatment (prednisone group). The DES and the prednisone groups will be compared to the control group to investigate the expected clinical advantage. The primary endpoint of the study is the event-free survival of cardiovascular death, myocardial infarction and recurrence of ischemia-needing repeated target vessel revascularization at 1 year. Secondary endpoints are the event-free survival analysis at 2 and 3 years, the restenosis rate at 9 months, and cost-effectiveness at 1, 2 and 3 years. SAMPLE SIZE: The expected primary endpoint rates are 90% for DESs and for prednisone-treated patients and 77% for BMSs. The study was designed as a superiority trial, to compare DES, and BMS and prednisone, with BMS alone. A sample size of 118 patients per group provides an 80% power, assuming a complete 12-month follow-up information available for each patient. To obviate for cases of drop out, the sample size was increased to 375 patients to be enrolled in five Italian hospitals. CONCLUSION: This study will provide a magnitude of the net clinical and economic benefits of DES and of the safety and efficacy of BMS and cortisone compared to the standard use of BMS alone in nondiabetic patients with coronary artery disease.