Haemodynamic effects of sacubitril/valsartan in advanced heart failure.

AIMS: The angiotensin receptor-neprilysin inhibitor (ARNI), sacubitril/valsartan, has been shown to be effective in treatment of patients with heart failure (HF), but limited data are available in patients with advanced disease. This retrospective observational study assessed the effects of ARNI treatment in patients with advanced HF. METHODS AND RESULTS: We reviewed medical records of all advanced HF patients evaluated at our centre for unconventional therapies from September 2016 to January 2019. We studied 44 patients who started ARNI therapy and who had a haemodynamic assessment before beginning ARNI and after 6 ± 2 months. The primary endpoint was variation in pulmonary pressures and filling pressures at 6 months after starting ARNI therapy. Mean patient age was 51.6 ± 7.4 years; 84% were male. At 6 ± 2 months after starting ARNI, there was significant reduction of systolic pulmonary artery pressure [32 mmHg, interquartile range (IQR) 27-45 vs. 25 mmHg, IQR 22.3-36.5; P < 0.0001] and mean pulmonary artery pressure (20 mmHg, IQR 15.3-29.8 vs. 17 mmHg, IQR 13-24.8; P = 0.046). Five of 22 patients (23%) were deferred from the heart transplant list because of improvement, whereas four were listed de novo. After 23 ± 9 months, three patients were treated with a left ventricular assist device implantation, whereas six patients underwent heart transplantation (one in emergency conditions for refractory ventricular tachycardia). CONCLUSIONS: Sacubitril/valsartan is effective in reducing filling pressures and pulmonary pressures in patients with advanced HF. The absence of adverse events during follow-up suggests that sacubitril/valsartan is safe and well-tolerated in this cohort of patients.

Correlation between intracoronary physiology and myocardial perfusion imaging in patients with severe aortic stenosis.

BACKGROUND: Aortic stenosis (AS) is frequently associated with coronary artery disease (CAD). However, the best tool to functionally assess CAD in AS remains undetermined. Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) have never been validated in AS. METHODS: FFR, iFR and stress single photon emission computed tomography (SPECT) were performed in a consecutive series of 28 patients with severe AS and 41 borderline coronary lesions during the work-up for valve replacement. RESULTS: Both FFR and iFR were correlated with an abnormal SPECT. At ROC analysis, FFR yielded an AUC = 0.91 with negative predictive value (NPV) = 95% in detecting ischemia according to SPECT. iFR showed significant worse agreement with myocardial perfusion imaging compared to FFR (59% vs 85%, p = 0.014). Specifically, a significant larger proportion of false positive measurements (negative SPECT and iFR < 0.89) was observed using iFR vs FFR: 39% vs 12%, p = 0.011. Using a pre-specified 0.82 cut-off, the iFR agreement with SPECT increased to 73%. CONCLUSIONS: FFR yielded a good correlation with SPECT and a high NPV in detecting ischemia-provoking lesions. iFR diagnostic metrics were inferior compared with FFR and improved adopting a lower ischemic threshold.

Observations from a real-time, iFR-FFR "hybrid approach" in patients with severe aortic stenosis and coronary artery disease undergoing TAVI.

BACKGROUND: The complexity of coronary physiology in presence of severe aortic stenosis (AS) raises concerns about the reliability of pressure-derived indexes in this clinical setting. Furthermore, neither fractional flow reserve (FFR) nor instantaneous wave-free period (iFR) has been validated in AS. Combining iFR and FFR in a tailored decision-making strategy may help to increase simplicity, accuracy and safety of physiology-guided revascularization in AS. METHODS: In this prospective observational study iFR and FFR were measured before and after TAVI during the same procedure in patients with severe AS and concomitant coronary artery disease (CAD). All decisions about revascularization were based on post-TAVI FFR assessment. The best iFR "defer" and "treatment" values were identified according to their baseline negative (NPV) and positive predictive values (PPV) respectively. A post-hoc analysis was then performed to compare the hybrid iFR-FFR approach with the FFR-only strategy. RESULTS: Sixty-two patients underwent pre- and post-TAVI pressure-wire assessment and were included in the analysis. A "defer iFR value" >0.93 yielded a NPV of 98.4% (91.7%-99.9%) to exclude FFR non-significant stenosis (>0.80), and a "treatment iFR value" <0.83 had a PPV of 91.3% (72%-98.9%) to identify FFR-significant stenosis (≤0.80). A hybrid decision-making strategy based on iFR and FFR spared 63% of patients from adenosine, while maintaining 97% overall agreement with FFR lesions classification. CONCLUSION: A hybrid iFR-FFR diagnostic strategy is feasible and safe in patients with severe AS undergoing TAVI and allows to spare the majority of patients from adenosine, while maintaining a high agreement with FFR classification of coronary lesions.