The (virtual) assessment of coronary blood flow before and after treatment of severe aortic stenosis (VIRTU-AS)

Background: Transcatheter aortic valve implantation (TAVI) is a growing treatment modality for severe aortic stenosis, not only in the cohort of patients who would once have been unsuitable for surgical aortic valve replacement (SAVR), but also in lower risk patients. A significant proportion of patients undergoing TAVI have concomitant coronary artery disease. The best way to treat coronary disease in these patients remains contentious. Conventional assessments of ischaemia, such as fractional flow reserve (FFR) and the instantaneous wave-free ratio, are not validated in these patients. A better understanding of coronary physiology in these patients is required to optimise treatment pathways.
Hypotheses: Treatment of severe aortic stenosis with TAVI has long-term haemodynamic benefits with a measurable change in a) absolute coronary blood flow and microvascular function, b) symptoms and indices of coronary and myocardial physiology and c) LV mass.
Aim: To achieve a multi-modality assessment of the changes in coronary blood flow and microvascular function, before and after TAVI, correlating with expected reduction in LV mass.
Methods: Patients awaiting elective TAVI were recruited. Coronary angiography was performed and a pressure wire deployed in all diseased coronary arteries. Hyperaemia was induced and relevant parameters of coronary blood flow (resting full-cycle ratio, FFR, index of microcirculatory resistance and coronary flow reserve) were measured. Lesions associated with a positive FFR (≤0.80) were treated with PCI and the full range of coronary physiology repeated. Absolute coronary flow at rest and hyperaemia was modelled using virtuQ™ computational fluid dynamics software. Quantitative stress perfusion cardiac MRI was also performed to assess left ventricular parameters, global myocardial blood flow and coronary sinus flow. All measurements were repeated 3-6 months after TAVI.
Results: Pre-TAVI physiology data were obtained from 15 patients. Eight patients received PCI. Ten patients had cardiac MRI. Seven patients had post-TAVI physiology and cardiac MRI. The mean age was 81 years and 65% were male. There was a significant improvement in the coronary flow reserve from 1.45 to 2.3 (P<0.05) post-TAVI. The FFR increased from 0.87 to 0.89 (P<0.05) post-TAVI. There was no change in the index of microcirculatory resistance. There was a 20% reduction in coronary flow at rest from 178mL/min pre- to 146mL/min (P<0.05) post-TAVI, whilst hyperaemic coronary flow remained stable at a vessel-specific level. However, when myocardial blood flow was analysed using cardiac MRI, there was a 32% reduction in global hyperaemic flow from 554 to 374mL/min (P<0.05) and a 45% reduction in global resting flow from 478 to 265mL/min (P<0.05). The indexed left ventricular mass also regressed from 79g/m2 to 71g/m2 (P<0.05) post-TAVI. Coronary sinus flow and myocardial perfusion reserve did not change significantly.
Conclusion: There was a significant improvement in coronary flow reserve following TAVI, evidencing an improvement in the functional capacity of the myocardium to respond to stress. The mechanism for this was a 20% reduction in resting vessel-specific coronary blood flow, and a 45% reduction in global myocardial flow. The unchanged microvascular resistance suggests that resistance was not the reason for this. Rather, after TAVI, a much smaller portion of the microvascular bed is recruited. Resting flow fell due to a less demanding myocardium and regression of the baseline hyperaemic conditions, accompanied by an enhanced ability to respond to stress, and the expected reduction in LV mass.