Age-related structural remodelling of the coronary microcirculation

Background While it is broadly accepted that ageing is associated with impairment of coronary microvascular function, little is known on the underlying mechanisms. Diastolic microcirculatory conductance (DMVC) and the backward expansion wave (BEW) derived from wave intensity analysis (WIA) are two physiological indices derived from post-analysis of coronary pressure and flow that have been previously validated against endomyocardial biopsy micromorphometry, thus serving as metrics of structural microcirculatory remodelling applicable to in vivo assessment of the human coronary microcirculation. We investigated age-related changes in coronary microvascular structure in patients with stable angina without epicardial coronary stenoses. Methods This is an analysis of the IDEAL registry, including a total of 165 vessels without coronary stenosis interrogated with combined pressure/Doppler guidewires in non-diabetic patients. We calculated DMVCs and BEWs using dedicated software, and we compared them between patient groups according to age tertiles. We also calculated the prevalence of CMD, defined by reduced Coronary Flow Reserve (CFR <2.5), and calculated the prevalence of low BEW and low DMVC (values below the 25th percentile) in each group. Results The three study groups were defined as having 37-53; 54-66 and 67-77 years of age, respectively. Oldest (3rd tertile) patients show lower hyperemic flow velocity (46.7±14.4 vs 45.1±12.4 vs 38.4±11.5 cm.s-1, p=0.019), lower DMVC (1.90±0.71 vs 1.44±0.56 vs 1.37±0.67 cm.s-1.mmHg-1, p<0.001) and lower BEW intensity (5.9 [2.9-8.4] vs 4.8 [2.9-6.8] vs 4.4 [3.4-6.3] x106 W.m-2.s-1, p=0.094). Older age was also found to be an independent predictor of lower cumulative BEW intensity (B −0.10, 95% CI: −0.17 to −0.09, p=0.021) and lower DMVC (B −0.25 95% CI: −0.45 to −0.09, p=0.027). In patients with CMD as determined by CFR <2.5, the prevalence of BEW intensity and DMVC below the 25th percentile increased with age (25.0%, vs 52.0% vs 72.7%, for the 1st, 2nd and 3rd age tertiles, respectively, p=0.010). Conclusions Ageing is independently associated with structural microcirculatory remodelling that is reflected in BEW intensity and DMVC measurements and increased prevalence of structural CMD. These results are important in understanding non-obstructive mechanisms of myocardial ischemia in the elderly. CLINICAL PERSPECTIVE What is new? What are the clinical implications? ### Competing Interest Statement Dr. Lombardi has served as speaker for Phillips Dr. Travieso has received unconditional educational grants from Philips. Dr. Nijjer has served as speaker and / or advisory board member for Philips. Dr. Piek has served as speaker and / or advisory board member for Philips. Dr. van de Hoef is a consultant for Philips Dr. Echarravía-Pinto has received speaker fees from Boston Scientific Dr. Mejía-Renteria served as speaker at educational events organised by Abbott, Boston Scientific and Philips Healthcare Dr. Davies holds IP pertaining to iFR technology and is also a consultant and recipient of research funding from Philips Volcano. Dr. Escaned has served as speaker and / or advisory board member for Abbott, Boston Scientific and Philips. ### Funding Statement No funding was received ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics Committe of all involved centrers I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data that support the findings of this study are available on request from the corresponding author (JE) * APV : Average Peak Flow Velocity BCW : Backward Compression Wave BEW : Backward Expansion Wave BEW- EF : Backward Expansion Wave Energy Fraction C-BEW : Cumulative Backward Expansion Wave CFR : Coronary Flow Reserve CMD : Coronary Microcirculatory Dysfunction DMVC : Diastolic Microvascular Conductance IDEAL : Iberian-Dutch-English FCW : Forward Compression Wave FEW : Forward Expression Wave FFR : Fractional Flow Reserve HMR : Hyperemic Microvascular Conductance Pa : mean aortic pressure Pd : mean distal coronary pressure QCA : Quantitative Coronary Angiography WIA : Wave Intensity Analysis