Coronary Microcirculatory Dysfunction and Acute Cellular Rejection After Heart Transplantation

Background: Acute cellular rejection is a major determinant of mortality and re-transplantation after heart transplantation. We sought to evaluate prognostic implications of coronary microcirculatory dysfunction assessed by index of microcirculatory resistance (IMR) for risk of acute cellular rejection after heart transplantation. Methods: The current study prospectively enrolled 154 heart transplant recipients who underwent scheduled coronary angiography and invasive coronary physiologic assessment 1 month after transplantation. IMR is microcirculatory resistance under maximal hyperemia. By measuring hyperemic mean transit time using 3 injections (4 mL each) of room-temperature saline under maximal hyperemia, IMR was calculated as hyperemic distal coronary pressure × hyperemic mean transit time. The primary endpoint was biopsy-proven acute cellular rejection of grade ≥2R during 2 years of follow-up after transplantation and was compared using multivariable Cox proportional hazard regression according to IMR. The incremental prognostic value of IMR, in addition to the model with clinical factors, was evaluated by comparison of c-index, net reclassification index (NRI), and integrated discrimination index (IDI). Results: Mean age of recipients was 51.2±13.1 years (81.2% male), and cumulative incidence of acute cellular rejection was 19.0% at 2 years. Patients with acute cellular rejection had significantly higher IMR values at 1 month than those without acute cellular rejection (23.1±8.6 vs. 16.8±11.1, P=0.002). IMR was significantly associated with the risk of acute cellular rejection (per 5-unit increase: adjusted HR 1.18, 95% CI 1.04-1.34, P=0.011) and the optimal cut-off value of IMR to predict acute cellular rejection was 15. Patients with IMR≥15 showed significantly higher risk of acute cellular rejection than those with IMR<15 (34.4% vs. 3.8%, adjusted HR 15.3, 95% CI 3.6-65.7, P<0.001). Addition of IMR to clinical variables showed significantly higher discriminant and reclassification ability for risk of acute cellular rejection (C-index 0.87 vs. 0.74, P<0.001; NRI 1.05, P<0.001, IDI 0.20, P<0.001). Conclusions: Coronary microcirculatory dysfunction assessed by IMR measured early after heart transplantation showed significant association with the risk of acute cellular rejection. In addition to surveillance endomyocardial biopsy, early stratification using IMR could be a clinically useful tool to identify patients at higher risk of future acute cellular rejection after heart transplantation. Clinical Trial Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT02798731

Characterizing and Optimizing Piezoelectric Response of ZnO Nanowire/PMMA Composite-Based Sensor

Due to the outstanding coupling between piezoelectric and semiconducting properties of zinc oxide nanowires, ZnO NW-based structures have been demonstrating promising potential with respect to their applicability in piezoelectric, piezotronic and piezo-phototronic devices. Particularly considering their biocompatibility and biosafety for applications regarding implantable medical detection, this paper proposed a new concept of piezoelectric composite, i.e., one consisting of vertically aligned ZnO NW arrays and an insulating polymer matrix. First, the finite element method (FEM) was employed to drive optimization strategies through adjustment of the key parameters such as Young’s modules and the dielectric constant of the dielectric constituents, together with the density and dimension of nanowire (NW) itself. Second, to investigate the functionality of each individual layer of composite, different designed structures were fabricated and characterized in terms of electrical and piezoelectric properties. Next, experimental and simulation tests were performed, indicating that the decreasing thickness of the top poly(methyl methacrylate) layer (PMMA) can substantially enhance the piezoelectric sensitivity of the ZnO NW composite. Besides the further benefit of no polarization being needed, our material has a comparable charge coefficient (d33) with respect to other lead-free alternatives (e.g., BaTiO3), confirming the high sensing abilities of the developed structure based on vertically aligned ZnO NW arrays. Finally, a time-varying model combining piezoelectricity and electric circuit modules was investigated in detail, giving rise to an estimation of the d33 coefficient for ZnO NWs. Based on this study, the developed material is revealed to be highly promising in medical applications, particularly regarding the FFR technique, where coronary pressure can be measured through a piezoelectric sensor.

A Computational Analysis of the Influence of a Pressure Wire in Evaluating Coronary Stenosis

Cardiovascular disease is one of the world’s leading causes of morbidity and mortality. Fractional flow reserve (FFR) was proposed in the 1990s to more accurately evaluate the functional severity of intermediate coronary stenosis, and it is currently the gold standard in cardiac catheterization laboratories where coronary pressure and flow are routinely obtained. The clinical measurement of FFR relies on a pressure wire for the recording of pressures; however, in computational fluid dynamics studies, an FFR is frequently predicted using a wire-absent model. We aim to investigate the influence of the physical presence of a 0.014-inch (≈0.36 mm) pressure wire in the calculation of virtual FFR. Ideal and patient-specific models were simulated with the absence and presence of a pressure wire. The computed FFR reduced from 0.96 to 0.93 after inserting a wire in a 3-mm non-stenosed (pipe) ideal model. In mild stenotic cases, the difference in FFR between the wire-absent and wire-included models was slight. The overestimation in severe case was large but is of less clinical significance because, in practice, this tight lesion does not require sophisticated measurement to be considered critical. However, an absence of the pressure wire in simulations could contribute to an over-evaluation for an intermediate coronary stenosis.

Intra-Aortic Balloon Pump and Ischemic Cardiogenic Shock May Still Be a Valuable Association

The IABP gives rise to greater myocardial perfusion by increasing the coronary pressure gradient from the aorta to the coronary circulation at a time when the aortic valve is closed [...]

Fractional flow reserve

Fractional flow reserve is an index of the physiological significance of a coronary stenosis, defined as the ratio of maximal myocardial blood flow in the presence of the stenosis to the theoretically normal maximal myocardial blood flow (i.e. in the absence of the stenosis). This flow ratio can be calculated from the ratio of distal coronary pressure to central aortic pressure during maximal hyperaemia. More practically, fractional flow reserve indicates to what extent the epicardial segment can be responsible for myocardial ischaemia and, accordingly, fractional flow reserve quantifies the expected perfusion benefit from revascularization by percutaneous coronary intervention. Very limited evidence exists on the role on fractional flow reserve for bypass grafts.

Deferred versus performed revascularisation according to hyperaemic and nonhyperaemic physiological indexes in acute coronary syndrome: insights from the IRIS-FFR Registry

Background/Introduction Physiology-guided PCI in the ACS setting remains debatable. Purpose We aimed to determine the long-term prognostic utility of fractional flow reserve (FFR)- or resting distal coronary pressure to aortic pressure ratio (Pd/Pa)-directed percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) cases. Methods This study included 11,415 coronary stenoses in 7945 patients, including 1668 ACS cases who underwent FFR and resting Pd/Pa. The primary endpoint was the rate of a composite of cardiac death, spontaneous myocardial infarction (MI), and repeat revascularisation. Results During a median follow-up of 3.9 years (IQR: 2.0–4.9), 108 events (12 cardiac deaths, 9 MIs, and 100 revascularisations) of the primary endpoint occurred in 101 patients. In the deferred lesions with FFR &gt;0.80 or Pd/Pa &gt;0.91, the primary endpoint rate was higher in ACS patients than those with stable ischaemic heart disease (SIHD) (adjusted HR 1.87, 95% CI 1.37–2.55 for FFR; adjusted HR 1.78, 95% CI 1.34–2.38 for Pd/Pa). Among ACS patients with FFR ≤0.8 or Pd/Pa ≤0.91, performed revascularisation was associated with a lower rate of the primary endpoint compared to deferred PCI. (6.0% vs. 15.4%, adjusted HR 0.42, 95% CI 0.23–0.77 for FFR; 4.3% vs. 14%, adjusted HR 0.33–0.71, 95% CI 0.33–0.71 for Pd/Pa). However, performed and deferred groups had similar outcome rates in ACS patients with FFR &gt;0.80 or Pd/Pa &gt;0.91. Conclusion ACS patients who deferred revascularisation based on physiology had higher cardiovascular events than did those with SIHD. FFR- and resting Pd/Pa-directed decision-making for PCI is likely useful even in the ACS setting. Funding Acknowledgement Type of funding source: None