3D printing of heart valves.

3D printing technologies have the potential to revolutionize the manufacture of heart valves through the ability to create bespoke, complex constructs. In light of recent technological advances, we review the progress made towards 3D printing of heart valves, focusing on studies that have utilised these technologies beyond manufacturing patient-specific moulds. We first overview the key requirements of a heart valve to assess functionality. We then present the 3D printing technologies used to engineer heart valves. By referencing International Organisation for Standardisation (ISO) Standard 5840 (Cardiovascular implants - Cardiac valve prostheses), we provide insight into the achieved functionality of these valves. Overall, 3D printing promises to have a significant positive impact on the creation of artificial heart valves and potentially unlock full complex functionality.

Hepatic fat as a novel marker for high-risk coronary atherosclerotic plaque features in familial hypercholesterolaemia.

BACKGROUND & AIMS: Hepatic steatosis has been associated with increased risk of coronary artery disease. Individuals with familial hypercholesterolaemia have accelerated but variable progression of coronary artery disease. We investigated whether hepatic steatosis is associated with novel coronary atherosclerosis biomarkers in adults with heterozygous familial hypercholesterolaemia, using comprehensive coronary computed tomographic angiography. METHODS: We conducted a cross-sectional study of 213 asymptomatic patients with familial hypercholesterolaemia (median age 54.0 years, 59 % female) who underwent coronary computed tomographic angiography for cardiovascular risk assessment in an outpatient clinic. High-risk plaque features, plaque volume and pericoronary adipose tissue attenuation were assessed. From concurrently captured upper abdominal images, severity of hepatic steatosis was computed, as liver minus spleen computed tomography attenuation and stratified into quartiles. RESULTS: Of 213 familial hypercholesterolaemia patients, 59 % had coronary artery calcium, 36 % obstructive coronary artery disease (≥50 % stenosis) and 77 % high-risk plaque features. Increasing hepatic steatosis was associated with higher calcium scores, more high-risk plaque features and presence of obstructive coronary artery disease. Hepatic steatosis was associated with the presence of high-risk plaque features (OR: 1.48; 95 % CI: 1.09-2.00; p = 0.01), particularly in the proximal coronary segments (OR: 1.52; 95 % CI: 1.18-1.96; p = 0.001). Associations persisted on multivariable logistic regression analysis adjusting for cardiometabolic factors, obstructive coronary artery disease and calcium score. Hepatic steatosis was associated with higher plaque volumes (Q4: 499 mm3 vs Q1: 414 mm3, p = 0.02), involving mainly low attenuation and noncalcified plaques (both p = 0.03). No differences in pericoronary adipose tissue attenuation were observed. CONCLUSIONS: Hepatic steatosis is associated with multiple indices of advanced coronary atherosclerosis in familial hypercholesterolaemia patients, particularly high-risk plaque features, independent of conventional cardiovascular risk factors and markers. This may involve specific mechanisms related to hepatic steatosis. CLINICAL TRIAL NUMBER: N/A.

Characteristics and outcomes of patients with type 1 diabetes admitted with acute coronary syndromes.

AIMS: This study explored characteristics and outcomes of patients with type 1 diabetes mellitus (T1DM) and acute coronary syndromes (ACS). METHODS: A retrospective analysis of patients with T1DM admitted with ACS to an Australian hospital was conducted. Risk factor targets were defined by 2021 European Society of Cardiology Guidelines. Outcomes were defined as an adverse cardiovascular event (ACS, unplanned revascularisation, heart failure, stroke, or cardiovascular death) or all-cause mortality within six-months after discharge. RESULTS: 61 patients were included [age 58.5 ± 12.8 years, 39 % female]. Dyslipidaemia (85 %), hypertension (75 %), smoking (28 %), prior coronary artery disease (CAD) (44 %), and microvascular complications (62 %) were common. HbA1c, low-density lipoprotein cholesterol, and blood pressure targets were attained in 12 %, 36 % and 47 %, respectively. ST-elevation myocardial infarction (65 % versus 7 %, p < 0.001) and revascularisation (77 % versus 41 %, p = 0.008) were more common in those without prior CAD. Peak inpatient blood glucose correlated directly with peak troponin (p = 0.011) and inversely with left ventricular ejection fraction (p = 0.027). Nineteen patients experienced an adverse six-month outcome, with peripheral neuropathy (p = 0.039) and in-hospital hypoglycaemia (p = 0.012) being independent predictors. CONCLUSIONS: Patients with T1DM and ACS often do not meet guideline targets for cardiovascular risk factors, and frequently present with transmural infarctions. Dysglycemia and microvascular complications predict poorer outcomes.

Comparison of performance of self-expanding and balloon-expandable transcatheter aortic valves.

Objective: To evaluate the flow dynamics of self-expanding and balloon-expandable transcatheter aortic valves pertaining to turbulence and pressure recovery. Transcatheter aortic valves are characterized by different designs that have different valve performance and outcomes. Methods: Assessment of transcatheter aortic valves was performed using self-expanding devices (26-mm Evolut [Medtronic], 23-mm Allegra [New Valve Technologies], and small Acurate neo [Boston Scientific]) and a balloon-expandable device (23-mm Sapien 3 [Edwards Lifesciences]). Particle image velocimetry assessed the flow downstream. A Millar catheter was used for pressure recovery calculation. Velocity, Reynolds shear stresses, viscous shear stress, and pressure gradients were calculated. Results: The maximal velocity at peak systole obtained with the Evolut R, Sapien 3, Acurate neo, and Allegra was 2.12 ± 0.19 m/sec, 2.41 ± 0.06 m/sec, 2.99 ± 0.10 m/sec, and 2.45 ± 0.08 m/sec, respectively (P < .001). Leaflet oscillations with the flow were clear with the Evolut R and Acurate neo. The Allegra shows the minimal range of Reynolds shear stress magnitudes (up to 320 Pa), and Sapien 3 the maximal (up to 650 Pa). The Evolut had the smallest viscous shear stress magnitude range (up to 3.5 Pa), and the Sapien 3 the largest (up to 6.2 Pa). The largest pressure drop at the vena contracta occurred with the Acurate neo transcatheter aortic valve with a pressure gradient of 13.96 ± 1.35 mm Hg. In the recovery zone, the smallest pressure gradient was obtained with the Allegra (3.32 ± 0.94 mm Hg). Conclusions: Flow dynamics downstream of different transcatheter aortic valves vary significantly depending on the valve type, despite not having a general trend depending on whether or not valves are self-expanding or balloon-expandable. Deployment design did not have an influence on flow dynamics.

Prosthesis Geometrical Predictors of Leaflet Thrombosis Following Transcatheter Aortic Valve Replacement With Intra-Annular Prostheses.

OBJECTIVE: To determine the association between prosthesis geometry with leaflet thrombosis (LT). BACKGROUND: Leaflet thrombosis following transcatheter aortic valve replacement (TAVR) is a recognised entity. The association between prosthesis geometry with LT is unclear but maybe a potential modifiable factor in its prevention. METHODS: Patients who received an intra-annular TAVR prosthesis and were prospectively planned to undergo post-procedural computed tomography (CT) imaging were included. Leaflet thrombosis was defined as at least 50% restricted leaflet motion on CT. Prosthesis expansion and eccentricity was measured at prosthesis inflow, annulus and outflow levels. Prosthesis misalignment was defined as the average angle deviation between native and prosthesis leaflet commissure, greater than 30°. RESULTS: Prevalence of LT was 13.7% in 117 patients. None of the patients with LT were on anticoagulation therapy. Patients with LT had reduced prosthesis annular expansion (89.4±5.2% vs 97.0±4.4%, p<0.01), greater prosthesis misalignment (81.3% vs 48.5%, p=0.02) and deeper implants (6.3±1.7 mm vs 4.3±1.5 mm, p<0.01). Threshold for the presence of LT on ROC analysis was an implant depth of 5.7 mm (AUC [area under curve]=0.81). Independent predictors of LT were annular under-expansion (Odds ratio [OR] 1.4, 95% confidence interval [CI] 1.2-1.7, p=0.03) prosthesis misalignment (OR 6.8, 95%CI 1.1-45.5, p=0.04) and implant depth (OR 1.9, 95%CI 1.1-3.2, p=0.03). Anticoagulation therapy was a protective factor (OR 0.2; 95%CI 0.1-0.4, p<0.01). CONCLUSION: Geometrical predictors of LT post intra-annular TAVR were reduced prosthesis expansion at the annular level, lower implant depth and greater prosthesis misalignment. These factors may be important considerations during procedural planning for TAVR.

Prognostic value of coronary computed tomography angiographic derived fractional flow reserve: a systematic review and meta-analysis.

OBJECTIVES: To obtain more powerful assessment of the prognostic value of fractional flow reserveCT testing we performed a systematic literature review and collaborative meta-analysis of studies that assessed clinical outcomes of CT-derived calculation of FFR (FFRCT) (HeartFlow) analysis in patients with stable coronary artery disease (CAD). METHODS: We searched PubMed and Web of Science electronic databases for published studies that evaluated clinical outcomes following fractional flow reserveCT testing between 1 January 2010 and 31 December 2020. The primary endpoint was defined as 'all-cause mortality (ACM) or myocardial infarction (MI)' at 12-month follow-up. Exploratory analyses were performed using major adverse cardiovascular events (MACEs, ACM+MI+unplanned revascularisation), ACM, MI, spontaneous MI or unplanned (>3 months) revascularisation as the endpoint. RESULTS: Five studies were identified including a total of 5460 patients eligible for meta-analyses. The primary endpoint occurred in 60 (1.1%) patients, 0.6% (13/2126) with FFRCT>0.80% and 1.4% (47/3334) with FFRCT ≤0.80 (relative risk (RR) 2.31 (95% CI 1.29 to 4.13), p=0.005). Likewise, MACE, MI, spontaneous MI or unplanned revascularisation occurred more frequently in patients with FFRCT ≤0.80 versus patients with FFRCT >0.80. Each 0.10-unit FFRCT reduction was associated with a greater risk of the primary endpoint (RR 1.67 (95% CI 1.47 to 1.87), p<0.001). CONCLUSIONS: The 12-month outcomes in patients with stable CAD show low rates of events in those with a negative FFRCT result, and lower risk of an unfavourable outcome in patients with a negative test result compared with patients with a positive test result. Moreover, the FFRCT numerical value was inversely associated with outcomes.

Neosinus and Sinus Flow After Self-Expanding and Balloon-Expandable Transcatheter Aortic Valve Replacement.

OBJECTIVES: The aim of this study was to evaluate flow dynamics in the aortic sinus and the neosinus (NS) after transcatheter heart valve (THV) implantation in valve-in-valve (ViV). BACKGROUND: Leaflet thrombosis may occur on THVs and affect performance and durability. Differences in flow dynamics may affect the risk for leaflet thrombosis. METHODS: Hemodynamic assessment following THV implantation in a surgical aortic valve was performed in a left heart simulator under pulsatile physiological conditions. Assessment was performed using a 23-mm polymeric surgical aortic valve (not diseased) and multiple THV platforms, including self-expanding devices (26-mm Evolut, 23-mm Allegra, small ACURATE neo) and a balloon-expandable device (23-mm SAPIEN 3). Particle image velocimetry was performed to assess flow in the sinus and NS. Sinus and NS washout, shear stress, and velocity were calculated. RESULTS: Sinus and NS washout was fastest and approximately 1 cardiac cycle for each with the Evolut, ACURATE neo, and Allegra compared with the SAPIEN 3, with washout in 2 and 3 cardiac cycles, respectively. The Allegra showed the largest shear stress distribution in the sinus, followed by the SAPIEN 3. In the NS, all 4 valves showed equal likelihoods of occurrence of shear stress <1 Pa, but the Allegra showed the highest likelihoods of occurrence for shear stress >1 Pa. The velocities in the sinus and NS were 0.05, 0.078, 0.080, and 0.075 m/s for Evolut, SAPIEN 3, ACURATE neo, and Allegra ViV, respectively. CONCLUSIONS: Sinus and NS flow dynamics differ substantially among THVs after ViV. Self-expanding supra-annular valves seem to have faster washouts compared with an equivalent-size balloon-expandable THV.

Clinical predictors and sequelae of computed tomography defined leaflet thrombosis following transcatheter aortic valve replacement at medium-term follow-up.

BACKGROUND: The clinical predictors and sequelae of leaflet thrombosis (LT) following transcatheter aortic valve replacement (TAVR) is still unclear. Therefore, our aim was to determine the clinical predictors and sequelae at mid-term follow-up of computed tomography (CT)-defined LT following TAVR. METHODS AND RESULTS: We performed a prospective evaluation with a 320-multislice CT following TAVR for the presence of LT, defined as hypo-attenuated leaflet thickening (HALT). Four-dimensional CT image-rendering was performed to determine the presence of reduced leaflet motion (RELM). 172 patients [89 (51.7%) male, mean age 82.8 ± 5.7 years] treated with commercially available TAVR device (Lotus 54%, CoreValve 32% and Sapien 3 14%) were included, with median CT-scan at 6.0 weeks post-TAVR. Prevalence of HALT was 14.0% (24 cases) and RELM was 9.8% (17 cases). On multivariate analysis, patients with HALT were less prescribed oral anticoagulation (OAC) (OR 9.9), received larger TAVR prostheses (OR 5.7) and higher rates of moderate-severe para-valvular regurgitation (PVR) (OR 16.3). There was no difference in clinical outcomes at a median follow-up of 2.3 years. Patients with RELM had significantly higher transvalvular gradients after discharge when compared to those without RELM. CONCLUSIONS: Absence of OAC, large TAVR prostheses and moderate-severe PVR were predictors for LT. Transvalvular gradients were higher in patients that developed RELM but not HALT. Further studies are warranted to determine the long-term impact of LT on TAVR durability. Prevalence of different sub-types of CT-defined LT (HALT and RELM) and the clinical predictors of developing LT following TAVR. CT computed tomography, HALT hypo-attenuated leaflet thickening, LT leaflet thrombosis, RELM reduced leaflet motion, TAVR transcatheter aortic valve replacement.

Fractional Flow Reserve following Percutaneous Coronary Intervention.

Fractional flow reserve (FFR) is routinely used to determine lesion severity prior to percutaneous coronary intervention (PCI). However, there is an increasing recognition that FFR may also be useful following PCI to identify mechanisms leading to restenosis and the need for repeat revascularization. Post-PCI FFR is associated with the presence and severity of stent under-expansion and may help identify peri-stent-related complications. FFR pullback may also unmask other functionally significant lesions within the target vessel that were not appreciable on angiography. Recent studies have confirmed the prognostic utility of performing routine post-PCI FFR and suggest possible interventional targets that would improve stent durability. In this review, we detail the theoretical basis underlying post-PCI FFR, provide practical tips to facilitate measurement, and discuss the growing evidence supporting its use.

Bioprosthetic aortic valve leaflet thrombosis detected by multidetector computed tomography is associated with adverse cerebrovascular events: a meta-analysis of observational studies.

AIMS: Leaflet thrombosis (LT) has become increasingly recognised following transcatheter and surgical aortic bioprosthetic valve (ABV) replacement and can be reliably identified by multidetector computed tomography (MDCT). However, it is an ongoing debate whether MDCT-defined LT is associated with adverse cerebrovascular outcomes. We sought to perform a systematic review and meta-analysis in order to assess the incidence and clinical outcomes associated with MDCT-defined leaflet thrombosis following (ABV) replacement. METHODS AND RESULTS: Electronic databases were searched for studies that performed mandatory MDCT imaging following ABV replacement. The primary endpoint was the incidence of cerebrovascular events, defined as a composite of stroke or transient ischaemic attack (TIA). Secondary endpoints included major adverse cerebrovascular and cardiovascular events (MACCE), stroke, TIA, death or myocardial infarction. In total, six studies met the inclusion criteria with 11.6% (198/1,704) of patients having MDCT-defined LT. The prevalence of LT following transcatheter and surgical ABV replacement was 13.2% and 3.6%, respectively. Cerebrovascular events were significantly increased in patients with LT (odds ratio [OR] 3.38, 95% CI: 1.78-6.41, p<0.001). The risk of MACCE (OR 2.10, 95% CI: 1.21-3.64, p<0.001) and TIA (OR 5.86, 95% CI: 2.05-16.75, p<0.001) was also increased in patients with LT, although there were no differences in the incidence of stroke (OR 2.43, 95% CI: 1.00-5.93, p=0.05), death (OR 0.92, 95% CI: 0.42-2.03, p=0.84) or myocardial infarction (OR 1.72, 95% CI: 0.34-9.78, p=0.54) between groups. CONCLUSIONS: MDCT-defined LT following ABV replacement is associated with a significantly increased risk of adverse cerebrovascular events. Further prospective studies are required to ascertain whether LT can be prevented or treated with pharmacological strategies.

Effect of aorto-ventricular angulation on procedural success in transcatheter aortic valve replacements with the Lotus Valve system.

OBJECTIVE: To determine the effect of aorto-ventricular angulation (AA) on procedural success with the Lotus Valve system. BACKGROUND: AA, the angulation of the aortic valve basal plane, may affect the deployment of transcatheter aortic valve replacements (TAVRs). The Lotus Valve system is fully repositionable and delivered on a pre-shaped catheter which may alter the impact of AA on its deployment. The effect of AA on procedural and clinical outcomes with the Lotus valve is unreported. METHODS: Consecutive patients who underwent transfemoral TAVR with the Lotus Valve system were analyzed. AA was determined on pre-procedural multi-detector computed tomography imaging. Device success, procedural characteristics, and clinical events were assessed according to Valve Academic Research Consortium-2 (VARC2) definitions. RESULTS: One hundred sixty-five patients were analyzed (48% male, mean age 84 years). The mean AA was 47.8 degrees. Patients were, therefore, divided into low AA (AA < 48°) or high AA (AA ≥ 48°). Baseline characteristics were similar in both cohorts. Device success and procedural outcomes were also similar including procedure time, contrast dose, and need to reposition. There was no difference in degree of moderate or greater para-valvular regurgitation (PVR) (0% vs. 3%, P = 0.09). Clinical outcomes of death, stroke, myocardial infarction, and other major VARC2 endpoints were similar. CONCLUSION: AA did not affect device success or clinical outcome with the Lotus Valve system. The Lotus' unique design features may have mitigated the impact of AA by improving the accuracy, ease of valve positioning, and reducing PVR.

Intra-aortic balloon pump: indications, efficacy, guidelines and future directions.

PURPOSE OF REVIEW: The intra-aortic balloon pump (IABP) has been used as a cardiac assist device in various clinical situations since 1968 on the basis of the physiological principles and observational data, with little randomized data until recently. RECENT FINDINGS: Recently published randomized controlled trials (RCTs) and meta-analyses have demonstrated acceptable safety for IABP but have raised doubt over efficacy in acute myocardial infarction (MI) both with and without cardiogenic shock. RCTs and meta-analyses have provided limited and qualified support for the efficacy of IABP in high-risk percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG). There remains only observational data to support the efficacy of IABP in other niche indications, including mechanical complications of MI (acute severe mitral regurgitation and ventricular septal rupture) and refractory ventricular arrhythmia. SUMMARY: Current randomized trial data and meta-analyses support the safety of IABP, but provide limited or no support for its efficacy in the treatment of high-risk MI, MI complicated by cardiogenic shock or the use of prophylactic IABP in high-risk PCI and CABG. Further studies to inform optimal patient selection, timing and use of associated therapies are required to characterize the role of IABP in contemporary practice and optimize outcome in high-risk patient subsets.