Commissural alignment and the ACURATE neo2 transcatheter aortic valve: Impact on valve performance.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is increasingly being used to treat severe aortic stenosis in younger patients. Accordingly, lifetime management regarding future reintervention and coronary access is a concern. AIMS: To assess the impact of commissural alignment on ACURATE neo2 transcatheter aortic valve (TAV) performance. METHODS: COMALIGN-neo2 was an observational, retrospective study enrolling consecutive TAVR patients treated with the ACURATE neo2 (October 2021 to October 2022). The degree of commissural (mis)-alignment (CMA) with the native aortic valve commissures was determined and transvalvular gradient, effective orifice area, patient-prosthesis mismatch (PPM), and aortic regurgitation (AR) were assessed. RESULTS: Among 825 patients, the mean age was 80.7 years and 42% were female. Commissural alignment was achieved in 60% of cases; mild (26%), moderate (9%), and severe misalignment (5%) were found less often. Severe PPM occurred more frequently in patients with severe CMA (14.7%) compared to aligned valves (p = 0.034). By multivariate analysis, severe CMA (odds ratio [OR]: 3.12, 95% confidence interval [CI] [1.09-8.90]; p = 0.033) and lack of postdilatation (OR: 3.85, [1.33-11.1]; p = 0.012) were associated with severe PPM. Higher rates of ≥mild AR (51.4%) were found in TAVs implanted with severe CMA compared to aligned (34.3%), mildly (38.1%) or moderately (36.0%) misaligned TAVs (p = 0.030). Multivariate analysis identified severe CMA (OR: 2.05, [1.05-4.02]; p = 0.037) to be an independent predictor of ≥mild AR. CONCLUSIONS: COMALIGN-neo2 is the largest study to date assessing the impact of commissural alignment on acute TAV performance. Severe CMA with the ACURATE neo2 platform was associated with worse valve hemodynamics and increased risk for mild AR.

Age-related structural remodelling of the coronary circulation.

BACKGROUND: While it is broadly accepted that ageing is associated with impairment of coronary microvascular function, little is known about the underlying mechanisms. AIMS: We investigated age-related changes in coronary microvascular structure in patients with stable angina without epicardial coronary stenoses. METHODS: In an analysis of the IDEAL registry, a total of 165 vessels without coronary stenosis were interrogated with combined pressure/Doppler guidewires. We calculated diastolic microvascular conductance (DMVC) and backward expansion wave (BEW), and compared them between age tertiles. We calculated the prevalence of CMD, defined by reduced coronary flow reserve (CFR), and the prevalence of low BEW and low DMVC 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 showed 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] × 106 W m-2 s-1, p = 0.094). Older age was independently associated with lower BEW intensity (B: -0.10, 95% confidence interval [CI]: -0.17 to -0.09, p = 0.021) and DMVC (B: -0.25 95% CI: -0.45 to -0.09, p = 0.027). In patients with 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%, p = 0.010). CONCLUSIONS: Ageing is independently associated with structural microcirculatory remodeling that is reflected in BEW intensity and DMVC measurements, and with an increased prevalence of structural CMD. These results are important to understand non-obstructive mechanisms of myocardial ischemia in the elderly.

Coronary microvascular dysfunction is associated with impaired cognitive function: the Cerebral-Coronary Connection study (C3 study).

BACKGROUND: It remains unknown whether the presence of coronary microcirculatory dysfunction (CMD) correlates with its equivalent condition in the brain, cerebral small vessel disease (CSVD). The cerebral-coronary connection (C3), a prospective blinded study, investigated the prevalence of CMD in patients with coronary artery disease (CAD) and its association with CSVD and cognitive function. METHODS AND RESULTS: Patients with documented CAD fulfilling inclusion criteria underwent physiological assessment of epicardial vessels and the microcirculation using intracoronary pressure and Doppler. Coronary microcirculation-related indices included coronary flow reserve (CFR) and hyperaemic microvascular resistance. Brain magnetic resonance imaging, transcranial Doppler (TCD), and neurocognitive examination were performed. Overall, 67 patients were included in the study (mean age 66 years, 73% female). Patients with abnormal CFR (<2.0) (55.2%) showed higher burden of white-matter hyperintensities: 43.2 vs. 20.0% (P = 0.044). After statistical adjustment, low CFR was associated with lower grey matter volume (P = 0.024) and with parameters of white-matter microstructural damage in diffusion-tensor imaging (lower fractional anisotropy and higher mean diffusivity, P = 0.029 and P = 0.032, respectively). Low CFR was associated with higher resistive (P = 0.027) and pulsatility (P = 0.043) values on TCD, and worse neurocognitive test scores (lower mini mental state examination, P = 0.025, and slower Trail Making Test A, P = 0.034). CONCLUSIONS: Coronary microcirculatory dysfunction is frequent in patients with CAD and correlates with CSVD, abnormal cerebral flow haemodynamics, and significant cognitive impairment. These findings support the hypothesis that microvascular dysfunction in the heart and the brain are part of a single pathological process affecting microcirculation in patients with CAD. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT04131075.

Age-related changes in the coronary microcirculation influencing the diagnostic performance of invasive pressure-based indices and long-term patient prognosis.

OBJECTIVES: Investigate age-related changes in coronary microvascular function, its effect on hyperemic and non-hyperemic indices of stenosis relevance, and its prognostic implications. BACKGROUND: Evidence assessing the effect of age on fractional flow reserve (FFR), resting mean distal intracoronary pressure/mean aortic pressure (Pd/Pa), and microcirculatory function remains scarce. METHODS: This is a post hoc study of a large prospective international registry (NCT03690713) including 1134 patients (1326 vessels) with coronary stenoses interrogated with pressure and flow guidewires. Age-dependent correlations with functional indices were analyzed. Prevalences of FFR, resting Pd/Pa, and coronary flow reserve (CFR) classification agreement were assessed. At 5 years follow-up, the relation between resting Pd/Pa, CFR, and their age-dependent implications on FFR-guided percutaneous coronary intervention (PCI) deferral (deferred if FFR > 0.80) were investigated using vessel-oriented composite outcomes (VOCO) composed of death, myocardial infarction, and repeated revascularization. RESULTS: Age correlated positively with FFR (r = 0.08, 95% confidence interval [CI]: 0.03 to 0.13, p = 0.005), but not with resting Pd/Pa (r = -0.03, 95% CI:-0.09 to 0.02, p = 0.242). CFR correlated negatively with age (r = -0.15, 95% CI: -0.21 to -0.10, p < 0.001) due to a significant decrease in maximal hyperemic flow in older patients. Patients over 60 years of age with FFR-guided deferred-PCI abnormal resting Pd/Pa or abnormal CFR had increased risk of VOCO (hazard ratio [HR]: 2.10, 95% CI: 1.15 to 4.36, p = 0.048; HR: 2.46, 95% CI:1.23 to 4.96, p = 0.011; respectively). CONLUSIONS: Aging is associated with decrease in microcirculatory vasodilation, as assessed with adenosine-based methods like CFR. In patients older than 60 years in whom PCI is deferred according to FFR > 0.80, CFR and resting Pd/Pa have an incremental value in predicting future vessel-oriented patient outcomes.

Invasive evaluation of coronary microvascular dysfunction.

Coronary microvascular dysfunction (CMD) is a prevalent cause of ischemic heart disease and is associated with poorer quality of life and worse patient outcomes. Both functional and structural abnormalities of the microcirculation can generate ischemia in the absence of epicardial stenosis or worsen concomitant obstructive coronary artery disease (CAD). The invasive assessment of CMD allows for the evaluation of the entirety of the coronary vascular tree, from the large epicardial vessels to the microcirculation, and enables the study of vasomotor function through vasoreactivity testing. The standard evaluation of CMD includes vasomotor assessment with acetylcholine, as well as flow- and resistance-derived indices calculated with either thermodilution or Doppler guidewires. Tailored treatment based upon the information gathered from the invasive evaluation of CMD has been demonstrated to reduce the burden of angina; therefore, a thorough understanding of these procedures is warranted with the aim of improving the quality of life of the patient. This review summarizes the most widespread approaches for the invasive evaluation of CMD, with a focus on patients with ischemia and non-obstructive CAD.

Neurological outcomes of transcatheter aortic valve implantation with or without cerebral embolic protection devices: A meta-analysis.

INTRODUCTION: Cerebral embolic protection devices (CEPDs) are designed to prevent embolization of debris during transcatheter aortic valve implantation (TAVI). Current evidence from randomized clinical trials (RCTs) and observational studies is controversial. AIMS: The purpose of this meta-analysis was to study the influence of CEPDs on stroke, silent ischemic lesions and neurocognitive function. METHODS: A systematic search was conducted including RCTs or adjusted observational studies comparing TAVI with or without CEPDs. Pooled odds ratios, risk ratios or standardized mean differences with 95% confidence intervals were calculated using the inverse of variance method. Risk of bias sensitivity analyses and meta regression for CEPD type were also conducted. RESULTS: Five RCTs and five adjusted observational studies were included (n= 159,865). Mean age of the patients was 81.1 (SD 1.04) years in CEPDs and 81 (SD 1.86) in non-CEPD. The overall quality of evidence using the GRADE system for each endpoint was low to very low, mainly due to serious risk of bias, inconsistency and imprecision. Random effects meta-analysis detected no significant differences between CEPD and non-CEPD (OR= 0.74; 95% CI 0.51-1.07; P= 0.105; I2= 82.1%) for 30-day stroke. This finding was consistent in meta regression for CEPD type and subgroup analyses by study type and CEPD type. No significant differences between groups were observed in cerebral DW-MRI assessment and neurocognitive function evaluation. CONCLUSION: In the present meta- analysis of five RCTs and five adjusted observational studies, the use of a CEPD during TAVI was not associated with a significant benefit on 30- day stroke, total lesion volume per patient, number of ischemic lesions per patient and neurocognitive function assessments.

Clinical Profile and 30-Day Mortality of Invasively Managed Patients with Suspected Acute Coronary Syndrome During the COVID-19 Outbreak.

The COVID-19 pandemic severely disrupted cardiovascular care during the spring of 2020 in Europe. Our study analyzed the clinical profile, COVID-19 impact, and 30-day prognosis of invasively managed patients with acute coronary syndrome (ACS) compared to a historical cohort.All invasively managed ACS patients from March 1st to April 30th, 2020 were compared to a cohort from the same timeframe of 2019 (n = 316). COVID-19 confirmed cases were defined by a positive SARS-CoV-2 polymerase chain reaction (PCR) test (CoV+). The primary outcome was all-cause 30-day mortality and multivariable predictors of this outcome.A 40.4% reduction in ACS patients was noted (198 cases in 2019 to 118 in 2020), and 11% of 2020 ACS patients were CoV+. Baseline characteristics were similar between groups. There were significantly more in-hospital patients with ACS (15.3% versus 6.1%, P = 0.007), and fewer patients were found to have a culprit lesion (58.5% versus 74.2%, P = 0.004) in 2020 compared to 2019. Thirty-day mortality in 2020 (7%) was not different from that in 2019 (4.2%), P = 0.294, but it was significantly higher in CoV+ patients (23.1%) compared to that in negative SARS-CoV-2 PCR test (CoV-) patients (5%), P = 0.047, in the 2020 group. In the multivariate analysis, CoV+ was an independent mortality predictor (OR = 9.8, 95% CI = 1.48-64.78), along with the left ventricular ejection fraction (LVEF) (OR = 0.91, 95% CI = 0.86-0.97), P = 0.0006.This study found increased 30-day mortality of invasively managed CoV+ ACS patients compared to that of CoV- patients during the 2020 COVID-19 spring outbreak. In the multivariable analysis, a SARS-CoV-2 positive test was independently associated with 30-day mortality. Further investigations of the underlying physiopathological relations between COVID-19 and ACS are warranted.

Coronary Revascularization Guided With Fractional Flow Reserve or Instantaneous Wave-Free Ratio: A 5-Year Follow-Up of the DEFINE FLAIR Randomized Clinical Trial.

Importance: The differences between the use of fractional flow reserve (FFR) or instantaneous wave-free ratio (iFR) in the long term are unknown. Objective: To compare long-term outcomes of iFR- and FFR-based strategies to guide revascularization. Design, Setting, and Participants: The DEFINE-FLAIR multicenter study randomized patients with coronary artery disease to use either iFR or FFR as a pressure index to guide revascularization. Patients from 5 continents with coronary artery disease and angiographically intermediate severity stenoses who underwent hemodynamic interrogation with pressure wires were included. These data were analyzed from March, 13, 2014, through April, 27, 2021. MAIN OUTCOME MEASURES: Five-year major adverse cardiac events (MACE) (a composite of all-cause death, nonfatal myocardial infarction, and unplanned revascularization), as well as the individual components of the combined end point. Results: At 5 years of follow-up, no significant differences were found between the iFR (mean age [SD], 65.5 [10.8] years; 962 male [77.5%]) and FFR (mean age [SD], 65.2 [10.6] years; 929 male [74.3%]) groups in terms of MACE (21.1% vs 18.4%, respectively; hazard ratio [HR], 1.18; 95% CI, 0.99-1.42; P = .06). While all-cause death was higher among patients randomized to iFR, it was not driven by myocardial infarction (6.3% vs 6.2% in the FFR study arm; HR, 1.01; 95% CI, 0.74-1.38; P = .94) or unplanned revascularization (11.9% vs 12.2% in the FFR group; HR, 0.98; 95% CI, 0.78-1.23; P = .87). Furthermore, patients in whom revascularization was deferred on the basis of iFR or FFR had similar MACE in both study arms (17.9% in the iFR group vs 17.5% in the FFR group; HR, 1.03; 95% CI, 0.79-1.35; P = .80) with similar rates of the components of MACE, including all-cause death. On the contrary, in patients who underwent revascularization after physiologic interrogation, the incidence of MACE was higher in the iFR group (24.6%) compared with the FFR group (19.2%) (HR, 1.36; 95% CI, 1.07-1.72; P = .01). Conclusions and relevance: At 5-year follow up, an iFR based-strategy was not statistically different than an FFR strategy to guide revascularization in terms of MACE, nonfatal myocardial infarction, and unplanned revascularization. Trial Registration: ClinicalTrials.gov Identifier: NCT02053038.

Angiography-versus wire-based microvascular resistance index to detect coronary microvascular obstruction associated with ST-segment elevation myocardial infarction.

BACKGROUND: Microvascular obstruction (MVO) measured by cardiac magnetic resonance (CMR) after ST-segment elevation myocardial infarction (STEMI) has important prognostic implications. While invasive index of microvascular resistance (IMR) have been shown to predict the occurrence and extent of MVO, the role of the angiography-based microvascular resistance (Angio-IMR) for this purpose remains unknown. The present study aims to perform a head-to-head comparison of wire-based and angiography-derived microcirculatory resistance (IMR and Angio-IMR, respectively) for the detection of MVO. METHODS: Patients with a first STEMI and multivessel disease underwent CMR for detection of MVO, and angio-IMR and IMR measurements during PPCI and at 30 day follow up, both in STEMI culprit and non-culprit vessels. RESULTS: 58 patients were included (mean age 60.7 ± 9.9 years, 82% male). At the time of PPCI, angio-IMR and IMR exhibited significant correlation (r = 0.70, P < 0.001), and agreement (coefficient of agreement 0.58). Both indices showed good predictive value of MVO [Angio IMR: AUC 0.79 (95% CI: 0.667-0.928); IMR: AUC 0.70 (95% CI: 0.539-0.853); p = 0.15]. Angio-IMR 40 U and IMR 34 U were identified as best cut-offs for prediction of MVO. In non-culprit vessels, angio-IMR and IMR also correlated well (rho = 0.59, p < 0.001), with overall lower mean values compared to culprit vessels (Angio-IMR: 36 vs. 23; IMR: 39 vs. 22, p < 0.001 for both comparisons). CONCLUSION: Angio-IMR constitutes a valid alternative to wire-based IMR in predicting MVO in STEMI. Angio-IMR and IMR show a good correlation in the acute and subacute STEMI phases, both in culprit and non-culprit vessels.

Influence of procedural timing on the preventive yield of percutaneous patent foramen ovale closure.

BACKGROUND: The benefit of patent foramen ovale closure (PFOC) ≤9 months after a cryptogenic stroke has been demonstrated in several randomised clinical trials. There is, however, insufficient data to support PFOC in non-recent cryptogenic strokes. AIMS: The objective of the study was to evaluate the effectiveness of PFOC in relation to the time since the patient's most recent cryptogenic cerebrovascular event (CVE) or systemic embolism (SE). METHODS: We conducted a multicentre, retrospective cohort study with international participation, to assess the results of an early closure (EC, <9 months) for secondary prevention versus a delayed closure (DC, ≥9 months). Recurrence of CVE/SE following PFOC was evaluated as the primary endpoint. RESULTS: 496 patients were included (65% in the EC and 35% in the DC group). With the exception of a larger defect size in the DC group (tunnel width 6 (4-14) vs 12 (6-16) mm, p=0.005), similar clinical and echocardiographic baseline features were observed between the groups. No differences were observed regarding the type of devices used for PFOC, procedural success rate (99.4 in EC vs 98.8% DC group) and periprocedural complications (2.1% vs 0.8%). Median follow-up was 2.0 (1.2-4.2) years in the whole study population. Recurrence of CVE/SE (3.9% vs 2.6%, p=0.443), death (1.4% vs 1.0%, p=0.697), residual shunt 12 months after PFOC, or antithrombotic treatment strategy were comparable in both groups during follow-up. A subanalysis comparing very delayed PFOC (≥24 months) also showed no differences in recurrence (4.2% in the <24-month vs 3.4% in the ≥24-month group, p=0.770). CONCLUSION: Patients undergoing PFOC before and after 9 months after the index event had a comparable recurrence rate of CVE/SE. These findings suggest that PFOC might be recommended in cryptogenic CVE/SE which are more remote than 9 months.

Impact of coronary calcium morphology on intravascular lithotripsy.

BACKGROUND: Coronary calcification negatively impacts optimal stenting. Intravascular lithotripsy (IVL) is a new calcium modification technique. AIMS: We aimed to assess the impact of different calcium morphologies on IVL efficacy. METHODS: This was a prospective, multicentre study (13 tertiary referral centres). Optical coherence tomography (OCT) was performed before and after IVL, and after stenting. OCT-defined calcium morphologies were concentric (mean calcium arc >180°) and eccentric (mean calcium arc ≤180°). The primary outcomes were angiographic success (residual stenosis <20%) and the presence of fracture by OCT in concentric versus eccentric lesions. RESULTS: Ninety patients were included with a total of 95 lesions: 47 concentric and 48 eccentric. The median number of pulses was 60 (p=1.00). Following IVL, the presence of fracture was not statistically different between groups (79.0% vs 66.0% for concentric vs eccentric; p=0.165). The number of fractures/lesion (4.2±4.4 vs 2.3±2.8; p=0.018) and ≥3 fractures/lesion (57.1% vs 34.0%; p=0.029) were more common in concentric lesions. Angiographic success was numerically but not statistically higher in the concentric group (87.0% vs 76.6%; p=0.196). By OCT, no differences were noted in final minimum lumen area (5.9±2.2 mm2 vs 6.2±2.1 mm2; p=0.570), minimum stent area (5.9±2.2 mm² vs 6.25±2.4 mm2; p=0.483), minimum stent expansion (80.9±16.7% vs 78.2±19.8%), or stent expansion at the maximum calcium site (100.6±24.2% vs 95.8±27.3%) (p>0.05 for all comparisons of concentric vs eccentric, respectively). Calcified nodules were found in 29.5% of lesions; these were predominantly non-eruptive (57%). At the nodule site, dissection was more common than fracture with stent expansion of 103.6±27.2%. CONCLUSIONS: In this prospective, multicentre study, the effectiveness of IVL followed by stenting was not significantly affected by coronary calcium morphology.

A Prospective, Multicenter, Real-World Registry of Coronary Lithotripsy in Calcified Coronary Arteries: The REPLICA-EPIC18 Study.

BACKGROUND: Intravascular lithotripsy (IVL) has demonstrated effectiveness in the treatment of calcified lesions in selected patients with stable coronary disease. OBJECTIVES: The authors sought to assess the performance of coronary IVL in calcified coronary lesions in a real-life, all comers, setting. METHODS: The REPLICA-EPIC18 study prospectively enrolled consecutive patients treated with IVL in 26 centers in Spain. An independent core laboratory performed the angiographic analysis and event adjudication. The primary effectiveness endpoint assessed procedural success (successful IVL delivery, final diameter stenosis <20%, and absence of in-hospital major adverse cardiovascular events [MACE]). The primary safety endpoint measured freedom from MACE at 30 days. A predefined substudy compared outcomes between acute coronary syndrome (ACS) and chronic coronary syndrome (CCS) patients. RESULTS: A total of 426 patients (456 lesions) were included, 63% of the patients presenting with ACS. IVL delivery was successful in 99% of cases. Before IVL, 49% of lesions were considered undilatable. The primary effectiveness endpoint was achieved in 66% of patients, with similar rates among CCS patients (68%) and ACS patients (65%). Likewise, there were no significant differences in angiographic success after IVL between CCS and ACS patients. The rate of MACE at 30 days (primary safety endpoint) was 3% (1% in CCS and 5% in ACS patients [P = 0.073]). CONCLUSIONS: Coronary IVL proved to be a feasible and safe procedure in a "real-life" setting, effectively facilitating stent implantation in severely calcified lesions. Patients with ACS on admission showed similar angiographic success rates but showed a trend toward higher 30-day MACE compared with patients with CCS. (REPLICA-EPIC18 study [Registry of Coronary Lithotripsy in Spain]; NCT04298307).

Procedural and Technological Innovations Facilitating Ultra-low Contrast Percutaneous Coronary Interventions.

Ultra-low-dose contrast percutaneous coronary intervention (PCI) is a valuable approach in selected complex high-risk patients with renal failure. One of the objectives of ultra-low contrast PCI is to decrease the probability of developing postprocedural contrast-induced nephropathy (CIN), which predominately affects patients with baseline renal dysfunction. CIN is associated with poor clinical outcomes and increased healthcare-related costs. Another two clinical scenarios in which reduced dependence on contrast administration by the operator may contribute to improved safety are PCI in complex, high-risk indicated patients and in shock. In this review, we discuss the procedural techniques and recent technological innovations that enable ultra-low-dose contrast PCI to be performed in the cardiac cath lab.

Coronary Physiology as Part of a State-of-the-Art Percutaneous Coronary Intervention Strategy: Lessons from SYNTAX II and Beyond.

The use of coronary physiology allows for rational decision making at the time of PCI, contributing to better patient outcomes. Yet, coronary physiology is only one aspect of optimal revascularization. State-of-the-art PCI must also consider other important aspects such as intracoronary imaging guidance and specific procedural expertise, as tested in the SYNTAX II study. In this review, we highlight the technical aspects pertaining to the use of physiology as used in that trial and offer a glimpse into the future with emerging physiologic metrics, including functional coronary angiography, which have already established themselves as useful indices to guide decision making.

Transcatheter aortic valve durability: a contemporary clinical review.

Encouraged by randomized controlled trials demonstrating non-inferiority of transfemoral transcatheter aortic valve implantation (TAVI) compared to surgical aortic valve replacement (SAVR) across all surgical risk categories, there has been a dramatic increase in the use of TAVI in a younger patient cohort with severe aortic stenosis, endorsed by both European and American Cardiac Societies. However, the standard use of TAVI in younger, less co-morbid patients with a longer life expectancy can only be supported if there is sound data demonstrating long-term durability of transcatheter aortic valves (TAVs). In this article, we have reviewed available randomized and observational registry clinical data pertaining to TAV long-term durability, placing emphasis on trials and registries using the new standardized definitions of bioprosthetic valve dysfunction (BVD) and bioprosthetic valve failure (BVF). Despite inherent difficulties in interpreting the available data, the determination reached is that the risk of structural valve deterioration (SVD) is potentially lower after TAVI than SAVR at 5 to 10 years, and that the two treatment modalities have a similar risk of BVF. This supports the adoption of TAVI in younger patients evident in current practice. However, the routine use of TAVI in younger patients with bicuspid aortic valve stenosis should be cautioned due to insufficient long-term TAV durability data in this particular patient population. Finally, we highlight the importance of future research into the unique potential mechanisms that can potentially contribute to TAV degeneration.

Angiography-derived assessment of coronary microcirculatory resistance in patients with suspected myocardial ischaemia and non-obstructive coronary arteries.

BACKGROUND: Myocardial ischaemia with non-obstructive coronary arteries (INOCA) represents a challenging and frequent, but largely underdiagnosed, condition. AIMS: We aimed to investigate the feasibility and diagnostic value of angiography-derived coronary microcirculatory resistance in patients with INOCA syndrome. METHODS: This is an investigator-driven, prospective and blinded study. The diagnostic yield of angiography-derived index of coronary microcirculatory resistance (angio-IMR) was investigated against thermodilution-derived IMR (thermo-IMR) in patients with clinically indicated coronary angiography due to suspected myocardial ischaemia and angiographically normal or non-obstructive coronary arteries. The angio-IMR was derived from resting angiograms (contrast-flow angio-IMR [cAngio-IMR]) by an expert analyst blinded to the thermo-IMR. An independent, blinded, physiology core laboratory analysed the raw intracoronary physiology data and provided the final thermo-IMR values. RESULTS: A total of 104 patients (108 coronary vessels) were analysed after fulfilling predefined inclusion criteria. Most patients were female (67%). Obstructive epicardial disease was angiographically (percent diameter stenosis <50%) and physiologically (fractional flow reserve>0.80) ruled out in all cases. Median thermo-IMR and cAngio-IMR were 16.6 (12.7, 23.0) and 16.8 (12.8, 23.1) units, respectively (median difference -0.31, 95% confidence interval: -1.53 to 1.00; p=0.654). cAngio-IMR showed good correlation (Pearson coefficient 0.76; p<0.001), agreement (mean bias 0.4), discriminatory power (area under the curve from the receiver operator characteristics 0.865; p<0.001) and accuracy (85%), compared to thermo-IMR (≥25 U). CONCLUSIONS: Evaluating coronary microcirculatory resistance in patients with INOCA syndrome using cAngio-IMR is feasible and accurate. By circumventing the need of coronary instrumentation and hyperaemic drugs, this method may facilitate the assessment of coronary microcirculatory resistance in patients with suspected INOCA. CLINICALTRIALS: gov: NCT04827498.

Comprehensive Assessment of Myocardial Ischemia Mechanisms in the Catheterization Laboratory: Design and Rationale of the Advanced Invasive Diagnosis Strategy for Patients with Stable Coronary Syndromes Undergoing Coronary ANGIOgraphy - the AID-ANGIO Study.

BACKGROUND: The diagnostic yield of invasive coronary angiography (ICA) to identify obstructive coronary artery disease in the context of chronic coronary syndromes (CCS) is very low. Furthermore, myocardial ischemia may have a non-obstructive origin, which cannot be detected by ICA. METHODS: AID-ANGIO is an observational, prospective, single-cohort, multicenter study, intended to evaluate the diagnostic yield of adopting a hierarchical strategy to assess obstructive and non-obstructive causes of myocardial ischemia in an all-comers population of patients with CCS at the time of ICA. The primary endpoint will investigate the additional diagnostic value of such strategy over angiography alone regarding the identification of ischemia-generating mechanisms. SUMMARY: An estimated sample of consecutive 260 patients with CCS referred by their clinicians to ICA, will be enrolled. In a stepwise manner, a conventional ICA will be performed as the initial diagnostic tool. Those patients with severe-grade stenosis will not undergo further assessment and an obstructive origin for myocardial ischemia will be assumed. Subsequently, the remainder with intermediate-grade stenosis will be assessed with pressure guidewires. Those with a negative result from physiological evaluation and those without epicardial coronary stenosis will be further studied for ischemia of non-obstructive origin, including microvascular dysfunction and vasomotor disorders. The study will be conducted in two steps. Firstly, ICA images will be displayed to patient's referring clinicians, who will be asked to identify the existent epicardial stenosis, their angiographic severity and probable physiological relevance, together with a tentative therapeutic approach. Then, the diagnostic algorithm will continue to be applied and, considering the whole gathered information, a definite therapeutic plan will be consensually established by the interventional cardiologist and patient's referring clinicians. CONCLUSION: The AID-ANGIO study will assess the additional diagnostic yield of a hierarchical strategy over ICA alone to identify ischemia-generating mechanisms in patients with CCS and its impact on therapeutic approach. Positive results of the study might support a streamlined invasive diagnostic process for patients with CCS.

Mid-Term Angiographic and Intracoronary Imaging Results Following Intracoronary Lithotripsy in Calcified Coronary Artery Disease: Results From Two Tertiary Referral Centres.

BACKGROUND: Intracoronary lithotripsy (IVL) is a safe and effective treatment for coronary calcification. Angiographic and intracoronary imaging follow-up have not yet been described. We aimed to describe the mid-term angiographic outcomes following IVL. METHODS: Patients successfully treated with IVL in two tertiary referral hospitals were included. Repeat angiography and intracoronary imaging was performed. Quantitative coronary angiography (QCA) and optical coherence tomography (OCT) analyses were performed using dedicated workstations. RESULTS: Twenty patients were included; mean age 67.1 years, left anterior descending artery 55 %. Median IVL balloon size was 3.0 mm and a median of 60 pulses were delivered per vessel. Percentage stenosis by QCA was 60 % [IQR 51-70] reducing to 20 % post stenting (p < 0.001). On OCT, 88.9 % had circumferential calcium. IVL resulted in fractures in 88.9 %. Resulting minimum stent expansion was 91.75 % [IQR 81.5-108]. Follow-up was at a median of 22.7 months [IQR16.4-25.5]. Percentage stenosis by QCA was 22.5 % [IQR 14-30] and not significantly different from the index procedure (p > 0.05). Minimum stent expansion by OCT was 85 % [IQR 72-97]. Late luminal loss was 0.15 mm [IQR -0.25 to 0.69]. Binary angiographic instent restenosis (ISR) was 10 % (2 of 20 patients). OCT demonstrated a predominantly homogenous neointimal pattern with high backscatter. CONCLUSION: Following successful IVL treatment, repeat angiography demonstrated preserved stent parameters in the majority of patients with favorable vascular healing properties by OCT. A binary restenosis rate of 10 % was observed. These results suggest durable results following IVL treatment of severe coronary calcification however larger studies are warranted.

Safety of coronary revascularization deferral based on fractional flow reserve and instantaneous wave-free ratio in patients with chronic kidney disease.

BACKGROUND: The safety of revascularization deferral according to pressure wire examination in patients with chronic kidney disease (CKD) has not been fully established. METHODS: From a retrospective cohort of 439 patients in whom revascularization was deferred after physiological assessment, we examined the incidence of patient-oriented composite endpoint (POCE: all-cause death, myocardial infarction [MI] and unplanned revascularization) in patients with CKD (estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m²) and without it. RESULTS: At 4 years of follow-up, the primary endpoint was met by 25.0% of patients with CKD and by 14.4% of patients without CKD (hazard ratio [HR] 1.56, 95% confidence interval [CI] 0.96-2.53, p = 0.071). The incidence of POCE was even higher in patients with an eGFR < 30 mL/min/1.73 m²: 43.8% (HR 3.10, 95% CI 1.08-8.92, p = 0.036). However, no differences were observed in the incidence of MI (4.2% vs. 4.4% in non-CKD), target vessel revascularization (5.8% vs. 5.9%), and target vessel MI (0.8% vs. 4.6%). CONCLUSIONS: Patients with CKD in whom pressure-wire evaluation led to deferral of coronary revascularization develop more POCE in the long term, compared to patients with normal renal function. However, the increase in POCE in patients with CKD was seldom related to deferred vessels, thus suggesting an epiphenomenon of an intrinsically higher cardiovascular risk of CKD patients.