Coronary microvascular dysfunction in patients undergoing transcatheter aortic valve implantation.

OBJECTIVES: This study aimed to evaluate the prognostic value of coronary microvascular dysfunction (CMD) at long term after transcatheter aortic valve implantation (TAVI) and to explore its relationship with extravalvular cardiac damage (EVCD). Moreover, we sought to test the correlation between angiography-derived index of microcirculatory resistance (IMRangio) and invasive IMR in patients with aortic stenosis (AS). METHODS: This was a retrospective analysis of the Verona Valvular Heart Disease Registry (Italy) including 250 patients (83 (80-86) years, 53% female) with severe AS who underwent TAVI between 2019 and 2021. IMRangio was calculated offline using a computational flow model applied to coronary angiography obtained during the TAVI workup. CMD was defined as IMRangio ≥30 units.The primary endpoint was the composite of cardiovascular death and rehospitalisation for heart failure (HF). Advanced EVCD was defined as pulmonary circulation impairment, severe tricuspid regurgitation or right ventricular dysfunction.The correlation between IMR and IMRangio was prospectively assessed in 31 patients undergoing TAVI. RESULTS: The primary endpoint occurred in 28 (11.2%) patients at a median follow-up of 22 (IQR 12-30) months. Patients with CMD met the primary endpoint more frequently than those without CMD (22.9% vs 2.8%, p<0.0001). Patients with CMD were more frequently characterised by advanced EVCD (33 (31.4%) vs 27 (18.6%), p=0.024). CMD was an independent predictor of adverse outcomes (adjusted HR 6.672 (2.251 to 19.778), p=0.001) and provided incremental prognostic value compared with conventional clinical and imaging variables. IMRangio demonstrated fair correlation with IMR. CONCLUSIONS: CMD is an independent predictor of cardiovascular mortality and HF after TAVI.

Coronary physiology assessments: historical overview and future challenges.

Coronary physiological assessment has garnered extensive application in managing patients with coronary artery disease, encompassing both acute and chronic scenarios. Beyond the historical purpose as tool to define the hemodynamic significance of a given artery lesion, coronary artery physiology allows for a complete investigation of epicardial and microvascular circulation. The longitudinal assessment of the distribution pattern of coronary disease based on pressure wire technology provides crucial information to define the best management and procedural planning. Moreover, post-percutaneous coronary intervention physiology reassessment showed a strong association with clinical outcomes and, more importantly, it can spot residual pressure gradients potentially amenable to further intervention and optimization. Growing evidence about the non-invasive angiography-based indices helps to overcome the limitations of the use of intracoronary physiology. This review aims to provide an overview of different utilizations of coronary physiology offering a historical perspective with a particular focus on current challenges and future potential applications.

Characterisation of coronary microvascular dysfunction in patients with severe aortic stenosis undergoing TAVI.

BACKGROUND: Microvascular resistance reserve (MRR) is a validated measure of coronary microvascular function independent of epicardial resistances. AIMS: We sought to assess whether MRR is associated with adverse cardiac remodelling, a low-flow phenotype and extravalvular cardiac damage (EVCD) in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI). METHODS: Invasive thermodilution-based assessment of the coronary microvascular function of the left anterior descending artery was performed in a prospective, multicentre cohort of patients undergoing TAVI. Coronary microvascular dysfunction (CMD) was defined as the lowest MRR tertile of the study cohort. Haemodynamic measurements were performed at baseline and then repeated immediately after TAVI. EVCD and markers of a low-flow phenotype were assessed with echocardiography. RESULTS: A total of 134 patients were included in this study. Patients with low MRR were more frequently females, had a lower estimated glomerular filtration rate and a higher rate of atrial fibrillation. MRR was significantly lower in patients with advanced EVCD (median 1.80 [1.26-3.30] vs 2.50 [1.87-3.41]; p=0.038) and in low-flow, low-gradient AS (LF LG-AS) (median 1.85 [1.20-3.04] vs 2.50 [1.87-3.40]; p=0.008). Overall, coronary microvascular function tended to improve after TAVI and, in particular, MRR increased significantly after TAVI in the subgroup with low MRR at baseline. However, MRR was significantly impaired in 38 (28.4%) patients immediately after TAVI. Advanced EVCD (adjusted odds ratio 3.08 [1.22-7.76]; p=0.017) and a low-flow phenotype (adjusted odds ratio 3.36 [1.08-10.47]; p=0.036) were significant predictors of CMD. CONCLUSIONS: In this observational, hypothesis-generating study, CMD was associated with extravalvular cardiac damage and a low-flow phenotype in patients with severe AS undergoing TAVI.

Comprehensive Angiography-Derived Functional Assessment of Epicardial and Microvascular Coronary Disease. Correlation With Non-invasive Myocardial Stress Imaging.

Coronary angiography (CA) is poorly correlated with non-invasive myocardial stress imaging (NSI) and myocardial ischemia is often observed in patients with unobstructed coronary arteries. Moreover, the diagnostic performance of combined epicardial and microcirculatory angiography-derived physiological assessment and its correlation with NSI remains unknown. A total of 917 coronary vessels in 319 patients who underwent both CA and NSI were included in this multicenter observational retrospective analysis. Quantitative flow ratio (QFR) and angiography-derived index of microcirculatory resistance (IMRangio) analyses were performed to estimate coronary epicardial and microcirculatory function respectively. NSI demonstrated evidence of myocardial ischemia in 76% of the cases. IMRangio (36 [22 to 50] vs 29 [21 to 41], p <0.001) was significantly higher and QFR (0.92 [0.78 to 0.99] vs 0.97 [0.91 to 0.99], p <0.001) was significantly lower in vessels subtending ischemic territories. Overall, the diagnostic accuracy of QFR was moderate (area under the curve of receiver operating characteristic [AUCROC] 0.632 [95% confidence interval [CI] 0.589 to 0.674], p <0.0001) but it was higher in patients with normal microcirculatory function (AUCROC = 0.726 [95% CI 0.669 to 0.784], p <0.0001, p Value for AUCROC comparison = 0.009). Combined QFR/IMRangio assessment provided incremental diagnostic performance compared with the evaluation of epicardial or microcirculatory districts in isolation (p Value for AUC comparison <0.0001) and it was able to identify the predominant mechanism of myocardial ischemia in 77% of the patients with positive NSI. Our study suggests the value of a combined angiography-derived assessment of epicardial and microvascular function for the definition of the predominant mechanism of myocardial ischemia in patients with suspected coronary artery disease.

Angiography-Derived Index of Microcirculatory Resistance to Define the Risk of Early Discharge in STEMI.

BACKGROUND: Patients with ST-segment-elevation myocardial infarction but no coronary microvascular injury are at low risk of early cardiovascular complications (ECC). We aim to assess whether nonhyperemic angiography-derived index of microcirculatory resistance (NH-IMRangio) could be a user-friendly tool to identify patients at low risk of ECC, potentially candidates for expedited care pathway and early hospital discharge. METHODS: Retrospective analysis of 2 independent, international, prospective, observational cohorts included 568 patients with ST-segment-elevation myocardial infarction. NH-IMRangio was calculated based on standard coronary angiographic views with 3-dimensional-modeling and computational analysis of the coronary flow. RESULTS: Overall, ECC (a composite of cardiovascular death, cardiogenic shock, acute heart failure, life-threatening arrhythmias, resuscitated cardiac arrest, left ventricular thrombus, post-ST-segment-elevation myocardial infarction mechanical complications, and rehospitalization for acute heart failure or acute myocardial infarction at 30 days follow-up), occurred in 54 (9.3%) patients. NH-IMRangio was significantly correlated with pressure/thermodilution-based index of microcirculatory resistance (r=0.607; P<0.0001) and demonstrated good accuracy in predicting ECC (area under the curve, 0.766 [95% CI, 0.706-0.827]; P<0.0001). Importantly, ECC occurred more frequently in patients with NH-IMRangio ≥40 units (18.1% versus 1.4%; P<0.0001). At multivariable analysis, NH-IMRangio provided incremental prognostic value to conventional clinical, angiographic, and echocardiographic features (adjusted-odds ratio, 14.861 [95% CI, 5.177-42.661]; P<0.0001). NH-IMRangio<40 units showed an excellent negative predictive value (98.6%) in ruling out ECC. Discharging patients with NH-IMRangio<40 units at 48 hours after admission would reduce the total in-hospital stay by 943 days (median 2 [1-4] days per patient). CONCLUSIONS: NH-IMRangio is a valuable risk-stratification tool in patients with ST-segment-elevation myocardial infarction. NH-IMRangio guided strategies to early discharge may contribute to safely shorten hospital stay, optimizing resources utilization.

The role of invasive and non-invasive imaging technologies and calcium modification therapies in the evaluation and management of coronary artery calcifications.

The treatment of coronary artery disease (CAD) has advanced significantly in recent years due to improvements in medical therapy and percutaneous or surgical revascularization. However, a persistent obstacle in the percutaneous management of CAD is coronary artery calcification (CAC), which portends to higher rates of procedural challenges, post-intervention complications, and overall poor prognosis. With the advent of novel multimodality imaging technologies spanning from intravascular ultrasound to optical coherence tomography to coronary computed tomography angiography combined with advances in calcium debulking and modification techniques, CACs are now targets for intervention with growing success. This review will summarize the most recent developments in the diagnosis and characterization of CAC, offer a comparison of the aforementioned imaging technologies including which ones are most suitable for specific clinical presentations, and review the CAC modifying therapies currently available.

Periprocedural antithrombotic strategies in acute coronary syndromes undergoing percutaneous coronary intervention: Have we discarded bivalirudin too soon?

BACKGROUND: Publication of the BRIGHT-4 trial results has restimulated discussion about the optimal periprocedural antithrombotic strategy for patients undergoing percutaneous coronary intervention (PCI) with acute coronary syndromes (ACS). It is possible that variation in the infusion duration, may contribute to observed differences in safety-efficacy profiles of bivalirudin in this clinical setting. METHODS: Up to December 2022, randomized controlled trials (RCTs) comparing bivalirudin (either administered peri-procedurally or accompanied by postprocedural infusion) and heparin, both with or without GPI, were searched and entered in a frequentist network meta-analysis. Co-primary endpoints were trial-defined major adverse composite events (MACE) and major bleeding. Incident rate ratios (IRR) and 95 % confidence intervals (CI) were estimated. RESULTS: 10 RCTs (N = 57,137 patients/month) were included. As compared to heparin, prolonged bivalirudin infusion resulted in lower rates of major bleeding (IRR 0.58, 95 % CI 0.36-0.91), but there was no differences in MACE rates between these strategies. With regard to NACE, prolonged bivalirudin infusion yielded lower risk (IRR 0.86, 95 % CI 0.77-0.96), whereas both bivalirudin and heparin increased risk when coupled with GPI (IRR 1.24, 95 % CI 1.01-1.51 and IRR 1.24, 95 % CI 1.06-1.44, respectively). Both these combination strategies also increased minor bleeding rates (IRR 1.49, 95 % CI 1.16-1.93 and IRR 1.58, 95 % CI 1.29-1.95, respectively, for bivalirudin and heparin). Results were consistent across several sensitivity analyses. CONCLUSION: In patients with ACS undergoing PCI, procedural bivalirudin administration followed by prolonged infusion results in lower major bleeding rates, but there does not appear to be a difference in observed MACE.

Proof of concept study on coronary microvascular function in low flow low gradient aortic stenosis.

OBJECTIVES: We hypothesised that low flow low gradient aortic stenosis (LFLGAS) is associated with more severe coronary microvascular dysfunction (CMD) compared with normal-flow high-gradient aortic stenosis (NFHGAS) and that CMD is related to reduced cardiac performance. METHODS: Invasive CMD assessment was performed in 41 consecutive patients with isolated severe aortic stenosis with unobstructed coronary arteries undergoing transcatheter aortic valve implantation (TAVI). The index of microcirculatory resistance (IMR), resistive reserve ratio (RRR) and coronary flow reserve (CFR) were measured in the left anterior descending artery before and after TAVI. Speckle tracking echocardiography was performed to assess cardiac function at baseline and repeated at 6 months. RESULTS: IMR was significantly higher in patients with LFLGAS compared with patients with NFHGAS (24.1 (14.6 to 39.1) vs 12.8 (8.6 to 19.2), p=0.002), while RRR was significantly lower (1.4 (1.1 to 2.1) vs 2.6 (1.5 to 3.3), p=0.020). No significant differences were observed in CFR between the two groups. High IMR was associated with low stroke volume index, low cardiac output and reduced peak atrial longitudinal strain (PALS). TAVI determined no significant variation in microvascular function (IMR: 16.0 (10.4 to 26.1) vs 16.6 (10.2 to 25.6), p=0.403) and in PALS (15.9 (9.9 to 26.5) vs 20.1 (12.3 to 26.7), p=0.222). Conversely, left ventricular (LV) global longitudinal strain increased after TAVI (-13.2 (8.4 to 16.6) vs -15.1 (9.4 to 17.8), p=0.047). In LFLGAS, LV systolic function recovered after TAVI in patients with preserved microvascular function but not in patients with CMD. CONCLUSIONS: CMD is more severe in patients with LFLGAS compared with NFHGAS and is associated with low-flow state, left atrial dysfunction and reduced cardiac performance.

Angiography-Derived and Sensor-Wire Methods to Assess Coronary Microvascular Dysfunction in Patients With Acute Myocardial Infarction.

ST-segment elevation myocardial infarction (STEMI) treatment with primary percutaneous coronary intervention has dramatically impacted prognosis. However, despite satisfactory angiographic result, occurrence or persistence of coronary microvascular dysfunction after revascularization still affects long-term outcomes. The diagnostic and therapeutic value of understanding the status of coronary microcirculation is gaining attention in the cardiology community. However, current methods to assess microvascular function (namely, cardiac magnetic resonance and invasive wire-based coronary physiology) remain, at least in part, limited by technical and logistic aspects. On the other hand, angiography-based indices of microcirculatory resistance are emerging as valid and user-friendly tools with potential impact on prognostic stratification of patients with STEMI. This review provides an overview about conventional and novel methods to assess coronary microvascular dysfunction in patients with STEMI. The authors also provide a proposed procedural algorithm to facilitate optimal use of wire-based and angiography-based indices in the acute setting of STEMI.

Burden of ventricular arrhythmias at 12-lead 24-hour ambulatory ECG monitoring in middle-aged endurance athletes versus sedentary controls.

BACKGROUND: Whether prolonged and intense exercise increases the incidence of ventricular arrhythmias in middle-aged athletes remains to be established. DESIGN: Prospective, case-control. METHODS: We studied 134 healthy competitive athletes >30 years old (median age 45 (39-51) years, 83% males) who had been engaged in 9 ± 2 h per week of endurance sports activity (running, cycling, triathlon) for 13 ± 4 consecutive years. One hundred and thirty-four age- and gender-matched individuals served as controls. Both groups underwent 12-lead 24-h ambulatory electrocardiogram monitoring, which included a training session in athletes. Ventricular arrhythmias were evaluated in terms of number, complexity (i.e. couplet, triplet or non-sustained ventricular tachycardia), exercise-inducibility and morphology. RESULTS: Thirty-five (26%) athletes and 31 (23%) controls showed >10 isolated premature ventricular beats or ≥1 complex ventricular arrhythmia ( p = 0.53). Athletes with ventricular arrhythmias were older (median 48 versus 43 years old, p = 0.03) but did not differ with regard to hours of training and years of activity compared with athletes without ventricular arrhythmias. Ten (7%) athletes and six (5%) controls showed >500 premature ventricular beats/24 h ( p = 0.30): the most common ventricular arrhythmia morphologies were infundibular (six athletes and five controls) and fascicular (two athletes and one control). CONCLUSIONS: The prevalence of ventricular arrhythmias at 24-hour ambulatory electrocardiogram monitoring did not differ between middle-aged athletes and sedentary controls and was unrelated to the amount and duration of exercise. These findings do not support the hypothesis that endurance sports activity increases the burden of ventricular arrhythmias. Among individuals with frequent premature ventricular beats, the predominant ectopic QRS morphologies were consistent with the idiopathic and benign nature of the arrhythmia.

Ventricular Arrhythmias in Young Competitive Athletes: Prevalence, Determinants, and Underlying Substrate.

BACKGROUND: Whether ventricular arrhythmias (VAs) represent a feature of the adaptive changes of the athlete's heart remains elusive. We aimed to assess the prevalence, determinants, and underlying substrates of VAs in young competitive athletes. METHOD AND RESULTS: We studied 288 competitive athletes (age range, 16-35 years; median age, 21 years) and 144 sedentary individuals matched for age and sex who underwent 12-lead 24-hour ambulatory electrocardiographic monitoring. VAs were evaluated in terms of number, complexity (ie, couplet, triplet, or nonsustained ventricular tachycardia), exercise inducibility, and morphologic features. Twenty-eight athletes (10%) and 13 sedentary individuals (11%) showed >10 isolated premature ventricular beats (PVBs) or ≥1 complex VA (P=0.81). Athletes with >10 isolated PVBs or ≥1 complex VA were older (median age, 26 versus 20 years; P=0.008) but did not differ with regard to type of sport, hours of training, and years of activity compared with the remaining athletes. All athletes with >10 isolated PVBs or ≥1 complex VA had a normal echocardiographic examination; 17 of them showing >500 isolated PVBs, exercise-induced PVBs, and/or complex VA underwent additional cardiac magnetic resonance, which demonstrated nonischemic left ventricular late gadolinium enhancement in 3 athletes with right bundle branch block PVBs morphologic features. CONCLUSIONS: The prevalence of >10 isolated PVBs or ≥1 complex VA at 24-hour ambulatory electrocardiographic monitoring did not differ between young competitive athletes and sedentary individuals and was unrelated to type, intensity, and years of sports practice. An underlying myocardial substrate was uncommon and distinctively associated with right bundle branch block VA morphologic features.