Complete vs Culprit-Only Revascularization in Older Patients With Myocardial Infarction and High Bleeding Risk: A Randomized Clinical Trial.

Importance: Patients with high bleeding risk (HBR) have a poor prognosis, and it is not known if they may benefit from complete revascularization after myocardial infarction (MI). Objective: To investigate the benefit of physiology-guided complete revascularization vs a culprit-only strategy in patients with HBR, MI, and multivessel disease. Design, Setting, and Participants: This was a prespecified analysis of the Functional Assessment in Elderly MI Patients With Multivessel Disease (FIRE) randomized clinical trial data. FIRE was an investigator-initiated, open-label, multicenter trial. Patients 75 years or older with MI and multivessel disease were enrolled at 34 European centers from July 2019 through October 2021. Physiology treatment was performed either by angiography- or wire-based assessment. Patients were divided into HBR or non-HBR categories in accordance with the Academic Research Consortium HBR document. Interventions: Patients were randomized to either physiology-guided complete revascularization or culprit-only strategy. Main Outcomes and Measures: The primary outcome comprised a composite of death, MI, stroke, or revascularization at 1 year. Secondary outcomes included a composite of cardiovascular death or MI and Bleeding Academic Research Consortium (BARC) types 3 to 5. Results: Among 1445 patients (mean [SD] age, 81 [5] years; 917 male [63%]), 1025 (71%) met HBR criteria. Patients with HBR were at higher risk for the primary end point (hazard ratio [HR], 2.01; 95% CI, 1.47-2.76), cardiovascular death or MI (HR, 1.89; 95% CI, 1.26-2.83), and BARC types 3 to 5 (HR, 3.28; 95% CI, 1.40-7.64). The primary end point was significantly reduced with physiology-guided complete revascularization as compared with culprit-only strategy in patients with HBR (HR, 0.73; 95% CI, 0.55-0.96). No indication of interaction was noted between revascularization strategy and HBR status for primary and secondary end points. Conclusions and Relevance: HBR status is prevalent among older patients with MI, significantly increasing the likelihood of adverse events. Physiology-guided complete revascularization emerges as an effective strategy, in comparison with culprit-only revascularization, for mitigating ischemic adverse events, including cardiovascular death and MI. Trial Registration: ClinicalTrials.gov Identifier: NCT03772743.

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.

Impact of pre-admission physical activity on benefits of physiology-guided complete revascularization in older patients with myocardial infarction: insights from the FIRE trial.

AIMS: The present analysis from the Functional Assessment in Elderly Myocardial Infarction Patients with Multivessel Disease (FIRE) trial aims to explore the significance of pre-admission physical activity and assess whether the benefits of physiology-guided complete revascularization apply consistently to sedentary and active older patients. METHODS AND RESULTS: Patients aged 75 years or more with myocardial infarction (MI) and multivessel disease were randomized to receive physiology-guided complete revascularization or culprit-only strategy. The primary outcome was a composite of death, MI, stroke, or any revascularization within a year. Secondary endpoints included the composite of cardiovascular death or MI, as well as single components of the primary endpoint. Pre-admission physical activity was categorized into three groups: (i) absent (sedentary), (ii) light, and (iii) vigorous. Among 1445 patients, 692 (48%) were sedentary, whereas 560 (39%) and 193 (13%) performed light and vigorous physical activity, respectively. Patients engaging in light or vigorous pre-admission physical activity exhibited a reduced risk of the primary outcome compared with sedentary individuals [light hazard ratio (HR) 0.70, 95% confidence interval (CI) 0.55-0.91 and vigorous HR 0.14, 95% CI 0.07-0.91, respectively]. These trends were also observed for death, cardiovascular death, or MI. When comparing physiology-guided complete revascularization vs. culprit-only strategy, no significant interaction was observed for primary and secondary endpoints when stratified by sedentary or active status. CONCLUSION: In older patients with MI, pre-admission physical activity emerges as a robust and independent prognostic determinant. Physiology-guided complete revascularization stands out an effective strategy in reducing ischaemic adverse events, irrespective of pre-admission physical activity status. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT03772743.

The Functional Assessment in Elderly Myocardial Infarction Patients with Multivessel Disease (FIRE) trial has shown that physiology-guided complete revascularization reduces ischaemic adverse events in older patients with myocardial infarction (MI) and multivessel disease. Older patients who engage in light or vigorous physical activity before hospitalization for MI have a reduced risk of the primary composite outcome of death, MI, stroke, or ischaemia-driven revascularization. These benefits extend to all secondary cardiovascular outcomes as well. In the present subanalysis of the FIRE trial, we find that the positive prognosis associated with physiology-guided complete revascularization holds true even for patients with a sedentary lifestyle. This means that this type of revascularization can effectively reduce ischaemic adverse events in older patients with MI and multivessel disease, regardless of their physical activity levels.

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.

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.

Outpatient tricuspid regurgitation in the community: Clinical context and outcome.

BACKGROUND AND AIMS: Epidemiology of tricuspid regurgitation (TR) is poorly known and its burden in the community is challenging to define. We aimed to evaluate the prevalence of TR in a geographically defined area and its outcome, in particular overall survival and hospitalization, considering different clinical contexts. METHODS: We retrospectively analyzed consecutive outpatients referred between 2006 and 2013 for echocardiography and clinical evaluation. Patients with at least moderate TR were included and five different clinical settings were defined: concomitant significant left-sided valvular heart disease (LVHD-TR), heart failure (HF-TR), previous open-heart valvular surgery (postop-TR), pulmonary hypertension (PHTN-TR) and isolated TR (isolated-TR). Primary endpoint was a composite outcome of all-cause mortality or first hospitalization for HF. RESULTS: Of 6797 consecutive patients with a clinical visit and echocardiograms performed in routine practice in a geographically defined community, moderate or severe TR was found in 4.8% of patients (327) . During median follow-up of 6.1 years, TR severity was a determinant of event-free survival. Analyzed for each clinical subset, eight-year event-free survival was 87 ± 7% for postop-TR subgroup, 75 ± 7% for isolated-TR, 67 ± 6% for PHTN-TR, 58 ± 6% for LHVD -TR and 52 ± 11% for HF-TR. CONCLUSION: Moderate or more TR is a notable finding in the community and has impact on event-free survival in all clinical settings, with the worst outcomes when associated with relevant left-sided valvular heart disease and HF.

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.

#FullPhysiology: a systematic step-by-step guide to implement intracoronary physiology in daily practice.

#FullPhysiology is a comprehensive and systematic approach to evaluate patients with suspected coronary disease using PressureWire technology (Abbott Vascular, Santa Clara, CA, USA). This advancement in technology enables the investigation of each component of the coronary circulation, including epicardial, microvascular, and vasomotor function, without significantly increasing procedural time or technical complexity. By identifying the predominant physiopathology responsible for myocardial ischemia, #FullPhysiology enhances precision medicine by providing accurate diagnosis and facilitating tailored interventional or medical treatments. This overview aims to provide insights into modern coronary physiology and describe a systematic approach to assess epicardial flow-limiting disease, longitudinal physiological vessel analysis, microvascular and vasomotor dysfunction, as well as post- percutaneous coronary intervention (PCI) physiological results.

Integrated Assessment of Computational Coronary Physiology From a Single Angiographic View in Patients Undergoing TAVI.

BACKGROUND: Angiography-derived computational physiology is an appealing alternative to pressure-wire coronary physiology assessment. However, little is known about its reliability in the setting of severe aortic stenosis. This study sought to provide an integrated assessment of epicardial and microvascular coronary circulation by means of single-view angiography-derived physiology in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI). METHODS: Pre-TAVI angiographic projections of 198 stenotic coronary arteries (123 patients) were analyzed by means of Murray's law-based quantitative flow ratio and angiography microvascular resistance. Wire-based reference measurements were available for comparison: fractional flow reserve (FFR) in all cases, instantaneous wave-free ratio in 148, and index of microvascular resistance in 42 arteries. RESULTS: No difference in terms of the number of ischemia-causing stenoses was detected between FFR ≤0.80 and Murray's law-based quantitative flow ratio ≤0.80 (19.7% versus 19.2%; P=0.899), while this was significantly higher when instantaneous wave-free ratio ≤0.89 (44.6%; P=0.001) was used. The accuracy of Murray's law-based quantitative flow ratio ≤0.80 in predicting pre-TAVI FFR ≤0.80 was significantly higher than the accuracy of instantaneous wave-free ratio ≤0.89 (93.4% versus 77.0%; P=0.001), driven by a higher positive predictive value (86.9% versus 50%). Similar findings were observed when considering post-TAVI FFR ≤0.80 as reference. In 82 cases with post-TAVI angiographic projections, Murray's law-based quantitative flow ratio values remained stable, with a low rate of reclassification of stenosis significance (9.9%), similar to FFR and instantaneous wave-free ratio. Angiography microvascular resistance demonstrated a significant correlation (Rho=0.458; P=0.002) with index of microvascular resistance, showing an area under the curve of 0.887 (95% CI, 0.752-0.964) in predicting index of microvascular resistance ≥25. CONCLUSIONS: Angiography-derived physiology provides a valid, reliable, and systematic assessment of the coronary circulation in a complex scenario, such as severe aortic stenosis.

Prognostic value of ΔSYNTAX% score in octogenarians undergoing percutaneous coronary intervention.

OBJECTIVES: To verify whether incomplete revascularisation (IR), quantified using the rSYNTAX (Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) score and ΔSYNTAX% score, could predict short- (in-hospital mortality) and long-term outcomes (12-month mortality) in octogenarians undergoing percutaneous coronary intervention (PCI). METHODS & RESULTS: A retrospective analysis of 665 consecutive octogenarian patients presenting for PCI to a UK centre was performed. The baseline SYNTAX and rSYNTAX scores were assessed from angiographic images. ΔSYNTAX% score was calculated (ΔSYNTAX% = ((SYNTAX - rSYNTAX)/SYNTAX) × 100%)) to measure the relative completeness of revascularisation. Kaplan-Meier analysis assessed survival at 12 months by tertiles of rSYNTAX and ΔSYNTAX% scores. Increasing ΔSYNTAX% score was associated with reduced in-hospital mortality (P = 0.017), and improved survival benefit (log rank 14.8, P = 0.001) at 12 months. CONCLUSIONS: Enhancing the completeness of revascularisation in octogenarians selected to undergo PCI is associated with a lower in-hospital mortality and a survival benefit at 12 months.

Cost-effectiveness analysis of pressure-controlled intermittent coronary sinus occlusion in elective percutaneous coronary intervention.

OBJECTIVES: Percutaneous coronary intervention (PCI) represents the standard treatment for ST-elevated myocardial infarction, nevertheless, mortality and heart failures are frequent. Pressure-controlled intermittent coronary sinus occlusion (PiCSO) might reduce infarct size showing better patients' outcomes. We evaluated the cost-effectiveness of PCI+PiCSO compared to PCI from the National Healthcare Service (NHS) perspective in Italy. METHODS: A Markov model was developed to estimate life years (LYs), quality-adjusted life years (QALYs) and costs. A micro-costing analysis has been performed to inform the cost of PCI+PiCSO procedure. Sensitivity analyses were performed to test the robustness of the model results. RESULTS: Considering a willingness-to-pay threshold of 50,000€/QALY for the ICUR and a cost for PCI+PiCSO procedure of 14,654€, the innovative strategy may be cost-effective compared to PCI alone from the Italian NHS perspective, showing an ICUR of 17,530€/QALY (ICER 14,631€/LY) over a lifetime horizon; the probabilistic sensitivity analysis showed that PCI+PiCSO is cost-effective in 78.8% of simulations.Considering the above mentioned willingness-to-pay threshold, PCI+PiCSO strategy would be cost-effective over a lifetime horizon considering a cost for PCI+PiCSO procedure lower than 28,160€. CONCLUSION: PCI+PiCSO procedure may be considered a cost-effective technology that allows reducing cardiac events, while improving patients' life expectancy and quality of life.

Intracoronary physiology-guided percutaneous coronary intervention in patients with diabetes.

OBJECTIVE: The risk of vessel-oriented cardiac adverse events (VOCE) in patients with diabetes mellitus (DM) undergoing intracoronary physiology-guided coronary revascularization is poorly defined. The purpose of this work is to evaluate the risk of VOCE in patients with and without DM in whom percutaneous coronary intervention (PCI) was performed or deferred based on pressure-wire functional assessment. METHODS: This is a retrospective analysis of a multicenter registry of patients evaluated with fractional flow reserve (FFR) and/or non-hyperaemic pressure ratio (NHPR). Primary endpoint was a composite of VOCE including cardiac death, vessel-related myocardial infarction (MI), and ischemia-driven target vessel revascularization (TVR). RESULTS: A large cohort of 2828 patients with 3353 coronary lesions was analysed to assess the risk of VOCE at long-term follow-up (23 [14-36] months). Non-insulin-dependent-DM (NIDDM) was not associated with the primary endpoint in the overall cohort (adjusted Hazard Ratio [aHR] 1.18, 95% CI 0.87-1.59, P = 0.276) or in patients with coronary lesions treated with PCI (aHR = 1.30, 95% CI 0.78-2.16, P = 0.314). Conversely, insulin-dependent diabetes mellitus (IDDM) demonstrated an increased risk of VOCE in the overall cohort (aHR 1.76, 95% CI 1.07-2.91, P = 0.027), but not in coronary lesions undergoing PCI (aHR 1.26, 95% CI 0.50-3.16, P = 0.621). Importantly, in coronary lesions deferred after functional assessment IDDM (aHR 2.77, 95% CI 1.11-6.93, P = 0.029) but not NIDDM (aHR = 0.94, 95% CI 0.61-1.44, P = 0.776) was significantly associated with the risk of VOCE. IDDM caused a significant effect modification of FFR-based risk stratification (P for interaction < 0.001). CONCLUSION: Overall, DM was not associated with an increased risk of VOCE in patients undergoing physiology-guided coronary revascularization. However, IDDM represents a phenotype at high risk of VOCE.

Management of failed stenting of the unprotected left main coronary artery.

Percutaneous coronary intervention (PCI) is increasingly accepted as treatment for unprotected left main coronary artery (ULMCA) disease especially in those patients who are unsuitable for cardiac surgery. Treatment of any stent failure is associated with increased complexity and worse clinical outcomes when compared with de novo lesion revascularization. Intracoronary imaging has provided new insight into mechanisms of stent failure and treatment options have developed considerably over the last decade. There is paucity of evidence on the management strategy for stent failure in the specific setting of ULMCA. Treating any left main with PCI requires careful consideration and consequently treatment of failed stents in ULMCA is complex and provides unique challenges. Consequently, we provide an overview of ULMCA stent failure, proposing a tailored algorithm to guide best management and decision in daily clinical practice, with a special focus on intracoronary imaging characterization of causal mechanisms and specific technical and procedural considerations.

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.

Acute Response in the Noninfarcted Myocardium Predicts Long-Term Major Adverse Cardiac Events After STEMI.

BACKGROUND: Acute ST-segment elevation myocardial infarction (STEMI) has effects on the myocardium beyond the immediate infarcted territory. However, pathophysiologic changes in the noninfarcted myocardium and their prognostic implications remain unclear. OBJECTIVES: The purpose of this study was to evaluate the long-term prognostic value of acute changes in both infarcted and noninfarcted myocardium post-STEMI. METHODS: Patients with acute STEMI undergoing primary percutaneous coronary intervention underwent evaluation with blood biomarkers and cardiac magnetic resonance (CMR) at 2 days and 6 months, with long-term follow-up for major adverse cardiac events (MACE). A comprehensive CMR protocol included cine, T2-weighted, T2∗, T1-mapping, and late gadolinium enhancement (LGE) imaging. Areas without LGE were defined as noninfarcted myocardium. MACE was a composite of cardiac death, sustained ventricular arrhythmia, and new-onset heart failure. RESULTS: Twenty-two of 219 patients (10%) experienced an MACE at a median of 4 years (IQR: 2.5-6.0 years); 152 patients returned for the 6-month visit. High T1 (>1250 ms) in the noninfarcted myocardium was associated with lower left ventricular ejection fraction (LVEF) (51% ± 8% vs 55% ± 9%; P = 0.002) and higher NT-pro-BNP levels (290 pg/L [IQR: 103-523 pg/L] vs 170 pg/L [IQR: 61-312 pg/L]; P = 0.008) at 6 months and a 2.5-fold (IQR: 1.03-6.20) increased risk of MACE (2.53 [IQR: 1.03-6.22]), compared with patients with normal T1 in the noninfarcted myocardium (P = 0.042). A lower T1 (<1,300 ms) in the infarcted myocardium was associated with increased MACE (3.11 [IQR: 1.19-8.13]; P = 0.020). Both noninfarct and infarct T1 were independent predictors of MACE (both P = 0.001) and significantly improved risk prediction beyond LVEF, infarct size, and microvascular obstruction (C-statistic: 0.67 ± 0.07 vs 0.76 ± 0.06, net-reclassification index: 40% [IQR: 12%-64%]; P = 0.007). CONCLUSIONS: The acute responses post-STEMI in both infarcted and noninfarcted myocardium are independent incremental predictors of long-term MACE. These insights may provide new opportunities for treatment and risk stratification in STEMI.

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 index of microvascular resistance in takotsubo syndrome.

Coronary microvascular dysfunction (CMD) has been proposed as a key driver in the etiopathogenesis of Takotsubo syndrome (TTS), likely related to an "adrenergic storm" upon a susceptible microvascular circulation. The aim of our manuscript was to assess CMD in patients with TTS through the computation of the angiography-derived index of microcirculatory resistance (IMR) and its correlation with clinical presentation. Coronary angiograms of 41 consecutive TTS patients were retrospectively analyzed to derive angiography-based indices of CMD. Three indices (NH-IMRangio, AngioIMR and A-IMR) were calculated based on quantitative flow ratio. CMD was defined as an IMRangio value ≥ 25 units. The correlation between CMD and clinical presentation was then assessed. Median age was 76 years, 85.7% were women and mean left ventricular ejection fraction (LVEF) at first echocardiogram was 41.2%. Angiography-derived IMR was higher in left anterior descending artery (LAD) than circumflex and right coronary artery with either NH-IMRangio (53.9 ± 19.8 vs 35.8 ± 15.4 vs 40.8 ± 18.5, p-value < 0.001), AngioIMR (47.2 ± 17.3 vs 31.8 ± 12.2 vs 37.3 ± 13.7, p-value < 0.001) or A-IMR (52.7 ± 19 vs 36.1 ± 14.1 vs 41.8 ± 16.1, p-value < 0.001). All patients presented CMD with angiography-derived IMR ≥ 25 in at least one territory with each formula. Angiography-derived IMR in LAD territory was significantly higher in patients presenting with LVEF impairment (≤ 40%) than in those with preserved ventricular global function (NH-IMRangio: 59.3 ± 18.1 vs 46.3 ± 16.0 p-value = 0.030; AngioIMR: 52.9 ± 17.8 vs 41.4 ± 14.2, p-value = 0.037; A-IMR: 59.2 ± 18.6 vs 46.3 ± 17.0, p-value = 0.035). CMD assessed with angiography-derived IMR is a common finding in TTS and it is inversely correlated with LV function. The available formulas have a substantial superimposable diagnostic performance in assessing coronary microvascular function.

Functional Patterns of Coronary Disease: Diffuse, Focal, and Serial Lesions.

The physiological assessment of coronary lesions is influenced by the pattern and distribution of coronary artery disease (CAD), including focal lesions, serial lesions, diffuse disease, and mixed patterns. These various patterns of CAD impact the accuracy of pressure wire and angiography-derived physiology indexes, and diffuse disease in particular is an important determinant of the anticipated outcome of percutaneous coronary intervention. Therefore, identification of the physiological pattern of disease provides relevant information for the management of CAD and percutaneous coronary intervention procedural planning. At present, the classification of physiological patterns and its implications for the tailored management of a patient with CAD are poorly defined. This state-of-the-art review provides an overview of the available evidence on functional patterns of CAD with a special focus on their diagnostic and therapeutic implications. It also aims to provide clear definitions of physiological patterns of CAD based on the available evidence and expert opinion. A practical algorithm is provided to optimize the use of pressure wire and angiography-derived indexes of coronary physiology in the settings of focal, serial, and diffuse lesions, with the addition of intracoronary imaging in selected cases.