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Background: Patients with aortic stenosis may continue to have an increased risk of heart failure, arrhythmias, and death after successful transcatheter aortic valve implantation. Renin-angiotensin system inhibitors may be beneficial in this setting. We aimed to explore whether ramipril improves the outcomes of patients with aortic stenosis after transcatheter aortic valve implantation., Methods and Results: PROBE (Prospective Randomized Open, Blinded Endpoint) was a multicenter trial comparing ramipril with standard care (control) following successful transcatheter aortic valve implantation in patients with left ventricular ejection fraction >40%. The primary end point was the composite of cardiac mortality, heart failure readmission, and stroke at 1-year follow-up. Secondary end points included left ventricular remodeling and fibrosis. A total of 186 patients with median age 83 years (range 79-86), 58.1% women, and EuroSCORE-II 3.75% (range 3.08-4.97) were randomized to receive either ramipril (n=94) or standard treatment (n=92). There were no significant baseline, procedural, or in-hospital differences. The primary end point occurred in 10.6% in the ramipril group versus 12% in the control group ( P =0.776), with no differences in cardiac mortality (ramipril 1.1% versus control group 2.2%, P =0.619) but lower rate of heart failure readmissions in the ramipril group (3.2% versus 10.9%, P =0.040). Cardiac magnetic resonance analysis demonstrated better remodeling in the ramipril compared with the control group, with greater reduction in end-systolic and end-diastolic left ventricular volumes, but nonsignificant differences were found in the percentage of myocardial fibrosis., Conclusions: Ramipril administration after transcatheter aortic valve implantation in patients with preserved left ventricular function did not meet the primary end point but was associated with a reduction in heart failure re-admissions at 1-year follow-up., Registration: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT03201185.

Background: The FIRE trial (Functional Assessment in Elderly Myocardial Infarction Patients With Multivessel Disease) enrolled 1445 older (aged ≥75 years) patients with myocardial infarction and multivessel disease in Italy, Spain, and Poland. Patients were randomized to physiology-guided complete revascularization or treatment of the only culprit lesion. Physiology-guided complete revascularization significantly reduced ischemic adverse events at 1 year. This prespecified analysis investigated the changes between the 2 study groups in angina status, quality of life, physical performance, and frailty., Methods: Patients underwent validated scales at hospital discharge (baseline) and 1 year later. Angina status was evaluated using the Seattle Angina Questionnaire, health-related quality of life by EQ visual analog scale, physical performance by short physical performance battery, and frailty by the clinical frailty scale. Mixed models for repeated measures analysis were used to study the association between the treatment arms, time, and scales., Results: Baseline and 1-year Seattle Angina Questionnaire, EQ visual analog scale, short physical performance battery, and clinical frailty scale were collected in around two-thirds of the entire FIRE study population. The mean age was 80.9±4.6 years (female sex, 35.9%). Overall, 35.3% were admitted for ST-segment-elevation myocardial infarction, whereas the others were admitted for non-ST-segment-elevation myocardial infarction. Physiology-guided complete revascularization, compared with culprit-only revascularization, was associated with greater improvement in terms of angina status (Seattle Angina Questionnaire summary score, 7.3 [95% CI, 6.1-8.6] points), health-related quality of life (EQ visual analog scale, 6.2 [95% CI, 4.4-8.1] points), and physical performance (short physical performance battery, 1.1 [95% CI, 0.9-1.3] points). After 1 year, patients randomized to culprit-only revascularization experienced a deterioration in frailty status (clinical frailty scale, 0.2 [95% CI, 0.1-0.3] points), which was not observed in patients randomized to physiology-guided complete revascularization., Conclusions: The present analysis suggested that a physiology-guided complete revascularization is associated with consistent benefits in terms of angina status, quality of life, physical performance, and the absence of further deterioration of the frailty status., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03772743., Competing Interests: Dr Campo received research grants and personal fees from Abbott Vascular and personal fees from Menarini, Amgen, and Sanofi, outside the submitted work. Dr Biscaglia received personal fees from Abbott Vascular, outside the submitted work. The other authors report no conflicts.

Introduction and Objectives: Catheter-directed therapy (CDT) for acute pulmonary embolism (PE) is an emerging therapy that combines heterogeneous techniques. The aim of the study was to provide a nationwide contemporary snapshot of clinical practice and CDT-related outcomes., Methods: This Investigator-initiated multicenter registry aimed to include consecutive patients with intermediate-high risk (IHR) or high-risk (HR), acute PE eligible for CDT. The primary outcome of the study was in-hospital all-cause death., Results: A total of 253 patients were included, of whom 93 (36.8%) had HR-PE, and 160 (63.2%) had IHR-PE with a mean age of 62.3±15.1 years. Local thrombolysis was performed in 70.8% and aspiration thrombectomy in 51.8%, with 23.3% of patients receiving both. However, aspiration thrombectomy was favored in the HR-PE cohort (80.6% vs 35%; P<.001). Only 51 patients (20.2%) underwent CDT with specific PE devices. The success rate for CDT was 90.9% (98.1% of IHR-PE patients vs 78.5% of HR-PE patients, P<.001). In-hospital mortality was 15.5%, and was highly concentrated in the HR-PE patients (37.6%) and significantly lower in IHR-PE patients (2.5%), P<.001. Long-term (24-month) mortality was 40.2% in HR-PE patients vs 8.2% in IHR-PE patients (P<.001)., Conclusions: Despite the high success rate for CDT, in-hospital mortality in HR-PE is still high (37.6%) compared with very low IHR-PE mortality (2.5%)., (Copyright © 2023 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Twitch-independent tension has been demonstrated in cardiomyocytes, but its role in heart failure (HF) is unclear. We aimed to address twitch-independent tension as a source of diastolic dysfunction by isolating the effects of chamber resting tone (RT) from impaired relaxation and stiffness., Methods: We invasively monitored pressure-volume data during cardiopulmonary exercise in 20 patients with hypertrophic cardiomyopathy, 17 control subjects, and 35 patients with HF with preserved ejection fraction. To measure RT, we developed a new method to fit continuous pressure-volume measurements, and first validated it in a computational model of loss of cMyBP-C (myosin binding protein-C)., Results: In hypertrophic cardiomyopathy, RT (estimated marginal mean [95% CI]) was 3.4 (0.4-6.4) mm Hg, increasing to 18.5 (15.5-21.5) mm Hg with exercise ( P <0.001). At peak exercise, RT was responsible for 64% (53%-76%) of end-diastolic pressure, whereas incomplete relaxation and stiffness accounted for the rest. RT correlated with the levels of NT-proBNP (N-terminal pro-B-type natriuretic peptide; R=0.57; P =0.02) and with pulmonary wedge pressure but following different slopes at rest and during exercise (R 2 =0.49; P <0.001). In controls, RT was 0.0 mm Hg and 1.2 (0.3-2.8) mm Hg in HF with preserved ejection fraction patients and was also exacerbated by exercise. In silico, RT increased in parallel to the loss of cMyBP-C function and correlated with twitch-independent myofilament tension (R=0.997)., Conclusions: Augmented RT is the major cause of LV diastolic chamber dysfunction in hypertrophic cardiomyopathy and HF with preserved ejection fraction. RT transients determine diastolic pressures, pulmonary pressures, and functional capacity to a greater extent than relaxation and stiffness abnormalities. These findings support antimyosin agents for treating HF., Competing Interests: Disclosures None.

Introduction and Objectives: Pulmonary vascular remodeling is common among patients with advanced heart failure. Right heart catheterization is the gold standard to assess pulmonary hypertension, but is limited by indirect measurement assumptions, a steady-flow view, load-dependency, and interpretation variability. We aimed to assess pulmonary vascular remodeling with intravascular optical coherence tomography (OCT) and to study its correlation with hemodynamic data., Methods: This observational, prospective, multicenter study recruited 100 patients with advanced heart failure referred for heart transplant evaluation. All patients underwent right heart catheterization together with OCT evaluation of a subsegmentary pulmonary artery., Results: OCT could be performed and properly analyzed in 90 patients. Median age was 57.50 [interquartile range, 48.75-63.25] years and 71 (78.88%) were men. The most frequent underlying heart condition was nonischemic dilated cardiomyopathy (33 patients [36.66%]). Vascular wall thickness significantly correlated with mean pulmonary artery pressure, pulmonary vascular resistance, and transpulmonary gradient (R coefficient=0.42, 0.27 and 0.32 respectively). Noninvasive estimation of pulmonary artery systolic pressure, acceleration time, and right ventricle-pulmonary artery coupling also correlated with wall thickness (R coefficient of 0.42, 0.27 and 0.49, respectively). Patients with a wall thickness over 0.25mm had significantly higher mean pulmonary pressures (37.00 vs 25.00mmHg; P=.004) and pulmonary vascular resistance (3.44 vs 2.08 WU; P=.017)., Conclusions: Direct morphological assessment of pulmonary vascular remodeling with OCT is feasible and is significantly associated with classic hemodynamic parameters. This weak association suggests that structural remodeling does not fully explain pulmonary hypertension., (Copyright © 2022 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Background: The "weekend effect" has been associated with worse clinical outcomes. Our aim was to compare off-hours vs. regular-hours peripheral venoarterial extracorporeal membrane oxygenation (VA-ECMO) in cardiogenic shock patients., Methods: We analyzed in-hospital and 90-day mortality among 147 consecutive patients treated with percutaneous VA-ECMO for medical reasons between July 1, 2013, and September 30, 2022, during regular-hours (weekdays 8:00 a.m.-10:00 p.m.) and off-hours (weekdays 10:01 p.m.-7:59 a.m., weekends, and holidays)., Results: The median patient age was 56 years (interquartile range [IQR] 49-64 years) and 112 (72.6%) were men. The median lactate level was 9.6 mmol/L (IQR 6.2-14.8 mmol/L) and 136 patients (92.5%) had a Society for Cardiovascular Angiography and Interventions (SCAI) stage D or E. Cannulation was performed off-hours in 67 patients (45.6%). In-hospital mortality was similar in off-hours and regular hours (55.2% vs. 56.3%, p = 0.901), as was the 90-day mortality (58.2% vs. 57.5%, p = 0.963), length of hospital stay (31 days [IQR 16-65.8 days] vs. 32 days [IQR 18-63 days], p = 0.979), and VA-ECMO related complications (77.6% vs. 70.0%, p = 0.305)., Conclusions: Off-hours and regular-hours percutaneous VA-ECMO implantation in cardiogenic shock of medical cause have similar results. Our results support well-designed 24/7 VA-ECMO implantation programs for cardiogenic shock patients.

Objective: In patients with advanced heart failure, the intravascular optical coherence tomography (OCT) of subsegmental pulmonary artery measurements is correlated with right heart catheterization parameters. Our aim was to study the prognostic value of pulmonary OCT, right heart catheterization data, and the echocardiographic estimation of pulmonary pressure in patients studied for elective heart transplants., Methods: This research is an observational, prospective, multicenter study involving 90 adults with a one-year follow-up., Results: A total of 10 patients (11.1%) died due to worsening heart failure before heart transplantation, 50 underwent a heart transplant (55.6%), and 9 died in the first year after the transplant. The patients with and without events (mortality or heart failure-induced hospitalization) had similar data regarding echocardiography, right heart catheterization, and pulmonary OCT (with a median estimated pulmonary artery systolic pressure of 42.0 mmHg, interquartile range (IQR) of 30.3-50.0 vs. 47.0 mmHg, IQR 34.6-59.5 and p = 0.79, median pulmonary vascular resistance of 2.2 Wood units, IQR 1.3-3.7 vs. 2.0 Wood units, IQR 1.4-3.2 and p = 0.99, and a median pulmonary artery wall thickness of 0.2 ± 0.5 mm vs. 0.2 ± 0.6 mm and p = 0.87)., Conclusion: Pulmonary vascular remodeling (evaluated with echocardiography, right heart catheterization, and pulmonary OCT) was not associated with prognosis in a selected sample of adults evaluated for elective heart transplants. Pulmonary OCT is safe and feasible for the evaluation of these patients.

Important breakthroughs have considerably improved the outcomes of the percutaneous treatment of valvular heart diseases during the last decades. However, calcium deposition and progressive calcification of the left-sided heart valves present a challenge with prognostic implications that have not been addressed until recently. In the case of native mitral stenosis with no surgical options, a compelling need for tackling heavily calcified valves has led to the development of novel debulking techniques and to the use of aortic balloon-expandable bioprosthesis in the mitral position. In this section of the special issue "Mitral Valve Disease: State of the Art", we will review standard approaches and indications for the treatment of native mitral stenosis; summarize these two innovative solutions and their evidence, describing both procedures in a "step-by-step" fashion; and briefly comment on future directions in this field.

Background: Endothelial and microvascular dysfunction are frequently found in the non-culprit territory in patients with acute myocardial infarction (AMI). We aimed to determine whether an impaired coronary physiology of the non-culprit territory impacts long-term prognosis., Methods: FISIOIAM was an observational single-center study which included patients with AMI and another coronary artery lesion in a different territory. Intracoronary physiology of the non-culprit artery was analyzed early after primary percutaneous coronary intervention of the culprit artery, using fractional flow reserve (FFR), index of microcirculatory resistance (IMR), coronary flow reserve (CFR), endothelium-dependent CFR (eCFR) and macrovascular endothelial function . Patients were followed for a composite outcome of cardiovascular death, non-fatal myocardial infarction, coronary revascularization, and hospitalization due to heart failure or unstable angina., Results: A total of 84 patients (mean age: 62 ± 10 years) were included and functional abnormalities were detected in 93% of them. During follow-up (median of 1422 days; interquartile range, 1287-1634), 13.1% of the patients experienced at least one adverse cardiovascular event. Kaplan-Meier analysis revealed that patients with a CFR < 2 had a higher risk of events (Hazard Ratio, HR: 4.97, 95% Confidence Interval, CI, 1.32-18.75), whereas other parameters such as FFR, IMR, eCFR, and macrovascular endothelial function had no effect. A low CFR was an independent predictor of cardiovascular events, even after adjustment for age and traditional cardiovascular risk factors (adjusted HR: 6.62, 95% CI, 1.30-33.70)., Conclusions: The presence of abnormal coronary microvascular function as measured by a CFR < 2 in the non-culprit territory predicts future risk of adverse cardiovascular events., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Introduction and Objectives: Despite advances in treatment, patients with acute myocardial infarction (AMI) still exhibit unfavorable short- and long-term prognoses. In addition, there is scant evidence about the clinical outcomes of patients with AMI and coronavirus disease 2019 (COVID-19). The objective of this study was to describe the clinical presentation, complications, and risk factors for mortality in patients admitted for AMI during the COVID-19 pandemic., Methods: This prospective, multicenter, cohort study included all consecutive patients with AMI who underwent coronary angiography in a 30-day period corresponding chronologically with the COVID-19 outbreak (March 15 to April 15, 2020). Clinical presentations and outcomes were compared between COVID-19 and non-COVID-19 patients. The effect of COVID-19 on mortality was assessed by propensity score matching and with a multivariate logistic regression model., Results: In total, 187 patients were admitted for AMI, 111 with ST-segment elevation AMI and 76 with non-ST-segment elevation AMI. Of these, 32 (17%) were diagnosed with COVID-19. GRACE score, Killip-Kimball classification, and several inflammatory markers were significantly higher in COVID-19-positive patients. Total and cardiovascular mortality were also significantly higher in COVID-19-positive patients (25% vs 3.8% [ P < .001] and 15.2% vs 1.8% [ P  = .001], respectively). GRACE score > 140 (OR, 23.45; 95%CI, 2.52-62.51; P  = .005) and COVID-19 (OR, 6.61; 95%CI, 1.82-24.43; P  = .02) were independent predictors of in-hospital death., Conclusions: During this pandemic, a high GRACE score and COVID-19 were independent risk factors associated with higher in-hospital mortality. Full English text available from :www.revespcardiol.org/en., (© 2020 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Myocardial infarction (MI) in elderly patients is associated with unfavorable prognosis, and it is becoming an increasingly prevalent condition. The prognosis of elderly patients is equally impaired in ST-segment elevation (STE) or non-STE (NSTE), and it is markedly worsened by the common presence of multivessel disease (MVD). Given the limited evidence available for elderly patients, it has not yet been established whether, as for younger patients, a complete revascularization strategy in MI patients with MVD should be advocated. We present the design of a dedicated study that will address this research gap., Methods and Design: The FIRE trial is a prospective, randomized, international, multicenter, open-label study with blinded adjudicated evaluation of outcomes. Patients aged 75 years and older, with MI (either STE or NSTE), MVD at coronary artery angiography, and a clear culprit lesion will be randomized to culprit-only treatment or to physiology-guided complete revascularization. The primary end point will be the patient-oriented composite end point of all-cause death, any MI, any stroke, and any revascularization at 1 year. The key secondary end point will be the composite of cardiovascular death and MI. Quality of life and physical performance will be evaluated as well. All components of the primary and key secondary outcome will be tested also at 3 and 5 years. The sample size for the study is 1,400 patients., Implications: The FIRE trial will provide evidence on whether a specific revascularization strategy should be applied to elderly patients presenting MI and MVD to improve their clinical outcomes., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Approximately 30-50% of patients with ST-segment elevation acute myocardial infarction have multivessel disease. The physiology of the non-culprit artery (NCA) is complex and represents a challenge to physicians as, while these plaques are presumably stable, clinical data show that they frequently lead to major adverse cardiovascular events. In addition the presence of microvascular and endothelial dysfunction may have prognostic implications and interfere with current physiological indices for stenosis severity assessment. In this review we aim to summarize current methods to study the microcirculation, discuss the evidence available regarding the endothelium and the microvascular compartment of the NCA; the best strategies to perform a complete revascularization based on proven ischemia; real limitations associated to hyperemic stenosis indices; and the potential role of novel resting-indices in this specific acute context., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction and Objectives: Renal denervation is a percutaneous intervention for the treatment of resistant hypertension. Randomized studies have shown contradictory results on its efficacy. We present the results of a renal denervation registry for the treatment of resistant hypertension in real-life patients in Spain., Methods: Multicenter registry of consecutive patients with resistant hypertension treated with renal denervation in Spain between 2009 and 2018., Results: We included 125 patients (mean age, 56 years; 41% female; mean onset of hypertension 14±9 years previously). Office systolic and diastolic blood pressure and ambulatory blood pressure monitoring decreased 6 months after the intervention (166±20/95±16 to 149±22/87±16 mmHg and 151±14/89±12 to 143±15/84±11, both P <.0001). At 12 months, the blood pressure reduction was maintained and the number of antihypertensive drugs decreased from 4.9±1.2 to 4.4±1.5 (P=.0001). There were no significant procedure-related complications. The response rate to denervation at 1 year was 80%, but there were wide differences between centers., Conclusions: In patients with resistant hypertension, treatment with renal denervation was related to a decrease in office blood pressure and, more importantly, in ambulatory blood pressure monitoring, with a significant reduction in pharmacological treatment., (Copyright © 2019. Published by Elsevier España, S.L.U.)

Background: The assessment of vascular remodeling using optical coherence tomography (OCT) has been previously described in some types of pulmonary hypertension. However, evidence about its feasibility and clinical utility for evaluation of pulmonary arterial vasculopathy in advanced heart failure (HF) is scarce. Optical Coherence Tomography Observation of Pulmonary Ultra-Structural Changes in Heart Failure (OCTOPUS-CHF) study is designed to study the correlation between OCT-morphometric parameters and hemodynamic data measured or derived from right heart catheterization (RHC)., Methods: OCTOPUS-CHF is an observational, prospective, multicentre study aiming to recruit 100 patients with advanced HF referred for heart transplantation (HTx) evaluation. As part of such evaluation, all patients will undergo RHC in order to rule out severe pulmonary hypertension. After RHC, a Dragonfly™ OPTIS™ imaging catheter will be used to perform OCT evaluation of a right-lower-lobe pulmonary artery with a luminal diameter ≤ 5 mm. The primary objective is to study the correlation of OCT parameters with hemodynamic RHC data. The secondary objective is to determine if OCT parameters improve prognostic stratification., Conclusions: The OCTOPUS-CHF study will investigate the feasibility and clinical utility of pulmonary arterial vasculopathy evaluation with OCT in advanced HF patients and its correlation with hemodynamic RHC data. The ability of OCT-morphometric parameters to improve prognostic stratification will also be tested., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: The safety and feasibility of ambulatory PCI has been demonstrated in selected patients with "simple" lesions, but it is not well known whether it could be applied in more "complex" scenarios., Methods: Main objective is to assess the feasibility and safety of ambulatory complex PCI. Prospective multicentre registry of 1047 consecutive patients planned for ambulatory trans-radial PCI. Outcomes in patients with "complex angioplasty" (CA group: 313 (30%)) were analysed and compared with those of "simple angioplasty" (SA group: 734, 70%). The feasibility (% of patients finally discharged) and safety (MACE at 24 h and at 1 month) were compared between groups. We also analyse admissions, visits to the emergency department and minor vascular complications., Results: Feasibility was higher for SA (80.6% vs. 63.6%, OR 1.89, 95% CI 1.52-2.35, p < 0.001). Ambulatory PCI was very safe in both groups. In CA no MACE occurred at 24 h (vs. 0.17% SA) or 30 days (vs. 0.68% in SA). There were also no differences in re-admissions, visits to the emergency department or minor vascular complications (there was a non-significant tendency to higher rate of radial occlusion at 1 month in the CA group, 5.5% vs. 2.7%, p: 0.07)., Conclusions: The feasibility of ambulatory PCI in selected patients with complex lesions is lower than in simple lesions, however when it is possible, it is as safe as in selected patients with simple lesions., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Key Points: The right ventricle of the mammal heart is highly sensitive to the afterload imposed by a combination of the pulmonary circulation and the retrograde contribution of the left heart. Right ventricular afterload can be analysed in terms of pulmonary artery input impedance, which we were able to decompose as the result of the harmonic frequency responses of the pulmonary vessels and the left heart attached in series. Using spectral methods, we found a natural matching between the pulmonary vasculature and the left chambers of the heart. This coupling implies that the upstream transmission of the left heart frequency-response has favourable effects on the pulmonary tree. This physiological mechanism protects the right ventricle against acute changes in preload, and its impairment may be a relevant contribution to right ventricle dysfunction in pulmonary hypertension., Abstract: The right ventricle (RV) of the mammal heart is highly sensitive to the afterload imposed by the pulmonary circulation, and the left heart (LH) retrogradely contributes significantly to this vascular load. Transmission-line theory anticipates that the degree of matching between the frequency responses of the pulmonary vasculature and the LH should modulate the global right haemodynamic burden. We measured simultaneous high-fidelity flow (pulmonary artery) and pressure (pulmonary artery and left atrium) in 18 healthy minipigs under acute haemodynamic interventions. From these data, we decomposed the impedance spectra of the total right-circulation system into the impedance of the pulmonary vessels and the harmonic response of the LH. For frequencies above the first harmonic, total impedance was below the pulmonary impedance during all phases (P < 0.001; pooled phases), demonstrating a favourable effect of the LH harmonic response on RV pulsatile load: the LH harmonic response was responsible for a 20% reduction of pulse pulmonary artery pressure (P < 0.001 vs. a theoretical purely-resistive response) and a 15% increase of pulmonary compliance (P = 0.009). This effect on compliance was highest during acute volume overload. In the normal right circulation, the longitudinal impedance of the pulmonary vasculature is matched to the harmonic response of the LH in a way that efficiently reduces the pulmonary pulsatile vascular load. This source of interaction between the right and left circulations of mammals protects the RV against excessive afterload during acute volume transients and its disruption may be an important contributor to pulmonary hypertension., (© 2019 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Background: Approximately half of the patients presenting with ST-segment-elevation myocardial infarction (STEMI) have multivessel disease. The physiology of the nonculprit artery has not been thoroughly studied to date. We sought to characterize the coronary physiology of the nonculprit artery in the early phase after STEMI and determine the real prevalence of microvascular and endothelial dysfunction., Methods and Results: Patients with STEMI and another coronary artery lesion in a different territory were prospectively included in an observational single-center study. The protocol took place after revascularization of the culprit artery and comprised 3 phases: first, epicardial endothelial functional assessment using intracoronary acetylcholine; second, epicardial severity quantification based on fractional flow reserve, and nonendothelial microvascular function with coronary flow reserve and the index of microvascular resistance; third, endothelium-dependent microvascular function assessment based on the endothelial coronary flow reserve. Eighty-four patients were included. Mean age was 62±10 years, and 86.9% were men. Only 6 subjects had a nonpathological study: macrovascular endothelial dysfunction was present in 60% of the patients; fractional flow reserve ≤0.8, coronary flow reserve <2, and index of microvascular resistance >25 were evident in 34%, 37%, and 28% of the subjects respectively; and microvascular endothelial dysfunction (endothelial coronary flow reserve <1.5) was observed in 44%. In hospital-mortality was 0%, and no major complications occurred. At 6-month follow-up, there were no events related to the nonculprit artery., Conclusions: Microvascular and endothelial dysfunction in the nonculprit artery territory in patients with STEMI are very common. In 93% of the patients, we found functional abnormalities. Acetylcholine administration in the early phase post-STEMI in patients with multivessel disease is safe.

Objectives: The aim of this study was to determine the prognosis and specific complications of patients with prosthetic mitral valves (PMVs) undergoing transcatheter aortic valve replacement (TAVR)., Background: TAVR is performed relatively often in patients with PMVs, but specific risks are not well described., Methods: A multicenter analysis was conducted, including patients with severe symptomatic aortic stenosis who underwent TAVR at 10 centers. Patients' clinical characteristics and outcomes were evaluated according to the presence of a PMV., Results: The mean age of the study population (n = 2,414) was 81 ± 8 years, and 48.8% were men. A total of 91 patients (3.77%) had PMVs. They were more commonly women, younger, and had higher surgical risk. PMVs were implanted a median of 14 years before TAVR, and most patients had mechanical prostheses (73.6%). Eighty-six patients (94.5%) were on long-term vitamin K inhibitor therapy, and bridging antithrombotic therapy was administered in 59 (64.8%). TAVR device embolization occurred in 6.7% (vs. 3.3% in the non-PMV group; p = 0.127), in all instances when distance between the PMV and the aortic annulus was <7 mm. Mortality rates did not show a difference, but the rate of bleeding was higher in patients with PMV (24.2% vs. 16.1%; p = 0.041), even in those treated via the transfemoral approach (22.2% vs. 13.9%; p = 0.048). Indeed, bleeding complications, prior atrial fibrillation, chronic obstructive pulmonary disease, surgical risk, and New York Heart Association functional class were independent predictors of mortality., Conclusions: TAVR presents similar mortality irrespective of the presence of a PMV. However, patients with PMVs had higher bleeding risk that was independently associated with higher mortality. Risk for valve embolization was relatively high, but it occurred only in patients with PMV-to-aortic annulus distances <7 mm., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Introduction and Objectives: The exponential increase in coronary interventions plus the generalization of the radial approach represent the ideal scenario for starting outpatient angioplasty programs with the aim of reducing the costs while maintaining safety. This article reports data from a multicenter Spanish registry on fully ambulatory transradial angioplasty in selected patients for the first time., Methods: Prospective registry of elective outpatient transradial-ulnar angioplasty in patients with stable coronary disease. Patients were discharged the same day and were followed up at 24hours and 30 days. Safety and feasibility were analyzed., Results: Of the 723 patients included (76% male; age, 66.6±10.5 years), 533 (73.7%) were finally discharged after 4 to 12hours of surveillance. Among the remaining 190 (26.7%) patients, the most common reason for hospitalization was clinical instability after the procedure (60.5%). Independent predictors of admission were a history of peripheral artery disease, a higher baseline creatinine level, ad hoc performance of the procedure, and multivessel disease. At 24hours, there was 1 major adverse event in 1 patient (0.19%), who required hospitalization for major bleeding not related to vascular access. At 30 days, there were 3 major adverse events (0.56%): 1 subacute stent thrombosis, 1 revascularization of a vessel other than the treated vessel, and 1 minor stroke. Eight patients (1.5%) required admission at 30 days., Conclusions: The application of an outpatient transradial-ulnar angioplasty program with discharge after 4 to 12 hours' surveillance is safe and feasible in well-selected patients., (Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Objectives: The goal of this study was to determine the functional impact of paradoxical low-gradient aortic stenosis (PLGAS) and clarify whether the relevance of the valvular obstruction is related to baseline flow., Background: Establishing the significance of PLGAS is particularly challenging., Methods: Twenty symptomatic patients (77 ± 6 years of age; 17 female subjects) with PLGAS (mean gradient 28 ± 6 mm Hg; aortic valve area 0.8 ± 0.1 cm 2 ; ejection fraction 66 ± 7%) underwent cardiopulmonary exercise testing combined with right-heart catheterization and Doppler echocardiographic measurements., Results: Aortic valve area increased by 84 ± 23% (p < 0.001) and, in 70% of subjects, it reached values >1.0 cm 2 at peak exercise. Stroke volume index and blood pressure increased by 83 ± 56% and 26 ± 16%, respectively (both p < 0.0001). Peak oxygen consumption inversely correlated with the rate of increase in pulmonary capillary wedge pressure (PCWP) (PCWP slope: R = -0.61; p = 0.004). In turn, the PCWP slope was determined by changes in the valvular and vascular load but not by the rest of the indices of aortic stenosis. The functional impact of PLGAS was also not related to baseline flow. Agreement between Doppler echocardiography and the Fick technique was good up to intermediate workload., Conclusions: In symptomatic patients with PLGAS, the capacity to dynamically reduce vascular and valvular loads determines the effect of exercise on PCWP, which, in turn, conditions the functional status. A critically fixed valvular obstruction may not be the main mechanism of functional impairment in a large proportion of patients with PLGAS. Exercise echocardiography is suitable to study the dynamics of PLGAS., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Physicians cannot rely solely on the angiographic appearance of epicardial coronary artery stenosis when evaluating patients with myocardial ischemia. Instead, sound knowledge of coronary vascular physiology and of the methods currently available for its characterization can improve the diagnostic and prognostic accuracy of invasive assessment of the coronary circulation, and help improve clinical decision-making. In this article we summarize the current methods available for a thorough assessment of coronary physiology.

Background: Systemic arterial load impacts the symptomatic status and outcome of patients with calcific degenerative aortic stenosis (AS). However, assessing vascular properties is challenging because the arterial tree's behavior could be influenced by the valvular obstruction., Objectives: This study sought to characterize the interaction between valvular and vascular functions in patients with AS by using transcatheter aortic valve replacement (TAVR) as a clinical model of isolated intervention., Methods: Aortic pressure and flow were measured simultaneously using high-fidelity sensors in 23 patients (mean 79 ± 7 years of age) before and after TAVR. Blood pressure and clinical response were registered at 6-month follow-up., Results: Systolic and pulse arterial pressures, as well as indices of vascular function (vascular resistance, aortic input impedance, compliance, and arterial elastance), were significantly modified by TAVR, exhibiting stiffer vascular behavior post-intervention (all, p < 0.05). Peak left ventricular pressure decreased after TAVR (186 ± 36 mm Hg vs. 162 ± 23 mm Hg, respectively; p = 0.003) but remained at >140 mm Hg in 70% of patients. Wave intensity analysis showed abnormally low forward and backward compression waves at baseline, increasing significantly after TAVR. Stroke volume decreased (-21 ± 19%; p < 0.001) and correlated with continuous and pulsatile indices of arterial load. In the 48 h following TAVR, a hypertensive response was observed in 12 patients (52%), and after 6-month follow-up, 5 patients required further intensification of discharge antihypertensive therapy., Conclusions: Vascular function in calcific degenerative AS is conditioned by the upstream valvular obstruction that dampens forward and backward compression waves in the arterial tree. An increase in vascular load after TAVR limits the procedure's acute afterload relief., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Direct injury to the right coronary artery as a result of reparative operation on the tricuspid valve is a rare, probably underdiagnosed, but serious complication, which often involves dramatic clinical consequences. So far, only five cases have been described in the literature., Methods: We describe our single-center experience of this complication, and review and analyze relevant clinical and anatomic considerations related to this entity. Cases previously reported in the literature were also reviewed., Results: We describe four cases of direct injury to the right coronary artery in patients undergoing tricuspid annuloplasty (DeVega annuloplasty, 3; ring annuloplasty, 1) in our institution since 2005. All patients had right ventricular dilatation and severely dilated tricuspid annulus. Right coronary artery occlusion always occurred between the right marginal artery and the crux of the heart. Patients presented with hemodynamic or electrical instability. Coronary flow could be restored in 2 patients (percutaneously 1; surgically 1), both of whom finally survived, while it was not technically possible in the other 2 (1 died)., Conclusions: Occlusion of the right coronary artery in patients undergoing tricuspid annuloplasty is a rare complication that may occur if great annulus dilatation is present, thus altering both normal annular geometry and the relationship between the right coronary artery and the tricuspid annulus, particularly when DeVega annuloplasty is performed. Such an entity should be considered in the immediate postoperative period in an unstable patient, especially when complementary tests support this diagnosis. Prompt recognition and treatment can positively affect the patient's outcome, most often by means of an emergency revascularization strategy., (Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Introduction and Objectives: The treatment of severe symptomatic aortic stenosis has been revolutionized by the technique of transcatheter valve replacement. The purpose of this study was to present the outcomes and predictors of mortality in patients enrolled between 2010 and 2011 in the Transcatheter Aortic Valve Replacement National Registry., Methods: We collected 131 preprocedural, 31 periprocedural, and 76 follow-up variables, and analyzed the immediate implant success rate, the 30-day safety endpoint, and all-cause 30-day and mid-term (mean follow-up, 244 days) mortality., Results: From January 2010 to December 2011, a total of 1416 patients were included: 806 with Edwards valves and 610 with CoreValves. The implant success and 30-day mortality rates were 94% and 8%, respectively, without differences between types of valves and approaches. The 30-day safety endpoint and mid-term mortality rates were 14% and 16%, respectively, which were also similar between groups. The presence of comorbidities (renal failure, peripheral vascular disease, ejection fraction, and atrial fibrillation), the need for conversion to surgery, and at least moderate aortic regurgitation after transcatheter aortic valve implantation were identified as independent predictors of in-hospital and mid-term mortality., Conclusions: The prognosis of valve implant patients could be improved by including comorbidities in patient selection and by minimizing the degree of residual aortic regurgitation to optimize the results of the procedure., (Copyright © 2013 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.)

First randomized clinical trials have demonstrated that stem cell therapy can improve cardiac recovery after the acute phase of myocardial ischemia and in patients with chronic ischemic heart disease. Nevertheless, some trials have shown that conflicting results and uncertainties remain in the case of mechanisms of action and possible ways to improve clinical impact of stem cells in cardiac repair. In this paper we will examine the evidence available, analyze the main phase I and II randomized clinical trials and their limitations, discuss the key points in the design of future trials, and depict new directions of research in this fascinating field.