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Acute coronary syndrome, cardiac surgery, and cardiac structural interventions are among the most common situations leading to allogeneic red blood cell consumption due to the prevalence of bleeding and anemia. The wide variability in the use of transfusions derives from the current lack of data, and the absence of strong evidence and clear guideline recommendations. The current approach is to avoid unnecessary blood transfusions and limit their use to life-saving conditions; this conservative strategy derives from often controversial and inconclusive results of observational and randomized studies where liberal and restricted red blood transfusion strategies seemed to have similar outcomes. The pivotal question for future research lies in elucidating whether blood transfusions function as an active participant or merely a catalyst in amplifying adverse events. The present review aims to summarize the current literature data and critically analyze the available evidence for red blood transfusions in cardiac interventions., Competing Interests: The authors declare no conflict of interest. Francesco Pelliccia is serving as of the Editorial Board members and Guest Editors of this journal, and Marco Zimarino is serving as one of the Editorial Board members of this journal. We declare that Francesco Pelliccia and Marco Zimarino had no involvement in the peer review of this article and have no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to Lloyd W. Klein and Antonio Mangieri., (Copyright: © 2024 The Author(s). Published by IMR Press.)

Objective: Bleeding is frequent during transcatheter aortic valve implantation (TAVI), especially when performed through a transapical approach (TA), and is associated with a worse prognosis. The present study aims to test the implication of red blood cell (RBC) transfusion and the optimal transfusion strategy in this context., Methods: Among 11,265 participants in the multicenter TRITAVI (Transfusion Requirements in Transcatheter Aortic Valve Implantation) registry, 548 patients (4.9%) who received TA-TAVI at 19 European centers were included. One-to-one propensity score matching was performed to reduce treatment selection bias and potential confounding among transfused versus non-transfused patients. The primary endpoint of the study was the 30-day occurrence of all-cause mortality., Results: 209 patients (38 %) received RBC transfusions. The primary endpoint occurred in 47 (8.6 %) patients. Propensity score matching identified 188 pairs of patients with and without RBC transfusion. In the propensity score-matched analysis, RBC transfusion was associated with increased 30-day mortality (HR 3.35, 95 % CI 1.51 - 7.39; p = 0.002). At multivariable cox regression analysis, RBC transfusion was an independent predictor of 30-day mortality (HR 3.07, 95 % CI 1.01-9.41, p = 0.048), as well as baseline ejection fraction (HR 0.96, 95 % CI 0.92-0.99, p = 0.043), and acute kidney injury (HR 3.95, 95 % CI 1.11-14.05, p = 0.034)., Conclusions: RBC transfusion is an independent predictor of short-term mortality in patients undergoing TA-TAVI, regardless of major bleeding.Clinical trial registration: https://www.clinicaltrials.gov Unique identifier: NCT03740425., 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., (© 2024 The Author(s).)

Background: Dialysis is a rare but serious complication after transcatheter aortic valve replacement. We analyzed the large multicenter TRITAVI (transfusion requirements in transcatheter aortic valve implantation) registry in order to develop and validate a clinical score assessing this risk., Methods and Results: A total of 10 071 consecutive patients were enrolled in 19 European centers. Patients were randomly assigned (2:1) to a derivation and validation cohort. Two scores were developed, 1 including only preprocedural variables (TRITAVIpre) and 1 also including procedural variables (TRITAVIpost). In the 6714 patients of the derivation cohort (age 82±6 years, 48% men), preprocedural factors independently associated with dialysis and included in the TRITAVIpre score were male sex, diabetes, prior coronary artery bypass graft, anemia, nonfemoral access, and creatinine clearance <30 mL/min per m 2 . Additional independent predictors among procedural features were volume of contrast, need for transfusion, and major vascular complications. Both scores showed a good discrimination power for identifying risk for dialysis with C-statistic 0.78 for TRITAVIpre and C-statistic 0.88 for TRITAVIpost score. Need for dialysis increased from the lowest to the highest of 3 risk score groups (from 0.3% to 3.9% for TRITAVIpre score and from 0.1% to 6.2% for TRITAVIpost score). Analysis of the 3357 patients of the validation cohort (age 82±7 years, 48% men) confirmed the good discrimination power of both scores (C-statistic 0.80 for TRITAVIpre and 0.81 for TRITAVIpost score). Need for dialysis was associated with a significant increase in 1-year mortality (from 6.9% to 54.4%; P =0.0001)., Conclusions: A simple preprocedural clinical score can help predict the risk of dialysis after transcatheter aortic valve replacement.

Background: Transcatheter left atrial appendage occlusion (LAAO) has emerged as an alternative treatment for stroke prevention in patients with atrial fibrillation (AF) at high risk of thromboembolism, who cannot tolerate long-term oral anticoagulation (OAC). Questions persist regarding effectiveness and safety of this treatment and the optimal post-interventional antithrombotic regimen after LAAO., Methods: We retrospectively gathered data from 428 patients who underwent percutaneous LAAO in 6 Italian high-volume centres, aimed at describing the real-world utilization, safety, and effectiveness of LAAO procedures, also assessing the clinical outcomes associated with different antithrombotic strategies., Results: Among the entire population, 20 (4.7 %) patients experienced a combination of pericardial effusion and periprocedural major bleeding: 8 (1.9 %) pericardial effusion, 1 (0.3 %) fatal bleeding, and 3 (0.7 %) non-fatal procedural major bleeding. Patients were discharged with different antithrombotic regimens: dual (DAPT) (27 %) or single (SAPT) (26 %) antiplatelet therapy, OAC (27 %), other antithrombotic regimens (14 %). Very few patients were not prescribed with antithrombotic drugs (6 %). At a medium 523 ± 58 days follow-up, 14 patients (3.3 %) experienced all-cause death, 6 patients (1.4 %) cardiovascular death, 3 patients (0.7 %) major bleeding, 10 patients (2.6 %) clinically relevant non-major bleeding, and 3 patients (0.7 %) ischemic stroke. At survival analysis, with DAPT as the reference group, OAC therapy was associated with better outcomes., Conclusions: Our findings confirm that LAAO is a safe procedure. Different individualized post-discharge antithrombotic regimens are now adopted, likely driven by the perceived thrombotic and hemorrhagic risk. The incidence of both ischemic and bleeding events tends to be low., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Daniele Sacchetta: payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Medtronic. Fabrizio Ricci: support for attending meetings and/or travel from Bayer. Antonio Dello Russo: consultant for Abbott and Medtronic. Giuseppe Patti: grant or contract from Abbott, Chiesi, Biotronic, Boston; consulting fees from Amgen, Sanofi, Novartis, Daichi Sankyo, Amarin, Aurora BioPharma, Malesci, PIAM, Boheringer Ingheleim, Bayer, Pfizer/BMS, Astra Zeneca, Biotronik, Terumo, Medtronic, Abbott, Edwards, Amicus, Novo Nordisk, Chiesi; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Amgen, Sanofi, Novartis, Daichi Sankyo, Amarin, Aurora BioPharma, Malesci, PIAM, Boheringer Ingheleim, Bayer, Pfizer/BMS, Astra Zeneca, Biotronik, Terumo, Medtronic, Abbott, Edwards, Amicus, Novo Nordisk, Chiesi; participation on a Data Safety Monitoring Board or Advisory Board for Amgen, Daichi Sankyo, Amarin, Aurora Bayer, Pfizer/BMS, MSD. Giulia Renda: grant or contract to my Institution from Bayer and Janssen/Bristol-Myers Squibb (not related to the manuscript); speaker/consultant/advisory board fees from Bayer, Boehringer Ingelheim, Menarini; support for attending meetings from Bayer and Daiichi Sankyo., (© 2024 The Author(s).)

Background: Optimal duration of dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI) of a bifurcation stenosis is still debated. We evaluated the impact of DAPT duration on clinical outcomes in all-comers patients undergoing bifurcation PCI included in the European Bifurcation Club (EBC) registry., Methods: We enrolled 2284 consecutive patients who completed at least 18 months follow-up. The cumulative occurrence of major adverse cardiac and cardiovascular events (MACCE), defined as a composite of overall-death, non-fatal myocardial infarction (MI), target vessel revascularization (TVR) and stroke were evaluated. Bleedings classified as Bleeding Academic Research Consortium (BARC) ≥3 were evaluated too., Results: Patients were divided into 3 groups: short DAPT (<6-months, N.=375); standard DAPT (≥6-months but ≤12-months, N.=636); prolonged DAPT (>12-months, N.=1273). At 24 months follow-up MACCE-free survival was significantly lower in short DAPT patients (Log-Rank: 45.23, P for trend <0.001). MACCE occurred less frequently in the prolonged DAPT group (148 [11.6%]) as compared with both the short (83 [22.1%] HR: 0.48 [0.37-0.63], P<0.001) and standard DAPT groups (137 [21.5%] HR:0.51 [0.41-0.65], P<0.001). These differences remain after propensity score adjustment (respectively, HR: 0.27 [0.20-0.36] and HR: 0.44 [0.34-0.57]). Such finding was consistent in patients presenting with both acute and chronic coronary syndromes. BARC≥3 bleedings were 0.3% in the standard DAPT, 1.6% in short and 1.9% in prolonged DAPT groups., Conclusions: In the "real-world" EBC registry of patients undergoing PCI of coronary artery bifurcation stenosis, a prolonged DAPT duration was associated with a significantly lower risk of MACCE and a potential increased risk of major bleedings.

Aims: To identify the best strategy to achieve complete revascularization (CR) in patients with ST-elevation myocardial infarction (STEMI) and multi-vessel disease (MVD)., Methods and Results: We systematically reviewed the literature for randomized controlled trials (RCTs) comparing IRA-only PCI and CR guided by angiography or fractional flow reserve (FFR) in MVD-STEMI. Both frequentist (classical) and Bayesian network meta-analysis were performed, including a comparative hierarchy estimation of the probability to reduce the primary composite endpoint of all-cause death and new myocardial infarction (MI). We identified 11 RCTs, including 8193 STEMI patients. Compared with IRA-only strategy, CR significantly reduced the primary endpoint (OR: 0.73; 95%CI0.55-0.97). We observed non-significant difference between angiography and FFR guidance in reducing the primary endpoint (OR: 0.73, 95% CI 0.35-1.57). The Bayesian probability analysis ranked angio-guided CR as the best intervention yielding lowest risk of all-cause death or new MI (SUCRA92%)., Conclusions: In patients with MVD-STEMI, CR is associated with a reduction in all-cause mortality and new MI compared with IRA-only PCI. Angio-guided CR is associated with the lowest risk of all-cause death or new MI, therefore the role of FFR-guidance in this setting is questionable., Condensed Abstract: Both frequentist and Bayesian network meta-analysis were performed to compare infarct-related artery (IRA)-only percutaneous coronary intervention (PCI) and complete revascularization (CR) guided by angiography or fractional flow reserve (FFR) in multivessel disease (MVD) and acute ST-elevation myocardial infarction (STEMI). Eleven randomized controlled trials were identified, including 8193 STEMI patients. Compared with IRA-only strategy, CR significantly reduced the incidence of the composite endpoint of all-cause death and new myocardial infarction without significant difference in angio-guided and FFR-guided CR. The Bayesian probability analysis ranked angio-guided CR as the best intervention yielding lowest risk of the composite endpoint and, therefore the role of FFR-guidance in this setting is questionable., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Current evidence supports device-based transcatheter interventions for the management of patients with structural heart disease, proving well their safety and efficacy; transcatheter aortic valve implantation (TAVI), transcatheter edge-to-edge repair (TEER) of mitral or tricuspid valves, and left atrial appendage occlusion (LAAO) are expanding their role in contemporary practice. Currently, guidelines recommend performing TAVI in 'Heart Valve Center' with interventional cardiology and institutional on-site cardiac surgery (iOSCS), while no site limitation has been defined for TEER and LAAO. The growing number of candidates for transcatheter interventions generates long waiting times with negative consequences on mortality, morbidity, hospitalization, and functional deterioration. Therefore, a debate on the feasibility of TAVI in centres without iOSCS has been set up. Data from randomized controlled trials and registries failed to document any difference in outcomes and in conversion rate to emergent surgical bailout in centres with or without iOSCS; on the other hand, a direct relationship with TAVI complications has been clearly documented for learning curve and centre volume. Therefore, the role of iOSCS for TAVI, as well as for other transcatheter interventions, should be carefully explored., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background and Aims: Cryptogenic stroke (CS) is associated with a high rate of recurrences and adverse outcomes at long-term follow-up, especially due to its unknown etiology that often leads to ineffective secondary prevention. Asymptomatic atrial fibrillation (AF) could play an important pathophysiological role. Some studies have pointed to left atrial (LA) and left ventricular (LV) systolic and diastolic dysfunction as surrogate markers of AF. The aim of the study is to evaluate the relationship between echocardiographic parameters of LA and LV function, and the occurrence of AF revealed by continuous ECG monitoring in a cohort of patients with CS., Methods: Single-center prospective cohort study. Seventy-two patients with CS with insertable cardiac monitors (ICM) underwent transthoracic echocardiography (TTE). TTE was focused on LA and LV function, including both standard and longitudinal strain-derived parameters. All detected AF episodes lasting more than 2 min were considered., Results: Continuous ECG monitoring revealed subclinical AF in 23 patients (32%) at an average of 6.5 months after ICM implantation. Many echocardiographic parameters, indicating LA volume and LV systolic/diastolic function, were significantly associated with the occurrence of AF, suggesting the worst atrial function in the AF group. Furthermore, multivariable regression analysis revealed that peak atrial contraction strain and left ventricular strain were independently associated with AF (adjusted OR = 0.72, CI 95% 0.48-0.90, p = 0.005, and adjusted OR = 0.69, CI 95% 0.46-0.95, p = 0.041, respectively)., Conclusion: In patients with CS, LA and LV strain analysis add predictive value for the occurrence of AF over clinical and morpho-functional echocardiographic parameters. Impaired booster pump strain and LV longitudinal strain are strong and independent predictors of AF., Competing Interests: FR: speaker/consultant fee from Boehringer Ingelheim, Daiichi Sankyo. SP: speaker/consultant fee from Astra Zeneca, Bayer. GR: speaker/consultant fee from Astra Zeneca, Bayer, BMS-Pfizer, Boehringer Ingelheim, Daiichi Sankyo. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bufano, Radico, D'Angelo, Pierfelice, De Angelis, Faustino, Pierdomenico, Gallina and Renda.)

Objectives: We aim to define whether the timing of microaxial left ventricular assist device (IMLVAD) implantation might impact on mortality in acute myocardial infarction (AMI) cardiogenic shock (CS) patients who underwent primary percutaneous coronary intervention (PPCI)., Background: Despite the widespread use of PPCI, mortality in patients with AMI and CS remains high. Mechanical circulatory support is a promising bridge to recovery strategy, but evidence on its benefit is still inconclusive and the optimal timing of its utilization remains poorly explored., Methods: We compared clinical outcomes of upstream IMLVAD use before PPCI versus bailout use after PPCI in patients with AMI CS. A systematic review and meta-analysis of studies comparing the two strategies were performed. Effect size was reported as odds ratio (OR) using bailout as reference group and a random effect model was used. Study-level risk estimates were pooled through the generic inverse variance method (random effect model)., Results: A total of 11 observational studies were identified, including a pooled population of 6759 AMI-CS patients. Compared with a bailout approach, upstream IMLVAD was associated with significant reduction of 30-day (OR = 0.65; 95% confidence interval [CI] = 0.51-0.82; I 2  = 43%, adjusted OR = 0.54; 95% CI = 0.37-0.59; I 2  = 3%, test for subgroup difference p = 0.30), 6-month (OR = 0.51; 95% CI = 0.27-0.96; I 2  = 66%), and 1-year (OR = 0.56; 95% CI = 0.39-0.79; I 2  = 0%) all-cause mortality. Incidence of access-related bleeding, acute limb ischemia and transfusion outcomes were similar between the two strategies., Conclusion: In patients with AMI-CS undergoing PPCI, upstream IMLVAD was associated with reduced early and midterm all-cause mortality when compared with a bailout strategy., (© 2022 Wiley Periodicals LLC.)

Background and Objectives: The absence of obstructive coronary artery disease (CAD) in patients with angina is common, but its prognosis is debated. We investigated outcomes of such patients to identify predictors of cardiovascular events., Methods: We selected 1014 patients with angina, evidence of myocardial ischemia at the electrocardiogram (ECG) exercise test or imaging stress tests, and nonobstructive CAD (absence of lumen diameter reduction ≥50%) at coronary angiography between 1999 and 2015. Note that, 1905 age- and risk factors-matched asymptomatic subjects served as "real-world" comparators. The primary endpoint was the occurrence of all-cause death or myocardial infarction., Results: At 6-years median follow-up (interquartile range, 3-9 years), the primary endpoint occurred in 53 patients (5.5%, 0.92/100 person-years). Besides similar event rates compared with asymptomatic subjects (hazard ratio [HR] 0.85, 95% confidence interval [CI] 0.62-1.15, p = 0.28), the index population showed a very heterogeneous prognosis. Patients with nonobstructive CAD (HR 1.85, 95% CI 1.02-3.37, p = 0.04, compared with "normal" coronary arteries) and ischemia at imaging tests (HR 2.11, 95% CI 1.07-4.14, p = 0.03, compared with ischemia detected only at the ECG exercise test) were at higher risk and those with both these components showing even >10-fold event rates as compared with the absence of both. Three-hundred and twenty-five patients (34%) continued to experience angina, 69 (7.2%) underwent repeat coronary angiography, and 14 (1.5%) had consequent coronary revascularization for atherosclerosis progression., Conclusion: Apart from the impaired quality of life, angina without obstructive CAD has an overall benign but very heterogeneous prognosis. Nonobstructive CAD and myocardial ischemia at imaging tests both confer a higher risk., (© 2021 The Association for the Publication of the Journal of Internal Medicine.)

Patent foramen ovale (PFO) has a high prevalence in general population and can be implicated in cryptogenic stroke among young people. Recent trials have shown that transcatheter PFO closure is superior to medical treatment in the secondary prevention of ischaemic stroke. The benefit in the reduction of stroke recurrence is particularly evident in patients who have documentation of a PFO with high-risk characteristics. Therefore, after the assessment of a clear causal relationship with the event, a thoughtful documentation of anatomic (height, length, presence of an aneurysmatic or a floppy atrial septum, a prominent Eustachian valve or Chiari's network, an acute angle with the inferior vena cava) and functional high-risk characteristics is mandatory., (Published on behalf of the European Society of Cardiology. © The Author(s) 2021.)

Background: Women present specific risks for transcatheter aortic valve replacement (TAVI) but there are scarce sex-based analysis. The aim of this study was to explore the risk of vascular/bleeding complications in females vs. males that underwent TAVI and the impact of red blood cell (RBC) transfusion., Methods: TRITAVI-Women is a retrospective analysis in 13 European institutions. Propensity score based on pairs of different sex was performed and global outcomes, vascular/bleeding risk factors were determined. Afterwards, the female population of the study was divided into two groups according to the need of RBC transfusion and the risk for mortality, AKI, MI, stroke at 30-days and at 1-year were compared as a combined endpoint (primary endpoint) and separately (secondary endpoints)., Results: The global study population included 5837 patients. Females presented more advanced NYHA class, chronic kidney disease, and baseline anemia. Vascular/bleeding complications and RBC transfusion were more common in women. However, 1-year mortality was lower for women in the matched cohort (8.1% vs.10.3%, p = 0.028). The need for RBC transfusion was an independent predictor of higher incidence of the primary endpoint at 30-day and 1-year. The main predictor of RBC transfusion in women was the presence of baseline anemia., Conclusions: Women present lower risk of mortality than men at 1-year follow up, but not at 30-day due to higher rates of vascular/bleeding complications. RBC transfusion was also more often required in women and was an independent predictor or poorer outcomes. The treatment of pre-existing anemia before TAVI might improve the short-term results in women., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: There is no consensus on the benefit of red blood cell (RBC) transfusion after transcatheter aortic valve replacement., Methods: The multicenter Transfusion Requirements in Transcatheter Aortic Valve Implantation (TRITAVI) registry retrospectively included patients after transfemoral transcatheter aortic valve replacement; propensity score-matching identified pairs of patients with and without RBC transfusion. The primary end point was 30-day mortality; nonfatal myocardial infarction, cerebrovascular accident, and stage 2 to 3 acute kidney injury at 30 days were secondary end points. We repeated propensity score-matching according to the hemoglobin nadir, hemoglobin drop, and in the subgroup of uncomplicated patients, without major vascular complications or major bleeding., Results: Among 2587 patients, RBC transfusion was administered in 421 cases (16%). The primary end point occurred in 104 (4.0%) patients, myocardial infarction in 9 (0.4%), cerebrovascular accident in 38 (1.5%), and acute kidney injury in 125 (4.8%) cases. In the 842 propensity-matched patients, RBC transfusion was associated with increased mortality (hazard ratio, 2.07 [95% CI, 1.06-4.05]; P =0.034) and acute kidney injury (hazard ratio, 4.35 [95% CI, 2.21-8.55]; P <0.001). Interaction testing between RBC transfusion and mortality was not statistically significant in the above-mentioned subgroups, and such association was not documented in the corresponding propensity score-matched cohorts. In the multivariable Cox proportional hazards regression model, major vascular complications ( P =0.044), major bleeding ( P =0.041), and RBC transfusion ( P =0.048) were independent correlates of 30-day mortality., Conclusions: RBC transfusion correlates with increased mortality and acute kidney injury early after transcatheter aortic valve replacement and is an independent predictor of 30-day mortality, irrespective of periprocedural major bleeding and vascular complications. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03740425.

Objectives: To define the impact of side branch (SB) lesion length on clinical outcomes after percutaneous coronary intervention (PCI) on bifurcation lesions., Background: The role of the SB lesion length remains questionable in PCI planning and its implication on clinical outcome is controversial., Methods: Data from the retrospective multicenter EBC-P2BiTO registry were analyzed. The primary endpoint was the occurrence of major adverse cardiac events (MACE), defined as the composite of cardiac death, myocardial infarction excluding periprocedural, or stent thrombosis at 13 months median follow-up (IQR 11-28). By using propensity scores for inverse probability of treatment weighting (IPTW), the comparison of treatment groups was adjusted to correct for potential confounding., Results: Among 1,252 patients, SB was normal in 489 (39%), diseased in 763 (61%) cases. MACE occurred in 68 patients (5.4%). The optimal discriminant SB lesion length for MACE was ≥10 mm, with an area under the curve of 0.71 (p < .01). The incidence of MACE was higher among patients with SB lesions ≥10 mm (8%) than with normal SB (4.1%) (hazard ratio [HR], 2.8; 95% confidence interval [CI], 1.5-5.3; p = .001, IPTW-adjusted) or SB lesions <10 mm (5.1%) (HR, 1.5; 95% CI, 1.1-3.3; p = .048, IPTW-adjusted), being similar between these last two groups., Conclusions: In bifurcation PCI, SB lesion length ≥ 10 mm identifies patients at higher risk of MACE than those with <10 mm SB lesions and those without SB disease, considering that no differences were observed among these last two groups. Careful planning is mandatory when approaching bifurcations with long SB lesions., (© 2020 Wiley Periodicals, Inc.)

Background and Aim: Isolated exercise-induced pulmonary hypertension (ExPH) associates with cardiovascular (CV) events in patients with left heart disease. We investigated its prognostic significance in scleroderma patients at risk for pulmonary arterial hypertension (PAH)., Methods: In 26 consecutive scleroderma female patients with either low ( n = 13) or intermediate probability ( n = 13) of pulmonary hypertension (PH) at rest, we evaluated, both at time 0 and 1 year, prognostic determinants of CV risk: onset or progression of heart failure/syncope; worsening of functional class; functional performance at the 6-minute walking test and at cardiopulmonary exercise test; right atrial area; and pericardial effusion. We assigned a severity score 1-3 to each prognostic determinant, derived an overall CV risk score, and its 0-1 year change. Isolated ExPH during the cardiopulmonary exercise test (CPET) was defined as absence of PH at rest, reduced peak VO 2 , VE/VCO 2 >30 at anaerobic threshold, reduced O 2 pulse, and ΔVO 2 /ΔW <9 mL/min/W. We then correlated ExPH at time 0 with clinical worsening (risk score increase >20% after 1 year)., Results: ExPH was strongly associated with clinical worsening compared to patients without ExPH ( p = 0.005). In patients without ExPH, none had > 20% increased CV risk score after 1 year. Conversely, about 50% of patients with ExPH had such an increase, suggesting a worsening of prognosis., Conclusions: Isolated ExPH associates with higher cardiovascular risk and thus clinical worsening in scleroderma patients. The assessment of ExPH by CPET can thus contribute to a better risk stratification and the planning of a more adequate follow-up.

Background: The optimal treatment of patients undergoing percutaneous coronary interventions (PCI) for lesions located at coronary bifurcations is still debated., Methods: Data on 5036 consecutive patients who underwent PCI on coronary bifurcation at 17 major coronary intervention centers between January 2012 and December 2014 were collected., Results: Follow-up at a median 18 months (IQR 11-28) was available for 4506 patients (89%). Major Adverse Cardiac Events (MACE) occurred in 395 patients (8.8%): cardiac death in 152 (3.4%), myocardial infarction, excluding periprocedural, in 156 (3.5%) and stent thrombosis in 110 cases (2.4%). At multivariable Cox regression, left ventricular ejection fraction ≤30% (P < 0.001), bail-out stenting (beyond a planned strategy of either single or double stenting) (P < 0.001), admission for an acute coronary syndrome (P < 0.001), age >66 years (P < 0.001), multivessel disease (P < 0.001) and diabetes (P < 0.001) were independently associated with MACE. Sensitivity analysis identified premature discontinuation of dual antiplatelet therapy (DAPT) (P < 0.001) and side branch (SB) lesion length ≥9 mm (P < 0.05) as additional independent predictors of MACE., Conclusions: Beyond traditional risk factors, multivessel disease, the length of the SB lesion, "bail-out" stenting and premature DAPT discontinuation are independent predictors of mid-term MACE after PCI of coronary bifurcations. This highlights the importance of a carefully planned PCI strategy and adequate therapy adherence to improve the clinical outcomes in these patients., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01967615., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Bifurcating coronary lesions are a very common challenge in interventional cardiology because of the technical complexity in their treatment, the risk of side branch occlusion and an overall worse outcome when compared to non-bifurcating lesions. The presence of calcifications represents further complexity due to the difficulty in device delivery and stent expansion as well as enhanced risk of side branch occlusion. Rotational and orbital atherectomy, scoring and cutting balloons, coronary lithoplasty are available tools which have been introduced over the last three decades to overcome such issue. Nevertheless, their application in different contexts of bifurcations presents specific caveats and the studies directed at comparing such techniques have never been expressly oriented in the subset of the bifurcating lesion. In this paper, we review these devices and their usefulness in bifurcations by analyzing consistent data from clinical trials, and we propose a practical algorithm for the treatment of severely calcified bifurcating lesions according to their anatomical features.

Aims: The long-term prognosis of angina in patients without obstructive coronary artery disease (CAD) is uncertain. To assess the incidence of long-term adverse outcomes in such patients., Methods and Results: We searched PubMed, Cochrane Library, the Embase database, and the Clinical Trials Registry for studies published in English until January 2017, assessing the composite primary outcome of all-cause death and non-fatal myocardial infarction using random-effects models to estimate pooled incidences. We identified 54 studies, reporting outcomes in overall 35 039 patients (mean age 56, male/female ratio 0.51, 99 770 person-years) with angina and no obstructive CAD. After a median follow-up of 5 years (interquartile range 3-7 years), the pooled incidence of the primary outcome was 0.98/100 person-years [95% confidence interval (CI) 0.77-1.19%], with considerable heterogeneity among studies (I2 = 91%, P < 0.001). The primary outcome was associated with prevalent dyslipidaemia (P = 0.016), diabetes (P = 0.035), and hypertension (P = 0.016). Studies enrolling patients with less-than-obstructive CAD showed a higher incidence of the primary outcome (1.32/100 person-years, 95% CI 1.02-1.62) compared with studies including only patients with 'entirely normal' coronary arteries (0.52/100 person-years, 95% CI 0.34-0.79, respectively; P < 0.01). The incidence of the primary outcome did not differ significantly between studies enrolling only patients with documented myocardial ischaemia and those studies enrolling patients regardless of presence of ischaemia. However, ischaemia documented by non-invasive imaging techniques was associated with a higher incidence of events (P = 0.02). Overall, these patients, however, suffered from a high incidence of recurrent hospitalization., Conclusion: Angina without obstructive CAD has a heterogeneous prognosis. A main determinant of major adverse events is the presence of 'some' coronary atherosclerosis, with unequivocal myocardial ischaemia being associated with worse clinical outcomes. Patients' quality of life is also worsened by the high incidence of hospitalization, angina recurrence, and repeated coronary angiography.

In patients receiving permanent cardiac electrical stimulation, a high burden of apical right ventricular pacing is associated with an increased incidence of heart failure. Despite the large body of electrocardiographic, echocardiographic, and pathological data, mechanisms underlying this serious complication are not fully understood. Moreover, the empirical use of alternative right ventricular pacing sites, both in the experimental and in the clinical setting, has not provided better results in terms of clinical outcome. Recent data derived by echocardiographic particle image velocimetry of intracardiac flows have shown abnormal flow patterns in patients with dyssynchrony of left ventricular wall contraction, and the reversion to normal flow dynamics after successful electrical cardiac resynchronization therapy. This suggests that a normal intraventricular flow pattern is strongly dependent on the highly coordinated contraction of the ventricular wall segments and that an abnormal sequence of wall contraction may trigger the development of overt heart failure. This review summarizes the state of the art on this topic, highlighting postulated underlying basic mechanisms linking abnormal flow with the development of pacing-induced heart failure. This research line suggests the importance of studying intraventricular fluid dynamics as a new powerful tool for a more complete understanding of mechanisms involved, and ultimately to prevent pacing-related heart failure., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

Background: The exercise electrocardiographic stress test (ExET) is the most widely used non-invasive diagnostic method to detect coronary artery disease. However, the sole ST depression criteria (ST-max) have poor specificity for coronary artery disease in patients with left ventricular hypertrophy. We hypothesised that ST-segment depression/heart rate hysteresis, depicting the relative behaviour of ST segment depression during the exercise and recovery phase of the test might increase the diagnostic accuracy of ExET for coronary artery disease detection in such patients., Methods: In three cardiology centres, we studied 113 consecutive patients (mean age 66 ± 2 years; 88% men) with hypertension-related left ventricular hypertrophy at echocardiography, referred to coronary angiography after an ExET. The following ExET criteria were analysed: ST-max, chronotropic index, heart rate recovery, Duke treadmill score, ST-segment depression/heart rate hysteresis., Results: We detected significant coronary artery disease at coronary angiography in 61 patients (53%). At receiver-operating characteristic analysis, ST-segment depression/heart rate hysteresis had the highest area under the curve value (0.75, P < 0.001 when compared with the 'neutral' receiver-operating characteristic curve value of 0.5). Area under the curve values were 0.68 (P < 0.01) for the chronotropic index, 0.58 (P = NS) for heart rate recovery, 0.57 (P = NS) for ST-max and 0.52 (P = NS) for the Duke treadmill score., Conclusions: Among currently available ExET diagnostic variables, ST-segment depression/heart rate hysteresis offers a substantially better diagnostic accuracy for coronary artery disease than conventional criteria in patients with hypertension-related left ventricular hypertrophy., (© The European Society of Cardiology 2016.)

Background: Whether orthostatic hypotension (OH) is a risk factor for cardiovascular morbidity and death is uncertain. Currently available evidence derives from non-homogeneous and partly ambiguous studies., Objective: We aimed at assessing the relationship between OH and death or major adverse cardiac and cerebrovascular events (MACCEs) by integrating results of previous studies., Methods: We performed a meta-analysis of prospective observational studies reporting on the association between prevalent OH, mortality, and incident MACCE, published from 1966 through 2013. Mantel-Haenszel pooled estimates of relative risk (RR) and 95% confidence intervals (CIs) for all-cause death were assessed as the primary endpoint at the longest follow-up; incident coronary heart disease (CHD), heart failure (HF), and stroke were assessed as secondary endpoints. We also performed post hoc subgroup analyses stratified by age and a meta-regression analysis., Results: We identified a total of 13 studies, including an overall population of 121 913 patients, with a median follow-up of 6 years. Compared with the absence of OH, the occurrence of OH was associated with a significantly increased risk of all-cause death (RR 1.50; 95% CI 1.24-1.81), incident CHD (RR 1.41; 95% CI 1.22-1.63), HF (RR 2.25; 95% CI 1.52-3.33), and stroke (RR 1.64; 95% CI 1.13-2.37). When analysed according to age, pooled estimates of RR (95% CI) for all-cause death were 1.78 (1.25-2.52) for patients <65 years old, and 1.26 (0.99-1.62) in the older subgroup., Conclusion: Orthostatic hypotension is associated with a significantly increased risk of all-cause death, incident CHD, HF, and stroke., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Lung ultrasonography is an emerging, user-friendly and easy-to-use technique that can be performed quickly at the patient's bedside to evaluate several pathologic conditions affecting the lung. Ultrasound lung comets (ULCs) are an echographic sign of uncertain biophysical characterisation mostly attributed to water-thickened subpleural interlobular septa, but invariably associated with increased extravascular lung water. ULCs have thus been proposed as a complementary tool for the assessment and monitoring of acute heart failure and are now entering into statements in international recommendation documents. Adding lung ultrasonography to conventional echocardiography allows for performing an integrated cardiopulmonary ultrasound examination, and this is an important opportunity for the cardiologist. The technique allows the simultaneous gathering of considerable information about the heart and the lungs to investigate acute and chronic cardio-pulmonary conditions within a non-invasive, radiation-free, single-probe, all-in-one examination. We have here reviewed the pertinent literature on the physical origin of ULCs and on their role and importance in intensive and acute cardiac care settings. We also here propose a new algorithm aimed at implementing evaluation in the diagnostic work-up of patients with suspected acute heart failure., (© The European Society of Cardiology 2014.)

Angina and myocardial ischemia without obstructive coronary artery disease are common clinical findings, often neglected for the assumption of a good prognosis. Most often, such patients are neither further investigated nor offered specific treatment beyond reassurance. However, the absence of significant coronary stenoses on angiography does not necessarily imply a "healthy" coronary tree. In such cases, myocardial ischemia may result from different types of functional disease involving the epicardial coronary arteries, the coronary microcirculation, or both; an accurate assessment of these components should be systematically performed after exclusion of organic epicardial disease because a correct diagnosis has relevant prognostic and therapeutic implications. Here we discuss the basic principles of diagnostic tests in this setting and propose a diagnostic sequence of reasonable practical implementation that may help identify patients at risk of future cardiac events., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Because ST segment depression has limited diagnostic performance at exercise electrocardiography (ECG), ST segment depression/heart rate (ST/HR) hysteresis and cardiopulmonary exercise test (CPET)-derived parameters have been proposed as alternatives to diagnose exercise-induced myocardial ischemia. We compared the diagnostic performance of such parameters., Methods: We studied 56 subjects (45 men, 11 women, age 59.7 ± 13.6 years) referred for suspected exercise-induced myocardial ischemia with an equivocal ECG exercise test. All subjects serially underwent CPET and a myocardial single-photon emission computerized tomography (SPECT) perfusion imaging (as the gold standard for ischemia). Maximum ST depression at peak exercise (ST-max), the ST/HR hysteresis, ΔVO2/ΔWR b-b1 slope, ΔVO2/ΔWR (aa1-bb1), VO2/HR flattening duration and other CPET parameters were derived in all subjects., Results: On the basis of SPECT, 23 subjects (41%) were considered ischemic and 33 subjects (59%) non-ischemic. ST/HR hysteresis was higher (0.026 mV; 95% CI: 0.003 to 0.049 vs -0.016 mV; 95% CI: -0.031 to -0.001 mV) and ST-max was lower (-0.105 mV; 95% CI: -0.158 to -0.052 vs 0.032 mV; 95% CI: -0.001 to -0.066 mV) in ischemic vs non-ischemic subjects (P=0.004 and P=0.001, respectively). Among CPET parameters, ΔVO2/ΔWR b-b(1) slope was lower (9.4 ± 3.8) and ΔVO2/ΔWR (aa(1)-bb(1)) was higher (2.1 ± 2.6) in ischemic vs non-ischemic subjects (11.4 ± 2.3, P=0.005, and 1.1 ± 1.5, P=0.001, respectively). The ST/HR hysteresis had the highest area under the curve value, better (P<0.05) than any other parameters tested, thus showing the highest overall diagnostic performance., Conclusion: The ST/HR hysteresis is superior to CPET-derived parameters for detecting exercise-induced myocardial ischemia in patients with equivocal ECG exercise test results., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)