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Objectives:To describe the experience of coronary chronic total occlusions (CTOs)percutaneous coronary interventions (PCI) using antegrade fenestration and re‐entry(AFR) technique with a dedicated dual guidewire balloon (DGB).Background:Antegrade dissection and re‐entry (ADR) techniques has beenemphasized in recent worldwide CTO consensus documents. We investigated thefeasibility and safety of DGB as a dedicated device to perform guidewire‐based AFR.Methods and Results:Fourteen consecutive patients with complex CTO (J‐CTOscore: 3.1 ± 0.9) underwent DGB‐AFR in the years 2020–2021. DGB‐AFR consists inadvancing the DGB over a guidewire that reached the vessel distal to the CTO in anextra plaque fashion, inflating/deflating the DGB to create fenestration betweensubintimal space and the true lumen and advancing a proximal re‐entry guidewirethrough fenestration in the true lumen. DGB‐AFR alone was successful in 10 of 14(71%) cases, a rescue wire‐based ADR was needed in two cases for re‐entry into thetrue lumen with a total success rate in 12 of 14 (86%) cases. Among all DGB‐AFRcases, four (28%) were performed as a first‐line strategy while the remaining 10(71%) cases were performed as a bail‐out strategy after failure of other antegradecrossings for 30 min of procedural time. No DGB‐related complications wereobserved.Conclusions:DGB‐AFR is a user‐friendly reliable strategy for the treatment of manyCTO lesions. It can be used as bail‐out after failure of conventional antegrade wiringtechniques, achieving high procedural success rate and low occurrence of proceduraladverse events.

Background Coronary perforation is a life‐threatening complication of acute percutaneous coronary intervention (PCI) for chronic total occlusions (CTO), but data on midterm outcomes are limited. Methods and Results Data from LATAM (Latin American)‐CTO Registry (57 centers; 9 countries) were analyzed. We assessed the risk of 30‐day, 1‐year major adverse cardiac events of coronary perforation using time‐to‐event and weighted composite end point analysis having CTO PCI without perforation as comparators. Additionally, we studied the independent predictors of perforation in these patients. Of 2054 patients who underwent CTO PCI between 2015 and 2018, the median Multicenter CTO Registry in Japan and Prospective Global Registry for the Study of Chronic Total Occlusion Intervention‐Chronic total occlusions scores were 2.0 (1.0–3.0) and 1.0 (0.0–2.0), respectively. The perforation rate was 3.7%, of which 55% were Ellis class 1. After 1‐year coronary perforation had higher major adverse cardiac events rates (24.9% versus 13.3%; P P =0.04) and 1 year ( P P P =0.05), antegrade knuckle wire ( P =0.04), and right coronary artery CTO PCI ( P =0.05). Conclusions Coronary perforation was infrequent and associated with anatomical and procedural complexity, resulting in higher risk of hemorrhagic and ischemic events. Landmark and weighted analysis showed a sustained burden of major events between 6 months and 1 year follow‐up.

Chronic total occlusion (CTO) percutaneous coronary intervention (PCI) can improve patient symptoms, but it remains controversial whether it impacts subsequent clinical outcomes.In this systematic review and meta-analysis, we queried PubMed, ScienceDirect, Cochrane Library, Web of Science, and Embase databases (last search: September 15, 2021). We investigated the impact of CTO-PCI on clinical events including all-cause mortality, cardiovascular death, myocardial infarction (MI), major adverse cardiovascular event (MACE), stroke, subsequent coronary artery bypass surgery, target-vessel revascularization, and heart failure hospitalizations. Pooled analysis was performed using a random-effects model.A total of 58 publications with 54,540 patients were included in this analysis, of which 33 were observational studies of successful vs failed CTO-PCI, 19 were observational studies of CTO-PCI vs no CTO-PCI, and 6 were randomized controlled trials (RCTs). In observational studies, but not RCTs, CTO-PCI was associated with better clinical outcomes. Odds ratios (ORs) and 95% confidence intervals (CIs) for all-cause mortality, MACE, and MI were 0.52 (95% CI, 0.42-0.64), 0.46 (95% CI, 0.37-0.58), 0.66 (95% CI, 0.50-0.86), respectively for successful vs failed CTO-PCI studies; 0.38 (95% CI, 0.31-0.45), 0.57 (95% CI, 0.42-0.78), 0.65 (95% CI, 0.42-0.99), respectively, for observational studies of CTO-PCI vs no CTO-PCI; 0.72 (95% CI, 0.39-1.32), 0.69 (95% CI, 0.38-1.25), and 1.04 (95% CI, 0.46-2.37), respectively for RCTs.CTO-PCI is associated with better subsequent clinical outcomes in observational studies but not in RCTs. Appropriately powered RCTs are needed to conclusively determine the impact of CTO-PCI on clinical outcomes.

Coronary artery perforation (CAP) is a rare but potentially life-threatening complication of percutaneous coronary intervention (PCI), however if recognized and managed promptly, its adverse consequences can be minimized. Risk factors for CAP include the use of advanced PCI technique (such as atherectomy and chronic total occlusion interventions) and treatment of severely calcified lesions. There are 3 major types of CAP depending on location: (a) large vessel perforation, (b) distal vessel perforation, and (c) collateral perforation. Large vessel perforation is usually treated with implantation of a covered stent, whereas distal and collateral vessel perforations are usually treated with coil or fat embolization. In this article we provide a state-of-the-art overview of the contemporary management of CAP.

Patients with coronary microvascular dysfunction represent a widespread population, and despite the good prognosis, many of them, because of the angina symptoms, have a poor quality of life with strong limitations in their daily activities. In 2017, a new classification of microvascular dysfunction as well as a new definition of ischemia in patients with no obstructive coronary artery disease became available. This new definition improves Kemp's initial work, where cardiac X syndrome was initially described. This work summarizes the last updates on the subject with particular attention to the new classification of microvascular dysfunction, with particular attention to microvascular and vasospastic angina definition and diagnostic criteria.

Background: The relationship between left ventricular ejection fraction (LVEF) and the success and safety of coronary chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has received limited study. Methods: We examined the clinical characteristics and outcomes of CTO PCI in the Prospective Global Registry for the Study of CTO Intervention (PROGRESS-CTO) after stratifying patients by LVEF (≤35%, 36%–49%, and ≥50%). Results: A total of 7827 CTO PCI procedures with LVEF data were included. Mean age was 64 ± 10 years, 81% were men, 43% had diabetes mellitus, 61% had prior PCI, 45% had prior myocardial infarction, and 29% had prior coronary artery bypass graft surgery. Technical success was similar in the three LVEF strata: 85%, 86%, and 87%, p = 0.391 for LVEF ≤35%, 36%–49%, and ≥50%, respectively. In-hospital mortality was higher in lower LVEF patients (1.1%, 0.4%, and 0.3%, respectively, p = 0.001). In-hospital major adverse cardiovascular events (MACE) were numerically higher in lower EF patients (2.7%, 2.1%, and 1.9%, p = 0.271). At a median follow-up of 2 months (interquartile range: 19-350 days), patients with lower LVEF continued to have higher mortality (4.9%, 3.2%, and 1.4%, p < 0.001) while the MACE rates were similar (9.3%, 9.6%, and 7.4%, p = 0.172). Conclusion: CTO PCI can be performed with high technical success in patients with reduced LVEF but is associated with higher in-hospital and post-discharge mortality.

Background Recent improvement in clinical skills, technology and hardware has resulted in improved success rates with chronic total occlusion (CTO) percutaneous coronary intervention (PCI). We performed a study level pooled analysis from the five largest registries of percutaneous coronary intervention (PCI) of CTO. Research design and methods We conducted pooled analysis of 9500 patients in registries and data on procedural characteristics, technical success, and MACCE was collected. Results A total of 9500 patients were included in the analysis. Mean age was 65.4 years with previous CABG in 24.8%, reattempt procedure in 24.8% and mean JCTO score was 2.2. Final wiring strategy in hybrid algorithm-based registries was AWE in 40.8-58%, Retrograde in 24-35%, ADR in 16-25% and in Expert JCTO and EURO CTO was AWE in 72-75% and retrograde in 25-28%. Technical success was achieved in 87.8%. In hospital MACCE was 2.5 % (95% CI: 1.8 to 3.4%), mortality 0.44% (95% CI: 0.23 to 0.84%), stroke 0.2% (95% CI: 0.1 to 0.3%); myocardial infraction 1.6% (95% CI: 1.1 to 2.2%); and cardiac tamponade 0.8% (95% CI: 0.5 to 1.3 %). Conclusion CTO PCI is currently performed with high technical success rates and low complication rates in experienced hands utilizing various techniques.

The aim of this study was to identify independent predictors of procedural success after retrograde chronic total occlusion (CTO) percutaneous coronary intervention (PCI).Retrograde CTO PCI is an established technique, but predictors of success remain poorly understood.A multivariable logistic regression model was used to analyze potentially important demographic, clinical, anatomical, and technical aspects of retrograde CTO PCI cases uploaded to the multicenter European CTO (ERCTO) Club Registry.In calendar years 2018 and 2019, 2,364 retrograde CTO PCI cases constituted the primary analysis cohort. A primary retrograde strategy was used in 1,953 cases (82.6%), and an initial antegrade approach was converted to retrograde in 411 cases (17.4%). Procedural success was achieved in 1,820 cases (77.0%) and was more likely to occur after a primary retrograde attempt versus conversion from an initial antegrade approach (80.9% vs 58.4%; P 0.0001). After multivariable analysis, an absence of lesion calcification (OR: 1.86; 95% CI: 1.37-2.51; P 0.0001), a higher degree of distal vessel opacification (OR: 2.47; 95% CI: 1.72-3.55; P 0.0001), little or no proximal target vessel tortuosity (OR: 1.84; 95% CI: 1.28-2.64; P = 0.001), Werner collateral connection CC1 (OR: 4.87; 95% CI: 2.90-8.19; P 0.0001) or CC2 (OR: 5.33; 95% CI: 3.02-9.42; P 0.0001), and the top tertile of operator volume (120 cases over 2 years) (OR: 1.88; 95% CI: 1.26-2.79; P = 0.002) were associated with the greatest chance of achieving angiographic success.Less calcification with good distal vessel opacification, little or absent proximal vessel tortuosity, and visible collateral connections, along with high-volume operator status, were all independently predictive of angiographically successful retrograde CTO PCI.

Background Masses in the ascending aorta are an uncommon source of coronary embolism: thrombi located on atherosclerotic aortic plaques are the most frequent cause. A floating thrombus, without evidence of ascending aortic pathology has rarely been reported Method We report a case of an unusual aortic route thromboembolism leading ST segment elevation Myocardial Infarction (STEMI). The patient was referred to the Hub Hospital to undergo urgent coronarography. The examination excluded atherosclerotic coronary arteries disease but an unusual persistence of contrast dye was found at the level of non-coronary sinus. The trans-esophageal echocardiography showed a mobile pedunculated echogenic mass allocated in the non-coronary sinus of Valsalva, prolapsing into the right coronary ostium and leading his dynamic occlusion at every cardiac cycle. Results The patient underwent emergency cardiac surgery. An enormous thrombotic mass was removed from the left coronary sinus of Valsalva. No tears in the aortic route or aortic valve anomalies were found. He was discharged in good clinical conditions 12 days after his admission. Conclusion This case show the importance of a multidisciplinary approach to a such challenging scenario was successful. It emphasizes the role of heart team in the decision-making algorithm

Objectives We aimed to evaluate the efficacy and safety of antegrade fenestration and reentry (AFR) for chronic total occlusion (CTO) recanalization in a multicenter registry. Background Adoption of antegrade dissection/reentry (ADR) for CTO recanalization has been limited, and novel ADR techniques are needed. Methods AFR involves the balloon-induced creation of multiple fenestrations between the false and true lumen. A targeted true lumen reentry is subsequently achieved with a low tip-load polymer-jacketed guidewire. Following the initial description and dissemination of AFR, patients undergoing AFR-based CTO recanalization at nine centers were included in the present registry. Study endpoints were AFR success, procedural success, and target-lesion failure (TLF) on follow-up. Results We included 41 patients. Mean J-CTO score was 2.5 ± 1.4. In 80.5% of cases, AFR was performed after failed antegrade wire escalation. Another ADR technique was used before AFR in one-third of cases. AFR achieved distal true lumen reentry in n = 27/41 (65.9%) cases. In n = 14/41 (34.1%) cases with AFR failure, use of alternative techniques led to successful CTO recanalization in eight additional patients. The overall technical and procedural success rates were 85.4% and 82.9%, respectively. No AFR-related complications were observed. One-year TLF rate was 8.3% overall, with no differences between successful and failed AFR. Conclusions We report on AFR feasibility in a multicenter registry of patients undergoing CTO recanalization. We observed a moderate success rate, coupled with the absence of complications. Moreover, even a failed AFR attempt did not preclude the use of alternative techniques to achieve recanalization. Further studies should confirm and extend our findings.

Dual lumen microcatheters (DLMC) have become indispensable tools in the setting of percutaneous coronary intervention (PCI) of chronic total occlusion (CTO). Other than allowing preservation and treatment of bifurcated coronary branches within or in the proximity of the CTO-body, they enable the use of modified parallel wiring, antegrade dissection and re-entry, collateral selection and retrograde negotiation of the distal CTO-cap. This Euro-CTO consensus document describes current DLMCs and suggests a practical guide to anatomies and techniques in which these devices are applicable.

The aim of this randomized prospective study was to evaluate the quality of life (QoL) using the “Seattle Angina Questionnaire” (SAQ) in patients with chronic total occlusion (CTO) in coronary arteries treated with either percutaneous coronary intervention (PCI) or optimal medical therapy (OMT), or only with OMT. The potential benefits of recanalization of CTO by PCI have been controversial because of the scarcity of randomized controlled trials. A total of 100 patients with CTO were randomized (1:1) prospectively into the PCI CTO or the OMT group (50 patients in each group). There were no baseline differences in the SAQ scores between the groups, except for physical limitation scores (P = 0.03). During the mean follow-up (FUP) of 275 ± 88 days, patients in the PCI group reported less physical activity limitations (72.7 ± 21.3 versus 60.5 ± 27, P = 0.014), less frequent angina episodes (89.8 ± 17.6 versus 76.8 ± 27.1, P = 0.006), better QoL (79.9 ± 22.7 versus 62.5 ± 25.5, P = 0.001), greater treatment satisfaction (91.2 ± 13.6 versus 81.4 ± 18.4, P = 0.003), and borderline differences in angina stability (61.2 ± 26.5 versus 51.0 ± 23.7, P = 0.046) compared to patients in the OMT group. There were no significant differences in SAQ scores in the OMT group at baseline and during the FUP. There was a statistically significant increase in all five domains in the PCI group. Symptoms and QoL measured by the SAQ were significantly improved after CTO PCI compared to OMT alone.

myocardial infarction

Background and aims In the present study, we aimed to compare the clinical and coronary angiography features between South Asian and Caucasian patients with Acute Coronary Syndrome (ACS). In particular, we focused our analysis on the evaluation of recent cardiovascular risk markers, such as remnant cholesterol, corresponding to all plasma cholesterol minus HDL-C (high-density lipoprotein cholesterol) and LDL-C (low-density lipoprotein cholesterol), and the Monocyte-to-HDL-cholesterol ratio. We also compared values of several lipoprotein ratios and the Platelet-to-lymphocyte ratio, accurate predictors of coronary events and coronary artery disease. Methods and results We recruited 40 South Asian and 40 Caucasian patients admitted for ACS. Data were collected by consulting patients' medical records. We used Chi-square test and Student's t-test to analyse qualitative and quantitative variables, respectively. South Asian patients, compared to Caucasians, showed higher mean values of the parameters analysed: remnant cholesterol (32.6 ± 17 vs 26.5 ± 9.6), Monocyte-to-HDL-cholesterol ratio (26.4 ± 48.7 vs 16.5 ± 8.3), Platelet-to-lymphocyte ratio (124.7 ± 130.7 vs 120.5 ± 58.8). Moreover, higher mean values of several lipoprotein ratios were also found in South Asian patients compared to the control group. However, statistical significance was not reached for any of these differences observed. Conclusions The evaluation of the parameters analysed in this study might provide accurate information regarding the cardio-metabolic risk in South Asian patients. However, further studies with larger samples are needed to obtain more significant results.

Myocardial infarction with non-obstructive coronary arteries (MINOCA) is defined by clinical evidence of myocardial infarction (MI) with normal or near-normal coronary arteries on angiography. This condition is present in about 5% to 25% of patients presenting with acute coronary syndromes. MINOCA is a working diagnosis. Current guidelines and consensus recommend identification of underlying causes of MINOCA in order to optimize treatment, improve prognosis, and promote prevention of recurrent myocardial infarction. An accurate evaluation of patient history, symptoms and use of invasive and non-invasive imaging should lead to identification of epicardial or microvascular causes of MINOCA and differentiation from non-ischemic myocardial injury due to both cardiac (e.g. myocarditis) and non-cardiac disease (e.g. pulmonary embolism). In this review, we highlight the role of coronary imaging in differential diagnosis of patients presenting with MINOCA. Intravascular ultrasound and optical coherence tomography are well known technologies used in different settings from acute to chronic coronary syndromes. In MINOCA patients, coronary imaging could help to identify pathological alterations of the epicardial vessels that are not visible by coronary angiography such as plaque disruption, coronary dissection, coronary thromboembolism, coronary spasm, and coronary artery disease in patients presenting with takotsubo syndrome. In future, the widespread use of these technologies, in the right clinical context, could lead to optimization and personalization of treatment, and to better prognosis of patients presenting with MINOCA.

Despite the use of anti-anginal drugs and/or percutaneous coronary interventions (PCI) or coronary artery bypass grafting, the proportion of patients with coronary artery disease who have daily or weekly angina ranges from 2% to 24%. Refractory angina refers to long-lasting symptoms (for >3 months) due to established reversible ischaemia, which cannot be controlled by escalating medical therapy with the use of 2nd- and 3rd-line pharmacological agents, bypass grafting, or stenting. While there is uncertain prognostic benefit, the treatment of refractory angina is important to improve the quality of life of the patients affected. This review focuses on conventional pharmacological approaches to treating refractory angina, including guideline directed drug combination and dosages. The symptomatic and prognostic impact of advanced and novel revascularization strategies such as chronic total occlusion PCI, transmyocardial laser revascularization, coronary sinus occlusion, radiation therapy for recurrent restenosis, and spinal cord stimulation are also covered and recommendations of the 2019 ESC Guidelines on the Diagnosis and Management of Chronic Coronary Syndromes discussed. Finally, the potential clinical use of current angiogenetic and stem cell therapies in reducing ischaemia and/or pain is evaluated.

Patients with coronary microvascular dysfunction (CMVD) represent a widespread population and despite the good prognosis, many of them have a poor quality of life with strong limitations in their daily activities because of the angina symptoms. This article summarizes the most frequent clinical presentation pictures like stable and unstable microvascular angina. Main risk factors are discussed, followed by the latest updates on the subject about different pathogenic hypotheses, diagnosis and treatment. Not very well understood microvascular alterations, like slow flow phenomenon and no reflow are discussed and both prognosis and the impact of the disease in the quality of life are analyzed.

Objective: The aim of this study was to evaluate in patients with microvascular angina and heart failure with preserved ejection fraction, the speckle-tracking echocardiography, and longitudinal myocardial strain to evaluate the possible presence of alterations in heart failure with preserved ejection fraction patients compared with a control population. We also investigated the correlation between the longitudinal strain analysis and the TIMI frame count after coronary angiography. Methods: Our study was performed on a population 41 patients with microvascular angina that underwent coronary angiography and speckle-tracking echocardiography. We divided the sample into two categories: patients with heart failure with preserved ejection fraction (n-21) and patients without heart failure with preserved ejection fraction (n-20). We calculated TIMI frame count indices for each patient based on angiographic images. Results: Patients with heart failure with preserved ejection fraction had reduced global longitudinal strain values (−17.88) compared with the total control population, and this reduction was statistically significant (P=.028). This reduction was more marked in patients who had a significantly increased TIMI frame count. Therefore, a statistically significant correlation was observed between TIMI frame count and global longitudinal strain. Conclusion: Our results show that cardiac contractile mechanics are altered in patients with heart failure with preserved ejection fraction at a subclinical level hard to identifiable with conventional echocardiography. The dysfunction of the microcirculation and the consequent alteration of the TIMI frame count probably results in a reduction of myocardial performance.

Background: Accuracy of high sensitive troponin (hs-cTn) to detect coronary artery disease (CAD) in patients with renal insufficiency is not established. The aim of this study was to evaluate the prognostic role of hs-cTn T and I in patients with chronic kidney disease (CKD). Methods: All consecutive patients with chest pain, renal insufficiency (eGFR < 60 mL/min/1.73 m2) and high sensitive troponin level were included. The predictive value of baseline and interval troponin (hs-cTnT and hs-cTnI) for the presence of CAD was assessed. Results: One hundred and thirteen patients with troponin I and 534 with troponin T were included, with 95 (84%) and 463 (87%) diagnosis of CAD respectively. There were no differences in clinical, procedural and outcomes between the two assays. For both, baseline hs-cTn values did not differ be­tween patients with/without CAD showing low area under the curve (AUC). For interval levels, hs-cTnI was significantly higher for patients with CAD (0.2 ± 0.8 vs. 8.9 ± 4.6 ng/mL; p = 0.04) and AUC was more accurate for troponin I than hs-cTnT (AUC 0.85 vs. 0.69). Peak level was greater for hs-cTnI in patients with CAD or thrombus (0.4 ± 0.6 vs. 15 ± 20 ng/mL; p = 0.02; AUC 0.87: 0.79–0.93); no differences were found for troponin T assays (0.8 ± 1.5 vs. 2.2 ± 3.6 ng/mL; p = 1.7), with lower AUC (0.73: 0.69–0.77). Peak troponin levels (both T and I) independently predicted all cause death at 30 days. Conclusions: Patients with CKD presenting with altered troponin are at high risk of coronary disease. Peak level of both troponin assays predicts events at 30 days, with troponin I being more accurate than troponin T. (Cardiol J 2017; 24, 2: 139–150)

We present a successfully chronic total occlusions (CTO) coronary recanalisation with the subadventitial space by excimer laser atherectomy (ELCA) adjunctive therapy. Angiogram revealed non-significant diffuse disease of the left coronary system with a complex long proximal right coronary artery (RCA) CTO (J-CTO score 4) and collaterals (Rentrop Grade 2 and Werner classification CC1) from the septal branches (Figure 1, Panel A). CTO PCI of the RCA was then indicated and planned. Initially, antegrade approach and a retrograde approach technique were attempted without success. Thereafter, a rescue Antegrade Dissection Reentry strategy (ADR) was applied. A Pilot 200 (Abbott) was advanced in a knuckle fashion in subintimal space reaching the distal cap. A Conquest Pro 12 (Asahi) successfully re-entered true lumen in posterolateral (PL) (Figure 1, Panel B). However, none balloon was able to be advanced thereafter. Thus, a Spectranetics ELCA 0.9 mm X-80 with simultaneous saline flush, frequency 80 Hz and fluence 80mJ/mm2 (Figure 1, Panel C) was applied successfully. A workhorse wire was advanced into the posterior descendent artery (PDA) followed by a non-compliant Trek balloon (Abbott) 2.5 20 mm to PL. Pre-dilatation followed by stenting was performed supported by a Guideliner (Teleflex) extension catheter. A total of three drug-eluting stents Synergy (Boston Scientific) were implanted with good angiographic result (Figure 1, Panel D). Intravascular ultrasound showed that the wire went through the subintimal space (red arrow) in both mid and distal RCA (Figure 1, Panel E), with appropriate debulking of the subintimal lesion (red arrow) and haematoma around the vessel (blue arrow) (Figure 1, Panel F), and then re-entering near the bifurcation with resolution of the haematoma (red arrow) and with optimal stenting result (Figure 1, Panel G).

Chronic total occlusion (CTO) of the coronary arteries are relatively common, observed in approximatively 15-25% of patients with coronary artery disease undergoing coronary angiography. The right coronary artery represents the most common CTO vessel, which represents about half of the CTO cases.The CTO prevalence is much higher ( 90%) among patients with prior coronary artery bypass graft (CABG), while a CTO is found in only one tenth of patients referred for ST-elevation myocardial infarction (STEMI)

Currently, there is no effective therapy for COVID-19, and several approaches are under investigation. Nevertheless, some drugs are used off-label despite the absence of clear data on their effectiveness. Among these, hydroxychloroquine suppresses SARS-CoV-2 replication in vitro,1 and clinical trials are ongoing to evaluate its use as an anti-COVID-19 agent. To date, the FDA and EMA allow its use only in hospitalized patients with severe COVID-19 or in those at high risk, in cases where other trials are not feasible. According to a small non-randomized study, hydroxychloroquine’s efficacy might be enhanced by azithromycin, as the combination of these two drugs appeared to accelerate viral clearance.2 However, these findings were not substantiated by another study performed in severe COVID-19 cases.3 In addition to the lack of consistent or conclusive efficacy data of these drugs, whether they are used individually or in combination, concern is increasing about potential safety issues. Both hydroxychloroquine and azithromycin may lead to QT prolongation-related life-threatening arrhythmias through the blockage of the rapid delayed rectifier potassium current (IKr). Their combination seems to be more harmful than their single use. Importantly, the risk of azithromycin-mediated QT prolongation is higher in males and in elderly groups,4 that represent a large proportion of the COVID-19 population. Data from a recent Chinese report showed that 16.7% of hospitalized COVID-19 patients and 44.4% of those in intensive care units had arrhythmias.5 The two main mechanisms involved could be hypoxia and electrolyte abnormalities, common features in the acute phase of severe illness. These factors may further enhance the risk of arrhythmic toxicity associated with hydroxychloroquine or azithromycin. Therefore, strategies to mitigate this potential risk have been proposed. The American College of Cardiology suggested QT monitoring in order to discontinue azithromycin (if used) and/or reduce the hydroxychloroquine dose in the case of QT prolongation. While drugs currently used against COVID-19 may seem crucial to treat the infection (in the absence of better options), it is imperative to mitigate toxicity to guarantee the maximum possible safety. According to 2019 international guidelines by the American Thoracic Society and Infectious Diseases Society of America, in pneumonia patients with QT prolongation, macrolides should be replaced by tetracyclines. While providing a broad-spectrum antibiotic activity, compared with other antibiotics tetracyclines also display additional properties that can be advantageous in COVID-19. In particular, the tetracycline derivative minocycline exerts anti-inflammatory effects by suppressing proinflammatory cytokines, including interleukin-6 (IL-6), which plays a key role in COVID-19, and may inhibit poly(ADP-ribose) polymerase-1 (PARP-1) which seems to be implicated in SARS-CoV-2 replication.6,7 Moreover, minocycline displays a synergistic effect when added to hydroxychloroquine.8 Compared with azithromycin, minocycline does not prolong the QT interval, and experimental evidence suggests that it may even be beneficial in conditions associated with increased risk of QT prolongation or arrhythmia. In an experimental model of epilepsy, intrathecal administration of minocycline, by antagonizing the action of microglia, reduced autonomic nervous system activity and seizure-induced QT prolongation.9 In other murine models, treatment with minocycline attenuated ischaemia-induced arrhythmias by blocking the mitochondrial K-ATP channel and inhibiting the PI3K/Akt signalling pathway mediated by L-type calcium channels both involved in myocardial ischaemia-induced arrhythmias.10 Although not proven in humans yet, it is reasonable to believe that minocycline may prevent (or at least mitigate) the increased risk of QT prolongation, and potentially fatal arrhythmias, due to hydroxychloroquine/azithromycin combination therapy, while having the same efficacy as azithromycin but a lower arrhythmogenic effect. For these reasons, until clinical trials prove the efficacy of azithromycin alone or in combination with hydroxychloroquine, we suggest that, whenever antibiotic prophylaxis is needed, azithromycin should be replaced by minocycline.

OBJECTIVES The aim of the study was to evaluate the outcomes of retrograde versus antegrade approach in chronic total occlusion (CTO) percutaneous coronary intervention (PCI). BACKGROUND The retrograde approach has increased the success rate of CTO PCI but has been associated with a higher risk for complications. METHODS We conducted a meta-analysis of studies published between 2000 and August 2019 comparing the in-hospital and long-term outcomes with retrograde versus antegrade CTO PCI. RESULTS Twelve observational studies (10,240 patients) met our inclusion criteria (retrograde approach 2,789 patients, antegrade approach 7,451 patients). Lesions treated with the retrograde approach had higher J-CTO score (2.8 vs. 1.9, p

Atrial Fibrillation is the most common cardiac arrhythmia affecting people of all ages, principally the elderly. Cognitive decline and dementia are also prevalent diseases in elderly. The scientific community always showed interest in the possible association between these two pathological entities, both implicating social and economic burden. This has been confirmed by several longitudinal population-based studies. Some studies also revealed that the association between atrial fibrillation and dementia may be not related to history of stroke. Therefore, other pathophysiological mechanisms are likely implicated, so far unclear or undefined. The aim of the present review is to analyse the possible mechanisms underlying the frequent association between atrial fibrillation and cognitive impairment.

The study focuses on the evolution of practice, procedural outcomes, and in-hospital complications of chronic total occlusion percutaneous coronary intervention in Europe.Data from 17 626 procedures enrolled in European Registry of Chronic Total Occlusion between January 2008 and June 2015 were assessed. The mean patient age was 63.9±10.9 years; 85% were men. Procedural success increased from 79.7% to 89.3% through the study period. Patients enrolled during the years had increasing comorbidities and lesion complexity (J-CTO score [Multicenter CTO Registry of Japan] increased from 1.76±1.03 in 2008 to 2.17±0.91 in 2015; P for trend,0.001). Retrograde approach utilization steadily increased from 10.1% in 2008 to 29.9% in 2015 ( P for trend,0.001). Antegrade dissection reentry adoption was low, not exceeding 5.5%. In-hospital mortality decreased during the study period from 0.4% to 0.1% ( P for trend,0.001), whereas in-hospital complication rates remained essentially unchanged, in the range 4.4% to 5.2% ( P for trend, 0.390).Chronic total occlusion percutaneous coronary intervention has shown a steady increase in procedural success rate over time, with unchanged complication rates, despite the increasing complexity of the lesions attempted. The J-CTO score predictive value for procedural success was low for the entire registry and had no predictive ability for the retrograde approach.

Aims: The clinical value of percutaneous coronary intervention (PCI) for chronic coronary total occlusions (CTOs) is not established by randomized trials. This study should compare the benefit of PCI vs. optimal medical therapy (OMT) on the health status in patients with at least one CTO.Method and results: Three hundred and ninety-six patients were enrolled in a prospective randomized, multicentre, open-label, and controlled clinical trial to compare the treatment by PCI with OMT with a 2:1 randomization ratio. The primary endpoint was the change in health status assessed by the Seattle angina questionnaire (SAQ) between baseline and 12 months follow-up. Fifty-two percent of patients have multi-vessel disease in whom all significant non-occlusive lesions were treated before randomization. An intention-to-treat analysis was performed including 13.4% failed procedures in the PCI group and 7.3% cross-overs in the OMT group. At 12 months, a greater improvement of SAQ subscales was observed with PCI as compared with OMT for angina frequency [5.23, 95% confidence interval (CI) 1.75; 8.71; P = 0.003], and quality of life (6.62, 95% CI 1.78-11.46; P = 0.007), reaching the prespecified significance level of 0.01 for the primary endpoint. Physical limitation (P = 0.02) was also improved in the PCI group. Complete freedom from angina was more frequent with PCI 71.6% than OMT 57.8% (P = 0.008). There was no periprocedural death or myocardial infarction. At 12 months, major adverse cardiac events were comparable between the two groups.Conclusion: Percutaneous coronary intervention leads to a significant improvement of the health status in patients with stable angina and a CTO as compared with OMT alone.Trial registration: NCT01760083.

BACKGROUND The optimal strategy to treat bifurcation lesions (BFLs) in a percutaneous coronary intervention (PCI) for chronic total occlusions (CTOs) remains unknown. AIMS We sought to assess whether T-provisional or mini-crush is appropriate for BFLs within CTO vessels. PATIENTS AND METHODS From January 2011 to December 2013, patients who underwent successful CTO guidewire crossing and with a BFL within the CTO target vessel were enrolled prospectively and assigned randomly to either T-provisional stenting or the mini-crush technique for BFL treatment. One-year clinical follow-up was performed. Major adverse cardiac and cerebrovascular events (MACCE) were defined as the composite of cardiovascular death, myocardial infarction, target vessel revascularization, and stroke. RESULTS The prevalence of BFLs was 54.3%. A total of 146 patients with BFLs within CTO vessel were enrolled prospectively and assigned randomly to either T-provisional stenting (N=73) or the mini-crush technique (N=73). Angiographic and clinical success rates were similar in the two groups: 91.8 versus 97.2% (P=0.27) and 91.8 versus 94.5% (P=0.67), respectively.Although T-provisional stenting was associated with a nonsignificantly lower incidence of MACCE in case of BFLs located far from the CTO (9.3 vs. 22.2%; P=0.426), the mini-crush technique resulted in higher MACCE-free survival at 1 year in the presence of BFLs within the CTO body or close to the proximal or the distal cap (89.1 vs. 64.9%; P=0.007). CONCLUSION The mini-crush technique appeared to be associated with improved 1-year clinical and angiographic outcomes, particularly when used to treat BFLs located within the CTO body or close to the proximal or the distal cap.

Background Through contemporary literature, the optimal strategy to manage coronary chronic total occlusions (CTOs) remains under debate. Objectives The aim of the Italian Registry of Chronic Total Occlusions (IRCTO) was to provide data on prevalence, characteristics, and outcome of CTO patients according to the management strategy. Methods The IRCTO is a prospective real world multicentre registry enrolling patients showing at least one CTO. Clinical and angiographic data were collected independently from the therapeutic strategy [optimal medical therapy (MT), percutaneous coronary intervention (PCI), or coronary artery bypass grafting (CABG)]; a comparative 1-year clinical followup was performed. Results A total of 1777 patients were enrolled for an overall CTO prevalence of 13.3%. The adopted therapeutic strategies were as follows: MT in 826 patients (46.5%), PCI in 776 patients (43.7%), and CABG in the remaining 175 patients (9.8%). At 1-year follow-up, patients undergoing PCI showed lower rate of major adverse cardiac and cerebrovascular events (MACCE) (2.6% vs. 8.2% and vs. 6.9%; P < 0.001 and P < 0.01) and cardiac death (1.4% vs. 4.7% and vs. 6.3%; P < 0.001 and P < 0.001) in comparison with those treated with MT and CABG, respectively. After propensity scorematching analysis, patients treated with PCI showed lower incidence of cardiac death (1.5 vs. 4.4%; P < 0.001), acute myocardial infarction (1.1 vs. 2.9%; P = 0.03), and re-hospitalization (2.3 vs. 4.4% P = 0.04) in comparison with those managed by MT. Conclusions Our data showed how CTO PCI might significantly improve the survival and decrease MACCE occurrence at 1 year follow-up in comparison with MT and/or CABG.

Coronary chronic total occlusions (CTOs) are commonly encountered in patients undergoing coronary angiography. Several observational studies have demonstrated that successful CTO revascularization is associated with better cardiovascular outcomes and enhanced quality of life (QOL). However, in the absence of randomized trials, its prognostic benefit for patients remains debated. Over the past decade, the interest of the interventional community in CTO percutaneous coronary intervention (PCI) has exponentially grown due to important developments in dedicated equipment and techniques, resulting in high success and low complication rates. Both European and American guidelines have assigned a class IIa (level of evidence B) recommendation for CTO PCI. In the current review, we focus on the impact of CTO revascularization on clinical outcomes and QOL and on appropriate patient selection, and we provide a critical assessment of the current guidelines and recommendations on CTO PCI.

Chronic total occlusions (CTOs) represent a common lesion subset observed in patients who undergo coronary angiography. During the past decade, the interest of the interventionist community in CTOs has exponentially grown with fast advancement in dedicated equipment and techniques, which has resulted in high rates of procedural success and low rates of complications. Although different observational studies have shown that CTO revascularization was associated with good clinical outcome, its real benefit for patients remains to be determined, particularly in the absence of randomized trials. In addition, compared with non-CTO lesions, the American and European guidelines downgraded percutaneous coronary intervention in the setting of CTOs. In this viewpoint, we try to identify patients who would benefit from CTO recanalization, and discuss the issues that might improve the appropriateness of CTO percutaneous coronary intervention.

Bifurcation lesions represent a distinct lesion subset associated with an increased risk of procedural complications. Data on the incidence, treatment, and outcome of bifurcation lesions associated with chronic total occlusions are limited.Among chronic total occlusion procedures performed by a single experienced operator, patients with a bifurcation lesion within the chronic total occlusion vessel and a side branch reference diameter greater than or equal to 2.0 mm were enrolled.A total of 905 patients (mean age 61.1±9.5 years, men 89.4%) were treated for 922 chronic total occlusion lesions. Among these, 244 bifurcation lesions were observed (26.5%). The procedural time was significantly longer in bifurcation lesions (139±67 vs. 124±68 min; P=0.003), with greater use of contrast load (470±193 vs. 436±227 ml; P=0.04) and higher number of stents (3.1±1.5 vs. 2.9±1.4; P=0.035). Overall, an angiographic success was achieved in 91.1% of cases with a higher rate in nonbifurcation lesions (92.5 vs. 87.3%; P=0.04). Coronary perforations were more often observed in bifurcation lesions (4.9 vs. 1.7%; P0.001), resulting in more tamponades (2.4 vs. 0.2%; P0.001). True bifurcations were encountered in the majority of cases (86.8%) and required more two-stent techniques than false bifurcations (50 vs. 18.8%; P=0.001).The incidence of bifurcation lesions in chronic total occlusions is higher than that reported in continuous lesions. The presence of a bifurcation lesion increases the complexity of the procedure and may lead to less angiographic success and more periprocedural complications.

Objectives The study sought to assess the outcome of percutaneous coronary intervention (PCI) of chronic total occlusions (CTOs) in patients with low left ventricular ejection fraction (LVEF) (≤35%). Background Data regarding the outcome of PCI in patients with low LVEF affected by CTO are scarcely reported. Methods The authors performed a prospective longitudinal multicenter study including consecutive patients undergoing elective PCI of CTOs. Patients were subdivided into 3 groups: group 1 (LVEF ≥50%), group 2 (LVEF 35% to 50%), and group 3 (LVEF ≤35%). Results A total of 839 patients (mean 64.6 ± 10.5 years of age, 87.7% men) underwent CTO PCI attempts. Baseline LVEF ≤35% was present in 72 (8.6%) patients. The angiographic success was high (overall 93.6%) and similar among the 3 groups (93.5% vs. 94.4% vs. 91.7%, respectively; all p = NS). In group 3, no periprocedural complications of CTO PCI were observed. Mean clinical follow-up of 16.3 ± 8.2 months duration was available in 781 (93.1%) patients including those with LVEF ≤35%. At 2 years, major cardiac and cerebrovascular events (MACCE) free survival was similar in the 3 groups (86% vs. 82.8% vs. 75.2%; all p = NS). In patients with LVEF ≤35%, LVEF improved significantly in the presence of a successful CTO PCI from 29.1 ± 3.4% to 41.6 ± 7.9% (p < 0.001). Conclusions In CTO patients with low LVEF, PCI could represent a safe and effective revascularization strategy achieving good midterm outcome and LVEF improvement.

Chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has significantly evolved during recent years. High success rates are being achieved by experienced centers and operators, but not at less-experienced centers. Use of CTO crossing algorithms can help improve the success and efficiency of these potentially lengthy procedures. There is a paucity of clinical trial data examining clinical outcomes of CTO PCI, which is critical for further adoption and refinement of the procedure. We provide a detailed overview of the clinical evidence and current available crossing strategies, with emphasis on recent developments and techniques.

BACKGROUND The Nobori biolimus-eluting stent (BES) is a biodegradable polymer drug-eluting stent (DES). Several studies have shown its noninferiority in comparison with durable polymer DES. AIM We sought to investigate the efficacy and the safety of Nobori BES in an all-comer population undergoing a percutaneous coronary intervention. PATIENTS AND METHODS A total of 12 912 patients with 19 947 coronary lesions, undergoing percutaneous coronary intervention with Nobori BES implantation at 200 centres around the world between August 2010 and December 2015, were included in this prospective registry. Patients were stratified into four groups according to the total stent length, with cutoffs at 18, 24 and 28 mm. The primary endpoint was the occurrence of major adverse cardiac events defined as the composite of cardiac death, target vessel myocardial infarction and clinically driven target lesion revascularization at 1 year. RESULTS At 1 year, the major adverse cardiac events rate was the highest (4.6%) in the fourth quartile of stent length (>28 mm), whereas the overall rate of the primary endpoint in the all cohort was 3.5%. Both target lesion revascularization and target vessel revascularization rates were significantly higher in patients with longer stent length was implanted (all P

Intravascular ultrasound has been used for20 years to guide percutaneous coronary intervention in different subsets of coronary lesions. During the last decade, the interest in percutaneous coronary intervention for chronic total occlusion (CTO) has increased dramatically, leading to high success rates. Failure of guidewire crossing is the most common reason for failed CTO attempts. Certain angiographic features, such as blunt proximal CTO cap, tortuosity, heavy calcification, and lack of visibility of path in the distal vessel, increase procedural difficulty. A better understanding of the behavior of the guidewire within the CTO segment may represent a key issue to achieve successful outcome. In this respect, intravascular ultrasound imaging might have potential roles in the recanalization of CTOs. In this paper, we focused on the usefulness and the applications of intravascular ultrasound imaging in percutaneous CTO recanalization, underlying its impact on clinical outcome.

The OAT trial and its angiographic substudy TOSCA-2, along with a number of published commentaries, represents examples of over-interpretation of clinical study results. A study that achieved no statistically significant result for any of the study endpoints can only claim to have proven that their null hypothesis cannot be rejected. The lack of power due to a reduction of patient numbers by one third, and an unexpected low event rate, makes it not unlikely that another trial would be able to disprove the null hypothesis. These statistical facts should be accepted by the authors and commentators. Instead, the inconclusive results were interpreted in such a way that they might apply to patient populations which had not been represented in the original trial (like CTOs without prior MI, or with viable myocardium), or for patients who could have been included, such as multivessel high risk patients, but had not been so by the investigators choice. Furthermore, major problems of the study are ignored, such as accepting TIMI 2 flow as a procedural success.

The aims of this study were to describe the 10-year experience of a single operator dedicated to chronic total occlusion (CTO) and to establish a model for predicting technical failure.During the last decade, the interest in percutaneous coronary interventions (PCIs) of chronic total occlusions (CTOs) has increased, allowing the improvement of success rate.One thousand nineteen patients with CTO underwent 1,073 CTO procedures performed by a single CTO-dedicated operator. The study population was subdivided into 2 groups by time period: period 1 (January 2005 to December 2009, n = 378) and period 2 (January 2010 to December 2014, n = 641). Observations were randomly assigned to a derivation set and a validation set (in a 2:1 ratio). A prediction score was established by assigning points for each independent predictor of technical failure in the derivation set according to the beta coefficient and summing all points accrued.Lesions attempted in period 2 were more complex in comparison with those in period 1. Compared with period 1, both technical and clinical success rates significantly improved (from 87.8% to 94.4% [p = 0.001] and from 77.6% to 89.9% [p 0.001], respectively). A prediction score for technical failure including age ≥75 years (1 point), ostial location (1 point), and collateral filling Rentrop grade 2 (2 points) was established, stratifying procedures into 4 difficulty groups: easy (0), intermediate (1), difficult (2), and very difficult (3 or 4), with decreasing technical success rates. In derivation and validation sets, areas under the curve were comparable (0.728 and 0.772, respectively).With growing expertise, the success rate has increased despite increasing complexity of attempted lesions. The established model predicted the probability of technical failure and thus might be applied to grading the difficulty of CTO procedures.

Objective We report our initial experience with extracorporeal membrane oxygenation (ECMO) use in elective high-risk complex percutaneous coronary intervention (PCI). Background ECMO has been employed as hemodynamic support in patients with cardiac arrest and hemodynamic shock. Methods We performed a single-center prospectical study, enrolling all patients at very high-risk for coronary artery bypass grafting (CABG). Major adverse cardiac and cerebrovascular events (MACCE) were defined as a composite of death, acute myocardial infarction (MI), stroke and further need for revascularization. Results Twelve patients underwent elective high-risk PCI with ECMO support (mean age = 63.5 ± 8.7 years). The mean SYNTAX score was 30.1 ± 10.1. All PCI procedures were successful and no in-hospital MACCE was observed. At 6-months, neither death nor MI was noticed. Two patients (17%) required further revascularization, and one patient required chronic hemodialysis. Conclusions Elective high-risk PCI supported by ECMO is a viable alternative for patients who are at very high risk for CABG.

A 63-year-old female patient presented 15 years after coronary artery bypass graft surgery (CABG) with severe angina pectoris. Invasive coronary angiography revealed occluded bypass grafts, occluded left anterior descending, and right coronary artery (RCA) with a patent left circumflex artery as a last remaining vessel. After non-invasive documentation of large inferior ischaemia by SPECT, percutaneous revascularization (PCI) …

Despite many attempts to improve the management of acute myocardial infarction, only small trends to shorter time intervals before treatment have been reported. The self-care solution developed by the European EPI-MEDICS project (2001-2004) is a novel, very affordable, easy-to-use, portable, and intelligent Personal ECG Monitor (PEM) for the early detection of cardiac ischemia and arrhythmia that is able to record a professional-quality, 3-lead electrocardiogram (ECG) based on leads I, II, and V2; derive the missing leads of the standard 12-lead ECG (thanks to either a generic or a patient-specific transform), compare each ECG with a reference ECG by means of advanced neural network-based decision-making methods taking into account the serial ECG measurements and the patient risk factors and clinical data; and generate different levels of alarms and forward the alarm messages with the recorded ECGs and the patient's Personal electronic Health Record (PHR) to the relevant health care providers by means of a standard Bluetooth-enabled, GSM/GPRS-compatible mobile phone. The ECG records are SCP-ECG encoded and stored with the PHR on a secure personal SD Card embedded in the PEM device. The alarm messages and the PHR are XML encoded. Major alarm messages are automatically transmitted to the nearest emergency call center. Medium or minor alarms are sent on demand to a central PEM Alarm Web Server. Health professionals are informed by a Short Message Service. The PEM embeds itself a Web server to facilitate the reviewing and/or update of the PHR during a routine visit at the office of the general physician or cardiologist. Eighty PEM prototypes have been finalized and tested for several weeks on 697 citizens/patients in different clinical and self-care situations involving end users (188 patients), general physicians (10), and cardiologists (9). The clinical evaluation indicates that the EPI-MEDICS concept may save lives and is very valuable for prehospitalization triage.

We aimed to determine the prevalence of iatrogenic aortic dissection in chronic total occlusion (CTO) recanalization procedures, and to assess the management strategy and outcome of such a complication.This study was a retrospective analysis of CTO percutaneous coronary intervention (PCI) cases performed by a single CTO experienced operator. Iatrogenic aortic dissection was defined as persistent contrast staining in the aortic cusp or root.Among 956 CTO PCI cases, iatrogenic aortic dissection occurred in 8 patients for an overall frequency of 0.83%. The right coronary artery was the CTO involved vessel in all cases with ostial location and severe calcifications in 37.5% and 62.5% of cases, respectively. Four patients underwent the antegrade approach and a retrograde strategy was adopted in the remaining 4 patients. The iatrogenic aortic dissection started from the right sinus of Valsalva in 87.5% of cases and catheter trauma was the presumed mechanism of dissection in most cases. Stenting of the entry point was performed in all cases, and dissection was limited (40 mm) in all patients. No patients required emergency surgery. One cardiac death was observed 12 days after the index procedure (12.5%), and a mean follow-up of 31.5 months was uneventful in the remaining 7 patients.CTO recanalization procedures might be associated with a greater incidence of iatrogenic aortic dissection than non-CTO PCI. The therapeutic strategy and outcome depend on the rapidity of the entry point sealing and the degree of extension of the dissection into the aorta in serial imaging assessment.