[Why to treat a total chronic coronary occlusion?] / Pourquoi traiter une occlusion coronaire totale chronique ?

Despite an incidence of about 15% of the patients undergoing coronary angiography, total chronic occlusions (CTO) are rarely revascularized by percutaneous angioplasty (PCI). Nevertheless, current evidence suggest that successful CTO-PCI improve symptoms, quality of live and long-term survival. During the last years, improvement of specific techniques for these complexes procedures and increasing experience of operators allow actually to obtain success and complications rates almost equivalent to non-CTO lesions angioplasty. This review focus on the clinical benefits of CTO revascularization and on appropriate patient selection.

Bien que présentes chez environ 15% des patients admis pour une coronarographie diagnostique, les occlusions coronaires totales chroniques (CTO) sont très rarement revascularisées par angioplastie percutanée. Pourtant, de nombreux éléments suggèrent que la revascularisation percutanée d'une CTO est associée à une amélioration des symptômes angineux, de la qualité de vie et de la survie à long terme. Ces dernières années, l'amélioration des techniques dédiées à ces procédures complexes et l'expérience croissante des opérateurs ont permis d'obtenir des taux de succès et de complications qui approchent ceux des lésions coronaires non-CTO. Cet article fait le point sur les principaux bénéfices de traiter une CTO et sur la sélection appropriée des patients.

Late gadolinium enhancement CMR in primary mitral regurgitation.

AIMS: The appropriate timing for surgery in severe asymptomatic primary mitral regurgitation (MR) remains controversial. It has been shown that late gadolinium enhancement on cardiovascular magnetic resonance (LGE CMR), which may identify myocardial fibrosis, is associated with a worse outcome in various cardiomyopathies. We sought to investigate the prevalence and significance of delayed enhancement in primary MR. METHODS: We prospectively included 41 patients with at least moderate primary MR and without overt signs of left ventricular (LV) dysfunction. Patients with evidence of coronary artery disease, arrhythmias or significant concomitant valvular disease were excluded. All patients were scheduled for transthoracic echocardiography and LGE CMR. RESULTS: A total of 39 patients had interpretable LGE CMR images. Among them, 12 (31%) had late contrast uptake of the LV wall. LGE CMR showed an infarct pattern in three patients, a pattern of mid-wall fibrosis in seven patients and two patients had a combined pattern. Patients with delayed enhancement on CMR had significant higher LV diameters (LV end-systolic diameter 39 ± 4 vs. 34 ± 5 mm, P = 0·002; LV end-diastolic diameter 57 ± 5 vs. 50 ± 5 mm, P = 0·001). There was a trend towards a higher indexed left atrial volume (55 ± 21 vs. 44 ± 13 mL/m², P = 0·06). By contrast, there was no significant association between myocardial contrast uptake and age, LV ejection fraction and MR severity. CONCLUSION: Left ventricular remodelling seems to be associated with the presence of delayed enhancement on CMR in primary MR. Further data are needed to determine whether LGE CMR can predict a less favourable outcome or could improve risk stratification in asymptomatic primary MR.

Assessment of left ventricular volumes and primary mitral regurgitation severity by 2D echocardiography and cardiovascular magnetic resonance.

BACKGROUND: Two-dimensional transthoracic echocardiography (2DTTE) remains the first-line diagnostic imaging tool to assess primary mitral regurgitation although cardiovascular magnetic resonance (CMR) has proven to establish left ventricular function more accurately and might evaluate mitral regurgitation severity more reliably. We sought to compare routine evaluation of left ventricular function and mitral regurgitation severity by 2DTTE with assessment by CMR in moderate to severe primary mitral regurgitation without overt left ventricular dysfunction. METHODS: We prospectively included 38 patients (79% of male, age 57 ± 14 years) with at least moderate primary mitral regurgitation, a left ventricular ejection fraction ≥60% and a left ventricular end-systolic diameter ≤45 mm. Patients with evidence of coronary artery disease, arrhythmias or significant concomitant valvular disease were excluded. All patients were scheduled for 2DTTE and CMR. RESULTS: Left ventricular end-diastolic and end-systolic volumes were significantly underestimated by 2DTTE in comparison with CMR, although there was a strong correlation (Pearson r = 0.81, p < 0.00001 and r = 0.7, p < 0.00001, respectively). Measurement of the regurgitant orifice was similar between 2DTTE PISA method and planimetry by CMR (47 ± 24 vs. 42 ± 16 mm2, p = 0.12) with a strong correlation between both imaging techniques (Pearson r = 0.76, p < 0.0001). By contrast, assessment of the regurgitant volume by 2DTTE and by phase contrast velocity mapping by CMR showed poor agreement. CONCLUSIONS: In moderate to severe primary mitral regurgitation without overt left ventricular dysfunction, 2DTTE significantly underestimates left ventricular remodelling in comparison to CMR. Measurement of the regurgitant orifice with planimetry by CMR shows good agreement with the PISA method by 2DTTE and thus may be a valuable alternative to assess mitral regurgitation severity.

Plant-based red colouration of shell beads 15,000 years ago in Kebara Cave, Mount Carmel (Israel).

Decorating the living space, objects, body and clothes with colour is a widespread human practice. While the habitual use of red mineral pigments (such as iron-oxide, e.g., ochre) by anatomically modern humans started in Africa about 140,000 years ago, the earliest documentation of the use of organic plant or animal-based red pigments is known from only 6,000 years ago. Here, we report the oldest reliable evidence of organic red pigment use 15,000 years ago by the first sedentary hunter-gatherers in the Levant. SEM-EDS and Raman Spectroscopy analyses of 10 red-stained shell beads enabled us to detect and describe the use of a colourant made of Rubiaceae plants roots (Rubia spp., Asperula spp., Gallium spp.) to colour personal adornments from the Early Natufian of Kebara cave, Mount Carmel, Israel. This adds a previously unknown behavioural aspect of Natufian societies, namely a well-established tradition of non-dietary plant processing at the beginning of the sedentary lifestyle. Through a combined multidisciplinary approach, our study broadens the perspectives on the ornamental practices and the chaînes opératoires of pigmenting materials during a crucial period in human history.

Bone aerophones from Eynan-Mallaha (Israel) indicate imitation of raptor calls by the last hunter-gatherers in the Levant.

Direct evidence for Palaeolithic sound-making instruments is relatively rare, with only a few examples recorded from Upper Palaeolithic contexts, particularly in European cultures. However, theoretical considerations suggest that such artefacts have existed elsewhere in the world. Nevertheless, evidence for sound production is tenuous in the prehistoric archaeological record of the Levant, the study of music and its evolution being sparsely explored. Here we report new evidence for Palaeolithic sound-making instruments from the Levant with the discovery of seven aerophones made of perforated bird bones in the Final Natufian site of Eynan-Mallaha, Northern Israel. Through technological, use-wear, taphonomic, experimental and acoustical analyses, we demonstrate that these objects were intentionally manufactured more than 12,000 years ago to produce a range of sounds similar to raptor calls and whose purposes could be at the crossroads of communication, attracting hunting prey and music-making. Although similar aerophones are documented in later archaeological cultures, such artificial bird sounds were yet to be reported from Palaeolithic context. Therefore, the discovery from Eynan-Mallaha contributes new evidence for a distinctive sound-making instrument in the Palaeolithic. Through a combined multidisciplinary approach, our study provides important new data regarding the antiquity and development of the variety of sound-making instruments in the Palaeolithic at large and particularly at the dawn of the Neolithic in the Levant.

The evolution of the CTO-PCI landscape in Belgium and Luxembourg: a four-year appraisal.

BACKGROUND: To chart the evolution of the CTO-PCI landscape in Belgium and Luxembourg, the Belgian Working Group on Chronic Total Occlusions (BWGCTO) was established in 2016. METHODS: Between May 2016 and December 2019, patients undergoing a CTO-PCI treatment were prospectively and consecutively enrolled. Twenty-one centres in Belgium and one in Luxembourg participated. Individual operators had mixed levels of expertise in treating CTO lesions. Demographic, angiographic, procedural parameters and incidence of major adverse cardiac and cerebrovascular events (MACCE) were systematically registered. RESULTS: Over a four-year enrolment period, 1832 procedures were performed in 1733 patients achieving technical success in 1474 cases (80%), with an in-hospital MACCE rate of 2.3%. Fifty-nine (3%) cases were re-attempt procedures of which 41 (69%) were successful. High-volume centres treated more complex lesions (mean J-CTO score: 2.15 ± 1.21) as compared to intermediate (mean J-CTO score: 1.72 ± 1.23; p < 0.001) and low-volume centres (mean J-CTO score: 0.99 ± 1.21; p = 0.002). Despite this, success rates did not differ between centres (p = 0.461). Overall success rates did not differ over time (p = 0.810). High-volume centres progressively tackled more complex CTOs while keeping success rates stable. In all centres, the most applied strategy was antegrade wire escalation (83%). High-volume centres more often successfully applied antegrade dissection and re-entry and retrograde techniques in lesions with higher complexity. CONCLUSION: With variable experience levels, operators treated CTOs with high success and relatively few complications. Although AWE remains the most used technique, it is paramount for operators to be skilled in all contemporary techniques in order to be successful in more complex CTOs.

Angioedema: a rare and sometimes delayed side effect of angiotensin-converting enzyme inhibitors.

The effects of angiotensin converting enzyme (ACE) inhibitors result from the inhibition of the ACE (kininase II) to ultimately influence both the renin-angiotensin system and the degradation of the bradykinin (BK) metabolism. ACE inhibitors block the degradation of BK and substance P by ACE. In addition, an active metabolite of BK (Des-Arg9-BK) is catalysed by kininase I and its degradation is controlled in part by the conversion enzyme. These molecules have been associated with increased plasma extravasation associated with ACE inhibitors. ACE inhibitors are the leading cause of drug-induced Angioedema (AE). Symptoms of AE mainly occur after the first month of treatment by ACE. However, very late onset cases, sometimes after several years of stable therapy, are also described in the literature. It has been observed that patients previously stable under ACE inhibitor will most likely develop AE soon after the addition of another medication, including the combination of aspirin or non-steroid anti-inflammatory drugs with ACE inhibitor which has proved to be the most common cause, accounting for close to 50% of all AE cases related to ACE inhibitors. This side effect of ACE inhibitors, sometimes very late and rare, deserves to be recalled.

Epicardial fat amount is associated with the magnitude of left ventricular remodeling in aortic stenosis.

Both genetic and environmental factors interact to control left ventricular (LV) remodeling in the context of aortic stenosis (AS). Epicardial adipose tissue (EAT) is a specific visceral adipose tissue with paracrine properties in close contact with the myocardium. We sought to assess determinants of EAT amount and its association with the magnitude and pattern of LV remodeling in patients suffering from severe AS. Between January 2014 and September 2017, we prospectively explored consecutive patients referred to our Heart Valve Center for SAVR presenting with severe AS and normal left ventricular ejection fraction (> 50%). Comprehensive transthoracic echocardiography (TTE) including assessment of LV remodeling and EAT amount were performed. 202 patients were included. EAT was significantly larger in elderly, diabetic and obese patients. EAT thickness was correlated positively with indexed LV mass in AS (r2 = 0.21; p < 0.0001) as well as severe LV remodeling pattern. Importantly, this observation persisted after adjustment for other factors associated with LV remodeling (ß ± SE = 1.74 ± 0.34; p < 0.0001). Large amounts of EAT are positively and independently associated with more pronounced and severe LV remodeling in severe AS. Further exploration regarding the impact of functional properties of EAT on LV remodeling is required.

Statin therapy modulates thickness and inflammatory profile of human epicardial adipose tissue.

BACKGROUND: Epicardial adipose tissue (EAT) thickness and pro-inflammatory status has been shown to be associated with several cardiac diseases, including aortic stenosis (AS). Thus, cardiac visceral fat could represent a potential new target for drugs. In the present study we evaluate the effect of statin therapy on EAT accumulation and inflammation. METHODS: Echocardiographic EAT thickness was assessed in 193 AS patients taking (n.87) and not taking (n.106) statins, undergoing cardiac surgery. To explore the association between statin therapy and EAT inflammation, EAT biopsies were obtained for cytokines immunoassay determination in EAT secretomes. An in vitro study was also conducted and the modulation of EAT and subcutaneous adipose tissue (SCAT) secretomes by atorvastatin was assessed in paired biopsies. RESULTS: Statin therapy was significantly associated with lower EAT thickness (p < 0.0001) and with lower levels of EAT-secreted inflammatory mediators (p < 0.0001). Of note, there was a significant correlation between EAT thickness and its pro-inflammatory status. In vitro, atorvastatin showed a direct anti-inflammatory effect on EAT which was significantly higher compared to the SCAT response to statin incubation (p < 0.0001). CONCLUSIONS: The present study indicates a robust association between statin therapy and reduced EAT accumulation in patients with AS. The present data also suggest a direct relationship between EAT thickness and its inflammatory status, both modulated by statin therapy. The in vitro results support the hypothesis of a direct action of statins on EAT secretory profile. Overall our data suggest EAT as a potential new therapeutic target for statin therapy.

Predicting Disease Progression and Mortality in Aortic Stenosis: A Systematic Review of Imaging Biomarkers and Meta-Analysis.

Background: Detecting among patients with aortic stenosis (AS) those who are likely to rapidly progress, yet potentially benefiting from prophylactic aortic valve replacement, is needed for improved patient care. The objective of this study was to evaluate the role of imaging biomarkers in predicting the progression to clinical symptoms and death in patients with AS. Methods: We searched the Pubmed and the International Clinical Trials Registry Platform databases for studies including patients with AS, and investigating imaging techniques, published in any language until Jan 1, 2018. Eligible sets of data include effect of imaging biomarkers relative to: (1) Overall mortality, (2) Cardiac mortality, and (3) Overall events (Symptom onset and Major Adverse Cardiovascular Events). Meta-analysis was used to examine associations between the imaging biomarkers and outcomes of AS using Random Effect models. Results: Eight studies and 1,639 patients were included after systematic review. Four studies investigated aortic valve calcification (AVC) whereas the remaining investigated biomarkers provided by cardiac magnetic resonance (CMR). Four articles investigated the presence of midwall fibrosis on late-gadolinium enhancement imaging, three reported its extent (LGE%) and two, the myocardial extracellular volume (ECV). By decreasing strength of association, there were significant associations between cardiac mortality and LGE% [Relative Risk (RR) = 1.05, 95% Confidence Interval (CI) 1.01-1.10]; overall mortality and AVC (RR = 1.19, 95%CI: 1.05-1.36); overall events and ECV (RR = 1.68, 95%CI: 1.17-2.41); cardiac mortality and midwall fibrosis (RR = 2.88, 95%CI: 1.12-7.39). Conclusion: AVC and myocardial fibrosis imaging biomarkers predict the outcomes in AS, and help understanding AS pathophysiology and setting therapeutic targets.

Coronary chronic total occlusion intervention: utility or futility.

INTRODUCTION: Despite an incidence of about 18-52% of the patients undergoing coronary angiography, chronic total occlusions (CTO) are rarely revascularised by percutaneous angioplasty (PCI). Nevertheless, current evidence suggests that successful CTO angioplasty improves symptoms, quality of life and long-term survival. During the last decade, the improvement of specific tools and techniques for these complex procedures, and the increasing experience of operators, have led to the achievement of success and complication rates almost equivalent to non-CTO angioplasty. Areas covered: This review focuses on the clinical benefits of CTO revascularization and on appropriate patient selection. Expert commentary: Current evidence suggests that successful CTO-PCI improves symptoms, quality of life and long-term survival. During the last years, the improvement of specific techniques for these complex procedures and the increasing experience of operators, have led to the achievement of success and complication rates almost equivalent to non-CTO lesion angioplasty.

Outcomes of Patients With Asymptomatic Aortic Stenosis Followed Up in Heart Valve Clinics.

Importance: The natural history and the management of patients with asymptomatic aortic stenosis (AS) have not been fully examined in the current era. Objective: To determine the clinical outcomes of patients with asymptomatic AS using data from the Heart Valve Clinic International Database. Design, Setting, and Participants: This registry was assembled by merging data from prospectively gathered institutional databases from 10 heart valve clinics in Europe, Canada, and the United States. Asymptomatic patients with an aortic valve area of 1.5 cm2 or less and preserved left ventricular ejection fraction (LVEF) greater than 50% at entry were considered for the present analysis. Data were collected from January 2001 to December 2014, and data were analyzed from January 2017 to July 2018. Main Outcomes and Measures: Natural history, need for aortic valve replacement (AVR), and survival of asymptomatic patients with moderate or severe AS at entry followed up in a heart valve clinic. Indications for AVR were based on current guideline recommendations. Results: Of the 1375 patients included in this analysis, 834 (60.7%) were male, and the mean (SD) age was 71 (13) years. A total of 861 patients (62.6%) had severe AS (aortic valve area less than 1.0 cm2). The mean (SD) overall survival during medical management (mean [SD] follow up, 27 [24] months) was 93% (1%), 86% (2%), and 75% (4%) at 2, 4, and 8 years, respectively. A total of 104 patients (7.6%) died under observation, including 57 patients (54.8%) from cardiovascular causes. The crude rate of sudden death was 0.65% over the duration of the study. A total of 542 patients (39.4%) underwent AVR, including 388 patients (71.6%) with severe AS at study entry and 154 (28.4%) with moderate AS at entry who progressed to severe AS. Those with severe AS at entry who underwent AVR did so at a mean (SD) of 14.4 (16.6) months and a median of 8.7 months. The mean (SD) 2-year and 4-year AVR-free survival rates for asymptomatic patients with severe AS at baseline were 54% (2%) and 32% (3%), respectively. In those undergoing AVR, the 30-day postprocedural mortality was 0.9%. In patients with severe AS at entry, peak aortic jet velocity (greater than 5 m/s) and LVEF (less than 60%) were associated with all-cause and cardiovascular mortality without AVR; these factors were also associated with postprocedural mortality in those patients with severe AS at baseline who underwent AVR (surgical AVR in 310 patients; transcatheter AVR in 78 patients). Conclusions and Relevance: In patients with asymptomatic AS followed up in heart valve centers, the risk of sudden death is low, and rates of overall survival are similar to those reported from previous series. Patients with severe AS at baseline and peak aortic jet velocity of 5.0 m/s or greater or LVEF less than 60% have increased risks of all-cause and cardiovascular mortality even after AVR. The potential benefit of early intervention should be considered in these high-risk patients.

Diagnostic accuracy of computed tomography coronary angiography in routine practice.

OBJECTIVES: The recent newer advances in computed tomography have dramatically changed our approach to imaging cardiac disease. This study sought to compare the diagnostic value of 16-multi-detector spiral computed tomography (MSCT) for detecting coronary artery stenosis. METHODS: A total of 88 consecutive patients (52 men, mean age 68 +/- 8 years) with atypical chest pain, stable angina or suspicion of ischaemia at stress test were studied by MSCT and invasive coronary angiography (ICA). The MSCT images and multiplanar reconstructions were analysed regarding the presence of > or =50% coronary artery lesion. RESULTS: All 88 scans obtained at a mean heart rate of 68 +/- 8 beats/min were interpretable. Sixteen coronary segments were evaluated in each patient. Of the 1320 segments examined, 148 (11%) showed poor image quality.A total of 150 significant lesions were detected using ICA, and 80 of 150 (53%) were detected by MSCT. Sensitivity, specificity, positive and negative predictive values were as follows: 53%, 97%, 68%, and 94%. Fifty-four patients had > or =50% coronary stenosis. The diagnosis was confirmed by MSCT in 42 patients and correctly ruled out in 30. By patient-based analysis, positive and negative predictive values were 91% and 71%. CONCLUSION: Although its specificity is high, the sensitivity of 16-slice MSCT for detecting > or =50% coronary stenosis in non-selected patients submitted to ICA is rather low suggesting that for daily practice the diagnostic value of this technique should be improved.

Non-invasive imaging of a giant right coronary artery due to a coronary fistula.

Coronary artery fistula is a relatively rare finding in patients undergoing diagnostic cardiac catheterization. Incidence, angiographic characteristics and natural history of coronary fistulas of this type have not been well defined in the literature. We report a case of a 54-year-old man in whom such abnormalities have been diagnosed with invasive and non-invasive coronary imaging and review the epidemiology, treatment and prognosis of coronary fistulas.

Multimodality imaging for the diagnosis and assessment of aortic stenosis severity.

INTRODUCTION: Aortic stenosis (AS) is the most common cause of valvular heart disease. Imaging plays a major role in the diagnosis and evaluation of AS severity. AREAS COVERED: The present review focuses on new emerging concepts in AS by stressing the substantial value of imaging into the understanding of the complex pathophysiology and management of AS. Expert commentary: Though, standard 2D echocardiography is often diagnostic multi-modality imaging can be required in patients with doubtful results or to refine the evaluation of AS.

Impact of Serial B-Type Natriuretic Peptide Changes for Predicting Outcome in Asymptomatic Patients With Aortic Stenosis.

BACKGROUND: The aim of this study was to determine the impact on the outcome of serial B-type natriuretic peptide (BNP) changes during follow-up in asymptomatic patients with ≥ moderate aortic stenosis (AS) and preserved left ventricular ejection fraction. METHODS: We prospectively screened 69 patients who underwent comprehensive transthoracic echocardiography, BNP level measurement at baseline and after every 6 or 12 months. Annualized BNP changes were calculated as the difference between the last and baseline BNP measurements divided by the duration of follow-up. The primary endpoint was the occurrence of symptoms, aortic valve replacement, or cardiovascular death. RESULTS: During a follow-up of 30 ± 19 months, 43 patients experienced a cardiac event. These patients were significantly older (73 ± 9 vs 65 ± 16 years; P = 0.010), had more often dyslipidemia (79% vs 42%; P = 0.038), more severe AS (peak velocity: 3.9 ± 0.6 vs 3.5 ± 0.6 m/s; P = 0.002), larger indexed left atrial area (10.2 ± 2.5 vs 8.7 ± 1.9 cm(2)/m(2); P = 0.006), and a higher increase in annualized BNP (+90 ± 155 vs +7 ± 49 pg/mL/y; P = 0.010). Patients with higher annualized BNP changes (> 20 pg/mL/y) had a significantly lower cardiac event-free survival (1 year: 63 ± 8% vs 97 ± 3%; 3 years: 31 ± 8% vs 68 ± 8%; P < 0.001). Using the multivariate Cox proportional hazards model, higher annualized BNP changes were significantly associated with increased risk of cardiac events (hazard ratio: 2.73, 95% confidence interval: 1.27-5.86; P = 0.010) after adjustment for age, dyslipidemia, and echocardiographic parameters. CONCLUSIONS: In asymptomatic patients with AS and preserved left ventricular ejection fraction, the use of serial BNP changes may help to anticipate development of class I indication for aortic valve replacement.

Elective ostial left main stenting: a tailored approach.

Elective left main (LM) stenting is increasingly performed as a valuable alternative to coronary artery bypass grafting. Nevertheless, clinical data are limited to registries, and randomized trials have not been published. Intravascular ultrasound (IVUS) has been recognized as an accurate tool for assessing optimal stent deployment. We hereby report the usefulness of IVUS in defining the interventional strategy in four consecutive patients presenting with severe, symptomatic ostial LM disease, and this in the era of drug-eluting stents. The first two patients were treated by a short drug-eluting stent for a critical LM stenosis as IVUS demonstrated a reference diameter < 3.7 mm. The third patient had a larger reference diameter and was treated with conventional stenting with optimization of the result by IVUS. IVUS was particularly helpful in all patients to confirm accurate stent placement in relation to the LM ostium and bifurcation. In another patient, based on IVUS findings, surgery was preferred. This patient with diabetes as a risk factor presented with comparable angiographic features. IVUS, however, showed diffuse disease without any healthy reference segment in the LM. All stented patients are asymptomatic at 15 +/- 7 months follow-up with negative stress testing. The present observation indicates that IVUS is an essential tool for strategic selection and to optimize percutaneous coronary intervention for LM disease.