Tricuspid valve disease and cardiac implantable electronic devices.

The role of cardiac implantable electronic device (CIED)-related tricuspid regurgitation (TR) is increasingly recognized as an independent clinical entity. Hence, interventional TR treatment options continuously evolve, surgical risk assessment and peri-operative care improve the management of CIED-related TR, and the role of lead extraction is of high interest. Furthermore, novel surgical and interventional tricuspid valve treatment options are increasingly applied to patients suffering from TR associated with or related to CIEDs. This multidisciplinary review article developed with electrophysiologists, interventional cardiologists, imaging specialists, and cardiac surgeons aims to give an overview of the mechanisms of disease, diagnostics, and proposes treatment algorithms of patients suffering from TR associated with CIED lead(s) or leadless pacemakers.

TRI-SCORE and benefit of intervention in patients with severe tricuspid regurgitation.

BACKGROUND AND AIMS: Benefit of tricuspid regurgitation (TR) correction and timing of intervention are unclear. This study aimed to compare survival rates after surgical or transcatheter intervention to conservative management according to a TR clinical stage as assessed using the TRI-SCORE. METHODS: A total of 2,413 patients with severe isolated functional TR were enrolled in TRIGISTRY (1217 conservatively managed, 551 isolated tricuspid valve surgery, and 645 transcatheter valve repair). The primary endpoint was survival at 2 years. RESULTS: The TRI-SCORE was low (≤3) in 32%, intermediate (4-5) in 33%, and high (≥6) in 35%. A successful correction was achieved in 97% and 65% of patients in the surgical and transcatheter groups, respectively. Survival rates decreased with the TRI-SCORE in the three treatment groups (all P < .0001). In the low TRI-SCORE category, survival rates were higher in the surgical and transcatheter groups than in the conservative management group (93%, 87%, and 79%, respectively, P = .0002). In the intermediate category, no significant difference between groups was observed overall (80%, 71%, and 71%, respectively, P = .13) but benefit of the intervention became significant when the analysis was restricted to patients with successful correction (80%, 81%, and 71%, respectively, P = .009). In the high TRI-SCORE category, survival was not different to conservative management in the surgical and successful repair group (61% and 68% vs 58%, P = .26 and P = .18 respectively). CONCLUSIONS: Survival progressively decreased with the TRI-SCORE irrespective of treatment modality. Compared to conservative management, an early and successful surgical or transcatheter intervention improved 2-year survival in patients at low and, to a lower extent, intermediate TRI-SCORE, while no benefit was observed in the high TRI-SCORE category.

Procedural and clinical outcomes of patients undergoing a TAVI in TAVI procedure: Rationale and design of the multicentre, prospective, observational ReTAVI registry.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is increasingly being used in younger patients and those with lower peri-procedural risk, meaning more patients will live long enough to experience structural valve deterioration (SVD) of the bioprosthesis, indicating repeated TAVI. Experience of repeated TAVI-transcatheter heart valve (THV) implantation into an index THV is limited. This registry aims to assess the peri-procedural and short-term safety, efficacy and durability of repeated TAVI. METHODS: The ReTAVI Prospective observational registry is an investigator-initiated, multicentre, international, prospective registry of patients undergoing repeated TAVI using balloon-expandable SAPIEN prosthesis to evaluate procedural and short-term safety, efficacy and durability as well as anatomical and procedural factors associated with optimal results. The registry will enrol at least 150 patients across 60 high-volume centres. Patients must be ≥18 years old, have had procedural success with their first TAVI, have index THV device failure, intend to undergo repeated TAVI and be considered suitable candidates by their local Heart Team. All patients will undergo a 30-day and 12-month follow-up. The estimated study completion is 2025. CONCLUSIONS: The registry will collect pre-, peri-, postoperative and 12-months data on patients undergoing repeated TAVI procedures with THVs for failure of the index THV and determine VARC-3-defined efficacy and safety at 30 days and functional outcome at 12 months. The registry will expand existing data sets and identify patient characteristics/indicators related to complications and clinical benefits for patients with symptomatic severe calcific degenerative aortic stenosis.

Use of cardiac imaging in chronic coronary syndromes: the EURECA Imaging registry.

BACKGROUND: The prospective, multicentre EURECA registry assessed the use of imaging and adoption of the European Society of Cardiology (ESC) Guidelines (GL) in patients with chronic coronary syndromes (CCS). METHODS: Between May 2019 and March 2020, 5156 patients were recruited in 73 centres from 24 ESC member countries. The adoption of GL recommendations was evaluated according to clinical presentation and pre-test probability (PTP) of obstructive coronary artery disease (CAD). RESULTS: The mean age of the population was 64 ± 11 years, 60% of patients were males, 42% had PTP >15%, 27% had previous CAD, and ejection fraction was <50% in 5%. Exercise ECG was performed in 32% of patients, stress imaging as the first choice in 40%, and computed tomography coronary angiography (CTCA) in 22%. Invasive coronary angiography (ICA) was the first or downstream test in 17% and 11%, respectively. Obstructive CAD was documented in 24% of patients, inducible ischaemia in 19%, and 13% of patients underwent revascularization. In 44% of patients, the overall diagnostic process did not adopt the GL. In these patients, referral to stress imaging (21% vs. 58%; P < 0.001) or CTCA (17% vs. 30%; P < 0.001) was less frequent, while exercise ECG (43% vs. 22%; P < 0.001) and ICA (48% vs. 15%; P < 0.001) were more frequently performed. The adoption of GL was associated with fewer ICA, higher proportion of diagnosis of obstructive CAD (60% vs. 39%, P < 0.001) and revascularization (54% vs. 37%, P < 0.001), higher quality of life, fewer additional testing, and longer times to late revascularization. CONCLUSIONS: In patients with CCS, current clinical practice does not adopt GL recommendations on the use of diagnostic tests in a significant proportion of patients. When the diagnostic approach adopts GL recommendations, invasive procedures are less frequently used and the diagnostic yield and therapeutic utility are superior.

Automatic identification of areas with low-voltage fragmented electrograms for the detection of the critical isthmus of atypical atrial flutters.

INTRODUCTION: Critical isthmuses of atypical atrial flutters (AAFLs) are usually located at slow conduction areas that exhibit fractionated electrograms. We tested a novel software, intended for integration with a commercially available navigation system, that automatically detects fractionated electrograms, to identify the critical isthmus in patients with AAFL ablation. METHODS AND RESULTS: All available patients were analyzed; 27 patients with 33 AAFLs were included. The PentaRay NAV catheter (Biosense Webster) was used for mapping. The novel software was retrospectively applied; fractionated points with duration ≥80 ms and bipolar voltage between 0.05 and 0.5 mV were highlighted on the surface of maps. In 10 randomly chosen AAFLs, an expert electrophysiologist evaluated the positive predictive value of the algorithm to detect true fractionation: 74.4%. We tested the capacity of the software to identify areas of fractionation (defined as clusters of ≥3 adjacent points with fractionation) at the critical isthmus of the AAFLs (defined using conventional mapping criteria). An area of fractionation was identified at the critical isthmus in 30 cases (91%). Globally, 144 areas of fractionation (median number per AAFL 4 [3-6]) were identified. Duration of the fractionation or the surface of the areas was not different between areas at critical isthmuses and the rest. Setting the fractionation score filter of the software in nine provided best performance. CONCLUSIONS: The novel software detected areas of fractionation at the critical isthmus in most AAFLs, which may help identify the critical isthmus in clinical practice.

Response rate in cardiac resynchronization therapy patients implanted with a left ventricular quadripolar lead and the MultiPoint™ pacing feature early activated. QUARTO III.

BACKGROUND: Although cardiac resynchronization therapy (CRT) is beneficial in most heart failure patients, up to 40% do not respond to CRT. It has been suggested that multipoint left ventricle pacing (MPP) would increase the response rate. AIM: To assess the CRT response rate at 6 months in patients implanted with a CRT device with the MPP feature activated early after the implant. METHODS: This was a multicentre, prospective, open-label and non-randomized study. The primary endpoint was response to biventricular pacing defined as >15% relative reduction in left ventricular end-systolic volume (LVESV) comparing echocardiography measurements performed at baseline and 6 months by a core laboratory. Among secondary endpoints the combined endpoint of mortality or all-cause hospitalizations was evaluated. Primary study endpoint and clinical outcomes were compared to a Quarto II control cohort. RESULTS: Totally, 105 patients were included. The response rate was 64.6% (97.5% lower confidence bound 53%). Mean relative reduction in LVESV was 25.3%, and mean absolute increase in LVEF was 9.4%. The subjects with device programmed using anatomical approach showed a trend towards higher responder rate than those using the electrical approach (72% vs. 61.1%, p = 0.32). Finally, the combined incidence of mortality and or all-cause hospitalizations at 6 month was 12.4%. CONCLUSIONS: Early activation of MPP was not associated to an advantage increasing echocardiography responders to CRT at 6 months of follow-up. Nevertheless, patients programmed using widest pacing cathodes had a numerically higher responder rate. Finally, early activation of MPP was associated to a low incidence of clinical endpoints at 6 months of follow-up.

Improving access to transcatheter aortic valve implantation across Europe by restructuring cardiovascular services: An expert council consensus statement.

Transcatheter aortic valve implantation (TAVI) is recommended for a growing range of patients with severe aortic stenosis in the European Society of Cardiology and European Association for Cardio-Thoracic Surgery (ESC/EACTS) 2021 Guidelines update. However, guideline implementation programs are needed to ensure the application of clinical recommendations which will favorably influence disease outcomes. An Expert Council was convened to identify whether cardiology services across Europe are set up to address the growing needs of patients with severe aortic stenosis for increased access to TAVI by identifying the key challenges faced in growing TAVI programs and mapping associated solutions. Wide variation exists across Europe in terms of TAVI availability and capacity to deliver the increased demand for TAVI in different countries. The recommendations of this Expert Council focus on the short-to-medium-term aspects where the most immediate, actionable impact can be achieved. The focus on improving procedural efficiency and optimizing the patient pathway via clinical practice and patient management demonstrates how to mitigate the current major issues of shortfall in catheterization laboratory, workforce, and bed capacity. Procedural efficiencies may be achieved through steps including streamlined patient assessment, the benchmarking of standards for minimalist procedures, standardized approaches around patient monitoring and conduction issues, and the implementation of nurse specialists and dedicated TAVI coordinators to manage organization, logistics, and early mobilization. Increased collaboration with wider stakeholders within institutions will support successful TAVI uptake and improve patient and economic outcomes. Further, increased education, collaboration, and partnership between cardiology centers will facilitate sharing of expertise and best clinical practice.

Inter-center reproducibility of standard and advanced echocardiographic parameters in the EACVI-AFib echo registry.

AIM: we sought to test the inter-center reproducibility of 16 echo laboratories involved in the EACVI-Afib Echo Europe. METHODS: This was done on a dedicated setting of 10 patients with sinus rhythm (SR) and 10 with persistent atrial fibrillation (AF), collected by the Principal Investigator. Images and loops of echo-exams were stored and made available for labs. The tested measurements included main echo-Doppler parameters, global longitudinal strain (GLS) and peak atrial longitudinal strain (PALS). RESULTS: Single measures interclass correlation coefficients (ICCs) of left ventricular mass and ejection fraction were suboptimal in both patients with SR and AF. Among diastolic parameters, ICCs of deceleration time were poor, in particular in AF (=.50). ICCs of left atrial size and function, besides optimal in AF, showed an acceptable despite moderate concordance in SR. ICC of GLS was .81 and .78 in SR and AF respectively. ICCs of PALS were suitable but lower in 4-chamber than in 2-chamber view. By depicting the boxplot of the 16 laboratories, GLS distribution was completely homogeneous in SR, whereas GLS of AF and PALS of both SR and AF presented a limited number of outliers. GLS mean ± SE of the 16 labs was 19.7 ± .36 (95% CI: 18.8-20.4) in SR and 16.5 ± .29 (95% CI: 15.9-17.1) in AF, whereas PALS mean ± SE was 43.8 ± .70 (95% CI: 42.3-45.3) and 10.2 ± .32 (95% CI: 9.5-10.9) respectively. CONCLUSION: While the utilization of some standard-echo variables should be discouraged in registries, the application of GLS and PALS could be largely promoted because their superior reproducibility, even in AF.

Characterization of high-power and very-high-power short-duration radiofrequency lesions performed with a new-generation catheter and a temperature-control ablation mode.

INTRODUCTION: High-power short-duration (HPSD) has been proposed to shorten procedure times while maintaining efficacy and safety. We evaluated the differences in size and geometry between radiofrequency lesions obtained with this method and conventional ones. METHODS AND RESULTS: Twenty-eight sets of 10 perpendicular radiofrequency applications were performed with two commercially available catheters: a temperature-controlled HPSD catheter (QDot-Micro) and a conventional power-controlled catheter (Thermocool SmartTouch) on porcine left ventricle. Different power settings (35, 40, 50, and 90 W), contact force (CF; 10 and 20 g), ablation index (AI; 400 and 550), and application times were combined to create conventional (35-40 W), HPSD (50 W) and very-high-power short-duration (VHPSD; 90 W) lesions, that were cross-sectioned and measured. About 4-s VHPSD lesions were smaller, shallower, and thinner than HPSD performed with the QDot-Micro catheter in any scenario of CF or AI (61 ± 7.8 mm3 , 6.1 ± 0.3 mm wide, and 2.9 ± 0.1 mm deep with 10 g; 72.2 ± 0.5 mm3 , 6.8 ± 0.3 mm wide, and 2.9 ± 0.2 mm deep with 20 g). Conventional and HPSD lesions performed with the temperature-controlled catheter were generally bigger, deeper, and wider than the ones obtained with the power-controlled catheter, as well as more consistent in size. This was especially true with the lower CF and AI scenario, while differences were less notable with other setting combinations. CONCLUSION: VHPSD lesions performed with QDot-Micro catheter were smaller than any other lesions, which is especially attractive for posterior left atrial wall ablation. On the contrary, conventional-powered and HPSD lesions performed with this catheter were equally sized (or even bigger with lower CF and AI objectives), as well as more consistent in size, which would guarantee transmurality in other locations.

The management of secondary mitral regurgitation in patients with heart failure: a joint position statement from the Heart Failure Association (HFA), European Association of Cardiovascular Imaging (EACVI), European Heart Rhythm Association (EHRA), and European Association of Percutaneous Cardiovascular Interventions (EAPCI) of the ESC.

Secondary (or functional) mitral regurgitation (SMR) occurs frequently in chronic heart failure (HF) with reduced left ventricular (LV) ejection fraction, resulting from LV remodelling that prevents coaptation of the valve leaflets. Secondary mitral regurgitation contributes to progression of the symptoms and signs of HF and confers worse prognosis. The management of HF patients with SMR is complex and requires timely referral to a multidisciplinary Heart Team. Optimization of pharmacological and device therapy according to guideline recommendations is crucial. Further management requires careful clinical and imaging assessment, addressing the anatomical and functional features of the mitral valve and left ventricle, overall HF status, and relevant comorbidities. Evidence concerning surgical correction of SMR is sparse and it is doubtful whether this approach improves prognosis. Transcatheter repair has emerged as a promising alternative, but the conflicting results of current randomized trials require careful interpretation. This collaborative position statement, developed by four key associations of the European Society of Cardiology-the Heart Failure Association (HFA), European Association of Percutaneous Cardiovascular Interventions (EAPCI), European Association of Cardiovascular Imaging (EACVI), and European Heart Rhythm Association (EHRA)-presents an updated practical approach to the evaluation and management of patients with HF and SMR based upon a Heart Team approach.

Prognostic implications of cardiac magnetic resonance feature tracking derived multidirectional strain in patients with chronic aortic regurgitation.

OBJECTIVE: Speckle-tracking echocardiography (STE) deformation parameters detect latent LV dysfunction in chronic aortic regurgitation (AR) and are associated with outcomes. The aim of the study was to evaluate cardiac magnetic resonance (CMR) feature tracking (FT) deformation parameters in asymptomatic patients with AR and implications in outcomes. METHODS: Fifty-five patients with AR and 54 controls were included. Conventional functional CMR parameters, aortic regurgitant volume, and fraction were assessed. CMR-FT analysis was performed with a dedicated software. Clinical data was obtained from hospital records. A combined endpoint included all-cause mortality, cardiovascular mortality, aortic valve surgery, or cardiovascular hospital admission due to heart failure. RESULTS: Left ventricular (LV) mechanics is impaired in patients with significant AR. Significant differences were noted in global longitudinal strain (GLS) between controls and AR patients (- 19.1 ± 2.9% vs - 16.5 ± 3.2%, p < 0.001) and among AR severity groups (- 18.3 ± 3.1% vs - 16.2 ± 1.6% vs - 15 ± 3.5%; p = 0.02 for AR grades I-II, III, and IV). In univariate and multivariate analyses, circumferential strain (GCS) and global radial strain (GRS) but not GLS were associated with and increased risk of the end point with a HR of 1.26 (p = 0.016, 1.04-1.52) per 1% worsening for GCS and 0.90 (p = 0.012, 0.83-0.98) per 1% worsening for GRS. CONCLUSIONS: CMR-FT myocardial deformation parameters are impaired in patients with AR not meeting surgical criteria. GLS decreases early in the course of the disease and is a marker of AR severity while GCS and GRS worsen later but predict a bad prognosis, mainly the need of aortic valve surgery. KEY POINTS: • CMR feature tracking LV mechanic parameters may be reduced in significant chronic AR with normal EF. • LV mechanics, mainly global longitudinal strain, worsens as AR severity increases. • LV mechanics, specially global radial and circumferential strain, is associated with a worse prognosis in AR patients.

Safety of low-dose oral minoxidil for hair loss: A multicenter study of 1404 patients.

BACKGROUND: The major concern regarding the use of low-dose oral minoxidil (LDOM) for the treatment of hair loss is the potential risk of systemic adverse effects. OBJECTIVE: To describe the safety of LDOM for the treatment of hair loss in a large cohort of patients. METHODS: Retrospective multicenter study of patients treated with LDOM for at least 3 months for any type of alopecia. RESULTS: A total of 1404 patients (943 women [67.2%] and 461 men [32.8%]) with a mean age of 43 years (range 8-86) were included. The dose of LDOM was titrated in 1065 patients, allowing the analysis of 2469 different cases. The most frequent adverse effect was hypertrichosis (15.1%), which led to treatment withdrawal in 14 patients (0.5%). Systemic adverse effects included lightheadedness (1.7%), fluid retention (1.3%), tachycardia (0.9%), headache (0.4%), periorbital edema (0.3%), and insomnia (0.2%), leading to drug discontinuation in 29 patients (1.2%). No life-threatening adverse effects were observed. LIMITATIONS: Retrospective design and lack of a control group. CONCLUSION: LDOM has a good safety profile as a treatment for hair loss. Systemic adverse effects were infrequent and only 1.7% of patients discontinued treatment owing to adverse effects.

Long-term outcomes of chronic coronary syndrome worldwide: insights from the international CLARIFY registry.

AIMS: Over the last decades, the profile of chronic coronary syndrome has changed substantially. We aimed to determine characteristics and management of patients with chronic coronary syndrome in the contemporary era, as well as outcomes and their determinants. METHODS AND RESULTS: Data from 32 703 patients (45 countries) with chronic coronary syndrome enrolled in the prospective observational CLARIFY registry (November 2009 to June 2010) with a 5-year follow-up, were analysed. The primary outcome [cardiovascular death or non-fatal myocardial infarction (MI)] 5-year rate was 8.0% [95% confidence interval (CI) 7.7-8.3] overall [male 8.1% (7.8-8.5); female 7.6% (7.0-8.3)]. A cox proportional hazards model showed that the main independent predictors of the primary outcome were prior hospitalization for heart failure, current smoking, atrial fibrillation, living in Central/South America, prior MI, prior stroke, diabetes, current angina, and peripheral artery disease. There was an interaction between angina and prior MI (P = 0.0016); among patients with prior MI, angina was associated with a higher primary event rate [11.8% (95% CI 10.9-12.9) vs. 8.2% (95% CI 7.8-8.7) in patients with no angina, P < 0.001], whereas among patients without prior MI, event rates were similar for patients with [6.3% (95% CI 5.4-7.3)] or without angina [6.4% (95% CI 5.9-7.0)], P > 0.99. Prescription rates of evidence-based secondary prevention therapies were high. CONCLUSION: This description of the spectrum of chronic coronary syndrome patients shows that, despite high rates of prescription of evidence-based therapies, patients with both angina and prior MI are an easily identifiable high-risk group who may deserve intensive treatment. CLINICAL REGISTRY: ISRCTN43070564.

Ivabradine Induces Cardiac Protection against Myocardial Infarction by Preventing Cyclophilin-A Secretion in Pigs under Coronary Ischemia/Reperfusion.

In response to cardiac ischemia/reperfusion, proteolysis mediated by extracellular matrix metalloproteinase inducer (EMMPRIN) and its secreted ligand cyclophilin-A (CyPA) significantly contributes to cardiac injury and necrosis. Here, we aimed to investigate if, in addition to the effect on the funny current (I(f)), Ivabradine may also play a role against cardiac necrosis by reducing EMMPRIN/CyPA-mediated cardiac inflammation. In a porcine model of cardiac ischemia/reperfusion (IR), we found that administration of 0.3 mg/kg Ivabradine significantly improved cardiac function and reduced cardiac necrosis by day 7 after IR, detecting a significant increase in cardiac CyPA in the necrotic compared to the risk areas, which was inversely correlated with the levels of circulating CyPA detected in plasma samples from the same subjects. In testing whether Ivabradine may regulate the levels of CyPA, no changes in tissue CyPA were found in healthy pigs treated with 0.3 mg/kg Ivabradine, but interestingly, when analyzing the complex EMMPRIN/CyPA, rather high glycosylated EMMPRIN, which is required for EMMPRIN-mediated matrix metalloproteinase (MMP) activation and increased CyPA bonding to low-glycosylated forms of EMMPRIN were detected by day 7 after IR in pigs treated with Ivabradine. To study the mechanism by which Ivabradine may prevent secretion of CyPA, we first found that Ivabradine was time-dependent in inhibiting co-localization of CyPA with the granule exocytosis marker vesicle-associated membrane protein 1 (VAMP1). However, Ivabradine had no effect on mRNA expression nor in the proteasome and lysosome degradation of CyPA. In conclusion, our results point toward CyPA, its ligand EMMPRIN, and the complex CyPA/EMMPRIN as important targets of Ivabradine in cardiac protection against IR.

Right ventricle assessment in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation.

INTRODUCTION: Limited data are available regarding the evaluation of right ventricular (RV) performance in patients with aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI). OBJECTIVE: To evaluate the prevalence of RV dysfunction in patients with severe AS undergoing TAVI and long-term changes. METHODS: Consecutive patients with severe AS undergoing TAVI from January 2016 to July 2017 were included. RV anatomical and functional parameters were analyzed: RV diameters, fractional area change, tricuspid annular plane systolic excursion (TAPSE), S-wave tissue Doppler of the tricuspid annulus (RV-S'TDI), global longitudinal strain (RV-GLS), and free wall strain (RV-FWS). Preprocedure and 1-year echo were analyzed. RESULTS: Final population included 114 patients, mean age 83.63 ± 6.31 years, and 38.2% women. The prevalence of abnormal RV function was high, variable depending on the parameter that we analyzed, and it showed a significant reduction 1 year after TAVI implantation: 13.9% vs 6.8% (TAPSE < 17mm), P = .04; 26.3% vs 20% (fractional area change < 35%), P = .048; 41.2% vs 29.2% (RV-S'TDI < 9.5cm/s), P = .04; 48.7% vs 39.5% (RV-GLS > [20]), P = .049; and 48.7% vs 28.9% (RV-FWS > [20]), P = .03. Significant differences were noted between patients with low-flow (LF) vs normal-flow (NF) AS in RV dysfunction prevalence as well as in RV function recovery which is less evident in LF compared with NF patients. CONCLUSIONS: RV dysfunction is high among symptomatic AS patients undergoing TAVI, with variable prevalence depending on the echocardiographic parameter used.

Cardio-Oncology Services: rationale, organization, and implementation.

AIMS: Anticancer therapies have extended the lives of millions of patients with malignancies, but for some this benefit is tempered by adverse cardiovascular (CV) effects. Cardiotoxicity may occur early or late after treatment initiation or termination. The extent of this cardiotoxicity is variable, depending on the type of drug used, combination with other drugs, mediastinal radiotherapy, the presence of CV risk factors, and comorbidities. A recent position paper from the European Society of Cardiology addressed the management of CV monitoring and management of patients treated for cancer. METHODS AND RESULTS: The current document is focused on the basis of the Cardio-Oncology (C-O) Services, presenting their rationale, organization, and implementation. C-O Services address the spectrum of prevention, detection, monitoring, and treatment of cancer patients at risk of cardiotoxicity and/or with concomitant CV diseases. These services require a multidisciplinary approach, with the aims of promoting CV health and facilitating the most effective cancer therapy. CONCLUSION: The expected growing volume of patients with cancer at risk of developing/worsening CV disease, the advent of new technological opportunities to refine diagnosis, and the necessity of early recognition of cancer therapy-related toxicity mandate an integrative multidisciplinary approach and care in a specialized environment. This document from the ESC Cardio-Oncology council proposes the grounds for creating C-O Services in Europe based on expert opinion.

Ivabradine-Stimulated Microvesicle Release Induces Cardiac Protection against Acute Myocardial Infarction.

Ivabradine can reduce heart rate through inhibition of the current I(f) by still unexplored mechanisms. In a porcine model of ischemia reperfusion (IR), we found that treatment with 0.3 mg/kg Ivabradine increased plasma release of microvesicles (MVs) over Placebo, as detected by flow cytometry of plasma isolated from pigs 7 days after IR, in which a tenfold increase of Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) containing (both high and low-glycosylated) MVs, was detected in response to Ivabradine. The source of MVs was investigated, finding a 37% decrease of CD31+ endothelial cell derived MVs, while CD41+ platelet MVs remained unchanged. By contrast, Ivabradine induced the release of HCN4+ (mostly cardiac) MVs. While no differences respect to EMMPRIN as a cargo component were found in endothelial and platelet derived MVs, Ivabradine induced a significant release of EMMPRIN+/HCN4+ MVs by day 7 after IR. To test the role of EMMPRIN+ cardiac MVs (EMCMV), H9c2 cell monolayers were incubated for 24 h with 107 EMCMVs, reducing apoptosis, and increasing 2 times cell proliferation and 1.5 times cell migration. The in vivo contribution of Ivabradine-induced plasma MVs was also tested, in which 108 MVs isolated from the plasma of pigs treated with Ivabradine or Placebo 7 days after IR, were injected in pigs under IR, finding a significant cardiac protection by increasing left ventricle ejection fraction and a significant reduction of the necrotic area. In conclusion ivabradine induces cardiac protection by increasing at least the release of EMMPRIN containing cardiac microvesicles.

Global longitudinal strain is a hallmark of cardiac damage in mitral regurgitation: the Italian arm of the European Registry of mitral regurgitation (EuMiClip).

BACKGROUND: The search for reliable cardiac functional parameters is crucial in patients with mitral regurgitation (MR). In the Italian arm of the European Registry of MR, we compared the ability of global longitudinal strain (GLS) and left ventricular (LV) ejection fraction (LVEF) to detect cardiac damage in MR. METHODS: Five hundred four consecutive patients with MR underwent a complete echo-Doppler exam. A total of 431, 53 and 20 patients had degenerative, secondary and mixed MR, respectively. The main echocardiographic parameters, including LV and left atrial (LA) size measurements, pulmonary artery systolic pressure (PASP) and GLS were compared between patients with mild MR (n = 392) vs. moderate to severe MR (n = 112). RESULTS: LVEF and GLS were related one another in the pooled population, and separately in patients with mild and moderate/severe MR (all p < 0.0001). However, a certain number of patients were above the upper or below the lower limits of the 95% confidence interval (CI) of the normal relation in the pooled population and in patients with mild MR. Only 2 patients were below the 95% CI in moderate to severe MR. After adjusting for confounders by separate multivariate models, LVEF and GLS were independently associated with LV and left atrial size in the pooled population and in mild and moderate/severe MR. GLS, but not LVEF, was also independently associated with PASP in patients with mild and moderate to severe MR. CONCLUSIONS: Both LVEF and GLS are independently associated with LV and LA size, but only GLS is related to pulmonary arterial pressure. GLS is a powerful hallmark of cardiac damage in MR.

The Role of Frailty in Acute Coronary Syndromes in the Elderly.

BACKGROUND: Myocardial infarction (MI) patients are increasingly older, and common risk scores include chronological age, but do not consider chronic comorbidity or biological age. Frailty status reflects these variables and may be independently correlated with prognosis in this setting. OBJECTIVE: This study investigated the impact of frailty on the prognosis of elderly patients admitted due to MI. METHODS: This prospective and observational study included patients ≥75 years admitted to three tertiary hospitals in Spain due to MI. Frailty assessment was performed at admission using the Survey of Health, Ageing and Retirement in Europe Frailty Index (SHARE-FI) tool. The primary endpoint was the composite of death or non-fatal reinfarction during a follow-up of 1 year. Overall mortality, reinfarction, the composite of death, reinfarction and stroke, major bleeding, and readmission rates were also explored. RESULTS: A total of 285 patients were enrolled. Frail patients (109, 38.2%) were older, with a higher score in the Charlson Comorbidity Index and with a higher risk score addressed in the GRACE and CRUSADE indexes. On multivariate analysis including GRACE, CRUSADE, maximum creatinine level, culprit lesion revascularization, complete revascularization, and dual antiplatelet therapy at discharge, frailty was an independent predictor of the composite of death and reinfarction (2.81, 95% CI 1.16-6.78) and overall mortality (3.07, 95% CI 1.35-6.98). CONCLUSION: Frailty is an independent prognostic marker of the composite of mortality and reinfarction and of overall mortality in patients aged ≥75 years admitted due to MI.

SOURCE 3: 1-year outcomes post-transcatheter aortic valve implantation using the latest generation of the balloon-expandable transcatheter heart valve.

AIMS: Transcatheter aortic valve implantation (TAVI) has developed from a procedure for patients with aortic stenosis inoperable or high risk for surgery, into a treatment option even for intermediate risk elderly patients. This development has been facilitated by the clinical learning curve and constant improvements of transcatheter heart valves used. We present total 1-year results of SOURCE 3, the European post-approval multicentre registry of the latest generation balloon expandable SAPIEN 3TM (Edwards Lifesciences, Irvine, CA, USA). METHODS AND RESULTS: Participating centres have submitted their consecutive experience with the SAPIEN 3, dependent on patients consent. Data were prospectively collected and all end point-related outcomes adjudicated according to VARC-2 definitions by an independent committee. Between July 2014 and October 2015, in total 1946 patients (mean age 81.6 ± 6.7 years, 52% male) were enrolled in 80 centres from 10 European countries. At 1 year, all-cause mortality was 12.6%, cardiovascular mortality 8.0%, stroke 3.1%, disabling stroke 1.4%, and rate of new pacemakers 13.2%. Causes of death were 62.0% cardiovascular and 38.0% non-cardiovascular, with heart failure (13.4%) and pulmonary complications (12.7%) being the main reasons for fatal outcomes. Multivariable analysis identified New York Heart Association Class IV and renal insufficiency as predictors of mortality, while higher BMI's improved survival. Severe (zero) and moderate paravalvular leakage (2.6%) was rare at 1 year. CONCLUSION: In SOURCE 3, we observe a low complication rate and mortality at 1 year. Given the low incidence of higher degree paravalvular leakages, this variable did no longer affect outcome. Clinicaltrial.gov number: NCT02698956.