Antiarrhythmic and Anti-Inflammatory Effects of Sacubitril/Valsartan on Post-Myocardial Infarction Scar.

BACKGROUND: Sacubitril/valsartan (Sac/Val) is superior to angiotensin-converting enzyme inhibitors in reducing the risk of heart failure hospitalization and cardiovascular death, but its mechanistic data on myocardial scar after myocardial infarction (MI) are lacking. The objective of this work was to assess the effects of Sac/Val on inflammation, fibrosis, electrophysiological properties, and ventricular tachycardia inducibility in post-MI scar remodeling in swine. METHODS: After MI, 22 pigs were randomized to receive ß-blocker (BB; control, n=8) or BB+Sac/Val (Sac/Val, n=9). The systemic immune response was monitored. Cardiac magnetic resonance data were acquired at 2-day and 29-day post MI to assess ventricular remodeling. Programmed electrical stimulation and high-density mapping were performed at 30-day post MI to assess ventricular tachycardia inducibility. Myocardial samples were collected for histological analysis. RESULTS: Compared with BB, BB+Sac/Val reduced acute circulating leukocytes (P=0.009) and interleukin-12 levels (P=0.024) at 2-day post MI, decreased C-C chemokine receptor type 2 expression in monocytes (P=0.047) at 15-day post MI, and reduced scar mass (P=0.046) and border zone mass (P=0.043). It also lowered the number and mass of border zone corridors (P=0.020 and P=0.05, respectively), scar collagen I content (P=0.049), and collagen I/III ratio (P=0.040). Sac/Val reduced ventricular tachycardia inducibility (P=0.026) and the number of deceleration zones (P=0.016). CONCLUSIONS: After MI, compared with BB, BB+Sac/Val was associated with reduced acute systemic inflammatory markers, reduced total scar and border zone mass on late gadolinium-enhanced magnetic resonance imaging, and lower ventricular tachycardia inducibility.

Atrial secondary tricuspid regurgitation: pathophysiology, definition, diagnosis, and treatment.

Atrial secondary tricuspid regurgitation (A-STR) is a distinct phenotype of secondary tricuspid regurgitation with predominant dilation of the right atrium and normal right and left ventricular function. Atrial secondary tricuspid regurgitation occurs most commonly in elderly women with atrial fibrillation and in heart failure with preserved ejection fraction in sinus rhythm. In A-STR, the main mechanism of leaflet malcoaptation is related to the presence of a significant dilation of the tricuspid annulus secondary to right atrial enlargement. In addition, there is an insufficient adaptive growth of tricuspid valve leaflets that become unable to cover the enlarged annular area. As opposed to the ventricular phenotype, in A-STR, the tricuspid valve leaflet tethering is typically trivial. The A-STR phenotype accounts for 10%-15% of clinically relevant tricuspid regurgitation and has better outcomes compared with the more prevalent ventricular phenotype. Recent data suggest that patients with A-STR may benefit from more aggressive rhythm control and timely valve interventions. However, little is mentioned in current guidelines on how to identify, evaluate, and manage these patients due to the lack of consistent evidence and variable definitions of this entity in recent investigations. This interdisciplinary expert opinion document focusing on A-STR is intended to help physicians understand this complex and rapidly evolving topic by reviewing its distinct pathophysiology, diagnosis, and multi-modality imaging characteristics. It first defines A-STR by proposing specific quantitative criteria for defining the atrial phenotype and for discriminating it from the ventricular phenotype, in order to facilitate standardization and consistency in research.

Patterns of aortic valve replacement in Europe and adoption by sex.

OBJECTIVE: Management of patients with severe aortic stenosis (AS) may differ according to the patient sex. This study aimed to describe patterns of aortic valve replacement (AVR) for severe AS across Europe, including stratification by sex. METHODS: Procedure volume data for surgical aortic valve replacement (SAVR) and transcatheter aortic valve implantation (TAVI) for six years (2015-2020) were extracted from national databases for Austria, Czech Republic, Denmark, England, Finland, France, Germany, Norway, Poland, Spain, Sweden, and Switzerland and stratified by sex. Patients per million population (PPM) undergoing AVR per year were calculated using population estimates from Eurostat. RESULTS: Between 2015 and 2019, AVR procedures grew at an average annual rate of 3.9%. In 2020, the average total PPM undergoing AVR across all countries was 339, with 51% of procedures being TAVI and 49% SAVR. AVR PPM varied widely between countries, with the highest and lowest in Germany and Poland, respectively. The average total PPM was higher for men than women (423 vs. 258), but a higher proportion of women (62%) than men (44%) received TAVI. The proportion of TAVI among total AVR procedures increased with age, with an overall average of 96% of men and 98% of women aged ≥85 years receiving TAVI; however, adoption of TAVI varied by country. CONCLUSIONS: The analysis of temporal trends in the adoption of TAVI vs. SAVR across Europe showed significant variations. Despite the higher use of TAVI vs. SAVR in women, overall rates of AV intervention in women were lower compared to men.

[Summary: International consensus statement on nomenclature and classification of the congenital bicuspid aortic valve and its aortopathy, for clinical, surgical, interventional and research purposes]. / Resumen: Consenso internacional para la nomenclatura y clasificación de la válvula aórtica bicúspide congénita y su aortopatía, con fines clínicos, quirúrgicos, intervencionistas y de investigación.

This consensus of nomenclature and classification for congenital bicuspid aortic valve and its aortopathy is evidence-based and intended for universal use by physicians (both pediatricians and adults), echocardiographers, advanced cardiovascular imaging specialists, interventional cardiologists, cardiovascular surgeons, pathologists, geneticists, and researchers spanning these areas of clinical and basic research. In addition, as long as new key and reference research is available, this international consensus may be subject to change based on evidence-based data1.

Este consenso de nomenclatura y clasificación para la válvula aórtica bicúspide congénita y su aortopatía está basado en la evidencia y destinado a ser utilizado universalmente por médicos (tanto pediatras como de adultos), médicos ecocardiografistas, especialistas en imágenes avanzadas cardiovasculares, cardiólogos intervencionistas, cirujanos cardiovasculares, patólogos, genetistas e investigadores que abarcan estas áreas de investigación clínica y básica. Siempre y cuando se disponga de nueva investigación clave y de referencia, este consenso internacional puede estar sujeto a cambios de acuerdo con datos basados en la evidencia1.

Device innovation in cardiovascular medicine: a report from the European Society of Cardiology Cardiovascular Round Table.

Research performed in Europe has driven cardiovascular device innovation. This includes, but is not limited to, percutaneous coronary intervention, cardiac imaging, transcatheter heart valve implantation, and device therapy of cardiac arrhythmias and heart failure. An important part of future medical progress involves the evolution of medical technology and the ongoing development of artificial intelligence and machine learning. There is a need to foster an environment conducive to medical technology development and validation so that Europe can continue to play a major role in device innovation while providing high standards of safety. This paper summarizes viewpoints on the topic of device innovation in cardiovascular medicine at the European Society of Cardiology Cardiovascular Round Table, a strategic forum for high-level dialogue to discuss issues related to the future of cardiovascular health in Europe. Devices are developed and improved through an iterative process throughout their lifecycle. Early feasibility studies demonstrate proof of concept and help to optimize the design of a device. If successful, this should ideally be followed by randomized clinical trials comparing novel devices vs. accepted standards of care when available and the collection of post-market real-world evidence through registries. Unfortunately, standardized procedures for feasibility studies across various device categories have not yet been implemented in Europe. Cardiovascular imaging can be used to diagnose and characterize patients for interventions to improve procedural results and to monitor devices long term after implantation. Randomized clinical trials often use cardiac imaging-based inclusion criteria, while less frequently trials randomize patients to compare the diagnostic or prognostic value of different modalities. Applications using machine learning are increasingly important, but specific regulatory standards and pathways remain in development in both Europe and the USA. Standards are also needed for smart devices and digital technologies that support device-driven biomonitoring. Changes in device regulation introduced by the European Union aim to improve clinical evidence, transparency, and safety, but they may impact the speed of innovation, access, and availability. Device development programmes including dialogue on unmet needs and advice on study designs must be driven by a community of physicians, trialists, patients, regulators, payers, and industry to ensure that patients have access to innovative care.

Integration of implantable device therapy in patients with heart failure. A clinical consensus statement from the Heart Failure Association (HFA) and European Heart Rhythm Association (EHRA) of the European Society of Cardiology (ESC).

Implantable devices form an integral part of the management of patients with heart failure (HF) and provide adjunctive therapies in addition to cornerstone drug treatment. Although the number of these devices is growing, only few are supported by robust evidence. Current devices aim to improve haemodynamics, improve reverse remodelling, or provide electrical therapy. A number of these devices have guideline recommendations and some have been shown to improve outcomes such as cardiac resynchronization therapy, implantable cardioverter-defibrillators and long-term mechanical support. For others, more evidence is still needed before large-scale implementation can be strongly advised. Of note, devices and drugs can work synergistically in HF as improved disease control with devices can allow for further optimization of drug therapy. Therefore, some devices might already be considered early in the disease trajectory of HF patients, while others might only be reserved for advanced HF. As such, device therapy should be integrated into HF care programmes. Unfortunately, implementation of devices, including those with the greatest evidence, in clinical care pathways is still suboptimal. This clinical consensus document of the Heart Failure Association (HFA) and European Heart Rhythm Association (EHRA) of the European Society of Cardiology (ESC) describes the physiological rationale behind device-provided therapy and also device-guided management, offers an overview of current implantable device options recommended by the guidelines and proposes a new integrated model of device therapy as a part of HF care.

Clinical and prognostic implications of left ventricular dilatation in heart failure.

AIMS: To assess the agreement between left ventricular end-diastolic diameter index (LVEDDi) and volume index (LVEDVi) to define LV dilatation and to investigate the respective prognostic implications in patients with heart failure (HF). METHODS AND RESULTS: Patients with HF symptoms and LV ejection fraction (LVEF) < 50% undergoing cardiac magnetic resonance (CMR) were evaluated retrospectively. LV dilatation was defined as LVEDDi or LVEDVi above the upper normal limit according to published reference values. Patients were followed-up for the combined endpoint of cardiovascular death or HF hospitalization during 5 years. A total of 564 patients (median age 64 years; 79% men) were included. LVEDDi had a modest correlation with LVEDVi (r = 0.682, p < 0.001). LV dilatation was noted in 84% of patients using LVEDVi-based definition and in 73% using LVEDDi-based definition, whereas 20% of patients displayed discordant definitions of LV dilatation. During a median follow-up of 2.8 years, patients with both dilated LVEDDi and LVEDVi had the highest cumulative event rate (HR 3.00, 95% CI 1.15-7.81, p = 0.024). Both LVEDDi and LVEDVi were independently associated with the primary outcome (hazard ratio 3.29, 95%, p < 0.001 and 2.8, p = 0.009; respectively). CONCLUSIONS: The majority of patients with HF and LVEF < 50% present both increased LVEDDi and LVEDVi whereas 20% show discordant linear and volumetric definitions of LV dilatation. Patients with increased LVEDDi and LVEDVi have the worst clinical outcomes suggesting that the assessment of these two metrics is needed for better risk stratification.

Assessment of the Severity of Aortic Regurgitation by Noninvasive Imaging : Non-invasive MMI for AR.

PURPOSE OF THE REVIEW: The role of multimodality imaging in the evaluation of patients with aortic regurgitation is summarized in this review. RECENT FINDINGS: The etiology (mechanism) of the aortic regurgitation and the severity of aortic regurgitation and hemodynamic consequences are key in the decision making of patients with severe aortic regurgitation. While echocardiography remains as the leading technique to assess all these parameters, other imaging techniques have become essential for the accurate assessment of aortic regurgitation severity and the timing of aortic intervention. The anatomic suitability of transcatheter aortic valve implantation in inoperable patients with severe aortic regurgitation is usually assessed with computed tomography. Aortic regurgitation is a prevalent disease with various pathophysiological mechanisms that need a personalized treatment. The evaluation of the mechanism and severity of aortic regurgitation can be initially performed with echocardiography. Three-dimensional techniques, including echocardiography, have become very relevant for accurate assessment of the regurgitation severity and its hemodynamic consequences. Assessment of myocardial tissue characteristics with cardiac magnetic resonance is key in the risk stratification of patients and in the timing of aortic intervention. Computed tomography is important in the assessment of aortic dimensions and selection of patients for transcatheter aortic valve implantation.

Association of right atrial strain and long-term outcome in severe secondary tricuspid regurgitation.

OBJECTIVE: Severe secondary tricuspid regurgitation (STR) causes significant right atrial (RA) volume overload, resulting in structural and functional RA-remodelling. This study evaluated whether patients with severe STR and reduced RA function, as assessed by RA-reservoir-strain (RASr), show lower long-term prognosis. METHODS: Consecutive patients, from a single centre, with first diagnosis of severe STR and RASr measure available, were included. Extensive echocardiographic analysis comprised measures of cardiac chamber size and function, assessed also by two-dimensional speckle-tracking strain analysis. Primary outcome was all-cause mortality, analysed from inclusion until death or last follow-up. The association of RASr with the outcome was evaluated by Cox regression analysis and Akaike information criterion. RESULTS: A total of 586 patients with severe STR (age 68±13 years; 52% male) were included. Patients presented with mild right ventricular (RV) dilatation (end-diastolic area 13.8±6.5 cm2/m2) and dysfunction (free-wall strain 16.2±7.2%), and with moderate-to-severe RA dilatation (max area 15.0±5.3 cm2/m2); the median value of RASr was 13%. In the overall population, 10-year overall survival was low (40%, 349 deaths), and was significantly lower in patients with lower RASr (defined by the median value): 36% (195 deaths) for RASr ≤13% compared with 45% (154 deaths) for RASr >13% (log-rank p=0.016). With a median follow-up of 6.6 years, RASr was independently associated with all-cause mortality (HR per 5% RASr increase:0.928; 95% CI 0.864 to 0.996; p=0.038), providing additional value over relevant clinical and echocardiographic covariates (including RA size and RV function/size). CONCLUSIONS: Patients with severe STR presented with significant RA remodelling, and lower RA function, as measured by RASr, was independently associated with all-cause mortality, potentially improving risk stratification in these patients.

The value of serial echocardiography in risk assessment of patients with paroxysmal atrial fibrillation.

Progression from paroxysmal to persistent atrial fibrillation (AF) is associated with increased morbidity and mortality. We examined the association of left atrial (LA) remodeling by serial echocardiography, and AF progression over an extended follow-up period. Two-hundred ninety patients (mean age 61  ±  11 years, 73% male) who underwent transthoracic echocardiography performed at first presentation for non-valvular paroxysmal AF (PAF) and repeat echocardiogram 1-year later, were followed for progression to persistent AF. LA and left ventricular (LV) dimensions, volumes, LA reservoir, conduit and booster pump strains, LV global longitudinal systolic strain (GLS) assessed by 2D speckle tracking, and PA-TDI (time delay between electrical and mechanical LA activation- reflecting the extent of LA fibrosis) were compared on serial echocardiography. Sixty-nine (24%) patients developed persistent AF over a mean follow-up period of 6.3 years. At baseline, patients with subsequent persistent AF had larger LA dimensions (46 mm vs. 42 mm, p < 0.001), indexed LA volumes (41 ml/m2 vs. 34 ml/m2, p < 0.001), lower LA reservoir and conduit strain (17.6% vs. 27.6%, p < 0.001; 10.5% vs. 16.3%, p < 0.001; respectively) and longer PA-TDI (155 ms vs. 132 ms, p < 0.001) compared to the PAF group. Patients with subsequent persistent AF showed over time significant enlargement in LA volumes (from 37.7 ml/m2 to 42.4 ml/m2, p < 0.001), lengthening of PA-TDI (from 142.2 ms to 162.2 ms, p = 0.002), and decline in LA reservoir function (from 21.9% to 18.1%, p = 0.024) after adjusting for age, gender, diabetes and LV GLS. There were no changes in LA diameter, LA conduit or booster pump function. Conversely, the PAF group showed no decline in LA function. Patients who developed persistent AF had larger LA size and impaired LA function and atrial conduction times at baseline, compared to patients who remained PAF. Over the 1-year time course of serial echocardiographic evaluation, there was progression of LA remodeling in patients who subsequently developed persistent AF, but not in patients who remained in PAF.

Impact of chronic obstructive pulmonary disease on right ventricular function and remodeling after aortic valve replacement.

BACKGROUND: Both chronic obstructive pulmonary disease (COPD) and right ventricular (RV) dysfunction are common factors that have been associated with poor prognosis after aortic valve replacement (AVR). Since there is still uncertainty about the impact of COPD on RV function and dilatation in patients undergoing AVR, we sought to explore RV function and remodeling in the presence and absence of COPD as well as their prognostic implications. METHODS: Patients who received surgical or transcatheter AVR due to severe AS were screened for COPD. Demographic and clinical data were collected at baseline while echocardiographic measurements were performed at baseline and 1 year after AVR. The study end-point was all-cause mortality. RESULTS: In total 275 patients were included, with 90 (33%) patients having COPD. At 1-year follow-up, mild worsening of tricuspid annular planar systolic excursion and RV dilatation were observed in patients without COPD, while there were significant improvements in RV longitudinal strain, RV wall thickness but dilatation of RV outflow tract distal dimension in the COPD group compared to the baseline. On multivariable analysis, the presence of COPD provided significant incremental prognostic value over RV dysfunction and remodeling. CONCLUSIONS: At 1-year after AVR, RV function and dimensions mildly deteriorated in non-COPD group whereas COPD group received significant benefit of AVR in terms of RV function and hypertrophy. COPD was independently associated with >2-fold all-cause mortality and had incremental prognostic value over RV dysfunction and remodeling.

Epidemiology, pathophysiology, diagnosis and management of chronic right-sided heart failure and tricuspid regurgitation. A clinical consensus statement of the Heart Failure Association (HFA) and the European Association of Percutaneous Cardiovascular Interventions (EAPCI) of the ESC.

Right-sided heart failure and tricuspid regurgitation are common and strongly associated with poor quality of life and an increased risk of heart failure hospitalizations and death. While medical therapy for right-sided heart failure is limited, treatment options for tricuspid regurgitation include surgery and, based on recent developments, several transcatheter interventions. However, the patients who might benefit from tricuspid valve interventions are yet unknown, as is the ideal time for these treatments given the paucity of clinical evidence. In this context, it is crucial to elucidate aetiology and pathophysiological mechanisms leading to right-sided heart failure and tricuspid regurgitation in order to recognize when tricuspid regurgitation is a mere bystander and when it can cause or contribute to heart failure progression. Notably, early identification of right heart failure and tricuspid regurgitation may be crucial and optimal management requires knowledge about the different mechanisms and causes, clinical course and presentation, as well as possible treatment options. The aim of this clinical consensus statement is to summarize current knowledge about epidemiology, pathophysiology and treatment of tricuspid regurgitation in right-sided heart failure providing practical suggestions for patient identification and management.