Left and Right Ventricular Longitudinal Systolic Function Following Aortic Valve Replacement in the PARTNER 2 Trial And Registry.

AIMS: Evaluation of left and right ventricular longitudinal systolic function may enhance risk stratification following aortic valve replacement (AVR). The study objective was to evaluate the changes in left and right ventricular longitudinal systolic function and RV-pulmonary artery (RV-PA) coupling from baseline to 30-days and 1-year after aortic valve replacement (AVR). METHODS AND RESULTS: LV longitudinal strain (LS), tricuspid annulus plane systolic excursion (TAPSE), and RV-PA coupling were evaluated in patients from the PARTNER-2A surgical AVR (SAVR) arm (n=985) and from the PARTNER-2 SAPIEN-3 registry (n=719). TAPSE and RV-PA coupling decreased significantly following SAVR, but remained stable following TAVR. Lower LV LS, TAPSE, or RV-PA coupling at baseline were associated with increased risk of the composite of death, hospitalization, and stroke at 5-years (Adjusted-HRs for LV LS<15%: 1.24 95%CI 1.05-1.45, p=0.001; TAPSE<14mm: 1.44 95%CI 1.21-1.73, p<0.001; RV/PA coupling<0.55mm/mmHg: 1.32 95% CI 1.07-1.63, p=0.011). Reduced TAPSE at baseline was the most powerful predictor of the composite endpoint at 5-years. Patients with LV ejection fraction <50% at baseline had increased risk of the primary endpoint with SAVR (HR: 1.34, 95%CI 1.08-1.68, p=0.009) but not with TAVR (HR: 1.12, 95%CI 0.88-1.42). Lower RV-PA coupling at 30-days showed the strongest association with cardiac mortality. CONCLUSION: SAVR but not TAVR was associated with a marked deterioration in RV longitudinal systolic function and RV-PA coupling. Lower TAPSE and RV-PA coupling at 30-days were associated with inferior clinical outcomes at 5-years. In patients with LVEF<50%, TAVR was associated with superior 5-year outcomes.

"Inherited cardiovascular disease mindset" can identify concealed inherited conditions at cardio-oncology evaluation: An opportunistic screening.

INTRODUCTION: Baseline cardiovascular (CV) risk stratification is recommended in all cancer patients. Integrating all clinical information (personal/family history, ECG and echocardiogram) can properly identify high-risk patients. We aimed to evaluate the concealed inherited CV conditions detected in mandatory CV screening performed at a Cardio-Oncology Unit. METHODS: retrospective study of all consecutive cancer patients referred to the Cardio-Oncology Unit for CV evaluation (2020-2023). Inherited CV conditions diagnosis and genetic testing was performed according to guidelines. RESULTS: 1984 cancer patients underwent CV screening. Sanger sequencing was indicated in 1 patient, excluding the genetic family disease. NGS sequencing was performed in 11 cancer patients with normal left ventricular ejection fraction (LVEF): 2 due to aortic syndrome evaluation (identifying 1 vascular Ehrler-Danlos syndrome due to COL3A1 p.Arg242Ter), 4 channelopathies (2 Long QT syndrome and 2 Brugada's), 4 hypertrophic cardiomyopathies and 1 non-dilated left ventricular cardiomyopathy (NDLVC). Among the 12 patients with reduced LVEF, one was diagnosed with NDLVC, and chemotherapy-induced dilated cardiomyopathy was only ascribable in 3 of them. CONCLUSION: Integrating clinical information at mandatory baseline CV toxicity risk cardio-oncology evaluation, can identify high-risk cancer patients with concealed inherited conditions. Keeping an "inherited cardiovascular disease-oriented mindset" to implement opportunist screenings is encouraged.

Percutaneous Transcatheter Edge-to-Edge Mitral Valve Repair With MitraClip System in the Era of G4.

The use of transcatheter edge-to-edge mitral valve repair (TEER) in symptomatic patients with severe mitral regurgitation (MR) has dramatically increased over the last few years. Current guidelines consider TEER as a reasonable option in symptomatic patients with primary or chronic secondary severe MR with high or prohibitive surgical risk and favorable anatomy. However, several anatomical and morphological mitral features have restricted the use of this mini-invasive technique in its early experience. The latest fourth generation (G4) of the MitraClip system has been recently introduced and includes the possibility of independent leaflet grasping and 4 different sizes. This technical update offers the possibility of selecting and combining multiple devices for complex mitral valve anatomies and challenging procedures, which helps expand the applications of TEER. The present review describes the potential advantages and the help of the MitraClip G4 devices to overcome various anatomic and morphologic issues in challenging cases with complex primary and secondary MR procedures.

Current status of transcatheter mitral valve replacement: systematic review and meta-analysis.

Introduction: Mitral Regurgitation (MR) has a strong impact on quality of life and on mid-term survival. Transcatheter mitral valve replacement (TMVR) is rapidly expanding and a growing number of studies have been published recently. Methods: A systematic review of studies reporting on clinical data for patients with symptomatic severe MR undergoing TMVR was performed. Early- and mid-term outcomes (clinical and echocardiographic) were evaluated. Overall weighted means and rates were calculated. Risk ratios or mean differences were calculated for pre- and post-procedural comparisons. Results: A total of 12 studies and 347 patients who underwent TMVR with devices clinically available or under clinical evaluation were included. Thirty-day mortality, stroke and major bleeding rates were 8.4%, 2.6%, and 15.6%, respectively. Pooled random-effects demonstrated a significant reduction of ≥ grade 3+ MR (RR: 0.05; 95% CI: 0.02-0.11; p < 0.001) and in the rates of patients in NYHA class 3-4 after the intervention (RR: 0.27; 95% CI: 0.22-0.34; p < 0.001). Additionally, the pooled fixed-effect mean difference for quality of life based on the KCCQ score yielded an improvement in 12.9 points (95% CI:7.4-18.4, p < 0.001), and exercise capacity improved by a pooled fixed-effect mean difference of 56.8 meters in the 6-minute walk test (95% CI 32.2-81.3, p < 0.001). Conclusions: Among 12 studies and 347 patients comprising the updated evidence with current TMVR systems there was a statistically significant reduction in ≥ grade 3+ MR and in the number of patients exhibiting poor functional class (NYHA 3 or 4) after the intervention. Overall rate of major bleeding was the main shortcoming of this technique.

Leaving obstacles aside: Antegrade paravalvular leakage closure after transcatheter aortic valve replacement.

Paravalvular leakage (PVL) is yet a potential and serious complication after transcatheter aortic valve replacement. Percutaneous PVL closure may be the treatment of choice upon failure of balloon postdilation in patients with excessive surgical risk. If the retrograde approach fails, an antegrade strategy might provide the solution.

Anatomical Changes after Transcatheter Edge-to-Edge Repair in Functional MR According to MitraClip Generation.

BACKGROUND: The use of mitral transcatheter edge-to-edge repair (TEER) is rapidly increasing. Anatomical changes have been described after TEER with the MitraClip system in patients with functional mitral regurgitation (MR), although no study has yet evaluated such anatomical impacts in patients treated with the G4 MitraClip generation. METHODS: This research constituted a prospective, single-center, observational study including consecutive patients with functional MR. Mitral three-dimensional images were obtained transesophageally with echocardiography before and immediately after TEER. Patients receiving the late-generation (G4) system were compared to those receiving early-generation systems. RESULTS: A total of 116 functional MR patients were evaluated, and 40 (34.5%) and 76 (65.5%) received a late-generation (G4) or early-generation device system, respectively. The baseline clinical and echocardiographic features were well-balanced between the groups. Overall, there was a significant reduction in mitral annular size after the intervention, and greater reductions in the anteroposterior diameter (4 mm vs. 3.54 mm, p = 0.03), annular perimeter (11.07 mm vs. 5.29 mm for 3D-perimeter, p = 0.001), and annular area (1.29 cm2 vs. 1.03 cm2, p = 0.002) were found for patients receiving the late G4 device generation compared to the early-generation systems. CONCLUSIONS: In patients with functional MR, we observed significant changes in mitral valve anatomy with a reduction in anteroposterior diameter, valve perimeter, and area. In our cohort, the extent of those changes was greater with the use of the new-generation G4 MitraClip system compared to prior device generations.

Early and mid-term outcomes of transcatheter tricuspid valve repair: systematic review and meta-analysis of observational studies.

INTRODUCTION AND OBJECTIVES: Severe tricuspid regurgitation (TR) is associated with poor prognosis when left untreated, and a growing number of studies on transcatheter tricuspid valve repair (TTVr) have been published over the last few months. METHODS: We performed a comprehensive systematic review of published literature providing clinical data on TTVr for patients with significant TR. Early and mid-term clinical and echocardiographic outcomes were evaluated. Risk ratios (RR) or mean differences (MD) were obtained when comparing pre- and postprocedural data. A sensitivity analysis was also performed according to the main approach for repair (edge-to-edge vs annuloplasty). RESULTS: A total of 19 studies (all observational or single-arm trials) and 991 patients who underwent isolated TTVr were included. Thirty-day mortality and stroke rates were 2.8% and 0.2%, respectively. Pooled random-effects resulted in a significant reduction of ≥ severe TR (RR, 0.33; 95%CI, 0.26-0.42; P < .001), vena contracta width (MD, 5.9mm; 95%CI, 4-7.9; P <.001), right ventricular end-diastolic diameter (MD, 3.5mm; 95%CI, 2.5-4.5; P <.001), and New York Heart Association (NYHA) class III or IV at last follow-up (RR, 0.32; 95%CI, 0.27-0.37; P <.001). Bleeding complications and residual ≥ severe TR were numerically higher in the annuloplasty-like group compared with edge-to-edge repair (13.3% vs 3.8% for bleeding and 40.4% vs 27.9% for residual severe TR). CONCLUSIONS: Among 991 patients comprising the early experience for several TTVr devices, there was a statistically significant reduction in ≥ severe TR, NYHA class III-IV, vena contracta width and right ventricular end-diastolic diameter after TTVr. Thus far, the edge-to-edge approach seems to be associated with a better safety profile.

Transcatheter tricuspid valve interventions: Current status and future perspectives.

The development of transcatheter therapies to treat valvular heart diseases has changed the rules of the game, particularly in the case of aortic stenosis and mitral regurgitation. In the last years, the tricuspid valve has also been the focus of these percutaneous techniques for several reasons: (1) tricuspid regurgitation is a frequent disease associated with poor clinical outcomes in spite of medical treatment, leading to end-stage right ventricular heart failure, (2) surgical tricuspid valve repair or replacement has been the treatment of choice for patients with tricuspid valve disease, but high mortality rates for isolated surgical tricuspid valve intervention have been reported in the literature, and (3) most patients with tricuspid pathology are ultimately denied cardiac surgery because of their comorbidity burden. Thus, in this context the development of less invasive catheter-based therapies would be of high clinical relevance. The present review provides an overview regarding the framework of chronic tricuspid regurgitation transcatheter therapeutic options, summarizes the transcatheter systems under clinical use or clinical evaluation with their technical features, and describes the updated current evidence in this challenging and evolving field.

Exploring the trends of adaptation and evolution of sclerites with regards to habitat depth in sea pens.

Octocorals possess sclerites, small elements comprised of calcium carbonate (CaCO3) that are important diagnostic characters in octocoral taxonomy. Among octocorals, sea pens comprise a unique order (Pennatulacea) that live in a wide range of depths. Habitat depth is considered to be important in the diversification of octocoral species, but a lack of information on sea pens has limited studies on their adaptation and evolution across depth. Here, we aimed to reveal trends of adaptation and evolution of sclerite shapes in sea pens with regards to habitat depth via phylogenetic analyses and ancestral reconstruction analyses. Colony form of sea pens is suggested to have undergone convergent evolution and the loss of axis has occurred independently across the evolution of sea pens. Divergences of sea pen taxa and of sclerite forms are suggested to depend on habitat depths. In addition, their sclerite forms may be related to evolutionary history of the sclerite and the surrounding chemical environment as well as water temperature. Three-flanged sclerites may possess the tolerance towards the environment of the deep sea, while plate sclerites are suggested to be adapted towards shallower waters, and have evolved independently multiple times. The common ancestor form of sea pens was predicted to be deep-sea and similar to family Pseudumbellulidae in form, possessing sclerites intermediate in form to those of alcyonaceans and modern sea pens such as spindles, rods with spines, and three-flanged sclerites with serrated edges sclerites, as well as having an axis and bilateral traits.

Different Phenotypes in Monozygotic Twins, Carriers of the Same Pathogenic Variant for Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a monogenic disease with autosomal dominant inheritance. Genotype−phenotype relationships are complex, with variable penetrance even within the same family. The involvement of other modulating genetic and environmental factors is unknown. We aimed to analyze the HCM in monozygotic twins, carriers of the same founder pathogenic variant MYBPC3 p.G263*. The relationship was verified using the PowerPlex 16 HS System kit. Phenotypic differences and environmental differences (overloading conditions, coexistence and location, lifestyle, sport, and intensity) were analyzed. Three pairs of twins genetically identical for all markers and carriers of MYBPC3 G263* were identified. No environmental differences were identified. One of the 89-year-old twins had symptomatic severe obstructive HCM that required septal ablation, while her twin has remained asymptomatic with mild phenotype >80 years. A 49-year-old twin had a severe phenotype of obstructive HCM and pending myectomy, while his twin had a mild asymptomatic phenotype. In the last pair of twins, one presented a much larger left ventricular hypertrophy than his identical twin. In summary, we present three pairs of HCM twin patients sharing not only the genetic cause of the inherited disease but the entire genetic background. Despite identical genetic information and the absence of other known clinical, environmental, or lifestyle differences, the severity of the HCM phenotype is strikingly different. These unexplained differences should prompt the study of other unknown modulating factors, either epigenetic or environmental.

Limited genomic reconstruction of SARS-CoV-2 transmission history within local epidemiological clusters.

A detailed understanding of how and when severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission occurs is crucial for designing effective prevention measures. Other than contact tracing, genome sequencing provides information to help infer who infected whom. However, the effectiveness of the genomic approach in this context depends on both (high enough) mutation and (low enough) transmission rates. Today, the level of resolution that we can obtain when describing SARS-CoV-2 outbreaks using just genomic information alone remains unclear. In order to answer this question, we sequenced forty-nine SARS-CoV-2 patient samples from ten local clusters in NW Spain for which partial epidemiological information was available and inferred transmission history using genomic variants. Importantly, we obtained high-quality genomic data, sequencing each sample twice and using unique barcodes to exclude cross-sample contamination. Phylogenetic and cluster analyses showed that consensus genomes were generally sufficient to discriminate among independent transmission clusters. However, levels of intrahost variation were low, which prevented in most cases the unambiguous identification of direct transmission events. After filtering out recurrent variants across clusters, the genomic data were generally compatible with the epidemiological information but did not support specific transmission events over possible alternatives. We estimated the effective transmission bottleneck size to be one to two viral particles for sample pairs whose donor-recipient relationship was likely. Our analyses suggest that intrahost genomic variation in SARS-CoV-2 might be generally limited and that homoplasy and recurrent errors complicate identifying shared intrahost variants. Reliable reconstruction of direct SARS-CoV-2 transmission based solely on genomic data seems hindered by a slow mutation rate, potential convergent events, and technical artifacts. Detailed contact tracing seems essential in most cases to study SARS-CoV-2 transmission at high resolution.

Confirmation of Aortic Stenosis Severity in Case of Discordance Between Aortic Valve Area and Gradient.

In this report, we illustrate the different flow-gradient patterns of aortic stenosis associated with discordant grading of stenosis severity at transthoracic echocardiography (TTE). The discordance among TTE parameters (mean gradient and aortic area) can be reconciled and true severity can be confirmed by ruling out potential measurements errors and by using multimodality imaging. (Level of Difficulty: Advanced.).

Etelis boweni sp. nov., a new cryptic deepwater eteline snapper from the Indo-Pacific (Perciformes: Lutjanidae).

A new species of Etelis is described based on 16 specimens collected from the Red Sea and Western Australia, with confirmed genetic records throughout the Indo-West Pacific. It is similar to and was often misidentified as Etelis carbunculus Cuvier, with both species sharing the diagnostic character of low number of developed gill rakers. Nonetheless, the two species are genetically divergent and differ morphologically in adult body length; proportions of eye, snout, cheek and caudal fin; shape of head, opercular spine and sagittal otolith; and coloration of the tip of the upper caudal fin. Etelis boweni has a wide Indo-west Pacific distribution that largely overlaps with E. carbunculus, and the two species are often caught on the same fishing line.

Aortic Valve Replacement in Low-Risk Patients With Severe Aortic Stenosis Outside Randomized Trials.

BACKGROUND: Recent randomized trials including low-risk patients showed positive results for transcatheter aortic valve replacement (TAVR) compared to surgical aortic valve replacement (SAVR), but patients with non-tricuspid aortic valve (NTAV), severe coronary artery disease (SevCAD), and those requiring concomitant mitral/tricuspid valve (CMTV) or concomitant ascending aorta replacement (CAAR) interventions were excluded. OBJECTIVES: This study sought to evaluate the presence and impact of the main clinical variables not evaluated in TAVR versus SAVR trials (NTAV, SevCAD, and CMTV or CAAR intervention) in a large series of consecutive low-risk patients with severe aortic stenosis (SAS) undergoing SAVR. METHODS: Single-center study including consecutive patients with SAS and low surgical risk (Society of Thoracic Surgeons score of <4%) undergoing SAVR. Baseline, procedural characteristics, and 30-day outcomes were prospectively collected. RESULTS: Of 6,772 patients with SAS who underwent SAVR between 2000 and 2019, 5,310 (78.4%) exhibited a low surgical risk (mean Society of Thoracic Surgeons score: 1.94 ± 0.87%). Of these, 2,165 patients (40.8%) had at least 1 of the following: NTAV (n = 1,468, 27.6%), SevCAD (n = 307, 5.8%), CMTV (n = 306, 5.8%), and CAAR (n = 560, 10.5%). The 30-day mortality and stroke rates for the overall low-risk SAS cohort were 1.9% and 2.4%, respectively. The mortality rate was similar in the SevCAD (2.6%) and CAAR (2.1%) groups versus the rest of the cohort (odds ratio [OR]: 1.79; 95% confidence interval [CI]: 0.85 to 3.75, and OR: 1.64; 95% CI: 0.88 to 3.05, respectively), lower in the NTAV group (0.9%; OR: 0.42; 95% CI: 0.22 to 0.81), and higher in the CMTV group (5.9%; OR: 2.61; 95% CI: 1.51 to 4.5). CONCLUSIONS: In a real-world setting, close to one-half of the low-risk patients with SAS undergoing SAVR exhibited at least 1 major criterion not evaluated in TAVR versus SAVR randomized trials. Clinical outcomes were better than or similar to those predicted by surgical scores in all groups but those patients requiring CMTV intervention. These results may help determine the impact of implementing the results of TAVR-SAVR trials in real practice and may inform future trials in specific groups.

Transcatheter aortic valve replacement in patients with paradoxical low-flow, low-gradient aortic stenosis: Incidence and predictors of treatment futility.

BACKGROUND: Few and controversial data exist on the outcomes of patients with paradoxical low-flow, low-gradient aortic stenosis (PLFLG-AS) following transcatheter aortic valve replacement (TAVR). This study aims to better characterize clinical outcomes and predictors of treatment futility in PLFLG-AS patients undergoing TAVR. METHODS: In this multicenter study, 318 patients with PLFLG-AS undergoing TAVR were categorized according to treatment futility, defined as all-cause mortality, poor functional status (NYHA class III-IV) or deterioration in functional class at 1-year follow-up. Clinical outcomes and the factors associated with treatment futility were assessed. RESULTS: The mean age of the patients was 81.0 ±â€¯8.3 years and 50.3% were women. At 1-year follow-up, 17.6% died and 12.9% had heart failure hospitalization. Residual impaired functional capacity (NYHA ≥ II) was present in 54.4% of patients who were alive at 1-year, and 9.8% remained in NYHA III/IV. The primary endpoint was observed in 103 (32.4%) patients, of which 54% died and 46% had a poor or worsening functional class. Factors independently associated with treatment futility were the presence of atrial fibrillation (AF) (OR:1.79, 95%CI, 1.04-3.10), chronic obstructive pulmonary disease (COPD) (OR:2.66, 95%CI, 1.50-4.74) and a lower SVi (OR per each decrease in 10 ml/m2:1.89, 95%CI, 1.06-3.45). The risk of treatment futility of patients with AF, COPD and a SVi < 30 ml/m2 was 66.38% (95%CI, 54.29%-78.48%). CONCLUSION: Close to one-third of patients with PLFLG-AS failed to derive a benefit from TAVR. The presence of AF, COPD and a low SVi were predictors of treatment futility. Being able to identify patients less likely to improve after the procedure may help to guide management and improve outcomes in patients with PLFLG-AS.

Intraprocedural high-degree atrioventricular block or complete heart block in transcatheter aortic valve replacement recipients with no prior intraventricular conduction disturbances.

BACKGROUND: Conduction disturbances are the most frequent complication of transcatheter aortic valve replacement (TAVR). However, no data exists regarding the outcomes of intraprocedural high-degree atrioventricular block (HAVB) or complete heart block (CHB) in patients without previous conduction disturbances. OBJECTIVES: The aim of this study was to evaluate the outcomes of intraprocedural-HAVB/CHB in patients without previous intraventricular conduction disturbances. METHODS: The occurrence of intraprocedural-HAVB/CHB was assessed in 676 consecutive patients undergoing TAVR, and two groups were established according to its duration: persistent-HAVB/CHB (PHAVB/CHB) and transient-HAVB/CHB (THAVB/CHB), not present at the end of the procedure. RESULTS: Intraprocedural-HAVB/CHB occurred in 50 patients (7.4%), being persistent in 32 (64.0%), and transient in 18 (36.0%). The use of Medtronic Corevalve Revalving System (MCRS) and a greater oversizing of the valve increased the risk of intraprocedural-HAVB/CHB (p < 0.001). Permanent pacemaker implantation (PPI) was more frequent in the PHAVB/CHB than in the THAVB/CHB group (96.9% vs. 33.3%; p < 0.001). At 1-month follow-up, the PHAVB/CHB group showed a 98% ventricular pacing rate (VPR) compared to 16% in the THAVB/CHB group (p < 0.001), and similar VPR were observed at 1-year follow-up (98% vs. 37%, p < 0.001). Left ventricular ejection fraction (LVEF) decreased at 1-year follow-up in patients with PHAVB/CHB (-3.9 ± 1.8%, p = 0.003). CONCLUSIONS: In TAVR recipients with no prior intraventricular conduction disturbances, intraprocedural-HAVB/CHB occurred in 7.4% of cases. HAVB/CHB was persistent in most cases and determined a high rate of PPI post-TAVR. Very high VPR at 1- and 12-month follow-up were observed, which in turn was associated with a negative effect on LVEF. These results support early PPI and close follow-up in patients developing intraprocedural-PHAVB/CHB.