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Journal of Clinical Medicine May 2024Among patients with suspected severe aortic stenosis (AS), discordance between effective orifice area (EOA) and transvalvular gradients is frequent and requires a...
Among patients with suspected severe aortic stenosis (AS), discordance between effective orifice area (EOA) and transvalvular gradients is frequent and requires a multiparametric workup including flow assessment and calcium-scoring to confirm true severe AS. The aim of this study was to assess direct planimetry, energy loss index (Eli) and dimensionless index (DI) as stand-alone parameters to identify non-severe AS in discordant cases. In this prospective cohort study, we included consecutive AS patients > 70 years with EOA < 1.0 cm referred for valve replacement between 2014 and 2017. AS severity was retrospectively reassessed using the multiparametric work-up recommended in the 2021 ESC/EACTS guidelines. DI and ELi were calculated, and valve area was measured by direct planimetry on transesophageal echocardiography. A total of 101 patients (mean age 82 y; 57% male) were included. Discordance between EOA and gradients was observed in 46% and non-severe AS found in 24% despite an EOA < 1 cm. Valve planimetry performed poorly, with an area under the ROC curve (AUC) of 0.64. At a cut-off value of >0.82 cm, sensitivity and specificity to identify non-severe AS were 67 and 66%, respectively. DI and ELi showed a higher diagnostic accuracy, with an AUC of 0.77 and 0.76, respectively. Cut-off values of >0.24 and >0.6 cm/m identified non-severe AS, with a high specificity of 79% and 91%, respectively. Almost one in four patients with EOA < 1 cm had non-severe AS according to guideline-recommended multiparametric assessment. Direct valve planimetry revealed poor diagnostic accuracy and should be interpreted with caution. Usual prognostic cut-off values for DI > 0.24 and ELI > 0.6 cm/m identified non-severe AS with high specificity and should therefore be included in the assessment of low-gradient AS.
PubMed: 38892930
DOI: 10.3390/jcm13113220 -
Journal of Clinical Medicine May 2024The primary objective of this study was to evaluate the initial experience in Germany with the Meril Myval™ (MM) transcatheter heart valve (THV) system for the...
The primary objective of this study was to evaluate the initial experience in Germany with the Meril Myval™ (MM) transcatheter heart valve (THV) system for the treatment of severe symptomatic aortic valve stenosis. The MM THV is a novel balloon-expandable valve with an expanded sizing matrix. Contemporary patients undergoing TAVI with the established Edwards Sapien™ (ES) THV served as the comparator group. : Between 1st March and 31 August 2020 a total of 134 patients (33% female, 80.1 ± 6.7 years; EuroScore II 4.7 ± 4.8) underwent TAVI with an MM (95% transfemoral) for severe aortic stenosis at six German tertiary care centers. Correct positioning of the THV was achieved in 98.5% (n = 132). Mean aortic gradients (MPG) were reduced from 42 ± 14 mmHg to 11 ± 5 mmHg. Mild postprocedural paravalvular leak (PVL) was observed in 62% (n = 82) patients, whereas only one patient had more than mild PVL. New permanent pacemaker implantation (PPI) was indicated in 15 patients (11%). Major vascular complications occurred in 6.7% (n = 9) patients. The in-hospital combined incidence of all-cause death and stroke was 4.5% (n = 6). In the comparator group that included 268 patients, the 30-day incidences of PPI, major vascular complications, and the composite of all-cause death and stroke were 16%, 1.9%, and 7.1%, respectively; MPGs were reduced from 44 ± 15 mmHg to 12.8 ± 4.6 mmHg and the more than mild PVL occurred in 0.7%. The MM is a promising novel THV system, with performance comparable to the established ES THVs. These findings await confirmation by ongoing randomized trials.
PubMed: 38892875
DOI: 10.3390/jcm13113163 -
International Journal of Molecular... May 2024Hypertrophic cardiomyopathy (HCM) is a heart condition characterized by cellular and metabolic dysfunction, with mitochondrial dysfunction playing a crucial role.... (Review)
Review
Hypertrophic cardiomyopathy (HCM) is a heart condition characterized by cellular and metabolic dysfunction, with mitochondrial dysfunction playing a crucial role. Although the direct relationship between genetic mutations and mitochondrial dysfunction remains unclear, targeting mitochondrial dysfunction presents promising opportunities for treatment, as there are currently no effective treatments available for HCM. This review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Reviews guidelines. Searches were conducted in databases such as PubMed, Embase, and Scopus up to September 2023 using "MESH terms". Bibliographic references from pertinent articles were also included. Hypertrophic cardiomyopathy (HCM) is influenced by ionic homeostasis, cardiac tissue remodeling, metabolic balance, genetic mutations, reactive oxygen species regulation, and mitochondrial dysfunction. The latter is a common factor regardless of the cause and is linked to intracellular calcium handling, energetic and oxidative stress, and HCM-induced hypertrophy. Hypertrophic cardiomyopathy treatments focus on symptom management and complication prevention. Targeted therapeutic approaches, such as improving mitochondrial bioenergetics, are being explored. This includes coenzyme Q and elamipretide therapies and metabolic strategies like therapeutic ketosis. Understanding the biomolecular, genetic, and mitochondrial mechanisms underlying HCM is crucial for developing new therapeutic modalities.
Topics: Humans; Cardiomyopathy, Hypertrophic; Oxidation-Reduction; Mutation; Signal Transduction; Animals; Mitochondria; Oxidative Stress; Reactive Oxygen Species
PubMed: 38892064
DOI: 10.3390/ijms25115855 -
EuroIntervention : Journal of EuroPCR... Jun 2024Cardiac fibrosis plays a major pathophysiological role in any form of chronic heart disease, and high levels are associated with poor outcome. Diffuse and focal cardiac...
BACKGROUND
Cardiac fibrosis plays a major pathophysiological role in any form of chronic heart disease, and high levels are associated with poor outcome. Diffuse and focal cardiac fibrosis are different subtypes, which have different pathomechanisms and prognostic implications. The total fibrosis burden in endomyocardial biopsy tissue was recently proved to play an independent prognostic role in aortic stenosis patients after transcatheter aortic valve implantation (TAVI).
AIMS
Here, for the first time, we aim to assess the specific impact of different fibrosis subtypes on sudden cardiac death (SCD) as a primary reason for cardiovascular mortality after TAVI.
METHODS
The fibrosis pattern was assessed histologically in the left ventricular biopsies obtained during TAVI interventions in 161 patients, who received a structured follow-up thereafter.
RESULTS
Receiver operating characteristic analyses, performed 6, 12, 24 and 48 months after TAVI, showed diffuse, but not focal, fibrosis as a significant predictor for SCD at all timepoints, with the highest area under the curve at the first time point and a decrease in its SCD predictivity over time. In both multivariate Cox proportional hazards and Fine-Gray competing risk models, including both fibrosis subtypes, as well as age, sex and ejection fraction, high diffuse fibrosis remained statistically significant. Accordingly, it represents an independent SCD predictor, most importantly for the occurrence of early events.
CONCLUSIONS
The burden of diffuse cardiac fibrosis plays an important and independent prognostic role regarding SCD early after TAVI. Therefore, the histological evaluation of fibrosis topography has value as a prognostic tool for TAVI patients and may help to tailor individualised approaches to optimise their postinterventional management.
Topics: Humans; Transcatheter Aortic Valve Replacement; Male; Female; Aged; Death, Sudden, Cardiac; Aortic Valve Stenosis; Aged, 80 and over; Fibrosis; Risk Factors; Myocardium; Prognosis
PubMed: 38887885
DOI: 10.4244/EIJ-D-23-01068 -
EuroIntervention : Journal of EuroPCR... Jun 2024Coronary access (CA) is a major concern in redo-transcatheter aortic valve implantation (TAVI) for failing supra-annular self-expanding transcatheter aortic valves...
BACKGROUND
Coronary access (CA) is a major concern in redo-transcatheter aortic valve implantation (TAVI) for failing supra-annular self-expanding transcatheter aortic valves (TAVs).
AIMS
This ex vivo study evaluated the benefit of leaflet splitting (LS) on subsequent CA after redo-TAVI in anatomies deemed at high risk of unfeasible CA.
METHODS
Ex vivo, patient-specific models were printed three-dimensionally. Index TAVI was performed using ACURATE neo2 or Evolut PRO (TAV-1) at the standard implant depth and with different degrees of commissural misalignment (CMA). Redo-TAVI was performed using the balloon-expandable SAPIEN 3 Ultra (TAV-2) at different implant depths with commissural alignment. Selective CA was attempted for each configuration before and after LS in a pulsatile flow simulator. The leaflet splay area was assessed on the bench.
RESULTS
In matched comparisons of 128 coronary cannulations across 64 redo-TAVI configurations, the overall feasibility of CA significantly increased after LS (60.9% vs 18.7%; p<0.001). The effect of LS varied according to the sinotubular junction height, TAV-1 design, TAV-1 CMA, and TAV-2 implant depth, given TAV-2 alignment. LS enabled CA for up to CMA 45° with the ACURATE neo2 TAV-1 and up to CMA 30° with the Evolut PRO TAV-1. The combination of LS and a low TAV-2 implant provided the highest feasibility of CA after redo-TAVI. The leaflet splay area ranged from 25.60 mm2 to 37.86 mm2 depending on the TAV-1 platform and TAV-2 implant depth.
CONCLUSIONS
In high-risk anatomies, LS significantly improves CA feasibility after redo-TAVI for degenerated supra-annular self-expanding platforms. Decisions on redo-TAVI feasibility should be carefully individualised, taking into account the expected benefit of LS on CA for each scenario.
Topics: Humans; Transcatheter Aortic Valve Replacement; Aortic Valve; Heart Valve Prosthesis; Prosthesis Design; Printing, Three-Dimensional; Aortic Valve Stenosis; Coronary Vessels; Prosthesis Failure; Reoperation
PubMed: 38887883
DOI: 10.4244/EIJ-D-24-00107 -
EuroIntervention : Journal of EuroPCR... Jun 2024
Topics: Humans; Transcatheter Aortic Valve Replacement; Aortic Valve Stenosis; Heart Valve Prosthesis; Aortic Valve; Male; Female; Aged; Treatment Outcome; Aged, 80 and over; Prosthesis Design
PubMed: 38887882
DOI: 10.4244/EIJ-D-23-01018 -
Circulation Jun 2024Valvular heart disease is a common cause of morbidity and mortality worldwide and has no effective medical therapy. Severe disease is managed with valve replacement... (Review)
Review
Valvular heart disease is a common cause of morbidity and mortality worldwide and has no effective medical therapy. Severe disease is managed with valve replacement procedures, which entail high health care-related costs and postprocedural morbidity and mortality. Robust ongoing research programs have elucidated many important molecular pathways contributing to primary valvular heart disease. However, there remain several key challenges inherent in translating research on valvular heart disease to viable molecular targets that can progress through the clinical trials pathway and effectively prevent or modify the course of these common conditions. In this scientific statement, we review the basic cellular structures of the human heart valves and discuss how these structures change in primary valvular heart disease. We focus on the most common primary valvular heart diseases, including calcific aortic stenosis, bicuspid aortic valves, mitral valve prolapse, and rheumatic heart disease, and outline the fundamental molecular discoveries contributing to each. We further outline potential therapeutic molecular targets for primary valvular heart disease and discuss key knowledge gaps that might serve as future research priorities.
PubMed: 38881493
DOI: 10.1161/CIR.0000000000001254 -
Journal of the American Heart... Jun 2024Transcatheter aortic valve replacement (TAVR) has become the standard of care for severe aortic stenosis treatment. Exponential growth in demand has led to prolonged...
BACKGROUND
Transcatheter aortic valve replacement (TAVR) has become the standard of care for severe aortic stenosis treatment. Exponential growth in demand has led to prolonged wait times and adverse patient outcomes. Social marginalization may contribute to adverse outcomes. Our objective was to examine the association between different measures of neighborhood-level marginalization and patient outcomes while on the TAVR waiting list. A secondary objective was to understand if sex modifies this relationship.
METHODS AND RESULTS
We conducted a population-based retrospective cohort study of 11 077 patients in Ontario, Canada, referred to TAVR from April 1, 2018, to March 31, 2022. Primary outcomes were death or hospitalization while on the TAVR wait-list. Using cause-specific Cox proportional hazards models, we evaluated the relationship between neighborhood-level measures of dependency, residential instability, material deprivation, and ethnic and racial concentration with primary outcomes as well as the interaction with sex. After multivariable adjustment, we found a significant relationship between individuals living in the most ethnically and racially concentrated areas (quintile 4 and 5) and mortality (hazard ratio [HR], 0.64 [95% CI, 0.47-0.88] and HR, 0.73 [95% CI, 0.53-1.00], respectively). There was no significant association between material deprivation, dependency, or residential instability with mortality. Women in the highest ethnic or racial concentration quintiles (4 and 5) had significantly lower risks for mortality (HR values of 0.52 and 0.56, respectively) compared with quintile 1.
CONCLUSIONS
Higher neighborhood ethnic or racial concentration was associated with decreased risk for mortality, particular for women on the TAVR waiting list. Further research is needed to understand the drivers of this relationship.
Topics: Humans; Male; Female; Transcatheter Aortic Valve Replacement; Retrospective Studies; Aged, 80 and over; Aortic Valve Stenosis; Aged; Waiting Lists; Ontario; Time-to-Treatment; Social Deprivation; Health Services Accessibility; Time Factors; Neighborhood Characteristics; Risk Factors; Healthcare Disparities; Sex Factors
PubMed: 38879459
DOI: 10.1161/JAHA.123.032450 -
Journal of the American Heart... Jun 2024Hypertrophic cardiomyopathy is a burdensome condition that inflicts both physical and psychological impairment on those with the disease, negatively impacting... (Observational Study)
Observational Study
BACKGROUND
Hypertrophic cardiomyopathy is a burdensome condition that inflicts both physical and psychological impairment on those with the disease, negatively impacting health-related quality of life (HRQoL). Given the abundance of evidence suggesting a role of physical activity (PA) in modulating HRQoL in healthy populations of children, we sought to determine the relationship between HRQoL and PA in children diagnosed with hypertrophic cardiomyopathy.
METHODS AND RESULTS
A multicenter prospective observational cohort study was conducted, with patients with hypertrophic cardiomyopathy aged 10 to 19 years being provided a wrist-worn activity tracker (Fitbit Charge HR) to wear for 14 days. Patients self-reported on Pediatric Quality of Life 4.0 quality of life inventory items, which were associated with PA metrics following covariate adjustment using linear regression. A total of 56 participants were recruited to the study. The median age at enrollment was 15.5 years (interquartile range, 13.8-16.8), and 16 out of 56 (29%) of the cohort were girls. The cohort reported decreased metrics of physical, psychosocial, and total summary scores compared with health reference populations, with scores comparable with that of published populations with chronic disease. Increased physical HRQoL scores were significantly associated with increased daily steps taken, distance traveled, and flights of stairs climbed.
CONCLUSIONS
These results show that impaired PA correlates with reduced HRQoL in children with hypertrophic cardiomyopathy, suggesting PA may partially mediate HRQoL in this population.
Topics: Humans; Quality of Life; Female; Adolescent; Cardiomyopathy, Hypertrophic; Male; Prospective Studies; Child; Exercise; Young Adult; Fitness Trackers; Health Status
PubMed: 38879453
DOI: 10.1161/JAHA.123.033968 -
Indian Heart Journal Jun 2024We evaluated empagliflozin in severe DAS patients with HF before AVR. HF patients with LVEF 30-80 % and NYHA functional class II-IV symptoms got empagliflozin 10 mg or...
We evaluated empagliflozin in severe DAS patients with HF before AVR. HF patients with LVEF 30-80 % and NYHA functional class II-IV symptoms got empagliflozin 10 mg or not within 6 months before AVR, along with SOC. Adding empagliflozin to the SOC before AVR reduced HF death or HHF by 73 % after 6-months in a group of 20 patients (RR 0.27; p = 0.022). Improving LVEF (+3.48 %, p < 0.001) and NT-proBNP levels (-3974.6 pg/mL) with empagliflozin in SOC before AVR significantly reduced in-hospital and 6-month mortality in this patient group. In severe DAS and HF patients, empagliflozin improved symptoms and prognosis.
PubMed: 38878965
DOI: 10.1016/j.ihj.2024.06.009