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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 -
Journal of Cardiothoracic Surgery Jun 2024Women undergoing cardiac surgery have been historically recognized to carry higher periprocedural mortality risk. We aimed to investigate the influence of sex on...
BACKGROUND
Women undergoing cardiac surgery have been historically recognized to carry higher periprocedural mortality risk. We aimed to investigate the influence of sex on clinical presentation, perioperative, and long-term outcomes in patients who undergo surgery for ascending aortic aneurysm.
METHODS
We conducted a retrospective review of 1148 consecutive patients (380 [33.1%] female) who underwent thoracic aortic surgery under moderate hypothermic circulatory arrest for ascending aortic aneurysms between 2001 and 2021. Baseline and operative characteristics, in-hospital mortality, and survival were compared between male and female patients before and after propensity-score-matched (PSM) analysis.
RESULTS
Women were significantly older (median age: 69 [IQR: 63-75] vs. 67 [IQR: 58-73]; P < 0.001), while men had a higher prevalence of aortic valve stenosis, bicuspid valve and coronary artery disease at the time of surgery (P < 0.05). After PSM, EuroSCORE II (4.36 [2.68; 6.87] vs. 3.22 [1.85; 5.31]; p < 0.001), and indexed aortic diameter were significantly higher in female patients (2.94 [2.68; 3.30] vs. 2.58 [2.38; 2.81] cm/m2, p < 0.001). In the matched cohort, men were more likely to experience postoperative delirium (18.1% vs. 11.5%; P = 0.002), and postoperative neurological deficits (6.7% vs. 3.0%, P = 0.044),. Female patients were more likely to receive postoperative packed red blood cells (p = 0.036) and fresh frozen plasma (p = 0.049). In-hospital and 30-day mortality was similar between both groups. Long-term survival was comparable between both groups with 88% vs. 88% at 5 years, 76% vs. 71% at 10 years, and 59% vs. 47% at 15 years.
CONCLUSION
Female patients required more transfusions, while males had a higher incidence of postoperative delirium and neurological deficits. Differences in preoperative age and timing of surgery between the sexes could be attributed to variations in comorbidity profiles and the greater prevalence of concomitant surgery indications in males.
Topics: Humans; Female; Male; Propensity Score; Retrospective Studies; Aged; Middle Aged; Sex Factors; Hospital Mortality; Aortic Aneurysm, Thoracic; Postoperative Complications; Treatment Outcome; Risk Factors; Aneurysm, Ascending Aorta
PubMed: 38877532
DOI: 10.1186/s13019-024-02646-6 -
Mathematical Biosciences and... May 2024The coronary artery constitutes a vital vascular system that sustains cardiac function, with its primary role being the conveyance of indispensable nutrients to the...
The coronary artery constitutes a vital vascular system that sustains cardiac function, with its primary role being the conveyance of indispensable nutrients to the myocardial tissue. When coronary artery disease occurs, it will affect the blood supply of the heart and induce myocardial ischemia. Therefore, it is of great significance to numerically simulate the coronary artery and evaluate its blood supply capacity. In this article, the coronary artery lumped parameter model was derived based on the relationship between circuit system parameters and cardiovascular system parameters, and the blood supply capacity of the coronary artery in healthy and stenosis states was studied. The aortic root pressure calculated by the aortic valve fluid-structure interaction (AV FSI) simulator was employed as the inlet boundary condition. To emulate the physiological phenomenon of sudden pressure drops resulting from an abrupt reduction in blood vessel radius, a head loss model was connected at the coronary artery's entrance. For each coronary artery outlet, the symmetric structured tree model was appended to simulate the terminal impedance of the missing downstream coronary arteries. The particle swarm optimization (PSO) algorithm was used to optimize the blood flow viscous resistance, blood flow inertia, and vascular compliance of the coronary artery model. In the stenosis states, the relative flow and fractional flow reserve (FFR) calculated by numerical simulation corresponded to the published literature data. It was anticipated that the proposed model can be readily adapted for clinical application, serving as a valuable reference for diagnosing and treating patients.
Topics: Humans; Coronary Vessels; Models, Cardiovascular; Computer Simulation; Algorithms; Coronary Circulation; Hemodynamics; Coronary Stenosis; Fractional Flow Reserve, Myocardial; Blood Flow Velocity; Blood Pressure; Coronary Artery Disease; Aortic Valve
PubMed: 38872561
DOI: 10.3934/mbe.2024258