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Journal of Molecular and Cellular... Jun 2024Mitochondrial (MITO) dysfunction occurs in the failing heart and contributes to worsening of heart failure (HF). Reduced aldehyde dehydrogenase 2 (ALDH2) in left...
Mitochondrial (MITO) dysfunction occurs in the failing heart and contributes to worsening of heart failure (HF). Reduced aldehyde dehydrogenase 2 (ALDH2) in left ventricular (LV) myocardium of diabetic hearts has been implicated in MITO dysfunction through accumulation of toxic aldehydes including and elevated levels of 4-hydroxy-2-nonenal (4HNE). This study examined whether dysregulation of MITO ALDH2 (mALDH2) occurs in mitochondria of the failing LV and is associated with increased levels of 4HNE. LV tissue from 7 HF and 7 normal (NL) dogs was obtained. Protein quantification of total mitochondrial ALDH2 (t-mALDH2), phosphorylated mALDH2 (p-mALDH2), total MITO protein kinase c epsilon (t-mPKCε), phosphorylated mPKCε (p-mPKCε) was performed by Western blotting, and total mALDH2 enzymatic activity was measured. Protein adducts of 4HNE-MITO and 4HNE-mALDH2 were also measured in MITO fraction by Western Blotting. Protein level of t-mALDH2 was decreased in HF compared with NL dogs (0.63 ± 0.07 vs 1.17 ± 0.08, < 0.05) as did mALDH2 enzymatic activity (51.39 ± 3 vs. 107.66 ± 4 nmol NADH/min/mg, < 0.05). Phosphorylated-mALDH2 and p-mPKCε were unchanged. 4HNE-MITO proteins adduct levels increased in HF compared with NL (2.45 ± 0.08 vs 1.30 ± 0.03 du, < 0.05) as did adduct levels of 4HNE-mALDH2 (1.60 ± 0.20 vs 0.39 ± 0.08, < 0.05). In isolated failing cardiomyocytes (CM) exposure to 4HNE decreased mALDH2 activity, increased ROS and 4HNE-ALDH2 adducts, and worsened MITO function. Stimulation of mALDH2 activity with ALDA-1 in isolated HF CMs compared to NL CMs improved ADP-stimulated respiration and maximal ATP synthesis to a greater extant (+47 % and +89 %, respectively). Down-regulation of mALDH2 protein levels and activity occurs in HF and contributes to MITO dysfunction and is likely caused by accumulation of 4HNE-mALDH2 adduct. Increasing mALDH2 activity (via ALDA-1) improved MITO function in failing CMs.
PubMed: 38938550
DOI: 10.1016/j.jmccpl.2024.100067 -
JACC. Advances Oct 2023Hypertrophic cardiomyopathy-both obstructive hypertrophic cardiomyopathy (oHCM) and nonobstructive hypertrophic cardiomyopathy (nHCM) subtypes-is the most common... (Review)
Review
Hypertrophic cardiomyopathy-both obstructive hypertrophic cardiomyopathy (oHCM) and nonobstructive hypertrophic cardiomyopathy (nHCM) subtypes-is the most common monogenic cardiomyopathy. Its structural hallmarks are abnormal thickening of the myocardium and hyperdynamic contractility, while its hemodynamic consequences are left ventricular outflow tract or intracavitary obstruction (in oHCM) and diastolic dysfunction (in both oHCM and nHCM). Several medical therapies are routinely used to improve these abnormalities with the goal to decrease symptom burden in patients with HCM. Current guidelines recommend nonvasodilating beta blockers as first-line and nondihydropyridine calcium channel blockers followed by disopyramide as second- and third-line medical therapies for symptomatic oHCM and give weaker recommendations for beta blockers and calcium channel blockers in nHCM. These recommendations are based on small studies-mostly nonrandomized-and expert opinion. Our review will summarize the available data on the effectiveness of commonly prescribed medications used in oHCM and nHCM to uncover knowledge gaps, but also new data on cardiac myosin inhibitors.
PubMed: 38938334
DOI: 10.1016/j.jacadv.2023.100622 -
BMC Cardiovascular Disorders Jun 2024The cardiac toxicity of radiotherapy (RT) can affect cancer survival rates over the long term. This has been confirmed in patients with breast cancer and lymphoma....
Application of two-dimensional speckle-tracking echocardiography in radiotherapy-related cardiac systolic dysfunction and analysis of its risk factors: a prospective cohort study.
BACKGROUND
The cardiac toxicity of radiotherapy (RT) can affect cancer survival rates over the long term. This has been confirmed in patients with breast cancer and lymphoma. However, there are few studies utilizing the two-dimensional speckle-tracking echocardiography (2D-STE) to evaluate the risk factors affecting radiation induced heart disease (RIHD), and there is a lack of quantitative data. Therefore, we intend to explore the risk factors for RIHD and quantify them using 2D-STE technology.
METHODS
We ultimately enrolled 40 patients who received RT for thoracic tumors. For each patient, 2D-STE was completed before, during, and after RT and in the follow up. We analyzed the sensitivity of 2D-STE in predicting RIHD and the relationship between RT parameters and cardiac systolic function decline.
RESULTS
Left ventricle global longitudinal strain (LVGLS), LVGLS of the endocardium (LVGLS-Endo), LVGLS of the epicardium (LVGLS-Epi), and right ventricle free-wall longitudinal strain (RVFWLS) decreased mid- and post-treatment compared with pre-treatment, whereas traditional parameters such as left ventricular ejection fraction (LVEF), cardiac Tei index (Tei), and peak systolic velocity of the free wall of the tricuspid annulus (s') did not show any changes. The decreases in the LVGLS and LVGLS-Endo values between post- and pre-treatment and the ratios of the decreases to the baseline values were linearly correlated with mean heart dose (MHD) (all P values < 0.05). The decreases in the LVGLS-Epi values between post- and pre-treatment and the ratios of the decreases to the baseline values were linearly correlated with the percentage of heart volume exposed to 5 Gy or more (V5) (P values < 0.05). The decrease in RVFWLS and the ratio of the decrease to the baseline value were linearly related to MHD and patient age (all P values < 0.05). Endpoint events occurred more frequently in the right side of the heart than in the left side. Patients over 56.5 years of age had a greater probability of developing right-heart endpoint events. The same was true for patients with MHD over 20.2 Gy in both the left and right sides of the heart.
CONCLUSIONS
2D-STE could detect damages to the heart earlier and more sensitively than conventional echocardiography. MHD is an important prognostic parameter for LV systolic function, and V5 may also be an important prognostic parameter. MHD and age are important prognostic parameters for right ventricle systolic function.
Topics: Humans; Female; Male; Middle Aged; Prospective Studies; Predictive Value of Tests; Aged; Ventricular Function, Left; Radiation Injuries; Risk Assessment; Systole; Cardiotoxicity; Risk Factors; Adult; Time Factors; Thoracic Neoplasms; Radiotherapy; Ventricular Function, Right; Echocardiography; Heart Disease Risk Factors; Stroke Volume
PubMed: 38937716
DOI: 10.1186/s12872-024-03981-1 -
Cardiovascular Engineering and... Jun 2024Venoarterial extracorporeal membrane oxygenation (VA ECMO) is used in patients with refractory cardiac or cardio-pulmonary failure. Native ventricular output interacts...
PURPOSE
Venoarterial extracorporeal membrane oxygenation (VA ECMO) is used in patients with refractory cardiac or cardio-pulmonary failure. Native ventricular output interacts with VA ECMO flow and may hinder sufficient oxygenation to the heart and the brain. Further on, VA ECMO leads to afterload increase requiring ventricular unloading. The aim of the study was to investigate aortic blood flow and oxygenation for various ECMO settings and cannula positions with a numerical model.
METHODS
Four different aortic cannula tip positions (ascending aorta, descending aorta, abdominal aorta, and iliac artery) were included in a model of a human aorta. Three degrees of cardiac dysfunction and VA ECMO support (50%, 75% and 90%) with a total blood flow of 6 l/min were investigated. Additionally, the Impella CP device was implemented under 50% support condition. Blood oxygen saturation at the aortic branches and the pressure acting on the aortic valve were calculated.
RESULTS
A more proximal tip orientation is necessary to increase oxygen supply to the supra-aortic and coronary arteries for 50% and 75% support. During the 90% support scenario, proper oxygenation can be achieved independently of tip position. The use of Impella reduces afterload by 8-17 mmHg and vessel oxygenation is similar to 50% VA ECMO support. Pressure load on the aortic valve increases with more proximal tip position and is decreased during Impella use.
CONCLUSIONS
We present a simulation model for the investigation of hemodynamics and blood oxygenation with various mechanical circulatory support systems. Our results underline the intricate and patient-specific relationship between extracorporeal support, cannula tip orientation and oxygenation capacity.
PubMed: 38937386
DOI: 10.1007/s13239-024-00739-w -
The Annals of Thoracic Surgery Jun 2024Although adverse technical events during aortic root replacement (ARR) are not uncommon and are extremely challenging, there is little literature to help surgeons...
BACKGROUND
Although adverse technical events during aortic root replacement (ARR) are not uncommon and are extremely challenging, there is little literature to help surgeons prepare for such situations. We describe our experience of outstanding technical events during ARR.
METHODS
This is a retrospective study of 830 consecutive ARR at a single center from 2012-2022. Technical events were defined as intraoperative events that led to an unplanned cardiac procedure, need for mechanical circulatory support, or additional aortic cross-clamping. Logistic regression identified factors associated with operative mortality and technical events.
RESULTS
Technical events occurred in 90 (10.8%) patients, and were attributed to bleeding (n=26), nonischemic ventricular dysfunction (n=23), residual valve disease (n=20), myocardial ischemia (n=19), and iatrogenic dissection (n=2). Prior sternotomy (OR 2.38 [1.36-4.19], p=0.002) and complex aortic valve disease (OR 3.09 [1.09-8.75], p=0.03) were associated with technical events. Patients with technical events had higher rates of operative mortality (6.7% vs 2.3%, p=0.03) and all major postoperative complications. Surgical indications of dissection (OR 13.57 [4.95-37.23], p<0.001) and complex aortic valve disease (OR 14.09 [3.67-54.02], p<0.001) but not adverse technical events (OR 2.42 [0.81-7.26], p=0.11) were associated with operative mortality.
CONCLUSIONS
Adverse technical events occur in 10.8% of ARR and were associated with reoperative sternotomies. Technical events are associated with increased postoperative complications.
PubMed: 38936593
DOI: 10.1016/j.athoracsur.2024.06.014 -
The Annals of Thoracic Surgery Jun 2024This study investigated the long-term outcomes of physiological and anatomical repair for corrected transposition of the great arteries and double outlet right ventricle...
BACKGROUND
This study investigated the long-term outcomes of physiological and anatomical repair for corrected transposition of the great arteries and double outlet right ventricle with discordant atrioventricular connection.
METHODS
This single-center retrospective study included 146 patients who underwent biventricular repair of corrected transposition of the great arteries or double outlet right ventricle with discordant atrioventricular connections from 1972 to 2023. Survival rate, freedom from reoperation, NYHA classification and incidence of systemic ventricular dysfunction in the long-term were compared between physiological repair group (PR group) and anatomical repair group (AR group).
RESULTS
PR group consisted of 55 patients with median age at repair of 10.3 years. Thirty-one patients underwent conventional Rastelli procedure and 24 patients underwent atrial and/or ventricular septal defect closure. AR group consisted of 91 patients with median age at repair of 5.8 years. Seventy-two patients underwent atrial switch plus Rastelli procedure and 19 patients underwent atrial plus arterial switch operation. The 30-year survival was 63.5% in PR group and 72.3% in AR group (p=0.448). The 30-year freedom from reoperation was 71.9% in PR group and 62.2% in AR group (p=0.220). There was a significant difference in incidence of systemic ventricular dysfunction between the groups (87.5% in PR group and 35.3% in AR group: p<0.001) and long-term survivors' NYHA classification (mean NYHA class of 1.9 in PR group and 1.5 in AR group: p=0.009).
CONCLUSIONS
The systemic ventricular function and general status in the long-term were significantly better in anatomical repair patients, suggesting the potential advantage of anatomical repair.
PubMed: 38936589
DOI: 10.1016/j.athoracsur.2024.06.010 -
Heart Rhythm Jun 2024Heart Rate Score (HRSc), the percent of atrial depolarizations in the largest paced/sensed 10-bpm histogram bin recorded in cardiac devices, is associated with several...
BACKGROUND
Heart Rate Score (HRSc), the percent of atrial depolarizations in the largest paced/sensed 10-bpm histogram bin recorded in cardiac devices, is associated with several adverse outcomes but it remains uncertain if HRSc independently predicts atrial high-rate episodes (AHREs) in patients with sinus node dysfunction (SND) undergoing pacemaker (PM) implantation.
OBJECTIVE
To determine if initial HRSc post-PM implant predicts new-onset AHREs in patients with SND.
METHODS
Patients had Boston Scientific PMs implanted for SND from 2012-2021 at Cleveland Clinic, University of Occupational and Environmental Health, Japan, Kyushu Rosai Hospital, and JCHO Kyushu Hospital. Patients were excluded if they had atrial fibrillation before PM implant or AHREs within 3-months post-implant. Subsequent AHREs post-implant were evaluated and correlated with HRSc.
RESULTS
Over 48.9 (IQR 25.7-50.4) months, 130 consecutive PM patients (76±10 years, 40% male) had a median initial HRSc of 74(57-86)%. AHREs defined by >1%, >6h/day burden, and ATR events>24h developed in 27/130(21%), 15/130(12%), and 9/130(7%), respectively. For each definition, patients with HRSc≥80% had higher occurrence of AHREs than those with HRSc<80% (both p=0.008, log-rank test). After adjusting for age, race, comorbidities, left ventricular ejection fraction, left atrial diameter, and cumulative %RA/RV pacing, initial HRSc ≥80% (HR:3.33, 95% CI:1.35-8.18; P=0.009) and male sex (HR:2.59, 95% CI:1.06-6.33; P=0.04) independently predicted AHREs.
CONCLUSION
HRSc≥80% is associated with new-onset, device-determined AHREs for patients undergoing PM implant for SND. HRSc may have prognostic and therapeutic implications.
PubMed: 38936446
DOI: 10.1016/j.hrthm.2024.06.046 -
JACC. Heart Failure Jun 2024The REDUCE LAP-HF II (Reduce Elevated Left Atrial Pressure in Patients With Heart Failure II) trial found that, compared with a sham procedure, the Corvia Atrial Shunt...
BACKGROUND
The REDUCE LAP-HF II (Reduce Elevated Left Atrial Pressure in Patients With Heart Failure II) trial found that, compared with a sham procedure, the Corvia Atrial Shunt did not improve outcomes in heart failure with preserved or mildly reduced ejection fraction. However, after 12-month follow-up, "responders" (peak-exercise pulmonary vascular resistance <1.74 WU and absence of a cardiac rhythm management device) were identified.
OBJECTIVES
This study sought to determine: 1) the overall efficacy and safety of the atrial shunt vs sham control after 2 years of follow-up; and 2) whether the benefits of atrial shunting are sustained in responders during longer-term follow-up or are offset by adverse effects of the shunt.
METHODS
The study analyzed 2-year outcomes in the overall REDUCE LAP-HF II trial, as well as in responder and nonresponder subgroups. The primary endpoint was a hierarchical composite of cardiovascular death or nonfatal ischemic/embolic stroke, total heart failure events, and change in health status.
RESULTS
In 621 randomized patients, there was no difference between the shunt (n = 309) and sham (n = 312) groups in the primary endpoint (win ratio: 1.01 [95% CI: 0.82-1.24]) or its individual components at 2 years. Shunt patency at 24 months was 98% in shunt-treated patients. Cardiovascular mortality and nonfatal ischemic stroke were not different between the groups; however, major adverse cardiac events were more common in those patients assigned to the shunt compared with sham (6.9% vs 2.7%; P = 0.018). More patients randomized to the shunt had an increase in right ventricular volume of ≥30% compared with the sham control (39% vs 28%, respectively; P < 0.001), but right ventricular dysfunction was uncommon and not different between the treatment groups. In responders (n = 313), the shunt was superior to sham (win ratio: 1.36 [95% CI: 1.02-1.83]; P = 0.037, with 51% fewer HF events [incidence rate ratio: 0.49 [95% CI: 0.25-0.95]; P = 0.034]). In nonresponders (n = 265), atrial shunting was inferior to sham (win ratio: 0.73 [95% CI: 0.54-0.98]).
CONCLUSIONS
At 2 years of follow-up in REDUCE LAP-HF II, there was no difference in efficacy between the atrial shunt and sham groups in the overall trial group. The potential clinical benefit identified in the responder group after 1 and 2 years of follow-up is currently being evaluated in the RESPONDER-HF (Re-Evaluation of the Corvia Atrial Shunt Device in a Precision Medicine Trial to Determine Efficacy in Mildly Reduced or Preserved Ejection Fraction Heart Failure) trial. (Reduce Elevated Left Atrial Pressure in Patients With Heart Failure II [REDUCE LAP-HF II]; NCT03088033).
PubMed: 38934964
DOI: 10.1016/j.jchf.2024.04.011 -
Journal of Hypertension Aug 2024
Topics: Humans; Obesity; Ventricular Dysfunction, Left; Echocardiography; Meta-Analysis as Topic; Systole
PubMed: 38934188
DOI: 10.1097/HJH.0000000000003766 -
Fetal Diagnosis and Therapy Jun 2024The aim of this systematic review and meta-analysis was to evaluate fetal cardiac function in fetuses of mothers with diabetes compared to those of mothers without...
INTRODUCTION
The aim of this systematic review and meta-analysis was to evaluate fetal cardiac function in fetuses of mothers with diabetes compared to those of mothers without diabetes using 2D-STE.
METHODS
Embase, MEDLINE and CENTRAL were searched for observational studies on 2D-STE fetal left and right ventricular global longitudinal strain and strain rate that included singleton, non-anomalous pregnancies complicated by pregestational or gestational diabetes mellitus compared to uncomplicated pregnancies. The strain values were pooled per 4 weeks of gestation for meta-analysis using random-effects models.
RESULTS
Fifteen studies met the criteria, including 990 fetuses of diabetic mothers and 1,645 control fetuses. The study design was cross-sectional in fourteen studies and longitudinal in one study. Gestational age, type of diabetes, ultrasound device and 2D-STE software varied between the studies. Glycemic control and type of treatment were often lacking. In fetuses of diabetic mothers versus healthy mothers, left ventricular strain was significantly decreased (7 studies), increased (1 study) or not significantly different (7 studies). Right ventricular strain was decreased (7 studies), increased (1 study) or not different (2 studies). Left ventricular strain rate was decreased (3 studies), increased (1 study) or not different (2 studies). Right ventricular strain rate was increased (1 study) or not different (2 studies).
CONCLUSION
Fetuses of mothers with diabetes show evidence of systolic dysfunction, which is more visible in the right ventricle. Contradictory results are probably due to suboptimal study designs and variation in gestational age, diabetes severity, image acquisition and software. Large prospective longitudinal studies are needed to assess fetal myocardial function with 2D-STE in pregestational diabetes mellitus type 1 and 2 and gestational diabetes mellitus pregnancies. The influence of glycemic control, BMI and treatment should be evaluated.
PubMed: 38934164
DOI: 10.1159/000538413