-
Arteriosclerosis, Thrombosis, and... Jul 2024Myxomatous valve disease (MVD) is the most common cause of mitral regurgitation, leading to impaired cardiac function and heart failure. MVD in a mouse model of Marfan...
BACKGROUND
Myxomatous valve disease (MVD) is the most common cause of mitral regurgitation, leading to impaired cardiac function and heart failure. MVD in a mouse model of Marfan syndrome includes valve leaflet thickening and progressive valve degeneration. However, the underlying mechanisms by which the disease progresses remain undefined.
METHODS
Mice with gene variant recapitulate histopathologic features of Marfan syndrome, and Wnt (Wingless-related integration site) signaling activity was detected in (T-cell factor/lymphoid enhancer factor-β-galactosidase) reporter mice. Single-cell RNA sequencing was performed from mitral valves of wild-type and mice at 1 month of age. Inhibition of Wnt signaling was achieved by conditional induction of the secreted Wnt inhibitor Dkk1 (Dickkopf-1) expression in periostin-expressing valve interstitial cells of -Cre; mice. Dietary doxycycline was administered for 1 month beginning with MVD initiation (1-month-old) or MVD progression (2-month-old). Histological evaluation and immunofluorescence for ECM (extracellular matrix) and immune cells were performed.
RESULTS
Wnt signaling is activated early in mitral valve disease progression, before immune cell infiltration in mice. Single-cell transcriptomics revealed similar mitral valve cell heterogeneity between wild-type and mice at 1 month of age. Wnt pathway genes were predominantly expressed in valve interstitial cells and valve endothelial cells of mice. Inhibition of Wnt signaling in mice at 1 month of age prevented the initiation of MVD as indicated by improved ECM remodeling and reduced valve leaflet thickness with decreased infiltrating macrophages. However, later, Wnt inhibition starting at 2 months did not prevent the progression of MVD.
CONCLUSIONS
Wnt signaling is involved in the initiation of mitral valve abnormalities and inflammation but is not responsible for later-stage valve disease progression once it has been initiated. Thus, Wnt signaling contributes to MVD progression in a time-dependent manner and provides a promising therapeutic target for the early treatment of congenital MVD in Marfan syndrome.
Topics: Animals; Wnt Signaling Pathway; Disease Progression; Fibrillin-1; Disease Models, Animal; Mitral Valve; Mice; Intercellular Signaling Peptides and Proteins; Mice, Transgenic; Marfan Syndrome; Mitral Valve Insufficiency; Mice, Inbred C57BL; Inflammation; Male; Female; Cell Adhesion Molecules; Adipokines
PubMed: 38660802
DOI: 10.1161/ATVBAHA.123.320388 -
Circulation May 2024Tricuspid valve disease is an often underrecognized clinical problem that is associated with significant morbidity and mortality. Unfortunately, patients will often... (Review)
Review
Tricuspid valve disease is an often underrecognized clinical problem that is associated with significant morbidity and mortality. Unfortunately, patients will often present late in their disease course with severe right-sided heart failure, pulmonary hypertension, and life-limiting symptoms that have few durable treatment options. Traditionally, the only treatment for tricuspid valve disease has been medical therapy or surgery; however, there have been increasing interest and success with the use of transcatheter tricuspid valve therapies over the past several years to treat patients with previously limited therapeutic options. The tricuspid valve is complex anatomically, lying adjacent to important anatomic structures such as the right coronary artery and the atrioventricular node, and is the passageway for permanent pacemaker leads into the right ventricle. In addition, the mechanism of tricuspid pathology varies widely between patients, which can be due to primary, secondary, or a combination of causes, meaning that it is not possible for 1 type of device to be suitable for treatment of all cases of tricuspid valve disease. To best visualize the pathology, several modalities of advanced cardiac imaging are often required, including transthoracic echocardiography, transesophageal echocardiography, cardiac computed tomography, and cardiac magnetic resonance imaging, to best visualize the pathology. This detailed imaging provides important information for choosing the ideal transcatheter treatment options for patients with tricuspid valve disease, taking into account the need for the lifetime management of the patient. This review highlights the important background, anatomic considerations, therapeutic options, and future directions with regard to treatment of tricuspid valve disease.
Topics: Humans; Tricuspid Valve; American Heart Association; United States; Heart Valve Diseases; Tricuspid Valve Insufficiency; Heart Valve Prosthesis Implantation
PubMed: 38660790
DOI: 10.1161/CIR.0000000000001232 -
JACC. Cardiovascular Interventions Apr 2024
Topics: Humans; Cardiac Catheterization; Predictive Value of Tests; Treatment Outcome; Heart Valve Prosthesis Implantation; Hypertension, Pulmonary; Risk Factors; Time Factors; Tricuspid Valve; Tricuspid Valve Insufficiency; Risk Assessment; Female; Male; Arterial Pressure; Aged; Pulmonary Artery
PubMed: 38658125
DOI: 10.1016/j.jcin.2024.01.314 -
International Journal of Cardiology Aug 2024In congenital aortic valve disease, quantifying aortic regurgitation (AR) varies by the measurement site. Our study aimed to identify the optimal site for AR assessment...
BACKGROUND
In congenital aortic valve disease, quantifying aortic regurgitation (AR) varies by the measurement site. Our study aimed to identify the optimal site for AR assessment using 2D and 4D MR flow measurements, with a focus on vortices.
METHODS
We retrospectively analysed 31 patients with congenital aortic valve disease, performing 2D and 4D MR flow measurements at the aortic valve, sinotubular junction (STJ), ascending aorta (AAo), and using midpulmonary artery measurements as a reference. We assessed percentage AR and net forward volumes, calculated linear correlations, and plotted Bland-Altman plots. Net forward flow at all aortic sites were correlated with the main pulmonary artery. Differences in AR between 2D and 4D flows were linked to vortices detected by 4D streamlines.
RESULTS
The best agreement in % AR between 2D and 4D flows was at the aortic valve (mean difference 4D2D -2.9%, limits of agreement 8.7% to -14.3%; r = 0.7). Correlations weakened at STJ and AAo. Vortices in the ascending aorta led to AR overestimation in 2D measurements. Net forward flow at the aortic valve by 4D flow correlated closer with main pulmonary artery than did 2D flow. (Mean difference for 2D and 4D MR flow 7.5 ml and 4.2 ml, respectively).
CONCLUSIONS
For congenital aortic valve disease, the most accurate AR quantification occurs at the aortic valve using 2D and 4D MR flow. Notably, vortices in the ascending aorta can result in AR overestimation with 2D MR flow.
Topics: Humans; Aortic Valve Insufficiency; Retrospective Studies; Female; Male; Adult; Aortic Valve; Magnetic Resonance Imaging, Cine; Blood Flow Velocity; Middle Aged; Adolescent; Young Adult; Child; Aortic Valve Disease
PubMed: 38653434
DOI: 10.1016/j.ijcard.2024.132084 -
Current Cardiology Reports Jun 2024Speckle-tracking echocardiography (STE) can assess myocardial motion in non-LV chambers-including assessment of left atrial (LA) and right ventricular (RV) strain. This... (Review)
Review
PURPOSE OF REVIEW
Speckle-tracking echocardiography (STE) can assess myocardial motion in non-LV chambers-including assessment of left atrial (LA) and right ventricular (RV) strain. This review seeks to highlight the diagnostic, prognostic, and clinical significance of these parameters in heart failure, atrial fibrillation (AF), diastolic dysfunction, pulmonary hypertension (PH), tricuspid regurgitation, and heart transplant recipients.
RECENT FINDINGS
Impaired LA strain reflects worse LV diastolic function in individuals with and without HF, and this is associated with decreased exercise capacity. Initiating treatments targeting these functional aspects may enhance exercise capacity and potentially prevent heart failure (HF). Impaired LA strain also identifies patients with a high risk of AF, and this recognition may lead to preventive strategies. Impaired RV strain has significant clinical and prognostic implications across various clinical scenarios, including HF, PH, tricuspid regurgitation, or in heart transplant recipients. STE should not be limited to the assessment of deformation of the LV myocardium. The use of LA and RV strain is supported by a substantial evidence base, and these parameters should be used more widely.
Topics: Humans; Echocardiography; Heart Atria; Atrial Fibrillation; Heart Transplantation; Hypertension, Pulmonary; Heart Failure; Tricuspid Valve Insufficiency; Prognosis; Heart Ventricles; Ventricular Dysfunction, Right; Ventricular Function, Right; Atrial Function, Left
PubMed: 38647564
DOI: 10.1007/s11886-024-02058-x -
Pediatric Blood & Cancer Jul 2024Tricuspid regurgitation velocity (TRV), measured by echocardiography, is a surrogate marker for pulmonary hypertension. Limited pediatric studies have considered the...
BACKGROUND
Tricuspid regurgitation velocity (TRV), measured by echocardiography, is a surrogate marker for pulmonary hypertension. Limited pediatric studies have considered the association between TRV and surrogate markers of end-organ disease.
METHODS
We conducted a cross-sectional study that evaluated the prevalence of elevated TRV ≥2.5 m/s and its associations with renal and cerebrovascular outcomes in children with sickle cell disease (SCD) 1-21 years of age in two large sickle cell cohorts, the University of Alabama at Birmingham (UAB) sickle cell cohort, and the Sickle Cell Clinical Research and Intervention Program (SCCRIP) cohort at St. Jude Children's Research Hospital. We hypothesized that patients with SCD and elevated TRV would have higher odds of having either persistent albuminuria or cerebrovascular disease.
RESULTS
We identified 166 children from the UAB cohort (mean age: 13.49 ± 4.47 years) and 325 children from the SCCRIP cohort (mean age: 13.41 ± 3.99 years) with echocardiograms. The prevalence of an elevated TRV was 21% in both UAB and SCCRIP cohorts. Elevated TRV was significantly associated with cerebrovascular disease (odds ratio [OR] 1.88, 95% confidence interval [CI]: 1.12-3.15; p = .017) and persistent albuminuria (OR 1.81, 95% CI: 1.07-3.06; p = .028) after adjusting for age, sex, treatment, and site.
CONCLUSION
This cross-sectional, multicenter study identifies associations between surrogate markers of pulmonary hypertension with kidney disease and cerebrovascular disease. A prospective study should be performed to evaluate the longitudinal outcomes for patients with multiple surrogate markers of end-organ disease.
Topics: Humans; Anemia, Sickle Cell; Male; Female; Child; Adolescent; Tricuspid Valve Insufficiency; Cross-Sectional Studies; Cerebrovascular Disorders; Child, Preschool; Young Adult; Infant; Kidney Diseases; Echocardiography; Adult; Follow-Up Studies; Prognosis
PubMed: 38644595
DOI: 10.1002/pbc.31002 -
European Journal of Heart Failure Apr 2024Mitral regurgitation (MR) is highly prevalent among patients with heart failure and preserved ejection fraction (HFpEF). Despite this combination being closely... (Review)
Review
Mitral regurgitation (MR) is highly prevalent among patients with heart failure and preserved ejection fraction (HFpEF). Despite this combination being closely associated with unfavourable outcomes, it remains relatively understudied. This is partly due to the inherent heterogeneity of patients with HFpEF. To address this gap, dissecting HFpEF into mechanism-based phenotypes may offer a promising avenue for advancing our comprehension of these complex intertwined conditions. This review employs the validated CircAdapt model to explore the haemodynamic implications of moderate to severe MR across a well-defined spectrum of myocardial disease, characterized by impaired relaxation and reduced myocardial compliance. Both heart failure and mitral valve disease share overlapping symptomatology, primarily attributed to elevated pulmonary pressures. The intricate mechanisms contributing to these elevated pressures are multifaceted, potentially influenced by diastolic dysfunction, left atrial myopathy, and MR. Accurate evaluation of the haemodynamic and clinical impact of MR necessitates a comprehensive approach, taking into account the characteristics of both the left atrium and left ventricle, as well as their intricate interactions, which may currently be underemphasized in diagnostic practice. This holistic assessment is imperative for enhancing our understanding and refining therapeutic strategies within this patient cohort.
Topics: Humans; Mitral Valve Insufficiency; Heart Failure; Stroke Volume; Heart Atria; Heart Ventricles; Mitral Valve; Hemodynamics
PubMed: 38629747
DOI: 10.1002/ejhf.3231 -
Journal of the American Heart... Apr 2024The interaction between right ventricular (RV) function and pulmonary hypertension is crucial for prognosis of patients with severe functional tricuspid regurgitation....
Prognostic Implication of Right Ventricular Free Wall Longitudinal Strain and Right Atrial Pressure Estimated By Echocardiography in Patients With Severe Functional Tricuspid Regurgitation.
BACKGROUND
The interaction between right ventricular (RV) function and pulmonary hypertension is crucial for prognosis of patients with severe functional tricuspid regurgitation. RV free wall longitudinal strain (RVFWLS) has been reported to detect RV systolic dysfunction earlier than other conventional parameters. Although pulmonary artery systolic pressure measured by Doppler echocardiography is often underestimated in severe functional tricuspid regurgitation, right atrial pressure (RAP) estimated by echocardiography may be viewed as a prognostic factor. Impact of RAP and RVFWLS on outcome in patients with severe functional tricuspid regurgitation remains unclear. The aim of the present study was to investigate prognostic implication of RAP, RVFWLS, and their combination in this population.
METHODS AND RESULTS
We retrospectively examined 377 patients with severe functional tricuspid regurgitation. RAP, pulmonary artery systolic pressure, RV fractional area change, and RVFWLS were analyzed. RAP of 15 mm Hg was classified as elevated RAP. All-cause death at 2-year follow-up was defined as the primary end point. RVFWLS provided better prognostic information than RV fractional area change by receiver operating characteristic curve analysis. In the multivariable Cox regression analysis, elevated RAP and RVFWLS of ≤18% were independent predictors of clinical outcome. Patients with RVFWLS of ≤18% had higher risk of all-cause death than those without by Kaplan-Meier curve analysis. Furthermore, when patients were stratified into 4 groups by RAP and RVFWLS, the group with elevated RAP and RVFWLS of ≤18% had the worst outcome.
CONCLUSIONS
Elevated RAP and RVFWLS of ≤18% were independent predictors of all-cause death. The combination of elevated RAP and RVFWLS effectively stratified the all-cause death.
Topics: Humans; Tricuspid Valve Insufficiency; Prognosis; Retrospective Studies; Atrial Pressure; Echocardiography; Ventricular Dysfunction, Right; Ventricular Function, Right
PubMed: 38609840
DOI: 10.1161/JAHA.123.033196 -
Alternative Therapies in Health and... Apr 2024This study evaluates the effects of valve surgery on safety and cardiac function in patients with valvular heart disease complicated by pulmonary arterial hypertension...
OBJECTIVE
This study evaluates the effects of valve surgery on safety and cardiac function in patients with valvular heart disease complicated by pulmonary arterial hypertension (PAH), focusing on postoperative outcomes influenced by age, heart function grade, and PAH severity.
METHODS
A retrospective analysis was conducted on 307 valve surgery patients from April 2017 to April 2022. The cohort had a mean age of 57.6 years, with 56.9% males, and was stratified by NYHA functional class II-IV. Outcomes assessed included mortality, complication rates, left ventricular ejection fraction (LVEF), and pulmonary artery systolic pressure (PASP), with statistical analysis performed using t-tests and chi-square tests for continuous and categorical data, respectively.
RESULTS
Postoperative outcomes varied significantly with age, NYHA class, and PASP grade. Patients aged ≤60 exhibited an average PASP reduction of 44.46% in the male group and 44.44% in the female group and an LVEF improvement of 5.28% in the male group and 5.80% in the female group. However, these patients showed a higher risk of postoperative complications, such as renal failure, arrhythmia, low cardiac output syndrome, respiratory insufficiency, (23.31%), and a higher mortality rate (13.53%)(P < .05). Higher NYHA classes correlated with increased postoperative risks of complications and mortality rates, and elevated PASP grades were associated with larger improvements in PASP and LVEF but also higher postoperative risks.
CONCLUSION
Valve surgery in valvular heart disease with PAH is influenced by patient age, functional status, and PAH severity. Despite advances in surgical techniques, there remains a notable gap in understanding the nuanced interplay between these conditions and the variable outcomes of valve surgery. This study addresses this research gap, offering comprehensive insights into how age, heart function, and PAH severity influence postoperative outcomes. These findings are crucial for clinicians, providing a more informed basis for tailored treatment strategies, and ultimately enhancing patient care in this complex clinical scenario.Healthcare providers should consider the age-specific benefits and risks of valve surgery in patients with valvular heart disease and pulmonary arterial hypertension. Tailored decision-making, particularly for those aged ≤60, higher NYHA classes, or severe PAH, is essential for optimizing individual outcomes.
PubMed: 38607223
DOI: No ID Found -
Circulation. Cardiovascular... May 2024Anatomic selection for Harmony valve implant is determined with the aid of a screening report and perimeter plot (PP) that depicts the perimeter-derived radius along the...
BACKGROUND
Anatomic selection for Harmony valve implant is determined with the aid of a screening report and perimeter plot (PP) that depicts the perimeter-derived radius along the right ventricular outflow tract (RVOT) and projects device oversizing. The PP provides an estimation of suitability for implant, but its sensitivity as a screening method is unknown. This study was performed to describe anatomic features and outcomes in patients who underwent Harmony TPV25 implant despite a PP that predicted inadequate oversizing.
METHODS
We reviewed RVOT anatomic features and measurements in patients who underwent transcatheter pulmonary valve replacement with the Harmony TPV25 device despite a PP that predicted inadequate oversizing.
RESULTS
This study included 22 patients. There were no unsuccessful implants or adverse valve-related events. Anatomic features varied, but all patients fit into 1 of 3 anatomic types characterized by differences in RVOT dimensions. Type 1 patients (n=9) had a long RVOT with a choke point and a wide main pulmonary artery. Type 2 patients (n=6) had a short RVOT that was pyramidal in shape, with no choke point, and extensive main pulmonary artery lengthening/expansion during systole. Type 3 patients (n=7) had a short, bulbous main pulmonary artery with a choke point and an open pulmonary artery bifurcation.
CONCLUSIONS
Transcatheter pulmonary valve replacement with the Harmony valve is feasible in some patients whose PP fit analysis predicts inadequate oversizing. All cases in this series fit into 1 of 3 anatomic patterns, which are not identified in the screening report. Implanters must review cases individually to assess the feasibility of the implant.
Topics: Humans; Pulmonary Valve; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Cardiac Catheterization; Prosthesis Design; Treatment Outcome; Male; Female; Adolescent; Young Adult; Child; Adult; Retrospective Studies; Predictive Value of Tests; Pulmonary Valve Insufficiency; Patient Selection; Clinical Decision-Making; Recovery of Function; Hemodynamics
PubMed: 38606564
DOI: 10.1161/CIRCINTERVENTIONS.123.013889