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European Journal of Pharmacology Jun 2024Pulmonary hypertension (PH) is a malignant pulmonary vascular disease with a poor prognosis. Although the development of targeted drugs for this disease has made some...
Pulmonary hypertension (PH) is a malignant pulmonary vascular disease with a poor prognosis. Although the development of targeted drugs for this disease has made some breakthroughs in recent decades, PH remains incurable. Therefore, innovative clinical treatment methods and drugs for PH are still urgently needed. DYZY01 is a new drug whose main ingredient is high-purity cannabidiol, a non-psychoactive constituent of cannabinoids that was demonstrated to have anti-inflammatory and anti-pyroptosis properties. Several recent studies have found cannabidiol could improve experimental PH, whereas the mechanistic effect of it warrants further investigation. Thus, this study aimed to investigate whether DYZY01 can treat PH by inhibiting inflammation and pyroptosis and to reveal its underlying mechanism. We established hypoxia and monocrotaline (MCT)-induced PH rat models in vivo and treated them with either DYZY01 (10,50 mg/kg/d) or Riociguat (10 mg/kg/d) by oral administration. The mean pulmonary arterial pressure (mPAP), right ventricular hypertrophy index (RVHI), and extent of vascular remodeling were measured. Meanwhile, the effect of DYZY01 on human pulmonary arterial endothelial cells (HPAECs) was assessed in vitro. The results indicated that DYZY01 significantly reduced mPAP and RVHI in PH rats and reversed the extent of pulmonary vascular remodeling. This improvement may have been achieved by reducing endothelial cell pyroptosis via inhibiting the NF-κB/NLRP3/Caspase-1 pathway. Furthermore, DYZY01 could improve endothelial vascular function, possibly by regulating the secretion of vasodilator factors and inhibiting the proliferation and migration of pulmonary endothelial cells.
PubMed: 38942262
DOI: 10.1016/j.ejphar.2024.176785 -
Journal of the American Society of... Jun 2024Cardiac amyloidosis is a diffuse disease affecting all cardiac chambers. The value of right ventricular free-wall (RVfw) strain is uncertain as an echocardiographic red...
AIMS
Cardiac amyloidosis is a diffuse disease affecting all cardiac chambers. The value of right ventricular free-wall (RVfw) strain is uncertain as an echocardiographic red flag. We hypothesized that RVfw strain is of added value for diagnostic and prognostic purposes in patients with transthyretin cardiac amyloidosis (ATTR-CA).
METHOD
ATTR-CA diagnosis required positive Tc-99m pyrophosphate (PYP) scintigraphy and negative serum clonal dyscrasia. Patients with left ventricular hypertrophy (LVH) (interventricular septal thickness ≥1.2cm) by echocardiography and negative PYP scintigraphy served as controls after exclusion of AL-CA. Longitudinal strain was computed with speckle tracking echocardiography.
RESULTS
We studied, 108 subjects with ATTR-CA and 106 controls with LVH, retrospectively. RVfw strain was independently associated with the diagnosis of ATTR-CA after adjusting for classical echocardiographic parameters, namely, relative apical sparing (RAS), e' and E/e'. RVfw strain ≥-16% was incremental to LV RAS in the overall group and in the subgroup without extreme wall thickness (≤1.4 cm) (Harrell's-C, net reclassification improvement (NRI) = 0.213, p<0.001and NRI 0.463, p=0.015, respectively). Major adverse cardiovascular and cerebrovascular events (MACCE: heart failure hospitalization, stroke, death) occurred in 47 ATTR-CA patients, during follow-up (median: 38, range: 6-60 months). RVfw strain ≥-16% was associated with 3-fold increased risk of MACCE in ATTR-CA patients independently of age, comorbidities, BNP and tafamidis treatment. RVfw strain was additive to LVEF for risk stratification (X 10.2, p =0.017).
CONCLUSION
RVfw strain >-16% has incremental value to LV RAS for the differential diagnosis of ATTR-CA among LVH phenotypes, and is associated with poor prognosis.
PubMed: 38942217
DOI: 10.1016/j.echo.2024.06.006 -
Journal of Clinical Hypertension... Jun 2024Salt-sensitive hypertension is common among individuals with essential hypertension, and the prevalence of left ventricular hypertrophy (LVH) has increased. However,...
Salt-sensitive hypertension is common among individuals with essential hypertension, and the prevalence of left ventricular hypertrophy (LVH) has increased. However, data from early identification of the risk of developing LVH in young adults with salt-sensitive hypertension are lacking. Thus, the present study aimed to design a nomogram for predicting the risk of developing LVH in young adults with salt-sensitive hypertension. A retrospective analysis of 580 patients with salt-sensitive hypertension was conducted. The training set consisted of 70% (n = 406) of the patients, while the validation set consisted of the remaining 30% (n = 174). Based on multivariate analysis of the training set, predictors for LVH were extracted to develop a nomogram. Discrimination curves, calibration curves, and clinical utility were employed to assess the predictive performance of the nomogram. The final simplified nomogram model included age, sex, office systolic blood pressure, duration of hypertension, abdominal obesity, triglyceride-glucose index, and estimated glomerular filtration rate (eGFR). In the training set, the model demonstrated moderate discrimination, as indicated by an area under the receiver operating characteristic (ROC) curve of 0.863 (95% confidence interval: 0.831-0.894). The calibration curve exhibited good agreement between the predicted and actual probabilities of LVH in the training set. Additionally, the validation set further confirmed the reliability of the prediction nomogram. In conclusions, the simplified nomogram, which consists of seven routine clinical variables, has shown good performance and clinical utility in identifying young adults with salt-sensitive hypertension who are at high risk of LVH at an early stage.
PubMed: 38940286
DOI: 10.1111/jch.14863 -
JACC. Advances Jan 2024In patients with chronic kidney disease (CKD), fibroblast growth factor (FGF)-23 is suspected to cause death or cardiovascular disease by inducing left ventricular...
BACKGROUND
In patients with chronic kidney disease (CKD), fibroblast growth factor (FGF)-23 is suspected to cause death or cardiovascular disease by inducing left ventricular hypertrophy (LVH).
OBJECTIVES
This study aims to quantify the mediational effect of LVH in the hypothetical causal pathway from FGF-23 to long-term adverse outcomes.
METHODS
From 3,939 adults with CKD stages 2 to 4 enrolled in the CRIC (Chronic Renal Insufficiency Cohort) study, 2,368 participants with available data of FGF-23, left ventricular mass index at 1 year, and covariates were included. We employed linear and Cox proportional hazards regression models to investigate the association between FGF-23 and LVH, all-cause mortality, atrial fibrillation (AF), or congestive heart failure (CHF). Mediation analysis was used within a counterfactual framework to decompose the effect of FGF-23 into natural direct and indirect effects.
RESULTS
Among 2,368 participants (mean age: 57.7 years, 1,252 males, median FGF-23 level: 138.8 RU/mL), left ventricular mass index was positively correlated with FGF-23. During a median of 12.0, 11.1, and 11.1 years, FGF-23 was associated with all-cause mortality (HR: 1.62, 95% CI: 1.24-2.12), AF (HR: 1.58, 95% CI: 1.12-2.24), and CHF (HR: 1.32, 95% CI: 0.95-1.84) when the highest quartile was compared to the lowest quartile. LVH mediated 7.4%, 11.2%, and 21.9% of the effect of FGF-23 on all-cause mortality, AF, and CHF, respectively.
CONCLUSIONS
In CKD patients, FGF-23 had a minor effect on the development of long-term adverse outcomes through LVH. Other potential mediators and the validity of negative effect of FGF-23 should be explored.
PubMed: 38939808
DOI: 10.1016/j.jacadv.2023.100747 -
JACC. Advances May 2024Persistent left ventricular hypertrophy after transcatheter aortic valve replacement (TAVR) has been associated with poor outcomes. Angiotensin-converting enzyme...
BACKGROUND
Persistent left ventricular hypertrophy after transcatheter aortic valve replacement (TAVR) has been associated with poor outcomes. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), due to their favorable effects on ventricular remodeling, have been hypothesized to improve outcomes post-TAVR, yet there are no recommendations regarding their use.
OBJECTIVES
This study aimed to compare the outcomes of patients receiving ACEIs/ARBs with those not receiving ACEIs/ARBs after TAVR.
METHODS
We performed a literature search on PubMed and Cochrane Library until June 14, 2023, and included all studies comparing clinical outcomes between patients given ACEIs/ARBs and those not given ACEIs/ARBs after TAVR. All-cause mortality was the primary outcome. We used a random effects model with appropriate corrections to calculate relative risk (RR) and CIs, with all analyses carried out using R v4.0.3.
RESULTS
We included ten studies on the use of ACEIs/ARBs post-TAVR. Patients on ACEIs/ARBs had lower risk of all-cause mortality (RR: 0.74, 95% CI: 0.65-0.86, I = 62%, chi-square < 0.01), cardiovascular mortality (RR: 0.70, 95% CI: 0.56-0.88, I = 0%, chi-square = 0.54), and new-onset atrial fibrillation (RR: 0.71, 95% CI: 0.52-0.96, I = 0%, chi-square = 0.59). Patients on ACEIs/ARBs had a similar risk of myocardial infarction, heart failure, stroke, new permanent pacemaker implantation, acute kidney injury, major bleeding, vascular complications, aortic regurgitation, and mitral regurgitation.
CONCLUSIONS
We found that patients receiving ACEIs/ARBs had a lower risk of all-cause mortality, cardiovascular mortality, and new-onset atrial fibrillation. Risk of other outcomes was similar to patients not receiving ACEIs/ARBs. Randomized clinical trials are needed to explore the benefits of ACEIs/ARBs post-TAVR, so that definitive guidelines can be developed.
PubMed: 38939627
DOI: 10.1016/j.jacadv.2024.100927 -
Frontiers in Public Health 2024Cardiovascular disease remains the leading cause of mortality on a global scale. Individuals who possess risk factors for cardiovascular disease, such as high blood... (Review)
Review
Cardiovascular disease remains the leading cause of mortality on a global scale. Individuals who possess risk factors for cardiovascular disease, such as high blood pressure (BP) and obesity, face an elevated risk of experiencing organ-specific pathophysiological changes. This damage includes pathophysiological changes in the heart and peripheral vascular systems, such as ventricular hypertrophy, arterial stiffening, and vascular narrowing and stenosis. Consequently, these damages are associated with an increased risk of developing severe cardiovascular outcomes including stroke, myocardial infarction, heart failure, and coronary heart disease. Among all the risk factors associated with cardiovascular disease, high blood pressure emerges as the most prominent. However, conventional resting BP measurement methods such as auscultatory or oscillometric methods may fail to identify many individuals with asymptomatic high BP. Recently, exercise BP has emerged as a valuable diagnostic tool for identifying real (high) blood pressure levels and assessing underlying cardiovascular risk, in addition to resting BP measurements in adults. Furthermore, numerous established factors, such as low cardiorespiratory fitness and high body fatness, have been confirmed to contribute to exercise BP and the associated cardiovascular risk. Modifying these factors may help reduce high exercise BP and, consequently, alleviate the burden of cardiovascular disease. A significant body of evidence has demonstrated cardiovascular disease in later life have their origins in early life. Children and adolescents with these cardiovascular risk factors also possess a greater propensity to develop cardiovascular diseases later in life. Nevertheless, the majority of previous studies on the clinical utility of exercise BP have been conducted in middle-to-older aged populations, often with pre-existing clinical conditions. Therefore, there is a need to investigate further of the factors influencing exercise BP in adolescence and its association with cardiovascular risk in early life. Our previously published work showed that exercise BP is a potential useful method to detect adolescents with increased cardiovascular risk. Children and adolescents with cardiovascular risk factors are more likely to develop cardiovascular diseases later in life. However, previous studies on the clinical utility of exercise BP have largely focused on middle-to-older aged populations with pre-existing clinical conditions. Therefore, there is a need to investigate further the factors influencing exercise BP in adolescence and its association with future cardiovascular risk. Our previous studies, which focused on exercise BP measured at submaximal intensity, have shown that exercise BP is a potentially useful method for identifying adolescents at increased cardiovascular risk. Our previous findings suggest that improving cardio-respiratory fitness and reducing body fatness may help to reduce the risk of developing cardiovascular disease and improve overall cardiovascular health. These findings have important implications for the development of effective prevention and early detection strategies, which can contribute to improved public health outcomes.
Topics: Humans; Child; Adolescent; Cardiorespiratory Fitness; Cardiovascular Diseases; Blood Pressure; Exercise; Risk Factors; Male; Heart Disease Risk Factors; Female
PubMed: 38939566
DOI: 10.3389/fpubh.2024.1298612 -
JACC. Advances Jul 2023
PubMed: 38939013
DOI: 10.1016/j.jacadv.2023.100434 -
JACC. Advances Jul 2023Obesity cardiomyopathy (OCM) can be associated with sudden cardiac death (SCD) but its pathologic features are not well described.
BACKGROUND
Obesity cardiomyopathy (OCM) can be associated with sudden cardiac death (SCD) but its pathologic features are not well described.
OBJECTIVES
The objective of this study was to characterize the clinical and pathological features of OCM associated with SCD.
METHODS
This was a retrospective case control autopsy study. OCM was identified by an increased heart weight (>550 g in males; >450 g in females) in individuals with obesity (body mass index [BMI] ≥30 kg/m) in the absence of other causes. Cases of OCM with SCD were compared to sex and age matched SCD controls with obesity or with normal weight (BMI 18.5-24.9 kg/m) and morphologically normal hearts. Autopsy measures included: heart weight, atrial dimensions, ventricular wall thickness, and epicardial adipose tissue. Fibrosis was assessed microscopically.
RESULTS
Of 6,457 SCD cases, 53 cases of OCM were identified and matched to 106 controls with obesity and 106 normal weight controls. The OCM mean age at death of individuals with OCM was 42 ± 12 with a male predominance (n = 34, 64%). Males died younger than females (40 ± 13 vs 45 ± 10, = 0.036). BMI was increased in OCM cases compared to controls with obesity (42 ± 8 vs 35 ± 5). The average heart weight was 598 ± 93 g in OCM. There were increases in right and left ventricular wall thickness (all < 0.05) in OCM cases compared to controls. Right ventricular epicardial fat was increased in OCM compared to normal weight controls only. Left ventricular fibrosis was identified in 7 (13%) cases.
CONCLUSIONS
OCM may be a specific pathological entity associated with SCD. It is most commonly seen in young males with increased BMI.
PubMed: 38938994
DOI: 10.1016/j.jacadv.2023.100414 -
Annals of Noninvasive Electrocardiology... Jul 2024A 23-year-old male with a history of ventricular pre-excitation and atrial flutter presented for evaluation after recurrent syncope. The possible mechanism of syncope...
A 23-year-old male with a history of ventricular pre-excitation and atrial flutter presented for evaluation after recurrent syncope. The possible mechanism of syncope erroneously attributed to pre-excited atrial flutter with fast heart rates in the first hospitalization. The patient was found to have advanced heart block and PRKAG2 genetic mutation in the second hospitalization. The genetic findings and clinical features are consistent with PRKAG2 syndrome (PS). PS is a rare, autosomal dominant inherited disease, characterized by ventricular pre-excitation, supraventricular tachycardia, and cardiac hypertrophy. It is frequently followed by atrial-fibrillation-induced ventricular fibrillation and advanced heart blocks. An accurate differential diagnosis of syncope is important because of the different arrhythmic features and clinical course of PS.
Topics: Humans; Male; Young Adult; Electrocardiography; Accessory Atrioventricular Bundle; Diagnosis, Differential; Syncope; AMP-Activated Protein Kinases; Syndrome
PubMed: 38937983
DOI: 10.1111/anec.13134 -
The Journal of Thoracic and... Jun 2024Left ventricular septal myotomy provides a favorable prognosis for children with hypertrophic obstructive cardiomyopathy (HOCM). However, some children still suffer from...
OBJECTIVE
Left ventricular septal myotomy provides a favorable prognosis for children with hypertrophic obstructive cardiomyopathy (HOCM). However, some children still suffer from recurrent left ventricular outflow tract obstruction (LVOTO) after surgery. Poor prognosis exists for HOCM caused by PTPN11 mutation. Therefore, the aim of this study was to determine the clinical features of recurrent obstruction in children with HOCM caused by pathogenic mutations in the PTPN11 gene.
METHODS
A total of 56 children were diagnosed with HOCM underwent septal myectomies. Whole exome sequencing of 49 pediatric cardiomyopathies associated genes (including PTPN11) were performed. We performed hematoxylin-eosin(H&E), Masson, and wheat germ agglutinin (WGA)staining of tissues positive for PTPN11 and those negative for PTPN11 were conducted.
RESULTS
Whole exome sequencing results showed 11 PTPN11 mutation (19.6%) children. In long-term follow-up (median 37 months, maximum 9 years), children with PTPN11 mutation had 6(54.5%) recurrent LVOTO compared with other groups (P=.015), but similar survival rates(P=.514). The mean postoperative time to recurrent obstruction was 22±27 months. Children with PTPN11 mutation were 9-fold more likely to experience the risk associated with recurrent obstruction (95% CI = 1.77-45.81, P<.001). H&E, Masson and WGA staining also revealed more cardiomyocyte hypertrophy in PTPN11 mutation tissues. See Figure 4 for a graphical abstract of the study.
CONCLUSION
Children with PTPN11 mutation-associated hypertrophic cardiomyopathy have a higher risk of recurrent LVOTO.
PubMed: 38936599
DOI: 10.1016/j.jtcvs.2024.06.012