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Journal of Clinical Medicine May 2024Although takotsubo syndrome (TTS) is characterized by transient systolic dysfunction of the left ventricle (LV), the time course and mechanism of LV function recovery...
Although takotsubo syndrome (TTS) is characterized by transient systolic dysfunction of the left ventricle (LV), the time course and mechanism of LV function recovery remain elusive. The aim of this study is to evaluate cardiac functional recovery in TTS via serial cardiac magnetic resonance feature tracking (CMR-FT). In this Japanese multicenter registry, patients with newly diagnosed TTS were prospectively enrolled. In patients who underwent serial cardiovascular magnetic resonance (CMR) imaging at 1 month and 1 year after the onset, CMR-FT was performed to determine the global circumferential strain (GCS), global radial strain (GRS) and global longitudinal strain (GLS). We compared LV ejection fraction, GCS, GRS and GLS at 1 month and 1 year after the onset of TTS. Eighteen patients underwent CMR imaging in one month and one year after the onset in the present study. LV ejection fraction had already normalized at 1 month after the onset, with no significant difference between 1 month and 1 year (55.8 ± 9.2% vs. 58.9 ± 7.3%, = 0.09). CMR-FT demonstrated significant improvement in GCS from 1 month to 1 year (-16.7 ± 3.4% vs. -18.5 ± 3.2%, < 0.01), while there was no significant difference in GRS and GLS between 1 month and year (GRS: 59.6 ± 24.2% vs. 59.4 ± 17.3%, = 0.95, GLS: -12.8 ± 5.9% vs. -13.8 ± 4.9%, = 0.42). Serial CMR-FT analysis revealed delayed improvement of GCS compared to GRS and GLS despite of rapid recovery of LV ejection fraction. CMR-FT can detect subtle impairment of LV systolic function during the recovery process in patients with TTS.
PubMed: 38892953
DOI: 10.3390/jcm13113238 -
Journal of Clinical Medicine May 2024Cardiac sarcoidosis (CS) is characterized by various arrhythmic manifestations ranging from catastrophic sudden cardiac death secondary to ventricular arrhythmia, severe... (Review)
Review
Cardiac sarcoidosis (CS) is characterized by various arrhythmic manifestations ranging from catastrophic sudden cardiac death secondary to ventricular arrhythmia, severe conduction disease, sinus node dysfunction, and atrial fibrillation. The management of CS is complex and includes not only addressing the arrhythmia but also controlling the myocardial inflammation resultant from the autoimmune reaction. Arrhythmic manifestations of CS carry significant prognostic implications and invariably affect long-term survival in these patients. In this review, we focus on management of arrhythmic manifestation of cardiac sarcoidosis as well as risk stratification for sudden cardiac death in these patients.
PubMed: 38892878
DOI: 10.3390/jcm13113165 -
Journal of Clinical Medicine May 2024Congenitally corrected transposition of the great arteries (cc-TGA) is a defect characterized by arterio-ventricular and atrioventricular disconcordance. Most patients...
Congenitally corrected transposition of the great arteries (cc-TGA) is a defect characterized by arterio-ventricular and atrioventricular disconcordance. Most patients have co-existing cardiac abnormalities that warrant further treatment. Some patients do not require surgical intervention, but most undergo physiological repair or anatomical surgery, which enables them to reach adulthood. We aimed to evaluate mortality risk factors in patients with cc-TGA. We searched the PubMed database and included 10 retrospective cohort studies with at least a 5-year follow-up time with an end-point of cardiovascular death a minimum of 30 days after surgery. We enrolled 532 patients, and 83 met the end-point of cardiovascular death or equivalent event. As a risk factor for long-term mortality, we identified New York Heart Association (NYHA) class ≥III/heart failure hospitalization (OR = 10.53; 95% CI, 3.17-34.98) and systemic ventricle dysfunction (SVD; OR = 4.95; 95% CI, 2.55-9.64). We did not show history of supraventricular arrhythmia (OR = 2.78; 95% CI, 0.94-8.24), systemic valve regurgitation ≥moderate (SVR; OR = 4.02; 95% Cl, 0.84-19.18), and pacemaker implantation (OR = 1.48; 95% Cl, 0.12-18.82) to affect the long-term survival. In operated patients only, SVD (OR = 4.69; 95% CI, 2.06-10.71) and SVR (OR = 3.85; 95% CI, 1.5-9.85) showed a statistically significant impact on survival. The risk factors for long-term mortality for the entire cc-TGA population are NYHA class ≥III/heart failure hospitalization and systemic ventricle dysfunction. In operated patients, systemic ventricle dysfunction and at least moderate systemic valve regurgitation were found to affect survival.
PubMed: 38892838
DOI: 10.3390/jcm13113127 -
International Journal of Molecular... Jun 2024Modified mRNAs (modRNAs) are an emerging delivery method for gene therapy. The success of modRNA-based COVID-19 vaccines has demonstrated that modRNA is a safe and...
Modified mRNAs (modRNAs) are an emerging delivery method for gene therapy. The success of modRNA-based COVID-19 vaccines has demonstrated that modRNA is a safe and effective therapeutic tool. Moreover, modRNA has the potential to treat various human diseases, including cardiac dysfunction. Acute myocardial infarction (MI) is a major cardiac disorder that currently lacks curative treatment options, and MI is commonly accompanied by fibrosis and impaired cardiac function. Our group previously demonstrated that the matricellular protein CCN5 inhibits cardiac fibrosis (CF) and mitigates cardiac dysfunction. However, it remains unclear whether early intervention of CF under stress conditions is beneficial or more detrimental due to potential adverse effects such as left ventricular (LV) rupture. We hypothesized that CCN5 would alleviate the adverse effects of myocardial infarction (MI) through its anti-fibrotic properties under stress conditions. To induce the rapid expression of CCN5, ModRNA- was synthesized and administrated directly into the myocardium in a mouse MI model. To evaluate CCN5 activity, we established two independent experimental schemes: (1) preventive intervention and (2) therapeutic intervention. Functional analyses, including echocardiography and magnetic resonance imaging (MRI), along with molecular assays, demonstrated that modRNA-mediated gene transfer significantly attenuated cardiac fibrosis and improved cardiac function in both preventive and therapeutic models, without causing left ventricular rupture or any adverse cardiac remodeling. In conclusion, early intervention in CF by ModRNA- gene transfer is an efficient and safe therapeutic modality for treating MI-induced heart failure.
Topics: Animals; Humans; Male; Mice; CCN Intercellular Signaling Proteins; Disease Models, Animal; Fibrosis; Gene Transfer Techniques; Genetic Therapy; Mice, Inbred C57BL; Myocardial Infarction; Myocardium; RNA, Messenger; Ventricular Remodeling
PubMed: 38892449
DOI: 10.3390/ijms25116262 -
International Journal of Molecular... Jun 2024Increased mitochondrial reactive oxygen species (ROS) formation is important for the development of right ventricular (RV) hypertrophy (RVH) and failure (RVF) during...
Does Cell-Type-Specific Silencing of Monoamine Oxidase B Interfere with the Development of Right Ventricle (RV) Hypertrophy or Right Ventricle Failure in Pulmonary Hypertension?
Increased mitochondrial reactive oxygen species (ROS) formation is important for the development of right ventricular (RV) hypertrophy (RVH) and failure (RVF) during pulmonary hypertension (PH). ROS molecules are produced in different compartments within the cell, with mitochondria known to produce the strongest ROS signal. Among ROS-forming mitochondrial proteins, outer-mitochondrial-membrane-located monoamine oxidases (MAOs, type A or B) are capable of degrading neurotransmitters, thereby producing large amounts of ROS. In mice, MAO-B is the dominant isoform, which is present in almost all cell types within the heart. We analyzed the effect of an inducible cardiomyocyte-specific knockout of MAO-B (cmMAO-B KO) for the development of RVH and RVF in mice. Right ventricular hypertrophy was induced by pulmonary artery banding (PAB). RV dimensions and function were measured through echocardiography. ROS production (dihydroethidium staining), protein kinase activity (PamStation device), and systemic hemodynamics (in vivo catheterization) were assessed. A significant decrease in ROS formation was measured in cmMAO-B KO mice during PAB compared to Cre-negative littermates, which was associated with reduced activity of protein kinases involved in hypertrophic growth. In contrast to littermates in which the RV was dilated and hypertrophied following PAB, RV dimensions were unaffected in response to PAB in cmMAO-B KO mice, and no decline in RV systolic function otherwise seen in littermates during PAB was measured in cmMAO-B KO mice. In conclusion, cmMAO-B KO mice are protected against RV dilatation, hypertrophy, and dysfunction following RV pressure overload compared to littermates. These results support the hypothesis that cmMAO-B is a key player in causing RV hypertrophy and failure during PH.
Topics: Animals; Hypertrophy, Right Ventricular; Monoamine Oxidase; Hypertension, Pulmonary; Mice; Mice, Knockout; Reactive Oxygen Species; Myocytes, Cardiac; Heart Failure; Male; Disease Models, Animal; Heart Ventricles; Ventricular Dysfunction, Right
PubMed: 38892401
DOI: 10.3390/ijms25116212 -
International Journal of Molecular... May 2024The association between vitamin D deficiency and cardiovascular disease remains a controversial issue. This study aimed to further elucidate the role of vitamin D...
Ablation of Vitamin D Signaling in Cardiomyocytes Leads to Functional Impairment and Stimulation of Pro-Inflammatory and Pro-Fibrotic Gene Regulatory Networks in a Left Ventricular Hypertrophy Model in Mice.
The association between vitamin D deficiency and cardiovascular disease remains a controversial issue. This study aimed to further elucidate the role of vitamin D signaling in the development of left ventricular (LV) hypertrophy and dysfunction. To ablate the vitamin D receptor (VDR) specifically in cardiomyocytes, VDR mice were crossed with Mlcv2-Cre mice. To induce LV hypertrophy experimentally by increasing cardiac afterload, transverse aortic constriction (TAC) was employed. Sham or TAC surgery was performed in 4-month-old, male, wild-type, VDR, Mlcv2-Cre, and cardiomyocyte-specific VDR knockout (VDR) mice. As expected, TAC induced profound LV hypertrophy and dysfunction, evidenced by echocardiography, aortic and cardiac catheterization, cardiac histology, and LV expression profiling 4 weeks post-surgery. Sham-operated mice showed no differences between genotypes. However, TAC VDR mice, while having comparable cardiomyocyte size and LV fibrosis to TAC VDR controls, exhibited reduced fractional shortening and ejection fraction as measured by echocardiography. Spatial transcriptomics of heart cryosections revealed more pronounced pro-inflammatory and pro-fibrotic gene regulatory networks in the stressed cardiac tissue niches of TAC VDR compared to VDR mice. Hence, our study supports the notion that vitamin D signaling in cardiomyocytes plays a protective role in the stressed heart.
Topics: Animals; Myocytes, Cardiac; Mice; Hypertrophy, Left Ventricular; Receptors, Calcitriol; Vitamin D; Gene Regulatory Networks; Fibrosis; Signal Transduction; Male; Disease Models, Animal; Mice, Knockout; Inflammation
PubMed: 38892126
DOI: 10.3390/ijms25115929 -
Cells May 2024During mammalian heart development, the clustered genes encoding peptide hormones, Natriuretic Peptide A (; ANP) and B (; BNP), are transcriptionally co-regulated and... (Review)
Review
During mammalian heart development, the clustered genes encoding peptide hormones, Natriuretic Peptide A (; ANP) and B (; BNP), are transcriptionally co-regulated and co-expressed predominately in the atrial and ventricular trabecular cardiomyocytes. After birth, expression of and a natural antisense transcript becomes restricted to the atrial cardiomyocytes. Both and are induced by cardiac stress and serve as markers for cardiovascular dysfunction or injury. gene products are extensively used as diagnostic and prognostic biomarkers for various cardiovascular disorders. Membrane-localized guanylyl cyclase receptors on many cell types throughout the body mediate the signaling of the natriuretic peptide ligands through the generation of intracellular cGMP, which interacts with and modulates the activity of cGMP-activated kinase and other enzymes and ion channels. The natriuretic peptide system plays a fundamental role in cardio-renal homeostasis, and its potent diuretic and vasodilatory effects provide compensatory mechanisms in cardiac pathophysiological conditions and heart failure. In addition, both peptides, but also CNP, have important intracardiac actions during heart development and homeostasis independent of the systemic functions. Exploration of the intracardiac functions may provide new leads for the therapeutic utility of natriuretic peptide-mediated signaling in heart diseases and rhythm disorders. Here, we review recent insights into the regulation of expression and intracardiac functions of and during heart development, homeostasis, and disease.
Topics: Humans; Homeostasis; Animals; Natriuretic Peptides; Heart; Heart Diseases
PubMed: 38891063
DOI: 10.3390/cells13110931 -
European Heart Journal. Case Reports Apr 2024Desmoplakin cardiomyopathy has been recently classified as a non-dilated left ventricular cardiomyopathy, which is characterized by inflammatory-like episodes followed...
BACKGROUND
Desmoplakin cardiomyopathy has been recently classified as a non-dilated left ventricular cardiomyopathy, which is characterized by inflammatory-like episodes followed by left ventricular fibrosis/dysfunction and ventricular arrhythmias. Specific management is unclear.
CASE SUMMARY
We report a detailed case of a 46-year-old Caucasian woman presenting with repeated sudden cardiac arrests who was diagnosed with a new variant in the desmoplakin gene. Because the initial 18F-fluorodeoxyglucose positron emission tomography scan showed significant hypermetabolism, she was treated with immunosuppressors, with only minimal improvement on imaging.
DISCUSSION
Desmoplakin cardiomyopathy should be considered in the differential diagnosis of inflammatory cardiomyopathies. Little is known about the use of immunosuppressive treatments, but it could be reasonable for some selected patients.
PubMed: 38887779
DOI: 10.1093/ehjcr/ytae160 -
ERJ Open Research May 2024Worldwide, 1-2% of children are born premature and at risk for developing bronchopulmonary dysplasia (BPD). Preterm-born adults are at risk for early cardiovascular...
BACKGROUND
Worldwide, 1-2% of children are born premature and at risk for developing bronchopulmonary dysplasia (BPD). Preterm-born adults are at risk for early cardiovascular disease. The role of BPD is unclear. This study aims to examine cardiorespiratory function during submaximal exercise in young adult survivors of extreme prematurity, with or without BPD.
METHODS
40 preterm-born young adults, 20 with BPD (median gestational age 27 weeks, interquartile range (IQR) 26-28 weeks) and 20 without BPD (median gestational age 28 weeks, IQR 27-29 weeks) were prospectively compared to age-matched at term-born adults (median gestational age 39 weeks, IQR 38-40 weeks). Participants underwent exercise testing and cardiovascular magnetic resonance with submaximal exercise.
RESULTS
Resting heart rate in BPD subjects was higher than in at term-born subjects (69±10 mL 61±7 mL, p=0.01). Peak oxygen uptake during maximal cardiopulmonary exercise testing was decreased in BPD subjects (91±18% 106±17% of predicted, p=0.01). In BPD subjects, cardiac stroke volume change with exercise was impaired compared to at term-born subjects (11±13% 25±10%; p<0.001). With exercise, left ventricular end-diastolic volume decreased more in preterm-born subjects with without BPD (-10±8% -3±8%; p=0.01) and compared to at term-born subjects (0±5%; p<0.001). Exploratory data analysis revealed that exercise stroke volume and end-diastolic volume change were inversely correlated with oxygen dependency in those born prematurely.
CONCLUSIONS
In preterm-born young adults, particularly those with BPD, resting cardiac function, exercise performance and cardiac response to exercise is impaired compared to controls. Exercise cardiovascular magnetic resonance may reveal an important predisposition for heart disease later in life.
PubMed: 38887679
DOI: 10.1183/23120541.00501-2023 -
Journal of Korean Medical Science Jun 2024Heart failure with preserved ejection fraction (HFpEF) is prevalent and associated with a poor prognosis, imposing a significant burden on society. Arterial stiffness is... (Review)
Review
Heart failure with preserved ejection fraction (HFpEF) is prevalent and associated with a poor prognosis, imposing a significant burden on society. Arterial stiffness is increasingly recognized as a crucial factor in the pathophysiology of HFpEF, affecting diagnosis, management, and prognosis. As a hallmark of vascular aging, arterial stiffness contributes to increased afterload on the left ventricle (LV), leading to diastolic dysfunction, a key feature of HFpEF. Elevated arterial stiffness is linked with common cardiovascular risk factors in HFpEF, such as hypertension, diabetes and obesity, exacerbating the progression of disease. Studies have demonstrated that patients with HFpEF exhibit significantly higher levels of arterial stiffness compared to those without HFpEF, highlighting the value of arterial stiffness measurements as both diagnostic and prognostic tools. Moreover, interventions aimed at reducing arterial stiffness, whether through pharmacological therapies or lifestyle modifications, have shown potential in improving LV diastolic function and patient outcomes. Despite these advancements, the precise mechanisms by which arterial stiffness contributes to HFpEF are still not fully understood, necessitating the need for further research.
Topics: Vascular Stiffness; Humans; Heart Failure; Stroke Volume; Risk Factors; Ventricular Function, Left; Prognosis
PubMed: 38887204
DOI: 10.3346/jkms.2024.39.e195