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Journal of Feline Medicine and Surgery Nov 2021Hypertrophic cardiomyopathy (HCM) is the most common form of feline cardiomyopathy observed clinically and may affect up to approximately 15% of the domestic cat...
PRACTICAL RELEVANCE
Hypertrophic cardiomyopathy (HCM) is the most common form of feline cardiomyopathy observed clinically and may affect up to approximately 15% of the domestic cat population, primarily as a subclinical disease. Fortunately, severe HCM, leading to heart failure or arterial thromboembolism (ATE), only occurs in a small proportion of these cats.
PATIENT GROUP
Domestic cats of any age from 3 months upward, of either sex and of any breed, can be affected. A higher prevalence in male and domestic shorthair cats has been reported.
DIAGNOSTICS
Subclinical feline HCM may or may not produce a heart murmur or gallop sound. Substantial left atrial enlargement can often be identified radiographically in cats with severe HCM. Biomarkers should not be relied on solely to diagnose the disease. While severe feline HCM can usually be diagnosed via echocardiography alone, feline HCM with mild to moderate left ventricular (LV) wall thickening is a diagnosis of exclusion, which means there is no definitive test for HCM in these cats and so other disorders that can cause mild to moderate LV wall thickening (eg, hyperthyroidism, systemic hypertension, acromegaly, dehydration) need to be ruled out.
KEY FINDINGS
While a genetic cause of HCM has been identified in two breeds and is suspected in another, for most cats the cause is unknown. Systolic anterior motion of the mitral valve (SAM) is the most common cause of dynamic left ventricular outflow tract obstruction (DLVOTO) and, in turn, the most common cause of a heart murmur with feline HCM. While severe DLVOTO is probably clinically significant and so should be treated, lesser degrees probably are not. Furthermore, since SAM can likely be induced in most cats with HCM, the distinction between HCM without obstruction and HCM with obstruction (HOCM) is of limited importance in cats. Diastolic dysfunction, and its consequences of abnormally increased atrial pressure leading to signs of heart failure, and sluggish atrial blood flow leading to ATE, is the primary abnormality that causes clinical signs and death in affected cats. Treatment (eg, loop diuretics) is aimed at controlling heart failure. Preventive treatment (eg, antithrombotic drugs) is aimed at reducing the risk of complications (eg, ATE).
CONCLUSIONS
Most cats with HCM show no overt clinical signs and live a normal or near-normal life despite this disease. However, a substantial minority of cats develop overt clinical signs referable to heart failure or ATE that require treatment. For most cats with clinical signs caused by HCM, the long-term prognosis is poor to grave despite therapy.
AREAS OF UNCERTAINTY
Genetic mutations (variants) that cause HCM have been identified in a few breeds, but, despite valiant efforts, the cause of HCM in the vast majority of cats remains unknown. No treatment currently exists that reverses or even slows the cardiomyopathic process in HCM, again despite valiant efforts. The search goes on.
Topics: Animals; Cardiomyopathies; Cardiomyopathy, Hypertrophic; Cat Diseases; Cats; Echocardiography; Heart Ventricles; Male; Systole
PubMed: 34693811
DOI: 10.1177/1098612X211020162 -
Bioengineered Dec 2021Cardiac dysfunction is a common complication of sepsis, and is attributed to severe inflammatory responses. Ferroptosis is reported to be involved in sepsis-induced...
Cardiac dysfunction is a common complication of sepsis, and is attributed to severe inflammatory responses. Ferroptosis is reported to be involved in sepsis-induced cardiac inflammation. Therefore, we speculated that ferrostatin-1 (Fer-1), a ferroptosis inhibitor, improves cardiac dysfunction caused by sepsis. An intraperitoneal injection of lipopolysaccharide (LPS) was performed to induce a rat cardiac dysfunction model. Echocardiography, cardiac histopathology, biochemical and western blot results were analyzed. Twelve hours after the LPS injection, LPS-treated rats exhibited deteriorating cardiac systolic function, increased levels of cardiac injury markers and levels of ferroptosis markers prostaglandin endoperoxide synthase 2 (PTGS2). Additionally, LPS increased iron deposition in the myocardium, with downregulating ferroportin (FPN, SLC40A1) and transferrin receptor (TfR)expression, and upregulating ferritin light chain (FTL) and ferritin heavy chain (FTH1) expression. Meanwhile, LPS also increased lipid peroxidation in the rat heart by decreasing the expression of glutathione peroxidase 4 (GPX4). Moreover, the expression of inflammatory cytokines, such as tumor necrosis-alpha (TNF-α), interleukin-1 (IL-1β), and interleukin-6 (IL-6), and inflammatory cell infiltration were also increased following LPS challenge. Finally, the abovementioned adverse effects of LPS were relieved by Fer-1 except for TfR expression. Mechanistically, Fer-1 significantly reduced the levels of toll-like receptor 4 (TLR4), phospho-nuclear factor kappa B (NF-κB), and phospho-inhibitor of kappa Bα (IκBα) in LPS-treated rats. In summary, these findings imply that Fer-1 improved sepsis-induced cardiac dysfunction at least partially via the TLR4/NF-κB signaling pathway.
Topics: Animals; Cyclohexylamines; Electrocardiography; Heart; Inflammation; Lipopolysaccharides; Male; Myocardium; NF-KappaB Inhibitor alpha; NF-kappa B; Phenylenediamines; Rats, Wistar; Sepsis; Survival Analysis; Systole; Toll-Like Receptor 4; Rats
PubMed: 34787054
DOI: 10.1080/21655979.2021.2001913 -
Clinical and Translational Medicine Jan 2021As a pattern recognition receptor, Toll-like receptor 7 (TLR7) widely presented in the endosomal membrane of various cells. However, the precise role and mechanism of...
BACKGROUND
As a pattern recognition receptor, Toll-like receptor 7 (TLR7) widely presented in the endosomal membrane of various cells. However, the precise role and mechanism of TLR7 in septic cardiomyopathy remain unknown. This study aims to determine the role of TLR7 in cardiac dysfunction during sepsis and explore the mechanism of TLR7 in septic cardiomyopathy.
METHODS
We generated a mouse model of septic cardiomyopathy by challenging with lipopolysaccharide (LPS). TLR7-knockout (TLR7 ), wild-type (WT) mice, cardiac-specific TLR7-transgenic (cTG-TLR7) overexpression, and littermates WT (LWT) mice were subjected to septic model. Additionally, to verify the role and mechanism of TLR7 in vitro, we transfected neonatal rat ventricular myocytes (NRVMs) with Ad-TLR7 and TLR7 siRNA before LPS administration. The effects of TLR7 were assessed by Ca imaging, western blotting, immunostaining, and quantitative real-time polymerase chain reaction (qPCR).
RESULTS
We found that TLR7 knockout markedly exacerbated sepsis-induced systolic dysfunction. Moreover, cardiomyocytes isolated from TLR7 mice displayed weaker Ca handling than that in WT mice in response to LPS. Conversely, TLR7 overexpression alleviated LPS-induced systolic dysfunction, and loxoribine (TLR7-specific agonist) improved LPS-induced cardiac dysfunction. Mechanistically, these optimized effects were associated with enhanced the adenosine (cAMP)-protein kinase A (PKA) pathway, which upregulated phosphorylate-phospholamban (p-PLN) (Ser16) and promoted sarco/endoplasmic reticulum Ca ATPase (Serca) and Ryanodine Receptor 2 (RyR2) expression in the sarcoplasmic reticulum (SR), and ultimately restored Ca handling in response to sepsis. While improved Ca handling was abrogated after H89 (a specific PKA inhibitor) pretreatment in cardiomyocytes isolated from cTG-TLR7 mice. Consistently, TLR7 overexpression improved LPS-induced Ca -handling decrement in NRVMs. Nevertheless, TLR7 knockdown showed a deteriorative phenotype.
CONCLUSIONS
Our data demonstrated that activation of TLR7 protected against sepsis-induced cardiac dysfunction through promoting cAMP-PKA-PLN pathway, and we revealed that TLR7 might be a novel therapeutic target to block the septic cardiomyopathy and support systolic function during sepsis.
Topics: Animals; Cardiomyopathies; Disease Models, Animal; Male; Membrane Glycoproteins; Mice; Mice, Inbred C57BL; Sepsis; Systole; Toll-Like Receptor 7
PubMed: 33463061
DOI: 10.1002/ctm2.266 -
Circulation. Cardiovascular Imaging Sep 2019The ratios of tricuspid annular plane systolic excursion (TAPSE)/echocardiographically measured systolic pulmonary artery pressure (PASP), fractional area...
Validation of the Tricuspid Annular Plane Systolic Excursion/Systolic Pulmonary Artery Pressure Ratio for the Assessment of Right Ventricular-Arterial Coupling in Severe Pulmonary Hypertension.
BACKGROUND
The ratios of tricuspid annular plane systolic excursion (TAPSE)/echocardiographically measured systolic pulmonary artery pressure (PASP), fractional area change/invasively measured mean pulmonary artery pressure, right ventricular (RV) area change/end-systolic area, TAPSE/pulmonary artery acceleration time, and stroke volume/end-systolic area have been proposed as surrogates of RV-arterial coupling. The relationship of these surrogates with the gold standard measure of RV-arterial coupling (invasive pressure-volume loop-derived end-systolic/arterial elastance [Ees/Ea] ratio) and RV diastolic stiffness (end-diastolic elastance) in pulmonary hypertension remains incompletely understood. We evaluated the relationship of these surrogates with invasive pressure-volume loop-derived Ees/Ea and end-diastolic elastance in pulmonary hypertension.
METHODS
We performed right heart echocardiography and cardiac magnetic resonance imaging 1 day before invasive measurement of pulmonary hemodynamics and single-beat RV pressure-volume loops in 52 patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension. The relationships of the proposed surrogates with Ees/Ea and end-diastolic elastance were evaluated by Spearman correlation, multivariate logistic regression, and receiver operating characteristic analyses. Associations with prognosis were evaluated by Kaplan-Meier analysis.
RESULTS
TAPSE/PASP, fractional area change/mean pulmonary artery pressure, RV area change/end-systolic area, and stroke volume/end-systolic area but not TAPSE/pulmonary artery acceleration time were correlated with Ees/Ea and end-diastolic elastance. Of the surrogates, only TAPSE/PASP emerged as an independent predictor of Ees/Ea (multivariate odds ratio: 18.6; 95% CI, 0.8-96.1; P=0.08). In receiver operating characteristic analysis, a TAPSE/PASP cutoff of 0.31 mm/mm Hg (sensitivity: 87.5% and specificity: 75.9%) discriminated RV-arterial uncoupling (Ees/Ea <0.805). Patients with TAPSE/PASP <0.31 mm/mm Hg had a significantly worse prognosis than those with higher TAPSE/PASP.
CONCLUSIONS
Echocardiographically determined TAPSE/PASP is a straightforward noninvasive measure of RV-arterial coupling and is affected by RV diastolic stiffness in severe pulmonary hypertension.
CLINICAL TRIAL REGISTRATION
URL: https://www.clinicaltrials.gov. Unique identifier: NCT03403868.
Topics: Biomarkers; Cardiac Catheterization; Disease Progression; Echocardiography, Doppler; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Magnetic Resonance Imaging; Male; Middle Aged; Prospective Studies; Registries; Systole; Tricuspid Valve; Ventricular Dysfunction, Right
PubMed: 31500448
DOI: 10.1161/CIRCIMAGING.119.009047 -
Journal of Clinical Hypertension... Mar 2021Isolated systolic hypertension (ISH) is the most common type of essential hypertension in the elderly and young adults. With rapid industrialization and population... (Review)
Review
Isolated systolic hypertension (ISH) is the most common type of essential hypertension in the elderly and young adults. With rapid industrialization and population aging, the prevalence of ISH in Asia will rise substantially. Asian populations have distinct epidemiological features, risk factors and are especially vulnerable to ISH. There is a pressing need for Asian countries to formulate their unique strategies for control of ISH. In this review, we focus on the (1) epidemiology and pathophysiology, (2) risk factors and impact on outcomes, and (3) treatment goal and strategy for ISH in Asia.
Topics: Aged; Asia; Humans; Hypertension; Prevalence; Risk Factors; Systole; Young Adult
PubMed: 33249701
DOI: 10.1111/jch.14111 -
Current Cardiology Reports Dec 2022Heart failure results in the high incidence and mortality all over the world. Mechanical properties of myocardium are critical determinants of cardiac function, with... (Review)
Review
PURPOSE OF REVIEW
Heart failure results in the high incidence and mortality all over the world. Mechanical properties of myocardium are critical determinants of cardiac function, with regional variations in myocardial contractility demonstrated within infarcted ventricles. Quantitative assessment of cardiac contractile function is therefore critical to identify myocardial infarction for the early diagnosis and therapeutic intervention.
RECENT FINDINGS
Current advancement of cardiac functional assessments is in pace with the development of imaging techniques. The methods tailored to advanced imaging have been widely used in cardiac magnetic resonance, echocardiography, and optical microscopy. In this review, we introduce fundamental concepts and applications of representative methods for each imaging modality used in both fundamental research and clinical investigations. All these methods have been designed or developed to quantify time-dependent 2-dimensional (2D) or 3D cardiac mechanics, holding great potential to unravel global or regional myocardial deformation and contractile function from end-systole to end-diastole. Computational methods to assess cardiac contractile function provide a quantitative insight into the analysis of myocardial mechanics during cardiac development, injury, and remodeling.
Topics: Humans; Myocardial Contraction; Diastole; Myocardium; Heart; Systole
PubMed: 36301405
DOI: 10.1007/s11886-022-01814-1 -
JACC. Cardiovascular Imaging Mar 2020
Topics: Cardiac Resynchronization Therapy; Humans; Systole
PubMed: 32139037
DOI: 10.1016/j.jcmg.2019.10.026 -
The Cochrane Database of Systematic... Nov 2021Hypertension is considered to be a serious health problem worldwide. Controlling and lowering blood pressure are of significant benefit to people with hypertension... (Review)
Review
BACKGROUND
Hypertension is considered to be a serious health problem worldwide. Controlling and lowering blood pressure are of significant benefit to people with hypertension because hypertension is a risk factor for stroke, heart disease, and cardiovascular disease. Roselle, the tropical plant Hibiscus sabdariffa, also commonly called sour tea or red tea, has been used as both a thirst-quenching drink and for medicinal purposes.
OBJECTIVES
To assess the effect of Roselle on blood pressure in people with primary hypertension.
SEARCH METHODS
For this update, the Cochrane Hypertension Information Specialist searched the following databases and trials registers for randomised controlled trials (RCTs): the Cochrane Hypertension Specialised Register (to 6 August 2021), Cochrane Central Register of Controlled Trials (CENTRAL; 2021, Issue 7), MEDLINE Ovid (1946 to 5 August 2021), Embase Ovid (1974 to 5 August 2021), ProQuest Dissertations & Theses (to 6 August 2021), Web of Science Clarivate (to 7 August 2021), Food Science and Technology Abstracts Clarivate (to 7 August 2021), the WHO International Clinical Trials Registry Platform (to 6 August 2021), and the US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov (to 6 August 2021). We searched Google Scholar and OpenSIGLE. We also handsearched local and regional Chinese databases: CBM, CMCC, TCMLARS, CNKI, CMAC, and the Index to Chinese Periodical Literature (to 14 September 2020), as well as Thai databases (ThaiJO, CUIR, TDC, CMU e-Theses, TCTR) (to 3 October 2020). There were no language or publication date restrictions.
SELECTION CRITERIA
We sought RCTs evaluating the use of any forms of Roselle with placebo or no treatment in adults with hypertension. Our primary outcome was change in trough and/or peak systolic and diastolic blood pressure (SBP, DBP). Secondary outcomes were withdrawals due to adverse effects, change in pulse pressure, and change in heart rate.
DATA COLLECTION AND ANALYSIS
All search results were managed using Covidence and re-checked for the number of records, inclusion and exclusion of studies with Mendeley reference management software. We used standard methodological procedures expected by Cochrane. Two review authors worked independently in parallel for screening (titles and abstracts, and full reports), data extraction, risk of bias assessment, and assessment of the certainty of the evidence using the GRADE approach. Any disagreements were resolved by discussion or by consultation with the third review author if necessary. We presented mean difference (MD) of change in SBP and DBP with their corresponding 95% confidence interval (CI).
MAIN RESULTS
For this update, only one RCT with a parallel-group design involving 60 participants with type 2 diabetes mellitus fulfilled the inclusion criteria. This study investigated the effect of Roselle extract capsules (total dose of 5600 mg) compared with placebo (lactose) at eight weeks. The study was at low risk of selection bias, performance bias, and detection bias. Conversely, it was at high risk of attrition bias, reporting bias, and other bias (baseline imbalance). We have very little confidence in the effect estimate of Roselle on change-from-baseline in both SBP and DBP between the two groups. The MD of change in SBP was 1.65, 95% CI -7.89 to 11.19 mmHg, 52 participants, very low-certainty evidence. The MD of change in DBP was 4.60, 95% CI -1.38 to 10.58 mmHg, 52 participants, very low-certainty evidence. Our secondary outcomes of withdrawals due to adverse effects, change in pulse pressure, and change in heart rate were not reported. Due to the limited available data, no secondary analyses were performed (subgroup and sensitivity analysis).
AUTHORS' CONCLUSIONS
The evidence is currently insufficient to determine the effectiveness of Roselle compared to placebo for controlling or lowering blood pressure in people with hypertension. The certainty of evidence was very low due to methodological limitations, imprecision, and indirectness. There is a need for rigorous RCTs that address the review question.
Topics: Adult; Blood Pressure; Cardiovascular Diseases; Hibiscus; Humans; Hypertension; Systole
PubMed: 34837382
DOI: 10.1002/14651858.CD007894.pub3 -
Morphologie : Bulletin de L'Association... Feb 2021The development of the myocardial band shows that it starts and ends at the origin of the great vessels and that the myocardium joins to these rings but does not...
OBJECTIVE
The development of the myocardial band shows that it starts and ends at the origin of the great vessels and that the myocardium joins to these rings but does not inserted into them. We always considered that there should be a fixed end of the muscle band that would allow it a helical rotation to fulfill its fundamental movements of shortening-torsion (systole) and elongation-distortion (suction).
MATERIAL AND METHODS
Seven young-bovine hearts (800-1000g) and seven human hearts (one embryo, 4g; one 10 years, 250g and five adult, 300g/average) were used for a detailed macrocoscopic and microscopic study.
RESULTS
We have found in all the bovine and human hearts studied a nucleus underlying the right trigone, whose osseus, chondroid or tendinous histological structure depends on the specimen analyzed. The microscopic analysis revealed in the hearts a trabecular osteochondral matrix (fulcrum) with segmental lines in bovines and in the ten-year-old human. In the fetus, it was found pre-chondroid areas in a myxoid stroma. In the adult human hearts, the histological analysis revealed a matrix similar to that of a tendon. All the hearts studied presented myocardial attachment to the rigid structure of the fulcrum. Myocardiocytes were not found neither at the left or rigth trigonous nor at the base of the valves.
CONCLUSIONS
The finding of the fulcrum gives support to the spiral myocardial band being the point of fixation that allows the helicoidal torsion.
Topics: Adult; Animals; Cattle; Child; Heart Ventricles; Humans; Myocardium; Rotation; Systole
PubMed: 32646845
DOI: 10.1016/j.morpho.2020.06.010 -
Current Opinion in Pulmonary Medicine Sep 2019Right ventricular (RV) function is an important determinant of morbidity and mortality in patients with pulmonary arterial hypertension (PAH). Although substantial... (Review)
Review
PURPOSE OF REVIEW
Right ventricular (RV) function is an important determinant of morbidity and mortality in patients with pulmonary arterial hypertension (PAH). Although substantial progress has been made in understanding the development of RV failure in the last decennia, this has not yet resulted in the development of RV selective therapies. In this review, we will discuss the current status on the treatment of RV failure and potential novel therapeutic strategies that are currently being investigated in clinical trials.
RECENT FINDINGS
Increased afterload results in elevated wall tension. Consequences of increased wall tension include autonomic disbalance, metabolic shift and inflammation, negatively affecting RV contractility. Compromised RV systolic function and low cardiac output activate renin-angiotensin aldosterone system, which leads to fluid retention and further increase in RV wall tension. This vicious circle can be interrupted by directly targeting the determinants of RV wall tension; preload and afterload by PAH-medications and diuretics, but is also possibly by restoring neurohormonal and metabolic disbalance, and inhibiting maladaptive inflammation. A variety of RV selective drugs are currently being studied in clinical trials.
SUMMARY
Nowadays, afterload reduction is still the cornerstone in treatment of PAH. New treatments targeting important pathobiological determinants of RV failure directly are emerging.
Topics: Diuretics; Heart Failure; Heart Ventricles; Humans; Hypertension, Pulmonary; Pulmonary Artery; Systole; Ventricular Function, Right
PubMed: 31365374
DOI: 10.1097/MCP.0000000000000610