Background Vascular calcification (VC) is a subclinical manifestation of vascular disease burden among older adults, conferring an elevated mortality risk. Biomarkers capable of detecting and risk-stratifying VC associated with advanced age remains unavailable, impeding our effort to provide optimal care to geriatric patients. Objectives In this study, we aimed to investigate whether circulating miR-125b served as a potential indicator for VC in relatively healthy older adults. Methods Community-dwelling older adults (age ≥65) were prospectively recruited during 2017, followed by clinical features documentation and VC rating based on aortic arch calcification (AAC) and abdominal aortic calcification (AbAC). Multiple logistic regression was done to evaluate the relationship between circulating miR-125b levels, VC presence and severity, followed by selecting the optimal cutoff point for VC diagnosis. Results A total of 343 relatively healthy older adults (median age, 73.8 years; 40% male; 59.8% having AAC) were enrolled, with a median circulating miR-125b level of 0.012 (interquartile range, 0.003-0.037). Those with more severe AAC had progressively decreasing miR-125b levels (p less then 0.001). Multiple regression analyses showed that having higher miR-125b levels based on the median value were associated with a substantially lower risk of AAC [odds ratio (OR) 0.022, 95% confidence interval (CI) 0.011-0.044] compared to those having lower ones. An optimal cutoff of miR-125b for identifying AAC in older adults was 0.008, with a sensitivity and specificity of 0.86 and 0.80, respectively. Similar findings were obtained when using AbAC as the endpoint. Conclusions We found that miR-125b serves as an independent indicator for VC in relatively healthy older adults, and may potentially be linked with VC pathophysiology.The cardiac Na+/H+ exchanger (NHE1) is a membrane glycoprotein fundamental for proper cell functioning due its multiple housekeeping tasks, including regulation of intracellular pH, Na+ concentration, and cell volume. In the heart, hyperactivation of NHE1 has been linked to the development of different pathologies. Several studies in animal models that reproduce the deleterious effects of ischemia/reperfusion injury or cardiac hypertrophy have conclusively demonstrated that NHE1 inhibition provides cardioprotection. Unfortunately, NHE1 inhibitors failed to reproduce these effects in the clinical arena. The reasons for those discrepancies are not apparent yet. However, a reasonable clue to consider would be that drugs that completely abolish the exchanger activity, including that its essential housekeeping function may not be the best therapeutic approach. Therefore, interventions tending to specifically reduce its hyperactive state without affecting its basal activity emerge as a novel potential gold standard. In this regard, a promising goal seems to be the modulation of the phosphorylation state of the cytosolic tail of the exchanger. Recent own experiments demonstrated that Sildenafil, a phosphodiesterase 5A inhibitor drug that has been widely used for the treatment of erectile dysfunction is able to decrease NHE1 phosphorylation, and hence reduce its hyperactivity. In connection, growing evidence demonstrates cardioprotective properties of Sildenafil against different cardiac pathologies, with the distinctive characteristic of directly affecting cardiac tissue without altering blood pressure. This mini-review was aimed to focus on the regulation of NHE1 activity by Sildenafil. For this purpose, experimental data reporting Sildenafil effects in different animal models of heart disease will be discussed.Background Takotsubo cardiomyopathy is triggered by emotional or physical stress. It is defined as a reversible myocardial dysfunction, usually with apical ballooning aspect due to apical akinesia associated with hyperkinetic basal left ventricular contraction. Described in cases of viral infections such as influenza, only few have been reported associated with novel coronavirus disease 2019 (COVID-19) in the recent pandemic. Case summary A 79-years-old man, with cardiovascular risk factors (type 2 diabetes and hypertension) and chronic kidney disease, presented to the emergency room for severe dyspnea after 8 days of presenting respiratory symptoms and fever. https://www.selleckchem.com/ Baseline electrocardiogram (ECG) was normal, but he presented marked inflammatory syndrome. He was transferred to an intensive care unit to receive mechanical ventilation within 6 h, due to acute respiratory distress syndrome. He presented circulatory failure 2 days after, requiring norepinephrine support (up to up to 1.04 μg/kg/min). Troponin T was elevated (637 ng/l). ECG showed diffuse T wave inversion. Echocardiography showed reduced left ventricular ejection fraction (LVEF 40%), with visual signs of Takotsubo cardiomyopathy. Cardiac failure resolved after 24 h with troponin T decrease (433 ng/l) and restoration of cardiac function (LVEF 60% with regression of Takotsubo features). Patient died after 15 days of ICU admission, due to septic shock from ventilator-acquired pneumonia. Cardiac function was then normal. Conclusion Mechanisms of Takotsubo cardiomyopathy in viral infections include catecholamine-induced myocardial toxicity and inflammation related to sepsis. Differential diagnoses include myocarditis and myocardial infarction. Evidence of the benefit of immunomodulatory drugs and dexamethasone are growing to support this hypothesis in COVID-19.Transcatheter mitral valve interventions are an evolving and growing field in which multimodality cardiac imaging is essential for diagnosis, procedural planning, and intraprocedural guidance. Currently, transcatheter mitral valve-in-valve with a balloon-expandable valve is the only form of transcatheter mitral valve replacement (TMVR) approved by the FDA, but valve-in-ring and valve-in-mitral annular calcification interventions are increasingly being performed. Additionally, there are several devices under investigation for implantation in a native annulus. Paravalvular leak (PVL) is a known complication of surgical or transcatheter valve implantation, where regurgitant flow occurs between the prosthetic sewing ring and the native mitral annulus. We sought to describe the role and applications of multimodality cardiac imaging for TMVR, and PVL closure, including the use of Cardiovascular Computed Tomography Angiography and 3-Dimensional Transesophageal Echocardiography for diagnosis, prosthetic valve evaluation, pre-procedural planning, and intraprocedural guidance, as well as evolving technologies such as fusion imaging and 3D printing.
Background Vascular calcification (VC) is a subclinical manifestation of vascular disease burden among older adults, conferring an elevated mortality risk. Biomarkers capable of detecting and risk-stratifying VC associated with advanced age remains unavailable, impeding our effort to provide optimal care to geriatric patients. Objectives In this study, we aimed to investigate whether circulating miR-125b served as a potential indicator for VC in relatively healthy older adults. Methods Community-dwelling older adults (age ≥65) were prospectively recruited during 2017, followed by clinical features documentation and VC rating based on aortic arch calcification (AAC) and abdominal aortic calcification (AbAC). Multiple logistic regression was done to evaluate the relationship between circulating miR-125b levels, VC presence and severity, followed by selecting the optimal cutoff point for VC diagnosis. Results A total of 343 relatively healthy older adults (median age, 73.8 years; 40% male; 59.8% having AAC) were enrolled, with a median circulating miR-125b level of 0.012 (interquartile range, 0.003-0.037). Those with more severe AAC had progressively decreasing miR-125b levels (p less then 0.001). Multiple regression analyses showed that having higher miR-125b levels based on the median value were associated with a substantially lower risk of AAC [odds ratio (OR) 0.022, 95% confidence interval (CI) 0.011-0.044] compared to those having lower ones. An optimal cutoff of miR-125b for identifying AAC in older adults was 0.008, with a sensitivity and specificity of 0.86 and 0.80, respectively. Similar findings were obtained when using AbAC as the endpoint. Conclusions We found that miR-125b serves as an independent indicator for VC in relatively healthy older adults, and may potentially be linked with VC pathophysiology.The cardiac Na+/H+ exchanger (NHE1) is a membrane glycoprotein fundamental for proper cell functioning due its multiple housekeeping tasks, including regulation of intracellular pH, Na+ concentration, and cell volume. In the heart, hyperactivation of NHE1 has been linked to the development of different pathologies. Several studies in animal models that reproduce the deleterious effects of ischemia/reperfusion injury or cardiac hypertrophy have conclusively demonstrated that NHE1 inhibition provides cardioprotection. Unfortunately, NHE1 inhibitors failed to reproduce these effects in the clinical arena. The reasons for those discrepancies are not apparent yet. However, a reasonable clue to consider would be that drugs that completely abolish the exchanger activity, including that its essential housekeeping function may not be the best therapeutic approach. Therefore, interventions tending to specifically reduce its hyperactive state without affecting its basal activity emerge as a novel potential gold standard. In this regard, a promising goal seems to be the modulation of the phosphorylation state of the cytosolic tail of the exchanger. Recent own experiments demonstrated that Sildenafil, a phosphodiesterase 5A inhibitor drug that has been widely used for the treatment of erectile dysfunction is able to decrease NHE1 phosphorylation, and hence reduce its hyperactivity. In connection, growing evidence demonstrates cardioprotective properties of Sildenafil against different cardiac pathologies, with the distinctive characteristic of directly affecting cardiac tissue without altering blood pressure. This mini-review was aimed to focus on the regulation of NHE1 activity by Sildenafil. For this purpose, experimental data reporting Sildenafil effects in different animal models of heart disease will be discussed.Background Takotsubo cardiomyopathy is triggered by emotional or physical stress. It is defined as a reversible myocardial dysfunction, usually with apical ballooning aspect due to apical akinesia associated with hyperkinetic basal left ventricular contraction. Described in cases of viral infections such as influenza, only few have been reported associated with novel coronavirus disease 2019 (COVID-19) in the recent pandemic. Case summary A 79-years-old man, with cardiovascular risk factors (type 2 diabetes and hypertension) and chronic kidney disease, presented to the emergency room for severe dyspnea after 8 days of presenting respiratory symptoms and fever. https://www.selleckchem.com/ Baseline electrocardiogram (ECG) was normal, but he presented marked inflammatory syndrome. He was transferred to an intensive care unit to receive mechanical ventilation within 6 h, due to acute respiratory distress syndrome. He presented circulatory failure 2 days after, requiring norepinephrine support (up to up to 1.04 μg/kg/min). Troponin T was elevated (637 ng/l). ECG showed diffuse T wave inversion. Echocardiography showed reduced left ventricular ejection fraction (LVEF 40%), with visual signs of Takotsubo cardiomyopathy. Cardiac failure resolved after 24 h with troponin T decrease (433 ng/l) and restoration of cardiac function (LVEF 60% with regression of Takotsubo features). Patient died after 15 days of ICU admission, due to septic shock from ventilator-acquired pneumonia. Cardiac function was then normal. Conclusion Mechanisms of Takotsubo cardiomyopathy in viral infections include catecholamine-induced myocardial toxicity and inflammation related to sepsis. Differential diagnoses include myocarditis and myocardial infarction. Evidence of the benefit of immunomodulatory drugs and dexamethasone are growing to support this hypothesis in COVID-19.Transcatheter mitral valve interventions are an evolving and growing field in which multimodality cardiac imaging is essential for diagnosis, procedural planning, and intraprocedural guidance. Currently, transcatheter mitral valve-in-valve with a balloon-expandable valve is the only form of transcatheter mitral valve replacement (TMVR) approved by the FDA, but valve-in-ring and valve-in-mitral annular calcification interventions are increasingly being performed. Additionally, there are several devices under investigation for implantation in a native annulus. Paravalvular leak (PVL) is a known complication of surgical or transcatheter valve implantation, where regurgitant flow occurs between the prosthetic sewing ring and the native mitral annulus. We sought to describe the role and applications of multimodality cardiac imaging for TMVR, and PVL closure, including the use of Cardiovascular Computed Tomography Angiography and 3-Dimensional Transesophageal Echocardiography for diagnosis, prosthetic valve evaluation, pre-procedural planning, and intraprocedural guidance, as well as evolving technologies such as fusion imaging and 3D printing.
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