2015 Vol. 12, No. 6
Background The induced pluripotent stem cell (iPSC) has shown great potential in cellular therapy of myocardial infarction (MI), while its application is hampered by the low efficiency of cardiomyocyte differentiation. The present study was designed to investigate the effects of cardiotrophin-1 (CT-1) on cardiomyocyte differentiation from mouse induced pluripotent stem cells (miPSCs) and the underlying mechanisms involved. Methods The optimal treatment condition for cardiomyocyte differentiation from miPSCs was established with ideal concentration (10 ng/mL) and duration (from day 3 to day 14) of CT-1 administration. Up-regulated expression of cardiac specific genes that accounted for embryonic cardiogenesis was observed by quantitative RT-PCR. Elevated amount of α-myosin heavy chain (α-MHC) and cardiac troponin I (cTn I) positive cells were detected by immunofluorescence staining and flow cytometry analysis in CT-1 group. Results Transmission electron microscopic analysis revealed that cells treated with CT-1 showed better organized sacromeric structure and more mitochondria, which are morphological characteristic of matured cardiomyocytes. Western blot demonstrated that CT-1 promotes cardiomyocyte differentiation from miPSCs partly via JAK2/STAT3/Pim-1 pathway as compared with control group. Conclusions These findings suggested that CT-1 could enhance the cardiomyocyte differentiation as well as the maturation of mouse induced pluripotent stem cell derived cardiomyocytes by regulating JAK2/STAT3/Pim-1signaling pathway.
Objective To assess the prevalence of and risk factors for postprandial hypotension (PPH) among old and very old Chinese men. Methods The study included 349 Chinese men aged 65 and older, grouped into two age categories: group 1 (old) included 163 men aged 65 to 80 years; group 2 (very old) included 186 men aged over 80 years. Blood pressure changes after meals were assessed every 15 min by ambulatory blood pressure monitoring. Symptoms after meal ingestion and after standing up and changes in the baseline condition relative to blood pressure changes were observed continuously. Additional baseline data included body mass index, medical history, and medication use. Results The prevalence of PPH was 59.3% overall and was significantly higher in group 2 than group 1 (63.4% vs. 54.6%, P P P = 0.02; OR = 1.86, 95% CI: 1.112?3.11, P = 0.018, respectively). In contrast, acarbose use was protective against PPH (OR = 0.4, 95% CI: 0.189?0.847, P = 0.017). The decrease in blood pressure during PPH was 20?40 mmHg and the maximum was 90 mmHg. PPH usually occurred at 30?60 min after a meal and lasted 30?120 min. Conclusions These findings demonstrate that the prevalence of PPH in men aged over 80 years is significantly higher than those in men aged 65 to 80 years, and the blood pressure decline is also higher for men aged over 80 years. In addition, hypertension and age were main risk factors for PPH in the older men, which suggest that preventing and treating PPH is worthwhile.
Background Endomyocardial biopsy (EMB) is an important tool when patients with inflammatoric cardiomyopathy (DCMi) are evaluated. We aimed to assess the clinical profile of elderly patients with DCMi on EMB. Methods Retrospective study of all consecutive patients hospitalized from January 2007 to December 2011 with clinical suspicion of DCMi undergoing EMB. Patients with evidence of DCMi on EMB (Group 1 ≥ 70 years, n = 85; Group 3 n = 418) were compared to patients of the same age group without evidence of DCMi on EMB (Group 2 ≥ 70 years, n = 45; Group 4 n = 147). Results Among 24,275 patients treated at our institution during the study period, 695 had clinical suspicion of DCMi and underwent EMB; 503 (2.1%) patients had DCMi on EMB. There were more male patients in Group 1, mean age was 74 ± 2.8 years, mean ejection fraction was 38% ± 14%. On presentation, signs of hemodynamic compromise (NYHA functional class III/IV, low cardiac output/index, and low cardiac power index) were more frequent in Group 1. EMB revealed viral genome in 78% of the patients, parvovirus B19 (PVB) was frequently encountered in both age groups (Group 1: 69.4% vs. Group 2: 59.6%); detection of more than one viral genome was more frequent in Group 1 (21.2% vs. 11.2%; P = 0.02) whereas the extent of immune response was significantly lower in individuals with advanced age. Conclusions In patients ≥ 70 years with DCMi on EMB signs of hemodynamic compromise, detection of multiple viral genomes together with an overall lower extent of immune response were more frequently observed.
Background P-wave dispersion (PWD), a measure of heterogeneity of atrial refractoriness, is defined as the difference between the maximum and minimum P-wave duration. In patients with severe aortic stenosis (AS), P-wave duration and PWD were shown to be increased, indicating atrial electrical remodeling. However, the effect of transcatheter aortic valve replacement (TAVR) on P-wave morphology has not been established yet. The aim of this study is to assess the short and long-term effects of TAVR with two types of bioprosthetic valves on P-wave duration and PWD in association with left atrial (LA) size. Methods Fifty-two (36 female) eligible patients in sinus rhythm who underwent transfemoral TAVR between June 01, 2012 and July 31, 2014 with either a Medtronic CoreValve (MCV) (n = 32) or an Edwards SAPIEN XT Valve (n = 20) were enrolled. Standard 12-lead electrocardiogram and echocardiographic evaluations were performed pre-procedurally, post-TAVR day one and 6 months post-TAVR. P-wave duration and PWD were measured and correlation analyses with echocardiographic variables were performed. Results P-wave duration and PWD were significantly decreased on post-TAVR day one (P P > 0.05). The decrease of LA diameter was found significant at the sixth-months of follow-up (P P > 0.05). A positive correlation was detected between minimum P-wave duration and maximum aortic valve gradients at post-TAVR day one (r = 0.297, P = 0.032). Conclusions P-wave duration and PWD were significantly reduced early after TAVR indicating early reverse atrial electrical remodeling. Moreover, structural reverse remodeling of atrium was detected at the 6-months of follow-up. The effects of two types of bioprosthetic valves on atrial remodeling were similar.
Objective To investigate the safety and efficacy of a self-developed novel multi-electrode radiofrequency ablation catheter (Spark) for catheter-based renal denervation (RDN). Methods A total of 14 experimental miniature pigs were randomly divided into four groups (55°& 5-watt, 55°& 8-watt, 65°& 5-watt, and 65° & 8-watt groups). Spark was used for left and right renal artery radiofrequency ablation. Blood samples collected from renal arteries and veins as well as renal arteriography were performed on all animals before, immediately after, and three months after procedure to evaluate the effects of Spark on the levels of plasma renin, aldosterone, angiotensin I, and angiotensin II as well as the pathological changes of renal arteries. Results One pig died of an anesthetic accident, 13 pigs successfully underwent the bilateral renal artery ablation. Compared with basic measurements, pigs in all the four groups had significantly decreased mean arterial pressure after procedure. Histopathological analysis showed that this procedure could result in intimal hyperplasia, significant peripheral sympathetic nerve damage in the renal arteries such as inflammatory cell infiltration and fibrosis in perineurium, uneven distribution of nerve fibers, tissue necrosis, severe vacuolization, fragmented and unclear nucleoli myelin degeneration, sparse axons, and interruption of continuity. In addition, the renal artery radiofrequency ablation could significantly reduce the levels of plasma renin, aldosterone, angiotensin I, and angiotensin II in pigs. Conclusions The results suggest that this type of multi-electrode catheter-based radiofrequency ablation could effectively remove peripheral renal sympathetic nerves and reduce the activity of systemic renin-angiotensin system in pigs, thus facilitating the control of systemic blood pressure in pigs.
Objective To investigate the clinical and perioperative characteristics of patients ≥ 75 who undergoing percutaneous coronary intervention (PCI) and to evaluate the risk factors related to short-term post-PCI mortality in this specific patients group. Methods 1,035 consecutive subjects who underwent PCI from December 2011 to November 2013 were divided into four categories: (1) patients with stable angina (SA) ≥ 75 years (n = 58); (2) patients with SA n = 218); (3) patients with acute coronary syndrome (ACS) ≥ 75 years (n = 155); (4) patients with ACS n = 604). A multivariable logistic regression analysis was conducted to detect risk factors of six-month mortality in patients ≥ 75 years who had undergone PCI. Clinical comorbidities, in-hospital biochemical indicators, perioperative data, in-hospital and six-month outcomes were analyzed and compared among the four groups. Results Compared with the younger group, pa?tients ≥ 75 years were more likely to have hypertension, history of stroke, chronic obstructive pulmonary disease, peripheral vascular disease, cardiogenic shock and malignant arrhythmia, and they were admitted to hospital with relative lower weight, hemoglobin, albumin, trigly?ceride, higher creatinine, uric acid, urea nitrogen and pro-BNP. Left main artery lesions, multi-vessel, calcified lesions, chronic totally occlusion were also more likely to be seen in the elderly group. Univariate analysis revealed that age ≥ 85 years, cardiogenic shock or severe arrhythmia at admission, emergency PCI, prior stroke and chronic kidney disease were related to six-month mortality in elderly patients ≥ 75 years who underwent PCI. Multivariable logistic regression showed that cardiogenic shock or severe arrhythmia at admission, chronic kidney disease and prior stroke were independent risk factors predicting six-month mortality in elderly patients ≥ 75 years who had undergone PCI. Conclusions Our data showed that, compared with patients under 75 years, elderly patients (≥ 75 years) who had undergone PCI had a relative higher risk of mortality, and more often accompanied with multi-comorbidities, severer admission conditions and complex coronary lesions. Better eva?luation of risk factors and more intensively care should be taken to patients ≥ 75 years who had undergone PCI therapy to reduce complications.
Objective To assesse the therapeutic effect of interventional therapy in aged patients with unprotected left main coronary artery (UPLM) lesions. Methods A total of 61 patients who were over 60 years and accepted interventional therapy of UPLM from January 2012 to November 2013 in our hospital were followed up for average 14.6 months by telephone call or outpatient visits. We analyzed the clinical features data of the interventional therapy and assessed the factors that likely influenced the clinical prognosis. Results The average age of the 61 patients was 73.9 years. The average left ventricular ejection fraction (LVEF) was 47.7%. The median of the estimated glomerular filtration rate (eGFR) was 52 mL/min per 1.73 mm2. The average SYNTAX score was 27.4 and the median of stent length was 36 mm. The cumulative incidence of cardiac death at 30 days and major adverse cardiac events (MACE) after one year was 6.6% and 32.5% estimated by Kaplan-Meier plots respectively. No severe hemorrhagic complications were observed during follow-up period. On multivariate regression analysis with a COX proportional hazards model, LVEF was an independent predictor of cardiac death at 30 days [Hazard ratio (HR): 0.7, P = 0.01]. As for MACE after one year, LVEF and eGFR were both independent predictors (HR: 0.91, P= 0.06 for LVEF, HR: 0.03, P = 0.097 for eGFR). Conclusions The interventional therapy for UPLM was effective and safe in aged patients. LVEF was the only predictor of cardiac death at 30 days, while LVEF and eGFR were both independent predictors of MACE after one year.
Objectives To investigate the relationship between serum uric acid (SUA) and left atrial spontaneous echo contrast (LA-SEC) in non-valvular atrial fibrillation (AF) patients. Methods We retrospectively screened 1,476 consecutive hospitalized patients with AF who underwent transesophageal echocardiography prior to radiofrequency catheter ablation, left atrial appendage closure and electric cardioversion at Guangdong General Hospital. Data on the clinical baseline characteristics of all patients were collected from electronic medical records and analyzed. Results After exclusion of patients with left atrial thrombus, 1,354 patients entered into present study and 57 were LA-SEC. The mean female SUA level (380.88 ± 94.35 μmol/L vs. 323.37 ± 72.19 μmol/L, P vs. 367.88 ± 68.50 μmol/L, P = 0.008) were both significantly higher in patients with LA-SEC than in the controls. The mean left atrial dimension (41.32 ± 5.12 mm vs. 36.12 ± 5.66 mm, P PConclusion SUA level is an independent risk factor and has a moderate predictive value for LA-SEC among non-valvular AF patients in Southern China.
Background Increased red blood cell distribution width (RDW) is associated with adverse outcomes in patients with heart failure (HF). The objective of this study was to compare the differences in the predictive value of RDW in patients with HF due to different causes. Methods We retrospectively investigated 1,021 HF patients from October 2009 to December 2011 at Fuwai Hospital (Beijing, China). HF in these patients was caused by three diseases; coronary heart disease (CHD), dilated cardiomyopathy (DCM) and valvular heart disease (VHD). Patients were followed-up for 21 ± 9 months. Results The RDW, mortality and survival duration were significantly different among the three groups. Kaplan–Meier analysis showed that the cumulative survival decreased significantly with increased RDW in patients with HF caused by CHD and DCM, but not in those with HF patients caused by VHD. In a multivariable model, RDW was identified as an independent predictor for the mortality of HF patients with CHD (P Conclusions RDW is a prognostic indicator for patients with HF caused by CHD and DCM; thus, RDW adds important information to NT-proBNP in CHD caused HF patients.
Background Biomarker-assisted diagnosis of acute aortic dissection (AAD) is important for diagnosis and treatment. However, identification of biomarkers for AAD in blood is a challenging task. The aim of this study is to search for new potentially microRNA (miRNAs) biomarkers in AAD. Methods The miRNAs expression profiles in ascending aortic tissue and plasma were examined by microarray analysis in two sets or groups. The tissue group was composed of four patients with AAD and four controls of healthy male organ donors. The plasma group included 20 patients with AAD and 20 controls without cardiovascular disease. Bioinformatics was used to analyze the potential targets of the differentially expressed miRNAs. Results Our study revealed that in AAD patients, the aortic tissue had 30 differentially expressed miRNAs with 13 up-regulated and 17 down-regulated, and plasma had 93 differentially expressed miRNAs, of which 33 were up-regulated and 60 were down-regulated. Four miRNAs were found to be up-regulated in both aortic tissue and plasma in AAD patients. The predicted miRNA targets indicated the four dysregulated miRNAs mainly targeted genes that were associated with cell-cell adhesion, extracellular matrix metabolism, cytoskeleton organization, inflammation, and multiple signaling pathways related to cellular cycles. Conclusions Four miRNAs, which are up-regulated both in aortic tissue and in plasma in AAD patients, have been identified in this study. These miRNAs might be potential diagnostic biomarkers for AAD. Larger sample investigations are needed for further verification.
Background Frailty is a new prognostic factor in cardiovascular medicine due to the aging and increasingly complex nature of elderly patients. It is useful and meaningful to prospectively analyze the manner in which frailty predicts short-term outcomes for elderly patients with acute coronary syndrome (ACS). Methods Patients aged ? 65 years, with diagnosis of ACS from cardiology department and geriatrics department were included from single-center. Clinical data including geriatrics syndromes were collected using Comprehensive Geriatrics Assessment. Frailty was defined according to the Clinical Frailty Scale and the impact of the co-morbidities on risk was quantified by the coronary artery disease (CAD)—specific index. Patients were followed up by clinical visit or telephone consultation and the median follow-up time is 120 days. Following-up items included all-cause mortality, unscheduled return visit, in-hospital and recurrent major adverse cardiovascular events. Multivariable regression survival analysis was performed using Cox regression. Results Of the 352 patients, 152 (43.18%) were considered frail according to the study instrument (5?7 on the scale), and 93 (26.42%) were considered moderately or severely frail (6?7 on the scale). Geriatrics syndromes including incontinence, fall history, visual impairment, hearing impairment, constipation, chronic pain, sleeping disorder, dental problems, anxiety or depression, and delirium were more frequently in frail patients than in non-frail patients (P = 0.000, 0.031, 0.009, 0.014, 0.000, 0.003, 0.022, 0.000, 0.074, and 0.432, respectively). Adjusted for sex, age, severity of coronary artery diseases (left main coronary artery lesion or not) and co-morbidities (CAD specific index) by Cox survival analysis, frailty was found to be strongly and independently associated with risk for the primary composite outcomes: all-cause mortality [Hazard Ratio (HR) = 5.393; 95% CI: 1.477?19.692, P = 0.011] and unscheduled return visit (HR = 2.832; 95% CI: 1.140?7.037, P = 0.025). Conclusions Comprehensive Geriatrics Assessment and Clinical Frail Scale were useful in evaluation of elderly patients with ACS. Frailty was strongly and independently associated with short-term outcomes for elderly patients with ACS.
Coronary artery calcification (CAC) is highly prevalent in patients with coronary heart disease (CHD) and is associated with major ad-verse cardiovascular events. There are two recognized type of CAC—intimal and medial calcification, and each of them have specific risk factors. Several theories about the mechanism of vascular calcification have been put forward, and we currently believe that vascular calcifi-cation is an active, regulated process. CAC can usually be found in patients with severe CHD, and this asymptomatic phenomenon make early diagnosis of CAC important. Coronary computed tomographic angiography is the main noninvasive tool to detect calcified lesions. Measurement of coronary artery calcification by scoring is a reasonable metric for cardiovascular risk assessment in asymptomatic adults at intermediate risk. To date, effective medical treatment of CAC has not been identified. Several strategies of percutaneous coronary interven-tion have been applied to CHD patients with CAC, but with unsatisfactory results. Prognosis of CAC is still a major problem of CHD patients. Thus, more details about the mechanisms of CAC need to be elucidated in order to improve the understanding and treatment of CAC.
Angiotensin (Ang)-(1-7) is recognized as a new bioactive peptide in renin-angiotensin system (RAS). Ang-(1-7) is a counter-regulatory mediator of Ang-II which appears to be protective against cardiovascular disease. Recent studies have found that Ang-(1-7) played an important role in reducing smooth muscle cell proliferation and migration, improving endothelial function and regulating lipid metabolism, leading to inhibition of atherosclerotic lesions and increase of plaque stability. Although clinical application of Ang-(1-7) is restricted due to its pharmacokinetic properties, identification of stabilized compounds, including more stable analogues and specific delivery compounds, has enabled clinical application of Ang-(1-7). In this review, we discussed recent findings concerning the biological role of Ang-(1-7) and related mechanism during atherosclerosis development. In addition, we highlighted the perspective to develop therapeutic strategies using Ang-(1-7) to treat atherosclerosis.
Repeat surgery has usually been considered the first choice to solve paravalvular leaks of prosthetic valves, but it carries a high operative risk, a high mortality rate and an increased risk for re-leaks. Percutaneous closure of such defects is possible, and different approaches and devices are used for this purpose. For mitral paravalvular leaks, constructing an arterio-venous wire loop for delivering the closure device through an antegrade approach is the most commonly used technique. Transcatheter closure can also be performed through a transapical approach or retrograde transfemoral arterial approach. We present a case of 68-year-old man with a mitral paravalvular leak that was successfully closed using an Amplatzer? Duct Occluder II, via retrograde transfemoral arterial approach under three-dimensional transesophageal echocardiographic guidance, without the use of a wire loop. The initial attempt to cross the paravalvular defect was unsuccessful, but the obstacle was finally overcome by introducing complex interventional techniques.
Platypnea-orthodeoxia syndrome (POS) is a rare clinical condition characterized by dyspnea and deoxygenation in the sitting or upright position relieved by supine position. The certain pathophysiological mechanisms is unknown, and this syndrome is frequently associated with other clinical entities, such as an intracardiac shunt, a pulmonary vascular shunt or a ventilation–perfusion mismatch. In cardiac POS, an atrial septal defect or patent foramen ovale (PFO) allows communication between the right- and left-sided circulations. A second defect, such as an enlarged ascending aorta, prominent eustachian valve, loculated pericardial effusion, or pneumonectomy, contributes to dynamic right-to-left shunting through the interatrial connection. The appropriate management is still debated; surgical or transcatheter percutaneous approaches to close the atrial septal defect or PFO may be considered. We describe an unusual presentation of late-onset POS in a 79-year-old man with a PFO and a dilated ascending aorta, successfully treated by percutaneous PFO closure. Our case suggests that the diagnosis of this rare clinical syndrome can be challenging in older patients complaining dyspnea, but it has important therapeutic implications and must be actively investigated in the presence of position-dependent hypoxemia. The percutaneous PFO closure in patients with POS is feasible, safe and effective even in elderly with comorbidities and frailty.