2015 Vol. 12, No. 4
There has been a significant decline in cardiovascular morbidity and mortality amidst pervasive advances in care, including percutaneous revascularization, mechanical circulatory support, and transcatheter valvular therapies. While advancing therapies may add significant longevity, they also bring about new end-of-life decision-making challenges for patients and their families who also must weigh the advantages of reduced mortality to the possibility of longer lives consisting of high morbidity, frailty, pain, and poor quality of living. Advance care entails options of withholding or withdrawing therapies, and has become a familiar part of cardiovascular care for older patients in Western countries. However, as advanced cardiovascular practices extend to developing countries, the interrelated concept of advance care is rarely straight forward as it is affected by local cultural traditions and mores, and can lead to very different inferences and use. This paper discusses the concepts of advance care planning, surrogate decision-making, orders for resuscitation and futility in patients with cardiac disease with comparisons of West to East, focusing particularly on the United States versus India.
In order to help older adults with cardiovascular disease navigate complex decisions, clinicians must know tenets of medical ethics and have good communication skills. The elements of decision making capacity and informed consent are reviewed, using relevant clinical examples to illustrate the basic concepts. The shared decision making model, by which clinician and patient work together to determine the plan of care, is described. Useful communication techniques to implement shared decision making are suggested.
Objective To evaluate immediate transcatheter aortic valve implantation (TAVI) results and medium-term follow-up in very elderly patients with severe and symptomatic aortic stenosis (AS). Methods This multicenter, observational and prospective study was carried out in three hospitals. We included consecutive very elderly (> 85 years) patients with severe AS treated by with TAVI. The primary endpoint was to evaluate death rates from any cause at two years. Results The study included 160 consecutive patients with a mean age of 87 ± 2.1 years (range from 85 to 94 years) and a mean logistic EuroSCORE of 18.8% ± 11.2% with 57 (35.6%) patients scoring ≥ 20%. Procedural success rate was 97.5%, with 25 (15.6%) patients experiencing acute complications with major bleeding (the most frequent). Global mortality rate during hospitalization was 8.8% (n = 14) and 30-day mortality rate was 10% (n = 16). Median follow up period was 252.24 ± 232.17 days. During the follow-up period, 28 (17.5%) patients died (17 of them due to cardiac causes). The estimated two year overall and cardiac survival rates using the Kaplan-Meier method were 71% and 86.4%, respectively. Cox proportional hazard regression showed that the variable EuroSCORE ≥ 20 was the unique variable associated with overall mortality. Conclusions TAVI is safe and effective in a selected population of very elderly patients. Our findings support the adoption of this new procedure in this complex group of patients.
Objective Doppler derived mitral peak early diastolic filling velocity to deceleration time ratio (E/DT) has been proposed as parameter for predicting prognosis in general population. This study prospectively investigates the incremental prognostic value of E/DT over clinical, conventional echocardiographic and mitral-Doppler variables in patients hospitalized for decompensated heart failure (HF). Methods We analyzed 95 HF patients (mean age 64.8 ± 12.2 years) hospitalized at our institution from January 2010 to March 2012. The primary end-point was cardiac death or hospitalization, whichever occurred first. Cox regression analysis was performed to identify significant predictors of outcomes. Results During follow-up (median 37.7 months) 13 patients died and 44 were hospitalized for a cardiac event. At univariable analysis, New York Heart Association (NYHA) functional class, furosemide dosage, lateral tricuspidal annular plane systolic excursion, deceleration time and E/DT were predictive of outcome. At multivariable analysis, E/DT was the only predictor of prognosis (hazard ratio = 1.02, P = 0.018), giving incremental prognostic information to clinical and other echocardio-graphic measures (global chi-square from 15.4 to 25.2; P = 0.032). Conclusions E/DT gives independent and incremental prognostic information in HF patients.
Background Myocardial infarction (MI) has likely contributed to the increased prevalence of heart failure (HF). As a result of reduced cardiac function, splanchnic blood flow decreases, causing ischemia in villi and damage to the intestinal barrier. The induction of heme oxygenase-1 (HO-1) could prevent, or lessen the effects of stress and inflammation. Thus, the effect and mechanism thereof of HO-1 on the intestines of rats with HF was investigated. Methods Male Wistar rats with heart failure through ligation of the left coronary artery were identified with an left ventricular ejection fraction (LvEF) of Results The rats receiving MI + CoPP injections exhibited a recovery in cardiac function, an amelioration of mesenteric microcirculation and change in morphology, a lower BT incidence, a reduction in serum and ileac NO and TNF-α levels, and an elevation in ileac HO-1, CO, and interleukin-10 (IL-10) levels compared to the MI (P P Conclusions HO-1 exerted a protective effect on the intestines of rats with HF by inhibiting the inflammation and amelioration of microcirculation through the CO pathway. This protective effect could be independent from the recovery of cardiac function.
Background Sarcopenia is a risk factor for metabolic disorders and cardiovascular disease, but the association between sarcopenia and cardiovascular risk factors according to age and obesity status in the general population remains unknown. We thus investigated these associations in the Korean population. Methods We included 8,958 and 8,518 subjects from the fifth Korean National Health and Nutrition Examination Survey (KNHANES) (from 2010 and 2011, respectively). The study was restricted to participants ≥ 20 years old who had completed the health examination survey, including whole body dual-energy X-ray absorptiometry scans. After exclusion, 7,366 subjects (3,188 men, 4,178 women) were included in our final analysis. Age was categorized according to three age groups (20–39, 40–59, and ≥ 60 years), and subjects were categorized according to their sarcopenic and obesity status. Cardiovascular risk was assessed with Framingham risk score (FRS). Results The sarcopenic obese group had a higher FRS than the non-sarcopenic obese group, which had a higher FRS than the non-sarcopenic non-obese group. Age-wise, the 20–39 year-old group showed a non-significant association between sarcopenia and FRS. In the 40–59 year-old group, regardless of obesity status, sarcopenic subjects had a higher FRS than non-sarcopenic subjects. In the ≥ 60 year-old group, sarcopenic subjects had a higher FRS than non-sarcopenic subjects for the non-obese group. Conclusions Sarcopenia was associated with cardiovascular disease and may be an early predictor of its susceptibility in both elderly and middle-aged subjects. Thus, management of sarcopenia is necessary to prevent cardiovascular disease.
Objective To evaluate the epicardial fat tissue thickness (EFTT) as a diagnostic criterion for geriatric patients with metabolic syndrome (MetS). Methods Sixty geriatric patients over 65 years of age were recruited for the study. Patients were divided into two groups: Group 1 (n = 30) consisted of patients with MetS; Group 2 (n = 30) consisted of patients without MetS. Echocardiography was used to measure EFTT in all patients, and blood samples were analyzed for biochemical parameters. Results Compared to Group 2, EFTT levels of Group 1 were statistically higher (P P Conclusions The present study demonstrated that serum EFTT levels were higher in geriatric patients with MetS and can therefore be used as a diagnostic criterion for MetS.
Background Despite the proven benefits of clopidogrel combined aspirin therapy for coronary artery disease (CAD), CAD patients with metabolic syndrome (MS) still tend to have coronary thrombotic events. We aimed to investigate the influence of metabolic risk factors on the efficacy of clopidogrel treatment in patients with CAD undergoing percutaneous coronary intervention (PCI). Methods Cohorts of 168 MS and 168 non-MS subjects with CAD identified by coronary angiography (CAG) were enrolled in our study. MS was defined by modified Adult Treatment Panel III criteria. All subjects had taken 100 mg aspirin and 75 mg clopidogrel daily for more than 1 month, and administered loading doses of 600 mg clopidogrel and 300 mg aspirin before PCI. Blood samples were taken 24 h after the loading doses of clopidogrel and aspirin. Platelet aggregation was measured using light transmittance aggregometry (LTA) and thrombelastography (TEG). Clopidogrel resistance was defined as more than 50% adenosine diphosphate (ADP) induced platelet aggregation as measured by TEG. Results Platelet aggregation inhibition rate by ADP was significantly lower in patients with MS as measured both by TEG (55% ± 31% vs. 68% ± 32%; P vs. 42% ± 29%; P P = 0.002], obesity [OR (95% CI): 3.608 (1.241–10.488); P = 0.018], high fasting plasma glucose level [OR (95% CI): 2.717 (1.176–6.277); P = 0.019] and hyperuricemia [OR (95% CI): 2.583 (1.095–6.094); P = 0.030] were all statistically risk factors for clopidogrel resistance. CAD patients with diabetes and obesity were more likely to have clopidogrel resistance than the CAD patients without diabetes and obesity [75% (61/81) vs. 43% (67/156); P Conclusions CAD patients with MS appeared to have poorer antiplatelet response to clopidogrel compared to those without MS. Obesity, diabetes and hyperuricemia were all significantly associated with clopidogrel resistance.
Objective To assess the prevalence of the bleeding complications in pacemaker implanted patients receiving different antiplatelet regimens, and the influence of each regimen on hospital stays after device implantation. Methods We prospectively enrolled 364 patients receiving the cardiac rhythm device implantations in Fuwai Hospital from July 2012 to December 2013. Bleeding complications including pocket hematoma, hemothorax, cardiac tamponade and blood transfusion requirement were measured as endpoints. Post operation hospital stay was also included in the endpoints. Results Bleeding complications were detected in 15 patients (14 with hematoma, one with hemothorax) out of all 364 patients (4.12%). Dual antiplatelet therapy (DAT) significantly increased hematoma (19.3%) compared with aspirin treatment (ASA) (3.2%, P = 0.001) and no antiplatelet therapy (1.9%, P P = 0.45). The post procedure hospital stay was longer in DAT group (5.45 ± 2.01 days) compared to those in the ASA group (3.65 ± 1.37 days, P P P = 0.007). Conclusions Among the Chinese patients undergoing device implantation in this study, the use of dual antiplatelet agents significantly increased the risk of pocket hematoma complications and led to a longer hospital stay. Use of aspirin alone did not increase the risk.
Background Cilostazol, an anti-platelet drug for treating coronary heart disease, has been reported to modulate immune cell functions. Plasmacytoid dendritic cells (pDCs) have been found to participate in the progression of atherosclerosis mainly through interferon α (IFN-α) production. Whether cilostazol influences pDCs activation is still not clear. In this study, we aimed to investigate the effects of cilostazol on cell activation and antigen presentation of pDCs in vitro in this study. Methods Peripheral blood mononuclear cells isolated by Ficoll centrifugation and pDCs sorted by flow cytometry were used in this study. After pretreated with cilostazol for 2 h, cells were stimulated with CpG-A, R848 or virus for 6 h or 20 h, or stimulated with CpG-B for 48 h and then co-cultured with na?ve T cell for five days. Cytokines in supernatant and intracellular cytokines were analyzed by ELISA or flow cytometry respectively. Results Our data indicated that cilostazol could inhibit IFN-α and tumor necrosis factor α (TNF-α) production from pDCs in a dose-dependent manner. In addition, the ability of priming na?ve T cells of pDCs was also impaired by cilostazol. The inhibitory effect was not due to cell killing since the viability of pDCs did not change upon cilostazol treatment. Conclusion Cilostazol inhibits pDCs cell activation and antigen presentation in vitro, which may explain how cilostazol protects against atherosclerosis.
Objectives To evaluate the association between a KCNQ1 mutation, R259H, and short QT syndrome (SQTS) and to explore the electrophysiological mechanisms underlying their association. Methods We performed genetic screening of SQTS genes in 25 probands and their family members (63 patients). We used direct sequencing to screen the exons and intron-exon boundaries of candidate genes that encode ion channels that contribute to the repolarization of the ventricular action potential, including KCNQ1, KCNH2, KCNE1, KCNE2, KCNJ2, CACNA1c, CACNB2b and CACNA2D1. In one of the 25 SQTS probands screened, we discovered a KCNQ1 mutation, R259H. We cloned R259H and transiently expressed it in HEK-293 cells; then, currents were recorded using whole cell patch clamp techniques. Results R259H-KCNQ1 showed significantly increased current density, which was approximately 3-fold larger than that of wild type (WT) after a depolarizing pulse at 1 s. The steady state voltage dependence of the activation and inactivation did not show significant differences between the WT and R259H mutation (P > 0.05), whereas the time constant of deactivation was markedly prolonged in the mutant compared with the WT in terms of the test potentials, which indicated that the deactivation of R259H was markedly slower than that of the WT. These results suggested that the R259H mutation can effectively increase the slowly activated delayed rectifier potassium current (IKs) in phase 3 of the cardiac action potential, which may be an infrequent cause of QT interval shortening. Conclusions R259H is a gain-of-function mutation of the KCNQ1 channel that is responsible for SQTS2. This is the first time that the R259H mutation was detected in Chinese people for the first time.
Background There is a paucity of data about the best lipid ratio predicting the severity of coronary artery disease (CAD) in patients with diabetes mellitus. We determined the relationship between five conventional lipid ratios and the extent of coronary artery lesions in Chinese Type 2 diabetics with stable angina pectoris (SAP). Methods A prospective cohort study within 373 Type 2 diabetic patients diagnosed with stable CAD by coronary angiography was performed. All patients were classified into three groups according to the tertiles of Gensini scores (GS, low group n = 143; intermediate group 8–28 points, n = 109; high group > 28 points, n = 121). Association between the ratios of apolipoprotein (apo) B and apoA-1, total cholesterol and high density lipoprotein cholesterol (TC/HDL-C), triglycerides and HDL-C (TG/HDL-C), low density lipoprotein cholesterol and HDL-C (LDL-C/HDL-C), Non-HDL-C/HDL-C and GS were evaluated using the receivers operating characteristic (ROC) curves and multivariate logistic regression models. Results The ratio of apoB/apoA-1, TC/HDL-C, LDL-C/HDL-C, and Non-HDL-C/HDL-C were correlated with Gensini scores. Area under the ROC curves for predicting high Gensini scores in the ratios of apoB/apoA-1, TC/HDL-C, LDL-C/HDL-C and Non-HDL-C/HDL-C were 0.62, 0.60, 0.59 and 0.60, respectively (P Conclusion Compared with other lipid parameters, the ratio of apoB/apoA-1 appears to be more significantly correlated with the extent of coronary artery lesions in Chinese diabetics, but it was not an independent predictor in these settings.
Backgound Recent studies have suggested a potential role for liraglutide in the prevention and stabilization of atherosclerotic vascular disease. However, the molecular mechanisms underlying the effect of liraglutide on atherosclerosis have not been well elucidated. The purpose of this study was to examine whether liraglutide protects against oxidative stress and fatty degeneration via modulation of AMP-activated protein kinase (AMPK)/sterol regulatory element binding transcription factor 1 (SREBP1) signaling pathway in foam cells. Methods Mouse macrophages Raw264.7 cells were exposed to oxidized low density lipoprotein (oxLDL) to induce the formation of foam cells. The cells were incubated with oxLDL (50 μg/mL), liraglutide (0.1, 0.5, 1 and 2 nmol/L) or exendin-3 (9-39) (1, 10 and 100 nmol/L) alone, or in combination. Oil Red O staining was used to detect intracellular lipid droplets. The levels of TG and cholesterol were measured using the commercial kits. Oxidative stress was determined by measuring intracellular reactive oxygen species (ROS), malondialdehyde (MDA) and superoxide dismutase 1 (SOD). Western blot analysis was used to examine the expression of AMPKα1, SREBP1, phosphorylated AMPKα1, phosphorylated SREBP1, glucagon-like peptide-1 (GLP-1) and GLP-1 receptor (GLP-1R). Results Oil Red O staining showed that the cytoplasmic lipid droplet accumulation was visibly decreased in foam cells by treatment with liraglutide. The TG and cholesterol content in the liraglutide-treated foam cells was significantly decreased. In addition, foam cells manifested an impaired oxidative stress following liraglutide treatment, as evidenced by increased SOD, and decreased ROS and MDA. However, these effects of liraglutide on foam cells were attenuated by the use of GLP-1R antagonist exendin-3 (9-39). Furthermore, we found that the expression level of AMPKα1 and phosphorylated AMPKα1 was significantly increased while the expression level of SREBP1 and phosphorylated SREBP1 was significantly decreased in foam cells following treatment with liraglutide. Conclusions This study for the first time demonstrated that the effect of liraglutide on reducing oxidative stress and fatty degeneration in oxLDL-induced Raw264.7 cells is accompanied by the alteration of AMPK/SREBP1 pathway. This study provided a potential molecular mechanism for the effect of liraglutide on reducing oxidative stress and fatty degeneration.
Background Atherosclerotic plaques indicate the occurrence of ischemia events and it is a difficult task for clinical physicians. Grape seed proanthocyanidin extract (GSPE) has been reported to exert an antiatherogenic effect by inducing regression of atherosclerotic plaques in animal experimental studies. In this study, the antiatherogenic effect of GSPE has been investigated in clinical use. Methods Consecutive 287 patients diagnosed with asymptomatic carotid plaques or abnormal plaque free carotid intima-media thickness (CIMT) were randomly assigned to the GSPE group (n = 146) or control group (n = 141). The patients in the GSPE group received GSPE 200 mg per day orally, while patients in the control group were only enrolled in a lifestyle intervention program. Carotid ultrasound examination was performed at baseline and 6, 12, 24 months during follow-up. Mean maximum CIMT (MMCIMT), plaque score, echogenicity of plaques and ischemic vascular events were recorded. Results As anticipated, after treatment, GSPE resulted in significant reduction in MMCIMT progression (4.2% decrease after six months, 4.9% decrease after 12 months and 5.8% decrease after 24 months) and plaque score (10.9% decrease after six months, 24.1% decrease after 12 months and 33.1% decrease after 24 months) for the primary outcome, while MMCIMT and plaque score were stable and even increased with the time going on in control group. The number of plaques and unstable plaques also decreased after treatment of GSPE. Furthermore, the carotid plaque can disappear after treatment with GSPE. The incidence rate for transitory ischemic attack (TIA), arterial revascularization procedure, and hospital readmission for unstable angina in GSPE group were statistically significant lower (P = 0.02, 0.08, 0.002, respectively) compared with the control group. Conclusions GSPE inhibited the progression of MMCIMT and reduced carotid plaque size in GSPE treated patients, and with extended treatment, the superior efficacy on MMCIMT and carotid plaque occurred. Furthermore, the GSPE group showed lower rates of clinical vascular events.
Background Sleep-disordered breathing (SDB) is known to occur frequently in and may predict worsening progression of patients with congestive heart failure (CHF). SDB is also known to play an important role in the development of idiopathic pulmonary arterial hyperten?sion (PAH) via inducing endothelial dysfunction and vascular remodeling, a pathological process that can be significantly influenced by factors such as osteoprotegerin (OPG) and endothelial progenitor cells (EPCs). The objective of this study is to determine if CHF with SDB is associated with changes in OPG, EPCs, and PAH. Methods EPCs were isolated, cultured, and quantified from CHF patients with SDB (n = 52), or without SDB (n = 68). OPG and N-terminal pro-brain natriuretic peptide (NT-proBNP) from each group was analyzed and correlated with EPCs and the mean pulmonary artery pressure (mPAP) measured by right heart catheterization. Results A significant decrease in circulating EPCs (29.30 ± 9.01 vs. 45.17 ± 10.51 EPCs/× 200 field; P vs. 551.29 ± 42.12 pg/mL; P vs. 3028.60 ± 811.90 ng/mL; P vs. 36.4 ± 4.1 mm Hg; P P = 0.037) and blood level of OPG (r = –0.53, P = 0.011). Although NT-proBNP was also increased significantly in patients with SDB, it had no correlation with either EPCs or RDI. Conclusions SDB due to hypoxemia from decompensated CHF is associated with (1) OPG elevation, (2) EPC depletion, and (3) mPAP elevation. The inverse relationship of circulating OPG with EPCs suggests a likely mechanism for hypoxemia and OPG in the development of pulmonary vascular dysfunction via depleting EPCs, thus worsening prognosis of CHF.
The elderly population is increasing worldwide, with subjects > 65 years of age constituting the fastest-growing age group. Furthermore, the elderly face the greatest risk and burden of cardiovascular disease mortality and morbidity. Although elderly patients, particularly those older > 75, have not been well represented in randomized clinical trials evaluating lipid-lowering therapy, the available evidence supporting the use of statin therapy in primary prevention in older individuals is derived mainly from subgroup analyses and post-hoc data. On the other hand, elderly patients often have multiple co-morbidities that require a high number of concurrent medications; this may increase the risk for drug-drug interactions, thereby reducing the potential benefits of statin therapy. The aim of this review was to present the relevant literature regarding statin use in the elderly for their primary cardiovascular disease, with the associated risks and benefits of treatment.
The klotho gene has been identified as an aging suppressor that encodes a protein involved in cardiovascular disease (CVD). The inactivation of the klotho gene causes serious systemic disorders resembling human aging, such as atherosclerosis, diffuse vascular calcification and shortened life span. Klotho has been demonstrated to ameliorate vascular endothelial dysfunction and delay vascular calcification. Furthermore, klotho gene polymorphisms in the human are associated with various cardiovascular events. Recent experiments show that klotho may reduce transient receptor potential canonical6 (TRPC6) channels, resulting in protecting the heart from hypertrophy and systolic dysfunction. Fibroblast growth factor23 (FGF23) is a bone-derived hormone that plays an important role in the regulation of phosphate and vitamin D metabolism. FGF23 accelerates urinary phosphate excretion and suppresses 1,25-dihydroxy vitaminD3 (1,25(OH)2D3) synthesis in the presence of FGF receptor1 (FGFR1) and its co-receptor klotho, principally in the kidney. The hormonal affects of circulating klotho protein and FGF23 on vascular and heart have contributed to an understanding of their roles in the pathophysiology of arterial stiffness and left ventricular hypertrophy. Klotho and FGF23 appear to play a critical role in the pathogenesis of vascular disease, and may represent a novel potential therapeutic strategy for clinical intervention.
The electrocardiogram (ECG) has broad applications in clinical diagnosis and prognosis of cardiovascular disease. Many researchers have contributed to its progressive development. To commemorate those pioneers, and to better study and promote the use of ECG, we reviewed and present here a systematic introduction about the history, hotspots, and trends of ECG. In the historical part, information including the invention, improvement, and extensive applications of ECG, such as in long QT syndrome (LQTS), angina, and myocardial infarction (MI), are chronologically presented. New technologies and applications from the 1990s are also introduced. In the second part, we use the bibliometric analysis method to analyze the hotspots in the field of ECG-related research. By using total citations and year-specific total citations as our main criteria, four key hotspots in ECG-related research were identified from 11 articles, including atrial fibrillation, LQTS, angina and MI, and heart rate variability. Recent studies in those four areas are also reported. In the final part, we discuss the future trends concerning ECG-related research. The authors believe that improvement of the ECG instrumentation, big data mining for ECG, and the accuracy of diagnosis and application will be areas of continuous concern.