2012 Vol. 9, No. 3
Managing patients with heart failure (HF) is a challenging task within itself, but the presence of associated worsening renal function can greatly increase mortality and morbidity. Early diagnosis and treatment is key to prevent re-hospitalizations and reduce healthcare costs. Biomarkers have long been established as highly sensitive and specific tools in diagnosing and prognosticating patients with HF. Reflecting distinct pathophysiological events and ongoing cellular insult, biomarkers have proven to be superior to conventional laboratory tests. Availability of better assays and rapid analysis has allowed the use of biomarkers as point-of-care tests in the emergency department and at the patient’s bed-side. Acute HF patients often go on to develop worsening renal function, termed as acute cardiorenal syndrome. The growing breadth of studies has shown the implications of combining multiple biomarkers to better chart outcomes and produce desirable results in such patients.
Objectives This study examined the protective effect of salubrinal and the mechanism underlying this protection on tunicamycin (TM)- and hypoxia-induced apoptosis in rat cardiomyocytes. Methods Neonatal rat cardiomyocytes were cultured from the ventricles of 1-day-old Wistar rats. Cells were exposed to different concentrations of salubrinal (10, 20, and 40 μmol/L) for 30 minutes followed by TM treatment or hypoxia for 36 hours. Apoptosis was measured by a multiparameter HCS (high content screening) apoptosis assay, TUNEL assay and flow cytometry. The phosphorylation of eukaryotic translation initiation factor 2 subunit alpha (p-eIF2α) and the expression of cleaved caspase-12 were determined by western blotting. C/EBP homologous protein (CHOP) was detected by immunocytochemistry. Results HCS, TUNEL assays and flow cytometry showed that salubrinal protected against apoptosis induced by TM or hypoxia. Western blotting showed that salubrinal protected cardiomyocytes against apoptosis by inducing eIF2α phosphorylation and down-regulating the expression of the endoplasmic reticulum stress-mediated apoptotic proteins, CHOP and cleaved caspase-12. Conclusions Our study suggests that salubrinal protects rat cardiomyocytes against TM- or hypoxia-associated apoptosis via a mechanism involving the inhibition of ER stress-mediated apoptosis.
Objectives To assess the regional diastolic function in patients with hypertrophic cardiomyopathy (HCM) by using single-beat, real-time, three-dimensional echocardiography (RT-3DE). Methods Sixty-five patients with HCM in sinus rhythm together with fifty age- and gender-matched normal controls were studied by two–dimensional echocardiography (2DE) and RT-3DE. The parameters analyzed by RT-3DE included: left ventricular (LV) volumes, left ventricular ejection fraction (LVEF), end diastolic sphericity index (EDSI), diastolic dyssynchrony index (DDI), dispersion end diastole (DISPED), and normalized 17 segmental volume-time curves. Results LVEF was slightly lower evaluated by RT-3DE compared with 2DE (63.2 ± 6.8% vs. 59.1 ± 6.4%, P P Conclusions Patients with HCM have presented regional diastolic dyssynchrony in the diastole phase, and this preclinical lesion can be recognized by single-beat RT-3DE.
A recent explosion in the amount of cardiovascular risk has swept across the globe. Primary prevention is the preferred method to lower cardiovascular risk. Lowering the prevalence of obesity is the most urgent matter, and is pleiotropic since it affects blood pressure, lipid profiles, glucose metabolism, inflammation, and atherothrombotic disease progression. Given the current obstacles, success of primary prevention remains uncertain. At the same time, the consequences of delay and inaction will inevitably be disastrous, and the sense of urgency mounts. Pathological and epidemiological data confirm that atherosclerosis begins in early childhood, and advances seamlessly and inexorably throughout life. Risk factors in childhood are similar to those in adults, and track between stages of life. When indicated, aggressive treatment should begin at the earliest indication, and be continued for many years. For those patients at intermediate risk according to global risk scores, C-reactive protein, coronary artery calcium, and carotid intima-media thickness are available for further stratification. Using statins for primary prevention is recommended by guidelines, is prevalent, but remains under prescribed. Statin drugs are unrivaled, evidence-based, major weapons to lower cardiovascular risk. Even when low density lipoprotein cholesterol (LDL-C) targets are attained, over half of patients continue to have disease progression and clinical events. Though clinical evidence is incomplete, altering or raising the blood high density lipoprotein cholesterol (HDL-C) level continues to be pursued. The aim of this review is to point out the attention of key aspects of vulnerable plaques regarding their pathogenesis and treatment.
Objectives Although development of new treatment modalities limited digoxin usage, digoxin intoxication is still an important issue which could be easily overlooked. In this report we analyzed a case series definitively diagnosed as digoxin intoxication in the modern era. Methods We analyzed 71 patients hospitalized with digoxin intoxication confirmed by history, complaints, clinical and electrocardiograph (ECG) findings, and serum digoxin levels > 2.0 ng/mL, during a five year period. The demographic and clinical data, indications for digoxin use, digoxin dosage, concurrent medications, laboratory data, hospital monitoring, and ECG findings were obtained from all patients. Results Thirty-eight of 71 patients (53.5%) had symptoms of heart failure during admission or later. Sixty-four percent of patients were older than 75 years. The percentage of females was 67%. Atrial fibrillation, hypertension and gastrointestinal complaints were more frequent in the females (64% in females, 30% in males, P = 0.007; 81% in female, 52% in males, P = 0.01; 50% in female, 17.3% in males, P = 0.008, respectively). The mortality rate during the hospital course was 7%. Conclusion This report demonstrated the reduced mortality rates in patients with digoxin intoxication over the study period. Gastrointestinal complaints are the most common symptoms in this population.
Objectives To evaluate the outcome of off-pump coronary artery bypass grafting (OPCABG) using a bilateral internal mammary artery (BIMA) Y configuration graft to achieve total arterial myocardial revascularization. Methods From October 2002 to December 2008, 208 patients (196 males and 12 females) underwent OPCABG using a BIMA Y configuration graft. The average age of the patients was 56.5 ± 11.3 years, with an age range of 33–78 years. A total of 167 (80.2%) cases had triple-vessel disease. Left main stem disease was found in 33 (15.9%) cases, and double-vessel disease was found in 8 (3.9%) cases. The semi-skeletonization technique was used to harvest the two internal mammary arteries (IMAs), and then the free right internal mammary artery was connected end-to-side to the left internal mammary artery (LIMA) in situ to complete the Y configuration graft. Off-pump and sequential anastomosis methods were used to perform coronary artery bypass surgery in all patients. Graft patency was assessed intra-operatively with the HT311 transit time flowmeter. Results A total of 728 distal anastomoses were performed in 208 patients, with the average being 3.5 ± 1.3 per person. No one died or experienced recurrent angina within 30 days after the operation. Conclusions OPCABG using the BIMA Y graft was safe and effective to achieve total arterial revascularization. This method avoids surgical operation on the ascending aorta and other incisions.
Percutaneous coronary intervention (PCI) for coronary bifurcation lesions has been associated with lower procedural success rates and worse clinical outcomes compared with PCI for simple coronary lesions. Angiographic evaluation alone is sometimes inaccurate and does not reflect the functional significance of bifurcation lesions. The fractional flow reserve (FFR) is an easily obtainable, reliable, and reproducible physiologic parameter. This parameter is epicardial lesion specific and reflects both degree of stenosis and the myocardial territory supplied by the specific artery. Recent studies have shown that FFR-guided provisional side branch intervention strategy for bifurcation lesions is feasible and effective and can reduce unnecessary complex interventions and related complications. However, an adequate understanding of coronary physiology and the pitfalls of FFR is essential to properly use FFR for PCI of complex bifurcation lesions.
Abdominal aortic aneurysm (AAA) is a relatively common pathology among the elderly. More people above the age of 80 will have to undergo treatment of an AAA in the future. This review aims to summarize the literature focusing on endovascular repair of AAA in the geriatric population. A systematic review of the literature was performed, including results from endovascular abdominal aortic aneurysm repair (EVAR) registries and studies comparing open repair and EVAR in those above the age of 80. A total of 15 studies were identified. EVAR in this population is efficient with a success rate exceeding 90% in all cases, and safe, with early mortality and morbidity being superior among patients undergoing EVAR against open repair. Late survival can be as high as 95% after 5 years. Aneurysm-related death over long-term follow-up was low after EVAR, ranging from 0 to 3.4%. Endovascular repair can be offered safely in the geriatric population and seems to compare favourably with open repair in all studies in the literature to date.
An 82-year-old female patient undergoing cardiogenic shock caused by atrioventricular junctional rhythm immediately after percutaneous coronary intervention (PCI) is described. Pharmacotherapy was invalid, and subsequent application of atrial pacing reversed the cardiogenic shock. PCI-related injury of sinuatrial nodal artery leading to acute atrial contractility loss, accompanied by atrioventricular junctional arrhythmia, was diagnosed. We recommend that preoperative risk evaluation be required for multi-risk patients. Likewise, emergent measures should to be established in advance. This case reminds us that atrial pacing can be an optimal management technique once cardiogenic shock has occurred.
Background The diagnosis of metabolic syndrome indicates a clustering of metabolic imbalances which in sum have been recognized as a major predictor of cardiovascular and all-cause mortality. The aim of this study was to assess the level of under-pharmacy and poly-pharmacy and its prognostic impact in elderly patients with metabolic syndrome. Methods Retrospective chart-review at a tertiary medical center, of 324 patients greater than 65 years of age who met the International Diabetes Foundation criteria for metabolic syndrome diagnosis [Body Mass Index (BMI) > 30 kg/m2, diagnosis of type 2 diabetes, hypertension, and dyslipidemia]. Results There were 60 (18.5%) patients in the low (≤ 5) medication burden group, 159 (49.1%) in the medium (> 5 and ≤ 10) medication burden group, and 105 (32.4%) in the high (> 10) medication burden group. At baseline, the groups differed only by systolic blood pressure. At two years follow-up, the medium group had significantly better improvement in high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), HbA1c, and systolic blood pressure compared to the low medication burden group and significantly better improvement in triglycerides, Haemoglobin A1c (HbA1c) and systolic blood pressure compared to the high medication group. Decrease in HDL-C was the only variable associated with strokes. High medication burden predicted hospitalization burden. The number of anti-hypertensives, history of tobacco use, low and high medication burdens and decrease in HDL-C were all associated with death. Conclusions Both poly-pharmacy and under-pharmacy are associated with a decreased therapeutic benefit among patients with metabolic syndrome in terms of important laboratory measurements as well as clinical outcomes such as myocardial infarctions, hospitalization, and death.
Objectives To evaluate the plasma atherosclerotic biomarkers in patients with type 2 diabetes mellitus (T2DM) and arteriosclerosis obliteran (ASO) when treated with Probucol plus Cilostazol in combination and individually. Methods In this open-label study, patients aged 40–75 years were randomized to receive conventional therapy alone, or with Cilostazol 100 mg bid, or with Probucol 250 mg bid, or with both in combination. Endpoints included changes in plasma biomarker and safety at 12 weeks. Results Of the 200 randomized pati?ents, 165 for per-protocol and 160 for the safety (QTc intervals) were set, respectively. Probucol significantly reduced total cholesterol (P P = 0.01), and high-density lipoprotein cholesterol (HDL-C) (P P = 0.002) and reducing triglycerides levels (P P = 0.065). No significant effects on the majority of the remaining biomarkers were found across the treatment groups. Conclusions We have confirmed that Ox-LDL could be a possible plasma atherosclerotic biomarker among the evaluated biomarkers, which reflected the synergetic effect of Cilostazol plus Probucol in patients with T2DM and ASO shown previously in preclinical studies.
Objectives To assess the safety of a cardiac rehabilitation program for older women with Congestive Heart Failure (CHF) and determine if certain factors influence adherence. Methods Women over the age of 65 with CHF attended an exercise program supervised by a physiotherapist. Quality of life was measured by the Minnesota Living with Heart Failure Questionnaire (MLHFQ) and severity of disease by the New York Heart Association (NYHA) Class. Subjects were classified into those who attended 90% or more of the sessions and those who attended less than 90% of the sessions. Results Fifty-one subjects were studied. Eight subjects did not attend any sessions. Of the 43 attendees, the average percentage of sessions attended was 87%. There were no significant differences between the two groups in age, MLHFQ or NYHA Class. There was only one adverse event out of 280 participant attendances. Conclusions The program had a high level of adherence in this population. Age, MLHFQ or NYHA Class did not impact on session attendance. Our data suggests this program is safe for this population. Further research is needed to determine other predictors of attendance and the examination of safety issues and long-term adherence to exercise in this population.
Background Although angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) are equally important in the treatment of hypertension, there is less evidence whether they have equal cardiovascular and cerebrovascular protective effects, especially in elder hypertensive patients. This study aims to clarify this unresolved issue. Methods This cross-sectional study included clinical data on 933 aged male patients with hypertension who received either an ARB or ACEI for more than two months between January 2007 and May 2011. The primary outcome was the composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. The secondary endpoints were unstable angina, new atrial fibrillation, and transient ischemic attack. Results The median follow-up time was 24 months. Age, drug types, cerebral infarction history, renal dysfunction history were the independent predictors of the primary endpoint. The risk of an occurrence of a primary endpoint event was higher in the ARB group than the ACEI group [P = 0.037, hazard ratios (HR): 2.124, 95% confidence interval (95% CI): 1.048–4.306]. The Kaplan-Meier method also suggests that the rate of primary endpoint occurrence was higher in the ARB group than the ACEI group (P = 0.04). In regard to the secondary endpoints, there were no significant differences between the two treatment arms (P = 0.137, HR: 1.454，95% CI: 0.888–2.380). Patient age and coronary heart disease history were independent predictors of the secondary endpoint. Conclusion ACEI were more effective than ARB in reducing cardiovascular and cerebrovascular morbidity and mortality in aged patients with hypertension.
Background Previous studies showed that overexpression of sarco-endoplasmic reticulum calcium ATPase (SERCA2a) in a variety of heart failure (HF) models was associated with greatly enhanced cardiac performance. However, it still undefined the effect of SERCA2a overexpression on the systemic inflammatory response and neuro-hormonal factors. Methods A rapid right ventricular pacing model of experimental HF was used in beagles. Then the animals underwent recombinant adeno-associated virus 1 (rAAV1) mediated gene transfection by direct intra-myocardium injection. HF animals were randomized to receive the SERCA2a gene, enhanced green fluorescent protein (control) gene, or equivalent phosphate buffered saline. Thirty days after gene delivery, the cardiac function was evaluated by echocardiographic testing. The protein level of SERCA2a was measured by western blotting. The proteomic analysis of left ventricular (LV) sample was determined using two-dimensional (2-D) gel electrophoresis and MALDI-TOF-MS. The serum levels of the systemic inflammatory and neuro-hormonal factors were assayed using radioimmunoassay kits. Results The cardiac function improved after SERCA- 2a gene transfer due to the significantly increased SERCA2a protein level. Beagles treated with SERCA2a had significantly decreased serum levels of the inflammatory markers (interleukin-6 and tumor necrosis factor-α) and neuro-hormonal factors (brain natriuretic peptide, endothelin-1 and angiotensin Ⅱ) compared with HF animals. The myocardial proteomic analysis showed that haptoglobin heavy chain, heat shock protein (alpha-crystallin-related, B6) were down-regulated, and galectin-1 was up-regulated in SERCA2a group compared with HF group, companied by up-regulated contractile proteins and NADH dehydrogenase. Conclusions These findings demonstrate that regional intramyocardial injections of rAAV1-SERCA2a vectors may improve global LV function, correlating with reverse activation of the systemic inflammatory, excessive neuroendocrine factors and the stress-associated myocardial proteins, suggesting that the beneficial effects of SERCA2a gene transfer may involve the attenuation of stress-associated reaction.