|Year : 2005 | Volume
| Issue : 1 | Page : 1-4
|Date of Web Publication||18-Jun-2010|
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
. Cardiovascular News. Heart Views 2005;6:1-4
Stem Cell Tissue Engineered Heart Valves: Dawn of a New Era?
An estimated 275,000 patients undergo heart valve replacement each year. However, existing solutions for valve replacement are complicated by the morbidity associated with lifelong anticoagulation of mechanical valves and the limited durability of bioprostheses. Recent advances in tissue engineering and our understanding of stem cell biology may provide a lifelong solution to these problems.
Mesenchymal stem cells were isolated from ovine bone marrow and characterized by their morphology and antigen expression through immunocytochemistry, flow cytometry, and capacity to differentiate into multiple cell lineages. A biodegradable scaffold was developed and characterized by its tensile strength and stiffness as a function of time in cell-conditioned medium. Autologous semilunar heart valves were then created in vitro using mesenchymal stem cells and the biodegradable scaffold and were implanted into the pulmonary position of sheep on cardiopulmonary bypass.
The valves were evaluated by echocardiography at implantation and after 4 months in vivo. Valves were explanted at 4 and 8 months and examined by histology and immunohistochemistry. Valves displayed a maximum instantaneous gradient of 17.2 - 1.33 mm Hg, a mean gradient of 9.7 - 1.3 mm Hg, an effective orifice area of 1.35 - 0.17 cm2, and trivial or mild regurgitation at implantation. Gradients changed little over 4 months of follow-up. Histology showed disposition of extracellular matrix and distribution of cell phenotypes in the engineered valves reminiscent of that in native pulmonary valves.
Stem-cell tissue-engineered heart valves can be created from mesenchymal stem cells in combination with a biodegradable scaffold and function satisfactorily in vivo for periods of > 4 months. Furthermore, such valves undergo extensive remodeling in vivo to resemble native heart valves.
CABG Associated with Higher Long-Term Survival Than Stenting for Patients with Two or More Diseased Coronary Arteries
Several studies have compared outcomes for coronary-artery bypass grafting (CABG) and percutaneous coronary intervention (PCI), but most were done before the availability of stenting, which has revolutionized the latter approach.
Researchers used New York's cardiac registries to identify 37,212 patients with multivessel disease who underwent CABG and 22,102 patients with multivessel disease who underwent PCI from January 1, 1997, to December 31, 2000. We determined the rates of death and subsequent revascularization within three years after the procedure in various groups of patients according to the number of diseased vessels and the presence or absence of involvement of the left anterior descending coronary artery. The rates of adverse outcomes were adjusted by means of proportional-hazards methods to account for differences in patients' severity of illness before revascularization.
Risk-adjusted survival rates were significantly higher among patients who underwent CABG than among those who received a stent in all of the anatomical subgroups studied. For example, the adjusted hazard ratio for the long-term risk of death after CABG relative to stent implantation was 0.64 (95 percent confidence interval, 0.56 to 0.74) for patients with three-vessel disease with involvement of the proximal left anterior descending coronary artery and 0.76 (95 percent confidence interval, 0.60 to 0.96) for patients with two-vessel disease with involvement of the nonproximal left anterior descending coronary artery. Also, the three-year rates of revascularization were considerably higher in the stenting group than in the CABG group (7.8 percent vs. 0.3 percent for subsequent CABG and 27.3 percent vs. 4.6 percent for subsequent PCI).
For patients with two or more diseased coronary arteries, CABG is associated with higher adjusted rates of long-term survival than stenting.
600-mg Clopidogrel Loading Dose Reduces Non-Responsiveness and Post-Treatment Platelet Aggregation in Patients Undergoing Coronary Stenting
Nonresponsiveness (NR) to clopidogrel has been reported after a 300-mg loading dose, hence, the relation of clopidogrel dose, the incidence of NR, and high post-treatment platelet aggregation (PA) in patients undergoing coronary stenting was studied.
Clopidogrel responsiveness and post-PA were measured in patients undergoing stenting (n = 190) randomly treated with either a 300-mg or a 600-mg clopidogrel load. Non-responsiveness was defined as <10% absolute change in platelet aggregation, and high post-PA was defined as >75th percentile aggregation after 300 mg clopidogrel.
Nonresponsiveness was lower after 600 mg compared to the 300-mg dose (8% vs. 28% and 8% vs. 32% with 5 and 20 ΅M ADP, respectively, p < 0.001). Among the patients with high post-PA after 300 mg clopidogrel, 62% to 65% had NR, whereas after the 600-mg dose, all of the patients with high post-PA had NR.
The study concluded that a 600-mg clopidogrel loading dose reduces the incidence of NR and high post-PA as compared to a 300-mg dose. Investigators suggest higher dosing strategies and methods to confirm platelet inhibition should be further investigated in order to optimally use clopidogrel in patients undergoing stenting.
Efficacy of Atorvastatin 80 mg and Pravastatin LDL 40 mg in reducing Cholesterol <70 mg/dl and C-Reactive Protein <2 mg/L
While secondary prevention guidelines for statin therapy suggest lowering LDL-C levels <70 mg/dl, it has been shown that clinical outcomes are improved when CRP levels are also lowered <2 mg/l. Therefore, a study was undertaken to compare the relative efficacy of different statin regimens in achieving the dual goals of low-density lipoprotein cholesterol (LDL-C) and C-reactive protein (CRP) reduction.
The relative efficacy of pravastatin 40 mg and atorvastatin 80 mg daily to reduce LDL-C and CRP among 3,745 acute coronary syndrome patients was analyzed. A total of 1,018 participants (27.1%) achieved the dual goals of LDL-C <70 mg/dl and CRP <2 mg/l. After adjustment for age, gender, smoking, diabetes, hypertension, obesity, and HDL-C, these individuals had a 28% lower risk of recurrent myocardial infarction or vascular death (relative risk = 0.72; 95% confidence interval 0.52 to 0.99). Of those who achieved dual goals, 80.6% received atorvastatin 80 mg, while 19.4% received pravastatin 40 mg (p < 0.001). Only 11% allocated pravastatin and 44% allocated atorvastatin achieved the goals of LDL-C <70 mg/dl and CRP <2 mg/l, and only 5.8% allocated pravastatin 40 mg and 26.1% allocated atorvastatin 80 mg reached the even lower goals of LDL-C <70 mg/dl and CRP <1 mg/l. The correlation coefficient for CRP measured at 30 days and at end of study was 0.61 (p < 0.001), a value almost identical to that for LDL-C over the same follow-up period (r = 0.62, p < 0.001).
While atorvastatin 80 mg was superior to pravastatin 40 mg in terms of achieving the dual goals of aggressive LDL-C and CRP reduction, neither agent brought the majority of patients below thresholds needed to maximize patient benefit.
Beneficial effects of exercise maybe due to "anti-inflammatory effect"
Physical activity is associated with a reduced incidence of coronary disease, but the mechanisms mediating this effect are not defined. There has been considerable recent interest in inflammation in the pathogenesis of cardiovascular disease. Some of the beneficial role of physical activity may result from its effects on the inflammatory process. PubMed was searched for articles published between 1975 through May 2004 using the terms exercise, physical activity, or physical fitness combined with C-reactive protein, inflammation, inflammatory markers, or cytokines. The review revealed 19 articles on the acute inflammatory response to exercise, 18 on cross-sectional comparisons of subjects by activity levels, and 5 examining prospectively the effects of exercise training on the inflammatory process. Exercise produces a short-term, inflammatory response, whereas both cross-sectional comparisons and longitudinal exercise training studies demonstrate a long-term "anti-inflammatory" effect. This anti-inflammatory response may contribute to the beneficial effects of habitual physical activity.
Serious Damage to Tricuspid Valve May Occur During Permanent Pacemaker or ICD Implantation
Severe tricuspid regurgitation caused by a PPM or ICD lead is an under-recognized but treatable etiology of severe right heart failure. The records of 41 patients who underwent tricuspid valve operation for severe tricuspid regurgitation caused by previously placed PPM or ICD leads was reviewed.
During surgery, severe tricuspid regurgitation was found to be caused by the PPM or ICD leads in all 41 patients. There was a perforation of the tricuspid valve leaflet by the PPM or ICD lead in 7 patients, lead entanglement in the tricuspid valve occurred in 4 patients, lead impingement of the tricuspid valve leaflets occurred in 16 patients, and lead adherence to the tricuspid valve occurred in 14 patients. The septal leaflet was most often perforated (6 of 7). In the preoperative evaluation, valve malfunction due to the PPM or ICD lead was diagnosed preoperatively in only 5 of 41 (12%) patients by transthoracic echocardiography. All patients underwent successful tricuspid valve operation (22 tricuspid valve replacement), with one perioperative death occurring. During follow-up (range, 1 to 99 months), there was one patient who died from left-sided heart failure and three patients died of other causes. The remaining patients showed improvement in signs and symptoms of heart failure.
Damage to the tricuspid valve by PPM or ICD leads may result in severe symptomatic tricuspid regurgitation and may not be overtly visualized by echocardiography. This etiology should be considered when evaluating patients with severe right heart failure after PPM or ICD implantation.
Nesiritide Increases Risk of Worsening Renal Function in Patients with Acutely Decompensated Heart Failure
Renal function is an important prognostic factor for patients with acutely decompensated heart failure (ADHF). We investigated the renal effects of nesiritide as treatment for ADHF.
Randomized clinical trials comparing nesiritide with either placebo or active control for ADHF were identified by electronic and manual searches and thorough review of US Food and Drug Administration files available via the website. Worsening renal function was defined as an increase in serum creatinine >0.5 mg/dL. Relative risk across all studies was determined by meta-analysis with Mantel-Haenszel fixed-effects models (RRMH). Risk of dialysis and medical intervention for worsening renal function were compared between therapies. Frequency of worsening renal function was determined from 5 randomized studies that included 1269 patients. Use of Food and Drug Administration-approved doses of nesiritide ( 0.03 ΅g · kg-1 · min-1) significantly increased the risk of worsening renal function compared with non-inotrope-based control (RRMH, 1.52; 95% CI, 1.16 to 2.00; P=0.003) or any control therapy, including non-inotrope- and inotrope-based therapies (RRMH, 1.54; 95% CI, 1.19 to 1.98; P=0.001). Even low-dose nesiritide (0.015 g · kg -1 · min -1 ) significantly increased risk (P=0.012 and P=0.006 compared with non-inotrope and inotrope-based controls, respectively), as did nesiritide administered at any dose up to 0.06 g · kg -1 · min -1 (P=0.002 and P=0.001, respectively). There was no difference in the need for dialysis between therapies.
Nesiritide significantly increases the risk of worsening renal function in patients with ADHF. Whether worsening renal function reflects hemodynamic effect or renal injury is unknown, but the prognostic importance of worsening renal function suggests the need for further investigation in appropriately powered clinical trials.
Cardiac perforation after device closure of atrial septal defects with the Amplatzer septal occluder
Cardiac perforation is a rare complication after transcatheter atrial septal defect (ASD) closure. To identify CP after transcatheter ASD closure with ASO, cardiac events (CE) describing definite CP, hemopericardium, pericardial effusion, cardiovascular collapse, or sudden death were analyzed. Cardiac events were identified from published literature (MEDLINE), medical device regulating agencies in North America and the European Commission, and AGA Medical Corporation (Golden Valley, Minnesota). Institutional cases were reviewed. Cardiac events were defined as early (pre-discharge) or late (post-discharge).
Twenty-nine cardiac events were identified. Five were excluded because findings were inconclusive for device-related CP. Ten patients were <18 years of age. Late cardiac events occurred in 66.6%; 25% presented weeks later (longest, three years). Three deaths were reported. Cardiac perforation occurred predominantly in the anterosuperior atrial walls and/or adjacent aorta.
Amplatzer septal occluder-associated CP uniquely involves the anterosuperior atrial walls and adjacent aorta. Pathophysiology remains poorly understood.
Incidence of Underlying Congenitally Malformed Aortic Valve Common in Isolated Aortic Stenosis
Aortic valve stenosis (with or without aortic regurgitation and without associated mitral stenosis) in adults in the Western world has been considered in recent years to most commonly be the result of degenerative or atherosclerotic disease.
Investigators examined operatively excised, stenotic aortic valves from 932 patients aged 26 to 91 years (mean - SD, 70 - 12), and none had associated mitral valve replacement or evidence of mitral stenosis: A total of 504 (54%) had congenitally malformed valves (unicuspid in 46 [unicommissural in 42; acommissural in 4] and bicuspid in 458); 417 (45%) had tricuspid valves (either absent or minimal commissural fusion); and 11 (1%) had valves of undetermined type. It is likely that the latter 11 valves also had been congenitally malformed. Of the 584 men, 343 (59%) had either a unicuspid or a bicuspid valve; of the 348 women, 161 (46%) had either a unicuspid or a bicuspid aortic valve.
The data from this large study of adults having isolated aortic valve replacement for aortic stenosis (with or without associated aortic regurgitation) and without associated mitral stenosis or mitral valve replacement strongly suggest that an underlying congenitally malformed valve, at least in men, is more common than a tricuspid aortic valve.
Risk of Cardiovascular Disease by Hysterectomy Status, With and Without Oophorectomy
Cardiovascular disease (CVD) is a leading cause of morbidity and mortality in women and may vary by hysterectomy (or oophorectomy) status. This study compared CVD risk factors and rates between postmenopausal women who had and had not undergone hysterectomy, with or without oophorectomy.
The analysis was conducted on 89,914 women in the Women's Health Initiative (WHI) Observational Study. Participants reported demographic characteristics, medical history, dietary habits, physical activity, medications, and previous hysterectomy (with or without oophorectomy). Baseline weight, height, waist circumference, and blood pressure were measured. CVD events were ascertained during 5.1 years of mean follow-up and adjudicated with standard criteria. Black, Hispanic, and American Indian women had higher rates of hysterectomy than white women (52.9%, 44.6%, and 49.2% versus 40.0%, respectively), and Asian/Pacific Islander women had lower rates (33.8%). Women with a hysterectomy (regardless of oophorectomy status) had an adverse risk profile at baseline compared with women with no hysterectomy, including a higher proportion of hypertension, diabetes, high cholesterol, obesity, and lower education, income, and physical activity (all P<0.01). Total mortality and fatal and nonfatal CVD were higher among women with a hysterectomy. Hysterectomy (regardless of oophorectomy status) was a significant predictor of CVD (HR: 1.26, P<0.001). After adjustment for demographic variables and CVD risk factors, the effect was reduced and nonsignificant.
Women with a hysterectomy had a worse risk profile and higher prevalence and incidence of CVD in this cohort. Multivariate models suggest that hysterectomy is not the major determinant of this outcome; rather, CVD risk may be due to the more adverse initial risk profile of women who had undergone hysterectomy.
Treatment with Azithromycin Ineffective for Secondary Prevention in Stable CAD
Epidemiologic, laboratory, animal, and clinical studies suggest that there is an association between Chlamydia pneumoniae infection and atherogenesis. The efficacy of one year of azithromycin treatment for the secondary prevention of coronary events was evaluated.
In a randomized, prospective trial, investigators assigned 4012 patients with documented stable coronary artery disease to receive either 600 mg of azithromycin or placebo weekly for one year. The participants were followed for a mean of 3.9 years at 28 clinical centers throughout the United States.
The primary end point, a composite of death due to coronary heart disease, nonfatal myocardial infarction, coronary revascularization, or hospitalization for unstable angina, occurred in 446 of the participants who had been randomly assigned to receive azithromycin and 449 of those who had been randomly assigned to receive placebo. There was no significant risk reduction in the azithromycin group as compared with the placebo group with regard to the primary end point (risk reduction, 1 percent [95 percent confidence interval, -13 to 13 percent]). There were also no significant risk reductions with regard to any of the components of the primary end point, death from any cause, or stroke. The results did not differ when the participants were stratified according to sex, age, smoking status, presence or absence of diabetes mellitus, or C. pneumoniae serologic status at baseline.
A one-year course of weekly azithromycin did not alter the risk of cardiac events among patients with stable coronary artery disease.
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