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Biomedical subjects

Alexander Battler

Publications and source records attributed to Alexander Battler.

At least 19 recordsLinked to original sources
PubMed2007

Catheter-based stem cell and gene therapy for refractory myocardial ischemia.

Intramyocardial delivery of genes and cells derived from bone marrow has been evaluated in several small studies of 'no-option' symptomatic patients with chronic ischemic coronary artery disease. Clinical experience with intramyocardial gene delivery is limited to genes encoding isoforms of vascular endothelial cell growth factor. In the largest study (Euroinject One), 80 patients were randomized to receive a plasmid encoding vascular endothelial cell growth factor 165 or placebo. The results of this study suggested no beneficial therapeutic effect of this strategy. The experience with stem cells is limited to use of autologous, nonexpanded, nonmanipulated bone-marrow-derived cells; thus, the number of injected stem cells reflects their natural proportion within the bone marrow. The results of these preliminary studies suggest this approach is feasible and has a high safety profile. Although no conclusion can yet be made regarding efficacy, the improved myocardial perfusion in all four studies described in this Review is encouraging. Data from assessments of individual patients, however, suggests a wide variability in response, underscoring the need for further bench and clinical investigations.

Angiogenesis Inducing Agents↗
PubMed2006

Angiogenesis induced by novel peptides selected from a phage display library by screening human vascular endothelial cells under different physiological conditions.

Angiogenesis is a process modulated by several endogenous vascular growth factors as well as by oxygen conditions. For example VEGF failed to induce useful therapeutic angiogenesis in clinical trials. We used a combinatory phage display peptide library screening on human umbilical endothelial cells under normoxia and hypoxia conditions in order to identify novel peptides that bind endothelial cells. The identified peptides induced angiogenesis as demonstrated by endothelial cell proliferation, migration and tube formation. Injection of peptides into the ears of mice resulted in increased numbers of blood vessels. Peptides did not induce VEGF receptor gene expression indicating a possible VEGF unrelated mechanism.

Amino Acid Sequence↗
PubMed2006

Unusual presentation of Takayasu arteritis.

Takayasu arteritis (TA) is an inflammatory arteritis involving large vessels, predominantly the aorta and its main branches. Angina pectoris or myocardial infarction may occur in 3-5% of patients. Symptomatic coronary artery disease may be in rare case the first sign of TA. We describe a case of a young woman in whom acute myocardial infarction and cardiogenic shock and stroke were the initial presentations of TA.

Adult↗
PubMed2006

Prognostic value of myocardial perfusion imaging in symptomatic and asymptomatic patients after percutaneous coronary intervention.

The aim of this study was to evaluate the value of myocardial perfusion imaging (MPI) in predicting major adverse cardiovascular events (MACE) in symptomatic and asymptomatic patients after percutaneous coronary intervention (PCI). We revised retrospectively patients after PCI that underwent MPI and were followed for a year for the presence of MACE. We found no differences in the incidence of MACE between symptomatic and asymptomatic patients. On multivariate analysis, the presence of ischemia by MPI was the most important independent predictor of MACE (OR 5.09, CI 95% 2.15-12.05, p < 0.001). The presence of myocardial ischemia by MPI performed after PCI, and no symptom status, predicts a worse outcome during 1 year of follow-up.

Aged↗
PubMed2006

Urgent cardiac resynchronization therapy in patients with decompensated chronic heart failure receiving inotropic therapy. A case series.

BACKGROUND: It remains unknown whether patients with severe decompensated class IV heart failure (HF) receiving intravenous inotropic treatment benefit from cardiac resynchronization therapy (CRT). METHODS: We identified patients who underwent urgent CRT implantation due to decompensated class IV HF necessitating intravenous inotropic therapy. RESULTS: Of 10 patients with chronic ischemic cardiomyopathy (median QRS duration of 170 ms), CRT implantation was associated with symptomatic improvement in 8 patients. The mortality rate was 50% during a median follow-up of 9.5 months, with a median CRT-to-death duration of 6 months. CONCLUSIONS: CRT was feasible among class IV patients receiving inotropic treatment and was associated with clinical improvement.

Aged↗
PubMed2006

Age, clinical presentation, and outcome of acute coronary syndromes in the Euroheart acute coronary syndrome survey.

AIMS: Age is one of the most powerful determinants of prognosis in myocardial infarction, but there is comparatively little recent data across the whole spectrum of acute coronary syndromes (ACS). We examined the impact of increasing age on clinical presentation and hospital outcome in a large sample of patients with ACS. METHODS AND RESULTS: Patients (n = 10 253) from the Euroheart ACS survey in 103 hospitals in 25 countries were investigated. There was a significant inverse association between the age and the likelihood of presenting with ST-elevation. For each decade of life, the odds of presenting with ST-elevation decreased by 0.82 [95% confidence interval (CI) 0.79-0.84]; P < 0.0001. Elderly patients were considerably less often treated by cardiologists, less extensively investigated, and, when presenting with ST-elevation ACS, less likely to be treated with reperfusion. Compared with patients <55 years, the odds ratios of hospital mortality were 1.87 (1.21-2.88) at age 55-64, 3.70 (2.51-5.44) at age 65-74, 6.23 (4.25-9.14) at age 75-84, and 14.5 (9.47-22.1) among patients > or =85 years, with no major differences across different types of admission or discharge diagnoses. CONCLUSION: Elderly ACS patients were less likely to present with ST-elevation but had substantial in-hospital mortality, yet they were markedly less intensively treated and investigated.

Adult↗
PubMed2006

Safety and feasibility of transendocardial autologous bone marrow cell transplantation in patients with advanced heart disease.

The present report contains the final results of a Phase I study that evaluated the feasibility, safety, and potential efficacy of intramyocardial injection of autologous bone marrow (BM) in "no-option" patients with refractory angina and myocardial ischemia. Twenty-seven patients underwent electromechanic mapping-guided transendomyocardial injections (n = 12, 0.2 ml each) of unfractionated autologous BM cells directed to ischemic, noninfarcted myocardial territory. Patients were injected with 28 +/- 27 x 10(6)/ml nucleated cells containing 2.2 +/- 1.4% CD34+ cells. The autologous BM injection procedure was successful in all patients and was associated with no adverse events. At 3 months, the Canadian Cardiovascular Society angina score (3.2 +/- 0.5 vs 2.0 +/- 0.91, p = 0.001) and treadmill exercise duration (418 +/- 136 vs 489 +/- 142 seconds, p = 0.017) had improved significantly. The stress-induced ischemia score within the injected territories (118 segments) had also improved (2.2 +/- 0.8 vs 1.7 +/- 1.1, p < 0.001). At 1 year, the clinical improvement was sustained, although 5 patients had undergone revascularization procedures. The number of total injected nucleated cells (CD45+), progenitor cells (CD34+), and the magnitude of secreted vascular endothelial growth factor and macrophage chemoattractant protein-1 by cultured BM cells failed to predict the clinical response. In conclusion, the 3- and 12-month study results have indicated the safety of catheter-based transendocardial delivery of autologous BM cells in patients with advanced symptomatic ischemic heart disease and may suggest sustained potential efficacy. The cellular and humeral characteristics of autologous BM cells did not predict the clinical response, underscoring the advisability of additional mechanistic exploration.

Angina, Unstable↗
PubMed2006

Short-term triple therapy with aspirin, warfarin, and a thienopyridine among patients undergoing percutaneous coronary intervention.

OBJECTIVES: To assess bleeding complications among patients undergoing percutaneous coronary intervention (PCI) and receiving triple therapy of warfarin, aspirin, and a thienopyridine. BACKGROUND: Triple therapy of warfarin, aspirin, and a thienopyridine is strongly discouraged, given the potential risk of bleeding complications. METHODS AND RESULTS: Post-PCI patients receiving triple therapy thereafter underwent assessment for bleeding complications. Continuous variables are presented as median (25th-75th percentiles). The study group included 180 patients (80% males; age 65 (52, 75.5)). PCI was on an urgent/emergent basis in 86.6%. The main indications for warfarin use were left ventricular mural thrombus and atrial fibrillation (46.9 and 36.9% respectively). Glycoprotein IIb/IIIa receptor antagonists were used in 47.7%. Post-PCI triple therapy duration was 30 days (30, 30). During the post-triple therapy, 104 patients (57.8%) continued treatment with warfarin and aspirin for 376 days (150, 775). During the triple therapy period, 20 patients developed bleeding complications, (mean INR 2.1 +/- 0.7 at 7 (6, 8.5) days post-PCI): 2 major groin hematoma (initial phase of warfarin treatment during overlap with heparin) and 18 minor. During post-triple therapy, primarily under warfarin and aspirin, 19 patients developed bleeding complications: 1 major and 18 minor. CONCLUSION: Short-term triple therapy after PCI was not associated with prohibitively high bleeding complication rates, and thus should be favorably considered in patients with a clear indication for warfarin use.

Aged↗
PubMed2006

Characteristics and outcome of octogenarian population referred for myocardial perfusion imaging: comparison with non-octogenarian population with reference to gender.

BACKGROUND: Octogenarian patients referred for stress myocardial perfusion imaging (MPI) differ from younger (non-octogenarian) patients in that they have lower prevalence of risk factors for CAD, but more frequent ischemic events and higher cardiac mortality. HYPOTHESIS: The purpose of this study was to investigate the efficacy of MPI in octogenarian men and women compared with that in the younger population, and to compare the prognostic value of stress MPI in both populations. METHODS: We studied 162 consecutive patients aged > or = 80 years who were referred for stress MPI, and compared them with 253 consecutive patients aged < 80 years. Patients completed a questionnaire encompassing information about the existence of coronary risk factors, cardiac symptoms, coronary artery disease (CAD), myocardial infarction, coronary artery bypass graft, percutaneous transluminal coronary angioplasty, and results of stress MPI. The patients were followed up for cardiac mortality for a mean of 45 +/- 12 months. RESULTS: There were 61 women and 101 men (17% of all referrals) with a mean age of 83 +/- 3 (range 80-90). Parameters of octogenarian patients demonstrated a significantly lower prevalence of non-insulin-dependent diabetes mellitus (p < 0.02), hypercholestrolemia (p < 0.001), and smoking (p = 0.001) compared with non-octogenarian patients. The prevalence of known CAD was similar, but the prevalence of abnormal resting electrocardiogram, left ventricular (LV) dilatation, and stress-induced ischemia was significantly higher in octogenarians (p < 0.002). Cardiac mortality rate per year was 4.3% in octogenarians versus 1.3% in the younger population (p < 0.0001). The independent predictors according to MPI of cardiac death were LV dilatation and presence of ischemia in octogenarians, and severity of ischemia in non-octogenarians. CONCLUSIONS: The octogenarian population referred for stress single-photon emission computed tomography differed from the non-octogenarian group in that it had a lower prevalence of risk factors for CAD, but more frequent ischemic events and higher cardiac mortality; however, MPI variables predict adverse outcome in both populations.

Age Distribution↗
PubMed2006

Antecedent left ventricular mass and infarct size in ST-elevation myocardial infarction.

BACKGROUND: Increased left ventricular mass index (LVMI) is associated with a greater incidence of acute myocardial infarction (AMI), but there are no data regarding its impact on infarct size. OBJECTIVES: The objective of this study was to determine whether LVMI impacts on infarct size. METHODS: We analyzed consecutive patients with a first ST-elevation AMI and successful reperfusion of the culprit artery who underwent an echocardiographic assessment of LVMI and regional wall motion score index (RWMSI) <72 hours post AMI. RESULTS: Of the 165 patients (76.4% men) with a mean age of 61.0 +/- 13.9 years, 53.9% had anterior wall involvement and 59.3% had increased LVMI. There were no significant differences in baseline characteristics between patients with and without increased LVMI, except for a greater prevalence of hypertension among patients with increased LVMI (44.0% vs 22.4%, P < .001). The distributions of anterior wall AMI location and culprit artery involvement were similar between the groups. Patients with increased LVMI were more likely to present with single-vessel coronary artery disease (P = .04) and heart failure upon presentation (P = .03). There was no significant difference between patients with and without increased LVMI in peak creatine kinase (2106.8 +/- 1642.7 vs 2551.2 +/- 2357.4 U/L, P = .16) or RWMSI (1.62 +/- 0.44 vs 1.61 +/- 0.38, P = .91). In addition, no correlation was observed between LVMI as a continuous variable and RWMSI (r = 0.11, P = .18) or peak creatine kinase values (r = 0.02, P = .81). CONCLUSIONS: Among patients with a first ST-elevation AMI and successful reperfusion, antecedent increased LVMI was fairly common and did not impact on infarct size.

Aged↗
PubMed2006

Tissue Doppler imaging in patients with advanced heart failure: relation to functional class and prognosis.

BACKGROUND: Tissue Doppler imaging (TDI) provides rapid assessment of systolic and diastolic myocardial function. However, the added value of TDI to standard Doppler echocardiographic measurements in predicting symptoms and outcome of advanced heart failure remains unknown. METHODS: The study cohort comprised 45 patients with congestive heart failure, defined as New York Heart Association functional class III and IV, who were referred to our department for evaluation for heart transplantation. Twenty healthy subjects were the controls. Conventional echo Doppler was used to assess left ventricular (LV) ejection fraction, peak velocities of transmitral early and late diastolic LV filling, the ratio of transmitral early to late LV filling velocity, and E-deceleration time. TDI measurements recorded at the mitral annulus included systolic velocity, early and late diastolic velocities, and the ratio of early to late diastolic velocity. The ratio of transmitral early LV filling velocity to early diastolic TDI velocity of the mitral annulus (E/E') was calculated. All patients were followed for cardiac-related death and hospitalization for heart failure. RESULTS: Patients with functional class IV had a significantly higher E/E' ratio than did patients with functional class III (12.9 +/- 2.8 vs 8.3 +/- 1.7, p < 0.001) and the controls (5.4 +/- 1.3, p < 0.001). Except for transmitral late filling velocity, all conventional echo Doppler parameters and TDI variables significantly correlated with functional class. On multivariate stepwise analysis, however, the E/E' ratio was the only independent predictor of functional class (p = 0.003). E/E' also correlated with cardiac mortality and hospitalization. CONCLUSION: Conventional Doppler indices and TDI parameters correlated with functional class in patients with advanced heart failure. The E/E' ratio, which probably reflects high LV end-diastolic pressure, was the best measure for differentiating patients with functional class III and IV, and it also correlated with cardiac mortality and hospitalization for worsening heart failure, thereby providing additional value to standard echocardiographic measures.

Adult↗
PubMed2006

Is increased body mass index associated with a cardioprotective effect after ST-segment-elevation myocardial infarction?

Recent studies highlighted the 'obesity paradox' after revascularization, suggesting a 'cardioprotective' effect of obesity. We assessed the association of BMI and regional wall motion score (RWMS) and peak CK and cTnI values (markers of infarct size) and 30-day survival among consecutive first ST-segment-elevation myocardial infarction patients who underwent successful primary PCI. Of the 164 patients, we found no difference in infarct size among the different groups, BMI < or = 25 kg/m2, 25 < BMI < or = 30 kg/m2, and BMI > 30 kg/m2, and no association between BMI as continuous variable and these variables. Thirty-day death rates were not statistically different among the three groups (10, 5, 2%, respectively, P = 0.83). Increased BMI does not confer any protective effect on the heart during acute ischemia.

Angioplasty, Balloon, Coronary↗
PubMed2006

Isolation of an adult blood-derived progenitor cell population capable of differentiation into angiogenic, myocardial and neural lineages.

Blood-derived adult stem cells were previously considered impractical for therapeutic use because of their small numbers. This report describes the isolation of a novel human cell population derived from the peripheral blood, termed synergetic cell population (SCP), and defined by the expression of CD31Bright, CD34+, CD45-/Dim and CD34Bright, but not lineage-specific features. The SCP was capable of differentiating into a variety of cell lineages upon exposure to defined culture conditions. The resulting cells exhibited morphological, immunocytochemical and functional characteristics of angiogenic, neural or myocardial lineages. Angiogenic cell precursors (ACPs) expressed CD34, CD133, KDR, Tie-2, CD144, von Willebrand factor, CD31Bright, concomitant binding of Ulex-Lectin and uptake of acetylated low density lipoprotein (Ac-LDL), secreted interleukin-8, vascular endothelial growth factor and angiogenin and formed tube-like structures in vitro. The majority of CD31Bright ACP cells demonstrated Ac-LDL uptake. Neural cell precursors (NCPs) expressed the neuronal markers Nestin, betaIII-Tubulin, and Neu-N, the glial markers GFAP and O4, and responded to neurotransmitter stimulation. Myocardial cell precursors (MCPs) expressed Desmin, cardiac Troponin and Connexin 43. In conclusion, the simple and rapid method of SCP generation and the resulting considerable quantities of lineage-specific precursor cells makes it a potential source of autologous treatment for a variety of diseases.

Adult↗
PubMed2006

Predictors of left ventricular dysfunction in patients with first acute anterior myocardial infarction undergoing primary angioplasty.

BACKGROUND: The degree of left ventricular dysfunction determines the prognostic outcome of patients with acute myocardial infarction. OBJECTIVES: To define the clinical, angiographic and procedural variables related to LV dysfunction in patients with anterior wall AMI referred for primary percutaneous coronary intervention. METHODS: The sample included 168 patients treated by primary PCI for first anterior wall AMI. Clinical, demographic and medical data were collected prospectively into a computerized registry, and clinical outcome (death, reinfarction, major cardiovascular event) were evaluated during hospitalization and 30 days after discharge. Patients were divided into three groups by degree of LV dysfunction (mild, moderate, severe) and compared for clinical, angiographic and procedural variables. RESULTS: LV dysfunction was associated with pre-PCl renal failure (serum creatinine > 1.4 mg/dl), peripheral vascular disease, high peak creatine kinase level, longer door to balloon time, low TIMI flow grade before and after PCl, and use of an intraaortic balloon pump. On multivariate analysis adjusted for baseline differences, peak creatine kinase level (r = 0.3, P = 0.0001) and door to needle time (r = 0.2, P = 0.008) were the most significant independent predictors of moderate or severe LV dysfunction after anterior AMI. CONCLUSION: Abnormal LV function after first anterior AMI can be predicted by door to balloon time and the size of the infarction as assessed by creatine kinase levels. Major efforts should be made to decrease the time to myocardial reperfusion.

Angioplasty, Balloon, Coronary↗
PubMed2005

Comparison of diameter of ascending aorta in patients with severe aortic stenosis secondary to congenital versus degenerative versus rheumatic etiologies.

Aortic root dilation has been previously reported to be associated with aortic stenosis (AS), but data to support this statement are scarce. The dimensions of the aortic root were measured at 4 levels (annulus, sinuses, sinotubular junction, and ascending aorta) in 88 patients (mean age 71.2+/-9.7 years; 56% men) with severe AS who underwent intraoperative transesophageal echocardiography immediately before aortic valve replacement. These patients were compared with 76 gender- and age-matched patients without AS who underwent transesophageal echocardiography for various indications. The etiology of aortic valve stenosis was degenerative in 62 (70.5%), bicuspid aortic valve (BAV) in 15 (17.0%), and rheumatic in 11 (12.5%). The ascending aorta was significantly wider in AS with various etiologies (BAV, rheumatic, degenerative) than in the controls (39+/-6.9, 35.0+/-4.2, 33.1+/-4.1, and 31.3+/-3.7 mm, respectively; p<0.001). The dimensions of the sinuses and sinotubular junction were significantly less in those with AS of degenerative etiology than in the controls (29.5+/-4.0 vs 32.5+/-4.3 mm and 23.6+/-3.0 vs 26.8+/-3.0 mm, respectively, p<0.001). The prevalence of a dilated aorta (>37 mm) was 3.9%, 13.1%, 36.4%, and 60% in the control group and AS patients with degenerative, rheumatic, and BAV etiology, respectively (p<0.0001). In conclusion, patients with severe AS due to BAV had significant dilation of the aortic root. Patients with degenerative and rheumatic etiology had less remarkable dilation compared with control group, and most values were within the normal range.

Aged↗
PubMed2005

Balloon-floating right heart catheter monitoring for acute coronary syndromes complicated by heart failure--discordance between guidelines and reality.

PURPOSE: Current guidelines (class IIA recommendations) recommend balloon-floating right heart catheter monitoring (RHC) in particular for patients with ST elevation acute coronary syndromes (ACS) who have progressive heart failure (HF) or cardiogenic shock (CS), as well as for other ACS patients with hemodynamic instability. However, their implementation remains undetermined. The aim of the study was to analyze RHC use in ACS patients, in particular those with HF. SUBJECTS AND METHODS: The Euro Heart ACS Survey enrolled 10,484 ACS patients (ST elevation, no ST elevation and undetermined ECG). We analyzed the general RHC use, in particular in HF patients. RESULTS: Of the 10,234 patients with data regarding RHC use, RHC was used in 309 patients (3.0%). Patients with RHC presented more often with ST segment elevation ACS, symptoms other than angina, Killip class III/IV, lower systolic blood pressure and a higher heart rate. Of the 10,136 patients with documented HF status, 549 (5.4%) had CS, 2,529 (25.0%) had mild to moderate HF, and 7,058 (69.6%) had no HF. RHC was performed in 111 (20.2%) patients with CS, 87 (3.4%) patients with mild to moderate HF, and 109 (1.5%) patients without HF. In contrast, echocardiography was performed in 376 (68.4%) CS patients, 1,812 (71.6%) patients with mild to moderate HF, and 4,484 (63.5%) patients without HF. CONCLUSIONS: In contrast to the unequivocal recommendations to use RHC for hemodynamically unstable ACS patients, RHC is infrequently used in current clinical practice. Perhaps it has been supplanted by echocardiography, a noninvasive and readily available modality. Given the reserved use of RHC in ACS patients, and the reported complications associated with RHC, the guidelines regarding its use should be reconsidered.

Aged↗
PubMed2005

Family history, plasma homocysteine, and age at onset of symptoms of myocardial ischemia in patients with different methylenetetrahydrofolate reductase genotypes.

A high plasma homocysteine level is associated with early onset of coronary artery disease (CAD), particularly in homozygotes for the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene. Family history is a predictor of increased plasma homocysteine and may be involved in early-onset CAD. This study examined the relations among family history, plasma homocysteine, and age at onset of CAD, and the role of the MTHFR genotype in this context. We screened 284 patients who developed first symptoms of CAD at < or =65 years of age for fasting plasma homocysteine and the C677T mutation. On multiple regression analysis, homocysteine, family history, male gender, and smoking were independently associated with age at onset of CAD. However, separate analysis of patients who had the MTHFR 677 T/T genotype (n = 57) and those who did not (n = 209) showed that plasma homocysteine and family history were associated with earlier onset of CAD only in T/T homozygotes and that family history in patients who had this genotype was also associated with higher plasma homocysteine levels and a stronger association between plasma homocysteine and age at onset of CAD. In patients who had other genotypes, these associations were not observed, and earlier onset of CAD was associated only with male gender and smoking. Thus, the MTHFR genotype modifies the effects of family history and other risk factors on age at onset of CAD. In T/T homozygotes, family history is associated with earlier onset of CAD, higher plasma homocysteine levels, and a stronger association between plasma homocysteine and age at onset of CAD.

Age of Onset↗