Can Pharmacogenetic Variants in TPMT, MTHFR and SLCO1B1 Genes Be Used as Potential Markers of Outcome Prediction in Systemic Sclerosis Patients?

Systemic sclerosis (SSc) is a rare connective tissue disorder with highest morbidity and mortality among rheumatologic diseases. Disease progression is highly heterogeneous between patients, implying a strong need for individualization of therapy. Four pharmacogenetic variants, namely TPMT rs1800460, TPMT rs1142345, MTHFR rs1801133 and SLCO1B1 rs4149056 were tested for association with severe disease outcomes in 102 patients with SSc from Serbia treated either with immunosuppressants azathioprine (AZA) and methotrexate (MTX) or with other types of medications. Genotyping was performed using PCR-RFLP and direct Sanger sequencing. R software was used for statistical analysis and development of polygenic risk score (PRS) model. Association was found between MTHFR rs1801133 and higher risk for elevated systolic pressure in all patients except those prescribed with MTX, and higher risk for kidney insufficiency in patients prescribed with other types of drugs. In patients treated with MTX, variant SLCO1B1 rs4149056 was protective against kidney insufficiency. For patients receiving MTX a trend was shown for having a higher PRS rank and elevated systolic pressure. Our results open a door wide for more extensive research on pharmacogenomics markers in patients with SSc. Altogether, pharmacogenomics markers could predict the outcome of patients with SSc and help in prevention of adverse drug reactions.

Diagnostic and Therapeutic Implications of Long Non-Coding RNAs in Leukemia.

Leukemia is a heterogenous group of hematological malignancies categorized in four main types (acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML) and chronic lymphocytic leukemia (CLL). Several cytogenetic and molecular markers have become a part of routine analysis for leukemia patients. These markers have been used in diagnosis, risk-stratification and targeted therapy application. Recent studies have indicated that numerous regulatory RNAs, such as long non-coding RNAs (lncRNAs), have a role in tumor initiation and progression. When it comes to leukemia, data for lncRNA involvement in its etiology, progression, diagnosis, treatment and prognosis is limited. The aim of this review is to summarize research data on lncRNAs in different types of leukemia, on their expression pattern, their role in leukemic transformation and disease progression. The usefulness of this information in the clinical setting, i.e., for diagnostic and prognostic purposes, will be emphasized. Finally, how particular lncRNAs could be used as potential targets for the application of targeted therapy will be considered.

Expression Profiles of Long Non-Coding RNA GAS5 and MicroRNA-222 in Younger AML Patients.

Acute myeloid leukemia (AML) is a heterogeneous malignant disease both on clinical and genetic levels. AML has poor prognosis and, therefore, there is a constant need to find new prognostic markers, as well as markers that can be used as targets for innovative therapeutics. Recently, the search for new biomarkers has turned researchers' attention towards non-coding RNAs, especially long non-coding RNAs (lncRNAs) and micro RNAs (miRNAs). We investigated the expression level of growth arrest-specific transcript 5 (GAS5) lncRNA in 94 younger AML patients, and also the expression level of miR-222 in a cohort of 39 AML patients with normal karyotype (AML-NK), in order to examine their prognostic potential. Our results showed that GAS5 expression level in AML patients was lower compared to healthy controls. Lower GAS5 expression on diagnosis was related to an adverse prognosis. In the AML-NK group patients had higher expression of miR-222 compared to healthy controls. A synergistic effect of GAS5low/miR-222high status on disease prognosis was not established. This is the first study focused on examining the GAS5 and miR-222 expression pattern in AML patients. Its initial findings indicate the need for further investigation of these two non-coding RNAs, their potential roles in leukemogenesis, and the prognosis of AML patients.

Somatostatin receptor scintigraphy in the follow up of neuroendocrine neoplasms of appendix.

BACKGROUND: Neuroendocrine tumors of appendix (ANETs) known as carcinoids, are rare endocrine neoplasms originated from enterochromaffin cells of gastrointestinal tract. ANETs are the third most frequent (16.7%) gastrointestinal neuroendocrine tumors, with the incidence of 0.08-0.2 cases/100000 during one year. Incidental ANETs occur in 0.2%-0.7% of emergency surgical resections because of suspected appendicitis which is usually the first manifestation of ANET. Although there are a lot of papers about application of somatostatin receptor scintigraphy in gastrointestinal neuroendocrine tumors, there are very rare sporadic cases described about ANETs particularly. AIM: To establish the role of somatostatin receptor scintigraphy (SRS) in the management of patients with neuroendocrine tumors of appendix (ANET). METHODS: The total of 35 patients was investigated, 23 females and 12 males, average age (43.7 ± 17.3 years). All patients had histological diagnosis of ANET (34 carcinoids of appendix and one tubular carcinoid). Majority of tumors have been found incidentally during surgery of: Acute appendicitis (n = 15), perforated appendicitis (n = 2), ileus (n = 3), hysterectomy (n = 3), ruptured ovarian cyst (n = 2), caecal volvulus (n = 1), while 9 patients had diagnosis of appendiceal tumor before the surgery. Seventeen patients had tumor grade (G) G1, 12 G2 and 6 G3. The right hemicolectomy was performed in 13, while the rest of the patients had appendectomy only. SRS was done early (2 h) and late (24 h) after i.v. application of 740 MBq technetium-99m ethylenediamine-N, N'-diacetic acid Hydrazinonicotinyl-Tyr3-Octreotide (technetium-99m-Tektrotyd, Polatom, Poland). SRS was performed for restaging in all the patients after surgery. RESULTS: There were 12 true positive (TP), 19 true negative, 3 false positive and 1 false negative SRS result. Sensitivity of the method was 92.31%, specificity was 86.36%, positive predictive value was 80.00%, negative predictive value was 95.00% and accuracy 88.57%. Receiver operating characteristics analysis showed that SRS scintigraphy is a good test for detection TP cases [area under the curve of 0.850, 95% confidence interval (CI): 0.710-0.990, P < 001]. Single photon emission computed tomography contributed diagnosis in 7 TP findings. In 10 patients Krenning score was 4 and in 2 was 3. In 8 patients SRS significantly changed the management of the patients (in two surgery was repeated, in 4 somatostatin analogues and in two peptide receptor radionuclide therapy). Median progression-free survival in SRS positive patients was 52 months (95%CI: 39.7-117.3 mo) while in SRS negative patients it was 60 months (95%CI: 42.8-77.1 mo), without statistically significant difference between the two groups (P = 0.434). CONCLUSION: In conclusion, our results confirmed the value of SRS in the follow-up of the patients with ANET after surgery, if recurrences or metastases are suspected.

Effect of New-Onset Left Bundle Branch Block After Transcatheter Aortic Valve Implantation (CoreValve) on Mortality, Frequency of Re-Hospitalization, and Need for Pacemaker.

New-onset conduction disturbances are common after transcatheter aortic valve implantation (TAVI). The most common complication is left bundle branch block (LBBB). The clinical impact of new-onset LBBB after TAVI remains controversial. The aim of this study was to analyze the clinical impact of new-onset LBBB in terms of mortality and morbidity (need for pacemakers and admissions for heart failure) at long-term follow-up. From April 2008 to December 2014, 220 patients who had severe aortic stenosis were treated with the implantation of a CoreValve prosthesis. Sixty-seven of these patients were excluded from the analysis, including 22 patients with pre-existing LBBB and 45 with a permanent pacemaker, implanted previously or within 72 hours of implantation. The remaining 153 patients were divided into 2 groups: group 1 (n = 80), those with persistent new-onset LBBB, and group 2 (n = 73), those without conduction disturbances after treatment. Both groups were followed up at 1 month, 6 months, 12 months, and yearly thereafter. Persistent new-onset LBBB occurred in 80 patients (36%) immediately after TAVI; 73 patients (33%) did not develop conduction disturbances. The mean follow-up time of both groups was 32 ± 22 months (range 3 to 82 months), and there were no differences in time between the groups. There were no differences in mortality between the groups (39% vs 48%, p = 0.58). No differences were observed between the groups in re-hospitalizations for heart failure (11% vs 16%, p = 0.55). Group 1 did not require pacemaker implantation more often at follow-up (10% vs 13%, p = 0.38) than group 2. In conclusion, new-onset LBBB was not associated with a higher incidence of late need for a permanent pacemaker after CoreValve implantation. In addition, it was not associated with a higher risk of late mortality or re-hospitalization.

Modificación de la conducción auriculoventricular tras el implante de prótesis aórtica Core Valve / Atrioventricular conduction changes after corevalve transcatheter aortic valve implantation

Introducción y objetivos: Con frecuencia se producen alteraciones en la conducción tras el implante de una prótesis CoreValve. Se pretende analizar qué cambios se producen en la conducción cardiaca de pacientes con estenosis aórtica tratados con este tipo de prótesis. Métodos: Desde abril de 2008 hasta diciembre de 2013, se seleccionó a 181 pacientes con estenosis aórtica grave tratados con esta prótesis y estudiados mediante electrocardiograma. Se estudió a un subgrupo de 137 pacientes consecutivos (75,7%) mediante electrocardiogramas intracavitarios antes y tras implante protésico. El objetivo principal del estudio es la necesidad de marcapasos definitivo en las primeras 72 h tras el implante protésico. Se analizaron numerosas variables para predecir esta eventualidad. Resultados: Tras el implante, los intervalos PR y QRS se incrementaron de 173 ± 47 a 190 ± 52 ms (p < 0,01) y de 98 ± 22 a 129 ± 24 ms (p < 0,01), mientras que los intervalos AH y HV se alargaron de 95 ± 39 a 108 ± 41 ms (p < 0,01) y de 54 ± 10 a 66 ± 23 ms (p < 0,01). En total, 89 pacientes (49%) presentaron bloqueo de rama izquierda de novo y 33 (25%) precisaron marcapasos en las primeras 72 h. Los predictores independientes de marcapasos fueron el bloqueo de rama derecha basal y la profundidad protésica. Los intervalos intracavitarios carecieron de valor predictivo. Además, 13 pacientes requirieron marcapasos después de las 72 h. Conclusiones: El implante de prótesis CoreValve produce alta incidencia de alteraciones de la conducción; la más frecuente es el bloqueo de rama izquierda; el 25% de los pacientes precisaron marcapasos definitivo. La necesidad de marcapasos se relacionó con el bloqueo de rama derecha basal y la profundidad protésica (AU)

Introduction and objectives: Conduction disturbances often occur after CoreValve transcatheter aortic valve implantation. The aim was to analyze which cardiac conduction changes occur in patients with aortic stenosis treated with this type of prosthesis. Methods: A total of 181 patients with severe aortic stenosis treated with this prosthesis and studied by electrocardiography between April 2008 and December 2013 were selected. A subgroup of 137 (75.7%) consecutive patients was studied by intracardiac electrocardiogram before and after prosthesis implantation. The primary endpoint of the study was the need for a permanent pacemaker within 72 hours after prosthesis implantation. Numerous variables to predict this possibility were analyzed. Results: Following implantation, PR and QRS intervals were increased from 173 ± 47 ms to 190 ± 52 ms (P < .01) and from 98 ± 22 ms to 129 ± 24 ms (P < .01), whereas the A-H and H-V intervals were prolonged from 95 ± 39 ms to 108 ± 41 ms (P < .01) and from 54 ± 10 ms to 66 ± 23 ms (P < .01). A total of 89 (49%) patients had new-onset left bundle-branch block, and 33 (25%) required a pacemaker within the first 72 hours. The independent predictors for a pacemaker were baseline right bundle-branch block and prosthetic depth. Intracardiac intervals had no predictive value. In addition, 13 patients required a pacemaker after 72 hours. Conclusions: CoreValve prosthesis implantation has a high incidence of conduction disturbance, with left bundle-branch block being the most common. A total of 25% of patients required a permanent pacemaker. The need for a pacemaker was related to baseline right bundle-branch block and prosthetic depth (AU)

Atrioventricular Conduction Changes After CoreValve Transcatheter Aortic Valve Implantation.

INTRODUCTION AND OBJECTIVES: Conduction disturbances often occur after CoreValve transcatheter aortic valve implantation. The aim was to analyze which cardiac conduction changes occur in patients with aortic stenosis treated with this type of prosthesis. METHODS: A total of 181 patients with severe aortic stenosis treated with this prosthesis and studied by electrocardiography between April 2008 and December 2013 were selected. A subgroup of 137 (75.7%) consecutive patients was studied by intracardiac electrocardiogram before and after prosthesis implantation. The primary endpoint of the study was the need for a permanent pacemaker within 72 hours after prosthesis implantation. Numerous variables to predict this possibility were analyzed. RESULTS: Following implantation, PR and QRS intervals were increased from 173±47 ms to 190±52ms (P < .01) and from 98±22ms to 129±24 ms (P < .01), whereas the A-H and H-V intervals were prolonged from 95±39ms to 108±41ms (P < .01) and from 54±10ms to 66±23ms (P < .01). A total of 89 (49%) patients had new-onset left bundle-branch block, and 33 (25%) required a pacemaker within the first 72hours. The independent predictors for a pacemaker were baseline right bundle-branch block and prosthetic depth. Intracardiac intervals had no predictive value. In addition, 13 patients required a pacemaker after 72 hours. CONCLUSIONS: CoreValve prosthesis implantation has a high incidence of conduction disturbance, with left bundle-branch block being the most common. A total of 25% of patients required a permanent pacemaker. The need for a pacemaker was related to baseline right bundle-branch block and prosthetic depth.

Stent Repair for Complex Coarctation of Aorta.

OBJECTIVES: This study sought to determine whether several anatomic or evolving characteristics of the coarctation may create challenging conditions for treatment. BACKGROUND: Stent repair of coarctation of aorta is an alternative to surgical correction. METHODS: We analyzed our 21-year experience in the percutaneous treatment of complex coarctation of aorta. Adverse conditions for treatment were as follow: 1) complete interruption of the aortic arch (n = 11); 2) associated aneurysm (n = 18); 3) complex stenosis (n = 30); and 4) the need for re-expansion and/or restenting (n = 21). Twenty patients (33%) belonged to more than 1 group. Ten interruptions were type A and 1 was type B. The mean length of the interrupted aorta was 9 ± 11 mm. The associated aneurysms were native in 8 patients and after previous intervention in 10 patients. Aneurysm shapes were fusiform in 8 patients and saccular in 10. The following characteristics defined complex stenosis as long diffuse stenosis, very tortuous coarctation, or stenosis involving a main branch or an unusual location. Patients previously stented at an early age, required re-expansion and/or restenting after reaching 16 ± 5 years of age. RESULTS: Two patients had died by 1-month follow-up. The remaining 58 patients did well and were followed-up for a mean period of 10 ± 6 years. Late adverse events occurred in 3 patients (5%). All remaining patients are symptom-free, with normal baseline blood pressure. Imaging techniques revealed good patency at follow-up without associated aneurysm or restenosis. The actuarial survival free probability of all complex patients at 15 years was 92%. CONCLUSIONS: Stent repair of complex coarctation of aorta is feasible and safe. Initial results are maintained at later follow-up.

Immediate results and long-term clinical outcome of patients with unprotected distal left main restenosis: the CORPAL registry (Córdoba and Las Palmas).

OBJECTIVES: The goal of this study was to assess the immediate and long-term outcomes in patients undergoing percutaneous coronary intervention (PCI) for in-stent restenosis (ISR) in an unprotected distal left main coronary artery (UDLM). BACKGROUND: PCI for UDLM-ISR can be complex. Limited information is available on procedural and clinical outcomes. METHODS: Between May 2002 and February 2011, UDLM-ISR after drug-eluting stent implantation was observed in 79 of 1,102 patients (7%). Seventy-five were treated by repeat PCI using a simple approach (balloon/in-stent implantation) or a complex strategy (additional stent/double-stenting technique). A diagnosis of mild or severe restenosis was considered depending on the number of bifurcation segments affected (1 vs. >1). Major adverse cardiac events (MACE) were defined as cardiac death, target lesion revascularization, and myocardial infarction. RESULTS: ISR treatment was performed using a simple approach in 44 (58%) patients, and using a complex strategy in 31 (42%). After 46 ± 26 months, the MACE rate was 22%. Patients treated with a simple approach had a lower incidence of MACE at follow-up compared with patients treated with a complex strategy, regardless of the restenosis extent (mild restenosis: 93% vs. 67%, p < 0.05; severe: 70% vs. 23%, p < 0.05). On Cox regression analysis, diabetes was the only predictor of MACE (hazard ratio [HR]: 4.94; 95% confidence interval [CI]: 1.03 to 23.70; p < 0.05), whereas a simple strategy for ISR treatment was associated with lower risk (HR: 0.25; 95% CI: 0.08 to 0.79; p = 0.02). CONCLUSIONS: PCI for UDLM-ISR is safe and feasible, with a high rate of procedural success and an acceptable long-term MACE rate. A simple strategy, when applicable, appears to be a good treatment option, associated with a lower event rate at follow-up.

Optical coherence tomography evaluation of late strut coverage patterns between first-generation drug-eluting stents and everolimus-eluting stent.

OBJECTIVES: To compare strut coverage patterns between everolimus-eluting stent (EES) and first-generation drug-eluting stents (DES) at more than 12 months after successful implantation, using optical coherence tomography (OCT). BACKGROUND: No sufficient OCT data has been reported comparing late strut coverage patterns between EES and first-generation DES. The favorable late results after EES implantation could be related to lower rates of uncovered and malapposed struts. METHODS: A total of 66 DES (21 EES, 23 SES, and 22 PES) that were implanted at least 1 year in advance in 40 patients and met good late angiographic results were evaluated by OCT. The percentage of uncovered and malapposed struts, calculated as the ratio of uncovered or malapposed struts to total struts in all cross-sectional images per stent, was compared among the three groups. RESULTS: A total of 35,061 struts were analyzed: 11,967 from EES, 11,855 from SES, and 11m239 from PES. The average tissue coverage thickness of the struts per stent was greater in EES than in SES and PES (109 ± 40 µm vs. 72 ± 27 µm and 83 ± 26 µm, respectively; P = 0.001). The percentage of uncovered struts (1.9 ± 4.1% in EES vs. 11.6 ± 12.7% in SES, P = 0.01 and vs. 7.1 ± 5.2% in PES, P < 0.001) and malapposed struts (0.1 ± 0.3% in EES vs. 1.8 ± 3.5% in SES, P = 0.01 and vs. 3.5 ± 5.1% in PES, P = 0.02) was much lower in EES than in first-generation DES, with no significant differences between SES and PES. CONCLUSIONS: Late strut coverage patterns are not similar between EES and first-generation DES. EES showed a lower percentage of uncovered and malapposed struts.

Mejoría funcional en pacientes con miocardiopatía dilatada tras la infusión intracoronaria de células mononucleares autólogas de la médula ósea / Functional improvement in patients with dilated cardiomyopathy after the intracoronary infusion of autologous bone marrow mononuclear cells

Introducción y objetivos. Diferentes estudios han mostrado mejoría funcional en pacientes con miocardiopatía dilatada no isquémica tratada con terapia celular. Sin embargo, los factores que influyen en la respuesta no son bien conocidos. El presente estudio investiga los cambios funcionales y los factores que influyen en la mejora de la fracción de eyección a los 6 meses en 27 pacientes con miocardiopatía dilatada tratados con terapia celular intracoronaria. Métodos. Los pacientes recibieron una infusión intracoronaria de células mononucleares autólogas de la médula ósea (media de células infundidas, 10,2±2,9 × 108). En todos se efectuó análisis funcional y citometría de flujo de las células infundidas. Resultados. La ganancia en fracción de eyección observada a los 6 meses osciló entre el ¿9 y el 34% (media, 9%). Estos cambios formaron dos grupos de pacientes: 21 (78%) que mostraron una mejora significativa (ganancia media, 14±7%), frente a 6 (22%) que no mostraron respuesta (ganancia media, ¿5±3%). Los respondedores eran más jóvenes (50±12 frente a 62±9 años; p<0,04). Se encontró una correlación inversa (r=¿0,41; p<0,003) entre la ganancia en la fracción de eyección y los valores basales de lipoproteínas de alta densidad. La capacidad migratoria de las células infundidas a las 24h estaba significativamente reducida en el grupo de respondedores (factor de crecimiento del endotelio vascular, 5,4±1,7 × 108 frente a 8,1±2,3 × 108; p<0,009; factor 1 derivado de células estromales, 5,8±1,7 × 108 frente a 8,4±2,9 × 108; p<0,002). Conclusiones. Los pacientes más jóvenes con miocardiopatía dilatada y concentración plasmática de lipoproteínas de alta densidad más baja parecen tener mayor beneficio funcional tras la terapia celular. La mejoría funcional también parece aumentada en los pacientes con menor capacidad migratoria de las células infundidas (AU)

Introduction and objectives. Different studies have shown improvement in patients with idiopathic nonischemic dilated cardiomyopathy treated with cell-therapy. However, factors influencing responsiveness are not well known. This trial investigates functional changes and factors influencing the 6-month gain in ejection fraction in 27 patients with dilated cardiomiopathy treated with intracoronary cell-therapy. Methods. Patients received intracoronary infusion of autologous bone-marrow mononuclear cells (mean infused, 10.2 [2.9]×108). Flow cytometry and functional analyses of the cells were also performed. Results. The 6-month angiographic gain in ejection fraction ranged from −9% to 34% (mean, 9%). These changes were distinguished into 2 groups: 21 patients (78%) with a significant improvement at the 6-month evaluation (mean gain, 14 [7]%), and 6 patients who had no response (mean gain, −5 [3]%). The responders were younger as compared to the nonresponders (50 [12] years vs 62 [9] years; P<.04). There was an inverse correlation (r=−0.41; P<.003) between the gain in ejection fraction and the high density lipoprotein level, suggesting higher functional gain with low high density lipoprotein levels. The 24h migratory capability of the infused cells was significantly reduced in the responders’ group (5.4 [1.7]×108 vs 8.1 [2.3]×108; P<.009 for vascular endothelial growth factor and 5.8 [1.7]×108 vs 8.4 [2.9]×108; P<.002 for stromal cell-derived factor-1). Conclusions. Younger patients with dilated cardiomiopathy and lower plasma high density lipoprotein levels gain greater benefit from intracoronary cell-therapy. Functional improvement also seems to be enhanced by a lower migratory capacity of the infused cells (AU)

Functional improvement in patients with dilated cardiomyopathy after the intracoronary infusion of autologous bone marrow mononuclear cells.

INTRODUCTION AND OBJECTIVES: Different studies have shown improvement in patients with idiopathic nonischemic dilated cardiomyopathy treated with cell-therapy. However, factors influencing responsiveness are not well known. This trial investigates functional changes and factors influencing the 6-month gain in ejection fraction in 27 patients with dilated cardiomiopathy treated with intracoronary cell-therapy. METHODS: Patients received intracoronary infusion of autologous bone-marrow mononuclear cells (mean infused, 10.2 [2.9]×10(8)). Flow cytometry and functional analyses of the cells were also performed. RESULTS: The 6-month angiographic gain in ejection fraction ranged from -9% to 34% (mean, 9%). These changes were distinguished into 2 groups: 21 patients (78%) with a significant improvement at the 6-month evaluation (mean gain, 14 [7]%), and 6 patients who had no response (mean gain, -5 [3]%). The responders were younger as compared to the nonresponders (50 [12] years vs 62 [9] years; P<.04). There was an inverse correlation (r=-0.41; P<.003) between the gain in ejection fraction and the high density lipoprotein level, suggesting higher functional gain with low high density lipoprotein levels. The 24 h migratory capability of the infused cells was significantly reduced in the responders' group (5.4 [1.7]×10(8) vs 8.1 [2.3]×10(8); P<.009 for vascular endothelial growth factor and 5.8 [1.7]×10(8) vs 8.4 [2.9]×10(8); P<.002 for stromal cell-derived factor-1). CONCLUSIONS: Younger patients with dilated cardiomiopathy and lower plasma high density lipoprotein levels gain greater benefit from intracoronary cell-therapy. Functional improvement also seems to be enhanced by a lower migratory capacity of the infused cells.

Long-term outcome of patients with isolated thin discrete subaortic stenosis treated by balloon dilation: a 25-year study.

BACKGROUND: Transluminal balloon tearing of the membrane in a thin discrete subaortic stenosis is an alternative to membrane surgical resection. However, the long-term outcome of patients with isolated thin discrete subaortic stenosis treated by transluminal balloon tearing remains unknown. METHODS AND RESULTS: This 25-year study describes findings from 76 patients with isolated thin discrete subaortic stenosis who underwent percutaneous transluminal balloon tearing of the membrane and were followed up for a mean period of 16±6 years. The age at presentation had a wide range (2-67 years). The mean age at treatment was 19±16 years. Immediately after treatment, the subvalvular gradient decreased from 70±27 to 18±12 mm Hg (P<0.001). No significant postprocedural aortic regurgitation was observed. After a mean follow-up time of 16±6 years, 11 patients (15%) developed restenosis, 3 patients (4%) progressed to muscular obstructive disease, and 1 patient (1.3%) developed a new distant obstructive membrane. Twelve patients (16%) were redilated at a mean of 5±3 years after their first treatment, and 4 patients (5%) underwent surgery at a mean of 3±2 years after their first treatment. Fifty-eight patients (77%) remained alive and free of redilation or surgery at follow-up. Larger annulus diameter and thinner membranes were independent factors associated with better long-term results. CONCLUSIONS: Most patients (77%) with isolated thin discrete subaortic stenosis treated with transluminal balloon tearing of the membrane had sustained relief at subsequent follow-ups without restenosis, the need for surgery, progression to muscular obstructive disease, or an increase in the degree of aortic regurgitation.

Coronary bifurcation lesions treated with simple approach (from the Cordoba & Las Palmas [CORPAL] Kiss Trial).

The present report compared the incidence of 1-year clinical events in patients with bifurcation lesions that had been treated with a simple approach who were randomized to either a simultaneous final kissing balloon (KB) or an isolated side-branch (SB) balloon post-dilation. From February 2007 to December 2008, 293 patients with all types of Medina bifurcation lesions were enrolled in a prospective study. All patients underwent implantation of a sirolimus- or everolimus-eluting stent across the bifurcation and provisional SB stenting. Patients with no SB ostial compromise or those needing a second stent were excluded from the present study (n = 49). The eligible patients were randomly assigned to treatment with final KB inflation (n = 124, KB group) or isolated balloon after dilation (n = 120, non-KB group). No significant differences were found between the patients from the KB and non-KB groups in terms of age, risk factors, clinical status, or location of the bifurcation lesions. The angiographic data and immediate results were also similar in both groups. Four patients experienced a non-Q-wave acute myocardial infarction in the hospital: three (2%) from the KB group and one (1%) from the non-KB group. Two in-hospital deaths occurred in the non-KB group. Target lesion revascularization was required in 7 patients (3%): 5 from the KB group and 2 from the non-KB group. Late mortality occurred in 3 patients from the KB group and 2 patients from the non-KB group. The incidence of major events at 1 year (death, target lesion revascularization, or acute myocardial infarction) was similar in both groups: 11 (9%) from the KB group and 7 (6%) from the non-KB group (p = NS). In conclusion, no differences in the clinical outcome at 1 year of follow-up were observed between the patients with bifurcation lesions treated with a simple approach and either a simultaneous final KB or an isolated SB balloon post-dilation.

Use of the venture wire-control catheter for accessing side branches during provisional stenting: an option for bifurcations with an unfavorable anatomy.

We report our experience with the Venture wire-control catheter in 20 patients with bifurcation lesions in which it was impossible to access the side branch using conventional techniques. This device was always used as a last resort and was employed during different stages in the treatment of the bifurcation lesions (i.e. initially, after stenting of the main vessel or both). In 17 patients (85%), use of the Venture catheter resulted in the success of the procedure. Only one complication associated with a monorail catheter was recorded. It was resolved successfully. One patient died from heart failure 10 days after the procedure and two patients, in whom it was impossible to access the side branch, had non-Q-wave myocardial infarctions. In conclusion, the Venture catheter was effective and safe, and enabled the side branches of complex bifurcation lesions to be accessed.

Utilidad del catéter Venture para acceder al ramo lateral en la técnica de stent provisional: una alternativa para bifurcaciones con anatomías desfavorables / Use of the venture wire-control catheter for accessing side branches during provisional stenting: an option for bifurcations with an unfavorable anatomyd

Describimos nuestra experiencia con el catéter Venture en 20 pacientes con lesiones en bifurcación en los que fue imposible cruzar al ramo lateral con la tecnología habitual. Este dispositivo se utilizó siempre como último recurso y en diferentes etapas del tratamiento de la bifurcación (basal, post-stent en el vaso principal o en ambas). En 17 pacientes (85%), el catéter Venture condujo al éxito del procedimiento. Sólo se registró una complicación relacionada con un catéter monorraíl, la cual se resolvió exitosamente. Un paciente murió por insuficiencia cardiaca 10 días después del procedimiento y 2 pacientes, en los que fue imposible acceder al ramo lateral, sufrieron un infarto no-Q. En conclusión, el catéter Venture es útil y seguro, y permite acceder al ramo lateral en lesiones bifurcadas complejas (AU)

We report our experience with the Venture wirecontrol catheter in 20 patients with bifurcation lesions in which it was impossible to access the side branch using conventional techniques. This device was always used as a last resort and was employed during different stages in the treatment of the bifurcation lesions (i.e. initially, after stenting of the main vessel or both). In 17 patients (85%), use of the Venture catheter resulted in the success of the procedure. Only one complication associated with a monorail catheter was recorded. It was resolved successfully. One patient died from heart failure 10 days after the procedure and two patients, in whom it was impossible to access the side branch, had non-Q-wave myocardial infarctions. In conclusion, the Venture catheter was effective and safe, and enabled the side branches of complex bifurcation lesions to be accessed (AU)

Functional recovery following intracoronary infusion of autologous mononuclear bone marrow cells in patients with chronic anterior myocardial infarction and severely depressed ventricular function.

INTRODUCTION AND OBJECTIVES: Studies have shown that intracoronary infusion of mononuclear bone marrow cells improves ventricular function in patients with acute myocardial infarction. However, less information is available about the use of this therapy during the chronic phase of a myocardial infarction. This study involved an analysis of the clinical, echocardiographic and angiographic changes observed in 19 patients with a revascularized chronic anterior myocardial infarction and depressed ventricular function who were treated by cell therapy. METHODS: A series of patients were monitored during treatment and 6 months and 1 year after treatment. Autologous bone marrow was obtained by needle aspiration of the iliac crest and mononuclear cells were isolated by density-gradient centrifugation. An in vitro biological study of a sample of the infused cells was performed using fluorocytometry, phenotype marking and an analysis of the chemotactic properties of the cells. RESULTS: Six months and 1 year after cell therapy, a modest improvement was observed in clinical status and ventricular function, which was most pronounced in the group of patients who responded. Characteristically, these patients were revascularized close to the time of cell therapy. There was an inverse relationship between functional recovery and biological parameters that reflected a state conducive to cell migration. CONCLUSIONS: The intracoronary infusion of mononuclear bone marrow cells into patients with chronic anterior myocardial infarction appeared to result in a modest clinical and functional improvement after 6 months which was sustained up to 1 year after treatment.

[Regenerative therapy in patients with a revascularized acute anterior myocardial infarction and depressed ventricular function]. / Tratamiento regenerativo en pacientes con infarto agudo anterior revascularizado y función ventricular deprimida.

INTRODUCTION AND OBJECTIVES: It is difficult to distinguish the effects early revascularization and regenerative therapy have on left ventricular function in patients with acute myocardial infarction (AMI). This study was an investigation into three groups of patients who had a revascularized anterior wall AMI and depressed left ventricular function (i.e., ejection fraction < 45%). The aim was to compare changes in left ventricular function between patients who received regenerative therapy and those who did not. METHODS: Patients were randomly assigned to receive either an intracoronary infusion of autologous mononuclear bone marrow cells (Group I; n=10) or systemic administration of granulocyte colony-stimulating factor (G-CSF) (Group II; n=10), or to a control group (Group III; n=10). In Group I, intracoronary infusion was carried out 7(2) days after AMI. Group-II patients received a 10-day course of subcutaneous G-CSF injections, 10 .g/kg per day starting 5 days after AMI. Ventricular function was assessed at baseline and 3-month follow-up. RESULTS: A 20% increase in mean ejection fraction was observed in Group I, compared with increases of 4% (P<.01) and 6% (P<.05) in Groups II and III, respectively. CONCLUSIONS: Intracoronary infusion of mononuclear bone marrow cells in patients with AMI and poor ventricular function was associated with better short-term functional recovery than previously reported. However, mobilization of stem cells by G-CSF did not have a significant influence on functional recovery.

Tratamiento regenerativo en pacientes con infarto agudo anterior revascularizado y función ventricular deprimida / Regenerative therapy in patients with a revascularized acute anterior myocardial infarction and depressed ventricular function

Introducción y objetivos. La influencia de la revascularización precoz y del tratamiento regenerativo sobre la función ventricular en pacientes con infarto agudo de miocardio (IAM) resulta difícil de separar. En el presente estudio se analizan 3 grupos de pacientes con infarto de miocardio anterior revascularizado con función ventricular deprimida (fracción de eyección [FE] < 45%). Nuestro propósito fue comparar los cambios en la función ventricular entre los pacientes con y sin tratamiento regenerativo. Métodos. Los pacientes fueron asignados aleatoriamente para recibir una infusión intracoronaria de células mononucleares autólogas de la médula ósea (grupo I; n = 10), la administración sistémica de factor estimulante de colonias granulocíticas (G-CSF) (grupo II; n = 10), o como grupo control (grupo III; n = 10). En los pacientes del grupo I la infusión intracoronaria de células fue efectuada 7 ± 2 días tras el IAM. Los pacientes del grupo II recibieron inyección subcutánea de G-CSF (10 μg/kg/día) durante 10 días consecutivos, comenzando 5 días después del IAM. Se efectuaron estudios de función ventricular basalmente y a los 3 meses de seguimiento. Resultados. Se observó un incremento neto medio del 20% en FE en el grupo I, frente a un 4% (p < 0,01) y un 6% (p < 0,05) en los grupos II y III, respectivamente. Conclusiones. La infusión intracoronaria de células mononucleares de la médula ósea en pacientes con IAM y función ventricular deprimida se asocia con una recuperación funcional a corto plazo de mayor proporción que la publicada previamente. Sin embargo, la movilización de células madre con G-CSF no tuvo una influencia significativa en la recuperación funcional (AU)

Introduction and objectives. It is difficult to distinguish the effects early revascularization and regenerative therapy have on left ventricular function in patients with acute myocardial infarction (AMI). This study was an investigation into three groups of patients who had a revascularized anterior wall AMI and depressed left ventricular function (i.e., ejection fraction < 45%). The aim was to compare changes in left ventricular function between patients who received regenerative therapy and those who did not. Methods. Patients were randomly assigned to receive either an intracoronary infusion of autologous mononuclear bone marrow cells (Group I; n=10) or systemic administration of granulocyte colony-stimulating factor (G-CSF) (Group II; n=10), or to a control group (Group III; n=10). In Group I, intracoronary infusion was carried out 7(2) days after AMI. Group-II patients received a 10-day course of subcutaneous G-CSF injections, 10 μg/kg per day starting 5 days after AMI. Ventricular function was assessed at baseline and 3-month follow-up. Results. A 20% increase in mean ejection fraction was observed in Group I, compared with increases of 4% (P<.01) and 6% (P<.05) in Groups II and III, respectively. Conclusions. Intracoronary infusion of mononuclear bone marrow cells in patients with AMI and poor ventricular function was associated with better short-term functional recovery than previously reported. However, mobilization of stem cells by G-CSF did not have a significant influence on functional recovery (AU)

Drug-eluting stents for the treatment of bifurcation lesions: a randomized comparison between paclitaxel and sirolimus stents.

BACKGROUND: Drug-eluting stents have been shown to reduce restenosis in many types of lesions. The purpose of this article is to assess the efficacy of sirolimus- and paclitaxel-eluting stents in patients with bifurcation lesions. METHODS: Between June 2003 and October 2004, 205 patients were enrolled in a prospective randomized trial; 103 patients were assigned to sirolimus stents and 102 patients to paclitaxel stents. All patients were treated by provisional T-stenting. RESULTS: There were no differences between groups in terms of age, risk factors, clinical condition, location of the bifurcation lesion, or other technical factors. Angiographic data and immediate results were also similar in both groups. Three patients developed inhospital non-Q-wave acute myocardial infarction (2 from the sirolimus group and 1 from the paclitaxel group). Follow-up angiography was obtained in 109 patients (53%). In the sirolimus group, 5 patients developed restenosis (9%): 1 at the main vessel, 2 at the side branch, and 2 in both branches. In contrast, 16 patients from the paclitaxel group had restenosis (29%): 6 at the main vessel, 5 at the side branch, and 5 in both branches. Target lesion revascularization at 24 +/- 5 months post stenting occurred in 4 patients from the sirolimus group (4%) and in 13 from the paclitaxel group (13%) (P < .05). Late loss at the main vessel in the sirolimus group patients was 0.31 +/- 0.59 versus 0.60 +/- 0.77 mm in patients from the paclitaxel group (P < .05). CONCLUSIONS: Patients with bifurcation lesions treated by sirolimus showed significantly lower rates of late loss, restenosis and target lesion revascularization than patients treated with paclitaxel-eluting stents.