http://circ.ahajournals.org/content/vol120/issue15/
Volume 120, Issue 15; October 13, 2009
Abstract 1 of 8 (Circulation. 2009;120:1465-1473.)
© 2009 American Heart Association, Inc.
Arrhythmia/Electrophysiology
Coronary Artery Injury Due to Catheter Ablation in Adults
Presentations and Outcomes
Kurt C. Roberts-Thomson, MBBS, PhD; Daniel Steven, MD; Jens Seiler, MD, PhD; Keiichi Inada, MD; Bruce A. Koplan, MD; Usha B. Tedrow, MD, MSc; Laurence M. Epstein, MD; William G. Stevenson, MD
From the Cardiac Arrhythmia Division, Cardiovascular Division, Brigham and Women’s Hospital, and Harvard Medical School, Boston, Mass.
Background— Currently, only anecdotal information exists on the presentation and outcome of coronary arterial injury after ablation procedures.
Methods and Results— Four patients who sustained coronary artery injury of a cohort of patients undergoing 4655 consecutive ablation procedures (0.09%) are described. The patients’ mean age was 45±11 years, and 1.8±0.5 prior ablation attempts had been unsuccessful. Coronary injury occurred from epicardial ventricular tachycardia ablation in 2 patients (irrigated radiofrequency ablation in one and cryoablation in the other) and ablation within the middle cardiac vein with irrigated radiofrequency in 2 patients. All involved branches of the right coronary artery. Acute occlusion presenting with ST-segment elevation immediately after ablation was recognized during the procedure in 2 cases. Occlusion failed to respond to nitroglycerin or balloon dilation, and stenting was required in both cases. Acute myocardial infarction occurred 2 weeks after epicardial ablation as a result of occlusion of a right ventricular branch of the right coronary artery giving rise to the posterior descending coronary artery in 1 patient. A moderate asymptomatic stenosis was seen on angiography after epicardial cryoablation in 1 patient. All patients recovered and remained asymptomatic from the coronary injury and arrhythmias during 37±53 months of follow-up.
Conclusions— Coronary arterial injury after ablation procedures is rare. It may present acutely or several weeks after an ablation procedure. Acute occlusion appears to require coronary stenting. Unanticipated anatomic variations can predispose to coronary injury.
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Abstract 2 of 8 (Circulation. 2009;120:1474-1481.)
© 2009 American Heart Association, Inc.
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Cardiovascular Surgery
Predictors of Improvement of Unrepaired Moderate Ischemic Mitral Regurgitation in Patients Undergoing Elective Isolated Coronary Artery Bypass Graft Surgery
Martin Penicka, MD, PhD; Hana Linkova, MD; Otto Lang, MD, PhD; Richard Fojt, MD; Viktor Kocka, MD; Marc Vanderheyden, MD; Jozef Bartunek, MD, PhD
From the Departments of Cardiology (M.P., H.L., R.F., V.K.) and Nuclear Medicine (O.L.), Third Faculty of Medicine Charles University, Prague, Czech Republic, and Cardiovascular Center (M.V., J.B.), OLV Hospital, Aalst, Belgium.
Background— The persistence of moderate ischemic mitral regurgitation (IMR) after isolated coronary artery bypass graft surgery is an important independent predictor of long-term mortality. The aim of the present study was to identify predictors of postoperative improvement in moderate IMR in patients with ischemic heart disease undergoing elective isolated coronary artery bypass graft surgery.
Methods and Results— The study population consisted of 135 patients with ischemic heart disease (age, 65±9 years; 81% male) and moderate IMR undergoing isolated coronary artery bypass graft surgery. Fourteen patients died before the 12-month follow-up echocardiography and were excluded. At the 12-month follow-up, 57 patients showed no or mild IMR (improvement group), whereas 64 patients failed to improve (failure group). Before coronary artery bypass graft surgery, the improvement group had significantly more viable myocardium and less dyssynchrony between papillary muscles than the failure group (P<0.001). All other preoperative parameters were similar in both groups. Large extent (5 segments) of viable myocardium (odds ratio, 1.45; 95% confidence interval, 1.22 to 1.89; P<0.001) and absence (<60 ms) of dyssynchrony (odds ratio, 1.49; 95% confidence interval, 1.29 to 1.72; P<0.001) were independently associated with improvement in IMR. The majority (93%) of patients with viable myocardium and an absence of dyssynchrony showed an improvement in IMR. In contrast, only 34% and 18% of patients with dyssynchrony and nonviable myocardium, respectively, showed an improvement in IMR, whereas 32% and 49%, respectively, of these patients showed worsening of IMR (P<0.001).
Conclusion— Reliable improvement in moderate IMR by isolated coronary artery bypass graft surgery was observed only in patients with concomitant presence of viable myocardium and absence of dyssynchrony between papillary muscles.
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Abstract 3 of 8 (Circulation. 2009;120:1482-1490.)
© 2009 American Heart Association, Inc.
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Congenital Heart Disease
Predictors of Technical Success and Postnatal Biventricular Outcome After In Utero Aortic Valvuloplasty for Aortic Stenosis With Evolving Hypoplastic Left Heart Syndrome
Doff B. McElhinney, MD; Audrey C. Marshall, MD; Louise E. Wilkins-Haug, MD, PhD; David W. Brown, MD; Carol B. Benson, MD; Virginia Silva, MSN; Gerald R. Marx, MD; Arielle Mizrahi-Arnaud, MD; James E. Lock, MD; Wayne Tworetzky, MD
From the Departments of Cardiology (D.B.M., A.C.M., D.W.B., G.R.M., J.E.L., W.T.) and Anesthesiology, Perioperative and Pain Medicine (A.M.-A.), Children’s Hospital Boston, and Pediatrics, Harvard Medical School, Departments of Obstetrics and Gynecology (L.E.W.-H., V.S.) and Radiology (C.B.B.), Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass.
Background— Aortic stenosis in the midgestation fetus with a normal-sized or dilated left ventricle predictably progresses to hypoplastic left heart syndrome when associated with certain physiological findings. Prenatal balloon aortic valvuloplasty may improve left heart growth and function, possibly preventing evolution to hypoplastic left heart syndrome.
Methods and Results— Between March 2000 and October 2008, 70 fetuses underwent attempted aortic valvuloplasty for critical aortic stenosis with evolving hypoplastic left heart syndrome. We analyzed this experience to determine factors associated with procedural and postnatal outcome. The median gestational age at intervention was 23 weeks. The procedure was technically successful in 52 fetuses (74%). Relative to 21 untreated comparison fetuses, subsequent prenatal growth of the aortic and mitral valves, but not the left ventricle, was improved after intervention. Nine pregnancies (13%) did not reach a viable term or preterm birth. Seventeen patients had a biventricular circulation postnatally, 15 from birth. Larger left heart structures and higher left ventricular pressure at the time of intervention were associated with biventricular outcome. A multivariable threshold scoring system was able to discriminate fetuses with a biventricular outcome with {bfb} sensitivity and modest positive predictive value.
Conclusions— Technically successful aortic valvuloplasty alters left heart valvar growth in fetuses with aortic stenosis and evolving hypoplastic left heart syndrome and, in a subset of cases, appeared to contribute to a biventricular outcome after birth. Fetal aortic valvuloplasty carries a risk of fetal demise. Fetuses undergoing in utero aortic valvuloplasty with an unfavorable multivariable threshold score at the time of intervention are very unlikely to achieve a biventricular circulation postnatally.
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Abstract 4 of 8 (Circulation. 2009;120:1491-1497.)
© 2009 American Heart Association, Inc.
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Epidemiology and Prevention
Cardiovascular Benefit of Magnitude of Low-Density Lipoprotein Cholesterol Reduction
A Comparison of Subgroups by Age
Catherine R. Rahilly-Tierney, MD, MPH; Elizabeth V. Lawler, MPH, ScD; Richard E. Scranton, MD, MPH; J. Michael Gaziano, MD, MPH
From the Massachusetts Veterans Epidemiology and Research Information Center (C.R.R.-T., E.V.L., R.E.S., J.M.G.), Boston VA Healthcare System, Boston, Mass; Divisions of Aging, Cardiology, and Preventative Medicine (C.R.R.-T., E.V.L., R.E.S., J.M.G.), Brigham and Women’s Hospital, Boston, Mass; and VeroScience, LLC (R.E.S.), Tiverton, RI.
Background— We examined the effect of the magnitude of low-density lipoprotein cholesterol (LDL-C) reduction across subjects of various ages in a retrospective cohort study.
Methods and Results— We selected 20 132 male veterans at high risk for an acute cardiovascular event and who had 2 or more LDL-C measurements before their first documented acute myocardial infarction, revascularization, death, or censoring date. LDL-C reduction was categorized as no reduction (<10 mg/dL; reference), small reduction (between 10 and 40 mg/dL), moderate reduction (between 40 and 70 mg/dL), or large reduction (70 mg/dL). The primary outcome was combined acute myocardial infarction or revascularization. The first and last LDL-C levels in the databases were used to calculate the LDL-C reduction in patients who experienced no outcome or who died. Within each age quartile and in a subgroup of patients 80 years of age, a Cox proportional hazards model was used to determine hazard ratios for each category of LDL-C reduction compared with the reference category, with adjustment for age, body mass index, current smoking status, medications, and comorbidities. In all age groups, the magnitude of LDL-C reduction was proportional to the magnitude of cardiovascular risk reduction. Risk reduction for the combined outcome in patients who achieved a large LDL-C reduction was similar in all age quartiles, with multivariate-adjusted hazard ratios of approximately 0.30.
Conclusions— In a cohort of veterans at high risk for cardiovascular events, patients of all ages, including those 80 years or older, benefitted the most from large reductions in LDL-C.
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Abstract 5 of 8 (Circulation. 2009;120:1498-1504.)
© 2009 American Heart Association, Inc.
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Interventional Cardiology
Final 5-Year Results of the TAXUS II Trial
A Randomized Study to Assess the Effectiveness of Slow- and Moderate-Release Polymer-Based Paclitaxel-Eluting Stents for De Novo Coronary Artery Lesions
Sigmund Silber, MD; Antonio Colombo, MD; Adrian P. Banning, MD; Karl Hauptmann, MD; Janusz Drzewiecki, MD; Eberhard Grube, MD; Dariusz Dudek, MD; Donald S. Baim, MD
From the Cardiology Practice and Hospital (S.S.), Munich, Germany; San Raffaele Scientific Institute (A.C.), Milan, Italy; John Radcliffe Hospital (A.P.B.), Oxford, United Kingdom; Krankenhaus der Barmherzigen Brüder (K.H.), Trier, Germany; Silesian Medical University (J.D.), Katowice, Poland; HELIOS Heart Center (E.G.), Siegburg, Germany; Jagiellonian University (D.D.), Krakow, Poland; and Boston Scientific Corporation (D.S.B.), Natick, Mass.
Background— The TAXUS II trial was designed to evaluate the safety and efficacy of the commercialized slow-release (SR) and an investigation-only moderate-release (MR) polymer-based TAXUS paclitaxel-eluting stent compared with a bare-metal stent for the treatment of de novo coronary lesions.
Methods and Results— This prospective, randomized, double-blind, controlled trial enrolled 536 patients in 2 consecutive cohorts to compare TAXUS SR (n=131) and TAXUS MR (n=135) with an identical but uncoated bare-metal stent control (n=270). The present analysis reports final 5-year clinical outcomes of TAXUS II. At 5 years, both TAXUS SR and MR showed superior outcomes compared with control. The 5-year rates of major adverse cardiac events were 27.6%, 20.4%, and 15.1% (P=0.01); rates of target-vessel revascularization were 22.5%, 16.6%, and 9.0% (P=0.004); and rates of target-lesion revascularization were 18.4%, 10.3%, and 4.5% (P<0.001) for the control, TAXUS SR, and TAXUS MR groups, respectively. The rates of all-cause death and myocardial infarction were low and similar between groups, with 2 stent thromboses with bare-metal stents compared with no event beyond 2 years with either of the TAXUS stents.
Conclusions— TAXUS II is the first large TAXUS trial to have reached 5-year follow-up. Both the SR and MR stents lowered the rates of target-vessel and target-lesion revascularization, which indicates their sustained efficacy. Furthermore, the low overall rates of all death, myocardial infarction, and stent thrombosis support the long-term safety of the TAXUS stent system.
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Abstract 6 of 8 (Circulation. 2009;120:1505-1512.)
© 2009 American Heart Association, Inc.
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Interventional Cardiology
Long-Term Clinical Outcome After Fractional Flow Reserve–Guided Treatment in Patients With Angiographically Equivocal Left Main Coronary Artery Stenosis
Michalis Hamilos, MD, PhD*; Olivier Muller, MD, PhD*; Thomas Cuisset, MD; Argyrios Ntalianis, MD, PhD; Gregory Chlouverakis, PhD; Giovanna Sarno, MD; Olivier Nelis, RN; Jozef Bartunek, MD, PhD; Marc Vanderheyden, MD; Eric Wyffels, MD; Emanuele Barbato, MD, PhD; Guy R. Heyndrickx, MD, PhD; William Wijns, MD, PhD; Bernard De Bruyne, MD, PhD
From the Cardiovascular Centre Aalst, Aalst, Belgium (M.H., O.M., T.C., A.N., G.S., O.N., J.B., M.V., E.W., E.B., G.R.H., W.W., B.D.B.), and Laboratory of Biostatistics, Medical School, University of Crete, Crete, Greece (G.C.).
Background— Significant left main coronary artery stenosis is an accepted indication for surgical revascularization. The potential of angiography to evaluate the hemodynamic severity of a stenosis is limited. The aims of the present study were to assess the long-term clinical outcome of patients with an angiographically equivocal left main coronary artery stenosis in whom the revascularization strategy was based on fractional flow reserve (FFR) and to determine the relationship between quantitative coronary angiography and FFR.
Methods and Results— In 213 patients with an angiographically equivocal left main coronary artery stenosis, FFR measurements and quantitative coronary angiography were performed. When FFR was 0.80, patients were treated medically or another stenosis was treated by coronary angioplasty (nonsurgical group; n=138). When FFR was <0.80, coronary artery bypass grafting was performed (surgical group; n=75). The 5-year survival estimates were 89.8% in the nonsurgical group and 85.4% in the surgical group (P=0.48). The 5-year event-free survival estimates were 74.2% and 82.8% in the nonsurgical and surgical groups, respectively (P=0.50). Percent diameter stenosis at quantitative coronary angiography correlated significantly with FFR (r=–0.38, P<0.001), but a very large scatter was observed. In 23% of patients with a diameter stenosis <50%, the left main coronary artery stenosis was hemodynamically significant by FFR.
Conclusions— In patients with equivocal stenosis of the left main coronary artery, angiography alone does not allow appropriate individual decision making about the need for revascularization and often underestimates the functional significance of the stenosis. The favorable outcome of an FFR-guided strategy suggests that FFR should be assessed in such patients before a decision is made “blindly” about the need for revascularization.
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Abstract 7 of 8 (Circulation. 2009;120:1513-1523.)
© 2009 American Heart Association, Inc.
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Molecular Cardiology
Cardiomyocyte Differentiation of Human Induced Pluripotent Stem Cells
Limor Zwi, BSc; Oren Caspi, MD; Gil Arbel, MSc; Irit Huber, PhD; Amira Gepstein, PhD; In-Hyun Park, PhD; Lior Gepstein, MD, PhD
From the Sohnis Family Research Laboratory for Cardiac Electrophysiology and Regenerative Medicine, the Rappaport Family Institute for Research in the Medical Sciences (L.Z., O.C., G.A., I.H., A.G., L.G.), the Cardiology Department, Rambam Medical Center (L.G.), and the Biotechnology Interdisciplinary Unit (L.Z.), Technion–Israel Institute of Technology, Haifa, Israel, and the Division of Pediatric Hematology Oncology, Children’s Hospital, Boston, Mass (I.-H.P.).
Background— The ability to derive human induced pluripotent stem (hiPS) cell lines by reprogramming of adult fibroblasts with a set of transcription factors offers unique opportunities for basic and translational cardiovascular research. In the present study, we aimed to characterize the cardiomyocyte differentiation potential of hiPS cells and to study the molecular, structural, and functional properties of the generated hiPS-derived cardiomyocytes.
Methods and Results— Cardiomyocyte differentiation of the hiPS cells was induced with the embryoid body differentiation system. Gene expression studies demonstrated that the cardiomyocyte differentiation process of the hiPS cells was characterized by an initial increase in mesoderm and cardiomesoderm markers, followed by expression of cardiac-specific transcription factors and finally by cardiac-specific structural genes. Cells in the contracting embryoid bodies were stained positively for cardiac troponin-I, sarcomeric -actinin, and connexin-43. Reverse-transcription polymerase chain reaction studies demonstrated the expression of cardiac-specific sarcomeric proteins and ion channels. Multielectrode array recordings established the development of a functional syncytium with stable pacemaker activity and action potential propagation. Positive and negative chronotropic responses were induced by application of isoproterenol and carbamylcholine, respectively. Administration of quinidine, E4031 (IKr blocker), and chromanol 293B (IKs blocker) significantly affected repolarization, as manifested by prolongation of the local field potential duration.
Conclusions— hiPS cells can differentiate into myocytes with cardiac-specific molecular, structural, and functional properties. These results, coupled with the potential of this technology to generate patient-specific hiPS lines, hold great promise for the development of in vitro models of cardiac genetic disorders, for drug discovery and testing, and for the emerging field of cardiovascular regenerative medicine.
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Abstract 8 of 8 (Circulation. 2009;120:1524-1532.)
© 2009 American Heart Association, Inc.
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Molecular Cardiology
MicroRNA 217 Modulates Endothelial Cell Senescence via Silent Information Regulator 1
Rossella Menghini, PhD; Viviana Casagrande, BS; Marina Cardellini, MD; Eugenio Martelli, MD; Alessandro Terrinoni, PhD; Francesca Amati, PhD; Mariuca Vasa-Nicotera, MD; Arnaldo Ippoliti, MD; Giuseppe Novelli, PhD; Gerry Melino, MD; Renato Lauro, MD; Massimo Federici, MD
From the Department of Internal Medicine (R.M., V.C., M.C., R.L., M.F.), Department of Surgery (E.M., A.I.), IDI-IRCCS Biochemistry Laboratory, c/o Department of Experimental Medicine (A.T., G.M.), and Department of Biopathology and Imaging (F.A., G.N.), University of Rome Tor Vergata, Rome, Italy; and Medical Research Council (M.V.-N., G.M.), Toxicology Unit, University of Leicester, Leicester, United Kingdom.
Background— Aging is a major risk factor for the development of atherosclerosis and coronary artery disease. Through a microarray approach, we have identified a microRNA (miR-217) that is progressively expressed in endothelial cells with aging. miR-217 regulates the expression of silent information regulator 1 (SirT1), a major regulator of longevity and metabolic disorders that is progressively reduced in multiple tissues during aging.
Methods and Results— miR-217 inhibits SirT1 expression through a miR-217–binding site within the 3′-UTR of SirT1. In young human umbilical vein endothelial cells, human aortic endothelial cells, and human coronary artery endothelial cells, miR-217 induces a premature senescence-like phenotype and leads to an impairment in angiogenesis via inhibition of SirT1 and modulation of FoxO1 (forkhead box O1) and endothelial nitric oxide synthase acetylation. Conversely, inhibition of miR-217 in old endothelial cells ultimately reduces senescence and increases angiogenic activity via an increase in SirT1. miR-217 is expressed in human atherosclerotic lesions and is negatively correlated with SirT1 expression and with FoxO1 acetylation status.
Conclusions— Our data pinpoint miR-217 as an endogenous inhibitor of SirT1, which promotes endothelial senescence and is potentially amenable to therapeutic manipulation for prevention of endothelial dysfunction in metabolic disorders.

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