Calin V. Maniu

ACC/AHA/SCAI/AMA-Convened PCPI/NCQA 2013 performance measures for adults undergoing percutaneous coronary intervention: a report of the American College of Cardiology/American Heart Association Task Force on Performance Measures, the Society for Cardiovascular Angiography and Interventions, the American Medical Association-Convened Physician Consortium for Performance Improvement, and the National Committee for Quality Assurance.

American College of Cardiology (ACC)/American Heart Association (AHA) performance measure sets can serve as vehicles to accelerate appropriate translation of scientific evidence into clinical practice. These documents are intended to provide practitioners and institutions that deliver cardiovascular

Failure of Treatment for Chronic Mycobacterium abscessus Meningitis Despite Adequate Clarithromycin Levels in Cerebrospinal Fluid

We report a case of posttraumatic meningitis due to Mycobacterium abscessus, treated initially with oral clarithromycin and intravenous amikacin plus intrathecal amikacin. Despite cerebrospinal fluid (CSF) levels of clarithromycin and amikacin in excess of their in vitro minimum inhibitory concentrations for the organism, the CSF cultures remained continuously positive for M. abscessus. To our knowledge, this is the first documented case of M. abscessus meningitis and the first report of measured CSF levels of clarithromycin in a patient with meningitis, showing that even therapeutic CSF levels of clarithromycin and amikacin might not be successful in eradicating M. abscessus meningitis.

Titin Isoforms, Extracellular Matrix, and Global Chamber Remodeling in Experimental Dilated Cardiomyopathy Functional Implications and Mechanistic Insight

Background—Altered titin isoforms may modify cardiac function in heart failure (HF), but the nature of isoform switches and associated functional implications are not well defined. Limited studies have reported an increased compliant isoform (N2BA) expression in human systolic HF. Titin may also modulate stretch-regulated responses such as myocardial natriuretic peptide production. Methods and Results—We characterized titin isoform expression and extracellular matrix in all 4 cardiac chambers and the left ventricular (LV) epicardium and endocardium in normal dogs (n=6) and those with HF (n=6) due to tachypacing and characterized functional implications at the LV myofiber and chamber level. Recognizing the potential for uncoupling of the extracellular matrix and cardiomyocyte in tachypacing, myocardial natriuretic peptide production, a molecular marker of stretch-regulated responses, was also assessed. All chambers were dilated in HF, but the extracellular matrix was not increased. HF dogs had markedly lower N2BA in the atria and right ventricle. In failing LVs, N2BA was decreased only in the epicardium, where myofiber passive stiffness was increased. However, LV chamber mechanics were driven by the marked LV dilatation, with no increase in LV diastolic stiffness. Natriuretic peptide concentrations increased markedly in the endocardium in relation to increases in LV wall stress. Conclusions—Tachypacing HF is characterized by decreases in compliant titin isoform expression in the atria, right ventricle, and LV epicardium. However, LV chamber mechanics are principally determined by geometric and extracellular matrix changes rather than titin-based myofiber stiffness in this model. Stretch-regulated myocardial responses (natriuretic peptide production) appeared intact, suggesting that the mechanotransduction role of titin was not impaired in HF.

Patent Foramen Ovale Transcatheter Closure Device Thrombosis

The role of patent foramen ovale (PFO) in patients with cryptogenic stroke (stroke of unknown cause) remains controversial, although an association seems likely in younger patients with atrial septal aneurysms and PFO. The mechanism of cryptogenic stroke in these patients is presumed to be paradoxical embolism via right-to-left shunt across the PFO. The available options for treatment include medical therapy with antiplatelet or anticoagulant therapy or closure of the PFO surgically or with use of transcatheter PFO closure devices. We describe 2 cases of bilateral device thrombosis associated with use of a transcatheter PFO closure device (CardioSEAL). To our knowledge, only 1 other case of thrombosis associated with use of this device has been reported.

ACC/AHA/SCAI/AMA-Convened PCPI/NCQA 2013 Performance Measures for Adults Undergoing Percutaneous Coronary Intervention: A Report of the American College of Cardiology/American Heart Association Task Force on Performance Measures, the Society for Cardiovascular Angiography and Interventions

Brahmajee K. Nallamothu, MD, MPH, FACC, FAHA Carl L. Tommaso, MD, FACC, FAHA, FSCAI H. Vernon Anderson, MD, FACC, FAHA, FSCAI David J. Malenka, MD, FACC, FAHA Jeffrey L. Anderson, MD, FACC, FAHA, MACP Calin V. Maniu, MD, FACC, FAHA, FSCAI Joseph C. Cleveland Kevin W . McCabe , MD R . Adams Dudley, MD, MBA James D. Mortimer, Peter Louis Duffy, MD, MMM, FACC, FSCAI Manesh R. Patel, MD, FACC David P. Faxon, MD, FACC, FAHA Stephen D. Persell, MD, MPH Hitinder S. Gurm, MD, FACC John S. Rumsfeld, MD, PhD, FACC, FAHA Lawrence A. Hamilton, Kendrick A. Shunk, MD, PhD, FACC, FAHA, FSCAI Neil C. Jensen, MHA, MBA Sidney C. Smith Richard A. Josephson, MD, MS, FACC, FAHA, FAACVPR Stephen J. Stanko, MBA, BA, AA Brook Watts, MD, MS

Hemodynamic and Humoral Effects of Vasopeptidase Inhibition in Canine Hypertension

Abstract—Vasopeptidase inhibitors are potent new antihypertensive agents. The dual inhibition of ACE and neutral endopeptidase may result in synergistic humoral effects with unique hemodynamic actions. We investigated the hemodynamic and neurohumoral effects of vasopeptidase inhibition in conscious dogs made hypertensive by bilateral renal wrapping and subsequently instrumented for long-term assessment of left ventricular pressure and volume (n=8). Intravenous vasopeptidase inhibition (omapatrilat, 30 &mgr;mol/kg over 10 minutes) reduced peak left ventricular pressure (171±6 versus 130±6 mm Hg immediately after infusion, P <0.01) through arterial vasodilation (arterial elastance, 9.8±0.8 to 5.8±1.6 mm Hg/mL, P <0.01) and preload reduction (left ventricular end-diastolic volume, 51.1±6.8 to 46.0±6.9 mL, P <0.01). At 60 minutes, preload decreased further (40.5±5.9 mL, P <0.01 versus baseline). Vasopeptidase inhibition increased plasma levels of adrenomedullin (41.2±9.6 versus 72.3±15 pg/mL, P <0.01), whereas levels of the natriuretic peptides and cGMP were unchanged. Similar hemodynamic and humoral effects were observed with long-term therapy. Neither an equimolar dose of an ACE inhibitor (fosinopril) nor exogenous adrenomedullin had as potent of a hypotensive effect, and neither reduced preload. In summary, the potent short-term and long-term hypotensive effects of vasopeptidase inhibition were prominently mediated by preload reduction, an effect not reproduced by ACE inhibition nor adrenomedullin augmentation and not associated with enhanced natriuretic peptide levels. Combined arterial vasodilation and preload reduction may confer additional potency as well as unique cardioprotective effects. Synergistic effects on humoral and probably endothelial vasodilatory factors appear to be important in mediating the unique hemodynamic profile of vasopeptidase inhibition in this form of experimental hypertension.

Titin Isoforms, Extracellular Matrix, and Global Chamber Remodeling in Experimental Dilated CardiomyopathyCLINICAL PERSPECTIVE

Background—Altered titin isoforms may modify cardiac function in heart failure (HF), but the nature of isoform switches and associated functional implications are not well defined. Limited studies have reported an increased compliant isoform (N2BA) expression in human systolic HF. Titin may also modulate stretch-regulated responses such as myocardial natriuretic peptide production. Methods and Results—We characterized titin isoform expression and extracellular matrix in all 4 cardiac chambers and the left ventricular (LV) epicardium and endocardium in normal dogs (n=6) and those with HF (n=6) due to tachypacing and characterized functional implications at the LV myofiber and chamber level. Recognizing the potential for uncoupling of the extracellular matrix and cardiomyocyte in tachypacing, myocardial natriuretic peptide production, a molecular marker of stretch-regulated responses, was also assessed. All chambers were dilated in HF, but the extracellular matrix was not increased. HF dogs had markedly lower N2BA in the atria and right ventricle. In failing LVs, N2BA was decreased only in the epicardium, where myofiber passive stiffness was increased. However, LV chamber mechanics were driven by the marked LV dilatation, with no increase in LV diastolic stiffness. Natriuretic peptide concentrations increased markedly in the endocardium in relation to increases in LV wall stress. Conclusions—Tachypacing HF is characterized by decreases in compliant titin isoform expression in the atria, right ventricle, and LV epicardium. However, LV chamber mechanics are principally determined by geometric and extracellular matrix changes rather than titin-based myofiber stiffness in this model. Stretch-regulated myocardial responses (natriuretic peptide production) appeared intact, suggesting that the mechanotransduction role of titin was not impaired in HF.

Optical coherence tomography findings after chronic total occlusion interventions: Insights from the “AngiographiC evaluation of the everolimus-eluting stent in chronic Total occlusions” (ACE-CTO) study (NCT01012869)

BACKGROUND There is limited information on optical coherence tomography (OCT) findings after percutaneous coronary intervention (PCI) of chronic total occlusions (CTOs). OCT allows high resolution imaging that can enhance understanding of the vascular response after stenting of chronically occluded vessels. METHODS The Angiographic Evaluation of the Everolimus-Eluting Stent in Chronic Total Occlusions (ACE-CTO) study collected angiographic and clinical outcomes from 100 patients undergoing CTO PCI with the everolimus-eluting stent (EES). OCT was performed 8-months post stenting in 62 patients. Every third frame was analyzed throughout the course of the stented arterial segment. Lumen contours were semi-automatically traced and stent struts were manually delineated, with automatic measurement of the strut to lumen distance. Struts on the luminal side of the lumen contour were classified as malapposed if the distance to the lumen contour exceeded 0.108mm. RESULTS A total of 44,450 struts in 6047 frames were analyzed, of which 4113 9.3%, 95% confidence intervals [CI] 9.0% to 9.5%) were malapposed and 1230 (2.8%, 95% CI 2.6% to 2.9%) were uncovered. Fifty-five of 62 patients (88.7%, 95% CI 78.5% to 98.4%) had at least one malapposed stent strut and 50 patients (80.7%, 95% CI 69.2% to 88.6%) had at least one uncovered stent strut. Mean strut-intimal thickness of the apposed and malapposed struts was 0.126±0.140mm and -0.491±0.440mm, respectively. CONCLUSION High rates of stent strut malapposition and incomplete stent strut coverage were observed after CTO PCI using EES, highlighting unique challenges associated with stent implantation in CTOs.

Assessing coronary endothelial dysfunction.

To the Editor: Hollenberg and colleagues report that coronary endothelial dysfunction, as detected by abnormal epicardial and microvascular responses to acetylcholine, preceded the development of clinical end points after heart transplantation.1 Similarly, we have shown that coronary endothelial dysfunction has an important effect on prognosis in patients with early coronary atherosclerosis. Although we acknowledge the importance of their findings and their potential clinical impact, we have some reservations about their study methods. The investigators appropriately assessed the microcirculation by measuring the coronary blood flow response to acetylcholine infusion with the use of the Doppler guidewire. The previously validated method for measuring coronary blood flow with the Doppler guidewire involves combining the averaged pulse-wave Doppler velocities with flow, or luminal, area at the site of the …

THE ‘ANGIOGRAPHIC EVALUATION OF THE EVEROLIMUS-ELUTING STENT IN CHRONIC TOTAL OCCLUSIONS’ (ACE-CTO) STUDY

BACKGROUND There are limited data on outcomes after implantation of second-generation drug-eluting stents in coronary chronic total occlusions (CTOs). We aimed to evaluate the frequency of angiographic restenosis and clinical outcomes after implantation of the everolimus-eluting stent (EES) in coronary CTOs. METHODS One hundred patients undergoing successful CTO percutaneous coronary intervention using EES at our institution between 2009 and 2012 were enrolled. The primary study endpoint was binary in-segment restenosis at 8-month follow-up quantitative coronary angiography. Secondary endpoints included death, myocardial infarction, target-lesion and target-vessel revascularization, and symptom improvement. RESULTS Mean age was 64 ± 7 years and 99% of the patients were men. The successful crossing technique was antegrade wiring in 51 patients, antegrade dissection/reentry in 24 patients, and retrograde in 25 patients. Binary angiographic restenosis occurred in 46% of the patients (95% confidence interval [CI], 35%-57%). The pattern of restenosis was focal, proliferative, and total occlusion in 19 lesions (46%), 14 lesions (34%), and 8 lesions (20%), respectively. At 12 months, the incidences of death, myocardial infarction, target-lesion revascularization, and target-vessel revascularization were 2%, 2%, 37%, and 39%, respectively. At 12 months, symptoms were improved, unchanged, or worse compared with baseline in 89 patients, 8 patients, and 1 patient, respectively (2 patients died before the 12-month follow-up). On multivariable analysis, smaller stent diameter was associated with higher risk for binary angiographic restenosis. CONCLUSION High rates of angiographic restenosis and repeat revascularization were observed among patients receiving EES in coronary CTOs, but most had significant symptom improvement.