Long Term Outcomes of MGuard Stent Deployment in Saphenous Vein Grafts and Native Coronary Arteries: A Single Center Experience.

BACKGROUND: The MGuard™ stent (InspireMD, Tel Aviv, Israel) is a bare metal mesh-covered stent, developed to prevent no-reflow phenomenon during percutaneous coronary intervention (PCI) of saphenous vein grafts (SVG) and acute myocardial infarction (MI), both associated with significant atherothrombotic lesions. OBJECTIVES: To report on local experience with patients treated with the MGuard stent until follow-up at 1 year. METHODS: We followed 163 consecutive patients who underwent MGuard stent deployment during the period 2009 to 2014 in a large tertiary cardiac center in central Israel. RESULTS: The MGuard stent was used in 67% of patients who underwent SVG-PCI while 33% were treated for native coronary artery disease, the majority during ST-elevation MI (STEMI). The mean age was 67 years and 83% were males. The clinical presentation was STEMI in 30% and non-STEMI/unstable angina in 60% of patients. Of the total number of patients, 47% had diabetes and 29% had chronic kidney disease. All patients had follow-up at 1 year. Mortality in the native group was 1.9% vs. 10% in the vein graft cohort. ST was 2% in both groups. The major adverse cardiac event (MACE) rates were 11% in the native artery and 29% in the vein graft group, mainly due to respective target lesion revascularization/target vessel revascularization rates of 6% and 7% in the native vessel group and 11% and 15% in the SVG group. CONCLUSIONS: In suitable patients undergoing SVG-PCI or native lesion intervention during acute MI, the MGuard stent is a viable treatment strategy. Its potential merits and limitations warrant further evaluation.

Multi-contrast late enhancement CMR determined gray zone and papillary muscle involvement predict appropriate ICD therapy in patients with ischemic heart disease.

BACKGROUND: Myocardial infarct heterogeneity indices including peri-infarct gray zone are predictors for spontaneous ventricular arrhythmias events after ICD implantation in patients with ischemic heart disease. In this study we hypothesize that the extent of peri-infarct gray zone and papillary muscle infarct scores determined by a new multi-contrast late enhancement (MCLE) method may predict appropriate ICD therapy in patients with ischemic heart disease. METHODS: The cardiovascular magnetic resonance (CMR) protocol included LV functional parameter assessment and late gadolinium enhancement (LGE) CMR using the conventional method and MCLE post-contrast. The proportion of peri-infarct gray zone, core infarct, total infarct relative to LV myocardium mass, papillary muscle infarct scores, and LV functional parameters were statistically compared between groups with and without appropriate ICD therapy during follow-up. RESULTS: Twenty-five patients with prior myocardial infarct for planned ICD implantation (age 64±10 yrs, 88% men, average LVEF 26.2±10.4%) were enrolled. All patients completed the CMR protocol and 6-46 months follow-up at the ICD clinic. Twelve patients had at least one appropriate ICD therapy for ventricular arrhythmias at follow-up. Only the proportion of gray zone measured with MCLE and papillary muscle infarct scores demonstrated a statistically significant difference (P < 0.05) between patients with and without appropriate ICD therapy for ventricular arrhythmias; other CMR derived parameters such as LVEF, core infarct and total infarct did not show a statistically significant difference between these two groups. CONCLUSIONS: Peri-infarct gray zone measurement using MCLE, compared to using conventional LGE-CMR, might be more sensitive in predicting appropriate ICD therapy for ventricular arrhythmia events. Papillary muscle infarct scores might have a specific role for predicting appropriate ICD therapy although the exact mechanism needs further investigation.

Papillary muscle involvement in myocardial infarction: initial results using multicontrast late-enhancement MRI.

We hypothesized that multicontrast late-enhancement (MCLE) MRI would improve the identification of papillary muscle involvement (PM-MI) in patients with myocardial infarction (MI), compared with conventional late gadolinium enhancement (LGE) MRI using the inversion recovery fast gradient echo (IR-FGRE) technique. Cardiac LGE-MRI studies using both MCLE and IR-FGRE pulse sequences were performed on a 1.5 Tesla (T) MRI system in 23 patients following MI. In all patients, PM-MI was confirmed by the diagnostic criteria as outlined below: (a) the increased signal intensity of PM was the same or similar to that of adjacent hyper-enhanced left ventricular (LV) infarct segments; and (b) the hyper-enhanced PM region was limited to the PM area defined by precontrast cine images of steady-state free precession (SSFP). Visual contrast score was rated according to the differentiation between LV blood pool and hyper-enhanced infarct myocardium. Quantitative contrast-noise ratios (CNR) of infarct relative to blood pool and viable myocardium were also measured on MCLE and IR-FGRE images. Of these 23 patients, 13 studies demonstrated primarily involvement of the territories of the right coronary (RCA, 8 patients) and/or left circumflex (LCX, 5 patients) arteries and 10 involved the territories of left anterior descending artery (LAD) with some LCX involvement. Although both IR-FGRE and MCLE determined the presence and extent of LV MI, better visual contrast scores were achieved in MCLE (2.9 ± 0.3) compared with IR-FGRE (1.6 ± 0.8, P < 0.001). The CNRs of infarct relative to LV blood pool showed a significant statistical difference (n = 23, P < 0.00001) between MCLE (16.2 ± 7.2) and IR-FGRE images (4.8 ± 4.1), which is consistent with the result of visual contrast scores between infarct and LV blood pool. The CNRs of infarct versus viable myocardium did not demonstrate a significant statistical difference (n = 23, P = 0.61) between MCLE (14.4 ± 7.0) and IR-FGRE images (13.6 ± 6.1). MCLE clearly demonstrated PM-MI in all cases (100%, 23/23) while only 39% (9/23) could be visualized on the corresponding IR-FGRE images. In conclusion, MCLE imaging provides better contrast between blood pool and infarct myocardium, thus improving the determination of PM-MI.

Cannabis induced cardiac arrhythmias: a case series.

INTRODUCTION: Cannabis use is known to be associated with significant cardiovascular morbidity. We describe three cases of cannabis-related malignant arrhythmias, who presented to the cardiac department at our institution within the last 2 years. All three patients were known to smoke cannabis on daily basis. CASE SUMMARIES: Case 1: A 30-year-old male, presented with recent onset of palpitations. A 12-lead electrocardiogram (ECG), transthoracic echocardiogram (TTE), and blood tests were all normal. During an inpatient exercise treadmill test (ETT) he developed polymorphic ventricular tachycardia (VT), which converted spontaneously to supraventricular tachycardia (SVT) in the recovery phase of the test. Subsequent risk stratification with cardiac magnetic resonance imaging and coronary angiography showed no abnormalities and an electrophysiological study was negative for sustained VT, however, SVT was easily induced with rapid conversion to atrial fibrillation. The patient successfully stopped smoking all tobacco products including cannabis and was treated with beta-blockers, with no further episodes of arrhythmia. Case 2: A 30-year-old male presented to the Emergency Department with palpitations, chest pain, and dizziness that improved during exertion. His initial ECG demonstrated complete atrioventricular block (AVB). Subsequent traces showed Mobitz Type I and second-degree AVB, which converted to atrial flutter after exertion. Routine blood tests, TTE, and an ETT were all normal and he was discharged home with no conduction abnormalities. Case 3: A 24-year-old male presented with two episodes of syncope. Baseline examination was normal, with an ECG showing a low atrial rhythm. Interrogation of his implantable loop recorder showed episodes of early morning bradycardia episodes with no associated symptoms. DISCUSSION: Cannabis-related arrhythmia can be multiform regarding their presentation. Therefore, ambiguous combinations of arrhythmia should raise suspicion of underlying cannabis abuse, where clinically appropriate. Although causality with regards to cannabis use cannot be proven definitively in these cases, the temporal relationship between drug use and the onset of symptoms suggests a strong association.

Neoatherosclerosis - From basic concept to clinical implication.

Chronic inflammation within the coronary arteries with infiltration of macrophages into the endothelium results in atherosclerosis. Percutaneous coronary intervention (PCI) remains the standard of care for the treatment of most cases of atherosclerotic coronary artery disease (CAD). Intracoronary stents, either bare metal (BMS) or drug eluting (DES), can successfully treat luminal stenoses within the coronary arteries. Following successful PCI however, neointimal proliferation can develop within the deployed stent. Similar to the pathophysiology of native vessel atherosclerosis there is chronic inflammation within the neointima with infiltration of macrophages, a process called neoatherosclerosis, and can result in in-stent restenosis (ISR) and even acute thrombotic, coronary arterial occlusion following disruption of the neoatheroma. Neoatherosclerosis is a heterogeneous, pathobiological complication of PCI that can present more with angina recurrence or in its most extreme form with an acute coronary syndrome (ACS) In this review article, we will discuss possible mechanisms, clinical challenges, and the future therapies of neoatherosclerosis.

Reduction in operator radiation exposure during transradial coronary procedures using a simple lead rectangle.

OBJECTIVES: Transradial access for percutaneous coronary intervention (PCI) reduces procedural complications however, there are concerns regarding the potential for increased exposure to ionizing radiation to the primary operator. We evaluated the efficacy of a lead-attenuator in reducing radiation exposure during transradial PCI. METHODS AND RESULTS: This was a non-randomized, prospective, observational study in which 52 consecutive patients were assigned to either standard operator protection (n = 26) or the addition of the lead attenuator across their abdomen/pelvis (n = 26). In the attenuator group patients were relatively older with a higher prevalence of peripheral vascular disease (67.9 vs 58.7 p = 0.0292 and 12% vs 7.6% p < 0.001 respectively). Despite similar average fluoroscopy times (12.3 ± 9.8 min vs. 9.3 ± 5.4 min, p = 0.175) and average examination doses (111866 ± 80790 vs. 91,268 ± 47916 Gycm2, p = 0.2688), the total radiation exposure to the operator, at the thyroid level, was significantly lower when the lead-attenuator was utilized (20.2% p < 0.0001) as compared to the control group. Amongst the 26 patients assigned to the lead-attenuator, there was a significant reduction in measured radiation of 94.5% (p < 0.0001), above as compared to underneath the lead attenuator. CONCLUSIONS: Additional protection with the use of a lead rectangle-attenuator significantly lowered radiation exposure to the primary operator, which may confer long-term benefits in reducing radiation-induced injury. ADVANCES IN KNOWLEDGE: This is the first paper to show that a simple lead attenuator almost completely reduced the scattered radiation at very close proximity to the patient and should be considered as part of the standard equipment within catheterization laboratories.

Fractional Flow Reserve in the Transradial Era: Will Hand Vein Adenosine Infusion Suffice?: A Comparative Study of the Extent, Rapidity, and Stability of Hyperemia From Hand and Femoral Venous Routes of Adenosine Administration.

OBJECTIVES: The aim of this study was to assess adenosine infusion via a cannula in the back of the hand compared with central venous access to achieve peak hyperemia during fractional flow reserve (FFR). BACKGROUND: Adenosine is often used to induce maximal hyperemia when measuring FFR. The gold standard is continuous infusion via a large central vein; however, the increasing use of the transradial route for angiography makes it desirable to have an alternative route for adenosine. Peripheral venous access is frequently obtained in the hand, but concern exists as to whether adenosine delivery from this site can achieve adequate vasodilation for accurate FFR measurement. Our aim was to address this. METHODS: Subjects were selected from patients presenting for coronary angiography/intervention who required a pressure-wire study. Subjects received intravenous adenosine infusion sequentially via 2 routes: first, via a 20-gauge hand cannula, and then, after a washout period, via a 5- or 6-F femoral venous sheath. Adenosine was administered at 140 µg/kg/min from each site. Data interpretation was blinded. Minimal FFR achieved with intravenous adenosine from each infusion site was recorded as was the time to peak hyperemia. RESULTS: Paired (hand and femoral adenosine) recordings taken from 84 vessels in 61 patients were suitable for blinded analysis. The mean FFR measured using adenosine administered via hand and femoral routes was 0.85 with an SD of 0.08 (intraclass correlation=0.986). Time to peak hyperemia was longer on average with hand-administered adenosine compared with femoral adenosine administration (63 s vs. 43 s; mean difference, 22 s with a 95% confidence interval: 18 s to 27 s; p<0.0001). Formal comparison of FFR stability using Mann-Whitney analysis (2 tailed) gives p=0.43, indicating no significant evidence of a difference in stability between the 2 routes. CONCLUSIONS: Hand vein adenosine infusion produced FFR values very similar to those obtained using central femoral vein adenosine administration, with no systematic bias toward higher or lower reading from 1 site. This has important practical implications for radial access cases involving pressure-wire studies.

Magnetic resonance estimates of the extent and heterogeneity of scar tissue in ICD patients with ischemic cardiomyopathy predict ventricular arrhythmia.

BACKGROUND: The majority of patients receiving implantable cardioverter-defibrillator (ICD) implantation under current guidelines never develop sustained ventricular arrhythmia; therefore, better markers of risk for sustained ventricular tachycardia and/or ventricular fibrillation are needed. OBJECTIVE: The purpose of this study was to identify cardiac magnetic resonance arrhythmic risk predictors of ischemic cardiomyopathy before ICD implantation. METHODS: Forty-three subjects (mean age, 64.5 ± 11.9 years) with previous myocardial infarction who were referred for ICD implantation were evaluated by cardiac magnetic resonance imaging (MRI). The MRI protocol included left ventricular functional parameter assessment using steady-state free precession and late gadolinium enhancement MRI using inversion recovery fast gradient echo. Left ventricular functional parameters were measured using cardiac magnetic resonance software. Subjects were followed up for 6-46 months, and the events of appropriate ICD treatments (shocks and antitachycardia pacing) were recorded. RESULTS: Twenty-eight patients experienced 46 spontaneous episodes during a median follow-up duration of 30 months. The total myocardial infarct (MI) size (18.05 ± 11.44 g vs 38.83 ± 19.87 g; P = .0006), MI core (11.63 ± 7.14 g vs 24.12 ± 12.73 g; P = .0002), and infarct gray zone (6.43 ± 4.64 g vs 14.71 ± 7.65 g; P = .0004) were significantly larger in subjects who received appropriate ICD therapy than in those who did not experience an episode of ventricular tachycardia and/or ventricular fibrillation. Multivariate regression analyses for the infarct gray zone and MI core adjusted for New York Heart Association class, diabetes, and etiology (primary or secondary prevention) revealed that the gray zone and MI core were predictors of appropriate ICD therapies (P = .0018 and P = .007, respectively). CONCLUSION: The extent of MI scar may predict which patients would benefit most from ICD implantation.

The effect of percutaneous coronary intervention of chronically totally occluded coronary arteries on left ventricular global and regional systolic function.

BACKGROUND: Percutaneous coronary intervention (PCI) is frequently attempted to open chronic total occlusions (CTOs) and restore epicardial coronary flow. Data suggest adverse outcomes in the case of PCI failure. We hypothesized that failure to open a CTO might adversely affect regional cardiac function and promote deleterious cardiac remodelling, and success would improve global and regional cardiac function assessed using cardiac magnetic resonance and velocity vector imaging. METHODS: Thirty patients referred for PCI to a CTO underwent cardiac magnetic resonance examination before and after the procedure. Left ventricular function and transmural extent of infarction was assessed in these patients. Regional cardiac function using Velocity Vector Imaging version 3.0.0 (Siemens) was assessed in 20 patients. RESULTS: Successful CTO opening (thrombolysis in myocardial infarction 3 flow) occurred in 63% of patients. Left ventricular ejection fraction significantly increased after successful PCI (50 ± 13% to 54 ± 11%; P < 0.01). Global longitudinal strain (GLS) fell significantly in the failed group (Δ = -25 ± 17%; P = 0.02) in contrast with successful PCI in which GLS did not change (Δ 20 ± 32%; P = 0.17). GLS rate followed a pattern similar to GLS (failed, Δ -30 ± 17%; P < 0.01 vs success Δ 25 ± 48%; P = 0.34). In contrast, radial and circumferential strain/strain rate were not different between groups after success/failed PCI. CONCLUSIONS: Regional cardiac function assessment using velocity vector imaging showed a significant decline in GLS and GLS rate in patients in whom PCI failed to open a CTO, with no change in global measures of cardiac function.

Reproducible classification of infarct heterogeneity using fuzzy clustering on multicontrast delayed enhancement magnetic resonance images.

Delayed enhancement MRI (DE-MRI) can be used to identify myocardial infarct (MI). Classification of MI into the infarct core and heterogeneous periphery (called the gray zone) on conventional inversion-recovery gradient echo (IR-GRE) DE-MRI images has been related to inducibility for ventricular tachycardia. However, this classification is sensitive to image noise, depends on the signal intensity characteristics in a remote region of myocardium, and requires manual contours of the endocardial border. Image analysis and fuzzy clustering techniques were developed to analyze images acquired using a multicontrast delayed enhancement (MCDE) sequence in order characterize the infarct zones. The MCDE analysis is automated and uses data fitting of signal intensities acquired at multiple inversion times. In a study of 15 patients with chronic MI, the gray zones derived from IR-GRE and MCDE images were comparable. The variability in the gray zone size associated with random noise and operator input was significantly reduced using the MCDE-based analysis compared to the IR-GRE-based analysis. In summary, the MCDE approach yields a more reproducible measure of the infarct core and gray zones on any given data set.

Multicontrast late gadolinium enhancement imaging enables viability and wall motion assessment in a single acquisition with reduced scan times.

PURPOSE: To determine the accuracy of multicontrast late enhancement imaging (MCLE) in the assessment of myocardial viability and wall motion compared to the conventional wall motion and viability cardiac magnetic resonance imaging (MRI) pulse sequences. MATERIALS AND METHODS: Forty-one patients with suspected myocardial infarction were studied. Patients underwent assessment of cardiac function with cine steady-state free-precession (SSFP), followed by late gadolinium enhancement (LGE) imaging using inversion recovery gradient echo scanning (IR-GRE) sequence and MCLE. MCLE was compared to cine SSFP in the assessment of wall motion, ejection fraction (EF), left ventricular (LV) mass, LV end-diastolic volume (EDV), and to IR-GRE for measuring infarct size. RESULTS: MCLE, IR-GRE, and SSFP imaging demonstrated excellent agreement in the assessment of EF, LV infarct size, and LV mass (r > 0.95, P < 0.001 for all measures), as well as in the assessment of wall motion (kappa statistic 0.75). CONCLUSION: MCLE provided coregistered images for the assessment of viability and wall motion without loss of accuracy in the assessment of quantitative cardiac parameters. MCLE provides accurate quantitative cardiac assessment with reduced scan times compared to the conventional sequences and thus may be used as an alternative to conventional cine SSFP and IR-GRE imaging.

Identification of plasma protein biomarkers associated with idiopathic pulmonary arterial hypertension.

We have employed SELDI-TOF MS to screen for differentially expressed proteins in plasma samples from 27 patients with idiopathic pulmonary arterial hypertension (IPAH) and 26 healthy controls. One ion (m/z approximately 8600) that was found to be elevated in IPAH was validated by SELDI-TOF MS analysis of a second and separate set of plasma samples comprising 30 IPAH patients and 19 controls. The m/z 8600 was purified from plasma by sequential ion exchange and reverse-phase chromatographies and SDS-PAGE. It was identified, following trypsin digestion, by MS peptide analysis as the complement component, complement 4a (C4a) des Arg. Plasma levels of C4a des Arg measured by ELISA confirmed that the levels were significantly higher (p < 0.0001) in IPAH patients (2.12 +/- 0.27 microg/mL) compared with normal controls (0.53 +/- 0.05 microg/mL). A cut-off level of 0.6 microg/mL correctly classified 92% of IPAH patients and 80% of controls. Further studies will be needed to determine its performance as a diagnostic biomarker, whether used alone or in combination with other biomarkers. Nevertheless, this study demonstrates that putative biomarkers characteristic of IPAH can be identified using a conjoint SELDI-TOF MS - proteomics approach.

Bosentan decreases the plasma concentration of sildenafil when coprescribed in pulmonary hypertension.

AIMS: To determine whether bosentan decreases the plasma concentration of sildenafil in patients with pulmonary arterial hypertension. METHODS: Ten patients (aged 39-77 years) with pulmonary arterial hypertension in WHO functional class III received bosentan 62.5 mg twice daily for 1 month, then 125 mg twice daily for a second month. Sildenafil 100 mg was given as a single dose before starting bosentan (visit 1) and at the end of each month of bosentan treatment (visits 2 and 3). Sildenafil and its primary metabolite, desmethylsildenafil, were measured in plasma at 0 h and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18 and 24 h using liquid chromatography-tandem mass spectrometry. Statistical analysis was by repeated measures anova, using log transformed data where appropriate. RESULTS: Treatment with bosentan 62.5 mg twice daily for 4 weeks was associated with a two-fold increase in sildenafil clearance/F and a 50% decrease in the AUC (P < 0.001). Increasing the dose of bosentan to 125 mg twice daily led to a further increase in sildenafil oral clearance and decrease in the AUC (P < 0.001 vs. 62.5 mg bosentan). The ratio of AUC on bosentan treatment relative to that of visit 1 was 0.47 [95% confidence interval (CI) 0.36, 0.61] for visit 2 and 0.31 (95% CI 0.23, 0.41) for visit 3 (P < 0.001). Sildenafil C(max) fell from 759 ng ml(-1) on visit 1 to 333 ng ml(-1) on visit 3 (P < 0.01) and there was a significant decrease in the plasma half-life of sildenafil on the higher bosentan dose (P < 0.05). The AUC and plasma half-life of desmethylsildenafil was also decreased by bosentan in a dose-dependent manner (P < 0.01). CONCLUSIONS: Bosentan significantly decreases the plasma concentration of sildenafil when coadministered to patients with pulmonary hypertension.

Sildenafil versus Endothelin Receptor Antagonist for Pulmonary Hypertension (SERAPH) study.

RATIONALE: Phosphodiesterase type 5 (PDE5) inhibition has been proposed for the treatment for pulmonary arterial hypertension (PAH). OBJECTIVE: This study compared adding sildenafil, a PDE5 inhibitor, to conventional treatment with the current practice of adding bosentan, an endothelin receptor antagonist. METHODS: Twenty-six patients with PAH, idiopathic or associated with connective tissue disease, World Health Organization (WHO) functional class III, were randomized in a double-blind fashion to receive sildenafil (50 mg twice daily for 4 weeks, then 50 mg three times daily) or bosentan (62.5 mg twice daily for 4 weeks, then 125 mg twice daily) over 16 weeks. MEASUREMENTS: Changes in right ventricular (RV) mass (using cardiovascular magnetic resonance), 6-minute walk distance, cardiac function, brain natriuretic peptide, and Borg dyspnea index. MAIN RESULTS: When analyzed by intention to treat, there were no significant differences between the two treatment groups. One patient on sildenafil died suddenly. Patients on sildenafil who completed the protocol showed significant changes from baseline, namely, reductions in RV mass (-8.8 g; 95% confidence interval [CI], -2, -16; n = 13, p = 0.015) and plasma brain natriuretic peptide levels (-19.4 fmol x ml(-1); 95% CI, -5, -34; p = 0.014) and improvements in 6-minute walk distance (114 m; 95% CI, 67, 160; p = 0.0002), cardiac index (0.3 L x min(-1) x m(-2); 95% CI, 0.1, 0.4; p = 0.008), and systolic left ventricular eccentricity index (-0.2; 95% CI, -0.02, -0.37; p = 0.031). Bosentan improved 6-minute walk distance (59 m; 95% CI, 29, 89; n = 12, p = 0.001) and cardiac index (0.3; 95% CI, 0.1, 0.4; p = 0.008). CONCLUSIONS: Sildenafil added to conventional treatment reduces RV mass and improves cardiac function and exercise capacity in patients with PAH, WHO functional class III. Safety monitoring is important until more experience is obtained.