Orly Goitein

Intracoronary injection of in situ forming alginate hydrogel reverses left ventricular remodeling after myocardial infarction in Swine.

OBJECTIVES This study sought to determine whether alginate biomaterial can be delivered effectively into the infarcted myocardium by intracoronary injection to prevent left ventricular (LV) remodeling early after myocardial infarction (MI). BACKGROUND Although injectable biomaterials can improve infarct healing and repair, the feasibility and effectiveness of intracoronary injection have not been studied. METHODS We prepared a calcium cross-linked alginate solution that undergoes liquid to gel phase transition after deposition in infarcted myocardium. Anterior MI was induced in swine by transient balloon occlusion of left anterior descending coronary artery. At 4 days after MI, either alginate solution (2 or 4 ml) or saline was injected selectively into the infarct-related coronary artery. An additional group (n = 19) was treated with incremental volumes of biomaterial (1, 2, and 4 ml) or 2 ml saline and underwent serial echocardiography studies. RESULTS Examination of hearts harvested after injection showed that the alginate crossed the infarcted leaky vessels and was deposited as hydrogel in the infarcted tissue. At 60 days, control swine experienced an increase in left ventricular (LV) diastolic area by 44%, LV systolic area by 45%, and LV mass by 35%. In contrast, intracoronary injection of alginate (2 and 4 ml) prevented and even reversed LV enlargement (p < 0.01). Post-mortem analysis showed that the biomaterial (2 ml) increased scar thickness by 53% compared with control (2.9 +/- 0.1 mm vs. 1.9 +/- 0.3 mm; p < 0.01) and was replaced by myofibroblasts and collagen. CONCLUSIONS Intracoronary injection of alginate biomaterial is feasible, safe, and effective. Our findings suggest a new percutaneous intervention to improve infarct repair and prevent adverse remodeling after reperfused MI.

Deformation Dynamics and Mechanical Properties of the Aortic Annulus by 4-Dimensional Computed Tomography Insights Into the Functional Anatomy of the Aortic Valve Complex and Implications for Transcatheter Aortic Valve Therapy

OBJECTIVES The purpose of this study was to assess deformation dynamics and in vivo mechanical properties of the aortic annulus throughout the cardiac cycle. BACKGROUND Understanding dynamic aspects of functional aortic valve anatomy is important for beating-heart transcatheter aortic valve implantation. METHODS Thirty-five patients with aortic stenosis and 11 normal subjects underwent 256-slice computed tomography. The aortic annulus plane was reconstructed in 10% increments over the cardiac cycle. For each phase, minimum diameter, ellipticity index, cross-sectional area (CSA), and perimeter (Perim) were measured. In a subset of 10 patients, Youngs elastic module was calculated from the stress-strain relationship of the annulus. RESULTS In both subjects with normal and with calcified aortic valves, minimum diameter increased in systole (12.3 ± 7.3% and 9.8 ± 3.4%, respectively; p < 0.001), and ellipticity index decreased (12.7 ± 8.8% and 10.3 ± 2.7%, respectively; p < 0.001). The CSA increased by 11.2 ± 5.4% and 6.2 ± 4.8%, respectively (p < 0.001). Perim increase was negligible in patients with calcified valves (0.56 ± 0.85%; p < 0.001) and small even in normal subjects (2.2 ± 2.2%; p = 0.01). Accordingly, relative percentage differences between maximum and minimum values were significantly smallest for Perim compared with all other parameters. Youngs modulus was calculated as 22.6 ± 9.2 MPa in patients and 13.8 ± 6.4 MPa in normal subjects. CONCLUSIONS The aortic annulus, generally elliptic, assumes a more round shape in systole, thus increasing CSA without substantial change in perimeter. Perimeter changes are negligible in patients with calcified valves, because tissue properties allow very little expansion. Aortic annulus perimeter appears therefore ideally suited for accurate sizing in transcatheter aortic valve implantation.

The role of ECG-gated MDCT in the evaluation of aortic and mitral mechanical valves: initial experience.

OBJECTIVE The objective of our study was to evaluate the role of ECG-gated MDCT in the functional evaluation of mechanical prosthetic aortic and mitral valves. MATERIALS AND METHODS Twenty sequential patients with 23 mechanical prosthetic valves were evaluated with an ECG-gated 40- or 64-MDCT scanner. Multiplanar reformation, maximal-intensity-projection, volume-rendering, and volume-averaging techniques were used for visualization of valve leaflets in systole and diastole. The visibility of each mechanical valve was evaluated by consensus of a radiologist and a cardiologist using a subjective 5-point scale (0-4). MDCT findings were correlated with fluoroscopic opening and closing angle measurements and echocardiographic pressure gradient measurements in 11 and 19 valves, respectively. RESULTS The series included 18 bileaflet and five single-leaflet mechanical valves. The visibility score for the bileaflet mechanical valves was excellent (score of 4) in all 18 cases, but it was lower for single-leaflet valves (mean score, 2.8; range, 1-4) (p = 0.04). Bland-Altman plots showed high agreement between MDCT and fluoroscopy for measurements of opening and closing angles of bileaflet mechanical valves. In four patients, a stuck valve was seen on MDCT and was confirmed by fluoroscopy. Doppler echocardiography showed increased transvalvular pressure in two of the four patients with a stuck mitral valve and increased transaortic pressure in four patients with normal prosthetic aortic valve motion. CONCLUSION Our preliminary results suggest that MDCT is a promising technique for functional evaluation of bileaflet mechanical valves, allowing reliable measurements of opening and closing leaflet angles. However, the role of MDCT in the evaluation of single-leaflet valves might be limited.

Evidence for tissue iron overload in long-term hemodialysis patients and the impact of withdrawing parenteral iron

Erythropoiesis in long‐term hemodialyzed (LTH) patients is supported by erythropoietin (rHuEpo) and intravenous (IV) iron. This treatment may end up in iron overload (IO) in major organs. We studied such patients for the parameters of IO in the serum and in major organs.

Acute Myocarditis: Noninvasive Evaluation with Cardiac MRI and Transthoracic Echocardiography

OBJECTIVE The diagnosis of acute myocarditis is challenging. Nonspecific clinical presentation and an overlap with the diagnosis of acute myocardial infarction present a diagnostic dilemma. The purpose of this article is to describe the role of cardiac MRI and transthoracic echocardiography (TTE) in the diagnosis of acute myocarditis. MATERIALS AND METHODS Thirty-two sequential patients (all male; average age, 33 years) with clinically suspected myocarditis were included. All patients underwent cardiac MRI with sequences dedicated for the evaluation of myocardial delayed enhancement and TTE for the evaluation of wall motion abnormalities (WMAs). Nine patients were excluded because of diagnosis of acute myocardial infarction (n=2) or inadequate cardiac MRI technique (n=7). Retrospective analysis of the images of the remaining 23 patients was performed. RESULTS An epicardial pattern of abnormal patchy myocardial delayed enhancement was seen on cardiac MRI in 21 of 23 (91%) patients. WMAs were seen on TTE in eight of 23 (35%) patients. Regional rather than global involvement was seen mainly in the inferolateral segments, with a predominance in the midventricular portion. CONCLUSION Cardiac MRI might have a greater impact than TTE in confirming the presence of acute myocarditis and evaluating the extent of myocardial involvement. Cardiac MRI provides noninvasive imaging that may obviate invasive procedures such as coronary catheter angiography or endomyocardial biopsy.

Usefulness of Routine Use of Multidetector Coronary Computed Tomography in the “Fast Track” Evaluation of Patients With Acute Chest Pain

Recently published American Heart Association/American College of Cardiology guidelines suggest that multidetector computed tomography (MDCT) may be appropriate for investigating acute chest pain (ACP). Only a few small studies have evaluated the use of MDCT in ACP, where it was not part of routine investigation. We sought to evaluate the routine use of MDCT in a large cohort of patients presenting with ACP in a real-world setting. We studied 785 consecutive patients with ACP who underwent evaluation by MDCT or myocardial perfusion scintigraphy after an observation period of > or = 12 hours. Patients with findings suggestive of significant coronary artery disease (CAD) were referred to coronary angiography. Forty-two patients were hospitalized due to evidence of myocardial ischemia and 44 patients were discharged after the observation period. Of the remaining 699 patients, 340 underwent MDCT and 359 myocardial perfusion scintigraphy. In 22 patients (7%) multidetector computed tomogram showed significant CAD and in 32 (9%) patients myocardial perfusion scintigram showed significant ischemia. Significant CAD was confirmed by coronary angiography in 65% and 60%, respectively. Multidetector computed tomogram was nondiagnostic in 31 patients (9%). Extracardiac findings that might be related to ACP and/or necessitated further investigation were demonstrated by multidetector computed tomogram in 71 patients (21%). During 3-month follow-up, 1 patient (0.3%) with negative multidetector computed tomographic and 9 (3%) with negative myocardial perfusion scintigraphic findings developed an acute coronary syndrome or died. Rehospitalization, due to recurrent chest pain, occurred in 9 patients (3.3%) and 21 patients (7.2%), respectively. In conclusion, MDCT could be an appropriate alternative to traditional noninvasive techniques for investigating ACP.

The limited role of MRI in long-term follow-up of patients with Takayasu's arteritis

INTRODUCTION MRI and MRA are used for diagnosis and activity determination of patients with Takayasus arteritis (TA). However, there is a limited experience regarding the role of MRI in long-term follow-up of those patients. The aim of the present study was to evaluate the clinical usefulness of MRI in the long-term follow-up of patients with Takayasus disease. MATERIALS AND METHODS The clinical data of 11 TA patients, who obtained two or more follow-up MRI scans, was matched with the imaging results. MRI examinations were considered positive for disease activity when one of the following findings was noted: new arterial wall enhancement or interval appearance of anatomical changes (interval dilatation, stenosis or occlusion or new arterial wall irregularity). Conversely, MRI examinations were considered to show signs of improvement when local enhancement disappeared, or when a stenosis was relieved. Disease activity was determined by the combination of worsening localizing ischemic signs and symptoms, systemic signs and symptoms (malaise, fever, etc.), and elevated blood markers (CRP and ESR). RESULTS A total of 47 MRI examinations were performed in 11 patients (1 male, mean age 28, range 14-53 years) with a total follow-up time ranging between 12 and 56 months (average 36 months). MRI was positive for active disease at least once in nine out of the 11 patients (82%). The most commonly affected arteries were the aortic arch, the left subclavian artery and the left common carotid artery. No statistically significant correlation was found between clinical activity and MRI signs of activity. CONCLUSION Although MRI is a well established modality for primary diagnosis of TA, the present study suggests that it has a limited clinical role in the long-term follow-up of those patients when reactivation of disease is suspected.

Inverse Relationship Between Membranous Septal Length and the Risk of Atrioventricular Block in Patients Undergoing Transcatheter Aortic Valve Implantation.

OBJECTIVES This study sought to examine whether imaging of the atrioventricular (AV) membranous septum (MS) by computed tomography (CT) can be used to identify patient-specific anatomic risk of high-degree AV block and permanent pacemaker (PPM) implantation before transcatheter aortic valve implantation (TAVI) with self-expandable valves. BACKGROUND MS length represents an anatomic surrogate of the distance between the aortic annulus and the bundle of His and may therefore be inversely related to the risk of conduction system abnormalities after TAVI. METHODS Seventy-three consecutive patients with severe aortic stenosis underwent contrast-enhanced CT before TAVI. The aortic annulus, aortic valve, and AV junction were assessed, and MS length was measured in the coronal view. RESULTS In 13 patients (18%), high-degree AV block developed, and 21 patients (29%) received a PPM. Multivariable logistic regression analysis revealed MS length as the most powerful pre-procedural independent predictor of high-degree AV block (odds ratio [OR]: 1.35, 95% confidence interval [CI]: 1.1 to 1.7, p = 0.01) and PPM implantation (OR: 1.43, 95% CI: 1.1 to 1.8, p = 0.002). When taking into account pre- and post-procedural parameters, the difference between MS length and implantation depth emerged as the most powerful independent predictor of high-degree AV block (OR: 1.4, 95% CI: 1.2 to 1.7, p < 0.001), whereas the difference between MS length and implantation depth and calcification in the basal septum were the most powerful independent predictors of PPM implantation (OR: 1.39, 95% CI: 1.2 to 1.7, p < 0.001 and OR: 4.9, 95% CI: 1.2 to 20.5, p = 0.03; respectively). CONCLUSIONS Short MS, insufficient difference between MS length and implantation depth, and the presence of calcification in the basal septum, factors that may all facilitate mechanical compression of the conduction tissue by the implanted valve, predict conduction abnormalities after TAVI with self-expandable valves. CT assessment of membranous septal anatomy provides unique pre-procedural information about the patient-specific propensity for the risk of AV block.

No evidence for myocardial iron overload and free iron species in multitransfused patients with sickle/β0-thalassaemia

Iron overload (IO) in the heart is a life‐threatening complication in transfusion‐dependent patients with thalassaemia major (TM) and to a lesser extent in sickle cell disease (SCD), while no data are available in patients with sickle/β0‐thalassaemia. Iron deposition in the heart, liver and pancreas was assessed using T2* MRI sequences, as well as free iron species assays – non‐transferrin bound iron (NTBI) and labile plasma iron (LPI), in addition to serum ferritin, percentage transferrin saturation and serum hepcidin, in 10 multitransfused patients (>30 yr) with sickle/β0‐thalassaemia. None of the patients had iron deposition in the heart. Three patients had mild, one had moderate, and two had severe liver IO. Two patients had mild iron deposition in the pancreas. In all the patients, serum hepcidin levels were normal – NTBI and LPI were not detected. Possible explanations of these findings are discussed.

Macrophages dictate the progression and manifestation of hypertensive heart disease

BACKGROUND Inflammation has been implicated in the initiation, progression and manifestation of hypertensive heart disease. We sought to determine the role of monocytes/macrophages in hypertension and pressure overload induced left ventricular (LV) remodeling. METHODS AND RESULTS We used two models of LV hypertrophy (LVH). First, to induce hypertension and LVH, we fed Sabra salt-sensitive rats with a high-salt diet. The number of macrophages increased in the hypertensive hearts, peaking at 10 weeks after a high-salt diet. Surprisingly, macrophage depletion, by IV clodronate (CL) liposomes, inhibited the development of hypertension. Moreover, macrophage depletion reduced LVH by 17% (p<0.05), and reduced cardiac fibrosis by 75%, compared with controls (p=0.001). Second, to determine the role of macrophages in the development and progression of LVH, independent of high-salt diet, we depleted macrophages in mice subjected to transverse aortic constriction and pressure overload. Significantly, macrophage depletion, for 3 weeks, attenuated LVH: a 12% decrease in diastolic and 20% in systolic wall thickness (p<0.05), and a 13% in LV mass (p=0.04), compared with controls. Additionally, macrophage depletion reduced cardiac fibrosis by 80% (p=0.006). Finally, macrophage depletion down-regulated the expression of genes associated with cardiac remodeling and fibrosis: transforming growth factor beta-1 (by 80%) collagen type III alpha-1 (by 71%) and atrial natriuretic factor (by 86%). CONCLUSIONS Macrophages mediate the development of hypertension, LVH, adverse cardiac remodeling, and fibrosis. Macrophages, therefore, should be considered as a therapeutic target to reduce the adverse consequences of hypertensive heart disease.