Objectives This study aimed to demonstrate that the presence of late gadolinium enhancement (LGE) is a predictor of death and other adverse events in patients with suspected cardiac sarcoidosis. ...Background Cardiac sarcoidosis is the most important cause of patient mortality in systemic sarcoidosis, yielding a 5-year mortality rate between 25% and 66% despite immunosuppressive treatment. Other groups have shown that LGE may hold promise in predicting future adverse events in this patient group. Methods We included 155 consecutive patients with systemic sarcoidosis who underwent cardiac magnetic resonance (CMR) for workup of suspected cardiac sarcoid involvement. The median follow-up time was 2.6 years. Primary endpoints were death, aborted sudden cardiac death, and appropriate implantable cardioverter-defibrillator (ICD) discharge. Secondary endpoints were ventricular tachycardia (VT) and nonsustained VT. Results LGE was present in 39 patients (25.5%). The presence of LGE yields a Cox hazard ratio (HR) of 31.6 for death, aborted sudden cardiac death, or appropriate ICD discharge, and of 33.9 for any event. This is superior to functional or clinical parameters such as left ventricular (LV) ejection fraction (EF), LV end-diastolic volume, or presentation as heart failure, yielding HRs between 0.99 (per % increase LVEF) and 1.004 (presentation as heart failure), and between 0.94 and 1.2 for potentially lethal or other adverse events, respectively. Except for 1 patient dying from pulmonary infection, no patient without LGE died or experienced any event during follow-up, even if the LV was enlarged and the LVEF severely impaired. Conclusions Among our population of sarcoid patients with nonspecific symptoms, the presence of myocardial scar indicated by LGE was the best independent predictor of potentially lethal events, as well as other adverse events, yielding a Cox HR of 31.6 and of 33.9, respectively. These data support the necessity for future large, longitudinal follow-up studies to definitely establish LGE as an independent predictor of cardiac death in sarcoidosis, as well as to evaluate the incremental prognostic value of additional parameters.
In adults with congenital heart disease and a systemic right ventricle, subaortic ventricular systolic dysfunction is common. Echocardiographic assessment of systolic right ventricular (RV) function ...in these patients is important but challenging. The aim of the present study was to assess the reliability of conventional echocardiographic RV functional parameters to quantify the systolic performance of a subaortic right ventricle. We compared 56 contemporary echocardiograms and cardiac magnetic resonance studies in 37 adults, aged 26.9 ± 7.4 years, with complete transposition and a subaortic right ventricle. The fractional area change (FAC), lateral tricuspid annular plane systolic excursion, lateral RV systolic motion velocities by tissue Doppler, RV myocardial performance index, and the rate of systolic RV pressure increase (dp/dt) measured across the tricuspid regurgitant jet were assessed by echocardiography and correlated with the cardiac magnetic resonance-derived RV ejection fraction (EF). The mean RVEF was 48.0 ± 7.8%. FAC (r2 = 0.206, p = 0.001) and dp/dt (r2 = 0.173, p = 0.009) significantly correlated with RVEF, and the other nongeometric echocardiographic parameters failed to show a significant correlation with RVEF by linear regression analysis. FAC <33% and dp/dt <1,000 mm Hg/s identified a RVEF of <50% with a sensitivity of 77% and 69% and a specificity of 58% and 87%, respectively. In conclusion, in patients with a systemic right ventricle, routine nongeometric echocardiographic parameters of RV function correlated weakly with cardiac magnetic resonance-derived EF. RV FAC and the measurement of the rate of systolic RV pressure increase (dp/dt) should be preferentially used to assess systemic systolic function in adult patients with a subaortic right ventricle.
The aim of our study was to evaluate 3-dimensional (3D) color Doppler proximal isovelocity surface area (PISA) as a tool for quantitative assessment of mitral regurgitation (MR) against in vitro and ...in vivo reference methods. A customized 3D PISA software was validated in vitro against a flowmeter MR phantom. Sixty consecutive patients, with ≥mild MR of any cause, were recruited and the regurgitant volume (RVol) was measured by 2D PISA, 3D peak PISA, and 3D integrated PISA, using transthoracic (TTE) and transesophageal echocardiography (TEE). Cardiac magnetic resonance imaging (CMR) was used as reference method. Flowmeter RVol was associated with 3D integrated PISA as follows: y = 0.64 x + 4.7, r2 = 0.97, p <0.0001 for TEE and y = 0.88 x + 4.07, r2 = 0.96, p <0.0001 for TTE. The bias and limit of agreement in the Bland–Altman analysis were 6.8 ml −3.5 to 17.1 for TEE and −0.059 ml −6.2 to 6.1 for TTE. In vivo, TEE-derived 3D integrated PISA was the most accurate method for MR quantification compared to CMR: r2 = 0.76, y = 0.95 x − 3.95, p <0.0001; 5.1 ml (−14.7 to 26.5). It was superior to TEE 3D peak PISA ( r2 = 0.67, y = 1.00 x + 6.20, p <0.0001; −6.3 ml −33.4 to 21.0), TEE 2D PISA ( r2 = 0.54, y = 0.76 x + 0.18, p <0.0001; 8.4 ml −20.4 to 37.2), and TTE-derived measurements. It was also most accurate by receiver operating characteristic analysis (area under the curve 0.99) for the detection of severe MR, RVol cutoff = 48 ml, sensibility 100%, and specificity 96%. RVol and the cutoff to define severe MR were underestimated using the most accurate method. In conclusion, quantitative 3D color Doppler echocardiography of the PISA permits a more accurate MR assessment than conventional techniques and, consequently, should enable an optimized management of patients suffering from MR.
Background Recent studies report that intracoronary administration of autologous bone marrow mononucleated cells (BM-MNCs) may improve remodeling of the left ventricle after acute myocardial ...infarction (AMI). Subgroup analysis suggest that early treatment between days 4 and 7 after AMI is probably most effective; however, the optimal time point of intracoronary cell administration has never been addressed in clinical trials. Furthermore, reliable clinical predictors are lacking for identifying patients who are thought to have most benefit from cellular therapy. Study Design In a multicenter trial, 192 patients with AMI successfully treated by percutaneous coronary intervention (PCI) of the infarct-related artery will be randomized in a 1:1:1 pattern to 1 control and 2 BM-MNC treatment groups. The control group will be treated with state-of-the-art medical management. The treatment groups will receive intracoronary administration of autologous BM-MNC at 5 to 7 days or 3 to 4 weeks after the initial event, respectively. Left ventricular function as well as scar size, transmural extension, and regional wall motion score will be assessed by cardiac magnetic resonance (CMR) studies at baseline and after 4 and 12 months. Methods Fifty milliliters of bone marrow will be harvested by aspiration from the iliac crest and then carried by courier to a centralized cell processing facility. The mononucleated cell fraction will be isolated by density gradient centrifugation, washed, and resuspended in 10 mL of injection medium. The cells will be characterized by fluorescence-activated cell sorting analysis and tested for sterility and potency both “in vitro” and “in vivo.” Bone marrow MNC will then be reinfused directly in the infarct-related coronary artery. End points The primary end point is the change in global left ventricular (LV) ejection fraction by CMR at 4 months as compared to baseline. Comparisons will then be made between each of the prespecified therapy subgroups (early and late after AMI) and the control group. Secondary end points include change in infarct size, change in regional myocardial thickness, and wall motion at 4 and 12 months compared to baseline. Infarct extension (size and transmural extension), time delay to PCI, and coronary flow characteristics after PCI will be assessed as potential predictors of LV remodeling and change after cell therapy. Major adverse cardiac events (MACE) (death, myocardial infarction, coronary revascularization, rehospitalization for heart failure) will be assessed at 4, 12, and 24 months and time to MACE will be estimated. Discussion With the present study, we aim to determine the optimal time point of intracoronary administration of autologous BM-MNC after AMI on LV remodeling.
Objectives We examined the sodium-iodide symporter (NIS), which promotes in vivo cellular uptake of technetium 99m (99m Tc) or iodine 124 (124 I), as a reporter gene for cell tracking by ...single-photon emission computed tomography (SPECT) or positron emission tomography (PET) imaging. Background Stem cells offer the promise of cardiac repair. Stem cell labeling is a prerequisite to tracking cell fate in vivo. Methods The human NIS complementary deoxyribonucleic acid was transduced into rat cardiac-derived stem cells (rCDCs) using lentiviral vectors. Rats were injected intramyocardially with up to 4 million NIS+ -rCDCs immediately after left anterior descending coronary artery ligation. Dual isotope SPECT (or PET) imaging was performed, using99m Tc (or124 I) for cell detection and thallium 201 (or ammonia 13) for myocardial delineation. In a subset of animals, high resolution ex vivo SPECT scans of explanted hearts were obtained to confirm that in vivo signals were derived from the cell injection site. Results NIS expression in rCDCs did not affect cell viability and proliferation. NIS activity was verified in isolated transduced cells by measuring99m Tc uptake. NIS+ rCDCs were visualized in vivo as regions of99m Tc or124 I uptake within a perfusion deficit in the SPECT and PET images, respectively. Cells could be visualized by SPECT up to 6 days post-injection. Ex vivo SPECT confirmed that in vivo99m Tc signals were localized to the cell injection sites. Conclusions Ectopic NIS expression allows noninvasive in vivo stem cell tracking in the myocardium, using either SPECT or PET. The general approach shows significant promise in tracking the fate of transplanted cells participating in cardiac regeneration, given its ability to observe living cells using clinically applicable imaging modalities.
Structural abnormalities of the medial aorta have been described for conotruncal defects (e.g., tetralogy of Fallot TOF and complete transposition of the great arteries (dextrotransposition d-TGA). ...In TOF, progressive aortic dilation is a frequent finding. In patients with d-TGA with an atrial switch, this problem is less often described. The aim of the present study was to compare the extent of dilative aortopathy and aortic distensibility in adults with an atrial switch procedure (n = 39) to that in adults with repaired TOF (n = 39) and controls (n = 39), using cardiac magnetic resonance imaging. The groups were matched for age and gender. Diameters of the aorta indexed to the body surface area were significantly increased in the patients with d-TGA and TOF compared to that of the controls at the aortic sinus up to the level of the right pulmonary artery. On multivariate testing, the diagnosis of a conotruncal defect (β = 0.260; p = 0.003) and aortic regurgitant fraction (β = 0.405; p <0.001) were independent predictors of an increased aortic sinus diameter. Ascending aorta distensibility was significantly reduced in those with d-TGA and TOF compared to controls: 3.6 (interquartile range 1.5 to 4.4) versus 2.8 (interquartile range 2.0 to 3.7) versus 5.5 (interquartile range 4.8 to 6.9) ×10−3 mm Hg−1 (p <0.001). The independent predictors of ascending aorta distensibility were the diagnosis of a conotruncal defect (p <0.001) and age (p = 0.028). In conclusion, intrinsic aortopathy, manifested as increased ascending aortic diameters and reduced ascending aortic distensibility, is not only evident in adults with TOF, but also in adults with d-TGA and an atrial switch procedure. Long-term follow-up is needed to monitor the aortic size in both patient groups.
The aim of this study was to test the hypothesis that ear oximetry immediately after the release of a sustained Valsalva maneuver accurately detects patent foramen ovale (PFO). One hundred sixty-five ...scuba divers underwent transesophageal echocardiography (TEE; reference method) for PFO assessment. Ear oximetry of the right earlobe was performed in a different room within a time frame of 2 hours before or after TEE. The subject and the oximetry operator were unaware of the results of TEE. Oxygen saturation (SO2 ) measurements were obtained at baseline and during the release phase of 4 Valsalva maneuvers within 10 minutes, and the average SO2 change (SO2 at baseline minus SO2 at Valsalva release) was determined as the primary study end point. One hundred seventeen divers had no PFO, and 48 (29%) had PFO by TEE (mean age 39 ± 8 years). The average SO2 change was 0.79 ± 1.13% (i.e., a slight absolute SO2 decrease in response to the Valsalva maneuver) in the group without PFO and 1.67 ± 1.19% in the PFO group (p <0.0001). Using receiver-operating characteristic curve analysis, a PFO as defined by TEE could be detected at a threshold of a Valsalva-induced decrease in SO2 of ≥0.825 percentage points in comparison to baseline (sensitivity 0.756, specificity 0.706, area under the receiver-operating characteristic curve 0.763, p <0.0001, negative predictive value 0.882). In conclusion, the entirely noninvasive method of ear oximetry in response to repetitive Valsalva maneuvers is accurate and useful as a screening method for the detection of a PFO, as shown in this study of divers.
Objective Surgical treatment of mitral leaflet prolapse using artificial neochordae shows excellent outcomes. Upcoming devices attempt the same treatment in a minimally invasive way but target the ...left ventricular apex as an anchoring point, rather than the tip of the corresponding papillary muscle. In this study, cine cardiac magnetic resonance imaging was used to compare these 2 different anchoring positions and their dynamic relationship with the mitral leaflets. Methods Eleven healthy volunteers (mean age, 31 years; 6 female; mean ejection fraction, 62%) were examined by cardiac magnetic resonance imaging (3 Tesla, cine steady free precession technique with retrospective gating), whereby dedicated software enabled assessment of the physiologic distances among 3 anchoring sites (anterior papillary muscle, posterior papillary muscle, and apex) and the plane of the mitral annulus at the level of leaflet coaptation. These distances were measured in systole and diastole, and the performance of virtual neochordae was analyzed for the 3 potential anchoring sites. Results Length difference between systole and diastole for the 3 measured distances were 0.19 ± 0.11 cm (5.9% ± 3.4%) for the anterior papillary muscle, 0.19 ± 0.09 cm (6.7% ± 3.6%) for the posterior papillary muscle, and 1.52 ± 0.18 cm (17.8% ± 2.8%) for the left ventricular apex ( P = .001). Virtual neochordae between the leaflet and the left ventricular apex were first adjusted in systole to achieve leaflet coaptation. Leaflet tear in diastole can only be avoided if the width of the attached leaflet is larger than the systole–diastole length difference. On the other hand, if virtual neochordae are adjusted in diastole to avoid leaflet tear, residual leaflet prolapse during systole can result. Because the systole–diastole length difference for papillary muscle anchored chordae is smaller than for apical chordae by a factor 10, there is a strongly reduced risk of prolapse or tearing and the leaflet width is unimportant. Furthermore, if the neochordae attached to the anterior mitral leaflet uses the apex as a distal anchoring site, the angle α between the aortic valve plane and this mitral leaflet is significantly reduced in diastole and therefore increases the risk of systolic anterior motion. Conclusions Anchoring of neochordae at the papillary muscles, thereby mimicking the real anatomy, should be preferred over the left ventricular apex. Further analysis of dilated hearts and papillary muscle displacement is necessary to include the whole spectrum of pathologies.
Normothermic machine perfusion (NMP) is nowadays frequently utilized in liver transplantation. Despite commonly accepted viability assessment criteria, such as perfusate lactate and perfusate pH, ...there is a lack of predictive organ evaluation strategies to ensure graft viability. Hyperspectral imaging (HSI)-as an optical imaging modality increasingly applied in the biomedical field-might provide additional useful data regarding allograft viability and performance of liver grafts during NMP. MethodsTwenty-five deceased donor liver allografts were included in the study. During NMP, graft viability was assessed conventionally and by means of HSI. Images of liver parenchyma were acquired at 1, 2, and 4 h of NMP, and subsequently analyzed using a specialized HSI acquisition software to compute oxygen saturation, tissue hemoglobin index, near-infrared perfusion index, and tissue water index. To analyze the association between HSI parameters and perfusate lactate as well as perfusate pH, we performed simple linear regression analysis. ResultsPerfusate lactate at 1, 2, and 4 h NMP was 1.5 0.3-8.1, 0.9 0.3-2.8, and 0.9 0.1-2.2 mmol/L. Perfusate pH at 1, 2, and 4 h NMP was 7.329 7.013-7.510, 7.318 7.081-7.472, and 7.265 6.967-7.462, respectively. Oxygen saturation predicted perfusate lactate at 1 and 2 h NMP (R2 = 0.1577, P = 0.0493; R2 = 0.1831, P = 0.0329; respectively). Tissue hemoglobin index predicted perfusate lactate at 1, 2, and 4 h NMP (R2 = 0.1916, P = 0.0286; R2 = 0.2900, P = 0.0055; R2 = 0.2453, P = 0.0139; respectively). ConclusionsHSI may serve as a noninvasive tool for viability assessment during NMP. Further evaluation and validation of HSI parameters are warranted in larger sample sizes.
Late Results After Percutaneous Closure of Patent Foramen Ovale for Secondary Prevention of Paradoxical Embolism Using the Amplatzer PFO Occluder Without Intraprocedural Echocardiography: Effect of ...Device Size Andreas Wahl, Tony Tai, Fabien Praz, Markus Schwerzmann, Christian Seiler, Krassen Nedeltchev, Stephan Windecker, Heinrich P. Mattle, Bernhard Meier Percutaneous patent foramen ovale (PFO) closure using the Amplatzer PFO Occluder (AGA Medical Corporation, Golden Valley, Minnesota) was performed for secondary prevention of paradoxical embolism in 620 patients. The interventions were performed without intraprocedural echocardiography, and all were successful. There were 5 procedural complications (0.8%). Contrast transesophageal echocardiography at 6 months showed complete closure in 91% of patients. A minimal, moderate, or large residual shunt persisted in 6%, 2%, and 1%, respectively. Freedom from recurrent ischemic stroke, transient ischemic attack, or peripheral embolism was 99% at 1 year, 99% at 2 years, and 97% at 5 years. PFO closure under fluoroscopy only is safe and efficacious.
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